Shoji Kagami : Glomerular renin-angiotensin system activation - Implications in pathological glomerular remodeling. In Renin-Angiotensin System: Physiology, Role in Disease and Health Implications,, 2013.
Yasunobu Hayabuchi, Miho Sakata, Tatsuya Ohnishi and Shoji Kagami : Chapter 5: Mechanical Stretch and Intermediate-Conductance Ca2+-Activated K+ Channels in Arterial Smooth Muscle Cells. In Mechanically Gated Channels and Their Regulatio Mechanosensitivity in Cells and Tissues Vol. 6 p159-188, 2012.
22.
香美 祥二 : 降圧薬, 2012年.
23.
香美 祥二 : 紫斑病性腎炎, 2012年.
24.
香美 祥二 : 慢性腎炎症候群(IgA腎症を中心に), 東京，総合医学社, 2011年.
25.
香美 祥二 : 小児の急性腎炎症候群, 東京，医学書院, 2011年.
26.
香美 祥二, 二宮 恒夫 : 最新育児小児病学, 2010年9月.
27.
Yasunobu Hayabuchi, Miki Inoue, Miho Sakata and Shoji Kagami : Multidetector-row computed tomography evaluation in congenital heart disease patients, --- Additional information to echocardiography and conventional cardiac catheterization. In Congenital Heart Defects: Etiology, Diagnosis and Treatment ---, Nova Science Publishers, 2009.
We developed a novel method for detecting unmethylated insulin DNA in circulation that can be performed using a conventional real-time PCR system. This method would be useful for analyzing dynamic profiles of β-cells in human disease such as type 1 diabetes.
Keita Osumi, Ken-ichi Suga, Masashi Suzue, Ryuji Nakagawa and Shoji Kagami : Neonatal rebound hyperkalemia associated with ritodrine alone: a case report, BMC Pediatrics, Vol.21, No.1, 370, 2021.
(要約)
Betamimetics have been used for tocolysis extensively in the past, and one of them, ritodrine is widely used in Japan. Various adverse events have been reported for this agent, including newborn hypoglycemia and hypokalemia, as well as maternal hypokalemia and rebound hyperkalemia; however, cases of neonatal rebound hyperkalemia are not described in the literature. A male infant born at 36 weeks of gestation by cesarean section at a local maternity clinic suddenly entered cardiopulmonary arrest with ventricular tachycardia and fibrillation due to hyperkalemia (K, 8.7 mmol/L). No monitoring, examination of blood electrolyte levels, or infusions had been performed prior to this event. Maternal infusion of ritodrine (maximum dose, 170 μg/min) had been performed for 7 weeks prior to cesarean section. After resuscitation combined with calcium gluconate, the infant died at 4 months old due to serious respiratory failure accompanied by acute lung injury following shock. No cause of hyperkalemia other than rebound hyperkalemia associated with ritodrine was identified. This case report serves as a warning regarding the potential risk of neonatal rebound hyperkalemia in association with maternal long-term ritodrine administration.
Yuki Sakaki, Maki Urushihara, Takashi Nagai, Keisuke Fujioka, Shuji Kondo, Yukiko Kinoshita, Tomoki Hattori and Shoji Kagami : Urinary angiotensin converting enzyme 2 and disease activity in pediatric IgA nephropathy, The Journal of Medical Investigation : JMI, Vol.68, No.3.4, 292-296, 2021.
(要約)
Background : Our previous studies demonstrated that the intrarenal renin-angiotensin system (RAS) status was activated in pediatric patients with chronic glomerulonephritis. In the present study, we tested the hypothesis that angiotensin-converting enzyme 2 (ACE2) expression in the kidney is associated with the development of pediatric IgA nephropathy. Methods : We analyzed urinary ACE2 levels and ACE2 expression in the kidney tissues of pediatric patients with IgA nephropathy treated with RAS blockade. Paired tests were used to analyze changes from the first to the second biopsy. Results : Urinary ACE2 levels were significantly decreased after RAS blockade treatment, accompanied by decreased ACE2 expression levels in kidney tissues, urinary protein levels and mesangial hypercellularity scores. Urinary ACE2 levels at the first biopsy were positively correlated with the ACE2 expression levels. Conclusions : These data suggest that urinary ACE2 is associated with ACE2 expression in the diseased kidney, which correlates with the pathogenesis of IgA nephropathy in pediatric patients. J. Med. Invest. 68 : 292-296, August, 2021.
(キーワード)
Angiotensin-Converting Enzyme 2 / Biopsy / Child / Glomerulonephritis, IGA / Humans / Kidney / Renin-Angiotensin System
Yasunobu Hayabuchi, Yukako Honma and Shoji Kagami : Three-dimensional Imaging of Pulmonary Arterial Vasa Vasorum Using Optical Coherence Tomography in Patients After Bidirectional Glenn and Fontan Procedures, European Heart Journal Cardiovascular Imaging, Vol.22, No.8, 941-949, 2021.
(要約)
We evaluated pulmonary arterial (PA) vasa vasorum (VV) in Fontan candidate patients with a novel three-dimensional (3D) imaging technique using optical coherence tomography (OCT). This prospective study assessed the development of adventitial VV in the distal PA of 10 patients with bidirectional Glenn circulation (BDG group, 1.6 ± 0.3 years) and Fontan circulation (Fontan group, 3.3 ± 0.3 years), and in 20 children with normal PA haemodynamics and morphology (Control group, 1.5 ± 0.3 years). We assessed the PA VV with two-dimensional (2D) cross-sectional, multi-planar reconstruction (MPR), and volume rendering (VR) imaging. VV development was evaluated by the VV area/volume ratio, defined as the VV area/volume divided by the adventitial area/volume. Compared to the control group, the observed VV number and diameter on 3D images of MPR and VR were significantly higher, and curved and torturous-shaped VV were more frequently observed in the BDG and Fontan groups (P < 0.001, all). The median VV volume ratio was significantly greater in the BDG than in the control group (3.38% vs. 0.61%; P < 0.001). Although the VV volume ratio decreased significantly after the Fontan procedure (2.64%, P = 0.005 vs. BDG), the ratio remained higher than in the control group (P < 0.001 vs. control). 3D OCT imaging is a novel method that can be used to evaluate adventitial PA VV and may provide pathophysiological insight into the role of the PA VV in these patients.
mEFs) exogenously expressing each of these mutants, phorbol 12-myristate 13-acetate-stimulated shedding was strongly reduced compared with wild-type ADAM17. Thus, in vitro functional assays demonstrated that both missense variants cause the loss-of-function of ADAM17, resulting in the development of NISBD1. Our study further expands the spectrum of genetic pathology underlying ADAM17 in NISBD1 and establishes functional assay systems for its missense variants.
Ken-ichi Suga, Issei Imoto, Hiromichi Ito, Takuya Naruto, Aya Gohji, Keita Osumi, Narumi Tokaji, Yukako Homma, Akemi Ono, Yuko Ichihara, Miki Shono, Tatsuo Mori, Maki Urushihara, Ryuji Nakagawa, Yasunobu Hayabuchi and Shoji Kagami : Next-generation sequencing for the diagnosis of patients with congenital multiple anomalies and / or intellectual disabilities, The Journal of Medical Investigation : JMI, Vol.67, No.3, 4, 246-249, 2020.
(要約)
Background : In clinical practice, a large proportion of patients with multiple congenital anomalies and/or intellectual disabilities (MCA / ID) lacks a specific diagnosis. Recently, next-generation sequencing (NGS) has become an efficient strategy for genetic diagnosis of patients with MCA/ID. To review the utility of NGS for the diagnosis of patients with MCA / ID. Patients with MCA/ID were recruited between 2013 and 2017. Molecular diagnosis was performed using NGS-based targeted panel sequencing for 4,813 genes. Promising causative variants underwent confirmation by Sanger sequencing or chromosomal microarray. Eighteen patients with MCA/ID were enrolled in this study. Of them, 8 cases (44%) were diagnosed by targeted panel sequencing. Most of diagnosed patients were able to receive better counseling and more appropriate medical management. NGS-based targeted panel sequencing seems to be an effective testing strategy for diagnosis of patients with MCA/ID. J. Med. Invest. 67 : 246-249, August, 2020.
Ravi Savarirayan, Louise Tofts, Melita Irving, William Wilcox, A Carlos Bacino, Julie Hoover-Fong, Rosendo Font Ullot, Paul Harmatz, Frank Rutsch, B Michael Bober, E Lynda Polgreen, Ignacio Ginebreda, Klaus Mohnike, Joel Charrow, Daniel Hoernschemeyer, Keiichi Ozono, Yasemin Alanay, Paul Arundel, Shoji Kagami, Natsuo Yasui, K Klane White, M Howard Saal, Antonio Leiva-Gea, Felipe Luna-González, Hiroshi Mochizuki, Donald Basel, M Dania Porco, Kala Jayaram, Elena Fisheleva, Alice Huntsman-Labed and Jonathan Day : Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial., The Lancet, Vol.396, No.10252, 684-692, 2020.
(要約)
BioMarin Pharmaceutical.
(キーワード)
Absorptiometry, Photon / Achondroplasia / Adolescent / Biomarkers / Body Height / Bone Density / Child / Child, Preschool / Collagen Type X / Double-Blind Method / Female / Humans / Injection Site Reaction / Injections, Subcutaneous / Male / Natriuretic Peptide, C-Type / Osteogenesis
Maki Urushihara, Shuji Kondo, Yukiko Kinoshita, Natsuko Ozaki, Ariunbold Jamba, Takashi Nagai, Keisuke Fujioka, Tomoki Hattori and Shoji Kagami : (Pro)renin receptor promotes crescent formation via the ERK1/2 and Wnt/β-catenin pathways in glomerulonephritis., American Journal of Physiology, Renal Physiology, Vol.319, No.4, F571-F578, 2020.
(要約)
(Pro)renin receptor [(P)RR] has multiple functions, but its regulation and role in the pathogenesis in glomerulonephritis (GN) are poorly defined. The aims of the present study were to determine the effects of direct renin inhibition (DRI) and demonstrate the role of (P)RR on the progression of crescentic GN. The anti-glomerular basement membrane nephritis rat model developed progressive proteinuria (83.64 ± 10.49 mg/day) and glomerular crescent formation (percent glomerular crescent: 62.1 ± 2.3%) accompanied by increased macrophage infiltration and glomerular expression of monocyte chemoattractant protein (MCP)-1, (P)RR, phospho-extracellular signal-regulated kinase (ERK)1/2, Wnt4, and active β-catenin. Treatment with DRI ameliorated proteinuria (20.33 ± 5.88 mg/day) and markedly reduced glomerular crescent formation (20.9 ± 2.6%), induction of macrophage infiltration, (P)RR, phospho-ERK1/2, Wnt4, and active β-catenin. Furthermore, primary cultured parietal epithelial cells stimulated by recombinant prorenin showed significant increases in cell proliferation. Notably, while the ERK1/2 inhibitor PD98059 or (P)RR-specific siRNA treatment abolished the elevation in cell proliferation, DRI treatment did not abrogate this elevation. Moreover, cultured mesangial cells showed an increase in prorenin-induced MCP-1 expression. Interestingly, (P)RR or Wnt4-specific siRNA treatment or the β-catenin antagonist XAV939 inhibited the elevation of MCP-1 expression, whereas DRI did not. These results suggest that (P)RR regulates glomerular crescent formation via the ERK1/2 signaling and Wnt/β-catenin pathways during the course of anti-glomerular basement membrane nephritis and that DRI mitigates the progression of crescentic GN through the reduction of (P)RR expression but not inhibition of prorenin binding to (P)RR.
Keita Osumi, Ken-ichi Suga, Akemi Ono, Aya Gohji, Tatsuo Mori, Yukiko Kinoshita, Mikio Sugano, Yoshihiro Touda, Maki Urushihara, Ryuji Nakagawa, Yasunobu Hayabuchi, Issei Imoto and Shoji Kagami : Molecular diagnosis of an infant with TSC2/ PKD1 contiguous gene syndrome, Human Genome Variation, Vol.7, No.21, 2020.
(要約)
A 1-month-old Japanese infant with cardiac rhabdomyoma was diagnosed with / contiguous gene syndrome by targeted panel sequencing with subsequent quantitative polymerase chain reaction that revealed gross monoallelic deletion, including parts of two genes: exons 19-42 of and exons 2-46 of . Early molecular diagnosis can help to detect bilateral renal cyst formation and multidisciplinary follow-up of this multisystem disease.
Takahiro Tayama, Tatsuo Mori, Aya Goji, Yoshihiro Toda and Shoji Kagami : Improvement of epilepsy with lacosamide in a patient with ring chromosome 20 syndrome., Brain & Development, Vol.42, No.6, 473-476, 2020.
(要約)
Although VPA and LTG are generally effective for the treatment of ring chromosome 20 syndrome, they do not completely suppress seizures. LCM can be considered an effective option for seizure control in patients with this syndrome.
Natsumi Yamamura-Miyazaki, Toshimi Michigami, Kenichi Satomura, Maki Urushihara, Shoji Kagami and Katsusuke Yamamoto : Reduction in urinary angiotensinogen levels and improvement of proteinuria by renin-angiotensin system blockade in pediatric chronic kidney disease patients with very low birth weight., Pediatric Nephrology, Vol.35, No.7, 1307-1314, 2020.
(要約)
Children with low birth weight (LBW) have an increased risk of developing chronic kidney disease (CKD), and no effective strategies have been established to prevent the progression of CKD in these patients. Urinary angiotensinogen (UAGT) may represent a useful marker of intrarenal renin-angiotensin system (RAS) activation, which has been suggested to play a critical role in the development of hypertension and CKD. Herein, we conducted a prospective study to determine whether RAS blockade is beneficial for suppressing the progression of CKD in children with LBW, using UAGT as a surrogate marker of renal impairment. Nine children with CKD (stages: 1-2) who had very low birth weight (VLBW; < 1500 g) were started on RAS blockade with candesartan. We measured blood pressure and laboratory parameters, including urinary concentrations of angiotensinogen, protein, albumin, creatinine (Cr), and estimated glomerular filtration rate (eGFR), before and after candesartan treatment. Birth weight was 712 g (range, 536-800 g). Age at evaluation was 11.6 years (range, 10.3-15.6 years). After candesartan treatment for 47.6 ± 25.0 months, the UAGT to urinary Cr ratio decreased from 61.9 ± 44.7 to 16.8 ± 14.4 μg/g (p = 0.015). The urinary protein to Cr and albumin to Cr ratios also decreased (p = 0.008 and p = 0.012, respectively), whereas there was no significant change in eGFR. RAS blockade reduced UAGT levels and improved proteinuria/albuminuria in children with CKD who had VLBW. Suppression of intrarenal RAS activity may slow the progression of CKD in children with LBW.
Tatsuo Mori, Hiromichi Ito, Masafumi Harada, Sonoka Hisaoka, Yuki Matsumoto, Aya Goji, Yoshihiro Toda, Kenji Mori and Shoji Kagami : Multi-delay arterial spin labeling brain magnetic resonance imaging study for pediatric autism., Brain & Development, Vol.42, No.4, 315-321, 2020.
(要約)
We concluded that patients with ASD showed a statistically significant decline in CBF in regions associated with the mirror neuron system. The advantages of ASL MRI include low invasiveness (no radiation exposure) and short imaging time (approximately 5 min). Studies with larger sample sizes are required to establish the diagnostic value of ASL MRI for ASD.
Akemi Ono, Yasunobu Hayabuchi, Manami Tanaka and Shoji Kagami : Assessment of Right Ventricular Function by Isovolumic Acceleration of Pulmonary and Tricuspid Annulus in Surgically Repaired Tetralogy of Fallot, The Journal of Medical Investigation : JMI, Vol.67, No.1.2, 145-150, 2020.
(要約)
Assessment of right ventricular (RV) function is quite important in patients with surgically corrected tetralogy of Fallot (TOF). However, quantitative assessment of RV function remains challenging, mainly because of the complex RV geometry. This prospective study investigated isovolumic acceleration (IVA), a parameter of myocardial systolic function not influenced by either preload or afterload, using tissue Doppler imaging. We evaluated IVA measured on pulmonary annulus (PA-IVA) and tricuspid annulus (TA-IVA), because we considered that PA-IVA and TA-IVA correspond with systolic function of the RV outflow tract (RVOT) and RV basal function, respectively. Thirty-nine patients with surgically repaired TOF (TOF group) and 40 age-matched healthy children (control group) were enrolled in this study. No significant difference was seen between TA-IVA (2.5 ± 0.8 m/s2) and PA-IVA (2.4 ± 0.8 m/s2) in the control group. In the TOF group, PA-IVA (1.0 ± 0.5 m/s2) was significantly lower than TA-IVA (1.3 ± 0.6 m/s2, p < 0.05). Both TA-IVA and PA-IVA were significantly lower in the TOF group than in the control group (p < 0.05 each). We concluded that PA-IVA offers a useful index to assess RVOT function in TOF patients. J. Med. Invest. 67 : 145-150, February, 2020.
(キーワード)
isovolumic acceleration / right ventricular function / pulmonary annulus / terralogy of Fallot
Yuko Ichihara, Ken-ichi Suga, Maika Fukui, Naoto Yonetani, Miki Shono, Ryuji Nakagawa and Shoji Kagami : Serum biotin level during pregnancy is associated with fetal growth and preterm delivery, The Journal of Medical Investigation : JMI, Vol.67, No.1.2, 170-173, 2020.
(要約)
Background : Biotin is a water-soluble vitamin that plays various biological roles through histone modification, such as immune functions and fetal growth. Mammalian maternal biotin deficiency during gestation induces fetal growth restriction. Preterm infants are known to be marginal biotin deficiency. However, studies on the biotin status of pregnant women under various conditions are lacking. Method : This was a retrospective case control study to analyze serum biotin concentration during pregnancy and cord blood in normal pregnancy, preterm delivery and small-for-gestational-age (SGA). Results : Twenty pregnant women with normal term delivery, 35 with preterm delivery, 24 with SGA, and 10 non-pregnant adult women were enrolled. Serum biotin concentrations of pregnant women remained low from first to third trimester. The levels of serum biotin in cord blood showed a significant positive correlation with gestational age, and that of pregnant women showed a weak positive correlation with gestational age. The maternal serum biotin levels during second and third trimester of SGA group were significantly lower than those of normal term delivery. Conclusion : This study suggests that maternal biotin deficiency during pregnancy might be the risk of preterm labor or fetal growth restriction. Further studies are required to clarify the roles of biotin in perinatal medicine. J. Med. Invest. 67 : 170-173, February, 2020.
(キーワード)
Adult / Biotin / Female / Fetal Blood / Fetal Development / Fetal Growth Retardation / Humans / Infant, Small for Gestational Age / Pregnancy / Premature Birth / Retrospective Studies
Yasunobu Hayabuchi, Yukako Honma and Shoji Kagami : A novel index equivalent to the myocardial performance index for right ventricular functional assessment in children and adolescent patients., Scientific Reports, Vol.9, No.1, 19975, 2019.
(要約)
The aims of the present study were to develop and check the utility and feasibility of a novel right ventricular (RV) functional index (RV angular velocity; RVω, s) derived from the angular velocity in harmonic oscillator kinematics obtained from the RV pressure waveform. We hypothesized that RVω reflects the myocardial performance index (MPI), which represents global RV function. A total of 132 consecutive patients, ranging in age from 3 months to 34 years with various cardiac diseases were included in this prospective study. RVω was defined as the difference between the peak derivative of pressure (dP/dt_max - dP/dt_min) divided by the difference between the maximum and minimum pressure (Pmax - Pmin). RVω showed significant negative correlations with the pulsed-wave Doppler-derived myocardial performance index (PWD-MPI) and the tissue Doppler imaging-derived MPI (TDI-MPI) (r = -0.52 and -0.51, respectively; both p < 0.0001). RVω also showed significant positive correlations with RV fractional area change (RVFAC) and RV ejection fraction (RVEF) (r = 0.41 and 0.39, respectively; both p < 0.0001), as well as a significant negative correlation with tricuspid E/e' (r = -0.19, p = 0.0283). The clinical feasibility and utility of RVω for assessing global RV performance, incorporating both systolic and diastolic function, were demonstrated.
Keisuke Fujioka, Takashi Nagai, Yukiko Kinoshita, Maki Urushihara, Yuko Hamasaki, Seiichiro Shishido and Shoji Kagami : Successful treatment with voriconazole combined with amphotericin B-liposome for fluconazole-resistant pulmonary cryptococcosis after renal transplantation., CEN Case Reports, Vol.8, No.4, 261-265, 2019.
(要約)
Cryptococcosis is an invasive fungal infection that is common among organ transplant recipients, and it is challenging to treat among these patients because of their immunocompromised status. Fluconazole (FLCZ) is recommended as a first-line treatment modality for pulmonary cryptococcosis in organ transplant recipients. However, cases of FLCZ resistance among Cryptococcus neoformans isolates have been reported from the Asia Pacific region. Previous studies have reported the efficacy of voriconazole (VRCZ) in patients with FLCZ-resistant fungal infections. Herein, we report a case of FLCZ-resistant pulmonary cryptococcosis after renal transplantation that was successfully treated with VRCZ combined with amphotericin B-liposome (L-AMB). The patient was a-23-year-old woman who underwent living-donor kidney transplantation at age 20 years. She has attended our hospital since before for mental retardation, epilepsy, and dilated cardiomyopathy. At age 23 years, she presented to our hospital with fever and cough. She was diagnosed with pulmonary cryptococcosis based on positive-serum cryptococcal antigen. Chest radiography showed bilateral consolidations. Fosfluconazole (F-FLCZ) was administered, and her condition improved. However, she developed cough and fever again on day 60 of hospitalization. Cryptococcosis recurrence was suspected due to the high degree of cryptococcal antigen titers showed (1:2048) taken on the same day. Therefore, L-AMB was added, and F-FLCZ was substituted with VRCZ. Her condition improved, but L-AMB was discontinued due to hyponatremia, hypokalemia, and elevated serum creatinine. This indicates that VRCZ caused the remission. She was discharged after 6 months of admission. In conclusion, this case shows the efficacy of VRCZ combined with L-AMB for refractory pulmonary cryptococcosis.
Tatsuo Mori, Yoshihiro Touda, Hiromichi Ito, Kenji Mori, Tomohiro Kohmoto, Issei Imoto and Shoji Kagami : A 16q22.2-q23.1 deletion identified in a male infant with West syndrome., Brain & Development, 2019.
(要約)
In partial monosomy of the distal part of chromosome 16q, abnormal facial features, intellectual disability (ID), and feeding dysfunction are often reported. However, seizures are not typical and the majority of them were seizure-free. Here we present the case of a 16q22.2-q23.1 interstitial deletion identified in a male patient with severe ID, facial anomalies including forehead protrusions and flat nose bridge, patent ductus arteriosus, bilateral vocal cord atresia treated by tracheotomy, and West syndrome, which were developed 10months after birth. Although phenobarbital, sodium valproate (VPA), and zonisamide were not effective as monotherapies or combination therapies, the patient's epileptic seizures and electroencephalogram anomalies disappeared following combined therapy with lamotrigine and VPA. Although WW Domain Containing Oxidoreductase (WWOX), which is known as a cause of autosomal recessive epileptic encephalopathy, was included within the 6.8-Mb deleted region which identified by targeted panel sequencing and validated by chromosomal microarray analysis, no pathogenic variants were detected in the other allele of WWOX. Therefore, it is possible that other genes within or outside of the long deleted region or their interactions may cause West syndrome in this patient.
Makoto Irahara, Wakako Shinahara, Mayumi Sugimoto, Yukiko Ogawa, Keiji Shitsukawa, Kenji Kubota, Limin Yang, Yukihiro Ohya, Hirohisa Saito, Shoji Kagami, Kokichi Arisawa and Hiroshi Kido : Trajectories of class-switching-related egg and cow's milk allergen-specific immunoglobulin isotype formation and its modification by eczema with low- and high-affinity immunoglobulin E during early infancy, Immunity, Inflammation and Disease, Vol.7, No.2, 74-85, 2019.
(要約)
Allergen-specific immunoglobulin isotype formation associated with immunoglobulin class-switching during the lactation period is the immunological background for food allergy in infants. We analyzed the serial changes in the production of feeding type-related egg- and milk-specific immunoglobulin isotypes from birth to 6 months of age with or without eczema in 84 infants. Allergen-specific immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, IgA, and IgE levels of hen's egg and bovine milk were measured in cord blood and blood samples from infants at 2, 4, and 6 months of age by the densely carboxylated protein microarray. Formula and mixed feeding were associated with a rapid increase in cow's milk allergen-specific immunoglobulins and feeding type-related significant differences in casein-specific immunoglobulin levels were detected. Breast and mixed feeding were associated with slow but significant increase in ovalbumin-specific IgG1 and IgE levels, but not other immunoglobulins. We found two different immunoglobulin isotype formation at 6 months of age with low- or high-affinity IgE against ovalbumin. One isotype formation pattern had relatively high ovalbumin-specific IgG1 levels, detectable IgG2, and low-affinity IgE, while the other had low ovalbumin-specific IgG1 levels, undetectable IgG2, and high levels of high-affinity IgE. The incidence of eczema was significantly higher in the latter pattern (84.6%), compared with the remaining infants (42.2%). Feeding practice-related allergen sensitization and immunoglobulin isotype formation were identified during the lactation period. The development of eczema during the lactation period could potentially modify the immunoglobulin isotype formation with high levels of high-affinity IgE.
Yasunobu Hayabuchi, Yukako Homma and Shoji Kagami : Right Ventricular Myocardial Stiffness and Relaxation Components by Kinematic Model-Based Transtricuspid Flow Analysis in Children and Adolescents with Pulmonary Arterial Hypertension., Ultrasound in Medicine & Biology, Vol.45, No.8, 1999-2009, 2019.
(要約)
We hypothesized that the kinematic model-based parameters obtained from the transtricuspid E-wave would be useful for evaluating the right ventricular diastolic property in pediatric pulmonary arterial hypertension (PAH) patients. The model was parametrized by stiffness/elastic recoil k, relaxation/damping c and load x. These parameters were determined as the solution of m dx/dt + c dx/dt + kx = 0, which is based on the theory that the E-wave contour is determined by the interplay of stiffness/restoring force, damping/relaxation force and load. The PAH group had a significantly higher k and c compared with the control group (182.5 72.4 g/s vs. 135.7 49.5 g/s, p = 0.0232, and 21.9 6.5 g/s vs. 10.6 5.2 g/s, p <0.0001, respectively). These results indicate that in the PAH group, the right ventricle had higher stiffness/elastic recoil and inferior cross-bridge relaxation. The present findings indicate the feasibility and utility of using kinematic model parameters to assess right ventricular diastolic function.
竹内 竣亮, 須賀 健一, 庄野 実希, 中川 竜二, 香美 祥二 : Small for gestational age児の成長および神経学的発達の予後, 四国医学雑誌, Vol.75, No.1-2, 63-68, 2019年.
(要約)
(Background)Small for gestational age (SGA) infants have multiple risk factors for short stature, developmental disorders, and metabolic diseases in adulthood. Our institute which plays central roles in perinatal medicine in Tokushima prefecture has many high risk pregnant women, therefore a relatively large number of SGA infants admitted to neonatal intensive care unit (NICU) and growth care unit (GCU).(Objective)To elucidate the prognosis such as short stature, neurodevelopmental disorder and mental retardation of SGA infants discharged from NICU and GCU in our hospital.(Method)SGA patients discharged from NICU and GCU in our hospital between 2012 and 2014 were enrolled in this study. Clinical data were collected from medical charts.(Results)There were 106 SGA infants (19.5%) discharged from NICU/GCU for 3 years. We excluded patients with congenital malformation syndrome, chromosomal abnormality, neuromuscular disorder, death and lost of follow-up, and finally 75 SGA infants were enrolled. Four SGA infants (5%) required growth hormone (GH) treatment for short stature and all of them were promoted growth significantly. Three SGA infants (4%) showed attention deficit hyperactivity disorder and/or autism spectrum disorder, and 5 SGA infants (6%) presented with mental retardation.(Conclusion)This study revealed the prognosis of SGA infants discharged from NICU and GCU in our hospital. Further large cohort with long-term observation is required.
(キーワード)
small for gestational age / neurodevelopment / growth
Yasunobu Hayabuchi, Yukako Homma and Shoji Kagami : Optical coherence tomography for observing development of pulmonary arterial vasa vasorum after bidirectional cavopulmonary connection in children., PLoS ONE, Vol.14, No.4, e0215146, 2019.
(要約)
Hypoxia and low pulmonary arterial (PA) blood flow stimulate the development of systemic-to-pulmonary collateral blood vessels, which can be an adverse factor when performing the Fontan operation. The aim of this study was to use optical coherence tomography (OCT) to elucidate the morphological changes in PA vasculature after creation of a bidirectional cavopulmonary connection (BCPC) in children. This prospective study evaluated PA wall thickness and development of PA vasa vasorum (VV) in the distal PA of eight patients (BCPC group, 1.3 0.3 years) and 20 age-matched children with normal pulmonary artery hemodynamics and morphology (Control group, 1.4 0.3 years). VV development was defined by the VV area ratio, defined as the VV area divided by the adventitial area in cross-sectional images. There was no significant difference in PA wall thickness between the BCPC and control groups (0.12 0.03 mm vs. 0.12 0.02 mm, respectively). The VV area ratio was significantly greater in the BCPC group than in the Control group (14.5 3.5% vs. 5.3 1.6%, respectively; p<0.0001). OCT is a promising new tool for evaluating PA pathology, including the development of VV in patients after BCPC.
Miki Shono, Maki Urushihara, Kenichi Suga, Noriko Watanabe, Takahiko Saijo, Ryuji Nakagawa and Shoji Kagami : Enhanced angiotensinogen expression in neonates during kidney development., Clinical and Experimental Nephrology, Vol.23, No.4, 537-543, 2019.
(要約)
We recently demonstrated that preterm neonates have higher urinary angiotensinogen (AGT) levels than full-term neonates. Here, we tested the hypothesis that enhanced neonatal AGT expression is associated with intrarenal renin-angiotensin system (RAS) status during kidney development. We prospectively recruited neonates born at our hospital and healthy children with minor glomerular abnormalities between April 2013 and March 2017. We measured neonatal plasma and urinary AGT levels at birth and 1 year later and assessed renal AGT expression in kidney tissues from neonates and healthy children using immunohistochemical (IHC) analysis. Fifty-four neonates and eight children were enrolled. Although there were no changes in plasma AGT levels, urinary AGT levels were significantly decreased 1 year after birth. Urinary AGT levels at birth were inversely correlated with gestational age, and urinary AGT levels at birth and 1 year later were inversely correlated with estimated glomerular filtration rate 1 year after birth. IHC analysis showed that renal AGT expression in neonates was higher than that in healthy children and inversely correlated with gestational age. Enhanced AGT expression and urinary AGT excretion may reflect intrarenal RAS activation associated with kidney development in utero.
Shuji Kondo, Sato Matsuura, Jamba Ariunbold, Yukiko Kinoshita, Maki Urushihara, Kenichi Suga, Natsuko Ozaki, Takashi Nagai, Keisuke Fujioka and Shoji Kagami : Expression of NADPH oxidase and production of reactive oxygen species contribute to ureteric bud branching and nephrogenesis., The Journal of Medical Investigation : JMI, Vol.66, No.1.2, 93-98, 2019.
(要約)
Ureteric bud branching and nephrogenesis are performed through large-scale proliferation and apoptosis events during renal development. Reactive oxygen species (ROS), produced by NADPH oxidase, may contribute to cell behaviors, including proliferation and apoptosis. We investigated the role of NADPH oxidase expression and ROS production in developing kidneys. Immunohistochemistry revealed that NADPH oxidase componentswere expressed on epithelial cells in ureteric bud branches, as well as on immature glomerular cells and epithelial cells in nephrogenic zones. ROS production, detected by dihydroethidium assay, was strongly observed in ureteric bud branches and nephrogenic zones, corresponding with NADPH oxidase localization. Organ culture of E14 kidneys revealed that the inhibition of NADPH oxidase significantly reduced the number of ureteric bud branches and tips, consistent with reduced ROS production. This was associated with reduced expression of phosphorylated ERK1/2 and increased expression of cleaved caspase-3. Organ culture of E18 kidneys showed that the inhibition of NADPH oxidase reduced nephrogenic zone size, accompanied by reduced ROS production, fewer proliferating cell nuclear antigen-positive cells, lower p-ERK1/2 expression, and increased expression of cleaved caspase-3. These results demonstrate that ROS produced by NADPH oxidase might play an important role in ureteric bud branching and nephrogenesis by regulating proliferation and apoptosis. J.Med. Invest. 66 :93-98, February, 2019.
Ayumi Sasaki, Mayumi Sugimoto, Narumi Tokaji, Makoto Irahara, Koichi Okamoto, Hisanori Uehara and Shoji Kagami : Efficacy of an elimination diet in a patient with eosinophilic gastroenteritis : a pediatric case with multiple food allergies., The Journal of Medical Investigation : JMI, Vol.66, No.1.2, 201-204, 2019.
Yasunobu Hayabuchi, Yukako Homma, Mikio Sugano, Takashi Kitaichi and Shoji Kagami : Development of acquired intrapulmonary venous anastomosis contributing to establishment of Fontan circulation., Pulmonary Circulation, Vol.9, No.1, 2045894018814774, 2018.
(要約)
Pulmonary venous (PV) obstruction is associated with a poor prognosis, as well as a high risk of recurrence, following surgical treatment. It can also interfere with the successful completion of Fontan circulation in patients with complex congenital heart disease. A case of a patient who had right isomerism (also known as asplenia syndrome), total anomalous pulmonary venous connection (TAPVC), and a single right ventricle is presented. Although bilateral total occlusion of the inferior PVs was identified postoperatively, the formation of the anastomosis and collateral vessels into the superior and middle PVs enabled successful completion of Fontan circulation. Anastomoses and collateral flow of the PVs were found largely in the interlobar pleura and not in the lung parenchyma.
Tuba M. Ansary, Maki Urushihara, Yoshihide Fujisawa, Sayaka Nagata, Hidenori Urata, Daisuke Nakano, Hitomi Hirofumi, Kazuo Kitamura, Shoji Kagami and Akira Nishiyama : Effects of the selective chymase inhibitor TEI-F00806 on the intrarenal renin-angiotensin system in salt-treated angiotensin I-infused hypertensive mice., Experimental Physiology, Vol.103, No.11, 1524-1531, 2018.
(要約)
What is the central question of this study? Can chymase inhibition prevent angiotensin I-induced hypertension through inhibiting the conversion of angiotensin I to angiotensin II in the kidney? What is the main finding and its importance? Treatment with TEI-F00806 decreased angiotensin II content of the kidney, renal cortical angiotensinogen protein levels and chymase mRNA expression, and attenuated the development of hypertension. The effects of the selective chymase inhibitor TEI-F00806 were examined on angiotensin I (Ang I)-induced hypertension and intrarenal angiotensin II (Ang II) production in salt-treated mice. Twelve-week-old C57BL male mice were given a high-salt diet (4% NaCl + saline (0.9% NaCl)), and divided into three groups: (1) sham + vehicle (5% acetic acid in saline), (2) Ang I (1 μg kg min , s.c.) + vehicle, and (3) Ang I + TEI-F00806 (100 mg kg day , p.o.) (n = 8-10 per group). Systolic blood pressure was measured weekly using a tail-cuff method. Kidney Ang II content was measured by radioimmunoassay. Chronic infusion of Ang I resulted in the development of hypertension (P < 0.001), and augmented intrarenal chymase gene expression (P < 0.05), angiotensinogen protein level (P < 0.001) and Ang II content (P < 0.01) in salt-treated mice. Treatment with TEI-F00806 attenuated the development of hypertension (P < 0.001) and decreased Ang II content of the kidney (P < 0.05), which was associated with reductions in renal cortical angiotensinogen protein levels (P < 0.001) and chymase mRNA expression (P < 0.05). These data suggest that a chymase inhibitor decreases intrarenal renin-angiotensin activity, thereby reducing salt-dependent hypertension.
(キーワード)
Angiotensin I / Angiotensin II / Animals / 血圧 (blood pressure) / Chymases / 高血圧 (hypertension) / Kidney / 男性 (male) / Mice / Peptidyl-Dipeptidase A / レニン·アンジオテンシンシステム (Renin-angiotensin System)
Yukako Homma, Yasunobu Hayabuchi, Akemi Ono and Shoji Kagami : Pulmonary Artery Wall Thickness Assessed by Optical Coherence Tomography Correlates With Pulmonary Hemodynamics in Children With Congenital Heart Disease., Circulation Journal, Vol.82, No.9, 2350-2357, 2018.
(要約)
Pulmonary arterial (PA) wall thickening evaluated by optical coherence tomography (OCT) has been reported in adults with PA hypertension. The purpose of this study was to evaluate the feasibility of OCT for preoperative assessment of the PA wall in children with congenital heart disease (CHD). Methods and esults: Participants comprised 39 patients with ventricular septal defect, atrial septal defect, or patent ductus arteriosus. Attempts were made to evaluate vessels of various diameters using OCT. Clearly observed vessels that were optimal for evaluation were selected and classified into 4 subgroups by diameter of the lumen. Optimal depiction was obtained in 80 of 156 vessels in total, and 25 (64.1%), 34 (87.1%), 17 (43.6%), and 4 vessels (10.3%) in each of the 1.0-<2.0 mm, 2.0-<3.0 mm, 3.0-<4.0 mm, and 4.0-5.0 mm subgroups, respectively. Arterial walls in the 2.0-<3.0 mm subgroup were the most frequently delineated, and wall thickness correlated significantly with mean PA pressure, pulmonary vascular resistance index, pulmonary-to-systemic flow ratio, and PA capacitance index (r=0.56, 0.52, 0.37, and -0.49, respectively). The 3-layered appearance was delineated in 29 of 80 vessels (36.2%). This feature had no significant correlation with pulmonary hemodynamics. OCT represents a promising tool for evaluating the PA wall in children with CHD.
Yasunobu Hayabuchi, Ono Akemi, Homma Yukako and Shoji Kagami : Analysis of Right Ventricular Myocardial Stiffness and Relaxation Components in Children and Adolescents With Pulmonary Arterial Hypertension., Journal of the American Heart Association, Vol.7, No.9, e008670, 2018.
(要約)
The rate of left ventricular pressure decrease during isovolumic relaxation is traditionally assessed algebraically via 2 empirical indices: the monoexponential and logistic time constants (τ and τ). Since the pattern of right ventricular (RV) pressure decrease is quite different from that of the left ventricular, we hypothesized that novel kinematic model parameters are more appropriate and useful to evaluate RV diastolic dysfunction. Eight patients with pulmonary arterial hypertension (age 12.5±4.8 years) and 20 normal subjects (control group; age 12.3±4.4 years) were enrolled. The kinematic model was parametrized by stiffness/restoring Ek and damping/relaxation μ. The model predicts isovolumic relaxation pressure as a function of time as the solution of dP/dt+(1/μ)dP/dt+EkP=0, based on the theory that the pressure decay is determined by the interplay of inertial, stiffness/restoring, and damping/relaxation forces. In the assessment of RV diastolic function, τ and τ did not show significant differences between the pulmonary arterial hypertension and control groups (46.8±15.5 ms versus 32.5±14.6 ms, and 19.6±5.9 ms versus 14.5±7.2 ms, respectively). The pulmonary arterial hypertension group had a significantly higher Ek than the control group (915.9±84.2 s versus 487.0±99.6 s, <0.0001) and a significantly lower μ than the control group (16.5±4.3 ms versus 41.1±10.4 ms, <0.0001). These results show that the RV has higher stiffness/elastic recoil and lower cross-bridge relaxation in pulmonary arterial hypertension. The present findings indicate the feasibility and utility of kinematic model parameters for assessing RV diastolic function.
Yasunobu Hayabuchi, Akemi Ono, Yukako Homma and Shoji Kagami : Pulmonary annular motion velocity reflects right ventricular outflow tract function in children with surgically repaired congenital heart disease, Heart and Vessels, Vol.33, No.3, 316-326, 2018.
(要約)
Right ventricular (RV) dysfunction is generally evaluated using analyses of tricuspid annular motion. However, it represents only one aspect of RV performance. Whether measuring pulmonary annular motion velocity could serve as a novel way to evaluate global RV and/or RV outflow tract (RVOT) performance in pediatric congenital heart disease (CHD) patients with surgically repaired RVOT was evaluated. In this prospective study, tissue Doppler-derived pulmonary annular motion velocity was measured in children (aged 2-5 years) with RVOT reconstruction (RVOTR group, n = 48) and age-matched healthy children (Control, n = 60). The types of RVOTR procedures were as follows: pulmonary valve-sparing procedure (PVS, n = 7); transannular patch with monocusp valve reconstruction (TAP, n = 29); and RV-to-PA conduit reconstruction using a pericardial valve with expanded polytetrafluoroethylene conduit (Rastelli, n = 12). Pulmonary annular motion velocity waveforms comprised systolic bimodal (s1' and s2') and diastolic e' and a' waves in all participants. The peak velocities of s1', s2', e', and a' were significantly lower in the RVOTR group than in the control group (all p < 0.0001). Furthermore, these parameters depended significantly on the type of surgical procedure. The peak velocities of s1', s2', and e' had significant correlations with RVOT ejection fraction (RVOT-EF) (r = 0.56, 0.49, and 0.34, respectively), and RVOT fractional shortening (RVOT-FS) (r = 0.72, 0.55, and 0.41, respectively), although there were no significant correlations between pulmonary annular motion and global RV function, including RV ejection fraction (RVEF) and RV fractional area change (RVFAC) in the assessment of all RVOTR group patients. The pulmonary annular motion parameters in the PVS group had significant correlations with both global RV and RVOT performance. The TAP group showed significant correlations between RVOT function and pulmonary annular motion. The Rastelli group showed almost no significant correlations between RV/RVOT function and tissue Doppler parameters. Pulmonary annular motion velocity is a simple, rapid, reproducible, and useful method of assessing RVOT function in children with surgically repaired CHD.
H Kato, M Nangaku, H Okada and Shoji Kagami : Controversies of the classification of TMA and the terminology of aHUS., Clinical and Experimental Nephrology, Vol.22, No.4, 979-980, 2018.
Yasunobu Hayabuchi, Akemi Ono, Yukako Homma and Shoji Kagami : Temporal Sequential Pattern of Right Ventricular Free Wall Contraction in Normal Children., Circulation Journal, Vol.81, No.11, 1699-1706, 2017.
(要約)
The temporal sequence of right ventricular (RV) deformation is related to RV dysfunction. The sequence of RV free wall contraction was investigated.Methods and Results:In this prospective study, strain profiles using speckle-tracking echocardiography and tissue Doppler-derived pulmonary and tricuspid annular motion were assessed in 60 normal children. Circumferential RV free wall strain of 3 individual segments (anterior, lateral, and inferior) was evaluated. Longitudinal strain was assessed in 3 individual segments (RV outflow tract [RVOT], apical, and RV inflow tract [RVIT]). The isovolumetric contraction time (ICT) and the time interval between the onset of the QRS wave to the peak s' wave were measured for pulmonary and tricuspid annular motion velocities. The time to peak circumferential strain was significantly lower in the anterior than in the lateral and inferior segments (339.1±19.5, 358.3±21.8, and 366.6±22.4 ms, respectively; P<0.0001). Longitudinal deformation of the RVOT segment occurred before the apical and RVIT segments (351.8±23.1, 366.3±20.1, and 369.2±21.3 ms, respectively; P<0.0001). The ICT and the time to peak s' were significantly shorter in pulmonary than in tricuspid annular motion (49.4±10.1 vs 58.0±13.2 ms; and 104.7±12.2 vs. 160.5±27.1 ms; P<0.0001 for each). Longitudinal deformation of RVOT precedes RVIT. Circumferential deformation occurs in the anterior segment before the lateral and posterior segments. The presence of mechanical time heterogeneity appears important for RV performance.
Hiroyuki Ono, Kojiro Nagai, Eriko Shibata, Motokazu Matsuura, Seiji Kishi, Taizo Inagaki, Masanori Minato, Sakiya Yoshimoto, Sayo Ueda, Fumiaki Obata, Kenji Nishimura, Masanori Tamaki, Fumi Kishi, Taichi Murakami, Hideharu Abe, Yukiko Kinoshita, Maki Urushihara, Shoji Kagami and Toshio Doi : Re-recognition of Age-dependent Reference Range for the Serum Creatinine Level in Teenagers - A Case of Slowly Progressive Tubulointerstitial Nephritis which Occurred in an Adolescent., Internal Medicine, Vol.56, No.16, 2187-2193, 2017.
(要約)
For the first time, a 15-year-old boy was found to have a slight degree of proteinuria and microscopic hematuria during annual school urinalysis screening. His kidney function had already severely deteriorated. A kidney biopsy revealed tubulointerstitial nephritis (TIN) with diffuse inflammatory cell infiltration. His medical records showed his serum creatinine level to be 0.98 mg/dL two years ago, which was abnormally high considering his age. Although the etiology of slowly progressive TIN was unclear, glucocorticoid and immunosuppressant therapy improved his kidney function. This case report suggests that all doctors should recognize the reference range for the serum creatinine level in teenagers.
Asami Okada, Tomohiro Kohmoto, Takuya Naruto, Ichiro Yokota, Yumiko Kotani, Aki Shimada, Yoko Miyamoto, Rizu Takahashi, Aya Goji, Kiyoshi Masuda, Shoji Kagami and Issei Imoto : The first Japanese patient with mandibular hypoplasia, deafness, progeroid features and lipodystrophy diagnosed via POLD1 mutation detection., Human Genome Variation, Vol.4, 17031, 2017.
(要約)
Mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome is a rare autosomal dominant disorder caused by heterozygous mutations. To date, 13 patients affected by mutation-caused MDPL have been described. We report a clinically undiagnosed 11-year-old male who noted joint contractures at 6 years of age. Targeted exome sequencing identified a known mutation [NM_002691.3:c.1812_1814del, p.(Ser605del)] that diagnosed him as the first Japanese/East Asian MDPL case.
Yasunobu Hayabuchi, Akemi Ono, Yukako Homma and Shoji Kagami : Assessment of pulmonary arterial compliance evaluated using harmonic oscillator kinematics., Pulmonary Circulation, Vol.7, No.3, 666-673, 2017.
(要約)
We hypothesized that K, a harmonic oscillator kinematics-derived spring constant parameter of the pulmonary artery pressure (PAP) profile, reflects PA compliance in pediatric patients. In this prospective study of 33 children (age range = 0.5-20 years) with various cardiac diseases, we assessed the novel parameter designated as Kcalculated using the pressure phase plane and the equation K = (dP/dt_max)/([Pmax - Pmin])/2), where dP/dt_max is the peak derivative of PAP, and Pmax - Pmin is the difference between the minimum and maximum PAP. PA compliance was also calculated using two conventional methods: systolic PA compliance (sPAC) was expressed as the stroke volume/Pmax - Pmin; and diastolic PA compliance (dPAC) was determined according to a two-element Windkessel model of PA diastolic pressure decay. In addition, data were recorded during abdominal compression to determine the influence of preload on K. A significant correlation was observed between Kand sPAC (r = 0.52, P = 0.0018), but not dPAC. Significant correlations were also seen with the time constant (τ) of diastolic PAP (r = -0.51, P = 0.0026) and the pulmonary vascular resistance index (r = -0.39, P = 0.0242). No significant difference in Kwas seen between before and after abdominal compression. Khad a higher intraclass correlation coefficient than other compliance and resistance parameters for both intra-observer and inter-observer variability (0.998 and 0.997, respectively). These results suggest that Kcan provide insight into the underlying mechanisms and facilitate the quantification of PA compliance.
Hiromichi Ito, Kenji Mori, Masafumi Harada, Sonoka Hisaoka, Yoshihiro Touda, Tatsuo Mori, Aya Gohji, Yoko Abe, Masahito Miyazaki and Shoji Kagami : A Proton Magnetic Resonance Spectroscopic Study in Autism Spectrum Disorder Using a 3-Tesla Clinical Magnetic Resonance Imaging (MRI) System: The Anterior Cingulate Cortex and the Left Cerebellum., Journal of Child Neurology, Vol.32, No.8, 731-739, 2017.
(要約)
The pathophysiology of autism spectrum disorder (ASD) is not fully understood. We used proton magnetic resonance spectroscopy to investigate metabolite concentration ratios in the anterior cingulate cortex and left cerebellum in ASD. In the ACC and left cerebellum studies, the ASD group and intelligence quotient- and age-matched control group consisted of 112 and 114 subjects and 65 and 45 subjects, respectively. In the ASD group, γ-aminobutyric acid (GABA)+/ creatine/phosphocreatine (Cr) was significantly decreased in the anterior cingulate cortex, and glutamate (Glu)/Cr was significantly increased and GABA+/Cr was significantly decreased in the left cerebellum compared to those in the control group. In addition, both groups showed negative correlations between Glu/Cr and GABA+/Cr in the left cerebellum, and positive correlations between GABA+/Cr in the anterior cingulate cortex and left cerebellum. ASD subjects have hypoGABAergic alterations in the anterior cingulate cortex and hyperglutamatergic/hypoGABAergic alterations in the left cerebellum.
Tomomasa Terada, Maki Urushihara, Takahiko Saijo, Ryuji Nakagawa and Shoji Kagami : (Pro)renin and (pro)renin receptor expression during kidney development in neonates., European Journal of Pediatrics, Vol.176, No.2, 183-189, 2017.
(要約)
Although a recent study demonstrated that the (pro)renin receptor ((P)RR) was highly expressed in the developing kidney during the mouse embryonic development, the mechanism by which (P)RR supports renal development in humans is not fully understood. In this study, we examined the plasma levels of (pro)renin and soluble (P)RR (s(P)RR) in cord blood and neonates as well as (P)RR expression in human kidney tissues. Samples were collected from 57 preterm and 67 full-term human neonates. (Pro)renin and s(P)RR levels were measured using enzyme-linked immunosorbent assays. Additionally, we performed an immunohistochemical (IHC) analysis of kidney tissues from neonates and minor glomerular abnormalities in order to assess (P)RR expression in the kidney. Plasma (pro)renin and s(P)RR levels in cord blood were significantly higher in preterm neonates than in full-term neonates. Four weeks after birth, these differences were no longer evident for either plasma (pro)renin or s(P)RR levels between the two groups. Importantly, plasma (pro)renin and s(P)RR levels in cord blood were inversely correlated with gestational age. Furthermore, IHC indicated that renal expression levels of (P)RR in neonates were stronger than those in minor glomerular abnormalities. (P)RR may play a pivotal role in prenatal renal development in humans. What is Known: · Renal renin-angiotensin system (RAS) has several pathophysiologic functions not only in blood pressure regulation but also in pediatric renal disease. · Renal RAS activation plays a key role of renal development during gestation. What is New : · Plasma (pro)renin and soluble (pro)renin receptor (s(P)RR) levels in cord blood were significantly higher in preterm neonates than in full-term neonates. · Immunohistochemical analysis of kidney tissue indicated that renal expression levels of (P)RR in neonates were stronger than in minor glomerular abnormalities.
Aya Goji, Hiromichi Ito, Kenji Mori, Masafumi Harada, Sonoka Hisaoka, Yoshihiro Touda, Tatsuo Mori, Yoko Abe, Masahito Miyazaki and Shoji Kagami : Assessment of Anterior Cingulate Cortex (ACC) and Left Cerebellar Metabolism in Asperger's Syndrome with Proton Magnetic Resonance Spectroscopy (MRS)., PLoS ONE, No.1, e0169288, 2017.
(要約)
Proton magnetic resonance spectroscopy (1H MRS) is a noninvasive neuroimaging method to quantify biochemical metabolites in vivo and it can serve as a powerful tool to monitor neurobiochemical profiles in the brain. Asperger's syndrome (AS) is a type of autism spectrum disorder, which is characterized by impaired social skills and restrictive, repetitive patterns of interest and activities, while intellectual levels and language skills are relatively preserved. Despite clinical aspects have been well-characterized, neurometabolic profiling in the brain of AS remains to be clear. The present study used proton magnetic resonance spectroscopy (1H MRS) to investigate whether pediatric AS is associated with measurable neurometabolic abnormalities that can contribute new information on the neurobiological underpinnings of the disorder. Study participants consisted of 34 children with AS (2-12 years old; mean age 5.2 (±2.0); 28 boys) and 19 typically developed children (2-11 years old; mean age 5.6 (±2.6); 12 boys) who served as the normal control group. The 1H MRS data were obtained from two regions of interest: the anterior cingulate cortex (ACC) and left cerebellum. In the ACC, levels of N-acetylaspartate (NAA), total creatine (tCr), total choline-containing compounds (tCho) and myo-Inositol (mI) were significantly decreased in children with AS compared to controls. On the other hand, no significant group differences in any of the metabolites were found in the left cerebellum. Neither age nor sex accounted for the metabolic findings in the regions. The finding of decreased levels of NAA, tCr, tCho, and mI in the ACC but not in left cerebellar voxels in the AS, suggests a lower ACC neuronal density in the present AS cohort compared to controls.
Akemi Ono, Yasunobu Hayabuchi and Shoji Kagami : Coil occlusion of aberrant arteries to pulmonary sequestration in a case with pulmonary atresia with intact ventricular septum: successful treatment of repetitive myocardial ischaemic attacks, Cardiology in the Young, Vol.27, No.1, 193-195, 2017.
(要約)
In this study, we describe an infant case of pulmonary atresia with intact ventricular septum associated with ventriculo-coronary arterial communication for which a modified Blalock-Taussig shunt operation was performed. He experienced repeated myocardial ischaemic attacks. Further examination revealed pulmonary sequestration in the right lower lobe. He therefore underwent a bidirectional Glenn operation and coil occlusion of the feeding arteries. His myocardial ischaemic attacks subsequently improved.
Miki Watanabe, Ryuji Nakagawa, Tomohiro Kohmoto, Takuya Naruto, Ken-ichi Suga, Aya Goji, Hideaki Horikawa, Kiyoshi Masuda, Shoji Kagami and Issei Imoto : Exome-first approach identified a novel gloss deletion associated with Lowe syndrome., Human Genome Variation, Vol.3, 16037, 2016.
(要約)
Lowe syndrome (LS) is an X-linked disorder affecting the eyes, nervous system and kidneys, typically caused by missense or nonsense/frameshift OCRL mutations. We report a 6-month-old male clinically suspected to have LS, but without the Fanconi-type renal dysfunction. Using a targeted-exome sequencing-first approach, LS was diagnosed by the identification of a deletion involving 1.7 Mb at Xq25-q26.1, encompassing the entire OCRL gene and neighboring loci.
T Nagai, Maki Urushihara, Yukiko Kinoshita, A Jamba, Shuji Kondo and Shoji Kagami : Differential regulation of angiotensin II-induced extracellular regulated kiase-1/2 and -5 in progressive glomerulonephritis., Nephrology, Vol.21, No.11, 950-958, 2016.
(要約)
Extracellular signal regulated kinase (ERK)1/2 and ERK5 are key kinases of the signalling pathways involved in various cellular responses to kidney injury; however, the mechanistic links between those kinase and renin-angiotensin system (RAS) activations in glomerulonephritis (GN) have not been fully elucidated. In this study, we sought to clarify the potential roles of ERK1/2 and ERK5 via RAS activation in the pathogenesis of GN. A rat model of progressive GN was induced by anti-glomerular basement membrane (GBM) injection and the signal transduction pathway in angiotensin II (Ang II)-induced glomerular pathologic alterations were investigated in primary cultured mesangial cells (MCs). Rats developed typical cellular crescents in glomeruli on day 7 that progressed to severe fibrocellular crescents and glomerulosclerosis on day 28. Strong expression of phospho-ERK1/2 was observed on day 7 and phospho-ERK5 expression was markedly increased on day 28 of GN. An angiotensin II type 1 receptor blocker (ARB) suppressed those augmentations. Moreover, ARB treatment attenuated the increases in macrophage infiltration and PCNA-positive cells observed on day 7 in GN rats, as well as the increase in collagen type 1 expression on day 28. Consistently, MCs stimulated by Ang II showed significant increases in proliferation and the expression of MCP-1 and collagen type 1. Interestingly, while the ERK1/2 inhibitor PD98059 abolished the elevations in MCP-1 expression and cell proliferation, the ERK5 inhibitor BIX02189 abrogated the elevation in collagen type 1 expression. Altogether, these data suggest that ERK1/2 regulates acute inflammatory reactions, while ERK5 promotes the development of RAS-induced chronic glomerular fibrosis activation in GN.
(キーワード)
Angiotensin II / Angiotensin II Type 1 Receptor Blockers / Animals / Disease Models, Animal / Fibrosis / Glomerular Mesangium / Glomerulonephritis / Inflammation / Mitogen-Activated Protein Kinase 3 / Rats / Renin-Angiotensin System / Signal Transduction
Kazumi Okamura, Akiko Kitamura, Yoshiteru Sasaki, Hyun Doo Chung, Shoji Kagami, Kazuhiro Iwai and Koji Yasutomo : Survival of mature T cells depends on signaling through HOIP., Scientific Reports, Vol.6, 36135, 2016.
(要約)
T cell development in the thymus is controlled by a multistep process. The NF-B pathway regulates T cell development as well as T cell activation at multiple differentiation stages. The linear ubiquitin chain assembly complex (LUBAC) is composed of Sharpin, HOIL-1L and HOIP, and it is crucial for regulating the NF-B and cell death pathways. However, little is known about the roles of LUBAC in T-cell development and activation. Here, we show that in T-HOIP(linear) mice lacking the ubiquitin ligase activity of LUBAC, thymic CD4(+) or CD8(+) T cell numbers were markedly reduced with severe defects in NKT cell development. HOIP(linear) CD4(+) T cells failed to phosphorylate IB and JNK through T cell receptor-mediated stimulation. Mature CD4(+) and CD8(+) T cells in T-HOIP(linear) mice underwent apoptosis more rapidly than control T cells, and it was accompanied by lower CD127 expression on CD4(+)CD24(low) and CD8(+)CD24(low) T cells in the thymus. The enforced expression of CD127 in T-HOIP(linear) thymocytes rescued the development of mature CD8(+) T cells. Collectively, our results showed that LUBAC ligase activity is key for the survival of mature T cells, and suggest multiple roles of the NF-B and cell death pathways in activating or maintaining T cell-mediated adaptive immune responses.
Miki Watanabe, Ryuji Nakagawa, Takuya Naruto, Tomohiro Kohmoto, Ken-ichi Suga, Aya Goji, Shoji Kagami, Kiyoshi Masuda and Issei Imoto : A novel missense mutation of COL5A2 in a patient with Ehlers-Danlos syndrome., Human Genome Variation, Vol.3, 16030, 2016.
(要約)
Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders characterized by hyperextensible skin, joint hypermobility and soft tissue fragility. For molecular diagnosis, targeted exome sequencing was performed on a 9-year-old male patient who was clinically suspected to have EDS. The patient presented with progressive kyphoscoliosis, joint hypermobility and hyperextensible skin without scars. Ultimately, classical EDS was diagnosed by identifying a novel, mono-allelic mutation in COL5A2 [NM_000393.3(COL5A2_v001):c.682G>A, p.Gly228Arg].
Yasunobu Hayabuchi, Ono Akemi, Homma Yukako and Shoji Kagami : Noninvasive assessment of pulmonary arterial capacitance by pulmonary annular motion velocity in children with ventricular septal defect., Cardiovascular Ultrasound, Vol.14, No.1, 38, 2016.
(要約)
We hypothesized that longitudinal pulmonary arterial deformation during the cardiac cycle reflects pulmonary arterial capacitance. To examine this hypothesis, we assessed whether tissue Doppler-derived pulmonary annular motion could serve as a novel way to evaluate pulmonary arterial capacitance in pediatric patients with ventricular septal defect (VSD). In this prospective study, pulmonary annular velocity was measured in children (age, 6 months-5 years) with a preoperative VSD (VSD group, n = 35) and age-matched healthy children (Control group, n = 23). Pulmonary artery capacitance was calculated by two methods. Systolic pulmonary arterial capacitance (sPAC) was expressed as the stroke volume/pulmonary arterial pulse pressure. Diastolic pulmonary arterial capacitance (dPAC) was determined according to a two-element windkessel model of the pulmonary arterial diastolic pressure profile. Pulmonary annular velocity waveforms comprised systolic bimodal (s1' and s2') and diastolic e' and a' waves in all participants. The peak velocities of s1', s2', and e' were significantly lower in the VSD group than in the Control group. On multiple regression analysis, sPAC was an independent variable affecting the peak velocities of the s1', s2', and e' waves (β = 0.41, 0.62, and 0.35, respectively). The dPAC affected the s1' wave peak velocity (β = 0.34). The time durations of the s1' and e' waves were independently determined by the sPAC (β = 0.49 and 0.27). Pulmonary annular motion velocity evaluated using tissue Doppler is a promising method of assessing pulmonary arterial capacitance in children with VSD.
Maki Urushihara and Shoji Kagami : Role of the intrarenal renin-angiotensin system in the progression of renal disease., Pediatric Nephrology, Vol.32, No.9, 1471-1479, 2016.
(要約)
The intrarenal renin-angiotensin system (RAS) has many well-documented pathophysiologic functions in both blood pressure regulation and renal disease development. Angiotensin II (Ang II) is the major bioactive product of the RAS. It induces inflammation, renal cell growth, mitogenesis, apoptosis, migration, and differentiation. In addition, Ang II regulates the gene expression of bioactive substances and activates multiple intracellular signaling pathways that are involved in renal damage. Activation of the Ang II type 1 (AT1) receptor pathway results in the production of proinflammatory mediators, intracellular formation of reactive oxygen species, cell proliferation, and extracellular matrix synthesis, which in turn facilities renal injury. Involvement of angiotensinogen (AGT) in intrarenal RAS activation and development of renal disease has previously been reported. Moreover, studies have demonstrated that the urinary excretion rates of AGT provide a specific index of the intrarenal RAS status. Enhanced intrarenal AGT levels have been observed in experimental models of renal disease, supporting the concept that AGT plays an important role in the development and progression of renal disease. In this review, we focus on the role of intrarenal RAS activation in the pathophysiology of renal disease. Additionally, we explored the potential of urinary AGT as a novel biomarker of intrarenal RAS status in renal disease.
Miki Watanabe, Yasunobu Hayabuchi, Akemi Ono, Takuya Naruto, Hideaki Horikawa, Kiyoshi Masuda, Tomohiro Kohmoto, Ryuji Nakagawa, Hiromichi Ito, Shoji Kagami and Issei Imoto : Detection of 1p36 deletion by clinical exome-first diagnostic approach., Human Genome Variation, Vol.3, 16006, 2016.
(要約)
Although chromosome 1p36 deletion syndrome is considered clinically recognizable based on characteristic features, the clinical manifestations of patients during infancy are often not consistent with those observed later in life. We report a 4-month-old girl who showed multiple congenital anomalies and developmental delay, but no clinical signs of syndromic disease caused by a terminal deletion in 1p36.32-p36.33 that was first identified by targeted-exome sequencing for molecular diagnosis.
Tomohiro Kohmoto, Miki Shono, Takuya Naruto, Miki Watanabe, Ken-ichi Suga, Ryuji Nakagawa, Shoji Kagami, Kiyoshi Masuda and Issei Imoto : A novel frameshift mutation of CHD7 in a Japanese patient with CHARGE syndrome., Human Genome Variation, Vol.3, No.7, 16004, 2016.
(要約)
CHARGE syndrome is a rare autosomal dominant developmental disorder involving multiple organs. CHD7 is a major causative gene of CHARGE syndrome. We performed targeted-exome sequencing using a next-generation sequencer for molecular diagnosis of a 4-month-old male patient who was clinically suspected to have CHARGE syndrome, and report a novel monoallelic mutation in CHD7, NM_017780.3(CHD7_v001):c.2966del causing a reading frameshift [p.(Cys989Serfs*3)].
Mayumi Sugimoto, Norio Kamemura, Mizuho Nagao, Makoto Irahara, Shoji Kagami, Takao Fujisawa and Hiroshi Kido : Differential response in allergen-specific IgE, IgGs and IgA levels for predicting outcome of oral immunotherapy., Pediatric Allergy and Immunology, Vol.27, No.3, 276-282, 2016.
(要約)
The response to OIT was associated with significant increases in serum allergen-specific IgG1 levels after rush phase and high baseline IgA levels, compared with small changes in immunoglobulin response in low-responders. The characteristic IgG1 changes and IgA levels in the responders could be potentially useful biomarkers for the prediction of positive clinical response to OIT. This article is protected by copyright. All rights reserved.
Naoto Okada, Hiroyoshi Watanabe, Shoji Kagami and Keisuke Ishizawa : Ifosfamide and etoposide chemotherapy may interact with warfarin, enhancing the warfarin-induced anticoagulant response, International Journal of Clinical Pharmacology and Therapeutics, Vol.54, No.1, 58-61, 2015.
(要約)
To report a case of warfarin-response enhancement during administration of ifosfamide and etoposide chemotherapy. A 15-yearold boy with rhabdomyosarcoma was treated with a regimen of alternating cycles of vincristine, doxorubicin, and cyclophosphamide (VDC) chemotherapy and ifosfamide and etoposide (IE) chemotherapy. During VDC chemotherapy, occlusion of the left middle cerebral artery occurred, and warfarin was started. On day 3 of IE chemotherapy, the patient's international normalized ratio (INR) transiently increased from baseline 2.61 to 5.45. The INR returned to normal within 3 days after warfarin discontinuation. An increase in INR was observed between days 1 and 3 of subsequent cycles of IE chemotherapy but not during VDC chemotherapy. This INR increase was also observed during concomitant use of aprepitant, an inducer of the CYP2C9. There are no reports describing the interaction between warfarin and IE chemotherapy because coadministration of warfarin and IE chemotherapy is unusual. The Drug Interaction Probability Scale score of this interaction was 7, and it is probable that the enhancement of the warfarin response was caused by an interaction with IE chemotherapy. Moreover, in the present case, the enhancement of warfarin response was observed during concomitant use of aprepitant, which has been reported to weaken the warfarin response. Therefore, this interaction may be quite powerful and may increase the risk of warfarin toxicity. A patient who was administered both warfarin and IE chemotherapy experienced a rapid increase in INR, suggesting that INR should be closely monitored in patients receiving warfarin with IE chemotherapy.
(キーワード)
Adolescent / Anticoagulants / Cytochrome P-450 CYP2C9 Inhibitors / Drug Interactions / Etoposide / Humans / Ifosfamide / International Normalized Ratio / Male / Rhabdomyosarcoma / Warfarin
Yasunobu Hayabuchi, Ono Akemi and Shoji Kagami : Pulmonary annular motion velocity assessed using Doppler tissue imaging - Novel echocardiographic evaluation of right ventricular outflow tract function-, Circulation Journal, Vol.80, No.1, 168-176, 2015.
(要約)
We assessed whether measuring pulmonary annular motion velocity could serve as a novel method of evaluating right ventricular outflow tract (RVOT) performance in pediatric patients with heart disease. Tissue Doppler-derived pulmonary annular motion velocity was determined from the parasternal long-axis view of the RVOT. Pulmonary annular velocity was measured in children (age, 5-10 years) with an atrial septal defect (ASD), pulmonary arterial hypertension (PAH), surgically repaired tetralogy of Fallot (TOF) and healthy children (control). Pulmonary annular velocity waveforms comprised systolic bimodal (s1' and s2') and diastolic e' and a' waves in all groups. The peak velocity of s1' and s2' was significantly higher in the ASD group than in the controls (15.0±2.4 vs. 11.2±2.1 and 6.0±0.9 vs. 4.4±1.2 cm/s; P<0.01 and P<0.001, respectively). The s1' and s2' peak velocities were significantly lower in the PAH group (8.5±1.2 and 3.2±0.4 cm/s; P<0.05 for both), and in the group with TOF (5.3±2.2 and 3.4±1.4 cm/s; P<0.001 and P<0.05, respectively). The peak velocity of e' was significantly decreased in the PAH and TOF, compared with the control group (6.8±1.6 and 8.2±2.9 vs. 11.9±1.9 cm/s; P<0.001 for both). Pulmonary annular motion velocity determined using tissue Doppler imaging is a promising method of assessing RVOT function. (Circ J 2016; 80: 168-176).
Yasunobu Hayabuchi, Miho Sakata and Shoji Kagami : Right ventricular myocardial deformation patterns in children with congenital heart disease associated with right ventricular pressure overload., European Heart Journal Cardiovascular Imaging, Vol.16, No.8, 890-899, 2015.
(要約)
Longitudinal wall motion of the right ventricle (RV) has been thoroughly studied in patients with RV dysfunction. However, circumferential strain of the RV free wall has yet to be investigated. Therefore, this study was conducted to assess the utility of RV free wall circumferential strain. Strain profile curves were obtained using speckle tracking echocardiography from the subcostal left ventricular (LV) short-axis view in 30 normal children (normal group) and 25 patients with RV pressure overload (RVO group). The time-strain curves of three individual segmental (anterior, lateral, and inferior segments) and global circumferential deformations were evaluated. RV ejection fraction (RVEF), RV systolic pressure (RVSP), and RV fractional area change obtained in the four-chamber view and LV short-axis view [RVFAC (4CH) and RVFAC (SAX), respectively] were measured, and their relationships with RV free wall deformation were assessed. In the normal group, circumferential strain was significantly lower in the anterior segment than in the other segments. The inferior segment had a significantly larger strain than the other segments in the RVO group. Circumferential strain was predominant over longitudinal RV free wall strain in the RVO group (-18.4 ± 3.9 vs. -14.2 ± 3.8%, respectively; P < 0.005), whereas no significant difference between them was observed in the normal group (-23.0 ± 3.9 vs. -22.4 ± 4.7%, respectively). Global circumferential strain had a significantly higher correlation with RVFAC (4CH), RVFAC (SAX), RVEF, and RVSP than global longitudinal strain (P < 0.05 for all). RV free wall circumferential strain provides better information about RV function than longitudinal strain in children with RVO.
Yasunobu Hayabuchi, Miho Sakata and Shoji Kagami : Bronchogenic cyst compressing the pulmonary artery and the left atrium., European Heart Journal Cardiovascular Imaging, Vol.16, No.7, 746, 2015.
Maki Urushihara, T Nagai, Yukiko Kinoshita, S Nishiyama, Ken-ichi Suga, N Ozaki, A Jamba, Shuji Kondo, H Kobori and Shoji Kagami : Changes in urinary angiotensinogen posttreatment in pediatric IgA nephropathy patients., Pediatric Nephrology, Vol.30, No.6, 975-982, 2015.
(要約)
Recently, we demonstrated that urinary angiotensinogen (AGT) levels are increased and reflect intrarenal renin-angiotensin system (RAS) status in pediatric patients with chronic glomerulonephritis. Therefore, this study was performed to test the hypothesis that urinary AGT (UAGT) levels provide a specific index of intrarenal RAS status associated with RAS blockade treatment in pediatric IgA nephropathy (IgAN) patients. We measured plasma and UAGT levels and urinary transforming growth factor beta (TGF-β) levels, after which we performed immunohistochemical analysis of AGT, angiotensin II (Ang II), and TGF-β in 24 pediatric IgAN patients treated with RAS blockades for 2 years. Paired tests were used to analyze the changes from baseline to study end. Although there was no change in plasma AGT levels, UAGT and TGF-β levels were significantly decreased after RAS blockade, which was accompanied by the expression levels of AGT, Ang II, and TGF-β, as well as the magnitude of glomerular injury. Baseline UAGT levels positively correlated with diastolic blood pressure, urinary protein levels, scores for mesangial hypercellularity, and the expression levels of AGT, Ang II, and TGF-β in renal tissues. These data indicate that UAGT is a useful biomarker of intrarenal RAS activation, which is associated with glomerular injury during RAS blockade in pediatric IgAN patients.
(キーワード)
Adolescent / Angiotensin II / Angiotensin II Type 1 Receptor Blockers / Angiotensin-Converting Enzyme Inhibitors / Angiotensinogen / Biomarkers / Biopsy / Child / Enzyme-Linked Immunosorbent Assay / Female / Glomerulonephritis, IGA / Humans / Immunohistochemistry / Kidney / Male / Predictive Value of Tests / Renin-Angiotensin System / Time Factors / Transforming Growth Factor beta / Treatment Outcome / Urinalysis
Hydrogen peroxide-inducible clone-5 (Hic-5) is a transforming growth factor (TGF)-β1-inducible focal adhesion protein. We previously demonstrated that Hic-5 was localized in mesangial cells and its expression was associated with glomerular cell proliferation and matrix expansion in human and rat glomerulonephritis (GN). In the present study, we first assessed the role of Hic-5 in mesangioproliferative GN by injecting Habu venom into heminephrectomized wild type (Hic-5+/+) and Hic-5-deficient (Hic-5-/-) mice. Hic-5+/+ GN mice exhibited glomerular cell proliferation on day 7. Surprisingly, glomerular cell number and Ki-67-positive cells in Hic-5-/- GN mice were significantly greater than those in Hic-5+/+ GN mice on day 7, although the number of glomerular apoptotic cells and the expression of growth factors (platelet-derived growth factor-BB and TGF-β1) and their receptors were similarly increased in both Hic-5+/+ and Hic-5-/- GN mice. In culture experiments, proliferation assays showed that platelet-derived growth factor-BB and TGF-β1 enhanced the proliferation of Hic-5-/- mesangial cells compared with Hic-5+/+ mesangial cells. In addition, mitogenic regulation by Hic-5 was associated with altered and coordinated expression of cell cycle-related proteins including cyclin D1 and p21. The present results suggest that Hic-5 might regulate mesangial cell proliferation in proliferative GN in mice. In conclusion, modulation of Hic-5 expression might have a potential to prevent mesangial cell proliferation in the acute mitogenic phase of glomerulonephritis.
Nami Inoue, Hiroyoshi Watanabe, Kazumi Okamura, Shuji Kondo and Shoji Kagami : Are the equations for the creatinine-based estimated glomerular filtration rate applicable to the evaluation of renal function in Japanese children and adult patients receiving chemotherapy?, Clinical and Experimental Nephrology, Vol.19, No.2, 298-308, 2015.
(要約)
Equations for the creatinine-based estimated glomerular filtration rate (eGFR) were recently established for Japanese adults (>18 years old) and children (2-11 years old), respectively, but it is unclear whether eGFR can be as useful as 24-h creatinine clearance (CCr) for assessing renal function in patients receiving chemotherapy. This study examined the degree of concordance between eGFR and CCr and the risk factors leading to the overestimation of renal function by eGFR. A total of 53 data points of 19 children and 56 data points of 16 adults who received chemotherapy were analyzed retrospectively. Body mass index, serum creatinine concentration, 24-h urinary creatinine excretion (UCr), and nephrectomy were considered as risk factors for overestimation by eGFR. In the pediatric part of the study, 7 data points from 3 patients who underwent nephrectomy were included. The eGFR in patients with bilateral kidneys overestimated renal function to a greater degree than in patients with a unilateral kidney. In 45.7 % of pediatric patients with bilateral kidneys and in 19.6 % of adult patients, eGFR overestimated renal function. The risk factor for overestimation was lower UCr in pediatric patients with bilateral kidneys and adult patients. Concordance between eGFR and CCr in pediatric patients with a unilateral kidney should be assessed separately from that in patients with bilateral kidneys. In restricting calculation of eGFR to pediatric patients with bilateral kidneys and adult patients without little muscle mass, eGFR may be useful regardless of whether patients are receiving chemotherapy.
(キーワード)
Adult / Antineoplastic Agents / Area Under Curve / Body Mass Index / Child / Child, Preschool / Creatinine / Female / Glomerular Filtration Rate / Humans / Japan / Lactones / Male / Mathematical Concepts / Neoplasms / Nephrectomy / ROC Curve / Retrospective Studies / Risk Factors / Young Adult
M Suzue, Maki Urushihara, Ryuji Nakagawa, T Saijo and Shoji Kagami : Urinary angiotensinogen level is increased in preterm neonates., Clinical and Experimental Nephrology, Vol.19, No.2, 293-297, 2015.
(要約)
All components of the renin-angiotensin system (RAS) are abundantly synthesized in the developing kidney, suggesting that the RAS plays an important role in renal development. To examine this system in human neonates, we measured urinary angiotensinogen levels in preterm and full-term neonates and examined the relationship between urinary angiotensinogen levels and gestational age. Urine and plasma samples were collected from 20 preterm and 18 full-term neonates at birth. Angiotensinogen levels were measured using enzyme-linked immunosorbent assay. Plasma angiotensinogen concentrations were not increased in preterm neonates compared with that in full-term neonates (P = 0.7288). However, the urinary angiotensinogen-to-creatinine ratio was significantly higher in preterm neonates compared with that in full-term neonates (P = 0.0011). Importantly, the urinary angiotensinogen-to-creatinine ratio dropped significantly with increasing gestational age (P = 0.0010), whereas the plasma angiotensinogen concentration was not correlated with gestational age (P = 0.7814). These results suggest that urinary angiotensinogen levels may indicate the involvement of intrarenal RAS activation in prenatal renal development.
(キーワード)
Angiotensinogen / Biomarkers / Case-Control Studies / Creatinine / Gestational Age / Humans / Infant, Newborn / Premature Birth / Renin-Angiotensin System / Term Birth
Yasunobu Hayabuchi, Miho Sakata and Shoji Kagami : Assessment of the Helical Ventricular Myocardial Band Using Standard Echocardiography, Echocardiography, Vol.32, No.2, 310-318, 2015.
(要約)
The purpose of this study was to assess the feasibility of morphological and functional evaluation of the helical ventricular myocardial band using standard echocardiographic images. Echocardiographic data were obtained from 132 normal children. We attempted to identify the echogenic bright line serving as the boundary between the ascending and descending segments in the ventricular septum, and between the left and ascending segments in the left ventricular inferior wall in the helical myocardial band model proposed by Torrent-Guasp. Myocardial deformations on both sides of the bright line were compared using speckle tracking echocardiography. The bright line separating the ascending from descending segment was visible in the mid-ventricular septum in the four-chamber view in all subjects. This echogenic boundary was observed obliquely in the parasternal short-axis view in 116 subjects (87.9%). There was no significant difference in peak longitudinal or circumferential strain between the ascending and descending segments. However, the time from the QRS onset to peak circumferential strain was significantly lower in the descending than ascending segment (394.5 ± 37.0 vs. 432.7 ± 33.1 ms, P < 0.0001), whereas there was no significant difference in the time to peak longitudinal strain (394.4 ± 26.4 vs. 393.2 ± 24.1 ms). The bright line between the left and ascending segment was detected in the short-axis view from the subcostal region in 86 subjects (65.2%). The time to peak circumferential strain was significantly lower in the left than ascending segment (380.1 ± 32.0 vs. 435.7 ± 37.9 ms, P < 0.0001). There is a helical ventricular myocardial band that can be observed in standard echocardiographic images.
Yasunobu Hayabuchi, Miho Sakata and Shoji Kagami : Fibromyxoid excrescence of the aortic valve that manifested after catheterisation and required resection., Cardiology in the Young, Vol.25, No.2, 362-364, 2015.
(要約)
A 2-year-old boy developed fibromyxoid excrescence of the aortic valve 2 years after balloon dilatation for simple coarctation. Transthoracic echocardiography showed a mobile mass on the non-coronary cusp of the aortic valve. Definitive diagnosis was achieved after operative resection. This pathology was attributed to injury during catheter manipulation. Catheterised patients should be followed up carefully to avoid missing morphological changes.
Kenji Mori, Yoshihiro Touda, Hiromichi Ito, Tatsuo Mori, Keiko Mori, Aya Goji, Hiroko Hashimoto, Hiroe Tani, Masahito Miyazaki, Masafumi Harada and Shoji Kagami : Neuroimaging in autism spectrum disorders: 1H-MRS and NIRS study, The Journal of Medical Investigation : JMI, Vol.62, No.1-2, 29-36, 2015.
(要約)
Using proton magnetic resonance spectroscopy ((1)H-MRS), we measured chemical metabolites in the left amygdala and the bilateral orbito-frontal cortex (OFC) in children with autism spectrum disorders (ASD). The concentrations of N-acetylaspartate (NAA) in these regions of ASD were significantly decreased compared to those in the control group. In the autistic patients, the NAA concentrations in these regions correlated with their social quotient. These findings suggest the presence of neuronal dysfunction in the amygdala and OFC in ASD. Dysfunction in the amygdala and OFC may contribute to the pathogenesis of ASD. We performed a near-infrared spectroscopy (NIRS) study to evaluate the mirror neuron system in children with ASD. The concentrations of oxygenated hemoglobin (oxy-Hb) were measured with frontal probes using a 34-channel NIRS machine while the subjects imitated emotional facial expressions. The increments in the concentration of oxy-Hb in the pars opercularis of the inferior frontal gyrus in autistic subjects were significantly lower than those in the controls. However, the concentrations of oxy-Hb in this area were significantly elevated in autistic subjects after they were trained to imitate emotional facial expressions. The results suggest that mirror neurons could be activated by repeated imitation in children with ASD.
Yasunobu Hayabuchi, Miho Sakata and Shoji Kagami : Assessment of Two-Component Ventricular Septum: Functional Differences in Systolic Deformation and Rotation Assessed by Speckle Tracking Imaging., Echocardiography, Vol.31, No.7, 815-823, 2014.
(要約)
The purpose of this study was to elucidate functional differences in the right and left components of the ventricular septum (Rt and Lt, respectively). Strain, strain rate, rotation, and rotation rate profile curves of Rt and Lt were obtained using speckle tracking echocardiography in 38 normal children and adolescents. The echogenic bright line serving as the boundary separating Rt from Lt was consistently visible in the middle of the ventricular septum. There was no significant difference in peak strain or peak strain rate during systole between Rt and Lt. However, the time interval from the onset of QRS-wave to peak strain and peak strain rate were significantly lower in Lt than in Rt in terms of radial and circumferential deformation (P < 0.005, all), whereas there was no significant difference in longitudinal deformation in the time to peak strain or peak strain rate between Rt and Lt. Lt showed counterclockwise rotation, whereas Rt showed clockwise rotation (10.4 ± 2.9° vs. -10.2 ± 2.6°, P < 0.0001). Time to peak rotation was significantly lower in Lt than in Rt (201.7 ± 32.7 msec vs. 370.4 ± 31.2 msec, P < 0.0001). Morphologically and functionally the ventricular septum is a two-component structure. Evaluation of deformation and rotation of the 2 components would help in evaluating septal performance.
Akemi Ono, Yasunobu Hayabuchi, Miho Sakata, Yuko Ichihara, Shoji Kagami and Kazuhiro Mori : Right ventricular thrombosis in two patients with pulmonary atresia with intact ventricular septum, Journal of Echocardiography, Vol.12, No.2, 62-64, 2014.
Yasunobu Hayabuchi, Miho Sakata, Miki Inoue, Kazuhiro Mori and Shoji Kagami : Echocardiographic assessment of anomalous origin of the left coronary artery from the pulmonary artery, Journal of Echocardiography, Vol.12, No.2, 60-61, 2014.
Tatsuo Mori, Kenji Mori, Hiromichi Ito, Aya Goji, Masahito Miyazaki, Masafumi Harada, Kenji Kurosawa and Shoji Kagami : Age-related changes in a patient with Pelizaeus-Merzbacher disease determined by repeated 1H-magnetic resonance spectroscopy., Journal of Child Neurology, Vol.29, No.2, 283-288, 2014.
(要約)
A boy with Pelizaeus-Merzbacher disease underwent repeated evaluations by 3-Tesla (1)H-magnetic resonance spectroscopy (MRS). The patient showed overlap of the PLP1. Individuals selected as normal controls for (1)H-magnetic resonance spectroscopy consisted of healthy age-matched children. For (1)H-magnetic resonance spectroscopy, the center of a voxel was positioned in the right parietal lobe. (1)H-magnetic resonance spectroscopy was performed when the patient was 2, 6, 14, and 25 months old. γ-Aminobutyric acid concentration in early childhood was increased compared with that in normal controls. However, the γ-aminobutyric acid concentration in the Pelizaeus-Merzbacher disease patient was normalized at 14 and 25 months. No remarkable changes were observed in choline-containing compounds concentration at any time. These results suggest that the changes in metabolite concentrations during growth can reflect the pathological condition of Pelizaeus-Merzbacher disease. Furthermore, the lack of change in the choline-containing compounds concentration can be useful for differentiating Pelizaeus-Merzbacher disease from other white matter disorders.
Diabetic nephropathy (DN) is the major cause of end-stage renal failure. Oxidative stress is implicated in the pathogenesis of DN. Nitrosonifedipine (NO-NIF) is a weak calcium channel blocker that is converted from nifedipine under light exposure. Recently, we reported that NO-NIF has potential as a novel antioxidant with radical scavenging abilities and has the capacity to treat vascular dysfunction by exerting an endothelial protective effect. In the present study, we extended these findings by evaluating the efficacy of NO-NIF against DN and by clarifying the mechanisms of its antioxidative effect. In a model of type 2 DN (established in KKAy mice), NO-NIF administration reduced albuminuria and proteinuria as well as glomerular expansion without affecting glucose metabolism or systolic blood pressure. NO-NIF also suppressed renal and systemic oxidative stress and decreased the expression of intercellular adhesion molecule (ICAM)-1, a marker of endothelial cell injury, in the glomeruli of the KKAy mice. Similarly, NO-NIF reduced albuminuria, oxidative stress, and ICAM-1 expression in endothelial nitric oxide synthase (eNOS) knockout mice. Moreover, NO-NIF suppressed urinary angiotensinogen (AGT) excretion and intrarenal AGT protein expression in proximal tubular cells in the KKAy mice. On the other hand, hyperglycemia-induced mitochondrial superoxide production was not attenuated by NO-NIF in cultured endothelial cells. These findings suggest that NO-NIF prevents the progression of type 2 DN associated with endothelial dysfunction through selective antioxidative effects.
(キーワード)
Animals / Antioxidants / Cell Line / Diabetic Nephropathies / Humans / Male / Mice / Mice, Inbred C57BL / ノックアウトマウス (knockout mice) / Nifedipine / Nitric Oxide Synthase Type III / Nitroso Compounds / 酸化ストレス (oxidative stress)
Maki Urushihara, Yusuke Seki, Takahiro Tayama, Takashi Nagai, Yukiko Kinoshita, Ariunbold Jamba, Shuji Kondo and Shoji Kagami : Glomerular angiotensin-converting enzyme 2 in pediatric IgA nephropathy, American Journal of Nephrology, Vol.38, No.5, 355-367, 2013.
(要約)
Angiotensin-converting enzyme (ACE) 2 is a homolog of ACE and is thought to be a potent counter-regulator against ACE activity. However, the role of ACE2 has not been investigated in pediatric patients with IgA nephropathy (IgAN). This study was performed to examine the relationship between ACE2 expression and the development of pediatric IgAN. We performed immunohistochemical analysis of ACE2 and ACE in 39 patients with pediatric IgAN and 14 patients with minor glomerular abnormalities, and elucidated the effects of various cytokines on ACE2 expression in cultured human mesangial cells. ACE2 expression levels in glomeruli and tubules were positively correlated with the mesangial hypercellularity score, while ACE expression levels in glomeruli and tubules are not. Multiple regression analysis showed that the mesangial hypercellularity score correlated with the ACE2 expression level in glomeruli and the urinary protein-creatinine ratio. In IgAN patients not treated with a renin-angiotensin system blocker, ACE2 expression levels in glomeruli were significantly increased compared to patients with minor glomerular abnormalities. IgAN patients treated with a renin-angiotensin system blocker did not show this increase in ACE2 expression. Furthermore, cultured human MC showed increased ACE2 mRNA and protein after treatment with IL-1β, a pro-inflammatory cytokine in IgAN. In fact, glomerular expressions of IL-1β were remarkably increased in patients with IgAN. These data indicate that ACE2 expression in glomeruli is associated with mesangial hypercellularity in early lesions of pediatric IgAN.
Tatsuo Mori, Kenji Mori, Masashi Suzue, Hiromichi Ito and Shoji Kagami : Effective treatment of a 13-year-old boy with steroid-dependent ocular myasthenia gravis using tacrolimus, Brain & Development, Vol.35, No.5, 445-448, 2013.
(要約)
Over the past several years, tacrolimus has attracted attention as a new therapeutic drug for myasthenia gravis (MG), but few reports have considered its use for MG in pediatric patients, and most of these have focused on severe systemic MG. In this case report, we used tacrolimus to successfully treat a 13-year-old boy with ocular MG who had suffered from severe steroid complications, including a failure of thrive and osteoporosis. He first showed symptoms of ocular MG at age 2 years 3 months. At age 13 years, he was receiving PSL (3.75 mg/day), but the symptoms of ocular MG recurred. We increased the dosage of oral PSL up to 30 mg/day, and three courses of mPSL pulse therapy were applied, but these therapies had only limited effect, and his symptoms worsened. Tacrolimus was started at 0.4 mg/day (0.011 mg/kg/day), and every 2 weeks the dose was gradually increased by 0.2 mg/day. His symptoms of MG began to improve 3 weeks after the initial administration of tacrolimus. Approximately 3 months after the start of tacrolimus administration, PSL was discontinued. Currently, at 1 year and 4 months after the start of tacrolimus administration, while slight ptosis is observed in the evening, it does not influence his daily life, and his condition remains comparable to that when he stopped taking PSL. No adverse effects of tacrolimus have been recognized. In pediatric patients with steroid-dependent ocular MG without thymectomy, tacrolimus may be a safe and effective alternative to steroid and thymectomy.
Yasunobu Hayabuchi, Miho Sakata, Tatsuya Ohnishi, Inoue Miki and Shoji Kagami : Ratio of early diastolic tricuspid inflow to tricuspid lateral annulus velocity reflects pulmonary regurgitation severity but not right ventricular diastolic function in children with reparied terralogy of Fallot, Pediatric Cardiology, Vol.34, No.5, 1112-1117, 2013.
(要約)
The current study assessed relationships between the ratio of early diastolic tricuspid inflow to tricuspid lateral annular velocity (tricuspid E/e') and right ventricular (RV) function in children after tetralogy of Fallot (TOF) repair. The RV function of 25 asymptomatic children with surgically repaired TOF (age 3.3 ± 2.0 years) was assessed by echocardiography and cardiac catheterization. Right ventricular end-diastolic pressure and volume (RVEDP and RVEDV), systolic pressure, and ejection fraction, as well as mean pulmonary arterial pressure, mean right atrial pressure (RAP), and the severity of both pulmonary regurgitation (PR) and tricuspid regurgitation (TR) were assessed in terms of the contribution to tricuspid E/e'. Univariate analysis discovered a relationship between tricuspid E/e' and RVEDV (R(2) = 0172), pressure half-time of PR (PR-PHT) (R(2) = 0.173), and TR grade (R(2) = 0.145) (p < 0.01 for each). After multivariate adjustment, PR-PHT was significantly associated with tricuspid E/e' (β = 0.210; p < 0.001). Tricuspid E/e' was not significantly associated with RVEDP or RAP. In conclusion, tricuspid E/e' does not indicate RV diastolic function but reflects the severity of PR in asymptomatic children after TOF repair.
(キーワード)
Blood Flow Velocity / Cardiac Catheterization / Child / Child, Preschool / Diastole / Echocardiography / Female / Heart Function Tests / Humans / Infant / Male / Pulmonary Valve Insufficiency / Severity of Illness Index / Tetralogy of Fallot / Tricuspid Valve
H Sugiyama, H Yokoyama, H Sato, T Saito, Y Kohda, S Nishi, K Tsuruya, H Kiyomoto, H Iida, T Sakaki, M Higuchi, M Hattori, K Oka, Shoji Kagami, T Kawamura, T Takeda, H Hataya, Y Fukusawa, A Fukatsu, K Morozumi, N Yoshikawa, A Shimizu, H Kitamura, Y Yuzawa, S Matsuo, Y Kiyohara, K Joh, M Nagata, T Tagushi and H Makino : Committee for standardization of renal Pathological diagnosis; Committee for kidney disease registry; Japanese society of nephrology: Japan renal biopsy registry and japan kidney disease registry: Committee report for 2009 and 2010., Clinical and Experimental Nephrology, Vol.17, No.2, 155-173, 2013.
(要約)
The Japan Renal Biopsy Registry (J-RBR) was started in 2007 and the Japan Kidney Disease Registry (J-KDR) was then started in 2009 by the Committee for Standardization of Renal Pathological Diagnosis and the Committee for the Kidney Disease Registry of the Japanese Society of Nephrology. The purpose of this report is to describe and summarize the registered data from 2009 and 2010. For the J-KDR, data were collected from 4,016 cases, including 3,336 (83.1 %) by the J-RBR and 680 (16.9 %) other cases from 59 centers in 2009, and from 4,681 cases including 4,106 J-RBR cases (87.7 %) and 575 other cases (12.3 %) from 94 centers in 2010, including the affiliate hospitals. In the J-RBR, 3,165 native kidneys (94.9 %) and 171 renal grafts (5.1 %) and 3,869 native kidneys (94.2 %) and 237 renal grafts (5.8 %) were registered in 2009 and 2010, respectively. Patients younger than 20 years of age comprised 12.1 % of the registered cases, and those 65 years and over comprised 24.5 % of the cases with native kidneys in 2009 and 2010. The most common clinical diagnosis was chronic nephritic syndrome (55.4 % and 50.0 % in 2009 and 2010, respectively), followed by nephrotic syndrome (22.4 % and 27.0 %); the most frequent pathological diagnosis as classified by the pathogenesis was IgA nephropathy (31.6 % and 30.4 %), followed by primary glomerular diseases (except IgA nephropathy) (27.2 % and 28.1 %). Among the primary glomerular diseases (except IgA nephropathy) in the patients with nephrotic syndrome, membranous nephropathy was the most common histopathology in 2009 (40.3 %) and minor glomerular abnormalities (50.0 %) were the most common in 2010 in native kidneys in the J-RBR. Five new secondary and longitudinal research studies by the J-KDR were started in 2009 and one was started in 2010.
(キーワード)
Native kidney biopsy / Primary glomerulonephritis / IgA nephropathy / Membranous nephropathy / Renal grafts / National registry
Yasunobu Hayabuchi, Inoue Miki, Miho Sakata, Tatsuya Ohnishi and Shoji Kagami : Subclavian and pulmonary artery steal phenomenon in a patient with isolated left subclavian artery and right aortic arch., Journal of Clinical Ultrasound, Vol.41, No.4, 265-268, 2013.
(要約)
We describe a patient with an isolated left subclavian artery associated with right aortic arch, patent ductus arteriosus, and ventricular septal defect. As the isolated left subclavian artery is supplied by the left vertebral artery in which blood flows in the retrograde direction, this anomaly is usually responsible for a congenital subclavian steal phenomenon. Atrophy of the left cerebral hemisphere and inverted left vertebral arterial flow were clearly depicted by echoencephalography in this patient, whose subclavian artery was connected to the main pulmonary artery by a patent ductus arteriosus.
Miho Sakata, Yasunobu Hayabuchi, Inoue Miki, Tatsuya Ohnishi and Shoji Kagami : Left atrial volume change throughout the cardiac cycle in children with congenital heart disease associated with increased pulmonary blood flow: evaluation using a novel left atrium-tracking method., Pediatric Cardiology, Vol.34, No.1, 105-111, 2013.
(要約)
There is a paucity of data regarding the significance of left atrial (LA) volume and its changes throughout the cardiac cycle in pediatric patients with heart disease. The recently developed LA volume-tracking (LAVT) method can automatically construct the LA volume curve. The study group consisted of 48 pediatric patients with ventricular septal defect (n = 34) or patent ductus arteriosus (n = 14) and age-matched healthy controls. Maximum and minimum LA volumes (LAVmax and LAVmin, respectively) were measured. The total LA emptying volume (LAVtotal) was defined as LAVmax--LAVmin. Volume parameters were standardized by dividing by body surface area (BSA). The total LA emptying fraction (%LAVtotal) was defined as the ratio of LAVtotal to LAVmax. In the patient group, there was a positive correlation between the ratio of pulmonary to systemic blood flow (Qp/Qs) and LAVmax/BSA, LAVmin/BSA, and LAVtotal/BSA (r = 0.42, 0.44, and 0.34, respectively). LAVmin/BSA was positively correlated with the ratio of early mitral inflow velocity to early mitral annular diastolic tissue Doppler velocity (E/E') (r = 0.32). The %LAVtotal had a negative correlation with left-ventricular (LV) end-diastolic pressure (r = -0.32). There were significant correlations between serum B-type natriuretic peptide level and LAVmax/BSA, LAVmin/BSA, and %LAVtotal (r = 0.38, 0.49, and -0.35, respectively). The LAVT method is useful in the evaluation of LV diastolic function in pediatric patients with chronic LV volume overload.
Kenji Mori, Yoshihiro Touda, Hiromichi Ito, T Mori, A Goji, Emiko Fujii, M Miyazaki, Masafumi Harada and Shoji Kagami : A proton magnetic resonance spectroscopic study in autism spectrum disorders: amygdala and orbito-frontal cortex., Brain & Development, Vol.35, No.2, 139-145, 2013.
(要約)
We previously reported neural dysfunction in the anterior cingulate cortex and dorsolateral prefrontal cortex in autistic patients using proton magnetic resonance spectroscopy ((1)H-MRS). In this investigation, we measured chemical metabolites in the left amygdala and the bilateral orbito-frontal cortex (OFC), which are the main components of the social brain. We also examined the association between these metabolic findings and social abilities in subjects with autism. The study group included 77 autistic patients (3-6years old; mean age 4.1; 57 boys and 20 girls). The control subjects were 31 children (3-6years old; mean age 4.0; 23 boys and 8 girls). Conventional proton MR spectra were obtained using the STEAM sequence with parameters of TR=5 sec and TE=15 msec by a 1.5-tesla clinical MRI system. We analyzed the concentrations of N-acetylaspartate (NAA), creatine/phosphocreatine (Cr), and choline-containing compounds (Cho) using LCModel (Ver. 6.1). The concentrations of NAA in the left amygdala and the bilateral OFC in autistic patients were significantly decreased compared to those in the control group. In the autistic patients, the NAA concentrations in these regions correlated with their social quotient. These findings suggest the presence of neuronal dysfunction in the amygdala and OFC in autism. Dysfunction in the amygdala and OFC may contribute to the pathogenesis of autism.
(キーワード)
Amygdala / Aspartic Acid / Child / Child Development Disorders, Pervasive / Child, Preschool / Choline / Creatinine / Diagnostic and Statistical Manual of Mental Disorders / Female / Functional Laterality / Humans / Intelligence Tests / Magnetic Resonance Imaging / Magnetic Resonance Spectroscopy / Male / Phosphocreatine / Prefrontal Cortex / Protons
S Naruse, T Hashimoto, Kenji Mori, Y Tsuda, M Takahara and Shoji Kagami : Developmental changes in facial expression recognition in Japanese school-age children., The Journal of Medical Investigation : JMI, Vol.60, No.1-2, 114-120, 2013.
(要約)
Facial expressions hold abundant information and play a central part in communication. In daily life, we must construct amicable interpersonal relationships by communicating through verbal and nonverbal behaviors. While school-age is a period of rapid social growth, few studies exist that study developmental changes in facial expression recognition during this age. This study investigated developmental changes in facial expression recognition by examining observers' gaze on others' expressions. 87 school-age children from first to sixth grade (41 boys, 46 girls). The Tobii T60 Eye-tracker(Tobii Technologies, Sweden) was used to gauge eye movement during a task of matching pre-instructed emotion words and facial expressions images (neutral, angry, happy, surprised, sad, disgusted) presented on a monitor fixed at a distance of 50 cm. In the task of matching the six facial expression images and emotion words, the mid- and higher-grade children answered more accurately than the lower-grade children in matching four expressions, excluding neutral and happy. For fixation time and fixation count, the lower-grade children scored lower than other grade children, gazing on all facial expressions significantly fewer times and for shorter periods. It is guessed that the stage from lower grades to middle grades is a turning point in facial recognition.
(キーワード)
Age Factors / Asian Continental Ancestry Group / Child / Child Development / Facial Expression / Female / Humans / Male
N Kishi, Ken-ichi Suga, S Matsuura, Yukiko Kinoshita, Maki Urushihara, Shuji Kondo, E Kitano, M Hatanaka, H Kitamura, T Sato, A Maeda and Shoji Kagami : A case of infantile systemic lupus erythematosus with severe lupus nephritis and EBV infection, CEN Case Reports, Vol.2, No.2, 190-193, 2013.
H Yokoyama, H Sugiyama, H Sato, T Taguchi, T Nagata, S Matsuo, H Makino, T Watanabe, T Saito, Y Kiyohara, S Nishi, H Iida, K Morozumi, A Fukatsu, T Sasaki, K Tsuruya, Y Kohda, M Higuchi, H Kiyomoto, S Goto, M Hattori and Shoji Kagami : Renal disease in the elderly and the very elderly Japanese: analysis of the Japan Renal Biopsy Registry (J-RBR)., Clinical and Experimental Nephrology, Vol.16, No.6, 903-920, 2012.
(要約)
Data regarding renal disease in the elderly (age ≥65 years old) and very elderly (age ≥80 years old) Japanese are extremely limited. The aim of this study was to examine the causes of renal disease and their clinical presentations in elderly patients who underwent renal biopsy. From July 2007 to November 2011, all of the elderly native renal biopsy patients who had been registered in the Japan Renal Biopsy Registry (J-RBR; 2802 including 1596 males and 1206 females) were identified. Their data were compared with a control group of 7416 patients who ranged in age from 20 to 64 years old and were registered on the J-RBR over the same period. In addition, the clinical and pathological classifications of 276 very elderly patients were also analyzed. The indications for biopsy were nephrotic syndrome (NS) in 36.2 and 50.7 % of the elderly and the very elderly patients, chronic nephritic syndrome in 31.8 and 17.4 %, and acute kidney injury including rapidly progressive glomerulonephritis in 18.6 and 22.5 %, respectively. Primary glomerular disease was the most frequent diagnosis, followed by MPO-ANCA-positive nephritis, IgA nephropathy (IgAN), and diabetic nephropathy. In primary GN including IgAN, membranous nephropathy (MN) was the most frequent histological type, followed by IgAN and minor glomerular abnormalities. A comparison with the control group showed that MN, MPO-ANCA-positive nephritis, and amyloid nephropathy were more common in the elderly (P < 0.001), and IgAN was less common (P < 0.001). As for nephrotic syndrome in the elderly, MN was the most common histological type, followed by minimal change NS, diabetic nephropathy, amyloid nephropathy, and focal segmental glomerulosclerosis. There was a significant discrepancy between the urinary protein/creatinine ratio and daily proteinuria after the 7th decade of life. Renal biopsy is a valuable diagnostic tool, even in elderly and very elderly Japanese patients. In the future, modified clinical guidelines for elderly renal disease should be developed.
(キーワード)
Adult / Age Factors / Aged / Aged, 80 and over / Biopsy / Female / Glomerulonephritis / Glomerulonephritis, IGA / Humans / Incidence / Japan / Kidney / Kidney Diseases / Male / Middle Aged / Nephrotic Syndrome / Registries
Salah Mohamed El-Sayed, Rabab Mohamed Abou El-Magd, Yuji Shishido, Kazuko YORITA, Seongpil Chung, Diem Hong Tran, Takashi Sakai, Hiroyoshi Watanabe, Shoji Kagami and Kiyoshi Fukui : D-Amino acid oxidase-induced oxidative stress, 3-bromopyruvate and citrate inhibit angiogenesis, exhibiting potent anticancer effects, Journal of Bioenergetics and Biomembranes, Vol.44, No.5, 513-523, 2012.
(要約)
Angiogenesis is critical for cancer growth and metastasis. Steps of angiogenesis are energy consuming, while vascular endothelial cells are highly glycolytic. Glioblastoma multiforme (GBM) is a highly vascular tumor and this enhances its aggressiveness. D-amino acid oxidase (DAO) is a promising therapeutic protein that induces oxidative stress upon acting on its substrates. Oxidative stress-energy depletion (OSED) therapy was recently reported (El Sayed et al., Cancer Gene Ther, 19, 1-18, 2012). OSED combines DAO-induced oxidative stress with energy depletion caused by glycolytic inhibitors such as 3-bromopyruvate (3BP), a hexokinase II inhibitor that depleted ATP in cancer cells and induced production of hydrogen peroxide. 3BP disturbs the Warburg effect and antagonizes effects of lactate and pyruvate (El Sayed et al., J Bioenerg Biomembr, 44, 61-79, 2012). Citrate is a natural organic acid capable of inhibiting glycolysis by targeting phosphofructokinase. Here, we report that DAO, 3BP and citrate significantly inhibited angiogenesis, decreased the number of vascular branching points and shortened the length of vascular tubules. OSED delayed the growth of C6/DAO glioma cells. 3BP combined with citrate delayed the growth of C6 glioma cells and decreased significantly the number and size of C6 glioma colonies in soft agar. Human GBM cells (U373MG) were resistant to chemotherapy e.g. cisplatin and cytosine arabinoside, while 3BP was effective in decreasing the viability and disturbing the morphology of U373MG cells.
Tatsuo Mori, Kenji Mori, Emiko Fujii, Yoshihiro Touda, Masahito Miyazaki, Masafumi Harada, Toshiaki Hashimoto and Shoji Kagami : Evaluation of the GABAergic nervous system in autistic brain: (123)I-iomazenil SPECT study., Brain & Development, Vol.34, No.8, 648-654, 2012.
(要約)
To evaluate the GABA(A) receptor in the autistic brain, we performed (123)I-IMZ SPECT in patients with ASD. We compared (123)I-IMZ SPECT abnormalities in patients who showed intellectual disturbance or focal epileptic discharge on EEG to those in patients without such findings. The subjects consisted of 24 patients with ASD (mean age, 7.3±3.5 years), including 9 with autistic disorder (mean age, 7.0±3.7 years) and 15 with Asperger's disorder (mean age, 7.5±3.2 years). We used 10 non-symptomatic partial epilepsy patients (mean age, 7.8±3.6 years) without intellectual delay as a control group. For an objective evaluation of the (123)I-IMZ SPECT results, we performed an SEE (Stereotactic Extraction Estimation) analysis to describe the decrease in accumulation in each brain lobule numerically. In the comparison of the ASD group and the control group, there was a dramatic decrease in the accumulation of (123)I-IMZ in the superior and medial frontal cortex. In the group with intellectual impairment and focal epileptic discharge on EEG, the decrease in accumulation in the superior and medial frontal cortex was greater than that in the group without these findings. The present results suggest that disturbance of the GABAergic nervous system may contribute to the pathophysiology and aggravation of ASD, since the accumulation of (123)I-IMZ was decreased in the superior and medial frontal cortex, which is considered to be associated with inference of the thoughts, feelings, and intentions of others (Theory of Mind).
Maki Urushihara, Yukiko Kinoshita, Shuji Kondo and Shoji Kagami : Involvement of the intrarenal renin-angiotensin system in experimental models of glomerulonephritis., Journal of Biomedicine & Biotechnology, Vol.2012, 601786, 2012.
(要約)
The intrarenal renin-angiotensin system (RAS) has several pathophysiologic functions not only in blood pressure regulation but also in the development of glomerulonephritis (GN). Angiotensin II (Ang II) is the biologically active product of the RAS. Locally produced Ang II induces inflammation, renal cell growth, mitogenesis, apoptosis, migration, and differentiation, regulates the gene expression of bioactive substances, and activates multiple intracellular signaling pathways, leading to tissue damage. Activation of the Ang II type 1 (AT1) receptor pathway results in the production of proinflammatory mediators, cell proliferation, and extracellular matrix synthesis, which facilitates glomerular injury. Previous studies have shown that angiotensin-converting enzyme inhibitors and/or AT1 receptor blockers have beneficial effects in experimental GN models and humans with various types of GN, and that these effects are more significant than their suppressive effects on blood pressure. In this paper, we focus on intrarenal RAS activation in the pathophysiology of experimental models of GN.
N Watanabe, Yasunobu Hayabuchi, Ryuji Nakagawa, T Saijo and Shoji Kagami : Multidetector-row computed tomography evaluation of bilateral bronchial narrowing associated with increased pulmonary blood flow in children with congenital heart disease., Congenital Heart Disease, Vol.7, No.5, 410-416, 2012.
(要約)
Quantitative assessment of bilateral bronchial narrowing in children with congenital heart disease (CHD) with a left-to-right shunt has not yet been reported. In the present study, main bronchial size was evaluated bilaterally in normal subjects using multidetector-row computed tomography (MDCT), and the feasibility for diagnosis of bronchial narrowing in children with CHD associated with increased pulmonary blood flow was investigated. The short-axis diameter, long-axis diameter, and the cross-sectional area of the bilateral bronchi were measured immediately proximal to the origin of the superior lobar branch in 86 children aged 1-52 months. Subjects were divided into three groups as follows: group 1 (normal subjects; n = 52), group 2 (asymptomatic left-to-right shunt group; n = 25), and group 3 (symptomatic left-to-right shunt group with respiratory insufficiency; n = 9). Age, height, weight, and body surface area were significantly correlated with short- and long-axis bronchial diameters, and bronchial cross-sectional area in group 1. In group 2, the left bronchial cross-sectional area was significantly lower than group 1 (P < .001), whereas the right bronchial area was not significantly different. In group 3, the right bronchial area was significantly lower than that in groups 1 and 2 (P < .05). Although the left bronchial area in group 3 was significantly lower than in group 1 (P < .001), it was not significantly different from that in group 2. Our study suggests that MDCT can be used to quantify bilateral bronchial narrowing. Left main bronchial obstruction develops during the early stage of heart failure, followed by the development of right bronchial narrowing.
T Oonishi, Yasunobu Hayabuchi, Miho Sakata, Kenji Mori and Shoji Kagami : Stent placement in the ductus venosus of a neonate with total anomalous pulmonary venous return., Journal of Echocardiography, Vol.10, No.1, 27-29, 2012.
Salah Mohamed El-Sayed, Rabab Mohamed Abou El-Magd, Yuji Shishido, Seongpil Chung, Diem Hong Tran, Takashi Sakai, Hiroyoshi Watanabe, Shoji Kagami and Kiyoshi Fukui : 3-Bromopyruvate antagonizes effects of lactate and pyruvate, synergizes with citrate and exerts novel anti-glioma effects, Journal of Bioenergetics and Biomembranes, Vol.44, No.1, 61-79, 2012.
(要約)
Oxidative stress-energy depletion therapy using oxidative stress induced by D-amino acid oxidase (DAO) and energy depletion induced by 3-bromopyruvate (3BP) was reported recently (El Sayed et al., Cancer Gene Ther., 19, 1-18, 2012). Even in the presence of oxygen, cancer cells oxidize glucose preferentially to produce lactate (Warburg effect) which seems vital for cancer microenvironment and progression. 3BP is a closely related structure to lactate and pyruvate and may antagonize their effects as a novel mechanism of its action. Pyruvate exerted a potent H(2)O(2) scavenging effect to exogenous H(2)O(2), while lactate had no scavenging effect. 3BP induced H(2)O(2) production. Pyruvate protected against H(2)O(2)-induced C6 glioma cell death, 3BP-induced C6 glioma cell death but not against DAO/D-serine-induced cell death, while lactate had no protecting effect. Lactate and pyruvate protected against 3BP-induced C6 glioma cell death and energy depletion which were overcome with higher doses of 3BP. Lactate and pyruvate enhanced migratory power of C6 glioma which was blocked by 3BP. Pyruvate and lactate did not protect against C6 glioma cell death induced by other glycolytic inhibitors e.g. citrate (inhibitor of phosphofructokinase) and sodium fluoride (inhibitor of enolase). Serial doses of 3BP were synergistic with citrate in decreasing viability of C6 glioma cells and spheroids. Glycolysis subjected to double inhibition using 3BP with citrate depleted ATP, clonogenic power and migratory power of C6 glioma cells. 3BP induced a caspase-dependent cell death in C6 glioma. 3BP was powerful in decreasing viability of human glioblastoma multiforme cells (U373MG) and C6 glioma in a dose- and time-dependent manner.
Ken-ichi Suga, Shuji Kondo, S Matsuura, Yukiko Kinoshita, Maki Urushihara and Shoji Kagami : Glomerular expression of hydrogen peroxide-inducible clone-5 in human and rat progressive mesangial proliferative glomerulonephritis., Nephron. Experimental Nephrology, Vol.120, No.2, 59-68, 2012.
(要約)
Hydrogen peroxide-inducible clone-5 (Hic-5) is a transforming growth factor-β(1) (TGF-β(1))- and hydrogen peroxide (H(2)O(2))-inducible focal adhesion protein that may be necessary for maintaining the myofibroblastic phenotype in pathological scar formation. To investigate the involvement of Hic-5 in the pathogenesis of glomerulonephritis (GN), we examined the glomerular expression of Hic-5 in human and rat GN as well as the regulation of Hic-5 by TGF-β(1) in vitro. Immunohistochemical analyses showed that the expression of Hic-5 was increased in mesangial cells (MCs) in human mesangial proliferative GN. Hic-5 expression was significantly correlated not only with the levels of α-smooth muscle actin (α-SMA) and TGF-β(1), the accumulation of extracellular matrix, and the number of glomerular cells, but also with the urinary protein level in patients with GN. Glomerular Hic-5 expression increased in parallel with α-SMA expression in a rat model of mesangial proliferative GN. Combined therapy with an angiotensin type I receptor blocker and an antioxidant in this model improved the histology and the expression of Hic-5 and α-SMA. TGF-β(1) upregulated Hic-5 and α-SMA protein levels in human cultured MCs. Our findings suggest that Hic-5 is involved in changes in the MC phenotype to produce abnormal extracellular matrix remodeling in GN.
Salah Mohamed El-Sayed, Rabab Mohamed Abou El-Magd, Yuji Shishido, Seongpil Chung, Takashi Sakai, Hiroyoshi Watanabe, Shoji Kagami and Kiyoshi Fukui : D-amino acid oxidase gene therapy sensitizes glioma cells to the antiglycolytic effect of 3-bromopyruvate, Cancer Gene Therapy, Vol.19, No.1, 1-18, 2012.
(要約)
Glioma tumors are refractory to conventional treatment. Glioblastoma multiforme is the most aggressive type of primary brain tumors in humans. In this study, we introduce oxidative stress-energy depletion (OSED) therapy as a new suggested treatment for glioblastoma. OSED utilizes D-amino acid oxidase (DAO), which is a promising therapeutic protein that induces oxidative stress and apoptosis through generating hydrogen peroxide (H2O2). OSED combines DAO with 3-bromopyruvate (3BP), a hexokinase II (HK II) inhibitor that interferes with Warburg effect, a metabolic alteration of most tumor cells that is characterized by enhanced aerobic glycolysis. Our data revealed that 3BP induced depletion of energetic capabilities of glioma cells. 3BP induced H2O2 production as a novel mechanism of its action. C6 glioma transfected with DAO and treated with D-serine together with 3BP-sensitized glioma cells to 3BP and decreased markedly proliferation, clonogenic power and viability in a three-dimensional tumor model with lesser effect on normal astrocytes. DAO gene therapy using atelocollagen as an in vivo transfection agent proved effective in a glioma tumor model in Sprague-Dawley (SD) rats, especially after combination with 3BP. OSED treatment was safe and tolerable in SD rats. OSED therapy may be a promising therapeutic modality for glioma.
Kenji Mori, T Mori, Y Toda, Emiko Fujii, M Miyazaki, M Harada and Shoji Kagami : Decreased benzodiazepine receptor and increased GABA level in cortical tubers in tuberous sclerosis complex., Brain & Development, Vol.34, No.6, 478-486, 2012.
(要約)
To elucidate the functional characteristics of cortical tubers that might be responsible for epilepsy in tuberous sclerosis complex (TSC), proton magnetic resonance spectroscopy ((1)H-MRS) and [123I] iomazenil (123I-IMZ) single photon emission computed tomography (SPECT) were performed. (1)H-MRS using a clinical 3-tesla magnetic resonance imager was performed in four children with TSC and 10 age-and sex-matched healthy control subjects. A single voxel was set on the right parietal lobe in control subjects. In patients with TSC, a single voxel was set on the epileptogenic tuber in the parietal or temporal lobe, and another voxel was set on the contralateral normal-appearing brain region. N-Acetylaspartate (NAA), myo-Inositol (mIns) and Glutamate (Glu) were analyzed using a conventional STEAM (Stimulated Echo Acquisition Mode) method. The concentration of gamma-aminobutyric acid (GABA) was quantified using MEGA-Point Resolved Spectroscopy (PRESS). Interictal 123I-IMZ SPECT was examined in all four patients with TSC. A significant decrease in the NAA concentration and significant increases in the mIns and GABA concentrations were detected in the cortical tubers of all 4 patients. No significant difference was observed in Glu concentrations. In all of the cortical tubers detected by magnetic resonance imaging, 123I-IMZ binding was significantly decreased. Epileptogenesis in TSC might be caused by decreased inhibition secondary to the decrease in GABA receptors in dysplastic neurons of cortical tubers. An increase in the GABA concentration may compensate for decreased inhibition.
Shoji Kagami : Involvement of glomerular renin-angiotensin system (RAS) activation in the development and progression of glomerular injury., Clinical and Experimental Nephrology, Vol.16, No.2, 214-220, 2012.
(要約)
Recently, there has been a paradigm shift away from an emphasis on the role of the endocrine (circulating) renin-angiotensin system (RAS) in the regulation of the sodium and extracellular fluid balance, blood pressure, and the pathophysiology of hypertensive organ damage toward a focus on the role of tissue RAS found in many organs, including kidney. A tissue RAS implies that RAS components necessary for the production of angiotensin II (Ang II) reside within the tissue and its production is regulated within the tissue, independent of the circulating RAS. Locally produced Ang II plays a role in many physiological and pathophysiological processes such as hypertension, inflammation, oxidative stress, and tissue fibrosis. Both glomerular and tubular compartments of the kidney have the characteristics of a tissue RAS. The purpose of this article is to review the recent advances in tissue RAS research with a particular focus on the role of the glomerular RAS in the progression of renal disease.
(キーワード)
Angiotensin II / Animals / Disease Progression / Humans / Kidney Diseases / Kidney Glomerulus / Renin-Angiotensin System
Tatsuo Mori, Kenji Mori, Emiko Fujii, Yoshihiro Touda, Masahito Miyazaki, Masafumi Harada and Shoji Kagami : Neuroradiological and neurofunctional examinations for patients with 22q11.2 deletion., Neuropediatrics, Vol.42, No.6, 215-221, 2011.
(要約)
Since the neuroradiological features of patients with 22q11.2 deletion syndrome are not well-understood, examinations using functional imaging were performed in this study. Brain magnetic resonance imaging (MRI) and 1H-magnetic resonance spectroscopy (MRS) were performed using a clinical 3-Tesla MR imager in 4 patients with 22q11.2 deletion syndrome (2 boys and 2 girls; aged 2-6 years.) and 20 age- and sex-matched healthy control subjects. Furthermore, interictal 123I-iomazenil (IMZ) single photon emission computed tomography (SPECT) was examined in 2 of the 4 patients. Among the 4 patients with 22q11.2 deletion syndrome, 2 patients showed polymicrogyria and 1 patient showed agyria. Those patients with brain malformations also showed abnormal brain artery patterns and decreased accumulation of IMZ in 123I-IMZ SPECT. Although all 4 patients showed epileptic discharges in their electroencephalograms (EEG), one patient with polymicrogyria had no seizure episodes. Decreases in γ-aminobutyric acid (GABA) corresponding to the areas of polymicrogyria and/or epileptic discharges in EEG were shown in all patients except for the patient with agyria. Although consistent evidence was not seen in patients with 22q11.2 deletion syndrome in this study, brain malformations and disturbances of the GABAergic nervous system would be underlying mechanisms of the neurodevelopmental abnormalities in this syndrome.
Maki Urushihara and Shoji Kagami : Urinary angiotensinogen as a biomarker of nephropathy in childhood., International Journal of Nephrology, Vol.2011, 206835, 2011.
(要約)
While most circulating angiotensinogen (AGT) is synthesized in the liver, the kidneys also produce AGT. Recently, we reported that urinary AGT is mainly originated from AGT. Using newly developed human AGT ELISA, we measured urinary AGT levels in chronic glomerulonephritis (GN) patients and patients with type 1 diabetes in childhood. Urinary AGT level was positively correlated with diastolic blood pressure, urinary albumin, urinary protein levels, and urinary occult blood in chronic GN patients. Furthermore, urinary AGT level was significantly increased in chronic GN patients not treated with renin-angiotensin system (RAS) blockers compared with control subjects. Importantly, patients treated with RAS blockers had a marked attenuation of this increase. Also, urinary AGT level was significantly higher in patients with diabetic nephropathy in the premicroalbuminuric phase than in control subjects. These results suggest that urinary AGT reflects intrarenal RAS status in chronic GN and may be an early marker of diabetic nephropathy.
Yasunobu Hayabuchi, Miki Inoue, Noriko Watanabe, Miho Sakata, Tatsuya Ohnishi and Shoji Kagami : Consideration of the Pathological Features of Pediatric Congenital Heart Diseases Which Are Ideally Suitable for Diagnosing With Multidetector-row CT., Cardiology Research, Vol.2, No.4, 150-159, 2011.
(要約)
A lots of articles published regarding the usefulness of multidetector-row computed tomography (MDCT) in children with congenital heart disease (CHD) mostly describe that it can be an alternative to the invasive catheterization and angiography. The unique diagnostic features of this imaging modality have been largely ignored or disregarded. We described the pathological conditions that cannot be diagnosed by conventional angiography with cardiac catheterization but can be accurately diagnosed by MDCT. We retrospectively reviewed non-ECG-gated MDCT images acquired from 452 children and young adults with CHD between 2005 and 2010 in our institute. In this article, we focused on the diagnostic advantages of MDCT, and indicated five pathological conditions. (1) When Blalock-Taussig shunt total occlusion prevents catheter insertion into the artificial vessel and angiography is ruled out, the peripheral pulmonary artery during the peripheral pulmonary artery can be imaged and diagnosed using MDCT based on blood flow supplied from many small collateral vessels originating from the aorta. (2) The location and protrusion of the device in the vessel after coil embolization to treat patent ductus arteriosus can be accurately visualized by virtual endoscopy using MDCT. (3) Calcification of patches, synthetic blood vessels, and other prostheses that is indistinct on conventional angiograms is clear on MDCT. (4) Simultaneous MDCT observations of the anatomical relationships between arterial and venous systems on the same image can clarify the detail diagnosis for surgical treatment. (5) Compression of the airways by the great vessels and pulmonary segmental emphysematous change can be diagnosed by MDCT. Among patients with CHD, MDCT is useful not only as a non-invasive alternative to conventional angiography, but also as a tool for specific morphological diagnoses. In the future, it will be necessary to accumulate experience in the recognition of cardiovascular conditions under which MDCT is necessary and to perform as the appropriate examination.
Yasunobu Hayabuchi, Miho Sakata, Tatsuya Ohnishi and Shoji Kagami : A novel bilayer approach to ventricular septal deformation analysis by speckle tracking imaging in children with right ventricular overload, Journal of the American Society of Echocardiography, Vol.24, No.11, 1205-1212, 2011.
(要約)
The aim of this study was to evaluate functional differences between the left and right sides of the ventricular septum in children with right ventricular overload. Radial, longitudinal, and circumferential strain on both sides of the ventricular septum were compared using speckle-tracking echocardiography in patients with preoperative atrial septal defects (n = 22), postoperative tetralogy of Fallot (n = 23) and age-matched normal controls (n = 44). The duration between peak strain of the left and right ventricular septum (TLt-Rt) was also evaluated. Radial and circumferential strain in the control group were significantly higher on the left than the right ventricular septum (41.3 ± 12.8% vs 22.6 ± 6.8% and -28.0 ± 5.4% vs -22.5 ± 4.8%, respectively; P < .0001 for both), whereas longitudinal strain did not significantly differ (-22.0 ± 4.9% and -20.7 ± 5.2%, respectively). TLt-Rt was 52.9 ± 35.6, 33.4 ± 29.0, and 38.7 ± 31.0 msec for radial, longitudinal, and circumferential strain, respectively. Longitudinal and circumferential strain on both sides were significantly increased in patients with atrial septal defects compared with controls (P < .05), although radial strain was similar on both sides. Radial strain on the right side was significantly increased in patients with tetralogy of Fallot compared with controls (P < .05), whereas that on the left side was significantly reduced (P < .001). Longitudinal strain on both sides was significantly decreased (P < .01 and P < .001 for the left and right sides, respectively). In addition, TLt-Rt in patients with tetralogy of Fallot was significantly increased with radial and circumferential deformation (P < .05 for both). Deformation of both sides of the ventricular septum functionally differed. Bilayer analysis of the ventricular septum can help in the evaluation of right ventricular performance under volume and pressure overload.
Yasunobu Hayabuchi, Miki Inoue, Miho Sakata and Shoji Kagami : Multidetector-row computed tomography visualized peripheral pulmonary artery patency in a patient with occluded modified Blalock-Taussig shunt, International Journal of Cardiology, Vol.150, No.2, e57-e58, 2011.
(要約)
Multidetector-row computed tomography visualized peripheral pulmonary artery patency in a 19-year-old female with a single ventricle and an occluded Blalock-Taussig shunt whereas conventional invasive angiography did not.
Aya Fukumoto, Toshiaki Hashimoto, Kenji Mori, Yoshimi Tsuda, Kokichi Arisawa and Shoji Kagami : Head circumference and body growth in autism spectrum disorders., Brain & Development, Vol.33, No.7, 569-575, 2011.
(要約)
Research has shown that there is a relationship between increased head circumference and autism spectrum disorders (ASD). This study examined this relationship during the first year of life in subjects with ASD. We compared 280 children with ASD and 609 controls. In the ASD-male group, increases were observed in head circumference from 3 to 12months, in height from 3 to 9months, and in body weight from 3 to 6 and 12months. On the other hand, in the ASD-female group increases in head circumference, in body height, and in body weight were only observed at 3months. After adjusting for height, weight, and age, only the head circumference in the male ASD group was significantly increased from 6 to 9months after birth, reaching a peak at 6months after birth. No difference was found in the female ASD group. Although body overgrowth in the ASD group also started early after birth, the increase in head circumference was more marked than that in body growth. The values of physical measurements in the first year may be useful, minimally invasive parameters for the early detection of autism in combination with observing the timing of certain behaviors such as smiling, eye contact, crawling, pointing, and joint attention.
(キーワード)
Body Height / Body Weight / Cephalometry / Child Development Disorders, Pervasive / Female / Head / Humans / 小児 (infant) / Infant, Newborn / 日本 (Japan) / Male
Yasunobu Hayabuchi, Miki Inoue, Noriko Watanabe, Miho Sakata, Tatsuya Ohnishi and Shoji Kagami : Serum concentration of Heart-type fatty acid-binding protein in children and adolescents with congenital heart disease, Circulation Journal, Vol.75, No.8, 1992-1997, 2011.
(要約)
Serum heart-type fatty acid-binding protein (H-FABP) is widely applied as a marker of cardiac myocyte injury. Recently, it has been reported that levels of H-FABP are elevated in adult patients with chronic heart failure and thus provide useful prognostic information. The aim of the present study was to examine the relationships between serum H-FABP levels and pathophysiological characteristics in children and adolescents with congenital heart disease (CHD). Serum H-FABP levels were preoperatively and postoperatively measured in 238 consecutive patients with CHD aged 1-31 years. The relationships between H-FABP levels and severity of heart failure, circulatory status and laboratory data were cross-sectionally analyzed. Multivariate regression analysis indicated that serum H-FABP levels are independently affected by age, New York Heart Association functional class, creatine kinase MB, creatinine and arterial oxygen saturation (standard regression coefficients, -0.378, 0.237, 0.422, 0.615, and -0.210, respectively). Neither left ventricular ejection fraction nor B-type natriuretic peptide correlated with H-FABP levels. H-FABP could serve as a new monitoring tool to provide information that will guide the optimal therapy and management of CHD patients.
Yasunobu Hayabuchi, Miki Inoue, Noriko Watanabe, Miho Sakata, Manal Helmy Mohamed Nabo and Shoji Kagami : Minimum-intensity projection of multidetector-row computed tomography for assessment of pulmonary hypertension in children with congenital heart disease, International Journal of Cardiology, Vol.149, No.2, 192-198, 2011.
(要約)
The present study aimed to assess the feasibility of minimum-intensity projection (minIP) images for the evaluation of pulmonary hypertension (PH) in children with congenital heart disease (CHD). A total of 70 consecutive patients (mean age, 4.6 ± 4.4 years; range, 6 months-16 years) underwent multidetector-row computed tomography (MDCT) angiography of the thorax prior to cardiac catheterization and lung perfusion scintigraphy. Contiguous axial, coronal and sagittal minIP images of 5-mm thickness were reconstructed from the contrast-enhanced CT datasets. Two reviewers evaluated the images in consensus and qualitatively graded lung parenchyma attenuation as homogeneous (Class I), slightly heterogeneous lung attenuation that does not conform to the anatomic boundaries of the secondary pulmonary lobule (Class II), and mosaic pattern (Class III). MinIP attenuation grading results were then compared with those of perfusion scintigraphy. Furthermore, the relationships between the results of these modalities and mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) were evaluated. In 51 (73%) patients, concordant findings were observed between the modalities, although minIP showed a higher grade for heterogeneous images than did scintigraphy. mPAP and PVR showed significant difference among the minIP attenuation classes (p<0.0001 for both). High-grade heterogeneous minIP images were associated with high mPAP, high PVR, presence of major aortopulmonary collateral artery, and chromosomal abnormality. MinIP is a promising technique for depicting lung perfusion and can be used as superior alternative to scintigraphy in the evaluation of PH.
Maki Shimizu, Takanori Sekiguchi, Natsuko Kishi, Aya Goji, Tomoko Takahashi, Hiroko Kozan, Zenichi Sakaguchi, Yukiko Kinoshita, Sato Matsuura, Ken-ichi Suga, Maki Urushihara, Shuji Kondo, Shoji Kagami and Katsuaki Ohara : A case of a 6-year-old girl with anti-neutrophil cytoplasmic autoantibody-negative pauci-immune crescentic glomerulonephritis., Clinical and Experimental Nephrology, Vol.15, No.4, 596-601, 2011.
(要約)
A 6-year-old girl was admitted to our hospital with proteinuria, hematuria, skin rash and joint pain of the lower limbs. Due to rapid progression of renal insufficiency, hemodialysis and peritoneal dialysis were performed. She was diagnosed with rapidly progressive glomerulonephritis. Kidney biopsy showed severe crescent formation (50% of glomeruli) and no deposition of any immunoglobulins or complements. Serologically, anti-neutrophil cytoplasmic autoantibody (ANCA) was negative not only by ELISA against proteinase-3 and myeloperoxidase-ANCA but also by indirect immunofluorescent assay against cytoplasmic and perinuclear ANCA. Anti-glomerular basement membrane antibody was also negative. In the acute phase, proinflammatory cytokines such as soluble tumor necrosis factor receptor 1 (sTNFR1), soluble interleukin (IL)-2 receptor (sIL2R), IL-6 and chemokine IL-8 were elevated. The patient was diagnosed with ANCA-negative pauci-immune crescentic glomerulonephritis (CrGN). Intensive treatment with methylprednisolone pulse therapy, plasma exchange, and multiple drug therapy including prednisolone and cyclophosphamide resulted in histopathological improvement and complete remission of proteinuria. There was a possibility that sTNFR1, sIL2R, IL-6 and IL-8 might be involved in the initiation and progression of ANCA-negative pauci-immune CrGN, and to remove and suppress these cytokines might be an effective way to treat ANCA-negative pauci-immune CrGN.
Helmy Manal Mohamed Nabo, Yasunobu Hayabuchi, Miki Inoue, Noriko Watanabe, Miho Sakata, Tatsuya Ohnishi and Shoji Kagami : Pulmonary emphysematous changes in patients with congenital heart disease associated with increased pulmonary blood flow, --- Evaluatio using multidetector-row computed tomography ---, Heart, Lung & Circulation, Vol.20, No.9, 587-592, 2011.
(要約)
The present study aimed to evaluate the prevalence and the location of segmental emphysematous change in congenital heart disease (CHD) patients with increased pulmonary blood flow using multidetector-row computed tomography (MDCT). A total of 129 consecutive patients (mean age, 5.8±5.4 years; range, 1 month to 24 years) underwent MDCT angiography of the thorax. The frequency of emphysematous change was evaluated in patients with ventricular septal defect (VSD, n=61), atrial septal defect (ASD, n=27), patent ductus arteriosus (PDA, n=36) and complete atriventriclar septal defect (CAVSD, n=5). In 59 patients who underwent cardiac catheterisation, the relationships between the emphysematous change and both pulmonary to systemic blood flow ratio (Qp/Qs) and mean pulmonary arterial pressure (mPAP) were evaluated. The emphysematous change was detected in 57 patients (44.2%) out of 129 patients. The frequency of segmental emphysematous change in left side was higher than in right side (14.8% vs. 6.5%). Both Qp/Qs and mPAP affected the presence of emphysema. MDCT can provide accurate detection of segmental emphysema in patients with CHD. Emphysematous change is not uncommon pathological lesion in children and adolescents with CHD.
The aim of this study is to determine the signal transduction of membrane stretch on intermediate-conductance Ca(2+)-activated K(+) (IKca) channels in rat aorta smooth muscle cells using the patch-clamp technique. To stretch the cell membrane, both suction to the rear end of patch pipette and hypotonic shock were used. In cell-attached and inside-out patch configurations, the open probability of IKca channels increased when 20- to 45-mmHg suction was applied. Hyposmotic swelling efficiently increased IKca channel current. When the Ca(2+)-free solution was superfused, the activation of IKca current by the hyposmotic swelling was reduced. Furthermore, gadolinium (Gd(3+)) attenuated the activation of IKca channels induced by hyposmotic swelling, whereas nicardipine did not. In the experiments with Ca(2+)-free bath solution, pretreatment with GF109203X, a protein kinase C (PKC) inhibitor, completely abolished the stretch-induced activation of IKca currents. The stretch-induced activation of IKca channels was strongly inhibited by cytochalasin D, indicating a role for the F-actin in modulation of IKca channels by changes in cell stretching. These data suggest that cell membrane stretch activates IKca channels. In addition, the activation is associated with extracellular Ca(2+) influx through stretch-activated nonselective cation channels, and is also modulated by the F-actin cytoskeleton and the activation of PKC.
Miki Inoue, Yasunobu Hayabuchi and Shoji Kagami : Development of systemic-to-pulmonary collateral arteries in a patients with hypoplastic left heart syndrome after bilateral pulmonary artery banding, Cardiology in the Young, Vol.20, No.4, 465-467, 2010.
(要約)
We describe systemic-to-pulmonary collateral arteries that developed after bilateral pulmonary artery banding in a patient with hypoplastic left cardiac syndrome. The growth of collateral arteries should be evaluated carefully because bilateral pulmonary artery banding under prostaglandin E1 administration is considered an initial palliative option.
Ken-ichi Suga, Shuji Kondo, Sato Matsuura, Yukiko Kinoshita, E Kitano, M Hatanaka, H Kitamura, Y Hidaka, T Oda and Shoji Kagami : A case of dense deposit disease associated with a group A streptococcal infection without the involvement of C3NeF or complement factor H deficiency, Pediatric Nephrology, Vol.25, No.8, 1547-1550, 2010.
(要約)
A 14-year-old girl presented with acute glomerulonephritis. Tests revealed hypocomplementemia and elevated Antistreptolysin-O titers, and renal biopsy revealed endocapillary and mesangial proliferative glomerulonephritis with double contours of the glomerular basement membrane (GBM). Despite methylprednisolone pulse therapy and the administration of oral prednisolone, overt proteinuria and hypocomplementemia persisted. A second renal biopsy 6 months later confirmed the initial diagnosis of dense deposit disease (DDD) based on electron-dense deposits in the GBM. C3 nephritic factor (C3NeF) and a deficiency of complement factor H (CFH) were not evident. A nephritis-associated plasmin receptor (NAPlr), nephritogenic group A streptococcal antigen, and the plasmin activity by in situ zymography were been in both the first and second biopsy specimens. The patient received combined immunomodulatory therapy with prednisolone and mizoribine, and the urinary protein decreased to a mild level at 27 months after disease onset. These findings suggest that persistent glomerular NAPlr deposition may be associated with the pathogenesis of DDD in some patients without the involvement of C3NeF or CFH mutation and that DDD patients of this type may respond to immunomodulatory treatment.
Maki Urushihara, Shuji Kondo, Shoji Kagami and Hiroyuki Kobori : Urinary angiotensinogen accurately reflects intrarenal Renin-Angiotensin system activity., American Journal of Nephrology, Vol.31, No.4, 318-325, 2010.
(要約)
We recently reported that immunoreactivity of intrarenal angiotensinogen (AGT) is significantly increased in IgA nephropathy patients. Meanwhile, we have developed direct enzyme-linked immunosorbent assays to measure plasma and urinary AGT (UAGT) in humans. This study was performed to test the hypothesis that UAGT levels are increased in chronic glomerulonephritis patients. We analyzed 100 urine samples from 70 chronic glomerulonephritis patients (26 from IgA nephropathy, 24 from purpura nephritis, 8 from lupus nephritis, 7 from focal segmental glomerulosclerosis, and 5 from non-IgA mesangial proliferative glomerulonephritis) and 30 normal control subjects. UAGT-creatinine ratio (UAGT/UCre) was correlated positively with diastolic blood pressure (p = 0.0326), urinary albumin-creatinine ratio (p < 0.0001), urinary protein-creatinine ratio (p < 0.0001) and urinary occult blood (p = 0.0094). UAGT/UCre was significantly increased in chronic glomerulonephritis patients not treated with renin-angiotensin system (RAS) blockers compared with control subjects (p < 0.0001). Importantly, glomerulonephritis patients treated with RAS blockers had a marked attenuation of this augmentation (p = 0.0021). These data indicate that UAGT are increased in chronic glomerulonephritis patients and treatment with RAS blockers suppressed UAGT. The efficacy of RAS blockade to reduce the intrarenal RAS activity can be confirmed by measurement of UAGT in chronic glomerulonephritis patients.
(キーワード)
Adolescent / Adult / Angiotensinogen / Child / Child, Preschool / Female / Glomerulonephritis / Humans / Kidney / Male / Renin-Angiotensin System / Reproducibility of Results / Young Adult
Yasunobu Hayabuchi, Miki Inoue, Noriko Watanabe, Miho Sakata, ManalMH Nabo, Tetsuya Kitagawa, Takashi Kitaichi and Shoji Kagami : Assessment of systemic-pulmonary collateral arteries in children with cyanotic congenital heart disease using multidetector-row computed tomography: Comparison with conventional angiography, International Journal of Cardiology, Vol.138, No.3, 266-271, 2010.
(要約)
The present study aimed to assess the feasibility of multidetector-row computed tomography (MDCT) for the evaluation of systemic-pulmonary collateral (SPC) arteries in children with congenital heart disease associated with reduced pulmonary blood flow. Forty-eight consecutive patients (mean age 9+/-5 months; range, 0-30 months) underwent MDCT angiography of the thorax with a 16-detector row scanner prior to cardiac catheterization and operation. Conventional angiographic findings were used as a gold standard for the detection of SPC vessels. Findings on CT angiograms, including CT scans, maximum intensity projections, and three-dimensional volume-rendered images, were used to evaluate depiction of SPC arteries. Quantification of measurements at the SPC artery diameter was evaluated independently on MDCT and conventional invasive angiography. Among the 48 patients, 115 SPC arteries were identified with conventional angiography, and 94 SPC arteries were identified with MDCT. In 89 (77%) vessels, concordant findings were observed with both modalities, with adequate depiction in 53 vessels and suboptimal depiction in 36 vessels. In 26 (23%) vessels, MDCT was unable to identify SPC arteries. Further, CT angiography resulted in the false-positive identification of vessels in 5 cases. There was an excellent correlation between MDCT- and conventional angiography-based measurement of SPC vessel diameter (R(2)=0.83), although a systematic overestimation was observed with MDCT (bias 0.19+/-0.74 mm). This study demonstrates that MDCT is a potentially useful tool, which may have implications for planning percutaneous interventions and surgical repair in the future.
Maki Urushihara, Masanori Takamatsu, Maki Shimizu, Shuji Kondo, Yukiko Kinoshita, Kenichi Suga, Akiko Kitamura, Sato Matsuura, Masanori Yoshizumi, Toshiaki Tamaki, Hiroshi Kawachi and Shoji Kagami : ERK5 activation enhances mesangial cell viability and collagen matrix accumulation in rat progressive glomerulonephritis., American Journal of Physiology, Renal Physiology, Vol.298, No.1, F167-76, 2010.
(要約)
The mitogen-activated protein kinase (MAPK) cascade plays an important role in the regulation of various cellular functions in glomerulonephritis (GN). Here, we investigated whether extracellular signal-regulated kinase 5 (ERK5), a member of the MAPK family, is involved in the pathogenesis of chronic mesangioproliferative GN, using a rat model induced by uninephrectomy and anti-Thy-1 antibody injection. Immunostaining of kidneys obtained at different time points revealed that phospho-ERK5 was weakly expressed in control glomeruli but dramatically increased in a typical mesangial pattern after 28 and 56 days of GN. A semiquantitative assessment indicated that glomerular phospho-ERK5 expression closely paralleled the accumulation of extracellular matrix (ECM), collagen type I, as well as glomerular expression of reactive oxygen species (ROS) and ANG II. On the other hand, phospho-ERK1/2 expression increased on day 7 during the phase of enhanced mesangial cell (MC) proliferation and decreased thereafter. H(2)O(2) and ANG II each induced ERK5 phosphorylation by cultured rat MCs. Costimulation with both H(2)O(2) and ANG II synergistically increased ERK5 phosphorylation in MCs. Cultured MCs transfected with ERK5-specific small interference RNA showed a significant decrease in H(2)O(2) or ANG II-induced cell viability and soluble collagen secretion compared with control cells. Treatment of GN rats with an ANG II type 1 receptor blocker resulted in significant decreases in phospho-ERK5 expression and collagen accumulation accompanied by remarkable histological improvement. Taken together, these results suggest that MC ERK5 phosphorylation by ANG II or H(2)O(2) enhances cell viability and ECM accumulation in an experimental model of chronic GN.
Manal Helmy Mohamed Nabo, Yasunobu Hayabuchi, Miki Inoue, Noriko Watanabe, Miho Sakata and Shoji Kagami : Assessment of modified Blalock-Taussig shunt in children with congenital heart disease using multidetector-row computed tomography, Heart and Vessels, Vol.25, No.6, 529-535, 2010.
(要約)
The purpose of this study was to assess the feasibility of multidetector-row computed tomography (MDCT) for the evaluation of modified Blalock-Taussig (B-T) shunt in children with congenital heart disease associated with reduced pulmonary blood flow. A total of 25 consecutive patients (mean age, 2.6 ± 3.6 years; range, 2 months-16 years) underwent MDCT angiography of the thorax with a 16-detector row scanner prior to cardiac catheterization. A total of 39 shunts (right, 22; left, 17) were included in the study. Conventional angiographic findings were used as the gold standard for the detection of B-T shunts. Shunt diameter was measured quantitatively and independently at four sites (the subclavian artery site, the pulmonary artery site, the widest site, and the stenotic site) on MDCT and on conventional invasive angiography. All B-T shunts were depicted on multiplanar reconstruction (MPR), maximum intensity projection (MIP), curved planar reconstruction (CPR), and three-dimensional volume-rendered (VR) images, enabling evaluation in all patients except for one with occluded shunt. There were excellent correlations between MDCT- and conventional angiography-based measurements of shunt diameter at the subclavian artery site, pulmonary artery site, and the widest site (R² = 0.46, 0.74 and 0.64, respectively; p < 0.0001 for each), although systematic overestimation was observed for MDCT (mean percentage of overestimation, 23.1 ± 32.4%). Stenotic site diameter and degree of stenosis showed a mild correlation (R² = 010 and 0.25, respectively; p < 0.01 for each). This study demonstrates that MDCT is a promising tool for the detection of lesions in B-T shunts.
(キーワード)
Adolescent / Blalock-Taussig Procedure / Child / Child, Preschool / Feasibility Studies / Female / Heart Defects, Congenital / Humans / Infant / Japan / Linear Models / Male / Predictive Value of Tests / Pulmonary Artery / Pulmonary Circulation / Regional Blood Flow / Subclavian Artery / Time Factors / Tomography, X-Ray Computed / Treatment Outcome
Toshie Saito, Maki Urushihara, Yumiko Kotani, Shoji Kagami and Hiroyuki Kobori : Increased urinary angiotensinogen is precedent to increased urinary albumin in patients with type 1 diabetes., The American Journal of the Medical Sciences, Vol.338, No.6, 478-480, 2009.
(要約)
Thus, in patients, an increase in urinary angiotensinogen levels is observed, and this increase is precedent to an increase in urinary albumin levels, suggesting that urinary angiotensinogen may function as an early marker of diabetic nephropathy.
(キーワード)
Adolescent / Albuminuria / Angiotensinogen / Animals / Case-Control Studies / Diabetes Mellitus, Type 1 / Diabetic Nephropathies / Enzyme-Linked Immunosorbent Assay / Female / Humans / Male / Rats / Renin-Angiotensin System / Time Factors
Miki Inoue, Yasunobu Hayabuchi, Kazuhiro Mori, Katsunori Tatara and Shoji Kagami : Autonomic function in patients with Duchenne muscular dystrophy, Pediatrics International, Vol.51, No.1, 33-40, 2009.
(要約)
Assessing autonomic function is important for patients with chronic heart failure, but the way that autonomic function changes in patients with Duchenne muscular dystrophy (DMD) and correlates with other clinical parameters during their young age is not clearly known. Heart rate variability (HRV) during ambulatory electrocardiogram (ECG) was performed in 57 DMD patients (130 recordings) who were not receiving medication (mean age 15.3 +/- 4.5 years). The data were compared with the serum levels of brain natriuretic peptide (BNP), the shortening fraction (SF) of the left ventricle on echocardiography, and simple parameters of heart rate from 24 h ambulatory ECG. Among four parameters of HRV measurements (high frequency [HF]; percentage of adjacent normal R-R intervals that were >50 ms different for the entire 24 h recording [%RR50]; ratio of low to high frequency [LF/HF]; and standard deviation for all normal R-R intervals for the entire 24 h recording [SDNN]), SDNN was most frequently abnormal. Even when SF was normal, a significant percentage of patients exhibited, abnormal parasympathetic activity (HF, %RR50: 74%, 78%, respectively), sympathetic activity (LF/HF, 43%), and SDNN (96%). Similarly, even if serum BNP levels were normal, 86%, 89%, 59%, and 97% of the patients displayed abnormal autonomic function on these measurements, respectively. Mean heart rate at night most accurately predicted abnormality of SDNN. When the cut-off point for mean heart rate at night was 71 beats/min, the sensitivity and specificity of this parameter for predicting abnormal SDNN was 94% and 85%, respectively (P < 0.0001). In DMD, autonomic function, especially SDNN, was frequently abnormal, although conventional clinical examinations of cardiac function (BNP levels and SF) were normal. It is proposed that mean heart rate during night could be used as a simple measurement for evaluation of autonomic function.
Noriko Watanabe, Yasunobu Hayabuchi, Miki Inoue, Miho Sakata, Nabo Mohamed Helmy Manal, Ryuji Nakagawa, Takahiko Saijo and Shoji Kagami : Tracheal compression due to an elongated aortic arch in patients with congenital heart disease: evaluation using multidetector-row CT, Pediatric Radiology, Vol.39, No.10, 1048-1053, 2009.
(要約)
The airway can become obstructed as a result of compression by an elongated aortic arch. In this study we evaluated tracheal compression using multidetector-row CT in patients with congenital heart disease and an elongated aortic arch. The trachea was measured at the level of the aortic arch in 205 children and young adults and then the severity of tracheal compression was determined by measuring the tracheal diameter ratio (short axis diameter/long axis diameter). Patients were divided as follows: group I (normal aortic arch; n=166), group II (transversely running aortic arch; n=22), and group III (elongated aortic arch; n=17). From the viewpoint of the relationship of the great arteries, group II had D-malposition, and group III had L-malposition. Age, height, weight and body surface area were significantly correlated with the short and long axis diameter in group I. There was a negative correlation between tracheal diameter ratio and the physical size parameters. The tracheal diameter ratio in group III was 0.50+/-0.13, which was significantly lower than in groups I and II (P<0.01 and 0.05, respectively). Even apparently asymptomatic patients with an elongated aortic arch can have tracheal compression. An elongated aortic arch may be a useful predictor of tracheal compression.
Miho Sakata, Yasunobu Hayabuchi, Miki Inoue and Shoji Kagami : Stenting of ductus arteriosus in a neonate with truncus arteriosus and interrupted aortic arch associated with a right aortic arch, Pediatric Cardiology, Vol.30, No.8, 1180-1183, 2009.
(要約)
This report describes a case in which successful stenting of ductus arteriosus (DA) was performed for a 27-day-old boy with truncus arteriosus (TA) and interrupted aortic arch (IAA). The patent DA was associated with a right aortic arch. During the balloon catheter crossing of the ductus, the DA and descending aorta shifted toward the left side, making appropriate stent placement difficult. Additionally, the DA was longer than in previously reported cases with left aortic arch, thus requiring a longer stent. This experience suggests that DA stenting in neonates with TA and IAA averts surgical repair during the early neonatal period.
Yasuhisa Kanematsu, Kunihisa Yamaguchi, Hideki Ohnishi, Yuki Motobayashi, Keisuke Ishizawa, Yuki Izawa, Kazuyoshi Kawazoe, Shuji Kondo, Shoji Kagami, Shuhei Tomita, Koichiro Tsuchiya and Toshiaki Tamaki : Dietary doses of nitrite restore circulating nitric oxide level and improve renal injury in L-NAME-induced hypertensive rats, American Journal of Physiology, Renal Physiology, Vol.295, No.5, F1457-F1462, 2008.
(要約)
We have reported that pharmacological doses of oral nitrite increase circulating nitric oxide (NO) and exert hypotensive effects in Nomega-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. In this study, we examined the effect of a chronic dietary dose of nitrite on the hypertension and renal damage induced by chronic L-NAME administration in rats. The animals were administered tap water containing L-NAME (1 g/l) or L-NAME + nitrite (low dose: 0.1 mg/l, medium dose: 1 mg/l, high dose: 10 mg/l) for 8 wk. We evaluated blood NO levels as hemoglobin-NO adducts (iron-nitrosyl-hemoglobin), using an electron paramagnetic resonance method. Chronic administration of L-NAME for 8 wk induced hypertension and renal injury and reduced the blood iron-nitrosyl-hemoglobin level (control 38.8 +/- 8.9 vs. L-NAME 6.0 +/- 3.1 arbitrary units). Coadministration of a low dose of nitrite with L-NAME did not change the reduced iron-nitrosyl-hemoglobin signal and did not improve the L-NAME-induced renal injury. The blood iron-nitrosyl-hemoglobin signals of the medium dose and high dose of nitrite were significantly higher than that of L-NAME alone. Chronic administration of a medium dose of nitrite attenuated L-NAME-induced renal histological changes and proteinuria. A high dose of nitrite also attenuated L-NAME-induced renal injury. These findings suggest that dietary doses of nitrite that protect the kidney are associated with significant increase in iron-nitrosyl-hemoglobin levels. We conclude that dietary nitrite-derived NO generation may serve as a backup system when the nitric oxide synthase/L-arginine-dependent NO generation system is compromised.
Tatsushi Miyazaki, Katsunori Tatara, Kazuhiro Mori, Miki Inoue, Yasunobu Hayabuchi and Shoji Kagami : Segmental Myocardial Strain of the Left Ventricle in Patients With Duchenne Muscular Dystrophy Using Two-Dimensional Speckle Tracking Echocardiography, Journal of Echocardiography, Vol.6, No.4, 100-108, 2008.
Yasunobu Hayabuchi, Miki Inoue and Shoji Kagami : Rare venous connection causing severe hypoxia after Fontan operation, Interactive Cardiovascular and Thoracic Surgery, Vol.7, No.4, 718-719, 2008.
(要約)
We describe a rare case of cyanosis following the Fontan operation with right-to-left shunting at the venous level, that is, an azygos venous to pulmonary venous connection. Few cases with partial anomalous pulmonary venous connection to azygos vein have been reported; however, there have been no reports describing the connection from azygos vein to pulmonary vein, which results in desaturation after Fontan operation. Multidetector-row computed tomography (MDCT) was a useful tool to depict this vascular malformation.
Yuki Izawa, Masanori Yoshizumi, Keisuke Ishizawa, Yoshiko Fujita, Shuji Kondo, Shoji Kagami, Kazuyoshi Kawazoe, Koichiro Tsuchiya, Shuhei Tomita and Toshiaki Tamaki : Big mitogen-activated protein kinase 1 (BMK1)/extracellular signal regulated kinase 5 (ERK5) is involved in platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell migration, Hypertension Research, Vol.30, No.11, 1107-1117, 2007.
(要約)
Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. Recently, several studies have suggested that BMK1 plays an important role in the pathogenesis of cardiovascular disease. To clarify the pathophysiological significance of BMK1 in the process of vascular remodeling, we explored the molecular mechanisms of BMK1 activation in vascular smooth muscle cells (VSMCs). From the results of co-immunoprecipitation and immunoblotting analyses, it was found that platelet-derived growth factor (PDGF), a known potent mitogen, activated BMK1 and triggered the Gab1-SHP-2 interaction in rat aortic smooth muscle cells (RASMCs). The abrogation of SHP-2 phosphatase activity by transfection of the SHP-2-C/S mutant suppressed PDGF-stimulated BMK1 activation. Infection with an adenoviral vector expressing dominant-negative MEK5alpha, which can suppress PDGF-stimulated BMK1 activation to the control level, inhibited PDGF-induced RASMC migration. Moreover, we observed an increase of BMK1 activation in injured mouse femoral arteries. From these findings, it is suggested that BMK1 activation leads to VSMC migration induced by PDGF via Gab1-SHP-2 interaction, and that BMK1-mediated VSMC migration may play a role in the pathogenesis of vascular remodeling.
(キーワード)
Animals / Cell Movement / Humans / MAP Kinase Kinase 5 / Male / Mice / Mice, Inbred C57BL / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinase 7 / Muscle, Smooth, Vascular / Myocytes, Smooth Muscle / Phosphoproteins / Phosphorylation / Platelet-Derived Growth Factor / Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Rats
Yasunobu Hayabuchi, Kazuhiro Mori, Tetsuya Kitagawa, Miki Inoue and Shoji Kagami : Accurate quantification of pulmonary artery diameter in patients with cyanotic congenital heart diease using multidetector-row computed tomography, American Heart Journal, Vol.154, No.4, 783-788, 2007.
(要約)
The purpose of this study is to assess the feasibility of multidetector-row computed tomography (MDCT) for the quantitative evaluation of pulmonary artery morphology in children with congenital heart disease that is associated with reduced pulmonary blood flow. Quantification of measurements at the pulmonary artery annulus and right and left pulmonary arteries, and detection of stenoses exceeding 30% diameter reduction were evaluated independently on MDCT and conventional invasive angiography in 56 MDCT scans of 44 children. The diameters of the right and left pulmonary arteries were measured just proximal to the first branch and at the site of maximum stenosis. There was an excellent correlation between MDCT and conventional pulmonary angiography in quantifying the diameter of the right and left pulmonary arteries (R2 = 0.85 and 0.82, respectively), although a systematic overestimation was observed on MDCT (bias 0.38 +/- 0.49 and 0.28 +/- 0.54 mm, respectively). The pulmonary artery annulus diameter on MDCT scans moderately correlated with the measurement on conventional angiograms (R2 = 0.48). Multidetector-row computed tomography correctly detected 15 of 16 pulmonary artery stenotic lesions that were detected on invasive angiography. There was an excellent correlation between MDCT and conventional angiograms with respect to evaluation of stenotic sites (R2 = 0.82). Our findings showed a strong correlation of vessel diameter measurements between MDCT and invasive pulmonary angiography. This study demonstrates the feasibility of MDCT in assessing pulmonary artery size and morphology.
Yasunobu Hayabuchi, Kazuhiro Mori and Shoji Kagami : Virtual endoscopy using multidetector-row CT for coil occlusion of patent ductus arteriosus, Catheterization and Cardiovascular Interventions, Vol.70, No.3, 434-439, 2007.
(要約)
The objective of this study was to report the clinical value of virtual endoscopy using multidetector-row CT (MDCT) for coil occlusion of patent ductus arteriosus (PDA). We studied 10 consecutive patients with PDA undergoing cardiac catheterization and coil occlusion. All patients had previously undergone MDCT, and subsequently underwent transcatheter closure of ductus. MDCT evaluations were performed again in 1-3 months after occlusion. Virtual endoscopy showed the anatomy of the orifice of the ductus and spatial relations of adjacent structures from both the aortic and pulmonary sides in all patients. We were able to observe the inner space, and fly through the PDA. This approach is the virtual view of the catheter advancing during coil occlusion. Following occlusion, visualization of the coil can also be established by viewing from inside. Coil protrusion into the aortic and pulmonary sides was clearly observed. Virtual endoscopy provides unique information regarding the ductal lumen that is of use for the coil occlusion of PDA.
Yasunobu Hayabuchi, Kazuhiro Mori, Tetsuya Kitagawa, Sakata Miho and Shoji Kagami : Polytetrafluoroethylene graft calcification in patients with surgically repaired congenital heart disease:Evaluation using multidetector-row computed tomography, American Heart Journal, Vol.153, No.5, 806e1-806e8, 2007.
(要約)
Noninvasive determination of calcified prosthetic polytetrafluoroethylene (PTFE) is important in improving risk stratification. The purpose of this study is to assess the feasibility of multidetector-row computed tomography (MDCT) for the evaluation of PTFE calcification in patients with surgically repaired congenital heart disease and to evaluate the development and characteristics of calcification for specific surgical procedures. Seventy-six implanted PTFE grafts in 47 patients were evaluated by MDCT (Aquillion 16, Toshiba Corporation, Tokyo, Japan). Explanted PTFE grafts were evaluated histologically in 4 patients who underwent reoperation after MDCT scans. Calcification of prosthetic PTFE was detected in 5 of 29 cases (17%) for ventricular septal defect (VSD) patches, 26 of 32 (81%) for right ventricular outflow tract (RVOT) prosthesis, 2 of 8 (25%) for atrial septal patches of the Fontan procedure, and 7 of 7 (100%) for extracardiac conduits of total cavopulmonary connection. The CT attenuation of PTFE revealed significantly different values for VSD patches (114 +/- 61 Hounsfield units [HU]), RVOT prosthesis (243 +/- 132 HU), atrial septal patches (163 +/- 161 HU), and extracardiac conduits (230 +/- 29 HU) (P < .0001). The CT density value of VSD patches was significantly lower than those of RVOT grafts and extracardiac conduits (P < .05). The MDCT findings were consistent with histologic analysis in the evaluation of calcification. This study demonstrates that MDCT enables the evaluation of prosthetic PTFE graft calcification; PTFE grafts in 4 different implantation sites demonstrated distinctive features and the prevalence of calcification.
Kazuhiro Mori, Yasunobu Hayabuchi, Miho Sakata, Ryuji Nakagawa, Shoji Kagami, Katsunori Tatara, Y Hirayama and Y Abe : Myocardial strain imaging for early detection of cardiac involvement in patients with Duchenne's progressive muscular dystrophy., Echocardiography, Vol.24, No.6, 598-608, 2007.
(要約)
In patients with Duchenne's progressive muscular dystrophy (DMD), myocardial fibrosis begins from the epicardial half of the left ventricular posterior wall. Myocardial strain imaging by tissue Doppler echocardiography is a new method for assessing regional myocardial function. We hypothesized that this method might be useful for the early detection of subclinical myocardial involvement in DMD patients. Myocardial radial strain of the left ventricle was measured in 25 DMD patients (age: 14.8 +/- 3.1 years) with a normal left ventricular shortening fraction and 25 age-matched healthy controls. Peak systolic radial strain of the posterior wall in a short-axis view of the left ventricle was significantly lower in DMD patients compared to control subjects (P < 0.0001). In the interventricular septum, peak systolic radial strain was not significantly different between the two groups. Receiver operating characteristic curve analysis differentiated DMD patients from control patients with 92% sensitivity and 92% specificity, when the cutoff value for systolic peak strain of the posterior wall was 61%. When radial strain was measured separately for the inner and outer halves of the posterior wall, a systolic negative strain was more frequently observed in the outer half than in the inner half of the posterior wall (6/25 vs. 0/25, P < 0.05). Myocardial strain imaging in DMD patients was characterized by decreased peak systolic strain of the posterior wall despite normal standard echocardiographic findings. Strain measurement might be useful for early detection of subtle regional myocardial dysfunction.
(キーワード)
Adolescent / Adult / Child / Early Diagnosis / Echocardiography, Doppler / Heart / Heart Diseases / Heart Ventricles / Humans / Muscular Dystrophy, Duchenne / Observer Variation / Predictive Value of Tests / ROC Curve / Sensitivity and Specificity / Time Factors / Ventricular Dysfunction, Left
Yasunobu Hayabuchi, Yutaka Nakaya, Yasui Sonoko, Kazuaki Mawatari, Kazuhiro Mori, Suzuki Mitsujiro and Shoji Kagami : Angiotensin II activates intermediate-conductance Ca2+-activated K+ channels in arterial smooth muscle cells., Journal of Molecular and Cellular Cardiology, Vol.41, No.6, 972-929, 2006.
(要約)
Angiostensin II (Ang II) regulates the migration and proliferation of vascular smooth muscle cells. Recent studies indicate that intermediate-conductance Ca2+ -activated K+ (IKca) channels have an important role in cell migration and proliferation. It is not known, however, whether the action of Ang II is linked to IKca channel regulation. Here, we investigated the modulation of IKca channels by Ang II in artery smooth muscle cells. Functional IKca channel expression in cultured embryonic rat aorta smooth muscle (A10) cells was studied using the patch-clamp technique. These cells predominantly express IKca channels. In contrast, large-conductance Ca2+ -activated K+ (BKca) currents were rarely observed in excised patches. Ang II increased the IKca current in a contration-dependent manner. Losartan (1.0 microM), an AT1 selective antagonist, abolished the activation of IKca channels by Ang II. Pretreatment with 100 microM myristoylated protein kinase C inhibitor peptide 20-28 or 10 microM GF109203X completely abolished the AngII-induced activation of IKca currents, whereas the action of Ang II was not prevented in the presence of 100 microM Rp-cyclic 3', 5'-hydrogen phosphotiate adenosine triethylammonium, a protein kinase A inhibitor, or 1.0 microM KT-5823, a protein kinase G inhibitor. A membrane permeant analogue of diacylglycerol 1, 2-dioctanoyl-sn-glycerol (10 microM) induced the activation of IKca currents. These data suggest that Ang II activates IKca channels through the activation of protein kinase C, and the AT1 receptor is involved in the regulation of these channels.
(キーワード)
Angiotensin II / Angiotensin II Type 1 Receptor Blockers / Animals / Cells, Cultured / Diglycerides / Enzyme Inhibitors / Intermediate-Conductance Calcium-Activated Potassium Channels / Losartan / Muscle, Smooth, Vascular / Myocytes, Smooth Muscle / Patch-Clamp Techniques / Protein Kinase C / Rats / Receptor, Angiotensin, Type 1 / Signal Transduction
Shuji Kondo, Maki Shimizu, Maki Urushihara, Koichiro Tsuchiya, Masanori Yoshizumi, Toshiaki Tamaki, Akira Nishiyama, Hiroshi Kawachi, Fujio Shimizu, Quinn T. Mark, Lambeth J. David and Shoji Kagami : Addition of the antioxidant probucol to angiotensin II type I receptor antagonist arrests progression mesangioproliferative glomerulonephritis in the rat, Journal of the American Society of Nephrology, Vol.17, No.3, 783-794, 2006.
(要約)
Angiotensin II (Ang II) and reactive oxidative species (ROS) that are produced by NADPH oxidase have been implicated in the progression of glomerulonephritis (GN). This study examined the effect of simultaneously interrupting Ang II and ROS with an Ang II receptor blocker (ARB), candesartan, and a free radical scavenger, probucol, in a model of progressive mesangioproliferative GN induced by the injection of anti-Thy-1 antibody into uninephrectomized rats. Nephritic rats were divided into four groups and given daily oral doses of the following: Vehicle, 1% probucol diet, 70 mg/L candesartan in drinking water, and probucol plus candesartan. These treatments lasted until day 56. Vehicle-treated nephritic rats developed progressively elevated proteinuria and glomerulosclerosis. Candesartan kept proteinuria significantly lower than vehicle or probucol. The addition of probucol to candesartan normalized urinary protein excretion. Increases in BP in nephritic rats were lowered by these treatments, except with probucol. It is interesting that both glomerular cell number and glomerulosclerosis were significantly decreased by candesartan and normalized by the addition of probucol. Immunohistochemical studies for TGF-beta1, collagen type I, and fibronectin revealed that the combined treatment abolished glomerular fibrotic findings compared with candesartan. In addition, glomerular expression of NADPH oxidase components and superoxide production suggested that the combined treatment completely eliminated NADPH oxidase-associated ROS production. In conclusion, our study provides the first evidence that the antioxidant probucol, when added to an Ang II receptor blockade, fully arrests proteinuria and disease progression in GN. Furthermore, the data suggest that NADPH oxidase-associated ROS production may play a pivotal role in the progression of GN. The combination of probucol and candesartan may represent a novel route of therapy for patients with progressive GN.
(キーワード)
Angiotensin II Type 1 Receptor Blockers / Animals / Antioxidants / Biopsy, Needle / Blotting, Western / Disease Models, Animal / Disease Progression / Drug Therapy, Combination / Female / Glomerulonephritis, Membranoproliferative / Immunohistochemistry / Male / Probability / Probucol / Proteinuria / Rats / Rats, Sprague-Dawley / Sensitivity and Specificity
Miki Inoue, Kazuhiro Mori, Yasunobu Hayabuchi, Katsunori Tatara and Shoji Kagami : Mean heart rate at noght as a predictor for the evaluation of autonomic function in patietns with Duchenne progressive muscular dystrophy, Eur Heart J, Vol.27, suppl-685, 2006.
148.
Sakata Miho, Kazuhiro Mori, Yasunobu Hayabuchi, Suzuki Mitsujiro, Ryuji Nakagawa, Shoji Kagami and Baba Hirotaka : Myocardial systolic strain in normal children using a tissue tracking system, Journal of Echocardiography, Vol.4, No.1, 19-24, 2006.
Yoshihiro Touda, Kenji Mori, Toshiaki Hashimoto, Masahito Miyazaki, Satoshi Nozaki, Yasuyoshi Watanabe, Yasuhiro Kuroda and Shoji Kagami : Administration of secretin for autism alters dopamine metabolism in the central nervous system., Brain & Development, Vol.28, No.2, 99-103, 2005.
(要約)
We evaluated the clinical effects of intravenously administered secretin in 12 children with autism (age range: 4-6 years, median age: 9 years, boy:girl=8:4). In addition, we investigated the association between improvement in symptoms and changes in the cerebrospinal fluid (CSF) homovanillic acid (HVA),5-hydroxyindole-3-acetic acid (5-HIAA), and 6R-5,6,7,8-tetrahydro-L-biopterin (BH(4)) levels after administration. After administration of secretin, the Autism Diagnostic Interview-Revised (ADI-R) score improved in 7 of the 12 children. However, the score deteriorated in 2 of the 12 children (in the item of 'restricted and repetitive, stereotyped interests and behaviors'). The HVA and BH(4) levels in CSF were increased in all children with improvement in the ADI-R score. In contrast, no patient without the elevation of the BH(4) level showed improvement in the score. These findings suggest that secretin activated metabolic turnover of dopamine in the central nervous system via BH(4), improving symptoms.
Clinical evidence suggests a relationship between hypertension and insulin resistance, and cross-talk between angiotensin II (Ang II) and insulin signaling pathways may take place. We now report the effect of Ang II on insulin-induced glucose uptake and its intracellular mechanisms in vascular smooth muscle cells (VSMC). We examined the translocation of glucose transporter-4 (GLUT-4) and glucose uptake in rat aortic smooth muscle cells (RASMC). Mitogen-activated protein (MAP) kinases and Akt activities, and phosphorylation of insulin receptor substrate-1 (IRS-1) at the serine and tyrosine residues were measured by immunoprecipitation and immunoblotting. As a result, Ang II inhibited insulin-induced GLUT-4 translocation from cytoplasm to the plasma membrane in RASMC. Ang II induced extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) activation and IRS-1 phosphorylation at Ser307 and Ser616. Ang II-induced Ser307 and Ser616 phophorylation of IRS-1 was inhibited by a MEK inhibitor, PD98059, and a JNK inhibitor, SP600125. Ang II inhibition of insulin-stimulated IRS-1 tyrosyl phophorylation and Akt activation were reversed by PD98059 but not by SP600125. Ang II inhibited insulin-induced glucose uptake, which was also reversed by PD98059 but not by SP600125. It is shown that Ang II-induced ERK1/2 activation inhibits insulin-dependent glucose uptake through serine phophorylation of IRS-1 in RASMC.
Koichiro Tsuchiya, Yasuhisa Kanematsu, Masanori Yoshizumi, Hideki Ohnishi, Kazuyoshi Kirima, Yuki Izawa, Michiyo Shikishima, Tatsuhiro Ishida, Shuji Kondo, Shoji Kagami, Yoshiharu Takiguchi and Toshiaki Tamaki : Nitrite is an alternative source of NO in vivo, American Journal of Physiology, Heart and Circulatory Physiology, Vol.288, No.5, H2163-H2170, 2005.
(要約)
In this study, we investigated whether orally administered nitrite is changed to NO and whether nitrite attenuates hypertension in a dose-dependent manner. We utilized a stable isotope of [15N]nitrite (15NO2-) as a source of nitrite to distinguish between endogenous nitrite and that exogenously administered and measured hemoglobin (Hb)-NO as an index of circulating NO in whole blood using electron paramagnetic resonance (EPR) spectroscopy. When 1 mg/kg Na15NO2 was orally administered to rats, an apparent EPR signal derived from Hb15NO (A(Z) = 23.4 gauss) appeared in the blood. The peak blood HbNO concentration occurred at the first measurement after intake (5 min) for treatment with 1 and 3 mg/kg (HbNO: 4.93 +/- 0.52 and 10.58 +/- 0.40 microM, respectively) and at 15 min with 10 mg/kg (HbNO: 38.27 +/- 9.23 microM). In addition, coadministration of nitrite (100 mg/l drinking water) with N(omega)-nitro-L-arginine methyl ester (L-NAME; 1 g/l) for 3 wk significantly attenuated the L-NAME-induced hypertension (149 +/- 10 mmHg) compared with L-NAME alone (170 +/- 13 mmHg). Furthermore, this phenomenon was associated with an increase in circulating HbNO. Our findings clearly indicate that orally ingested nitrite can be an alternative to L-arginine as a source of NO in vivo and may explain, at least in part, the mechanism of the nitrite/nitrate-rich Dietary Approaches to Stop Hypertension diet-induced hypotensive effects.
Maki Urushihara, Shoji Kagami, Michinori Ito, Koji Yasutomo, Shuji Kondo, Akiko Kitamura, Akiyoshi Takahashi and Yasuhiro Kuroda : Transforming growth factor-β in renal disease with glycogen storage disease I, Pediatric Nephrology, Vol.19, No.6, 676-678, 2004.
(要約)
We report a 14-year-old patient with Japanese glycogen storage disease I (GSD-I) who was found to have proteinuria. Renal biopsy revealed massive tubular atrophy and interstitial fibrosis with mononuclear cell infiltration, but the glomeruli were almost normal. The epithelial cells of tubules contained periodic acid-Schiff-positive glycogen deposits digested by diastase. In an immunohistological study, transforming growth factor (TGF)-beta expression was increased in tubular epithelial cells compared with a normal control kidney specimen. These data suggest that increased TGF-beta expression is involved in the pathophysiology of renal interstitial fibrosis in a patient with GSD-I.
Keisuke Ishizawa, Masanori Yoshizumi, Koichiro Tsuchiya, Hitoshi Houchi, Kazuo Minakuchi, Yuki Izawa, Yasuhisa Kanematsu, Shoji Kagami, Masao Hirose and Toshiaki Tamaki : Dual effects of endothelin-1 (1-31): induction of mesangial cell migration and facilitation of monocyte recruitment through monocyte chemoattractant protein-1 production by mesangial cells, Hypertension Research, Vol.27, No.6, 433-440, 2004.
(要約)
We previously found that human chymase selectively cleaves big endothelin-1 (ET-1) at the Tyr31-Gly32 bond and produces 31-amino acid endothelins, ET-1 (1-31), without any further degradation products. In this study, we investigated the effect of ET-1 (1-31) on the migration of cultured rat mesangial cells (RMCs) and on cells of the human monocytic cell line, THP-1. In addition, we examined the interaction between RMCs and THP-1 cells using conditioned media from ET-1 (1-31)-stimulated RMCs. ET-1 (1-31) caused an increase in RMC migration in a concentration-dependent manner, and the degree of increase was similar to those by ET-1 and angiotensin II (All). The ET-1 (1-31)-induced increase in RMC migration was inhibited by BQ123, an endothelin ETA receptor antagonist, but not by BQ788, an endothelin ETB receptor antagonist. ET-1 (1-31) alone did not cause significant migration of THP-1 cells. However, significant recruitment of THP-1 cells was observed with conditioned media taken from ET-1 (1-31)-stimulated RMCs. The conditioned media-induced migration of THP-1 cells was inhibited by BQ123, but not by BQ788. Western blotting analysis of the lysate of RMCs revealed that the expression of monocyte chemoattractant protein-1 (MCP-1) protein in RMCs was increased by treatment with ET-1 (1-31). The addition of neutralizing antibody for MCP-1 to the medium inhibited the migration of THP-1 cells induced by conditioned media from ET-1 (1-31)-stimulated RMCs. These findings suggest that ET-1 (1-31) play a role in glomerulonephritis (GN) via dual effects that directly cause the migration of mesangial cells (MCs) and may be responsible for the recruitment of mononuclear cells mediated through the activation of MCs. Since human chymase has been reported to be involved in glomerular disease, ET-1 (1-31) may be among the mediators.
Maki Urushihara, Shoji Kagami, Koji Yasutomo, Michinori Ito, Shuji Kondo, Akiko Kitamura, Dag Malm, Helle Klenow, Oiviind Nilssen and Yasuhiro Kuroda : Sisters with α-mannosidosis and systemic lupus erythematosus, European Journal of Pediatrics, Vol.163, No.4-5, 192-195, 2004.
(要約)
Alpha-mannosidosis is an autosomal recessive disorder caused by deficiency of lysosomal alpha-mannosidase (LAMAN). Here, we report two sisters with alpha-mannosidosis who developed systemic lupus erythematosus (SLE). The sisters were both homozygous for a one bp deletion within the LAMAN gene resulting in a truncated gene product. The coincidence of alpha-mannosidosis and SLE are discussed with regard to both clinical and molecular findings. CONCLUSION: alpha-mannnosidosis may contribute to the onset of systemic lupus erythematosus in predisposed patients.
Yuki Suzaki, Masanori Yoshizumi, Shoji Kagami, Akira Nishiyama, Yuichi Ozawa, Moe Kyaw, Yuki Izawa, Yasuhisa Kanematsu, Koichiro Tsuchiya and Toshiaki Tamaki : BMK1 is activated in glomeruli of diabetic rats and in mesangial cells by high glucose conditions, Kidney International, Vol.65, No.5, 1749-1760, 2004.
(要約)
High glucose causes renal cell injury through various signal transduction pathways, including mitogen-activated protein (MAP) kinases cascades. Big MAP kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a recently identified MAP kinase family member and was reported to be sensitive to osmotic and oxidative stress. However, the role of BMK1 in diabetic nephropathy has not been elucidated yet. We investigated whether BMK1 is activated in the glomeruli of Otsuka Long Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus in comparison with the control Long Evans Tokushima Otsuka (LETO) rats. We also examined the effect of high glucose on BMK1 activity in cultured rat mesangial cells. BMK1 and ERK1/2 but not p38 were activated in the glomeruli of OLETF rats, which showed diabetic nephropathy at 52 weeks of age. High glucose, in addition to a high concentration of raffinose, caused rapid and significant activation of BMK1 in rat mesangial cells. MAP kinase/ERK kinase (MEK) inhibitors, U0126 and PD98059, both inhibited BMK1 activation by high glucose in a concentration-dependent manner. Protein kinase C (PKC) inhibition by GF109203X and PKC down-regulation with long-time phorbol myristate acetate (PMA) treatment both inhibited BMK1 and Src kinase activation. Src kinase inhibitors, herbimycin A and PP2, also inhibited high glucose-induced BMK1 activation. PKC inhibitors, Src inhibitors and MEK inhibitors, all inhibited cell proliferation by high glucose. Finally, transfection of dominant-negative MEK5, which is an upstream regulator of BMK1, abolished the BMK1-mediated rat mesangial cell proliferation stimulated by high glucose. In the present study, we demonstrated that high glucose activates BMK1 both in vivo and in vitro. It was suggested that high glucose induces PKC- and c-Src-dependent BMK1 activation. It could not be denied that BMK1 activation is induced through an osmotic stress-sensitive mechanism. BMK1-mediated mesangial cell growth may be involved in the pathogenesis of diabetic nephropathy.
Moe Kyaw, Masanori Yoshizumi, Koichiro Tsuchiya, Shoji Kagami, Yuki Izawa, Yoshiko Fujita, Nermin Ali, Yasuhisa Kanematsu, Kazunori Toida, Kazunori Ishimura and Toshiaki Tamaki : Src and Cas are essentially but differentially involved in angiotensin II-stimulated migration of vascular smooth muscle cell via extracellur signal-regulated kinase 1/2 and c-Jun NH2-terminal kinase activation, Molecular Pharmacology, Vol.65, No.4, 832-841, 2004.
(要約)
Angiotensin II (Ang II) plays an important role in several cardiovascular diseases associated with vascular smooth muscle cell (VSMC) growth and migration. Src activity is known to be required for the migration of a number of cell types. p130Cas was reported to be essential for cell migration and actin filament reorganization. Mitogen-activated protein (MAP) kinases were also reported to be critical regulatory factors for growth and migration of VSMC. However, precise intracellular mechanisms involving c-Src, p130Cas, and MAP kinases in Ang II-stimulated migration of VSMC have not been well elucidated. Here we demonstrated that Ang II rapidly and significantly stimulated tyrosine phosphorylation of Src and Cas and their association in rat aortic smooth muscle cells (RASMC). Ang II-stimulated tyrosine phosphorylation of Src and Cas and activation of ERK1/2 and JNK, but not p38, were potently inhibited by Src family tyrosine kinase inhibitors, herbimycin A (HA) and PP2. Ang II-stimulated Src and Cas association, tyrosine phosphorylation of Cas, and activation of ERK1/2 and JNK were suppressed in kinase-inactive Src (KI Src)-overexpressed RASMC. Ang II-stimulated JNK activation but not ERK1/2 activation was blocked in substrate domain-deleted Cas (DeltaSD Cas)-overexpressed RASMC. In addition, HA, PP2, ERK1/2 inhibitor, 2'-amino-3'-methoxyflavone (PD98059) and JNK inhibitor, and anthra[1,9-cd]pyrazol-6(2H)-one (SP600125) significantly inhibited Ang II-stimulated migration of RASMC. Ang II-induced colocalization of Src and Cas and migration were inhibited in both KI Src- and DeltaSD Cas-overexpressed RASMC. These findings suggest that Src and Cas are essentially but differentially involved in Ang II-stimulated migration of VSMC through the activation of ERK1/2 and JNK.
(キーワード)
Angiotensin II / Animals / Cell Adhesion / Cell Movement / Cells, Cultured / Cellular Apoptosis Susceptibility Protein / Enzyme Activation / Genes, src / JNK Mitogen-Activated Protein Kinases / Male / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinases / Muscle, Smooth, Vascular / リン酸化 (phosphorylation) / Rats / Rats, Sprague-Dawley / Tyrosine / Vinculin / src-Family Kinases
Shoji Kagami, M Urushihara, A Kitamura, S Kondo, Tetsuhiro Hisayama, M Kitamura, K Loster, W Reutter and Yasuhiro Kuroda : PDGF-BB enhances alpha1beta1 integrin-mediated activation of the ERK/AP-1 pathway involved in collagen matrix remodeling by rat mesangial cells., Journal of Cellular Physiology, Vol.198, No.3, 470-478, 2004.
(要約)
Platelet-derived growth factor-BB (PDGF-BB) has been implicated in the pathogenesis of progressive glomerulonephritis (GN). Previous studies have reported that PDGF-BB stimulates mesangial cells (MCs)-induced collagen matrix remodeling through enhancement of alpha1beta1 integrin-dependent migratory activity. To determine the cell signaling pathway responsible for abnormal MC-related mesangial matrix remodeling in progressive GN, we studied the involvement of the extracellular signal-regulated kinase (ERK)/activator protein-1 (AP-1) pathway in PDGF-BB-enhanced collagen gel contraction. Western blotting and gel shift assay revealed that MC-induced gel contraction resulted in ERK activation in parallel with that of AP-1 binding, peaking at 4 h and lasting at least for 24 h. Application of the MEK inhibitor, U0126, and the c-jun/AP-1 inhibitor, curcumin, inhibited gel contraction and AP-1 activity, respectively, dose dependently. PDGF-BB enhanced not only gel contraction but ERK phosphorylation and AP-1 activity by MCs. Marked inhibitory effects on PDGF-BB-induced gel contraction and ERK/AP-1 activity were observed in the presence of either function blocking anti-alpha1- or anti-beta1-integrin antibody or U0126. Consistently, AP-1-inactive MCs expressing a dominant-negative mutant of c-jun showed a significant decrease of PDGF-BB-induced gel contraction as compared with mock-transfected MCs. Finally, migration assay showed that ERK/AP-1 activity is required for PDGF-BB-stimulated alpha1beta1 integrin-dependent MC migration to collagen I. These results indicated that PDGF-BB enhances alpha1beta1 integrin-mediated collagen matrix reorganization through the activation of the ERK/AP-1 pathway that is crucial for MC migration. We conclude that the ERK/AP-1 pathway plays an important role in PDGF-BB-induced alpha1beta1 integrin-dependent collagen matrix remodeling; therefore, the inhibition of its pathway may provide a novel approach to regulate abnormal collagen matrix remodeling in progressive GN.
Tumor necrosis factor-alpha (TNF-alpha) stimulates expression of endothelial cell (EC) genes that may promote atherosclerosis in part by an activation of mitogen-activated protein (MAP) kinases. Ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]-one), a selenoorganic compound, is effective for acute ischemic stroke; however, its effect on EC has not yet been elucidated. We examined the effect of ebselen on TNF-alpha-induced MAP kinase activation and adhesion molecule expression in cultured human umbilical vein endothelial cells (HUVEC). Extracellular signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 were rapidly and significantly activated by TNF-alpha in HUVEC. TNF-alpha-induced JNK activation was inhibited by ebselen, whereas ERK1/2 and p38 were not affected. Apoptosis signal-regulated kinase 1 (ASK1) was suggested to be involved in TNF-alpha-induced JNK activation because transfection of kinase-inactive ASK1 inhibited TNF-alpha-induced JNK activation. Ebselen inhibited TNF-alpha-induced TNF receptor-associated factor 2 (TRAF2)-ASK1 complex formation and phosphorylation of stress-activated protein kinase ERK kinase 1 (SEK1), which is an upstream signaling molecule of JNK. Finally, TNF-alpha-induced activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) activation and resultant intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions were inhibited by ebselen. Specific inhibitors for JNK and NF-kappaB also inhibited TNF-alpha-induced ICAM-1 and VCAM-1 expressions in HUVEC. These findings suggest that ebselen prevents TNF-alpha-induced EC activation through the inhibition of TRAF2-ASK1-SEK1 signaling pathway, which leads to JNK activation. Inhibition of JNK by ebselen may imply its usefulness for the prevention of atherosclerosis relevant to EC activation.
Akira Nishiyama, Li Yao, Y Nagai, K Miyata, Masanori Yoshizumi, Shoji Kagami, Shuji Kondo, Hideyasu Kiyomoto, T Shokoji, Shoji Kimura, Masakazu Kohno and Youichi Abe : Possible Contributions of Rerative Oxygen Species and Mitoten-Activated Protein Kinase to Renal Injury in Aldosterone/Salt-Induced Hypertensive Rats, Hypertension, Vol.43, No.4, 841-848, 2004.
(要約)
Studies were performed to test the hypothesis that reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) contribute to the pathogenesis of aldosterone/salt-induced renal injury. Rats were given 1% NaCl to drink and were treated with one of the following combinations for 6 weeks: vehicle (0.5% ethanol, SC, n=6); aldosterone (0.75 microg/H, SC, n=8); aldosterone plus a selective mineralocorticoid receptor antagonist; eplerenone (0.125% in chow, n=8); aldosterone plus an antioxidant; and tempol (3 mmol/L in drinking solution, n=8). The activities of MAPKs, including extracellular signal-regulated kinases (ERK)1/2, c-Jun-NH2-terminal kinases (JNK), p38MAPK, and big-MAPK-1 (BMK1) in renal cortical tissues were measured by Western blot analysis. Aldosterone-infused rats showed higher systolic blood pressure (165+/-5 mm Hg) and urinary excretion of protein (106+/-24 mg/d) than vehicle-infused rats (118+/-3 mm Hg and 10+/-3 mg/d). Renal cortical mRNA expression of p22phox, Nox-4, and gp91phox, measured by real-time polymerase chain reaction, was increased in aldosterone-infused rats by 2.3, 4.3, and 3.0-fold, respectively. Thiobarbituric acid-reactive substances (TBARS) content in renal cortex was also higher in aldosterone (0.23+/-0.02) than vehicle-infused rats (0.09+/-0.01 nmol/mg protein). ERK1/2, JNK, and BMK1 activities were significantly elevated in aldosterone-infused rats by 3.3, 2.3, and 3.0-fold, respectively, whereas p38MAPK activity was not changed. Concurrent administration of eplerenone or tempol to aldosterone-infused rats prevented the development of hypertension (127+/-2 and 125+/-5 mm Hg), and the elevations of urinary excretion of protein (10+/-2 and 9+/-2 mg/day) or TBARS contents (0.08+/-0.01 and 0.11+/-0.01 nmol/mg protein). Furthermore, eplerenone and tempol treatments normalized the activities of ERK1/2, JNK, and BMK1. These data suggest that ROS and MAPK play a role in the progression of renal injury induced by chronic elevations in aldosterone.
(キーワード)
Aldosterone / Animals / Cyclic N-Oxides / Hypertension / JNK Mitogen-Activated Protein Kinases / Kidney Cortex / MAP Kinase Signaling System / Male / Membrane Transport Proteins / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinase 7 / Mitogen-Activated Protein Kinases / NADPH Dehydrogenase / NADPH Oxidase / Oxidative Stress / Phosphoproteins / Proteinuria / Rats / Rats, Sprague-Dawley / Reactive Oxygen Species / Sodium Chloride / Spin Labels / Spironolactone
Nermin Ali, Masanori Yoshizumi, Koichiro Tsuchiya, Moe Kyaw, Yoshiko Fujita, Yuki Izawa, Shinji Abe, Yasuhisa Kanematsu, Shoji Kagami and Toshiaki Tamaki : Ebsalen inhibits p38MAP kinase-mediated endothelial cell death by hydrogen peroxide., European Journal of Pharmacology, Vol.485, No.1-3, 127-135, 2004.
(要約)
Ebselen (2-phenyl-1, 2-benzisoselenazol-3[2H]-one) is a seleno-organic compound exhibiting both glutathione peroxidase and antioxidant activity. Although it has been reported that ebselen is effective against hydrogen peroxide (H(2)O(2))-induced cell death in several cell types, its effect on endothelial cell damage has not yet been elucidated. In the present study, we examined the effect of ebselen on H(2)O(2)-induced human umbilical vein endothelial cells (HUVECs) death, and its intracellular mechanism. Our findings showed that pretreatment of HUVECs with ebselen resulted in a significant recovery from H(2)O(2)-induced cell death in a concentration-dependent manner. In addition to the inhibition of lactate dehydrogenase (LDH) leakage, ebselen inhibited H(2)O(2)-induced cytochrome c release and caspase-3 activation and the resultant apoptosis in HUVECs. Moreover, it was observed that H(2)O(2) significantly stimulated activation of mitogen-activated protein (MAP) kinases, i.e., p38 MAP kinase, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK1/2). Ebselen inhibited H(2)O(2)-induced p38 MAP kinase, but not JNK or ERK1/2 activation. Furthermore, SB203580 (4-[4-fluorophenyl]-2-[4-methylsulfinylphenyl]-5-[4-pyridyl]-1H-imidazole), a specific p38 MAP kinase inhibitor, inhibited H(2)O(2)-induced p38 MAP kinase phosphorylation, cytochrome c release, caspase-3 activation, as well as cell death in HUVECs. These findings suggest that ebselen attenuates H(2)O(2)-induced endothelial cell death through the inhibition of signaling pathways mediated by p38 MAP kinase, caspase-3, and cytochrome c release. Thus, inhibition of p38 MAP kinase by ebselen may imply its usefulness for prevention and/or treatment of endothelial cell dysfunction, which was suggested to be the first step in the development of atherosclerosis.
Akira Nishiyama, Masanori Yoshizumi, Hirofumi Hitomi, Shoji Kagami, Shuji Kondo, Akira Miyatake, Megumu Fukunaga, Toshiaki Tamaki, Hideyasu Kiyomoto, Masakazu Kohno, Takatomi Shokoji, Shoji Kimura and Abe Youichi : The SOD mimetic tempol ameliorates glomerular injury and reduces MAPK activity in Dahl salt-sensitive rats., Journal of the American Society of Nephrology, Vol.15, No.2, 306-315, 2004.
(要約)
It was shown recently that renal injury in Dahl salt-sensitive (DS) hypertensive rats is accompanied by mitogen-activated protein kinase (MAPK) activation. The present study was conducted to elucidate the contribution of reactive oxygen species to MAPK activities and renal injury in DS rats. DS rats were maintained on high salt (H; 8.0% NaCl; n = 7) or low salt (L; 0.3% NaCl; n = 6) diets; H + a superoxide dismutase mimetic, tempol (3 mmol/L in drinking water; n = 8); or H + hydralazine (0.5 mmol/L in drinking water; n = 8) for 4 wk. Mean BP (MBP) in DS/H and DS/L rats was 185 +/- 7 and 113 +/- 3 mmHg, respectively. DS/H rats showed a higher ratio of urinary protein excretion and creatinine (U(protein)V/U(cr)V; 20.3 +/- 1.1) and a higher cortical collagen content (22 +/- 1 micro g/mg) than in DS/L rats (2.4 +/- 0.1 and 13 +/- 1 micro g/mg, respectively). The expression of p22-phox and Nox-1, essential components of NAD(P)H oxidase, in renal cortical tissue was approximately threefold higher in DS/H rats than in DS/L rats. Increased activities of renal cortical MAPK, including extracellular signal-regulated kinases (ERK) 1/ERK2 and c-Jun NH(2)-terminal kinases (JNK) were also observed in DS/H rats by 7.0 +/- 0.7- and 4.3 +/- 0.2-fold, respectively. Tempol treatment significantly decreased MBP (128 +/- 3 mmHg), U(protein)V/U(cr)V (4.8 +/- 0.4), and cortical collagen content (14 +/- 1 micro g/mg) and normalized ERK1/ERK2 and JNK activities in DS/H rats. Histologically, tempol markedly ameliorated progressive sclerotic and proliferative glomerular changes in DS/H rats. Hydralazine-treated DS/H rats showed similar MBP (127 +/- 5 mmHg) to tempol-treated DS/H rats. Hydralazine also decreased U(protein)V/U(cr)V (16.2 +/- 1.5) and cortical collagen content (19 +/- 1 micro g/mg) in DS/H rats. However, these values were significantly higher than those of tempol-treated rats. Furthermore, although hydralazine significantly reduced JNK activity (-56 +/- 3%), ERK1/ERK2 activities were unaffected. These data suggest that reactive oxygen species, generated by NAD(P)H oxidase, contribute to the progression of renal injury through ERK1/ERK2 activation in DS/H hypertensive rats.
(キーワード)
Animals / Collagen / Cyclic N-Oxides / JNK Mitogen-Activated Protein Kinases / Kidney Glomerulus / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinases / Proteinuria / Rats / Rats, Inbred Dahl / Spin Labels / p38 Mitogen-Activated Protein Kinases
Shuji Kondo, Shoji Kagami, Maki Shimizu, Akiko Kitamura, Maki Urushihara, Nobuo Satake, Keisuke Izumi and Yasuhiro Kuroda : The role of mast cells in acute tubulo-interstitial nephritis with uveitis, European Journal of Pediatrics, Vol.162, No.7-8, 496-499, 2003.
(要約)
We describe the clinicopathological characteristics of two patients with acute tubulo-interstitial nephritis with uveitis (TINU) with mast cells infiltrating the interstitium. The pathogenesis of TINU remains unknown, but a T-cell-mediated immune response was suggested to be involved. Recent studies have shown that infiltrating mast cells are closely associated with the development of renal interstitial fibrosis in glomerulonephritis. To address the role of mast cells in the renal interstitial injury in TINU, immunohistochemical studies were performed in renal biopsy sections using anti-human mast cell tryptase antibody specific for mast cells. In addition, we tried to detect CD68-positive macrophages to compare with the localisation of mast cells within the renal interstitium. Mast cells and macrophages could be detected in renal interstitial lesions of both patients. Massive infiltration of macrophages into interstitial lesions was observed, whereas mast cells were detected in a sporadic rather than a clustered manner, and associated with fibrotic lesions. Repeat renal biopsy findings suggested the involvement of these cells in the renal interstitial injury because the number of infiltrating mast cells and macrophages in the interstitium decreased with the improvements in clinical symptoms and pathological lesions. CONCLUSION: The present study showed that mast cells might play an important role in the development of renal interstitial injury in tubulo-interstitial nephritis with uveitis.
Akiko Kitamura, Shoji Kagami, Maki Urushihara, Syuji Kondo, Masanori Yoshizumi, Toshiaki Tamaki and Yasuhiro Kuroda : Endothelin-1 is a potent stimulator of a1b1 integrin-mediated collagen matrix remodeling by rat mesangial cells., Biochemical and Biophysical Research Communications, Vol.299, No.4, 555-561, 2002.
(要約)
Endothelin-1 (ET) is known to stimulate mesangial cell (MC) proliferation, extracellular matrix (ECM) synthesis, and thereby contribute to the progression of glomerulonephritis (GN). To clarify the molecular and cellular mechanisms of how ET is involved in the development of glomerular sclerosis, we investigated the influence of ET on the MC-alpha1beta1 integrin-mediated collagen matrix reorganization using a collagen gel contraction assay. ET enhanced MC-alpha1beta1 integrin-mediated gel contraction in a dose-dependent manner. Addition of the endothelin A (ETA) receptor antagonist, BQ123, into collagen gels abolished ET-induced gel contraction by MC. Cell behavior involved in ET-induced gel contraction was investigated in combination with function-blocking anti-alpha1-integrin antibody. Migration and adhesion assays revealed that ET stimulated alpha1beta1 integrin-mediated MC migration but did not influence cell adhesion to type I collagen (collagen I). Integrin-function blocking studies using anti-alpha1 integrin antibody indicated that MC-alpha1beta1 integrin is required not only for collagen-dependent migration, but also for gel contraction. Zymography showed that ET increased MC matrix metalloproteinase-2 (MMP-2) activity in a dose-dependent manner during MC-induced gel contraction process. Finally, flow cytometry analysis indicated that ET did not affect the cell surface expression of the MC-alpha1beta1 integrin within the collagen gel. These data suggested that ET promotes collagen matrix reorganization through the enhancement of MC-alpha1beta1 integrin-dependent migration and MMP-2 activity. We therefore conclude that ET is a potential molecule inducing pathological collagen matrix remodeling observed in progressive GN.
Shoji Kagami, Maki Urushihara, Shuji Kondo, Hayashi Toshihiko, Hiroko Yamano, Loster Kiemens, Vossmeyer Dorte, Reutter Werner and Yasuhiro Kuroda : Effects of Anti-α1 Integrin Subunit Antibody on Anti-Thy-1 Glomerulonephritis, Laboratory Investigation; a Journal of Technical Methods and Pathology, Vol.82, No.9, 1219-1227, 2002.
(要約)
alpha1beta1 integrin is a potential collagen-binding extracellular matrix receptor that mediates collagen-dependent cell adhesion, proliferation, migration, and collagen matrix assembly and thereby may participate in the wound healing and pathologic scarring observed in some damaged organs. To clarify the role of alpha1beta1 integrin predominantly expressed on the mesangial cell (MC) surface in nephritic glomeruli, we investigated the involvement of MC-alpha1beta1 integrin in rat anti-Thy-1 glomerulonephritis (GN) by administering function-blocking monoclonal mouse anti-rat alpha1 integrin subunit antibody (anti-alpha1 Ab). Assay of collagen types I and IV mixed gel contraction, an in vitro model of pathologic collagen matrix remodeling, with function-blocking anti-alpha1 Ab and anti-beta1 Ab, revealed that collagen I and IV matrix reorganization is mediated by MC-alpha1beta1 integrin. In addition, conditioned medium from isolated Day 3 anti-Thy-1 nephritic glomeruli showed increased activity of MC-alpha1beta1 integrin-induced mixed collagen gel contraction as compared with that from isolated normal rat glomeruli. Treatment of Day 3 conditioned medium with anti-platelet-derived growth factor-BB antibody significantly inhibited conditioned media-induced gel contraction, whereas treatment with anti-transforming growth factor-beta antibody did not have a significant effect. Rats that received anti-alpha1 Ab from the left renal artery 3 days after anti-Thy-1 GN induction showed significant decreases of glomerular hypercellularity and mesangial matrix accumulation, including collagen I and IV in the left kidney, compared with those rats in which the left kidney received control mouse IgG1. These results suggest that MC-alpha1beta1 integrin is an important extracellular matrix receptor mediating mesangial remodeling characterized by MC proliferation and mesangial matrix reorganization in anti-Thy-1 GN. Platelet-derived growth factor-BB may be involved in early collagen matrix reorganization leading to pathologic mesangial remodeling in this GN model.
Masanori Yoshizumi, Toshiaki Kogame, Yuki Suzaki, Yoshiko Fujita, Moe Kyaw, Kazuyoshi Kirima, Keisuke Ishizawa, Koichiro Tsuchiya, Shoji Kagami and Toshiaki Tamaki : Ebselen attenuates oxidative styress-induced apoptosis via the inhibition of the c jun N-terminal kinase and activator protein-1 signaling pathway in PC12 cells., British Journal of Pharmacology, Vol.136, No.7, 1023-1032, 2002.
(要約)
1: Ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]-one) is a selenoorganic compound exhibiting both glutathione peroxidase activity and antioxidant activity. Although it has been reported that ebselen is effective for oxidative stress-induced neuronal damage both in vivo and clinically, the precise mechanisms of the efficacy have not yet been elucidated. Thus, we hypothesized that ebselen may affect reactive oxygen species-induced mitogen-activated protein (MAP) kinase activation in cultured PC12 cells. 2: Our findings showed that hydrogen peroxide (H(2)O(2)) stimulated rapid and significant activation of extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and p38 in PC12 cells, which is a model of catecholamine-containing neurons. 3: H(2)O(2)-induced JNK activation was inhibited by ebselen, whereas ERK1/2 and p38 activation by H(2)O(2) were not affected by ebselen. 4: Inhibition by ebselen of H(2)O(2)-induced hydroxyl radical generation in PC12 cells was observed using electron paramagnetic resonance measurements. Ebselen also inhibited H(2)O(2)-induced increases in DNA binding activity of activator protein-1 (AP-1), a downstream transcription factor of JNK, composed of the c-Jun homo/heterodimer. 5: Finally, pretreatment of cells with ebselen resulted in a significant recovery from cell death including apoptosis by H(2)O(2) in PC12 cells. 6 These findings suggest that ebselen attenuates oxidative stress-induced neuronal cell death through the inhibition of the JNK and AP-1 signalling pathway. Thus, inhibition of JNK by ebselen may imply its usefulness for treatment of ischaemic cerebral diseases relevant to neuronal cell death.
(キーワード)
Analysis of Variance / Animals / Antioxidants / Apoptosis / Azoles / Cell Survival / DNA Fragmentation / Electron Spin Resonance Spectroscopy / Enzyme Activation / Hydrogen Peroxide / JNK Mitogen-Activated Protein Kinases / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinases / Organoselenium Compounds / Oxidative Stress / PC12 Cells / Rats / Reactive Oxygen Species / Signal Transduction / Time Factors / Transcription Factor AP-1 / p38 Mitogen-Activated Protein Kinases
Maki Urushihara, Shoji Kagami, Takeshi Kuhara, Toshiaki Tamaki and Yasuhiro Kuroda : Glomerular distribution and gelatinolytic activity of natrix metalloproteinases in human glomerulonephritis., Nephrology, Dialysis, Transplantation, Vol.17, No.7, 1189-1196, 2002.
(要約)
Matrix metalloproteinases (MMPs) have been implicated in the development of glomerular injury in rat experimental glomerulonephritis (GN). However, the significance of MMPs in human GN remains obscure. In order to evaluate the role of MMPs in human GN, we examined the glomerular distribution and gelatinolytic activities of MMP-2 and MMP-9 in human GN. We performed immunohistochemistry with polyclonal anti-MMP-2 and MMP-9 antibodies, and analysed gelatin zymograms of five isolated glomeruli from various types of human renal disease. The renal specimens investigated were from normal kidneys (n=5), IgA nephritis (n=20), Henoch-Schönlein nephritis (n=4), non-IgA mesangial proliferative GN (n=9), lupus nephritis (n=6), acute poststreptococcal GN (APSGN) (n=4) and diabetic nephropathy (DN) (n=4). MMP-2 immunoreactivity was not detected in normal controls or in any type of GN. MMP-9 staining, which was almost negative in normal glomeruli, was increased mainly in the mesangial region and corresponded to the level of glomerular cell proliferative changes in mesangial proliferative GN (IgA nephritis, Henoch-Schönlein nephritis, non-IgA mesangial proliferative GN and lupus nephritis). Positive but weak staining for MMP-9 was observed in mesangial areas in DN. In addition, double immunostaining showed that MMP-9 is colocalized in scattered neutrophils within diseased glomeruli in APSGN. MMP-9 gelatinolytic activity in five normal glomeruli was weakly detected. Consistent with the levels of immunostaining, MMP-9 glomerular activity was dramatically increased in nephritic glomeruli with IgA nephritis, lupus nephritis and DN. The gelatinolytic activity of MMP-2 was occasionally detectable in nephritic glomeruli. These results strongly suggest that MMP-9 plays an important role in abnormal mesangial proliferative changes in human GN.
Yuki Suzaki, Masanori Yoshizumi, Shoji Kagami, Hajime Koyama, Yutaka Taketani, Hitoshi Houchi, Koichiro Tsuchiya, Eiji Takeda and Toshiaki Tamaki : Hydrogen Peroxide Stimulates c-Src-mediated Big Mitogen-activated Protein Kinase 1(BMK1) and the MEF2C Signaling Pathway in PC12 Cells, The Journal of Biological Chemistry, Vol.277, No.11, 9614-9621, 2002.
(要約)
Reactive oxygen species, generated by reduction-oxidation (redox) reactions, have been recognized as one of the major mediators of ischemia and reperfusion injury in the brain. Reactive oxygen species-induced cerebral events are attributable, in part, to the change in intracellular signaling molecules including mitogen-activated protein (MAP) kinases. Big MAP kinase 1 (BMK1), also known as ERK5, is a newly identified member of the MAP kinase family and has been reported to be sensitive to oxidative stress. In the present study, we examined the effect of H(2)O(2) on BMK1 activity in PC12 cells, and we investigated the pathophysiological implication of BMK1. Findings showed that BMK1 was rapidly and significantly activated by H(2)O(2) in a concentration-dependent manner in PC12 cells. BMK1 activation by H(2)O(2) was inhibited by both PD98059 and U0126, which were reported to inhibit MEK5 as well as MEK1/2. c-Src was suggested to be involved in BMK1 activation from the experiments with herbimycin A and PP2, specific inhibitors of Src family kinases. Transfection of kinase-inactive Src also inhibited H(2)O(2)-induced BMK1 activation. In addition, H(2)O(2) treatment of cells induced an enhancement of DNA binding activity of MEF2C, a downstream transcription factor of BMK1 in PC12 cells. Finally, pretreatment of cells with PD98059 and U0126 resulted in an increase in cell death including apoptosis by H(2)O(2) in ERK1/2 down-regulated cells as well as in intact PC12 cells. These findings suggest that c-Src mediated BMK1 activation by H(2)O(2) may counteract ischemic cellular damage probably through the activation of MEF2C transcription factor.
Akiko Kitamura, Shoji Kagami, Maki Urushihara, Syuji Kondo, Masanori Yoshizumi, Toshiaki Tamaki and Yasuhiro Kuroda : Endothelin-1 is a potent stimulator of a1b1 integrin-mediated collagen matrix remodeling by rat mesangial cells., Biochemical and Biophysical Research Communications, Vol.299, 555-561, 2002.
171.
Shoji Kagami, K Urushihara, K. Loster, W. Reutter, Toshiaki Tamaki, Masanori Yoshizumi and Yasuhiro Kuroda : Requirement for tyrosine kinase-ERK1/2 signaling in a1b1 integrin-mediated collagen matrix remodeling by rat mesangial cells., Experimental Cell Research, Vol.268, No.2, 274-283, 2001.
(要約)
Abnormal mesangial extracellular matrix remodeling by mesangial cells (MCs) is the hallmark of progressive glomerulonephritis (GN). We recently showed, using a type I collagen gel contraction assay, that alpha 1 beta 1 integrin-dependent MC adhesion and migration are necessary cell behaviors for collagen matrix remodeling. To further determine the mechanism of alpha 1 beta 1 integrin-mediated collagen remodeling, we studied the signaling pathways of MCs that participate in the regulation of collagen gel contraction. Immunoprecipitation and phosphotyrosine detection revealed that gel contraction is associated with the enhanced activity and phosphorylation of ERK1/2 by MCs. The tyrosine kinase inhibitors herbimycin and genistein inhibited collagen gel contraction dose dependently. Furthermore, targeting ERK1/2 activity with a MEK inhibitor, PD98059, and antisense ERK1/2 hindered gel contraction in a dose-dependent manner. Similar inhibitory effects on gel contraction and ERK1/2 phosphorylation were observed when MC-mediated gel contraction was performed in the presence of function-blocking anti-alpha1 or anti-beta1 integrin antibodies. However, cell adhesion and migration assays indicated that PD98059 and antisense ERK1/2 blocked alpha 1 beta 1 integrin-dependent MC migration, but did not interfere with collagen adhesion, although there was a marked decrease in ERK1/2 phosphorylation and ERK1/2 protein expression in cell adhesion on type I collagen. None of the above could affect membrane expression of alpha 1 beta 1 integrin. These results suggested that ERK1/2 activation is critical for the alpha 1 beta 1 integrin-dependent MC migration necessary for collagen matrix reorganization. We therefore conclude that ERK1/2 may serve as a possible target for pharmacological inhibition of pathological collagen matrix formation in GN.
Koji Yasutomo, Horiuchi Takahiko, Shoji Kagami, Hiroshi Tsukamoto, Chinami Hashimura, Maki Urushihara and Yasuhiro Kuroda : Mutation in DNASE I in people with systemic lupus erythematosus, Nature Genetics, Vol.28, No.4, 313-314, 2001.
(要約)
Systemic lupus erythematosus (SLE) is a highly prevalent human autoimmune diseases that causes progressive glomerulonephritis, arthritis and an erythematoid rash. Mice deficient in deoxyribonuclease I (Dnase1) develop an SLE-like syndrome. Here we describe two patients with a heterozygous nonsense mutation in exon 2 of DNASE1, decreased DNASE1 activity and an extremely high immunoglobulin G titer against nucleosomal antigens. These data are consistent with the hypothesis that a direct connection exists between low activity of DNASE1 and progression of human SLE.
Shuji Kondo, Shoji Kagami, Hiroshi Kido, Strutz Frank, Muller A. Gerhard and Yasuhiro Kuroda : Role of Mast Cell Tryptase in Renal Interstitial Fibrosis, Journal of the American Society of Nephrology, Vol.12, No.8, 1668-1676, 2001.
(要約)
Renal interstitial fibrosis is characterized by increased proliferation of fibroblasts and excessive accumulation of extracellular matrix. Mast cell tryptase has been implicated in the development of tissue fibrosis in skin and lungs. However, the significance of mast cell tryptase in human renal diseases has not been investigated. The potential role of mast cell-derived tryptase in the development of renal fibrosis was studied using immunohistochemical techniques and cultured human renal fibroblast cell lines. Semiquantitative immunostaining analysis of samples from 70 patients with several renal diseases, including IgA glomerulonephritis (GN) (n = 30), non-IgA GN (n = 5), membranous GN (n = 5), focal segmental glomerulosclerosis (n = 4), minor glomerular abnormalities (n = 5), lupus nephritis (n = 3), and acute or chronic tubulointerstitial nephritis (n = 18), revealed that the degree of renal interstitial fibrosis was well correlated with the number of infiltrating tryptase-positive mast cells (P < 0.01). Mast cells could not be detected in damaged glomeruli in any form of renal disease. [(3)H]Thymidine uptake experiments demonstrated that DNA synthesis by cultured renal fibroblasts was increased with the concentration of tryptase (0.5 to 5 nM) coincubated with heparin and was suppressed by coincubation with the protease inhibitors leupeptin and benzamidine hydrochloride. Tryptase alone also increased DNA synthesis by fibroblasts but exhibited less effectiveness, compared with the combination of tryptase and heparin. Conversely, heparin alone suppressed DNA synthesis by fibroblasts. Metabolic [(35)S]methionine-labeling experiments with cultured renal fibroblasts indicated that tryptase increased the synthesis of fibronectin and collagen type I, in a dose-dependent manner. These findings suggest that mast cell tryptase plays a role in the proliferation and extracellular matrix protein production of renal interstitial fibroblasts and thus contributes to the development of renal interstitial fibrosis.
Daisuke Inui, Masanori Yoshizumi, Yuki Suzaki, Kazuyoshi Kirima, Koichiro Tsuchiya, Hitoshi Houchi, Shoji Kagami and Toshiaki Tamaki : Effect of Endothelin-1(1-31) on p38 Mitogen-Activated Protein Kinase in Cultured Human Mesangial Cells., Life Sciences, Vol.68, No.6, 635-645, 2000.
(要約)
It was reported that human chymase cleaves big endothelins (ETs) at the Tyr31-Gly32 bond and produces 31-amino acid ETs(1-31). In this study, we investigated the effect of ET-1(1-31) on p38 mitogen-activated protein kinase (p38-MAPK) activity in human mesangial cells (HMCs). By measuring the kinase activity, we demonstrated that ET-1 (1-31) activated the p38-MAPK dose-dependently (10(-9) M to 10(-7) M), which was inhibited by SB203580. The p38-MAPK activation induced by ET-1(1-31) peaked at 10 minutes. BQ123 almost abolished ET-1(1-31)-induced p38-MAPK activation, whereas BQ788 failed to inhibit it. These findings suggest that the stimulatory effect of ET-1(1-31) on p38-MAPK activation is mediated through ET(A) or ET(A)-like receptor. In conclusion, ET-1(1-31) induced increase in p38-MAPK activation in cultured HMCs.
Glomerular mesangial cell (MC) proliferation, hypertrophy, and abnormal matrix remodeling characterized by increased expression of fibronectin, laminin and collagen type IV, and neoexpression of collagen I and III are the main biological features of progressive glomerulonephritis (GN). Especially, persistent pathological matrix remodeling may lead to glomerular scar formation (glomerular scarring). We reported recently that alpha1beta1 integrin, a major collagen receptor for MCs, may be a potential adhesion molecule for MC-mediated pathological collagen matrix remodeling in GN. To address further the direct role of alpha1beta1 integrin in MC behavior, such as cell growth and matrix remodeling, alpha1beta1 integrin was overexpressed in MCs by transfecting an expression vector containing a full-length rat alpha1 integrin cDNA. Flow cytometry and immunoprecipitation analysis were applied for selection of transfectants with a stable expression of the alpha1 integrin subunit. The effect of alpha1beta1 integrin overexpression on MC biology was examined with a 3H-thymidine incorporation assay, flow cytometric analysis of cell size and DNA content, Western blot analysis of a cyclin-dependent-kinase inhibitor, p27Kip1, alpha-smooth muscle actin expression, and a collagen gel contraction assay. The alpha1 transfectants displayed a dramatic inhibition of 3H-thymidine incorporation as compared with the mock transfectants. Increased expression of the alpha1 subunit inversely correlated with cell cycle progression and paralleled the expression of p27Kip1 and alpha-smooth muscle actin, as well as the cell size in MCs. In addition, the alpha1-transfectants were able to enhance collagen matrix reorganization effectively. These results indicate that MC-alpha1beta1 integrin expression is a critical determinant of MC phenotypes, including cell growth, cell size, and collagen matrix remodeling ability, and thereby contributes to scar matrix remodeling (sclerosis) in GN.
Masanori Yoshizumi, Shoji Kagami, Yuki Suzaki, Koichiro Tsuchiya, Hitoshi Houchi, Tetsuhiro Hisayama, Hiroyuki Fukui and Toshiaki Tamaki : Effect of endothelin-1(1-31) on human mesangial cell proliferation, The Japanese Journal of Pharmacology, Vol.84, No.2, 146-155, 2000.
(キーワード)
Endothelin-1(1-31) / Human chymase / Extracellular signal-regulated kinase / Protein kinase C
177.
Shoji Kagami, Shuji Kondo, Klemens Loster, Werner Reutter, Takashi Kuhara, Koji Yasutomo and Yasuhiro Kuroda : Alpha1beta1 integrin-mediated collagen matrix remodeling by rat mesangial cells is differentially regulated by transforming growth factor-beta and platelet-derived growth factor-BB, Journal of the American Society of Nephrology, Vol.10, No.4, 779-789, 1999.
(要約)
Pathologic remodeling of mesangial matrix after glomerular injury is the central biologic feature of glomerular scarring (sclerosis). Transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF)-BB have been implicated in the development of glomerular scarring in rat and human glomerulonephritis. To clarify molecular and cellular mechanisms involved in abnormal mesangial remodeling, this study focused on the role of alpha1beta1 integrin, a collagen/laminin receptor, in rat mesangial cells, using collagen gel contraction as an experimental model of in vivo collagen matrix remodeling and scar formation. In addition, the influence of TGF-beta and PDGF-BB on mesangial cell (MC)-mediated collagen gel contraction in association with the alpha1beta1 integrin expression was evaluated. Integrin function blocking studies using anti-alpha1, beta1 subunit antibodies indicated that MC-alpha1beta1 integrin is essentially required not only for collagen-dependent adhesion/migration, but also for gel contraction. Protein synthesis and mRNA analysis experiments demonstrated that TGF-beta, but not PDGF-BB, increases the expression of alpha1beta1 integrin in mesangial cells cultured on plastic surface and in collagen gels. The upregulation of alpha1beta1 integrin expression by TGF-beta correlated with increases in gel contraction and collagen-dependent adhesion but not migration of mesangial cells. On the other hand, PDGF-BB enhanced MC-mediated gel contraction and migration without affecting cell adhesion to collagen I. Growth factor-induced collagen-dependent adhesion, migration, and gel contraction were significantly attenuated by incubation with anti-alpha1, beta1 subunit antibodies. Thus, these data indicate that alpha1beta1 integrin-mediated collagen matrix remodeling can be modulated by TGF-beta and PDGF-BB via different mechanisms. Alpha1 integrin-mediated mesangial matrix remodeling induced by TGF-beta or PDGF-BB may be a pathogenic mechanism leading to glomerular scarring.
Shoji Kagami, Shuji Kondo, Loster Klemens, Werner Reutter, Maki Urushihara, Akiko Kitamura, Shoko Kobayashi and Yasuhiro Kuroda : Collagen Type I Modulates the Platelet-Derived Growth Factor (PDGF) Regulation of the Growth and Expression of β1 Integrins by Rat Mesangial Cells, Biochemical and Biophysical Research Communications, Vol.252, No.3, 728-732, 1998.
(要約)
Mesangial cell (MC) proliferation and the deposition of collagen type I (collagen I) are the major pathological features in many types of glomerulonephritis (GN). Recent work suggested that beta-integrins play a critical role in the cell proliferation and extracellular matrix (ECM) remodeling observed in tissue repair after injury. To examine the involvement of beta-integrins in MC proliferation in association with the interaction of MCs with pathological collagen I, we investigated the effect of a prominent mitogen, platelet-derived growth factor-BB (PDGF-BB) on the growth and expression of beta-integrins by MCs cultured on plastic or in a three-dimensional collagen I gel. Immunoprecipitation using 35S-metabolic labeling, flow cytometry and a 3H-thymidine-uptake analysis demonstrated that PDGF-BB stimulated the cell mitogenicity and the expression of alpha5beta1 integrin (a fibronectin receptor), but not alpha1beta1 integrin (a collagen and laminin receptor) of MCs on plastic, in a dose-dependent manner. In contrast, MCs in the collagen I gels showed no significant changes in mitogenicity or alpha1beta1 and alpha5beta1 integrin expression, but increased alpha1beta1 integrin-mediated gel contraction was observed after PDGF-BB stimulation. Thus, the parallel up-regulation of MC-mitogenicity and alpha5beta1 integrin expression by PDGF-BB suggested that alpha5beta1 integrin is an important ECM receptor involved in the proliferative phenotype of MC. A spatial interaction between MCs and pathological collagen I in GN may influence the PDGF regulation of the MC phenotype regarding the cell growth and the expression of beta1 integrins.
Masanori Yoshizumi, Shokei Kim, Shoji Kagami, Akinori Hamaguchi, Koichiro Tsuchiya, Hitoshi Houchi, Hiroshi Iwao, Hiroshi Kido and Toshiaki Tamaki : Effect of endothelin-1(1-31)on extracellular signal-regulated kinase and proliferation of human coronary artery smooth muscle cells., British Journal of Pharmacology, Vol.125, No.5, 1019-1027, 1998.
180.
Takashi Kuhara, Shoji Kagami and Yasuhiro Kuroda : Expression of β1-Integrins on Activated Mesangial Cells in Human Glomerulonephritis, Journal of the American Society of Nephrology, Vol.8, No.11, 1679-1687, 1997.
(要約)
beta 1-integrins, a family of cell-surface receptors, mediate cell-matrix interactions that play a critical role in tissue development and tissue remodeling after injury. In this study, to clarify the importance of beta 1-integrins in human glomerulonephritis (GN), the relationship among the glomerular expression of beta 1-integrins, their ligand matrix components, alpha-smooth muscle actin (alpha-SM actin) as a marker of activated mesangial cells (MC), transforming growth factor-beta (TGF-beta), and glomerular cellularity in two normal kidneys, ten minimal change nephrotic syndrome, 23 immunoglobulin A (IgA) GN, 13 lupus GN, and four membranous GN kidneys were studied. Immunostaining was performed on frozen sections, using monoclonal anti-alpha-SM actin antibody and polyclonal antibodies against fibronectin, collagen type IV, laminin, each subunit of alpha 1 beta 1 (collagen/laminin receptor), alpha 5 beta 1 (fibronectin receptor) and TGF-beta. Quantitation of staining indicated that the glomerular expression of alpha 1 beta 1 and alpha 5 beta 1 integrins correlated with the mesangial amounts of their ligands, collagen type IV, laminin and fibronectin (P < 0.01), alpha-SM actin (P < 0.01), and TGF-beta (P < 0.01). In addition, a correlation was observed between an increased expression of alpha 1 beta 1 and alpha 5 beta 1 integrins and the degree of glomerular cell proliferation (P < 0.01). Double immunostaining showed that activated MC expressing alpha-SM actin strongly expressed alpha 1 beta 1 and alpha 5 beta 1 integrins, and these MC phenotypic alterations paralleled the level of glomerular TGF-beta staining (P < 0.01). In conclusion, enhanced expression of beta 1-integrins by activated MC may contribute to the pathological mesangial remodeling characterized by MC proliferation and matrix deposition in human GN. Increased glomerular TGF-beta appears to be involved in these MC phenotypic changes.
Shoji Kagami, Takashi Kuhara, Kaname Okada, Yasuhiro Kuroda, Border A. Wayne and Noble A. Nancy : Dual effects of angiotensin 2 on the plasminogen/plasmin system in rat mesangial cells, Kidney International, Vol.51, 664-671, 1997.
182.
Shoji Kagami, Border A. Wayne, Miller E Diane and Noble A. Nancy : Angiotensin 2 Stimulates Extracellular Matrix Protein Synthesis through Induction of Transforming Growth Factor-β Expression in Rat Glomerular Mesangial Cells, The Journal of Clinical Investigation, Vol.93, 2431-2437, 1994.
183.
Shoji Kagami, Border A. Wayne, Ruoslahti Erkki and Noble A. Nancy : Coordinated Expression of β1 Integrins and Transforming Growth Factor-β-Induced Matrix Proteins in Glomerulonephritis, Laboratory Investigation; a Journal of Technical Methods and Pathology, Vol.69, No.1, 68, 1993.
Narumi Tokaji, Hiromichi Ito, Tomohiro Kohmoto, Takuya Naruto, Rizu Takahashi, Aya Gohji, Tatsuo Mori, Yoshihiro Touda, Masako Saito, Shoichiro Tange, Kiyoshi Masuda, Shoji Kagami and Issei Imoto : A rare male patient with classic Rett syndrome caused by MeCP2_e1 mutation, American Journal of Medical Genetics. Part A., Vol.176A, No.3, 699-702, 2018.
(要約)
Rett syndrome (RTT) is a severe neurodevelopmental disorder typically affecting females. It is mainly caused by loss-of-function mutations that affect the coding sequence of exon 3 or 4 of methyl-CpG-binding protein 2 (MECP2). Severe neonatal encephalopathy resulting in death before the age of 2 years is the most common phenotype observed in males affected by a pathogenic MECP2 variant. Mutations in MECP2 exon 1 affecting the MeCP2_e1 isoform are relatively rare causes of RTT in females, and only one case of a male patient with MECP2-related severe neonatal encephalopathy caused by a mutation in MECP2 exon 1 has been reported. This is the first reported case of a male with classic RTT caused by a 5-bp duplication in the open-reading frame of MECP2 exon 1 (NM_001110792.1:c.23_27dup) that introduced a premature stop codon [p.(Ser10Argfs*36)] in the MeCP2_e1 isoform, which has been reported in one female patient with classic RTT. Therefore, both males and females displaying at least some type of MeCP2_e1 mutation may exhibit the classic RTT phenotype.
(キーワード)
Alternative Splicing / Base Sequence / 脳 (brain) / Child, Preschool / DNA Mutational Analysis / Exons / Genetic Association Studies / Genetic Predisposition to Disease / Humans / 磁気共鳴映像法 (magnetic resonance imaging) / 男性 (male) / Methyl-CpG-Binding Protein 2 / Mutation / Phenotype / Rett Syndrome
N Nakamura, Hiroyoshi Watanabe, Kazumi Okamura and Shoji Kagami : Assessment of renal function in Japanese children with malignancies using serum cystatin C., The Journal of Medical Investigation : JMI, Vol.65, No.3,4, 231-235, 2018.
(要約)
Several factors besides renal function influence serum cystatin C (CysC) levels. The present study evaluates the value of serum CysC and the equation for CysC based estimated glomerular filtration rate (CysC-eGFR) for Japanese children with malignancies. We collected information at 36 time points from 13 patients aged ≤ 17 years with malignancies. We assessed tumor activity, cell recovery phase after chemotherapy, neutropenia phase, inflammation response and medication with granulocyte-colony stimulating factor, steroid, and levothyroxine as risk factors associated with serum CysC levels. Although no 24-h creatinine clearance (CCr) data collected at 36 time points indicated renal dysfunction, serum CysC levels were above and below the reference values at four and five time points, respectively. The frequency of elevated serum CysC levels was higher in patients without therapy or with stable or progressive disease than among those with a complete or partial response (p = 0.0046). The correlation coefficient between CCr and CysC-eGFR was 0.355 (p = 0.054), but this improved to 0.663 (p = 0.0010) when restricted to patients with a complete or partial response. Levels of serum CysC might become elevated regardless of renal function, and CysC-eGFR might become unpredictable during the active phase of tumors. J. Med. Invest. 65:231-235, August, 2018.
Hiromichi Ito, Kenji Mori, Tatsuo Mori, A Goji and Shoji Kagami : Case of early childhood-onset narcolepsy with cataplexy: comparison with a monozygotic co-twin., Pediatrics International, Vol.56, No.5, 789-793, 2014.
(要約)
We describe here a rare case of early childhood-onset (5 years of age) narcolepsy. This case was interesting because of the ability to compare the patient's symptoms to the condition of her healthy monozygotic co-twin sister. The only environmental difference between the co-twins was head injury, which may be associated with the presence of narcolepsy. The co-twin was extroverted, sociable, reliable, and dexterous. In contrast, the patient could be described as introverted, gentle, honest and persevering, but was weak at conversation, assessment of a situation, memory, planning, activity (she was inactive), a sense of time, understanding of an analog clock, operating efficiency, and physical education (due to obesity). The sisters showed the same degree of appetite and dexterity with their fingers. Narcolepsy is often under-recognized or underdiagnosed, especially when the onset occurs in childhood. When we observe preschoolers with excessive daytime sleepiness, we should consider the possibility of narcolepsy with cataplexy.
Nami Inoue, Hiroyoshi Watanabe, Kazumi Okamura, Mika Sakaki, Teruyoshi Kageji, Shinji Nagahiro and Shoji Kagami : Atypical teratoid rhabdoid tumor in the cavernous sinus of a toddler presenting with oculomotor nerve palsy., Child's Nervous System, Vol.30, No.8, 1463-1466, 2014.
(要約)
Atypical teratoid rhabdoid tumor (ATRT) is a rare, highly malignant, and aggressive tumor of infancy. Although the prognosis of ATRT has been extremely poor, recently, the first prospective study for ATRT demonstrated improvement of prognosis. On the other hands, oculomotor nerve palsy is rare in children and the most frequent etiology is congenital. To our knowledge, only a few ATRT cases presenting with oculomotor nerve palsy have been reported, but ATRT originating from the cavernous sinus (CS) has not yet been reported. An 18-month-old girl with right oculomotor nerve palsy was admitted, and a small mass in the right CS was detected with brain MRI. Although she received steroid pulse therapy and antimicrobial therapy, the mass continued to enlarge. One month after admission, the mass was partially resected and diagnosed as ATRT. Multimodal therapy including anthracycline-based chemotherapy, intrathecal therapy, and cranial irradiation was performed. Twenty-nine months after resection, she was alive without tumor relapse, but the oculomotor nerve palsy persisted. This is the first reported case of ATRT located in the CS presenting with oculomotor nerve palsy. This case was successfully treated with partial removal of the tumor, a new chemotherapy regimen for ATRT and cranial X-ray irradiation.
Toshihiro Sawai, Masaomi Nangaku, Akira Ashida, Rika Fujimaru, Hiroshi Hataya, Yoshihiko Hidaka, Shinya Kaname, Hirokazu Okada, Waichi Sato, Takashi Yasuda, Yoko Yoshida, Yoshihiro Fujimura, Motoshi Hattori and Shoji Kagami : Diagnostic criteria for atypical hemolytic uremic syndrome proposed by the Joint Committee of the Japanese Society of Nephrology and the Japan Pediatric Society., Clinical and Experimental Nephrology, Vol.18, No.1, 4-9, 2014.
(要約)
Atypical hemolytic uremic syndrome (aHUS) is rare and comprises the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Recently, abnormalities in the mechanisms underlying complement regulation have been focused upon as causes of aHUS. The prognosis for patients who present with aHUS is very poor, with the first aHUS attack being associated with a mortality rate of ~25 %, and with ~50 % of cases resulting in end-stage renal disease requiring dialysis. If treatment is delayed, there is a high risk of this syndrome progressing to renal failure. Therefore, we have developed diagnostic criteria for aHUS to enable its early diagnosis and to facilitate the timely initiation of appropriate treatment. We hope these diagnostic criteria will be disseminated to as many clinicians as possible and that they will be used widely.
T Sawai, M Nangaku, A Ashida, R Fujimaru, H Hataya, Y Hidaka, S Kaname, H Okada, W Sato, T Yasuda, Y Yoshida, Y Fujimura, M Hattori and Shoji Kagami : Diagnostic criteria for atypical hemolytic uremic syndrome proposed by the Joint Committee of the Japanese Society of Nephrology and the Japan Pediatric Society., Pediatrics International, Vol.56, No.1, 1-5, 2014.
(要約)
Atypical hemolytic uremic syndrome (aHUS) is rare and comprises the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Recently, abnormalities in the mechanisms underlying complement regulation have been focused upon as causes of aHUS. The prognosis for patients who present with aHUS is very poor, with the first aHUS attack being associated with a mortality rate of approximately 25%, and with approximately 50% of cases resulting in end-stage renal disease requiring dialysis. If treatment is delayed, there is a high risk of this syndrome progressing to renal failure. Therefore, we have developed diagnostic criteria for aHUS to enable its early diagnosis and to facilitate the timely initiation of appropriate treatment. We hope these diagnostic criteria will be disseminated to as many clinicians as possible and that they will be used widely.
(キーワード)
Atypical Hemolytic Uremic Syndrome / Child / Diagnostic Techniques, Urological / Guidelines as Topic / Humans / Japan / Nephrology / Societies, Medical
Nami Inoue, Hiroyoshi Watanabe, Hiroo Takehara, M Hamazaki and Shoji Kagami : Refractory pediatric nonrhabdomyosarcoma soft tissue sarcoma associated with ectopic production of beta hCG and hypercalcemia induced by PTHrP., Pediatric Blood & Cancer, Vol.57, No.7, 1244-1246, 2011.
(要約)
A 3-month-old male with a mass on the right side of his back was admitted to our hospital. The tumor was a pathologically high-grade nonrhabdomyosarcoma soft tissue sarcoma (NRSTS). Treatment included subtotal tumor resection followed by chemotherapy. Elevation of serum beta hCG and hypercalcemia with detection of PTHrP was associated with tumor progression. The tumor was refractory to multiagent chemotherapy, and the patient died of the disease at 22 months of age. This case is novel in demonstrating a beta hCG secreting refractory NRSTS.
(キーワード)
Antineoplastic Agents / Chorionic Gonadotropin, beta Subunit, Human / Combined Modality Therapy / Fatal Outcome / Humans / Hypercalcemia / Infant / Male / Neoplasm Recurrence, Local / Parathyroid Hormone-Related Protein / Sarcoma / Soft Tissue Neoplasms
Ichiro Yokota, Maki Moritani, K Nishisho, T Miyoshi, Yumiko Kotani and Shoji Kagami : Detection of glucokinase gene defects in non-obese Japanese children diagnosed with diabetes by school medical examinations., Endocrine Journal, Vol.58, No.9, 741-746, 2011.
(要約)
We examined children who were diagnosed with asymptomatic type 2 diabetes by school medical examinations to investigate the existence of glucokinase (GCK) gene defects in this group. Among 20 children diagnosed with asymptomatic type 2 diabetes by school medical examinations between 2003 and 2009 at our 2 hospitals, 8 were classified as non-obese type. Among them, we screened 5 children (2 boys and 3 girls; age: 8-13 years) who had mild elevation of fasting plasma glucose (108-134 mg/dL) with slightly high internationally standardized HbA1c levels (6.3-6.9%) at first close examination. Written informed consent was obtained and all families agreed to participate in this study. We found 4 different mutations (G223S, G81C, S336X and T228M) in 4 of the examined children. The blood glucose control levels had not become worse in any children during the 2-6 years follow-up period. The inheritance of diabetes with GCK gene defect was later confirmed in 1 family. These results suggest that GCK gene defects exist in non-obese children who are diagnosed with asymptomatic diabetes by school medical examinations. Cases of diabetes that are caused by GCK mutations may not be as rare in Japanese subjects as previously described and could be found in patients tentatively diagnosed as type 2 diabetes.
(キーワード)
Adolescent / Child / DNA / Diabetes Mellitus, Type 2 / Female / Genetic Variation / Glucokinase / Humans / Japan / Male / Polymerase Chain Reaction / Polymorphism, Single Nucleotide / Sequence Analysis, DNA
Sato Matsuura, Shuji Kondo, Ken-ichi Suga, Yukiko Kinoshita, Maki Urushihara and Shoji Kagami : Expression of focal adhesion proteins in the developing rat kidney., The Journal of Histochemistry and Cytochemistry, Vol.59, No.9, 864-874, 2011.
(要約)
Focal adhesions play a critical role as centers that transduce signals by cell-matrix interactions and regulate fundamental processes such as proliferation, migration, and differentiation. Focal adhesion kinase (FAK), paxillin, integrin-linked kinase (ILK), and hydrogen peroxide-inducible clone-5 (Hic-5) are major proteins that contribute to these events. In this study, we investigated the expression of focal adhesion proteins in the developing rat kidney. Western blotting analysis revealed that the protein levels of FAK, p-FAK(397), paxillin, p-paxillin(118), and Hic-5 were high in embryonic kidneys, while ILK expression persisted from the embryonic to the mature stage. Immunohistochemistry revealed that FAK, p-FAK(397), paxillin, and p-paxillin(118) were strongly expressed in condensed mesenchymal cells and the ureteric bud. They were detected in elongating tubules and immature glomerular cells in the nephrogenic zone. Hic-5 was predominantly expressed in mesenchymal cells as well as immature glomerular endothelial and mesangial cells, suggesting that Hic-5 might be involved in mesenchymal cell development. ILK expression was similar to that of FAK in the developmental stages. Interestingly, ILK was strongly expressed in podocytes in mature glomeruli. ILK might play a role in epithelial cell differentiation as well as kidney growth and morphogenesis. In conclusion, the temporospatially regulated expression of focal adhesion proteins during kidney development might play a role in morphogenesis and cell differentiation.
H Sugiyama, H Yokoyama, H Sato, Y Kohda, S Nishi, K Tsuruya, H Kiyomoto, H Iida, T Sasaki, M Higuchi, M Hattori, K Oka, Shoji Kagami, M Nagata, T Kawamura, M Honda, Y Fukasawa, A Fukatsu, K Morozumi, N Yoshikawa, Y Yuzawa, S Matsuo, Y Kiyohara, K Joh, T Taguchi and H Makino : Japan Renal Biopsy Registry: the first nationwide, web-based, and prospective registry system of renal biopsies in Japan., Clinical and Experimental Nephrology, Vol.15, No.4, 493-503, 2011.
(要約)
The Committee for the Standardization of Renal Pathological Diagnosis and the Working Group for Renal Biopsy Database of the Japanese Society of Nephrology started the first nationwide, web-based, and prospective registry system, the Japan Renal Biopsy Registry (J-RBR), to record the pathological, clinical, and laboratory data of renal biopsies in 2007. The patient data including age, gender, laboratory data, and clinical and pathological diagnoses were recorded on the web page of the J-RBR, which utilizes the system of the Internet Data and Information Center for Medical Research in the University Hospital Medical Information Network. We analyzed the clinical and pathological diagnoses registered on the J-RBR in 2007 and 2008. Data were collected from 818 patients from 18 centers in 2007 and 1582 patients from 23 centers in 2008, including the affiliated hospitals. Renal biopsies were obtained from 726 native kidneys (88.8%) and 92 renal grafts (11.2%) in 2007, and 1400 native kidneys (88.5%) and 182 renal grafts (11.5%) in 2008. The most common clinical diagnosis was chronic nephritic syndrome (47.4%), followed by nephrotic syndrome (16.8%) and renal transplantation (11.2%) in 2007. A similar frequency of the clinical diagnoses was recognized in 2008. Of the native kidneys, the most frequent pathological diagnosis as classified by pathogenesis was immunoglobulin (Ig) A nephropathy (IgAN) both in 2007 (32.9%) and 2008 (30.2%). Among the primary glomerular diseases (except IgAN), membranous nephropathy (MN) was the most common disease both in 2007 (31.4%) and 2008 (25.7%). In a cross-sectional study, the J-RBR has shown IgAN to be the most common disease in renal biopsies in 2007 and 2008, consistent with previous Japanese studies. MN predominated in the primary glomerular diseases (except for IgAN). The frequency of the disease and the clinical and demographic correlations should be investigated in further analyses by the J-RBR.
(キーワード)
Adolescent / Adult / Aged / Aged, 80 and over / Biopsy / Child / Child, Preschool / Cross-Sectional Studies / Female / Glomerulonephritis, IGA / Glomerulonephritis, Membranous / Humans / Infant / Internet / Japan / Kidney / Kidney Diseases / Kidney Failure, Chronic / Kidney Transplantation / Male / Middle Aged / Nephrotic Syndrome / Registries
Hiromichi Ito, Kenji Mori, Miho Sakata, Etsuo Naito, M Harada and Shoji Kagami : Transient left temporal lobe lesion in Menkes disease may influence the generation of tonic spasms., Brain & Development, Vol.33, No.4, 345-348, 2011.
(要約)
We report a 7-month-old boy with Menkes disease who presented West syndrome. Magnetic resonance imaging (MRI) revealed atrophy of the frontal and parietal lobes, subdural hematoma on the right side, and left temporal lobe lesion (low intensity in T1-weighted imaging (T1-WI), high intensity in T2-weighted imaging (T2-WI) and low intensity in diffusion-weighted imaging (DW-I)) at 7 months of age. The apparent diffusion coefficient (ADC) was 1.68×10(-3)mm(2)/s in the left temporal lobe lesion and 1.15×10(-3)mm(2)/s on the contralateral side. (1)H-magnetic resonance spectroscopy ((1)H-MRS) revealed a decrease in N-acetylaspartate/(creatine+phosphocreatine) (NAA/Cr) (0.71) and a lactate peak in the left temporal lobe lesion. At 8 months of age, the left temporal lobe lesion disappeared, the ADC of this lesion was within the normal range (1.10×10(-3)mm(2)/s), and (1)H-MRS revealed a slight increase in NAA/Cr (1.12) and disappearance of the lactate peak. We suspected that the transient temporal lobe lesion in Menkes disease was mainly vasogenic edema. Electroencephalography (EEG) revealed left hemisphere dominant hypsarrhythmia and slowing in the left hemisphere. Ictal EEG revealed generalized slow wave burst with P3, T3 spike antecedence and the antecedent spike was consistent with left temporal lobe lesion. After disappearance of the left temporal lobe lesion, tonic spasms disappeared and EEG findings improved. In this case, the clinical course and ictal EEG suggested that epileptic activity from the left temporal lobe lesion may have given rise to tonic spasms.
Emiko Fujii, Kenji Mori, Masahito Miyazaki, Toshiaki Hashimoto, Masafumi Harada and Shoji Kagami : Function of the frontal lobe in autistic individuals: a proton magnetic resonance spectroscopic study, The Journal of Medical Investigation : JMI, Vol.57, No.1,2, 35-44, 2010.
(要約)
In this investigation, we studied differences in chemical metabolites in certain brain regions between autistic patients and normal control subjects. Proton magnetic resonance spectroscopy ((1)H-MRS) was used to evaluate functional activity in these regions. Specific regions studied were right and left dorsolateral prefrontal cortex(DLPFC) and the anterior cingulated cortex(ACC). In the ACC, the N-acetylaspartate(NAA)/creatine/phosphocreatine(Cr) ratio in autistic patients (n=31) was significantly lower than that in control subjects (n=28). The decrease in the NAA/Cr ratio for the ACC was much greater in the group with worst social ability. NAA/Cr for the left DLPFC and social ability of autistic patients also correlated well. Furthermore, NAA/Cr for the left DLPFC in the group with intelligence quotient (IQ) below 50 was significantly less than in controls. NAA/Cr for the right DLPFC in autistic patients was not decreased compared to controls, and did not correlate with IQ or social ability. These findings suggest neuronal dysfunction in the ACC and left DLPFC in autism, and also a relationship between social disability and metabolic dysfunction in these regions. Dysfunction in the ACC and the left DLPFC may contribute to the pathogenesis of autism.
Yasunobu Hayabuchi, Miho Sakata and Shoji Kagami : Multidetector Row Computed Tomography Evaluation in Pediatric Heart Diseases -Additional Information to Echocardiography and Conventional Cardiac Catherterization, International Journal of Pediatric Research, Vol.1, No.1, 1, Feb. 2015.
Hiromichi Ito, Kenji Mori and Shoji Kagami : Neuroimaging of stroke-like episodes in MELAS., Brain & Development, Vol.33, No.4, 283-288, 2011.
(要約)
Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) shows sudden neurological deficits that are called 'stroke-like episodes'. With regard to the pathophysiology of stroke-like episodes, so-called mitochondrial angiopathy and cytopathy theories have been proposed, but the subject is still controversial. To clarify this matter and to contribute to the development of a treatment for MELAS, we review here current neuroimaging research and consider the pathophysiology of stroke-like lesions. With regard to diffusion-weighted imaging findings, early reports often showed an elevated apparent diffusion coefficient (ADC) in stroke-like lesions; this was considered to be mainly vasogenic edema in the acute phase and is a different pattern than that in stroke. However, there has recently been an increase in the number of reports of a decrease in ADC; these cases are considered to be cytotoxic edema in the acute phase, which is compatible with stroke. With regard to (1)H-magnetic resonance spectroscopy findings in stroke-like lesions, a decrease in N-acetylaspartate and an increase in lactate have been reported. With regard to single photon emission computed tomography findings for stroke-like lesions in MELAS, an overall trend is hyperperfusion in the acute stage (within 1 month) of stroke-like episodes and hypoperfusion in the chronic stage (several months later). With regard to positron emission tomography, nearly all of these reports are consistent with the mitochondrial cytopathy theory. With regard to neuropathology in MELAS, the most common findings during the chronic stage of stroke-like episodes include foci of necrosis and peculiar vascular changes (abnormalities of mitochondria in small arteries). Concerning the pathology of the acute stage of stroke-like episodes, extensive petechial hemorrhage along the gyri of the cortex corresponding to acute stroke-like lesions has been reported. To clarify the true pathophysiology of stroke-like episodes, we offer three suggestions. First, we must define the precise onset of stroke-like episodes. Second, current studies are limited by the difficulty of imaging just before and just after (within a few minutes) the onset of stroke-like episodes. Third, we hope to establish an experimental animal model. We should conduct a simultaneous multimodal imaging and histological study just before and just after (within a few minutes) the onset of stroke-like episodes in an experimental animal model.
Shoji Kagami and Kondo Shuji : β1-integrins and glomerular injury, The Journal of Medical Investigation : JMI, Vol.51, No.1,2, 1-13, Feb. 2004.
(要約)
The renal glomerulus is composed of three types of glomerular cells (mesangial cell (MC), endothelial cell and podocyte) and extracellular matrix (ECM) consisting of the glomerular basement membrane (GBM) and mesangial matrix. It constitutes a highly specialized microcirculation in which the permeability characteristics of the capillary wall allow its unique filtration function. The proliferation of MCs, an increase of mesangial ECM and detachment podocyte from GBM are key biological features of progressive glomerulonephritis (GN), leading to glomerular scarring and dysfunction. Thus, the study of the molecular and cellular mechanisms responsible for pathological glomerular alterations may help to elucidate the pathogenesis of progressive glomerular diseases. A growing body of evidence indicates that beta1 integrin family (beta1 integrins), that mainly mediates cell adhesion to ECM, controls cell behaviors such as cell migration, proliferation, apoptosis and ECM assembly. In addition, a correlation between glomerular expression of beta1 integrins and their ligand ECM components is observed in various human and experimental GN, suggesting that altered beta1 integrins-mediated cell behaviors may contribute to the progression of GN. It is now becoming apparent that the expression of glomerular beta1 integrins is not only critical for maintaining the glomerular capillary permeability but it modulates cell signaling pathways regulating the cell phenotypes involved in the progression of glomerular diseases.
Maki Urushihara, Yukiko Kinoshita, Keisuke Fujioka and Shoji Kagami : Glomerular and urinary angiotensin converting enzyme 2 in pediatric IgA nephronpathy, The 16th Korea-China-Japan Pediatric Nephrology Seminar, Apr. 2018.
2.
Aya Gohji, Hiromichi Ito, N Tokaji, T Kohmoto, T Naruto, R Takahashi, Tatsuo Mori, Yoshihiro Touda, M Saito, S Tange, K Masuda, Shoji Kagami and I Imoto : A Rare Male Patient with Classic Rett Syndrome Caused by MeCP2_e1 Mutation., ASHG 2017 annual meeting, Oct. 2017.
3.
Keisuke Fujioka, Yukiko Kinoshita, Maki Urushihara, M Shimizu and Shoji Kagami : A case of glomerular phospholipase A receptor-positive idiopathic membranous nephropathy without deposition of complements, The 15th Japan-Korea-China Pediatric Nephrology Seminar, Apr. 2017.
4.
Maki Urushihara, T Nagai, Shuji Kondo, Toshiaki Tamaki, Yasumasa Ikeda and Shoji Kagami : (Pro)renin receptor-mediated ERK1/2 and Wnt signaling pathway in crescent glomerulonephritis., Kidney Week 2016, Nov. 2016.
5.
Yukiko Kinoshita, Keisuke Fujioka, T Nagai, N Ozaki, Maki Urushihara, Shuji Kondo and Shoji Kagami : Transition from MPGN type III to C3 glomerulonephritis in a girl with a prolonged Nephritis-associated plasmin receptor (NAPlr) deposition., 15th Asian Pacific Congress of Nephrology & 52nd Australian and New Zealand Society of Nephrology Annual Scientific Meeting, Sep. 2016.
6.
T Nagai, Maki Urushihara, Yukiko Kinoshita, Ariunbold Jamba, Shuji Kondo and Shoji Kagami : Extracellular signal regulated kinase-1/2 and -5 signaling pathways via renin angiotensin system activation play differential regulatory roles in progressive glomerulonephritis, ERA-EDTA 53rd Congress, May 2016.
7.
Aya Gohji, Hiromichi Ito, Kenji Mori, S Hisaoka, Yoshihiro Touda, Tatsuo Mori, Y Abe, M Miyazaki and Shoji Kagami : Metabolic dysfunction in anterior cingulate cortex using a magnetic resonance spectroscopy in Asperger's syndrome., Pediatric Academic Societies Meeting, May 2016.
8.
Teruyoshi Kageji, Yoshifumi Mizobuchi, Kohhei Nakajima, Hiroyoshi Watanabe, Kazumi Okamura, Shoji Kagami and Shinji Nagahiro : Intensive chemotherapy followed by reduced radiation dose for intracranial non-germinomatous germ cell tumors, 20th Annual Socientific Meeting and Education Day of the Society for Neuro-Oncology, Nov. 2015.
9.
N Miyake, H Tsukaguchi, E Koshimizu, A Shono, S Matsunaga, M Shiina, Y Mimura, S Imamura, T Hirose, K Okudela, K Nozu, Y Akioka, M Hattori, N Yoshikawa, A Kitamura, HI Cheong, Shoji Kagami, M Yamashita, A Fujita, S Miyatake, Y Tsurusaki, M Nakashima, H Saitsu, K Ohashi, N Imamoto, A Ryo, K Ogata, K Iijima and N Matsumoto : Biallelic Mutations in Nuclear Pore Conplex Subunit NUP107 Cause Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome, American Journal of Human Genetics, Vol.97, No.4, 555-566, Sep. 2015.
(要約)
The nuclear pore complex (NPC) is a huge protein complex embedded in the nuclear envelope. It has central functions in nucleocytoplasmic transport, nuclear framework, and gene regulation. Nucleoporin 107 kDa (NUP107) is a component of the NPC central scaffold and is an essential protein in all eukaryotic cells. Here, we report on biallelic NUP107 mutations in nine affected individuals who are from five unrelated families and show early-onset steroid-resistant nephrotic syndrome (SRNS). These individuals have pathologically focal segmental glomerulosclerosis, a condition that leads to end-stage renal disease with high frequency. NUP107 is ubiquitously expressed, including in glomerular podocytes. Three of four NUP107 mutations detected in the affected individuals hamper NUP107 binding to NUP133 (nucleoporin 133 kDa) and NUP107 incorporation into NPCs in vitro. Zebrafish with nup107 knockdown generated by morpholino oligonucleotides displayed hypoplastic glomerulus structures and abnormal podocyte foot processes, thereby mimicking the pathological changes seen in the kidneys of the SRNS individuals with NUP107 mutations. Considering the unique properties of the podocyte (highly differentiated foot-process architecture and slit membrane and the inability to regenerate), we propose a "podocyte-injury model" as the pathomechanism for SRNS due to biallelic NUP107 mutations.
Shuji Kondo, A Jamba, T Nagai, Yukiko Kinoshita, Maki Urushihara and Shoji Kagami : Hic-5 Controls Mesangial Cell Proliferation in Proliferative Glomerulonephritis in Mice, 7th Europaediatrics, May 2015.
11.
T Terada, M Urushihara, T Saijyo, Ryuji Nakagawa and Shoji Kagami : The prorenin and soluble (pro)renin receptor may be associated with prenatal renal development in humans, The 2015 Pediatric Academic Societies Annual Meeting, Apr. 2015.
12.
T Terada, Maki Urushihara, Takahiko Saijyou, Ryuji Nakagawa and Shoji Kagami : The prorenin and soluble (pro)renin receptor may be associated with prenatal renal development in humans, 4th International CNS Germ Cell Tumor Symposium, Apr. 2015.
13.
F Watanabe, N Inoue, K Okamura, Shinji Nagahiro, Yoshifumi Mizobuchi, Kohhei Nakajima, Teruyoshi Kageji and Shoji Kagami : Intensive Chemotherapy Followed by Reduced Dose Radiation for Intracranial Non-germinomatous Germ Cell, The 4th International CNS Germ Cell Tumor Symposium, Apr. 2015.
14.
Teruyoshi Kageji, Shoji Kagami, Kohhei Nakajima, Yoshifumi Mizobuchi and Shinji Nagahiro : Strategy and Clinical Results for Intracranial Non-germinomatous Germ Cell Tumors Induced Intensive, The 4th International CNS Germ Cell Tumor Symposium, Apr. 2015.
15.
Keiko Miyoshi, Taigo Horiguchi, Ayako Tanimura, Hiroko Hagita, Yoshihiro Touda, Shoji Kagami, Kenji Mori, Daisuke Tsuji, Kouji Itou and Takafumi Noma : Gaucher disease caused by possible atypical mechanism, Gordon Research Conference, USA,Texas,Galveston(Hotel Galvez), Mar. 2015.
Shoji Kagami : Renin angiotensin axis in renal development & disease: The cycle of life, Plenary lecture at XII Asian Congress of Pediatric Nephrology, Dec. 2014.
18.
T Nagai, T Furumoto, A Jamba, Yukiko Kinoshita, Maki Urushihara, Shuji Kondo and Shoji Kagami : The case of a 6-year-old boy with systemic lupus erythematosus complicated by membranous lupus nephritis and finger toe necrosis., XII Asian Congress of Pedatric Nephrology, Dec. 2014.
19.
T Terada, 漆原 真樹, 香美 祥二 : The prorenin and soluble (pro)renin receptor may be associated with prenatal renal development in humans., Kidney Week 2014, 2014年11月.
20.
Jamba Ariunbold, Shuji Kondo, Nagai Takashi, Maki Urushihara, Toshiaki Tamaki and Shoji Kagami : Hic-5 Regulates Mesangial Cell Proliferation via Altered and Coordinated Expression of Cell Cycle-Related Protein, American Society of Nephrology (ASN) Kidney Week 2014, Philadelphia, Nov. 2014.
21.
Maki Urushihara, Shuji Kondo, Kobori Hiroyuki, Toshiaki Tamaki and Shoji Kagami : Urinary angiotensinogen as a specific biomarker of intrarenal renin-angiotensin system status associated with glomerular injury in pediatric IgA nephropathy patients, American Society of Nephrology (ASN) Kidney Week 2014, Philadelphia, Nov. 2014.
22.
Shoji Kagami : Significance of local Renin Angiotensin System (RAS) in renal disease progression, Educational lecture in Department of Pediatrics, MNUMS, Aug. 2014.
23.
Shoji Kagami : Renal Renin Angiotensin System (RAS)- Supporting and Threatening the Circle of Life -, Medical Symposium in Mongolian National University of Medical Sciences (MNUMS), Aug. 2014.
24.
Mayumi Sugimoto, Norio Kamemura, Suzuki Koichi, Kubota Kenji, Nagao Mizuho, Fujisawa Takao, Shoji Kagami and Hiroshi Kido : Analysis of Allergen-Specific Immunoglobulin in Rush Oral Immunotherapy for Severe Food Allergy by a Highly Sensitive Allergen Microarray, European Academy of Allergy and Clinical Immunology Congress 2014, Jun. 2014.
25.
A Jamba, Shuji Kondo, Maki Urushihara, 永井 隆, J Kim-Kaneyama, A Miyazaki and Shoji Kagami : The Role of Hic-5 on Mesangial Cell Proliferation in Proliferative Glomerulonephritis in Mice., The 14th Asian Pacific Congress of Nephrology, May 2014.
26.
S Jamba, Shuji Kondo, Maki Urushihara, T Nagai, Toshiaki Tamaki and Shoji Kagami : Contribution of hydrogen peroxide-inducible clone-5 to the regulation of mesangial cell proliferation in mesangioproliferative glomerulonephritis, The annual meeting of American society of nephrology Kidney Week 2013, Nov. 2013.
27.
Y Seki, Maki Urushihara, T Tayama, T Nagai, Yukiko Kinoshita, A Jamba, Shuji Kondo and Shoji Kagami : Glomerular ACE2 expression is enhanced in pediatric IgA nephropathy, The Sixteenth Congress of the International Pediatric Nephrology Association, Aug. 2013.
28.
T Tayama, Maki Urushihara, Y Seki, Yukiko Kinoshita, T Nagai, A Jamba, Shuji Kondo and Shoji Kagami : Effect of direct renin inhibitor on renal inflammation and (pro)renin receptor in crescentic glomerulonephritis., The Sixteenth Congress of the International Pediatric Nephrology Association, Aug. 2013.
29.
M Sato, Shuji Kondo, Yukiko Kinoshita, Ken-ichi Suga, Maki Urushihara, K Natsuko, T Nagai, Jamba Ariunbold and Shoji Kagami : Reacitve oxygen species generated by NADPH oxidase contribute to ureteric bud branching and nephrogenesis., Pediatric Academic societies annual meeting 2012, Dec. 2012.
30.
Maki Urushihara, Yukiko Kinoshita, T Nagai, Shuji Kondo, A Jamba, T Tamaki and Shoji Kagami : Effect of aliskiren on renal inflammation and (pro)renin receptor in crescentic glomerulonephritis., The American Society of Nephrology Renal Week 2012, Oct. 2012.
31.
Shoji Kagami : Renal Protection with Renin-Angiotensin System Inhibitors in Pediatric CKD, 11th Asian Congress of Pediatric Nephrology2011, Jun. 2011.
32.
Shoji Kagami : Involvement of glomerular renin-angiotensin system(RAS) activation in development and progression of glomerular injury, 11th Asian Congress of Pediatric Nephrology, Jun. 2011.
33.
T Nagai, Yukiko Kinoshita, S Matsuura, Ken-ichi Suga, Maki Urushihara, Shuji Kondo and Shoji Kagami : A case of membranous nephropathy with cavernous hemangioma, 11th Asian Congress of Pediatric Nephrology 2011, Jun. 2011.
34.
S Matsuura, Shuji Kondo, Ken-ichi Suga, Yukiko Kinoshita, Maki Urushihara, M Takamatsu, M Shimizu, N Kishi and Shoji Kagami : A case of membranous nephropathy and open angle glaucoma complicated with asymptomatic Sjögrens syndrome, 11th Asian Congress of Pediatric Nephrology 2011, Jun. 2011.
35.
S Matsuura, Shuji Kondo, Yukiko Kinoshita, Ken-ichi Suga, Maki Urushihara, M Takamatsu, M Shimizu, N Kishi and Shoji Kagami : The role of NADPH oxidase (Nox) in ureteric bud branching and nephrogenesis, 11th Asian Congress of Pediatric Nephrology 2011, Jun. 2011.
36.
Maki Urushihara, Yukiko Kinoshita, S Matsuura, Ken-ichi Suga, M Takamatsu, M Shimizu, Shuji Kondo, H Kobori and Shoji Kagami : Urinary angiotensinogen as a biomarker of the intrarenal status of the renin-angiotensin system in patients with chronic glomerulonephritis, 11th Asian Congress of Pediatric Nephrology 2011, Jun. 2011.
37.
Shuji Kondo, S Matsuura, Yukiko Kinoshita, Ken-ichi Suga, Maki Urushihara, T Nagai, Toshiaki Tamaki and Shoji Kagami : The expression of NADPH oxidase and reactive oxygen species (ROS) production contribute to ureteric bud branching and nephrogenesis, World Congress of Nephrology 2011, Apr. 2011.
38.
Masaki Imanishi, Soichiro Tajima, Yoshitaka Kihira, Keisuke Ishizawa, Shuji Kondo, Shoji Kagami, Shuhei Tomita, Yasumasa Ikeda, Koichiro Tsuchiya and Toshiaki Tamaki : Increment intracellular labile iron enhances Angiotensin-induced intracellular adhesion molecule-1 (ICAM-1) expression in human glomerular endothelial cells, World congress of Nephrology 2011, Vancouver, Apr. 2011.
39.
Masaki Imanishi, Soichiro Tajima, Yoshitaka Kihira, Keisuke Ishizawa, Shuji Kondo, Shoji Kagami, Shuhei Tomita, Yasumasa Ikeda, Koichiro Tsuchiya and Toshiaki Tamaki : INCREMENT INTRACELLULAR LABILE IRON ENHANCES ANGIOTENSIN II-INDUCED INTRACELLULAR ADHESION MOLECULE-1 (ICAM-1) EXPRESSION IN HUMAN GLOMERULAR ENDOTHELIAL CELLS, World Congress of Nephrology 2011, 2011.
Shoji Kagami : The Roles for Integrins and Local Renin-Angiotensin System in Progressive Glomerulonephritis, Research-in-Progress Seminar, Pediatrics, Feinberg School of Medicine, Nov. 2010.
42.
Matsuura Sato, Shuji Kondo, Ken-ichi Suga, Yukiko Kinoshita, Maki Urushihara, Toshiaki Tamaki and Shoji Kagami : Reactive oxygen species (ROS) produced by NADPH oxidase contribute ureteric bud branching and nephrogenesis, ASN 2010, Colorado, Nov. 2010.
43.
Takashi Kaji, Kenji Mori, Souichirou Nakayama, Ryuuji Mitani, Kazuhisa Maeda, Shoji Kagami and Minoru Irahara : Prenatal diagnosis of total anomalous pulmonary venous connection to the portal vein with absence of ductus venosus : A case report, 20th World Congress on Ultrasound in Obstetrics and Gynecology, Prague, Czech, Oct. 2010.
44.
Etsuo Naito, Toshiaki Hashimoto, T Kumagai, S Yamashita, Yumiko Kotani and Shoji Kagami : Thiamine-responsive pyruvate dehydrogenase deficiency in two patients with normal development and muscular symptoms, The American Society of Human Genetics 60th Annual Meeting, Oct. 2010.
45.
木下 ゆき子, 近藤 秀治, 須賀 健一, Sato Matsuura, 漆原 真樹, 香美 祥二 : Candesartan Suppresses Glomerular Renin-Angiotensin System (RAS) Activation, Oxidative Stress and Progressive Glomerular Injury in Rat Anti-GBM GN, The 15th Congress of the International Pediatric Nephrology Association, 2010年8月.
46.
Sato Matsuura, Shuji Kondo, Ken-ichi Suga, Yukiko Kinoshita, Toshiaki Tamaki and Shoji Kagami : Expression and localization of focal adhesion proteins in the developing rat kidney, The 15th Congress of the International Pediatric Nephrology Association, Aug. 2010.
47.
Yasunobu Hayabuchi, Miki Inoue, Noriko Watanabe, Miho Sakata and Shoji Kagami : Serum concentration of heart-type fatty acid-binding protein in children and adolescents with congenital heart disease, The 3rd Congress of Asia-Pacific Pediatric Cardiac Society, Chiba, Jul. 2010.
48.
Shuji Kondo, Ken-ichi Suga, sato Matsuura, Yukiko Kinoshita, Maki Urushihara, Toshiaki Tamaki and Shoji Kagami : Enhanced expression of Hic-5 is involved in the development of human and rat mesangioproliferative glomerulonephritis, ISN-Nexus Kyoto Symposium 2010, Apr. 2010.
49.
Nabo Mohamed Helmy Manal, Yasunobu Hayabuchi, Miki Inoue, Noriko Watanabe, Miho Sakata and Shoji Kagami : Assessmentof modified Blalock-Taussig shunt in children with congenital heart disease using multidetector-row computed tomography, 5th China-Korea-Japan Pediatric Heart Forum, Beijing, Sep. 2009.
50.
Yasunobu Hayabuchi, Miki Inoue, Miho Sakata, Tetsuya Kitagawa, Takashi Kitaichi and Shoji Kagami : Assessment of systemic-pulmonary collateral arteries in children with cyanotic congenital heart disease using multidetector-row computed tomography: Comparison with conventional angiography, 5th World Congress of Paediatric Cardiology and Cardiac Surgery, Cairns, Jun. 2009.
51.
Kunihisa Yamaguchi, Keisuke Ishizawa, Shuhei Tomita, Koichiro Tsuchiya, Shuji Kondo, Shoji Kagami and Toshiaki Tamaki : Hypoxia-Inducible Factor-1α ameliorates ischemic acute renal failure and has a relation with a recovery from acute tubular necrosis, 41th ASN annual meeting, Philadelphia, Nov. 2008.
52.
Toshiaki Tamaki, Keisuke Ishizawa, Kunihisa Yamaguchi, Shuji Kondo, Shoji Kagami, Fukuhara Yayoi, Yuya Horinouchi and Koichiro Tsuchiya : Nitoroso-nifedipine is a new class drug to protect kidney against oxidative stress, 41th ASN annual meeting, Philadelphia, Nov. 2008.
53.
Maki Urushihara, Masanori Takamatsu, Maki Shimizu, Shuji Kondo, Akiko Kitamura, Yukiko Kinoshita, Keisuke Ishizawa, Toshiaki Tamaki and Shoji Kagami : The role of extracellular signal regulated kinase 5 in the accumulation of collagen matrix in rat mesangioproliferative glomerulonephritis, 40th ASN annual meeting, San Francisco, CA, Nov. 2007.
54.
Keisuke Ishizawa, Erika Miki, Arisa Hironaga, Koichiro Tsuchiya, Maki Urushihara, Shoji Kagami and Toshiaki Tamaki : Angiotensin II receptor blocker inhibits PDGF-induced cell migration in rat mesangial cells, 39th ASN annual meeting 2006, San Diego, Nov. 2006.
55.
Maki Urushihara, Masanori Takamatsu, Maki Shimizu, Shuji Kondo, Toshiaki Tamaki and Shoji Kagami : Extracellular signal regulated kinase 5 induces mesangial cell survival in rat progressive mesangioproliferative glomerulonephritis, 39th ASN annual meeting 2006, San Diego, Nov. 2006.
56.
Toshiaki Tamaki, Yasuhisa Kanematsu, Yuki Izawa, Hideki Ohnishi, Yuki Motobayashi, Shoji Kagami and Koichiro Tsuchiya : Chronic oral administration of nitrite restores circulating NO level and improves renal injury in L-NAME treated rats, 38th ASN annual meeting, Philadelphia, Nov. 2005.
57.
Maki Shimizu, Shuji Kondo, Maki Urushihara, Masanori Takamatsu, Toshiaki Tamaki and Shoji Kagami : Reactive Oxygen Species (ROS) is Pivotal Mediator for Glomerular Epithelial-Mesenchymal Transition (EMT) in Experimental Progressive Glomerulonephritis (GN), 38th ASN annual meeting, Philadelphia, Nov. 2005.
58.
Toshiaki Tamaki, Masumi Okamoto, Yasuhisa Kanematsu, Yuki Izawa, Shoji Kagami, Shuji Kondo, Masanori Yoshizumi and Koichiro Tsuchiya : Dietary dose of nitrite attenuates L-NAME-induced renal injury in rats, 3rd World Congress of Nephrology, Singapore, Jun. 2005.
59.
Toshiaki Tamaki, Masumi Okamoto, Yasuhisa Kanematsu, Yuki Izawa, Shoji Kagami, Shuji Kondo, Maki Shimizu, Masanori Yoshizumi and Koichiro Tsuchiya : Nitrite-derived nitric oxide formation following ischemia-reperfusion injury in rat kidney, 37th ASN annual meeting, St. Louis, MO, Oct. 2004.
60.
Shuji Kondo, Maki Shimizu, Koichiro Tsuchiya, Masanori Yoshizumi, Toshiaki Tamaki, Hiroshi Kawachi, Fujio Shimizu, Quinn T Mark, Lambeth J David, Yasuhiro Kuroda and Shoji Kagami : Add-on the antioxidant, probucol to angiotensin II type I receptor antagonist (ARB) arrests the progressive, St. Louis, MO, Oct. 2004.
61.
Shuji Kondo, M Shimizu, Koichiro Tsuchiya, Masanori Yoshizumi, Toshiaki Tamaki, H Kawachi, F Shimizu, Quinn MT, Lambeth DJ, Yasuhiro Kuroda and Shoji Kagami : Add-On the antioxidant,probucol to angiotensin 2 Type I receptor antagonist (ARB) arrests the progressive glomerulonephritis (GN) in the rat, 37th Annual meeting of American Society of Nephrology, St. Louis, 2004.
62.
A. Kitamura, Hiroyasu Tsukaguchi, Cheong HLL, Shoji Kagami, M Hattori, M Ikeda, K. Nozu, N. Yoshikawa, Toshio Doi, Y Choi and K. Iijima : Genetic scanning for 12 Asian families with steroid resistant nephrotic syndrome (SRN) based on haplotype analysis and computer simulation approach, 37th Annual meeting of American Society of Nephrology, St. Louis, 2004.
63.
M Hattori, Y Kobayashi, H Chikamoto, Koichiro Tsuchiya, S Gao, N Kobayashi, Shoji Kagami, P Mundel and K Ito : Induction of integrin-linked kinase (ILK) in mouse cultured podocytes after stimulation with plasma from recurrent-focal degmental glomerulosclerosis patients, 36th Annual meeting of American Society of Nephrology, San Diego, 2003.
64.
Toshiaki Tamaki, K Kirima, Masato Okamoto, S. Kondo, Shoji Kagami, Masanori Yoshizumi and Koichiro Tsuchiya : Oral nitrite increases the blood oxide and protects L-NAME-induced renal injury in rats, 36th Annual meeting of American Society of Nephrology, San Diego, 2003.
65.
S Kondo, Shoji Kagami, M Shimizu, A. Kitamura, Quinn MT, H Kawachi, F Shimizu and Yasuhiro Kuroda : Role of Gp91phox-containing NADPH oxidase in progressive model of rat mesangioproliferative glomerulonephritis (GN), 36th Annual meeting of American Society of Nephrology, San Diego, 2003.
66.
M. Shimizu, Hiroyasu Tsukaguchi, Shoji Kagami, A. Kitamura and Yasuhiro Kuroda : Enhanced expression of integrin-linked kinase (ILK) in crescent formation in experimental progressive glomerulonephritis (GN), 36th Annual meeting of American Society of Nephrology, San Diego, 2003.
67.
A. Kitamura, Hiroyasu Tsukaguchi, Shoji Kagami, M. Hattori, M. Ikeda, M. Honda, K. Nozu, N. Yoshikawa, Yasuhiro Kuroda, Toshio Doi and K. Iijima : Genetic Iinkage analysis of candidate ioci in Japanese families with steroid resistant nephrotic syndrome, 36th Annual meeting of American Society of Nephrology, San Diego, 2003.
68.
Shoji Kagami, S. Kondo, A. Kitamura, Maki Urushihara, H. Kawachi, F. Shimuzu and Yasuhiro Kuroda : Up-regulation of integrin-linked kinase (ILK) activity in the rat mesangioproliferative glomerulonephritis(GN), 35th Annual meeting of American Society of Nephrology, Philadelphia, 2002.
69.
Shoji Kagami, Maki Urushihara, S. Kondo, M Kitamura, K. Loster and Yasuhiro Kuroda : PDGF-BB enhances α1β1 integrin-mediated activation of ERK/AP-1 pathway involved in collagen matrix remodeling by rat mesangial cells(MCs), ASN/ISN World Congress of Nephrolpgy, San Francisco, 2001.
70.
S. Kondo, Shoji Kagami, Maki Urushihara, Koji Yasutomo, M. Kitamura, A. Kitamura, F. Strutz, G.A. Ler M and Yasuhiro Kuroda : TGF-b stimulates the collagen matrix remodeling abillity by human renal fibroblasts, ASN/ISN World Congress of Nephrolpgy, San Francisco, 2001.
71.
A. Kitamura, Shoji Kagami, S. Kondo, Maki Urushihara, S. Kobayashi, Koji Yasutomo, E. Yoshimura and Yasuhiro Kuroda : Endothelin-1 (ET) is a potent stimulator of α1β1 integrin-mediated collagen matrix remodeling by rat mesangial cells (MCs), ASN/ISN World Congress of Nephrolpgy, San Francisco, 2001.
72.
Maki Urushihara, Shoji Kagami, Koji Yasutomo, S. Kondo, A. Kitamura, H. Sugino, K. Tsuchida and Yasuhiro Kuroda : Expression of activin A and activin A receptor in human glomerulonephritis, ASN/ISN World Congress of Nephrolpgy, San Francisco, 2001.
岡田 朝美, T Kohmoto, T Naruto, I Yokota, Yumiko Kotani, A Shimada, Y Miyamoto, R Takahahi, A Goji, K Masuda, Shoji Kagami and Issei Imoto : The first Japanese patient of MDPL syndrome diagnosed via POLD1 mutation detection, 日本人類遺伝学会第62回大会, Nov. 2017.