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.
Junko Matsuda, Makiko Kido, Keiko Tadano-Aritomi, Ineo Ishizuka, Kumiko Tominaga, Kazunori Toida, Eiji Takeda, Kunihiko Suzuki and Yasuhiro Kuroda : Mutation in saposin D domain of sphingolipid activator protein gene causes urinary system defects and cerebellar Purkinje cell degeneration with accumulation of hydroxy fatty acid-containing ceramide in mouse, Human Molecular Genetics, Vol.13, No.21, 2709-2723, 2004.
Kumiko Tominaga, Junko Matsuda, Makiko Kido, Etsuo Naito, Ichiro Yokota, Kazunori Toida, Kazunori Ishimura, Kunihiko Suzuki and Yasuhiro Kuroda : Genetic Background Markedly Influences Vulnerability of the Hippocampal Neuronal Organization in the ''Twitcher'' Mouse Model of Globoid Cell Leukodystrophy, Journal of Neuroscience Research, Vol.77, No.4, 507-516, 2004.
(要約)
The twitcher mouse is well known as a naturally occurring authentic mouse model of human globoid cell leukodystrophy (GLD; Krabbe disease) due to genetic deficiency of lysosomal galactosylceramidase. The twitcher mice used most commonly are on the C57BL/6J background. We generated twitcher mice that were on the mixed background of C57BL/6J and 129SvEv, the standard strain for production of targeted mutations. Twitcher mice on the mixed background were smaller and had a shorter lifespan than were those on the C57BL/6J background. Many twitcher mice on the mixed background developed generalized seizures around 30 days that were never seen in twitcher mice on the C57BL/6J background. Neuropathologically, although the degree of the typical demyelination with infiltration of macrophages was similar in the central and peripheral nervous systems, in both strains, marked neuronal cell death was observed only in twitcher mice on the mixed background. In the hippocampus, the neuronal cell death occurred prominently in the CA3 region in contrast to the relatively well-preserved CA1 and CA2 areas. This neuropathology has never been seen in twitcher mice on the C57BL/6J background. Biochemically, the brain of twitcher mice on the mixed background showed much greater accumulation of lactosylceramide. Genetic background must be carefully taken into consideration when phenotype of mutant mice is evaluated, particularly because most targeted mutants are initially on a mixed genetic background and gradually moved to a pure background. These findings also suggest an intriguing possibility of important function of some sphingolipids in the hippocampal neuronal organization and maintenance.
Yuka Takehara, Kazuhiro Mori, Takuji Edagawa, Mayumi Sugimoto, Hiroo Takehara, Michinori Ito and Yasuhiro Kuroda : Presumed hypoplastic intrahepatic portal system due to patent ductus venosus: Importance of direct pcclusion test of ductus venosus under open laparotomy, Pediatrics International, Vol.46, No.4, 484-486, 2004.
Yoshihiro Touda, Kenji Mori, Toshiaki Hashimoto, Masahito Miyazaki and Yasuhiro Kuroda : [Efficacy of secretin for the treatment of autism]., No to Hattatsu, Vol.36, No.4, 289-295, 2004.
(要約)
We administered secretin intravenously to 14 patients with autism (9 to 14 years, 10 males; 4 females), and evaluated its clinical effect. We also measured cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) and 5-hydroxy-indole-3-acetic acid (5HIAA) before and after 4 weeks treatment, and compared them with the grade of improvement of the clinical symptoms assessed by the scores of Autism Diagnostic Interview-Revised (ADI-R). After injection of secretin, the ADI-R score increased in 8 patients, but declined in 3. Improvement was observed in functions such as sociability (interpersonal relationships), communication and speech improved, whereas in the others. symptoms such as hyperkinesias and stereotyped behavior became worse. The CSF levels of HVA was significantly increased in all of the patients showing an improvement in the ADI-R score. SHIAA levels also tended to increase, although this increase was not significant. These findings suggest that secretin promotes the metabolism of serotonin and dopamine in the central nervous system, which may contribute to improvement in clinical symptoms of autism.
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.
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.
Kazuhiro Mori, Takuji Edagawa, Miki Inoue, Masaki Nii, Ryuji Nakagawa, Yuka Takehisa, Yasuhiro Kuroda and Katsunori Tatara : Peak negative myocardial velocity gradient and wall-thickening velocity during early diastole are noninvasive parameters of left ventricular diastolic function in patients with Duchenne's progressive muscular dystrophy, Journal of the American Society of Echocardiography, Vol.17, No.4, 322-329, 2004.
(要約)
Myocardial velocity gradient and wall-thickening velocity were measured in the interventricular septum and left ventricular posterior wall (LVPW) by color-coded M-mode Doppler tissue echocardiography in patients with Duchenne's progressive muscular dystrophy (DMD) with a normal shortening fraction (n = 14) and age-matched control subjects (n = 40). In the LVPW, peak myocardial velocity gradients during systole and early diastole were significantly lower for patients with DMD than in control subjects (P <.0005, and P <.0001, respectively). Peak myocardial wall-thickening velocities of the LVPW during systole and early diastole were also lower for patients with DMD (P <.0005 and P <.0001, respectively). Mitral peak atrial to early filling velocity ratio was not significantly different between the 2 groups. The cut-off values of peak myocardial velocity gradients and wall-thickening velocities of the LVPW during early diastole for differentiation between patients with DMD and control subjects were -5.8/s and -6.0 cm/s, respectively (sensitivity/specificity: 93%/93% and 93%/85%, respectively). In conclusion, wall thinning during early diastole is frequently abnormal in patients with DMD, even when conventional echocardiographic findings are normal.
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.
Kazuhiro Mori, Ryuji Nakagawa, M Nii, T Edagawa, Y Takehara, M Inoue and Yasuhiro Kuroda : Pulsed wave Doppler tissue echocardiography assessment of the long axis function of the right and left ventricles during the early neonatal period, Heart, Vol.90, No.2, 175-180, 2004.
(要約)
To assess the long axis function of both ventricles during the early neonatal period by using pulsed wave Doppler tissue (PWDT) echocardiography. PWDT echocardiography was recorded from the lateral sites of the mitral and tricuspid annuluses and the tip of interventricular septum in 130 neonates within 24 hours after birth (day 0 group), in 135 neonates 1-7 days after birth (day 1-7 group), and in 131 healthy children (children group). Peak systolic motion velocity (Sw) of the three ventricular walls positively correlated with the number of days after birth (p < 0.005). Compared with the children group, in neonates Sw in the right ventricle and peak early diastolic motion velocity (Ew) and peak atrial systolic motion velocity in the interventricular septum were lower than in the remaining two walls (p < 0.0005, p < 0.0001, and p< 0.0001, respectively). Although peak mitral and tricuspid flow velocities during early diastole (E) correlated with the number of hours after birth in the day 0 group, there was no significant change in the Ew of either ventricle. The E:Ew ratio of both ventricles was significantly higher in both neonate groups than in the children group (p < 0.001). The E:Ew ratio of the left ventricle was higher in the day 0 group than in the day 1-7 group (p < 0.005). The two ventricles differ in their normal PWDT echocardiographic values and in the parameter change after birth during the early neonatal period, which may reflect differences in ventricular adaptation after birth.
(キーワード)
Echocardiography, Doppler, Pulsed / Gestational Age / Humans / Infant, Newborn / Observer Variation / Systole / Ventricular Function, Left / Ventricular Function, Right
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.
T Ogose, Tsutomu Watanabe, H Suzuya, M Kaneko, Toshihiro Onishi, Hiroyoshi Watanabe, R Nakagawa, Yasuhiro Okamoto, Nobuya Sano, Y Kozan and Yasuhiro Kuroda : Autoimmune hepatitis following allogeneic PBSCT from an HLA-matched sibling, Bone Marrow Transplantation, Vol.31, No.9, 829-832, 2003.
(要約)
A 7-year-old boy with acute lymphoblastic leukemia (ALL) in second remission received an allogeneic PBSCT from his HLA-matched sister. Acute grade II graft-versus-host disease (GVHD) resolved with corticosteroids. Chronic GVHD in the skin and oral mucosa at around day 60 responded to corticosteroids and cyclosporin A. At 6 months after the transplant, he developed hepatic dysfunction with elevated serum transaminases and gamma-globulin. Liver biopsy revealed chronic inflammation with lymphocytes and plasma cells in portal areas without destruction of bile ducts, suggesting autoimmune hepatitis. While rare, autoimmune hepatitis should be considered a potential long-term complication in patients with hepatic dysfunction in the late post-transplant phase.
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.
Kazuhiro Mori, Masafumi Harada and Yasuhiro Kuroda : Twisted atrioventricular valves in double inlet left ventricle, Cardiology in the Young, Vol.12, No.4, 401-403, 2002.
(要約)
Twisted atrioventricular connections usually occur in hearts with biventricular artioventricular connections. Here, we describe a case of twisted atrioventricular valves associated with double inlet left ventricle and discordant ventriculo-arterial connections. Color Doppler echocardiography, and cine magnetic resonance imaging, clearly demonstrated that the right atrioventricular valve was located anterior and superior to the left atrioventricular valve, and that the axes of the two atrioventricular valves crossed each other within the dominant left ventricle.
(キーワード)
Criss-cross heart / functionally univentricular heart / magnetic resonance imaging
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.
Kazuhiro Mori, Tetsuya Manabe, Masaki Nii, Yasunobu Hayabuchi, Yasuhiro Kuroda and K. Tatara : Plasma levels of natriuretic peptide and echocardiographic parameters in patients with Duchenne's progressive muscular dystrophy., Pediatric Cardiology, Vol.23, No.2, 160-166, 2002.
(要約)
We investigated the relationship between plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels and systolic and diastolic cardiac function, determined by echocardiography, in 63 patients with Duchenne's progressive muscular dystrophy (DMD) (age range 8-21 years). The relationship between shortening fraction of the left ventricle and ANP and BNP levels was curvilinear rather than linear: When the shortening fraction was >15%, increases in ANP and BNP levels were minimal. However, if the shortening fraction was <15%, both natriuretic peptide levels increased dramatically. Stepwise regression analysis revealed that only the deceleration time of the early diastolic filling wave predicted plasma BNP concentration among various diastolic echocardiographic parameters determined by mitral flow. Three patients died of cardiac dysfunction during a 2-year follow-up period. These patients had a severely decreased deceleration time (<65% of normal) in association with increases in both natriuretic peptide levels. In conclusion, plasma ANP and BNP levels are not sensitive markers for the early detection of cardiac systolic dysfunction in patients with DMD. However, in patients with systolic dysfunction, an increase in the concentrations of these peptides, associated with a decrease in the deceleration time of early diastolic filling, suggests poor prognosis.
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.
26.
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.
Kazuhiro Mori, Yasunobu Hayabuchi, Yasuhiro Kuroda, Masaki Nii and Tetsuya Manabe : Left ventricular wall motion velocities in healthy children measured by pulsed wave Doppler tissue echocardiography: normal values and relation to age and heart rate, Journal of the American Society of Echocardiography, Vol.13, No.11, 1002-1011, 2000.
(要約)
Left ventricular wall motion velocities were measured by pulsed wave Doppler tissue (PWDT) echocardiography in 131 healthy children (mean age 7.5 +/- 5.5 years) at the interventricular septum and the posterior wall in the left ventricular short-axis view, and at the interventricular septum and the lateral wall in the 4-chamber view. The systolic wave (Sw) consisted of 2 components, and the difference between the 2 components was greater in the lateral wall than in the other walls. The peak early diastolic wave (Ew) velocity was also highest in the lateral wall. Most variables during systole correlated with age. The ratio of peak atrial systolic wave (Aw) velocity to peak Ew velocity (Aw/Ew) correlated with heart rate. The Aw/Ew in each wall correlated with the ratio of late (A) to early (E) peak mitral flow, although regression slopes differed among different wall segments. In younger children with increased heart rates, the Aw/Ew ratio increased because the Ew velocity decreased, although the A/E ratio increased because of an increased A velocity. Normal values for the PWDT variables change with heart rate and age in the pediatric population. The data reported in this study can be used as normal values for left ventricular function for PWDT echocardiography.
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.
Kazuhiro Mori, Tetsuya Manabe, Masaki Nii, Yasunobu Hayabuchi, Yasuhiro Kuroda and Hiroshi Kitahata : Cyclic variation of integrated ultrasound backscatter in the left ventricle during the early neonatal period., American Heart Journal, Vol.140, No.3, 463-468, 2000.
(要約)
Significant changes in the contractility and histologic structure of the ventricular myocardium occur during the early neonatal period. Cyclic variation (CV) of ultrasonic integrated backscatter (IBS) reflects myocardial contractile performance. The aim of this study was to define normal values of and its serial changes in CV of IBS in the left ventricle of normal neonates. We recorded long-axis IBS images in 169 healthy neonates within 14 days after birth (mean 4.6 +/- 4.2 days) and in 84 infants and children (mean age 8.7 +/- 5.2 years). For each, we obtained CV of IBS in the interventricular septum (CV(IVS)) and the posterior wall (CV(PW)). In neonates, there was a significant linear correlation between CV and date after birth in measurements of both the interventricular septum and the posterior wall (r = 0.57 and 0. 60, respectively). In infants and children, there was no significant relation between age and CV(IVS) or CV(PW). In neonates >4 days after birth, the magnitude of CV(IVS) was not significantly different from that in infants or children. By contrast, the magnitude of CV(PW) was still significantly decreased in neonates >9 days after birth compared with that in infants and children (P <. 005). The ratio of CV(IVS) to CV(PW) (CV(IVS)/CV(PW)) was significantly higher in neonates than in infants and children (0.99 +/- 0.29 vs 0.80 +/- 0.22, P <.001). Both CV(IVS) and CV(PW) in neonates gradually increase after birth, indicating developmental maturation of the left ventricle. High values of CV(IVS)/CV(PW) might reflect the remnant of relatively high contractile performance in the right ventricle during fetal life.
Kazuhiro Mori, Yasunobu Hayabuchi, Yasuhiro Kuroda, Nii Masaki, Yuasa Yasuhiro and Taguchi Yoshiyuki : Retrograge holodiastolic flow in the abdominal aorta detected by pulsed Doppler echocardiography in patients with Kawasaki disease, European Journal of Pediatrics, Vol.159, No.7, 509-514, 2000.
(要約)
Retrograde holodiastolic flow in the abdominal aorta (retrograde flow) detected by pulsed Doppler echocardiography is usually noted in patients with aortic regurgitation or patent ductus arteriosus. Similar abnormal flow often is present in patients with acute phase Kawasaki Disease (KD). In 21 patients with acute phase KD, 15 had a retrograde flow. Retrograde flow was recognised in only 3 of patients with acute infection (n = 31) and in no healthy controls (n = 10). The ratio of the time velocity integral for diastolic retrograde flow to that for antegrade flow (regurgitant fraction) was significantly greater in patients with KD (median value 23%) than in patients with acute infection (1%) or healthy individuals (1%) (P < 0.001 for both). Four patients with coronary arterial involvement (one with an aneurysm and three with transient dilation of the coronary arteries) had a greater regurgitant fraction than the 17 patients without coronary arterial involvement (median values: 31% versus 18%, P < 0.05). The C-reactive protein was increased for a longer period of time in patients with KD with a greater regurgitant fraction (P < 0.01). Plasma nitric oxide (NO) metabolite concentrations were significantly greater in patients with KD than in those with acute infection or in healthy controls (P < 0.001 for both). There was a positive correlation between plasma NO metabolite concentrations and the regurgitant fraction in patients with KD (r = 0.69). Retrograde flow in the abdominal aorta is increased in patients with Kawasaki disease. Further studies are needed to clarify the causal relationship between the abnormal flow and the overproduction of nitric oxide.
Kazuhiro Mori, Yasunobu Hayabuchi and Yasuhiro Kuroda : Diagnosis and natural history of isolated congenital pulmonary regurgitation in fetal life, Cardiology in the Young, Vol.10, No.2, 162-165, 2000.
(要約)
We describe a rare instance of isolated pulmonary regurgitation caused by a dysplastic pulmonary valve which was detected prenatally. Fetal echocardiography demonstrated severe pulmonary regurgitation, and progressive cardiomegaly because of right ventricular volume overload. After birth, conservative therapy was successful in alleviating the pulmonary vascular resistance, and the pulmonary regurgitation gradually decreased.
Kenji Sasahara, Takashi Yamaoka, Maki Moritani, Katsuhiko Yoshimoto, Yasuhiro Kuroda and Mitsuo Itakura : Molecular Cloning and Tissue-specific Expression of a New Member of the Regenerating Protein Family, Islet Neogenesis-associated Protein-related Protein., Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Vol.1500, No.1, 142-146, 2000.
(要約)
Islet neogenesis-associated protein (INGAP) is a protein expressed during islet neogenesis. We have cloned a novel cDNA having a similar sequence to INGAP cDNA. The cDNA encodes 175 amino acids designated INGAP-related protein (INGAPrP). INGAP is expressed in cellophane-wrapped pancreas, but not in normal pancreas, whereas INGAPrP was abundantly expressed in normal pancreas.
Kenji Sasahara, Takashi Yamaoka, Maki Moritani, Masaki Tanaka, Hiroyuki Iwahana, Katsuhiko Yoshimoto, Jun-ichi Miyagawa, Yasuhiro Kuroda and Mitsuo Itakura : Molecular Cloning and Expression Analysis of a Putative Nuclear Protein, SR-25., Biochemical and Biophysical Research Communications, Vol.269, No.2, 444-450, 2000.
(要約)
We cloned a full-length mouse cDNA and its human homologue encoding a novel protein designated as "SR-25." In Northern blot analysis, SR-25 mRNA was expressed in all organs tested, and relatively abundant in testis and thymus. Deduced amino acid sequences of mouse SR-25 and human SR-25 showed 77.7% identity. SR-25 has a serine-arginine repeat (SR repeat) and two types of amino acid clusters: a serine cluster and a highly basic cluster. Based on the presence of many nuclear localizing signals and a similarity to RNA splicing proteins, SR-25 is strongly suggested to be a nuclear protein and may contribute to RNA splicing.
Yasunobu Hayabuchi, Suguru Matsuoka and Yasuhiro Kuroda : Plasma concentrations of atrial and brain natriuretic peptides and cyclic guanosine monophosphate in response to dobutamine infusion in patients with surgically repaired tetralogy of fallot, Pediatric Cardiology, Vol.20, No.5, 343-350, 1999.
(要約)
We examined the plasma concentrations of atrial and brain natriuretic peptides (ANP and BNP) and cyclic guanosine monophosphate (cGMP) during dobutamine infusion and their relationship with hemodynamic parameters in 14 patients with surgically repaired tetralogy of Fallot (TOF). Dobutamine was infused at an initial dose of 5 microgram/kg/min and increased by 5 microgram/kg/min up to 20 microgram/kg/min. The plasma ANP, BNP, and cGMP concentrations were determined before infusion, at the end of each stage, and 15 minutes after discontinuing dobutamine infusion. The plasma concentrations of ANP, BNP, and cGMP were elevated in all patients before dobutamine infusion. The ANP, BNP, and cGMP concentrations decreased in 11 of the 14 patients during dobutamine infusion. In contrast, the plasma ANP and BNP concentrations increased in the remaining 3 patients without a change in the cGMP concentration. The right ventricular pressure and volume were significantly elevated in these patients. The plasma cGMP concentration correlated with the ANP concentration (r = 0.62, p < 0.01) but not the BNP concentration. The plasma ANP concentration during dobutamine infusion correlated with right ventricular systolic pressure (r = 0.71, p < 0.05), mean right atrial pressure (r = 0.29, p < 0.05), and mean pulmonary capillary wedge pressure (r = 0.32, p < 0.05). The BNP concentration correlated with right ventricular volume (r = 0.61, p < 0.05) and systolic pressure (r = 0. 46, p < 0.05). In conclusion, rapid changes in ANP, BNP, and cGMP concentrations during dobutamine infusion reflect the changes in atrial and ventricle pressure and volume overload. In surgically repaired TOF, the ANP concentration is affected by right ventricular systolic pressure, right atrial pressure, and pulmonary capillary pressure. Furthermore, the BNP concentration reflects right ventricular pressure and volume overload.
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.
Kazuhiro Mori, Yasunobu Hayabuchi, Yasuhiro Kuroda, Yutaka Nakaya, Koichiro Tsuchiya and Hiroyuki Morimoto : Age-related endothelium-dependent vascular relazation in rat thoracic aorta in response to colforsin, Pediatrics International, Vol.41, No.6, 673-681, 1999.
(要約)
Colforsin, a novel water-soluble forskolin derivative, increases intracellular cyclic AMP by direct stimulation of adenylate cyclase and has strong positive inotropic and vasodilative effects. However, it is not known whether colforsin causes nitric oxide (NO) release and enhances endothelium-dependent vascular relaxation. We studied NO production and relaxation on exposure to colforsin in thoracic aorta from rats aged 4, 12 and 60 weeks. When a low concentration of colforsin was added to a solution bathing ring segments of aorta from 12-week-old rats, relaxation was greater in the ring segments with intact endothelium than in those from which the endothelium had been removed. A high concentration of colforsin induced the same degree of relaxation of ring segments with or without endothelium, probably by a direct effect on vascular smooth muscle cells. Production of NO in response to colforsin by cultured endothelial cells from 12-week-old rat aorta was demonstrated by the electron paramagnetic resonance spin trapping method. A low concentration of colforsin relaxed aortic segments with intact endothelium from 4-week-old rats more than those from 12-week-old or 60-week-old rats. Reversal of relaxation by NG-nitro L-arginine, an NO synthesis inhibitor, was most significant in arteries from 4-week-old rats. Production of NO after exposure to colforsin was greater in aortic segments from 4-week-old rats than older rats, as detected by an NO-selective electrode. Colforsin induces vasodilation in part by releasing NO from the endothelium in rat thoracic aorta. In addition to a direct vasodilative effect on the vascular smooth muscle cells, an endothelium-dependent vasodilative effect is also important in younger arteries.
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.
Yasunobu Hayabuchi, Suguru Matsuoka, Masahiro Kubo and Yasuhiro Kuroda : Usefulness of color kinesis imaging for evaluation of regional right ventricular wall motion in patients with surgically repaired tetralogy of Fallot., The American Journal of Cardiology, Vol.82, No.10, 1224-1229, 1998.
45.
Ichiro Yokota, Hideki Hayashi, Junko Matsuda, Etsuo Naito, Michinori Ito, Yousuke Ebina and Yasuhiro Kuroda : Effect of growth hormone on the translocation of GLUT4 and its relation to insulin-like and anti-insulin action., Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol.1404, No.3, 451-456, 1998.
(要約)
To elucidate the effect of growth hormone (GH) on the insulin signal transduction pathway leading to the translocation of glucose transporter-4 (GLUT4), we constructed Chinese hamster ovary cells that overexpressed GH receptor and GLUT4. Treatment with GH triggered GLUT4 translocation, and this translocation was completely inhibited by wortmannin. GH-induced GLUT4 translocation reached a maximum level after 30 min, and then gradually decreased and returned to the basal level after 2 h. Tyrosine phosphorylation of JAK2 also became maximal after 30 min and then gradually decreased. In contrast, GLUT4 translocation remained unchanged for 2 h after insulin treatment, and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) also remained constant for up to 2 h. Chronic GH treatment had almost no effect on insulin-stimulated Akt kinase activation and GLUT4 translocation. These results suggest that GH and insulin translocate GLUT4 in a similar manner, at least in part, and the difference in translocation depends on the difference in the tyrosine phosphorylation of JAK2 and IRS-1. The anti-insulin action of GH after chronic GH treatment does not appear to be mainly due to the inhibition of GLUT4 translocation.
(キーワード)
Androstadienes / Animals / CHO Cells / Cricetinae / Glucose Transporter Type 4 / Growth Hormone / インスリン (insulin) / インスリン抵抗性 (insulin resistance) / Monosaccharide Transport Proteins / Muscle Proteins / Receptors, Somatotropin / Time Factors / Transfection
Eiji Hosoi, Masao Hirose, Shyuich Hamano, Msako Morimoto and Yasuhiro Kuroda : Effect of MDR antagonists on the cidal activity of vincristine for cells expressing MDR-1 is superior to those expressing MRP, In.J.Oncology, Vol.13, 343-348, 1998.
Although endothelium-derived hyperpolarizing factor (EDHF) activity has been demonstrated in arteries from various species, EDHF has not been chemically identified, nor its mechanism of action characterized. To elucidate this mechanism, we tested the effect of EDHF on large-conductance Ca2+-activated K+ (K(Ca)) channels in porcine coronary artery smooth muscle cells. By using a patch-clamp technique, single-channel currents were recorded in cultured smooth muscle cells; the organ bath also contained a strip of porcine coronary with endothelium, which served as the source of endothelium-derived relaxing factor(s) including EDHF. Exposure of endothelium to 10(-6) M bradykinin activated K(Ca) channels in cultured smooth muscle cells in cell-attached patches. When the experiment was performed in the presence of 10 microM indomethacin and 30 microM N(G)-nitro-L-arginine (L-NNA), which block the generation of prostaglandin I2 (PGI2) and NO, respectively, K(Ca) channel activity was stimulated by bradykinin, indicating the direct involvement of EDHF in K(Ca) channel stimulation. Neither 10 microM methylene blue nor 25 microM Rp-cAMPS inhibited bradykinin-induced K(Ca) channel activity. In inside-out patches, the addition of bradykinin to the solution was without effect on K(Ca) channel activation. However, in the presence of 0.5 mM guanosine triphosphate (GTP) and 1.0 mM adenosine triphosphate (ATP) in the bath solution, K(Ca) channels was activated by bradykinin. In outside-out patches, the addition of bradykinin also increased K(Ca) channel activity, when GTP and ATP were added to the pipette solution. The addition of GDP-beta-S (100 microM) in the cytosolic solution completely blocked the activation K(Ca) channels induced by bradykinin in inside-out and outside-out patches. Pretreatment with 30 microM quinacrine, a phospholipase A2 inhibitor, or 3 microM 17-octadecynoic acid (17-ODYA), a cytochrome P450 inhibitor, in addition to indomethacin and L-NNA, abolished bradykinin-stimulated K(Ca) channel activity in cell-attached patches. Both 14,15-epoxyeicosatrienoic acid (EET) and 11,12-EET increased the open probabilities of K(Ca) channels in cell-attached patches. These results suggest that EDHF, released from endothelial cells in response to bradykinin, hyperpolarizes smooth muscle cells by opening K(Ca) channels. Furthermore, our data suggest that EDHF is an endothelium-derived cytochrome P450 metabolite of arachidonic acid. The effect of EDHF on K(Ca) channels is not associated with an increase of cAMP and cGMP. The activation of K(Ca) channels appears to be due to the activation of GTP-binding protein.
Shyuich Hamano, Masao Hirose, Eiji Hosoi and Yasuhiro Kuroda : Overcoming of cross-resistance to the cell-killing activityof oxygen radicals in VCR-resistant hematologic cell lines with cyclosporin-A, Anticancer Res., Vol.18, 1543-1548, 1998.
51.
Kazuhiro Mori, Yutaka Nakaya, Yasunobu Hayabuchi, Sakamoto Sadaichi, Matsuoka Suguru and Yasuhiro Kuroda : Lactate-induced vascular relaxation in porcine coronary arteries is mediated by Ca2+activated K+ channels, Journal of Molecular and Cellular Cardiology, Vol.30, No.2, 349-356, 1998.
(要約)
Under ischemic conditions and during strenuous exercise, lactate concentrations increase in coronary artery smooth muscle cells. Although lactate causes pH-independent vasorelaxation, the mechanisms responsible for this effect are unclear. We investigated the effect of lactate on K+ channels in smooth muscle cells from porcine coronary arteries. Neutralized lactate (3-100 mm) induced vasorelaxation in ring segments of porcine coronary arteries precontracted with KCl in a dose-dependent manner. One millimolar tetraethylammonium (TEA), an inhibitor of Ca2+-activated K+ channels (KCa channels), reversed the lactate-induced relaxation, while 60 microM glibenclamide, an inhibitor of ATP-sensitive K+ channels (KATP channels), did not. In both inside-out and cell-attached patch clamp technique with cultured smooth muscle cells, the KCa channels were activated by lactate. In inside-out patches, lactate activated KCa channels, even under acidic conditions. This is in contrast to the effect of H+ which inactivated KCa channels. We conclude that vasodilation of porcine coronary arteries induced by lactate is, at least in part, mediated by activation of KCa channels. This effect may be self-protective by maintaining coronary blood flow during ischemia.
Hisami Okumura, Eiji Takeda, Kazumi Takata, Emi Shuto, Ken-ichi Miyamoto, Toshiyuki Watanabe, Yoshifumi Kawano, Yoichi Takaue and Yasuhiro Kuroda : Total parenteral nutrition on energy metabolism in children undergoing autologous peripheral blood stem cell transplantation., The Journal of Medical Investigation : JMI, Vol.44, No.3-4, 199-203, 1998.
(要約)
The resting energy expenditure (REE) and the respiratory quotient (RQ) were measured longitudinally using indirect calorimetry to examine the effects of total parenteral nutrition (TPN) on energy metabolism in children undergoing autologous peripheral blood stem cell transplantation (PBSCT). There were six children (two males and four females) and the age ranged from five to 13 years (median, eight yrs). The diagnosis included acute lymphocytic leukemia (ALL; 4), neuroblastoma (NBL; 1) and primitive neuroectodermal tumor (PNET; 1). TPN was started after the patients were stabilized following PBSCT (group A; n = 3) or before the initiation of high-dose cytoreductive chemotherapy (HCC) (group B; n = 3). Duration of HCC before PBSCT was identical between the two groups (six to eight days). Average total calorie and protein intake during HCC was significantly higher for group B than for group A. The %REE, the percentage of REE to the predicted basal energy expenditure (BEE), in group A showed 133 +/- 19%, 129 +/- 14% and 146 +/- 11% during three periods of HCC (days -8 to -1 of PBSCT), bone marrow suppression (days 0 to 11 of PBSCT) and bone marrow recovery (days 12 to 22 of PBSCT), respectively. In contrast, those in group B were 10% to 20% lower than those in group A at all periods. Carbohydrate oxidation rates during HCC in group A were significantly lower than those in group B, and those were not different between both groups during post-PBSCT periods. Fat oxidation rates in both groups were similar at all stages of periods. In contrast, protein degradation rates in group A were significantly higher than those in group B at all stages of the period. From these results, we concluded that commencement of TPN administration prior to HCC in the patients undergoing PBSCT provides beneficial effects to maintain better energy metabolic and nutritional status.
Yasunobu Hayabuchi, Yutaka Nakaya, Suguru Matsuoka and Yasuhiro Kuroda : Hydrogen peroxide-induced vascular relaxtion in porcine coronary arteries is mediated by Ca2+-activated K+ channels, Heart and Vessels, Vol.13, 9-17, 1998.
54.
Eiji Hosoi, Shyuich Hamano, Masao Hirose and Yasuhiro Kuroda : Detection of histo-blood groop ABOmRNA in human chronic myeroid leukemia cell lines using reverse transcription-polymerase chain reaction(RT-PCR), Cancer Letters, Vol.133, 191-196, 1998.
55.
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.
Masao Hirose, Shyuich Hamano, Eiji Hosoi and Yasuhiro Kuroda : Correlation between permeability-related glycoprotein expression and susceptibility to oxygen radicals in vincristine-resistant hematologic cell lines, Cancer Letters, Vol.120, 179-184, 1997.
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.
60.
Kazuhiro Mori, matsuoka Suguru, Yasunobu Hayabuchi, Yasuhiro Kuroda and Tetsuya Kitagawa : Absence of the inferior vena cava in a patient with omphalocele: tow-dimensional echocardiographic and cineangiographic findings, Heart and vessels, Vol.11, No.2, 104-109, 1996.
61.
Yasunobu Hayabuchi, Suguru Matsuoka, Masahiro Kubo, Kazuhiro Mori, Katsunori Tatara and Yasuhiro Kuroda : Usefulness of QRST isointegral maps for the diagnosis of right ventricular pressure overload in patients with surgically repaired tetralogy of Fallot complicated with right bundle branch block, Journal of Electrocardiology, Vol.29, No.2, 111-117, 1996.
(要約)
Right ventricular pressure overload was evaluated in 29 patients, 8-12 years old, with surgically repaired tetralogy of Fallot by using body surface QRST isointegral maps. In patients with right ventricular systolic pressure above 50 mmHg, the maxima of the isointegral maps tended to shift toward the lower right-hand region of the map. The maximum value was significantly correlated with right ventricular systolic pressure (r = .58; P < .01). There was a correlation between the right ventricular systolic pressure and the percentage +2SD and percentage +5SD departure areas, which are defined as the area (expressed as a percentage of the total chest area) in which the QRST integral values are greater than the normal mean +2SD or +5SD, respectively (r = .61 and .84, P < .01). The QRST isointegral map can be used to evaluate right ventricular pressure overload in postoperative patients with tetralogy of Fallot complicated by right bundle branch block. The percentage +5SD departure area is the most valuable parameter for the quantitative evaluation of the right ventricular systolic pressure.
(キーワード)
Body Surface Potential Mapping / Bundle-Branch Block / Case-Control Studies / Child / Humans / Postoperative Complications / Signal Processing, Computer-Assisted / Tetralogy of Fallot / Ventricular Dysfunction, Right / Ventricular Pressure
L Mori, Suguru Matsuoka, Yoshinobu Hayabuchi, Yasuhiro Kuroda and Tetsuya Kitagawa : Abence of the inferior vena cava in a patient with omphalocele: Two-dimensional echocardiographic and cineangiographic findings., Heart and Vessels, Vol.11, No.2, 104-109, 1996.
(要約)
We report an unusual form of absence of the inferior vena cava (IVC) in a patient with a repaired omphalocele. Two sets of bilateral paravertebral veins served as the channels of systemic venous return from the lower half of the body. These veins were narrower than typical azygos or hemiazygos continuation in the absence of the IVC, with the result that a catheter from the femoral vein could not reach the right atrium (RA). Other associated venous-side anomalies were present, including a chamber between the hepatic vein (HV) and RA, narrowing and angulation at the junction between the HV and the chamber, and a subaortic innominate vein. All these anomalies were demonstrated by two-dimensional and color Doppler echocardiography. The recognition of these venous anomalies is important for cardiac catheterization or IVC cannulation for cardiopulmonary bypass in patients with omphalocele.
EE Antouniou, Matsuoka Suguru, Kazuhiro Mori, Yasunobu Hayabuchi and Yasuhiro Kuroda : Anomalous inferiorvena cava in association with omphalocele: a case report, Pediatric Radiology, Vol.25, No.4, 265-266, 1995.
(要約)
We present the case of a 6-year-old boy who had an omphalocele repaired at day 1 of life. He had a secundum atrial septal defect and an anomalous inferior vena cava of a type which has not been previously reported. Cine-MRI was a useful noninvasive tool for diagnosing the anomalous subaortic innominate vein and four immature vessels which make up the venous drainage systems of the lumbar region. The recognition of this malformation is important in planning and executing surgical repair or cardiac catheterization for postoperative patients with omphaloceles.
(キーワード)
子ども (children) / Heart Septal Defects, Atrial / Hernia, Umbilical / Humans / Magnetic Resonance Imaging, Cine / Male / Vena Cava, Inferior
Kazuhiro Mori, Matsuoka Suguru, Tatara Katusnori, Yasunobu Hayabuchi, Nii Masaki and Yasuhiro Kuroda : Echoicardiographic evaluation of the development of aortic valve prolapse in supracristal ventricular septal defect, European Journal of Pediatrics, Vol.154, No.3, 176-181, 1995.
73.
Matsuoka Suguru, EE Antoniou, Kazuhiro Mori, Yasunobu Hayabuchi and Yasuhiro Kuroda : The first report of a patient with interrupted inferior vena cava, multiple post-renal veins and azygos-hemiazygos continuation, Acta Pediatrica Japonica, Vol.37, No.4, 514-517, 1995.
Koji Yasutomo, Kenichi Maeda, Shigekazu Nagata, Hideyuki Nagasawa, Kaname Okada, A. Robert Good, Yasuhiro Kuroda and Kunisuke Himeno : Defective T cells from gld mice play a pivotal role in development of Thy-1.2+B220+ cells and autoimmunity, The Journal of Immunology, Vol.153, No.12, 5855-5864, 1994.
(要約)
The gld mouse represents a fascinating animal model of autoimmune disease, which is characterized by massive development of Thy-1.2+B220+ CD4-CD8- cells. These cells thus have double positive markers for T and B cells, but are double negative for CD4 and CD8 markers and are thus designated DN cells in the present context. An additional important feature in gld mice is a defect in expression of Fas ligand. To investigate the regulatory role of bone marrow-derived cells for the development of these DN cells and of gld autoimmunity, we constructed chimeric mice transplanted with fetal liver cells or fetal thymus from gld mice into nonirradiated severe combined immunodeficient (SCID) mice. These chimeric mice regenerated, developed both these DN cells and the gld autoimmune syndrome and also generalized lymphoproliferative disorders. However, when fetal liver cells from both gld and non-gld mice (C57BL/10 Thy-1.1 mice) were co-transplanted into SCID mice, the development of DN cells was apparently inhibited. Further, this inhibition was also seen in SCID mice that had been grafted with both gld and non-gld fetal thymus revealing the pivotal role played by T cells in development of DN cells. When B cells purified from non-gld (C3H+/+) mice were transplanted into SCID mice grafted with gld fetal thymus, the development of DN cells was not inhibited. Taken together, these findings indicate that T cells from non-gld mice inhibit the expression of gld features, e.g., lymphoproliferation, immune-based nephritic disease, and autoantibody production. These findings also suggest that the Fas ligand is selectively expressed on T cells.
Matsuoka Suguru, Tatara Katsunori, Yasunobu Hayabuchi, Taguchi Yoshiyuki, Kazuhiro Mori, Hirohito Honda, Susumu Ito, Yuasa Yasuto and Yasuhiro Kuroda : Serologic, virologic, and histologic characteristics of chronic phase hepatitis C virus disease in children infected by transfusion, Pediatrics, Vol.94, No.6, 919-922, 1994.
84.
Matsuoka Suguru, Tatara Katsunorii, Yasunobu Hayabuchi, Nii Masaki, Kazuhiro Mori and Yasuhiro Kuroda : Post-transfusion chronic hepatitis in children, Journal of Paediatrics and Child Health, Vol.30, No.6, 544-546, 1994.
(要約)
Two hundred and twenty-six patients who received blood products for open-heart surgery in childhood were screened by a second-generation enzyme-linked immunosorbent assay and with surrogate markers for hepatitis C virus (HCV) infection, such as alanine aminotransferase (ALT). Twenty-two (14%) of the 161 recipients who received blood products before 1989 and none of the subjects who had received blood products after 1990 (the year that the blood bank began to screen for HCV antibody) were HCV seropositive. Virologic and histologic studies showed that 10 (45%) of 24 seropositive patients had persistent hepatitis C virus infection, many with ongoing hepatitis. The remaining 12 seropositive patients with absent HCV RNA had normal ALT levels, indicating resolved hepatitis C infection. Enrolment in screening is important to detect chronic hepatitis C in children who received blood products prior to screening of blood donors for HCV antibody.
Yasunobu Hayabuchi, Suguru Matsuoka, Y Takahashi, Hiroshi Akita, Tetsuya Kitagawa, Itsuo Kato and Yasuhiro Kuroda : Hyperuricemia in an infant with Taussig-Bing anomaly and interruption of the aortic arch, Pediatric Cardiology, Vol.15, No.5, 249-251, 1994.
(要約)
Hyperuricemia is commonly recognized in adolescents and adults with cyanotic congenital heart disease. We report a case of a male infant with hyperuricemia, Taussig-Bing anomaly, and interruption of the aortic arch. The patient underwent correction of interrupted aortic arch and pulmonary arterial banding at the age of 7 days. Hyperuricemia appeared when he was 2 months old (max 17.7 mg/dl) and persisted until he underwent a Jatene operation at the age of 10 months. The hyperuricemia improved gradually after the disappearance of hypoxia and polycythemia. The laboratory findings suggest that hyperuricemia can result from uric acid overproduction due to secondary polycythemia, impairment of uric acid excretion by the kidney, or the acceleration of anaerobic metabolism. Allopurinol and benzbromarone together were partially effective treatments for hyperuricemia in this patient with cyanotic congenital heart disease.
(キーワード)
Abnormalities, Multiple / Aorta / Heart Defects, Congenital / Heart Septal Defects, Ventricular / Humans / Infant, Newborn / Male / Polycythemia / Transposition of Great Vessels / Uric Acid
Yasunobu Hayabuchi, Suguru Matsuoka, Masahiro Kubo, Hiroshi Akita and Yasuhiro Kuroda : Age-related criteria for signal-averaged electrocardiographic late potentials in children, Pediatric Cardiology, Vol.15, No.3, 107-111, 1994.
(要約)
This study examined the age-related criteria of signal-averaged electrocardiographic (SA-ECG) parameters in children. SA-ECGs were obtained in 82 healthy volunteers in six groups depending on age (group 1: 1 day to < 1 month; group 2: 1 month to < 1 year; group 3: 1 to < 6 years; group 4: 6 to < 12 years; group 5: 12 to < 20 years; group 6: 20 to < 40 years). To examine the effect of heart rate on the parameters of SA-ECG, right atrial pacings were performed in 4 children with a ventricular septal defect aged 1-7 years. The root mean square voltage (RMS) was high; and the filtered QRS (f-QRS) duration and the duration of the low amplitude signal (LAS) were low during childhood, especially in infants (group 2), compared with those in adults. Late duration (LD) had no significant difference among age groups. The criteria for ventricular late potential were as follows: RMS < 25 microV, LAS > 35 ms, f-QRS duration > 110 ms, and LD > 35 ms for those age 1 day to < 1 month; RMS < 40 microV, LAS > 30 ms, f-QRS duration > 100 ms, and LD > 35 ms for those age 1 month to < 1 year; RMS < 20 microV, LAS > 40 ms, f-QRS duration > 130 ms, and LD > 35 ms for those age 1 to < 20 years; and RMS < 15 microV, LAS > 45 ms, f-QRS duration > 135 ms, and LD > 35 ms for those age 20 to < 40 years. RMS and LAS correlated with f-QRS duration (r = -0.78 and 0.76, respectively; p < 0.05), suggesting that these parameters are associated with the thickness of the ventricular muscle and the ventricular conduction time. Right atrial pacing had no effect on the measured SA-ECG parameters. The age-related differences in SA-ECG parameters might be due to age-related differences in the thickness of the ventricular muscle and the ventricular conduction time but are not due to differences in the heart rate. The age difference of each parameter on SA-ECG should be considered for ventricular late potentials.
Yasunobu Hayabuchi, Suguru Matsuoka, Masaki Nii, Hiroko Suzuya and Yasuhiro Kuroda : Cerebral infarction in a patient with congenital heart block, Clinical Cardiology, Vol.21, 302-303, 1994.
95.
Yasunobu Hayabuchi, Suguru Matsuoka, Yoshio Takahashi, Hiroshi Akita, Tetsuya Kitagawa, Itsuo Katoh and Yasuhiro Kuroda : Hyperuricemia in an infant with Taussig-Bing anomaly and interruption of the aortic arch., Pediatr Cardiol, Vol.15, No.5, 249-251, 1994.
Kubo Masahiro, Matsuoka Suguru, Yasunobu Hayabuchi, Akita Hiroshi and Yasuhiro Kuroda : Abnormal signal-averaged electrocardiogram in patients with Duchenne muscular dystrophy: Comparisonof time and frequency domain analyses from the signal-averaged electrogram, Clincal Cardiology, Vol.16, No.10, 723-728, 1993.
Masahiro Kubo, Suguru Matsuoka, Yasunobu Hayabuchi, Hiroshi Akita, Yutaka Matsuka and Yasuhiro Kuroda : Abnormal signal-averaged electrocardiogram in patients with Duchenne muscular dystrophy: Comparison of time and frequency domain analyses from the signal-averaged electrocardiograms, Clincal Cardiology, Vol.16, No.5, 723-728, 1993.
106.
Hiroshi Akita, Suguru Matsuoka, Yoshiyuki Taguchi, Masahiro Kubo, Yasunobu Hayabuchi and Yasuhiro Kuroda : Abnormal findings in the signal-averaged electrocardiogram in patients with Ebstein's anomaly, Acta Paediatrica Japonica, Vol.35, No.4, 72-73, 1993.
Suguru Matsuoka, Hiroshi Akita, Yoshio Takahashi, Atsuko Nishioka, Yasunobu Hayabuchi and Yasuhiro Kuroda : Assessment of sinus node function in patients with congenital long QT syndrome, Japanese Circulation Journal, Vol.55, No.5, 487-489, 1991.
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.
2.
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.
3.
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.
4.
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.
5.
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.
6.
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.
7.
Kazuhiro Mori, Nii Masaki, Manabe Tetsuya, Yasunobu Hayabuchi and Yasuhiro Kuroda : Myocardial integrated backscatter in patients with Duchenne's progressive muscular dystrophy, The 3rd World Congress of Pediatric Cardiology and Cardiac Surgery, Tronto, Canada, Mar. 2001.
8.
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.
9.
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.
10.
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.
11.
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.
12.
Nii Masaki, Yuasa Yasuto, Kazuhiro Mori, Matsuoka Suguru, Yasunobu Hayabuchi and Yasuhiro Kuroda : Elevation of ventricular wall motion in postoperative patients with tetralogy of Fallot using intramyocardial pulsed Doppler echocardiography, 10th Congress of the International Cardiac Doppler Society, Takamatsu, Nov. 1998.
13.
Kazuhiro Mori, Yasunobu Hayabuchi, Yasuhiro Kuroda and Nii Masaki : Retrograde holodiastolic flow in the abdominal aorta detected by pulsed Doppler echocardiography in patients with Kawasaki disease- Its relation to plasma nitric oxide levels, 10th Congress of the International Cardiac Doppler Society, Takamatsu, Nov. 1998.
14.
Yasunobu Hayabuchi, Matsuoka Suguru, Tatara Katsunori, Nii Masaki and Yasuhiro Kuroda : The kinetics of the plasma levels of atrial and brain natriuretic peptide, and cyclic guanosine monophosphate to the dobutamine in surgically repaired tetralogy of Fallot, The 2nd World Congress of pediatric cardiology and cardiac surgery, Hawaii, USA, May 1997.
15.
Nii Masaki, Yasunobu Hayabuchi, Matsuoka Suguru and Yasuhiro Kuroda : Power spectrum analysis of heart rate variability in preterm infants, --- Relationship between apnea of prematuriry and autonomic function ---, The 2nd World Congress of Pediatric Cardiology and Cardiac Surgery, Hawaii, USA, May 1997.
16.
Yasunobu Hayabuchi, Matsuoka Suguru, Kazuhiro Mori and Yasuhiro Kuroda : Usefulness of QRST isointegral maps for the diagnosis of right ventricular pressure overload in patients with surgically reparied tetralogy of Fallot, 23rd International Congress on Electrocardiology, Cleveland, USA, Jul. 1996.
17.
Yasunobu Hayabuchi, Matsuoka Suguru, Kubo Masahiro, Kazuhiro Mori and Yasuhiro Kuroda : Signal averaged electrocardiograms in surgically repaired congenital heart disease patients, --- Fast Fourier Transform analysis ---, The 3rd international Congress of Heart Failure, Geneve, Switzerland, May 1995.
18.
Yasunobu Hayabuchi, Matsuoka Suguru, Akita Hiroshi, Kubo Masahiro, Kazuhiro Mori and Yasuhiro Kuroda : Fast Fourier Transform analysis of signal averaged electocardiograms in surgically repaired congenital heart disease patients, 12th World Congress of Cardiology, Berlin, Sep. 1994.