Tsuchigauchi Takeshi, Tetsuyuki Takahashi, Ohnishi Takamasa, Hirohisa Ogawa, Yoshimi Bando, Hisanori Uehara, Takizawa Tamatsu, Kaneda Shinya, Nakai Tokiko, Hiroshi Shiota and Keisuke Izumi : Low susceptibility to N-ethyl-N-nitrosourea-induced transplacental carcinogenesis in Long-Evans Cinnamon (LEC) rats, The Journal of Medical Investigation : JMI, Vol.56, No.3-4, 93-98, 2009.
(要約)
The Long-Evans Cinnamon (LEC) rat, an animal model of Wilson's disease, is resistant to a variety of chemical carcinogenesis except liver and colon. In the present study, N-ethyl-N-nitrosourea (ENU)-induced transplacental carcinogenesis was examined in male and female LEC, Long-Evans Agouti (LEA), a sibling line of the LEC rat, and F344 rats (n=21). ENU was administered to pregnant rats as a single s.c. injection at a dose of 60 mg/kg body weight on the 17th day after conception. Cerebral/spinal gliomas and trigeminal/spinal nerve schwannomas developed in both LEA and F344 rats at 30 weeks of age, but no nervous system tumors developed in LEC rats, the difference being statistically significant. Lung adenomas also developed in LEA and F344 rats, but not in LEC rats. Semiquantitative RT-PCR demonstrated that metallothionein (MT)1a, MT2 and O(6)-methylguanine-DNA methyltransferase (MGMT) mRNA levels in the liver of LEC rats were higher than those in F344 and LEA rats. In addition, Western blot analysis showed that MT (MT1 plus MT2) in the liver of LEC rats was also higher than that in other strains. Present results suggest that high levels of MT and/or MGMT contribute to the resistance to nitrosamine-induced carcinogenesis in LEC rats.
Maki Nisino, Dai Mizuno, Kimoto Takashi, Shinahara Wakako, Fukuta Akiho, Tunetomo Takei, Kaori Sumida, Seiichiro Kitamura, Hiroshi Shiota and Hiroshi Kido : Influenza vaccine with Surfacten, a modified pulmonary surfactant, induces systemic and mucosal immune responses without side effects in minipigs, Vaccine, Vol.27, No.41, 5620-5627, 2009.
(要約)
Immune responses and side effects of intranasally administered flu vaccine with the commercial product Surfacten, a modified bovine pulmonary surfactant, were investigated in minipigs. The use of minipigs was based on the anatomical resemblance of nasal lymph nodes, the principal antigen uptake site of respiratory mucosal immunity, between pig and human. Intranasal instillation of HA vaccine adjuvanted with Surfacten elicited significantly higher serum hemagglutination inhibition titers than the antigen alone, with wide cross-neutralizing activities of secretory IgA in nasal washes. No significant induction of inflammatory cytokines or migration of inflammatory cells was observed at the site of immunization or serum after the first immunization. These data suggest the potential usefulness of Surfacten for mucosal vaccination.
Asako Umehara, Mamiko Nishioka, Toshiyuki Obata, Yousuke Ebina, Hiroshi Shiota and Seiichi Hashida : A novel ultra-sensitive enzyme immunoassay for soluble human insulin receptor ectodomain and its measurement in urine from healthy subjects and patients with diabetes mellitus., Clinical Biochemistry, Vol.42, No.13-14, 1468-1475, 2009.
(要約)
OBJECTIVE: For the early identification of patients at risk of developing diabetes mellitus, and to prevent the onset of diabetes by performing dietary counseling and exercise guidance, we have developed an ultra-sensitive immune complex transfer enzyme immunoassay (ICT-EIA) to measure soluble human insulin receptor ectodomain (sIRalpha) in urine which is collected non-invasively. DESIGN AND METHODS: We developed ICT-EIA for sIRalpha and measured urinary sIRalpha from 106 healthy volunteers, 35 obese volunteers and 42 patients with diabetes. RESULTS: The detection limit of ICT-EIA (0.04 pg/mL), using a urine sample of as little as 100 microL, was a few hundred-fold higher than that of conventional ELISA. Using ICT-EIA, the urinary sIRalpha level in patients with diabetes (9.7+/-20.1 pg/mg creatinine) was significantly higher than those in healthy volunteers (1.4+/-0.9; P<0.001). CONCLUSION: ICT-EIA for sIRalpha may be useful as a good marker for evaluating diabetes risk.
Yuka Nagasaki, Maki Moritani, Toshihito Tanahashi, Dai Osabe, Kyoko Nomura, Yuka Fujita, Parvaneh Keshavarz, Kiyoshi Kunika, Naoto Nakamura, Toshikazu Yoshikawa, Eiichiro Ichiishi, Hiroshi Shiota, Natsuo Yasui, Hiroshi Inoue and Mitsuo Itakura : Lack of association of genetic variation in chromosome region 15q14-22.1 with type 2 diabetes in a Japanese population., BMC Medical Genetics, Vol.9, 22, 2008.
(要約)
BACKGROUND: Chromosome 15q14-22.1 has been linked to type 2 diabetes (T2D) and its related traits in Japanese and other populations. The presence of T2D disease susceptibility variant(s) was assessed in the 21.8 Mb region between D15S118 and D15S117 in a Japanese population using a region-wide case-control association test. METHODS: A two-stage association test was performed using Japanese subjects: The discovery panel (Stage 1) used 372 cases and 360 controls, while an independent replication panel (Stage 2) used 532 cases and 530 controls. A total of 1,317 evenly-spaced, common SNP markers with minor allele frequencies > 0.10 were typed for each stage. Captured genetic variation was examined in HapMap JPT SNPs, and a haplotype-based association test was performed. RESULTS: SNP2140 (rs2412747) (C/T) in intron 33 of the ubiquitin protein ligase E3 component n-recognin 1 (UBR1) gene was selected as a landmark SNP based on repeated significant associations in Stage 1 and Stage 2. However, the marginal p value (p = 0.0043 in the allelic test, OR = 1.26, 95% CI = 1.07-1.48 for combined samples) was weak in a single locus or haplotype-based association test. We failed to find any significant SNPs after correcting for multiple testing. CONCLUSION: The two-stage association test did not reveal a strong association between T2D and any common variants on chromosome 15q14-22.1 in 1,794 Japanese subjects. A further association test with a larger sample size and denser SNP markers is required to confirm these observations.
Toshihito Tanahashi, Keiko Shinohara, Parvaneh Keshavarz, Yuka Nagasaki, Katsuyuki Miyawaki, Kiyoshi Kunika, Maki Moritani, Naoto Nakamura, Toshikazu Yoshikawa, Hiroshi Shiota, Hiroshi Inoue and Mitsuo Itakura : The association of genetic variants in Krüppel-like factor 11 and Type 2 diabetes in the Japanese population., Diabetic Medicine, Vol.25, No.1, 19-26, 2008.
(要約)
Krüppel-like factor 11 (KLF11) is a transcriptional factor of the zinc finger domain family that regulates the expression of insulin. In North European populations, its common functional variant Q62R (rs35927125) is a strong genetic factor for Type 2 diabetes (P = 0.00033, odds ratio for G allele = 1.29, 95% CI 1.12-1.49). We examined the contribution of KLF11 variants to the susceptibility to Type 2 diabetes in a Japanese population. By re-sequencing Japanese individuals (n = 24, partly 96), we screened all four exons, exon/intron boundaries and flanking regions of KLF11. Verified single nucleotide polymorphisms (SNPs) were genotyped in 731 initial samples (369 control and 362 case subjects). Subsequently, we tested for association in 1087 samples (524 control and 563 case subjects), which were collected in different districts of Japan from the initial samples. We identified eight variants, including a novel A/C variant on intron 3, but no mis-sense mutations. In an association study, we failed to find any significant result of SNPs (minor allele frequency 8.2-46.2%) after correcting for multiple testing. Similarly, no haplotypes were associated with Type 2 diabetes. It is notable that the G allele in rs35927125 was completely absent in 1818 Japanese individuals. Genetic variants in KLF11 are unlikely to have a major effect of Type 2 diabetes in the Japanese population, although they were significantly associated in North European populations. These observations might help to determine the role of KLF11 variants in Type 2 diabetes in different populations.
(キーワード)
Adult / 分散分析 (analysis of variance) / Asian Continental Ancestry Group / Cell Cycle Proteins / Diabetes Mellitus, Type 2 / 女性 (female) / Gene Frequency / Genetic Predisposition to Disease / Genotype / Humans / インスリン (insulin) / 日本 (Japan) / Linkage Disequilibrium / 男性 (male) / Middle Aged / Repressor Proteins
Seiji Mitani, Shoichiro Fujisawa, Aya Mima, Hiroshi Shiota, Kenji Yanashima, Mitsue Takahara and Osamu Sueda : The Importance of Measuring Medical and Psychological Characteristics in Visibility Measurement of Persons with Low Visual Capability, Assistive Technology Research Series, Vol.20, 331-335, 2007.
Yukiko Yamashita, Hiroshi Inoue, Keshavarz Parvaneh, Katsuyuki Miyawaki, Yuka Nagasaki, Maki Moritani, Kiyoshi Kunika, Naoto Nakamura, Toshikazu Yoshikawa, Natsuo Yasui, Hiroshi Shiota, Toshihito Tanahashi and Mitsuo Itakura : SNPs in the KCNJ11-ABCC8 gene locus are associated with type 2 diabetes and blood pressure levels in the Japanese population., Journal of Human Genetics, Vol.52, No.10, 781-793, 2007.
(要約)
Many genetic association studies support a contribution of genetic variants in the KCNJ11-ABCC8 gene locus to type 2 diabetes (T2D) susceptibility in Caucasians. In non-Caucasian populations, however, there have been only a few association studies, and discordant results were obtained. Herein, we selected a total of 31 SNPs covering a 211.3-kb region of the KCNJ11-ABCC8 locus, characterized the patterns of linkage disequilibrium (LD) and haplotype structure, and performed a case-control association study in a Japanese population consisting of 909 T2D patients and 893 control subjects. We found significant associations between eight SNPs, including the KCNJ11 E23K and ABCC8 S1369A variants, and T2D. These disease-associated SNPs were genetically indistinguishable because of the presence of strong LD, as found previously in Caucasians. For the KCNJ11 E23K variant, the most significant association was obtained under a dominant genetic model (OR 1.32, 95% CI 1.09-1.60, P = 0.004). A meta-analysis of East Asian studies, comprising a total of 3,357 T2D patients (77.4% Japanese) and 2,836 control subjects (77.8% Japanese), confirmed the significant role of the KCNJ11 E23K variant in T2D susceptibility. Furthermore, we found evidence suggesting that the KCNJ11 E23K genotype is independently associated with higher blood-pressure levels.
(キーワード)
ATP-Binding Cassette Transporters / Aged / Asian Continental Ancestry Group / 血圧 (blood pressure) / Diabetes Mellitus, Type 2 / 女性 (female) / Humans / 日本 (Japan) / 男性 (male) / Middle Aged / Polymorphism, Single Nucleotide / Potassium Channels / Potassium Channels, Inwardly Rectifying / Receptors, Drug
Dai Osabe, Toshihito Tanahashi, Kyoko Nomura, Shuichi Shinohara, Naoto Nakamura, Toshikazu Yoshikawa, Hiroshi Shiota, Parvaneh Keshavarz, Yuka Nagasaki, Kiyoshi Kunika, Maki Moritani, Hiroshi Inoue and Mitsuo Itakura : Evaluation of sample size effect on the identification of haplotype blocks., BMC Bioinformatics, Vol.8, 200, 2007.
(要約)
Genome-wide maps of linkage disequilibrium (LD) and haplotypes have been created for different populations. Substantial sharing of the boundaries and haplotypes among populations was observed, but haplotype variations have also been reported across populations. Conflicting observations on the extent and distribution of haplotypes require careful examination. The mechanisms that shape haplotypes have not been fully explored, although the effect of sample size has been implicated. We present a close examination of the effect of sample size on haplotype blocks using an original computational simulation. A region spanning 19.31 Mb on chromosome 20q was genotyped for 1,147 SNPs in 725 Japanese subjects. One region of 445 kb exhibiting a single strong LD value (average |D'|; 0.94) was selected for the analysis of sample size effect on haplotype structure. Three different block definitions (recombination-based, LD-based, and diversity-based) were exploited to create simulations for block identification with theta value from real genotyping data. As a result, it was quite difficult to estimate a haplotype block for data with less than 200 samples. Attainment of a reliable haplotype structure with 50 samples was not possible, although the simulation was repeated 10,000 times. These analyses underscored the difficulties of estimating haplotype blocks. To acquire a reliable result, it would be necessary to increase sample size more than 725 and to repeat the simulation 3,000 times. Even in one genomic region showing a high LD value, the haplotype block might be fragile. We emphasize the importance of applying careful confidence measures when using the estimated haplotype structure in biomedical research.
Maki Moritani, Kyoko Nomura, Toshihito Tanahashi, Dai Osabe, Yuka Fujita, Shinohara Syuichi, Yuka Nagasaki, Parvaneh Keshavarz, Eiji Kudo, Naoto Nakamura, Toshikazu Yoshikawa, Eiichiro Ichiichi, Yoichiro Takata, Natsuo Yasui, Hiroshi Shiota, Kiyoshi Kunika, Hiroshi Inoue and Mitsuo Itakura : Genetic association of single nucleotide polymorphisms in endonuclease G-like 1 gene with type 2 diabetes in a Japanese population., Diabetologia, Vol.50, No.6, 1218-1227, 2007.
(要約)
In order to identify type 2 diabetes disease susceptibility gene(s) in a Japanese population, we applied a region-wide case-control association test to the 20.4 Mb region between D3S1293 and D3S2319 on chromosome 3p24.3-22.1, supported by linkage to type 2 diabetes and its related traits in Japanese and multiple populations. We performed a two-stage association test using 1,762 Japanese persons with 485 gene-centric, evenly spaced, common single nucleotide polymorphism (SNP) markers with minor allele frequency >0.1. For mouse studies, total RNA was extracted from various organs of BKS.Cg-+Lepr(db)/+Lepr(db) and control mice, and from MIN6, NIH3T3 and C2C12 cell lines. We detected a landmark SNP375 (A/G) (rs2051211, p = 0.000046, odds ratio = 1.33, 95% CI 1.16-1.53) in intron 5 of the endonuclease G-like 1 (ENDOGL1) gene. Systematic dense SNPs approach identified a susceptibility linkage disequilibrium (LD) block of 116.5 kb by |D'|, an LD units map and a critical region of 2.1 kb by r (2) in ENDOGL1. A haplotype-based association test showed that an at-risk haplotype is associated with disease status (p = 0.00001). The expression of ENDOGL1 was rather ubiquitous with relatively abundant expression in the brain and also in a pancreatic islet beta cell line. Mouse Endogl1 expression increased in pancreatic islets of hyperglycaemic BKS.Cg-+Lepr(db)/+Lepr(db) mice compared with that in control mice. Based on the population genetics, fine mapping of LD block and haplotype analysis, we conclude that ENDOGL1 is a candidate disease-susceptibility gene for type 2 diabetes in a Japanese population. Further analysis in a larger sample size is required to substantiate this conclusion.
(キーワード)
Adult / Aged / Body Mass Index / Case-Control Studies / Diabetes Mellitus, Type 2 / Endodeoxyribonucleases / Endonucleases / Female / Genetic Predisposition to Disease / Hemoglobin A, Glycosylated / Humans / Japan / Male / Middle Aged / Polymorphism, Single Nucleotide / Reference Values
Toshihito Tanahashi, Dai Osabe, Kyoko Nomura, Syuichi Shinohara, Hitoshi Kato, Eiichiro Ichiishi, Naoto Nakamura, Toshikazu Yoshikawa, Yoichiro Takata, Tatsuro Miyamoto, Hiroshi Shiota, Parvaneh Keshavarz, Yuka Nagasaki, Kiyoshi Kunika, Maki Moritani, Hiroshi Inoue and Mitsuo Itakura : Association study on chromosome 20q11.21-13.13 locus and its contribution to type 2 diabetes susceptibility in Japanese., Human Genetics, Vol.120, No.4, 527-542, 2006.
(要約)
Several linkage studies have predicted that human chromosome 20q is closely related to type 2 diabetes, but there is no clear evidence that certain variant(s) or gene(s) have strong effects on the disease within this region. To examine disease susceptibility variant in Japanese, verified SNPs from the databases, with a minor allele frequency larger than 0.15, were selected at 10-kb intervals across a 19.31-Mb region (20q11.21-13.13), which contained 291 genes, including hepatocyte nuclear factor 4alpha (HNF4alpha). As a result, a total of 1,147 SNPs were genotyped with TaqMan assay using 1,818 Japanese samples. By searching for HNF4alpha as a representative disease-susceptible gene, no variants of HNF4alpha were strongly associated with disease. To identify other genetic variant related with disease, we designed an extensive two-stage association study (725 first and 1,093 second test samples). Although SNP1146 (rs220076) was selected as a landmark within the 19.31 Mb region, the magnitude of the nominal P value (P = 0.0023) was rather weak. Subsequently, a haplotype-based association study showed that two common haplotypes were weakly associated with disease. All of these tests resulted in non-significance after adjusting for Bonferroni's correction and the false discovery rate to control for the impact of multiple testing. Contrary to the initial expectations, we could not conclude that certain SNPs had a major effect on this promising locus within the framework presented here. As a way to extend our observations, we emphasize the importance of a subsequent association study including replication and/or meta-analysis in multiple populations.
(キーワード)
Aged / Asian Continental Ancestry Group / Chromosome Mapping / Chromosomes, Human, Pair 20 / Diabetes Mellitus, Type 2 / Female / Gene Frequency / Genetic Predisposition to Disease / Genotype / Haplotypes / Hepatocyte Nuclear Factor 4 / Humans / 日本 (Japan) / Linkage Disequilibrium / Lod Score / Male / Middle Aged / Polymorphism, Single Nucleotide
Hitoshi Kato, Kyoko Nomura, Dai Osabe, Shuichi Shinohara, Osamu Mizumori, Rumi Katashima, Shoji Iwasaki, Koichi Nishimura, Masayasu Yoshino, Masato Kobori, Eiichiro Ichiishi, Naoto Nakamura, Toshikazu Yoshikawa, Toshihito Tanahashi, Parvaneh Keshavarz, Kiyoshi Kunika, Maki Moritani, Eiji Kudo, Kazue Tsugawa, Yoichiro Takata, Daisuke Hamada, Natsuo Yasui, Tatsuro Miyamoto, Hiroshi Shiota, Hiroshi Inoue and Mitsuo Itakura : Association of single nucleotide polymorphisms in the suppressor of cytokine signaling 2 (SOCS2) gene with type 2 diabetes in the Japanese., Genomics, Vol.87, No.4, 446-458, 2006.
(要約)
Several previous linkage scans in type 2 diabetes (T2D) families indicated a putative susceptibility locus on chromosome 12q15-q22, while the underlying gene for T2D has not yet been identified. We performed a region-wide association analysis on 12q15-q22, using a dense set of >500 single-nucleotide polymorphisms (SNPs), in 1492 unrelated Japanese individuals enrolled in this study. We identified an association between T2D and a haplotype block spanning 13.6 kb of genomic DNA that includes the entire SOCS2 gene. Evolutionary-based haplotype analysis of haplotype-tagging SNPs followed by a "sliding window" haplotypic analysis indicated SNPs that mapped to the 5' region of the SOCS2gene to be associated with T2D with high statistical significance. The SOCS2 gene was expressed ubiquitously in human and murine tissues, including pancreatic beta-cell lines. Adenovirus-mediated expression of the SOCS2 gene in MIN6 cells or isolated rat islets significantly suppressed glucose-stimulated insulin secretion. Our data indicate that SOCS2 may play a role in susceptibility to T2D in the Japanese.
Parvaneh Keshavarz, Hiroshi Inoue, Yukiko Yamashita, Kiyoshi Kunika, Toshihito Tanahashi, Naoto Nakamura, Toshikazu Yoshikawa, Natsuo Yasui, Hiroshi Shiota and Mitsuo Itakura : No evidence for association of ENPP1(PC-1)K121Q variant with risk of Type 2 diabetes in a Japanese population., Journal of Human Genetics, Vol.51, No.6, 559-566, 2006.
(要約)
Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1, also known as PC-1) inhibits insulin signal transduction pathway(s). Previous studies have demonstrated the K121Q variant of the ENPP1 gene to have a significant functional role in determining susceptibility to insulin resistance and type 2 diabetes (T2D). To assess whether the K121Q variant has any impact on T2D in Japanese, we undertook an extensive case-control association study using a total of 911 unrelated Japanese T2D patients and 876 control subjects. No significant difference was observed in either genotype distribution (P=0.95) or allele frequency (P=0.83) between T2D and control groups. Notably, the frequency of the ancestral Q121 allele, which is also present in other primates, was quite high in African-Americans, and showed a marked ethnic variation (77.3% in African-Americans, 16.7% in European Americans, 10.5% in Japanese and 4.2% in Han Chinese). Consequently, the pairwise F(ST )value (a classic measure of genetic distance between pairs of population) showed highly significant differentiations between African-American and non-African-American populations (F(ST)>0.3). Our results indicated that the K121Q variant of the ENPP1 gene has very little, if any, impact on T2D susceptibility in Japanese, but may play a role in the inter-ethnic variability in insulin resistance and T2D.
(キーワード)
African Americans / Alleles / Amino Acid Substitution / Asian Continental Ancestry Group / Case-Control Studies / Diabetes Mellitus, Type 2 / European Continental Ancestry Group / Female / Gene Frequency / Genetic Variation / Humans / インスリン抵抗性 (insulin resistance) / 日本 (Japan) / Male / Phosphoric Diester Hydrolases / Pyrophosphatases / Risk Factors
Tatsuro Miyamoto, Hiroshi Inoue, Yukiko Yamashita, Eiji Kudo, Takeshi Naito, Takako Mikawa, Yoichi Mikawa, Yasushi Isashiki, Dai Osabe, Shuichi Shinohara, Hiroshi Shiota and Mitsuo Itakura : Identification of a novel splice site mutation of the CSPG2 gene in a Japanese family with Wagner syndrome., Investigative Ophthalmology & Visual Science, Vol.46, No.8, 2726-2735, 2005.
(要約)
This linkage study confirmed the genetic homogeneity of the Wagner syndrome. CSPG2 encodes versican, a large chondroitin sulfate proteoglycan, which, in vitreous, binds to hyaluronan and link protein and forms large aggregates that are important for maintaining structural integrity. Although the CSPG2 gene has been excluded as a candidate for causing Wagner syndrome, these data emphasize the necessity of further mutational screening in new families and careful functional characterization.
Traian V Chirila, Mika Chirila, Yoshito Ikada, Hiroshi Eguchi and Hiroshi Shiota : A Historical Review of Artificial Cornea Research in Japan, --- Artificial Cornea in Japan ---, Japanese Journal of Ophthalmology, Vol.49, No.1, S1-S13, 2005.
(要約)
Little is known or understood about the history of artificial cornea (keratoprosthesis) in Japan, mainly because of the unavailability and linguistic inaccessibility of the relevant publications. Rather strangely also, the Japanese scholars themselves have manifested only slight interest in reviewing the topic, even in their own language. As a result, the research on artificial cornea in Japan showed in fact the same pattern of historical development as that seen in the Western world. After audacious beginnings in the 19th century, an interlude of about half a century followed, when the interest of ophthalmologists was deflected to penetrating keratoplasty as a means to fight corneal blindness. The introduction in medical use of man-made polymeric materials in the 1950s triggered a revival of research on artificial cornea in Japan, and the next two decades were rich in ideas, achievements, and a plethora of reports, all published in Japanese. In the 1980s, the developmental work on keratoprosthesis became incorporated into the field of biomaterials, and the creation of materials able to mimic the corneal tissue was established as a leading concept, resulting in original designs with some sophistication. At the same time. the English language started to be used extensively for dissemination of results. These trends have continued to date. Based on rigorous documentation, we traced the history of research on artificial cornea in Japan from its origin to our time.
(キーワード)
人工角膜 / 日本 (Japan) / 歴史的総説
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15717417
Yuki Hayashi, Naozumi Ishimaru, Rieko Arakaki, Shin-ichi Tsukumo, Hitomi Fukui, Kenji Kishihara, Hiroshi Shiota, Koji Yasutomo and Yoshio Hayashi : Effective Treatment of a Mouse Model of Sjogren's Syndrome With Eyedrop Administrasiton of Anti-CD4 Monoclonal Antibody, Arthritis and Rheumatism, Vol.50, No.9, 2903-2910, 2004.
(要約)
To determine whether eyedrop administration of an anti-CD4 monoclonal antibody (mAb) is effective in the treatment of Sjögren's syndrome (SS) using a mouse model of the disease. The anti-CD4 mAb was administered daily into the eyes of mice with SS from ages 4 to 8 weeks or ages 10 to 12 weeks. During treatment, tear volume was monitored and after final treatment, histologic features of the lacrimal and salivary glands, the phenotypes and function of T cells, and serum titers of anti-alpha-fodrin antibody were examined. Eyedrop administration of anti-CD4 mAb before the onset of SS prevented the autoimmune pathology seen in the lacrimal glands but not that in the salivary glands. Furthermore, eyedrop administration of anti-CD4 mAb after the development of SS inhibited mononuclear cell infiltration and the destruction of parenchyma only in the lacrimal glands. Eyedrop administration of anti-CD4 mAb suppressed the local activation of CD4+ T cells rather than deleting CD4+ T cells, which reduced the expansion of pathologic CD4+ T cells against alpha-fodrin. These results demonstrate the remarkable efficacy of anti-CD4 mAb eyedrops in the treatment of SS eye symptoms, which illustrates a new antibody-based therapeutic strategy for patients with eye problems caused by SS as well as other diseases.
Yuki Hayashi, Shin-ichi Tsukumo, Hiroshi Shiota, Kenji Kishihara and Koji Yasutomo : Antigen-Specific T Cell Repertoire Modification of CD4+CD25+ Regulatory T Cells, The Journal of Immunology, Vol.172, No.9, 5240-5248, 2004.
(要約)
T cell immune responses are regulated by the interplay between effector and suppressor T cells. Immunization with Ag leads to the selective expansion and survival of effector CD4(+) T cells with high affinity TCR against the Ag and MHC. However, it is not known if CD4(+)CD25(+) regulatory T cells (T(reg)) recognize the same Ag as effector T cells or whether Ag-specific TCR repertoire modification occurs in T(reg). In this study, we demonstrate that after a primary Ag challenge, T(reg) proliferate and TCR repertoire modification is observed although both of these responses were lower than those in conventional T cells. The repertoire modification of Ag-specific T(reg) after primary Ag challenge augmented the total suppressive function of T(reg) against TCR repertoire modification but not against the proliferation of memory CD4(+) T cells. These results reveal that T cell repertoire modification against a non-self Ag occurs in T(reg), which would be crucial for limiting excess primary and memory CD4(+) T cell responses. In addition, these studies provide evidence that manipulation of Ag-specific T(reg) is an ideal strategy for the clinical use of T(reg).
Kayo Shinomiya, Makoto Kajima, Hiroko Tajika, Hiroshi Shiota, Ryuji Nakagawa and Takahiko Saijyou : Renal failure caused by eyedrops containing phenylephrine in a case of retinopathy of prematurity, The Journal of Medical Investigation : JMI, Vol.50, No.3.4, 203-206, 2003.
(要約)
The patient was a low birth weight infant with a history of renal failure. She was referred to our department 29 days after birth to undergo fundus examination. She experienced renal failure after undergoing a mydriatic test and needed medical treatment. Eyedrops containing phenylephrine were instilled several times and additional drops were also instilled during the fundal examination using an eyelid retractor, therefore the blood concentration of the drug was elevated sufficiently to contract the renal vessels, ultimately inducing renal failure. The present case suggests that since the use of mydriatic eyedrops in low birth weight infants could induce renal failure, the following points should be considered: 1) Mydriatic eyedrops should be used with caution by monitoring mydriasis and avoiding excessive instillation; 2) After instillation, the lacrimal region should be compressed to prevent the flow of mydriatic drops to the nasolacrimal canal; and 3) Vital signs should be monitored to check the onset of any adverse reactions for 12 hours after fundal examination.
(キーワード)
Renal failure / mydriatic drug / phenylephrine / retinopathy of prematurity
Takashi Katome, Toshiyuki Obata, Rie Matsushima, Norihisa Masuyama, Lewis C. Cantley, Yukiko Gotoh, Kazuhiro Kishi, Hiroshi Shiota and Yousuke Ebina : Use of RNA interference-mediated gene silencing and adenoviral overexpression to elucidate the roles of AKT/protein kinase B isoforms in insulin actions, The Journal of Biological Chemistry, Vol.278, No.30, 28312-28323, 2003.
(要約)
Insulin plays a central role in the regulation of glucose homeostasis in part by stimulating glucose uptake and glycogen synthesis. The serine/threonine protein kinase Akt has been proposed to mediate insulin signaling in several processes. However, it is unclear whether Akt is involved in insulin-stimulated glucose uptake and which isoforms of Akt are responsible for each insulin action. We confirmed that expression of a constitutively active Akt, using an adenoviral expression vector, promoted translocation of glucose transporter 4 (GLUT4) to plasma membrane, 2-deoxyglucose (2-DG) uptake, and glycogen synthesis in both Chinese hamster ovary cells and 3T3-L1 adipocytes. Inhibition of Akt either by adenoviral expression of a dominant negative Akt or by the introduction of synthetic 21-mer short interference RNA against Akt markedly reduced insulin-stimulated GLUT4 translocation, 2-DG uptake, and glycogen synthesis. Experiments with isoform-specific short interference RNA revealed that Akt2, and Akt1 to a lesser extent, has an essential role in insulin-stimulated GLUT4 translocation and 2-DG uptake in both cell lines, whereas Akt1 and Akt2 contribute equally to insulin-stimulated glycogen synthesis. These data suggest a prerequisite role of Akt in insulin-stimulated glucose uptake and distinct functions among Akt isoforms.
(キーワード)
3T3 Cells / Adenoviridae / Animals / Base Sequence / 脳 (brain) / CHO Cells / COS Cells / Cricetinae / Deoxyglucose / Dose-Response Relationship, Drug / Gene Library / Gene Silencing / Genetic Techniques / Glucose Transporter Type 4 / Glycogen / Immunoblotting / インスリン (insulin) / Luciferases / Mice / Molecular Sequence Data / Monosaccharide Transport Proteins / Muscle Proteins / Plasmids / Precipitin Tests / Protein Isoforms / Protein Transport / Protein-Serine-Threonine Kinases / Proto-Oncogene Proteins / Proto-Oncogene Proteins c-akt / RNA Interference / Rats / Time Factors
Eiko Murata, Saimoon Sharmin, Hiroshi Shiota, Mayumi Shiota, Mihiro Yano and Hiroshi Kido : The effect of topically applied secretory leukocyte protease inhibitor on the eosinophil response in the late phase of allergic conjunctivitis, Current Eye Research, Vol.26, No.5, 271-276, 2003.
(要約)
This study examined the effects of secretory leukocyte protease inhibitor (SLPI), a protease inhibitor in tears, in allergic conjunctivitis. Conjunctiva of male Hartley guinea pigs sensitized with ovalbumin were treated with SLPI or the vehicle 10 min before antigen challenge or simultaneously. The animals were sacrificed after antigen challenges of 0-24 h duration, and the inhibition of eosinophil conjunctival migration and degranulation by SLPI was analyzed histochemically. The effects of SLPI on mast cell chymase and tryptase were also examined. Treatment of sensitized guinea pigs with SLPI suppressed the conjunctival recruitment and degranulation of eosinophils after antigen challenge for 6 h, inhibiting the development of allergic conjunctivitis. The effects of SLPI were observed at concentrations > or =0.1 microM, with a peak at 5 microM. SLPI inhibited chymase in a dose-dependent manner, but had no effect on tryptase. The topical SLPI application may be therapeutic in allergic conjunctivitis.
Fumiko Ueno, Hiroshi Shiota, Maki Miyaura, Akiko Yoshida, Akiko Sakurai, Junko Tatsuki, Hajime A Koyama, Hirofumi Akari, Akio Adachi and Mikako Fujita : Vpx and Vpr proteins of HIV-2 up-regulate the viral infectivity by a distinct mechanism in lymphocytic cells, Microbes and Infection, Vol.5, No.5, 387-395, 2003.
(要約)
Mutants of human immunodeficiency virus type 2 (HIV-2) carrying a frame-shift mutation in vpx, vpr, and in both genes were monitored for their growth potentials in a newly established lymphocytic cell line, HSC-F. Worthy of note, the replication of a vpx single mutant, but not vpr, was severely impaired in these cells, and that of a vpx-vpr double mutant was more damaged. Defective replication sites of the vpx single and vpx-vpr double mutants were demonstrated to be mapped, respectively, to the nuclear import of viral genome, and to both, this process and the virus assembly/release stage. While the mutational effect of vpr was small, the replication efficiency in one cycle of the vpx mutant relative to that of wild-type virus was estimated to be 10%. The growth phenotypes of the vpx, vpr, and vpx-vpr mutant viruses in HSC-F cells were essentially repeated in primary human lymphocytes. In primary human macrophages, whereas the vpx and vpx-vpr mutants did not grow at all, the vpr mutant grew equally as well as the wild-type virus. These results strongly suggested that Vpx is critical for up-regulation of HIV-2 replication in natural target cells by enhancing the genome nuclear import, and that Vpr promotes HIV-2 replication somewhat, at least in lymphocytic cells, at a very late replication phase.
N Katunuma, A Ohashi, E Sano, E Murata, Hiroshi Shiota, K Yamamoto, E Majima and QT Le : New cysteine protease inhibitors in physiological secretory fluids and their medical significance, Advances in Enzyme Regulation, Vol.43, No.1, 393-410, 2003.
Tomihiko Hirokawa, Tomoko Nishikage, Takehiro Moroe, Makoto Kajima, Masakazu Hayashi, Takeshi Naito, Shinta Yamane and Hiroshi Shiota : Visualization of Uveal Perfusion by Contrast-Enhanced Harmonic Ultrasonography at a Low Mechanical Index, --- A Pilot Animal Study ---, Journal of Ultrasound in Medicine, Vol.21, No.3, 299-307, 2002.
(キーワード)
contrast-enhanced ultrasonography / orbital blood perfusion / low mechanical index / harmonic imaging
Takashi Asahara, Kayo Shinomiya, Takeshi Naito and Hiroshi Shiota : Induction of Gene into the Rabbit Eye by Iontophoresis:Preliminary Report, Japanese Journal of Ophthalmology, Vol.45, No.1, 31-39, 2001.
(要約)
To assess the transfer of 6-carboxyfluorescein (6-FAM)-labeled phosphorothioate oligonucleotides(S-ODNs) into the ocular tissues, their stability, and possibility of injury to the ocular tissues. The S-ODNs(2 mL/eye)were transduced noninvasively into albino rabbit eyes.The iontophoresis group consisted of 6 rabbits (12 eyes); the control group consisted of 2 rabbits (4 eyes) given eye drops containing S-ODNs. Aqueous humor and vitreous humor were collected after iontophoresis, subjected to electrophoresis with a fluorescence DNA sequencer and analyzed by the Gene Scan program. Frozen sections, 10-microm thick, were prepared for observation under a fluorescence microscope. A plasmid 4.7 kbp in size that expresses green fluorescent protein (GFP) was induced into the 18 eyes of 9 rabbits by the same procedure. In the iontophoresis group, S-ODNs were detected in the anterior chamber 5 minutes after electrophoresis began and in the vitreous after 10 minutes. These S-ODNs maintained the same length as at the initial synthesis. The S-ODNs could also be detected in the posterior retina 20 minutes after electrophoresis. No evidence of degeneration or inflammation due to the above procedure was found in the ocular tissues. Fluorescence showing GFP gene expression was found in the cornea, the anterior chamber angle, and the ciliary subepithelial tissues. These findings show that iontophoresis is an effective method to induce genes into the rabbit eye.
(キーワード)
Gene transduction / green fluorescent protein / iontophoresis / phosphorothioatc oligonucleotide
Mariko Takahashi, Naozumi Ishimaru, Kumiko Yanagi, Kaoru Saegusa, Norio Haneji, Hiroshi Shiota and Yoshio Hayashi : Requirement for splenic CD4+ T cells in the immune privilege of the anterior chamber of the eye, Clinical and Experimental Immunology, Vol.116, No.2, 231-237, 1999.
After inducing 6-carboxyfluorescein (6-FAM)-labeled phosphorothioate oligonucleotides (S-ODNs) noninvasively into albino rabbit eyes by iontophoresis, we assessed the transfer of S-ODNs into the ocular tissues, their stability, and the possible presence of injury to the ocular tissues. The iontophoresis group consisted of 12 eyes of 6 rabbits and the control group consisted of 4 eyes of 2 rabbits given eye drops containing S-ODNs. Aqueous humor and vitreous humor were collected after iontophoresis, subjected to electrophoresis with a fluorescent DNA sequencer and analyzed by the Gene Scan program. Frozen sections at 10 microns were prepared for observations under a fluorescent microscope. A plasmid 4.7 kbp in size that expresses green fluorescent protein (GFP) was induced into 18 eyes of 9 rabbits by the same procedure. In the iontophoresis group, S-ODNs were detected in the anterior chamber 5 minutes after electrophoresis and in the vitreous 10 minutes after. These S-ODNs maintained the same length as at the initial synthesis. S-ODNs could also be detected in the posterior retina 20 minutes after electrophoresis. No evidence of degeneration or inflammation due to the above procedure was found in the ocular tissues. Fluorescence showing GFP gene expressions were found in the cornea, the anterior chamber angle, and the ciliary subepithelial tissues. These findings show that iontophoresis is an effective method to induce gene into rabbit eyes.
(キーワード)
イオントホレーゼ / ホスホロチオエート型オリゴヌクレオチド / Green fluorescent protein
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10214051
Eiji Kudo, Hiroshi Shiota, Takeshi Naito, K Satake and Mitsuo Itakura : Polymorphisms of Thymidine Kinase Gene in Herpes Simplex Virus Type 1, --- Analysis of Clinical Isolates From Herpetic Keratitis Patients and Laboratory Strains ---, Journal of Medical Virology, Vol.56, No.2, 151-158, 1998.
(要約)
Drug-resistance of herpes simplex virus (HSV) is caused most frequently by mutation of the viral thymidine kinase (TK) gene. To elucidate the significance of detecting nucleotide changes of the TK gene for screening drug-resistant viruses, the frequency and variation of the genetic polymorphisms in the whole coding region of the TK gene were studied in 14 acyclovir-susceptible HSV type 1 (HSV-1) clinical isolates from 14 patients with epithelial herpetic keratitis. Two reference HSV-1 laboratory strains, McKrae and PH, and two acyclovir-resistant variants of the PH strain were also studied as controls. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing detected nucleotide differences at 24 positions, and amino acid substitutions at 12 codons in the TK gene of the examined viruses. Nucleotide diversity of 0.0029 per base (the average number of nucleotide substitutions of 3.3 per 1,131 base pairs) in the TK gene in the clinical isolates was comparable to 0.0037 per base of the whole HSV-1 genome in Japanese isolates reported previously. PCR-SSCP analysis of the acyclovir-resistant strains easily detected aberrantly shifted bands by comparing them with those of the parental strain, followed by the quick determination of mutated sequences. These results suggest that detection of nucleotide changes of the TK gene is useful for serial observation of persistent or recurrent HSV infection as observed in immunocompromised hosts, but that it is not useful for screening drug-resistant viruses from nonepidemic clinical isolates because of the comparable genetic polymorphisms in the TK gene as in the whole HSV-1 genome.
Hiroshi Shiota, Keiko Nitta, Takeshi Naito, Yasuo Mimura and Tokumi Maruyama : Clinical evaluation of carbocyclic oxetanocin G eyedrops in the treatment of herpes simplex corneal ulcers, The British journal of Ophthalmology, Vol.80, No.5, 413-415, 1996.
(要約)
Acyclovir (ACV) ophthalmic ointment is effective in the treatment of herpetic keratitis. However, when applied, the ointment has an unpleasant feeling and some cases are resistant to ACV. A new antiviral compound, carbocyclic oxetanocin G (C.OXT-G) has potent anti-herpes simplex virus activity and high water solubility, so the clinical effect of C.OXT-G eyedrops on ulcerative herpetic keratitis was evaluated. Studies were conducted on the corneal ulcers in 37 eyes of 27 patients. Patients with typical dendritic or geographic corneal ulcers were treated with 0.1% C.OXT-G eyedrops, applied five times a day, together with eyedrops of an antibiotic applied four times a day. The eyes were examined at least twice a week until the ulcers healed, and thereafter at intervals for up to 3 months. All of the ulcers healed, their average healing time being 4.9 (SD 2.2) (range 2 to 9) days. The ulcers in 20 of the 37 eyes were induced by the use of corticosteroid or immunosuppressive drugs, and their average healing time was 4.8 (2.3) days. No adverse drug reactions were seen during the observation period in this trial. Eyedrops containing 0.1% C.OXT-G are excellent and safe for treatment of herpes simplex corneal ulcers in humans.
Takeshi Naito, Keiko Nitta, Yoshihito Kinouchi, Hiroshi Shiota and Yasuo Mimura : Effects of 9-(1,3-dihydroxy-2-propoxymethyl)guanine(DHPG)eye drops and cyclosporine eye drops in the treatment of herpetic stromal keratitis in rabbits, Current Eye Research, Vol.10, 201-203, 1991.
Takeshi Naito, Hiroshi Shiota, Keiko Nitta and Yasuo Mimura : Effects on herpes simplex virus type 1 of combined use of interferon-beta and anti-herpetic agents in vitro, Japanese Journal of Ophthalmology, Vol.34, No.1, 15-21, 1990.
(要約)
It has been shown that the use of interferon (IFN) alone has little or no therapeutic effect in the treatment of herpetic keratitis. However, IFN used in combination with anti-herpetic agents has high therapeutic efficacy. This interaction between IFN and anti-herpetic agents has not been elucidated clearly. In this study, the interaction between human fibroblast interferon (HuIFN-beta) and anti-herpetic agents, 5-iodo-2'-deoxyuridine (IDU), aciclovir (ACV) and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), was studied in vitro using VERO cells. After the formation of a monolayer of VERO cells, HuIFN-beta of various concentrations was added to the maintenance medium. After 24 hours incubation, the medium was removed and herpes simplex virus (HSV) type 1 was inoculated on the VERO cells. Then, anti-herpetic agents were added to the medium in various concentrations. After 48 hours incubation, plaques were counted and the reduction rate in numbers of plaque was calculated. It was found that the combination of HuIFN-beta with IDU, ACV or DHPG worked synergistically in the inhibition of HSV replication.
Hiroshi Shiota, Takeshi Naito and Yasuo Mimura : Anti-herpes simplex virus(HSV)effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine, Current Eye Research, Vol.6, No.1, 241-245, 1987.
90.
Takeshi Naito, Hiroshi Shiota and Yasuo Mimura : Side effects in the treatment of herpetic keratitis, Current Eye Research, Vol.6, No.1, 237-239, 1987.
Aim: We want to be able to detect diabetic risky subjects early, and to prevent the onset of diabetes mellitus by performing exercise guidance and offering nutritional education to them. Methods: Two ultrasensitve immunoassays (immune complex transfer enzyme immunoassay; ICT-EIA) for resistin and soluble insulin receptor-a (sIRα) were developed. Urine samples from the patients of diabetes mellitus (DM; n=70), the non-diabetes obese subjects (NDMO; n=43) and the non-diabetes non-obese subjects (NDMNO; n=78) were measured resistin and sIRα using ICT-EIAs. Results: Detection limits of ICT-EIA for resistin and sIRa were 2pg/ml and 0.05pg/ml, respectively. It is possible to measure resistin and sIRa in the urine directly. Resistin in the urine from DM, NDMO and NDMNO were 30.0±36.2, 15.4±17.2 and 17.8±17.4 ng/mg of creatinine, respectively. The urine concentrations of resistin in DM were significantly higher than in the non-diabetes subjects (NDMO and NDMNO) (P<0.05). sIRa in the urine from DM, NDMO and NDMNO were 11.4±21.8, 1.9±1.1 and 1.3±0.8 pg/mg of creatinine, respectively. The urine concentrations of sIRa in DM were significantly higher than in NDM and NDMNO (P<0.001 and P<0.001), respectively. Furthermore, resistin in the urine was positively correlated to sIRa, in the urine. Conclusion: Both resistin and sIRoc in the urine are good markers for the risk of diabetes mellitus. As a result, these markers will be effective for the evaluation of exercise guidance and nutritional education.
Khadka B. Kamal, Takeshi Naito, Makoto Kajima, Hiroshi Shiota, Junsuke Akura and Takayuki Kiryuu : Eye care project in Gaur, Nepal, The Journal of Medical Investigation : JMI, Vol.51, No.3,4, 230-233, 2004.
(要約)
The aim of the eye care project is to clear the backlog of cataract blindness for the people of Gaur and its surrounding districts in southeast Nepal. The purpose of this study is to analyze the progress of this eye care project. In mid 1997, the Nepal Netra Jyoti Sangh (NNJS), the national society for comprehensive eye care in Nepal, with financial support from the Association for Ophthalmic Cooperation to Asia (AOCA) and the 24 Hour Television (24HTV) Charity Committee established an eye hospital in the district headquarters of Gaur under the name of Narayani Eye Care Project (NECP). The hospital provides surgery, an outpatient department (OPD) and emergency services. We analyzed the number of patients, the number of surgeries and the profile of patients. The hospital was found to be providing services with modern equipment and instruments and the number of patients frequenting it had increased in accordance with the improved services. From mid 1997 until the end of 2002, the hospital provided services to a total of 122,093 patients and performed 6,143 major surgeries and 541 minor surgeries. It has been possible to conduct sight restorations of poor and blind individuals in this region at the Gaur eye hospital with the support of the NECP.
(キーワード)
Adolescent / Adult / Aged / Aged, 80 and over / Cataract Extraction / 子ども (children) / Child, Preschool / Delivery of Health Care / Female / Humans / 小児 (infant) / Infant, Newborn / Male / Middle Aged / Nepal
Nan Hu and Hiroshi Shiota : Emergence of resistance to carbocyclic oxetanocin G in herpes simplex virus type 1 and genetic analysis of resistant mutants, Acta Pharmacologica Sinica, Vol.25, No.7, 921-926, 2004.
(要約)
To elucidate the potentiality of emergence of drug-resistance to carbocyclic oxetanocin G (C.OXT-G), a new effective antiviral drug for herpetic keratitis during treatment and the mechanism of this drug resistance. A C.OXT-G resistant strain (C.OXT-Gr) was established by serially propagating the herpes simplex virus (HSV) -1 in African green monkey kidney (VERO) cells in the presence of C.OXT-G. After the drug sensitivity assay and the thymidine kinase (TK) activity assay, the molecular basis for the drug resistance was studied using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and PCR direct sequencing technology. After the 10th passage in 10 microm C.OXT-G, the ED50 of the C.OXT-Gr was 17.08-fold greater than that of the original strain on the average and the TK activities of these resistant strains were extremely reduced. PCR-SSCP analysis on TK gene of the wild HSV-1 and the C.OXT-Gr showed altered migration patterns in part 3 and part 4, while PCR-SSCP analysis on DNA polymerase gene showed no difference among the viruses. Sequence analysis revealed a deletion of G at position of 430 that caused frameshift, resulting in premature termination in the TK gene. The drug resistance to C.OXT-G may appear during the treatment due to the deficiency of TK activity caused by a single mutation in the TK gene of HSV-1.
Hiroshi Shiota, Hiroshi Eguchi, Hiroyuki Yunoki and Shigekazu Aoyama : CAN WE IMPLANT OUR KERATOPROSTHESIS FOR HUMANS AS A TEMPORARY USE?, ANALES DEL INSTITUTO BARRAQUER, Vol.31, No.2, 199, 2002.
15.
Hiroshi Shiota, Hiroshi Eguchi, Hiroyuki Yunoki and H. Amitani : EXPERIMENTAL EVALUATION OF OUR CERAMIC KERATOPROSTHESIS IN RABBITS, ANALES DEL INSTITUTO BARRAQUER, Vol.30, 181-182, 2001.
Nobuhiko Katunuma, Hiroshi Shiota and Trong Quang Le : Medical significance of cysteine protease inhibitors in mammalian secretory fluids, The Journal of Medical Investigation : JMI, Vol.50, No.3-4, 154-161, Aug. 2003.
(要約)
New cysteine protease inhibitors in human tears and milk and their medical significance are reviewed in this paper. As protective components against bacterial infection in the eyes, we detected four kinds of anti-bacterial proteins in normal human tears including lysozyme and three kinds of cysteine protease inhibitors. Using our reverse zymography of normal tears, three kinds of cysteine protease inhibitors were found to be 78kDa, 20kDa and 15kDa and were determined to be lactoferrin, Von Ebner's Gland (VEG) protein and cystatin S, respectively. All of them belong to the cystatin super family and VEG protein and cystatin S are well known cysteine protease inhibitors. The C-terminus area 17mer peptide, Y679-K695, of lactoferrin showed strong homology with a common active domain of the cystatin family and the synthesized peptide showed inhibition of cysteine proteases. Not only were disease-specific changes found in these inhibitor profiles, but also disease-specific new inhibitors in patients tears with certain autoimmune diseases. A 35kDa inhibitor, which was detected specifically in tears with Behcet's disease, an typical autoimmune disease, was determined to be a lacrimal acidic proline-rich protein based on the N-terminus sequence analysis. A 65kDa inhibitor of tears with Harada's autoimmune disease was determined to be an Ig heavy chain V-III region. In addition, lactoferrin content in Harada's disease was very low. We found two cathepsin inhibitors in bovine milk using reverse zymography, namely lactoferrin and beta-casein. The L133-Q151, in the human beta-casein molecule is the active inhibitory domain. They may play an important role in antiseptic and anti-infectious functions.
Kayo Shinomiya, Hiroshi Shiota, Yaeko Ohgi, Nobuyuki Itsuki, Ray Tabesh, Masashi Yamada and Masanori Kubo : Analysis of the Characteristics of Electrooculogram, Intl. Conf. on Biomedical and Pharmaceutical Engineering 2006, 428-431, Singapore, Dec. 2006.
(要約)
In an eyeball there is an electric potential between the cornea (positive) and retina (negative), so an eyeball can be modeled as a battery. In this report the usefulness of the model is examined by applying this battery model to the eye and estimating the weak current in the eye from the measured EOG.
(キーワード)
眼球電図 / クロストーク / 電池モデル / 電極
2.
Hiroshi Shiota, Takeshi Naito, Hiroshi Eguchi, T Takada and S Hata : 5,3,1 METHOD FOR THE TREATMENT OF HERPETIC KERATITIS, 4th International Conference on Ocular Infections, 6, Sapporo, Oct. 2005.
3.
Hiroshi Eguchi, Kayo Shinomiya, Akiko Iwata, Shino Takano and Hiroshi Shiota : A CASE OF PANOPHTHALMITIS CAUSED BY PANTOEA AGGLOMERANS, 4th International Conference on Ocular Infections, 64, Sapporo, Oct. 2005.
4.
Hiroshi Eguchi, Kayo Shinomiya, Akiko Iwata, Shino Hayashi and Hiroshi Shiota : A Case of Panophthalmitis Caused by Pantoea Agglomerans, The 4th International eyes infectious disease society, Oct. 2005.
5.
Hiroshi Shiota : DIANOSIS AND TREATMENT OF HERPETIC KERATITIS, 4th International Conference on Ocular Infections, 4, Sapporo, Oct. 2005.
6.
Hiroshi Shiota, M Inoue, Y Kubo, Y Hayashi, Hiroshi Eguchi and Takeshi Naito : Best Classification of Acanthamoeba Keratitis, ARVO 2005 GLOBAL NETWORKING, 113, Florida, May 2005.
7.
Hiroshi Eguchi, Y Kubo, S Takano, Hiroshi Shiota and M Yano : Malignant Glaucoma After Penetrating Keratoplasty, ARVO 2004, 203, Florida, Apr. 2005.
8.
Hiroshi Shiota, M Ishimura, T Miyamoto, S Takano, E Sano, Q.T Le and N Katsunuma : Detection of disease-specific cyctein protease inhibitors in tears, ARVO 2004, 25, Florida, Apr. 2005.
9.
Hiroshi Shiota, Shino Takano, Mayumi Ishimaru, Etsuko Sano and Q.T Le : Medical significances of new disease-specific cycteine protease inhibitors in tears, 4th International Conference on Cysteine Proteinases and their Inhibitors, 6, Portoroz, Slovenia, Sep. 2004.
10.
Hiroshi Shiota : Recent diagnosis and treatment of Herpes Simplex Keratitis, FYODOROV MEMORIAL LECTURES 2004, 10, Moscow, Jun. 2004.
11.
E Sano, T. Q Le, A Ohashi, Hiroshi Shiota and N Katunuma : Disease specific cysteine protease inhibitors in tears with autoimmune-disease, International Symposium on "Medical and Biological Perspectives in Proteases and Their Inhibitors, 41, 兵庫, Nov. 2003.
12.
Hiroshi Shiota : A KERATOPROSTHESIS FOR TEMPORARY USE IN HUMANS, XXXIXth International Congress of Ophthalmology, A37, Sydney, Apr. 2002.
13.
Hiroshi Shiota, Kayo Shinomiya, T Nishiuchi, S Inoue and Takeshi Naito : ASSOCIATION OF HERPETIC KERATITIS AND KERATOMYCOSIS IN THREE PATIENTS, XXXIXth International Congress of Ophthalmology, Sydney, Apr. 2002.
14.
Hiroshi Shiota, T HIROKAWA, Takeshi Naito, F UENO, J MINAKUCHI, M KYO and K TAKAHASHI : POINTS TO DEAL WITH CYTOMEGALOVIRUS RETINITIS PATIENTS AFTER KIDNEY TRANSPLANTATION, 10th International Conference on Immunobiology and Prophylaxis of Human Herpesvirus Infections, Osaka, Nov. 2001.
15.
Hiroshi Shiota and Hiroshi Eguchi : Can we implant our keratoprosthesis for humans as a temporary use?, 4th KPro - 6th IOSS JOINT MEETING, 38, Florida, May 2001.
16.
T Hirokawa, M Hayashi, H Murata, M Takebayashi, Kyoko Fuke, T Ohki, M Kajima, Takeshi Naito, S Yamane and Hiroshi Shiota : VISUALIZATION OF PERFUSION IMAGING USING ULTRASOUND CONTRAST AGENT AND HARMONIC ULTRASOUND IN RABBIT EYES, ARVO 2001, 92, Florida, May 2001.
17.
S Hata, Takeshi Naito, M Kajima and Hiroshi Shiota : INDUCTION OF APOPTOSIS IN THE GANGLION CELLS OF TRIGEMINAL GANGLIA BY INFECTION WITH HERPES SIMPLEX VIRUS TYPE 1, ARVO 2001, 10, Florida, Apr. 2001.