Biomedical subjects

Masao Ota

Publications and source records attributed to Masao Ota.

At least 19 recordsLinked to original sources

PubMed2006

Tyrosinase gene family and Vogt-Koyanagi-Harada disease in Japanese patients.

PURPOSE: The aim of the present study was to examine the genetic background of Vogt-Koyanagi-Harada (VKH) disease in a Japanese population by analyzing the tyrosinase gene family (TYR, TYRP1, and dopachrome tautomerase (DCT)). METHODS: 87 VKH patients and 122 healthy controls were genotyped using seven microsatellite markers on the candidate loci. We analyzed microsatellite (MS) polymorphisms at regions within tyrosinase gene family loci. In addition, the haplotype frequencies were also estimated and statistical analysis was performed. HLA-DRB1 genotyping was performed by the PCR-restriction fragment length polymorphism (RFLP) method. RESULTS: No significant evidence for an association was found. HLA-DRB1*0405 showed a highly significant association with VKH disease compared with the healthy controls (Pc=0.000000079), as expected. CONCLUSIONS: We concluded that there is no genetic susceptibility or increased risk attributed to the tyrosinase gene family. Our results suggest the need for further genetic study and encourage a search for novel genetic loci and predisposing genes in order to elucidate the genetic mechanisms underlying VKH disease.

Asian People↗

PubMed2006

Two critical genes (HLA-DRB1 and ABCF1)in the HLA region are associated with the susceptibility to autoimmune pancreatitis.

We have previously reported that autoimmune pancreatitis (AIP) is a bioclinical entity characterized by high serum immunoglobulin G4 concentrations and association with the HLA-DRB1*0405-DQB1*0401 haplotype. However, the precise identity of gene(s) within this haplotype directly responsible for AIP pathogenesis is yet to be established. To dissect the genetic contribution of the incriminated haplotype, we have now performed an association analysis within the human leukocyte antigen (HLA) region using various types of polymorphic markers. Genomic DNAs from 43 AIP patients and 213 unrelated Japanese controls were used in this analysis. In each DNA sample, we established the genotype of 25 microsatellite markers distributed throughout the HLA region, that of single nucleotide polymorphism within the 5'-flanking regions of the TNFA and IkBLI (also known as NFKBIL1) as well as HLA class I and II genes. The HLA-linked susceptibility regions for AIP were localized to two segments: HLA-DRB1 (*0405; OR = 3.20, P = 0.00063, Pc = 0.0016) -DQB1 (*0401; OR = 3.29, P = 0.00046, Pc = 0.0069) in the HLA class II and C3-2-11 microsatellite (allele 219; OR = 2.96, P = 0.0076, Pc = 0.099) in the HLA class I regions. Upon stratification analysis in search for a synergistic effect given the extensive linkage disequilibrium within the major histocompatibility complex, it was established that each segment contributed to disease pathogenesis. The two critical HLA regions for susceptibility to AIP are limited to the HLA-DRB1*0405-DQB1*0401 in the class II and the ABCF1 proximal to C3-2-11, telomeric of HLA-E, in the class I regions.

ATP-Binding Cassette Transporters↗

PubMed2006

Analysis of single nucleotide polymorphisms at 13 loci within the transforming growth factor-induced factor gene shows no association with high myopia in Japanese subjects.

A previous study in China first indicated that the transforming growth factor-induced factor (TGIF) is a probable candidate gene for high myopia. The purpose of our study was to investigate whether there are significant associations between high myopia and single nucleotide polymorphism (SNP) variants in the TGIF gene of Japanese subjects. Genomic DNA was collected from 330 Japanese subjects with high myopia and at a level refractive error was less than -9.25 Dsph and 330 randomized controls without high myopia. Thirteen SNPs were detected by polymerase chain reaction (PCR) and primer extension or by PCR and SNP-specific fluorogenic probes in all of the cases and controls. Thirteen SNPs were found within the TGIF genes of the cases and controls. Two of the SNPs were monomorphic and none of the 13 SNPs showed a significant result. The pairwise linkage disequilibrium (LD) mapping confirmed that these alleles have a comparatively strong LD index of >0.8 for D' and >0.4 for r(2). We found no statistical association between any of the 13 SNPs located on the TGIF gene and high myopia in Japanese subjects. Based on our study using Japanese subjects and the previous studies of TGIF gene polymorphism in Chinese and northern European subjects with myopia, there is no convincing evidence to prove a connection between nucleotide sequence variations in TGIF and high myopia.

Adult↗

PubMed2006

Lack of association between FCRL3 and FcgammaRII polymorphisms in Japanese type 1 autoimmune hepatitis.

Autoimmune hepatitis (AIH) is an organ-specific autoimmune disease characterized by chronic inflammation of the liver. Although the HLA-DRB1*0405 allele is associated with type 1 AIH in Japanese, the exact genetic etiology of AIH remains undefined. Recently, polymorphisms of Fcgamma receptors (FcgammaR) and Fc receptor-like gene 3 (FCRL3) were linked to a variety of autoimmune diseases, and may be at least partially responsible for susceptibility to AIH. In this study, we genotyped FcgammaRIIA, FcgammaRIIB, and four FCRL3 polymorphisms in 87 Japanese patients with type 1 AIH and 97 ethnically matched controls using the TaqMan assay. Although we were able to detect significantly lower serum IgG concentrations in AIH patients specifically with the FCRL3-110A/A genotype, we observed no difference in the distribution of the genotypes between patients and controls, implying that susceptibility to type 1 AIH in Japanese patients is not influenced by FcgammaRIIA, FcgammaRIIB, or FCRL3 polymorphisms.

Adult↗

PubMed2006

Expression of semaphorins, vascular endothelial growth factor, and their common receptor neuropilins and alleic loss of semaphorin locus in epithelial ovarian neoplasms: increased ratio of vascular endothelial growth factor to semaphorin is a poor prognostic factor in ovarian carcinomas.

Semaphorins (SEMAs) compete with vascular endothelial growth factor (VEGF) for receptor neuropilin 1 (NP1) and 2 (NP2) and suppress angiogenesis. To clarify the involvement of SEMA and VEGF in the development and progression of ovarian carcinoma, we analyzed the immunohistochemical expression of SEMA, VEGF, NP1, and NP2 in 105 epithelial ovarian tumors. In addition, loss of heterozygosity at SEMA gene loci was examined. Strong expression of SEMA was found in 48% of benign, 33% of borderline tumors, and 13% of carcinomas (P < .05). Positivity for SEMA was significantly decreased in stage IV carcinomas and the expression of SEMA was significantly lower in peritoneal metastases than in primary lesions. Expression of SEMA showed a weak inverse correlation with microvessel density, but the correlation was not statistically significant. Loss of heterozygosity at SEMA3B or SEMA3F was demonstrated in none of the benign tumors, 8% of borderline tumors, and 29% of carcinomas. Expression of NP1 and NP2 was significantly higher in carcinomas than in benign tumors (P < .0001 and .0002, respectively). Patients with ovarian carcinoma with a high VEGF/SEMA ratio showed poorer survival than those with a low VEGF/SEMA ratio (P = .005). Decreased expression of SEMA and increased expression of NP1 and NP2 are characteristics of ovarian carcinomas, and loss of SEMA expression may play an important role in ovarian carcinoma progression. A high VEGF/SEMA ratio has adverse prognostic significance in patients with ovarian carcinoma.

Female↗

PubMed2006

Validation of sensitive human leukocyte antigen-sequence-specific primer and probe typing in forensic DNA examination.

Validation studies were carried out with the commercially available HLA typing kit using a PCR-SPP (sequence-specific primer and probe) technique. This technique has made it possible to type class I (HLA-A and -B) and class II (HLA-DRB1 and -DQB1) alleles at low-resolution level with total 10 ng of template DNA, in addition to amplify directly from various forms of blood samples without DNA isolation procedure. Experimental examinations with bloodstains smeared on cotton cloth that were a week to 3 months old, bloodstains on gauze stored for 18 years, and buccal cells revealed that this HLA-SPP typing kit is a sensitive and reliable method for forensic investigations.

Base Sequence↗

PubMed2006

Rapid evolution of major histocompatibility complex class I genes in primates generates new disease alleles in humans via hitchhiking diversity.

A plausible explanation for many MHC-linked diseases is lacking. Sequencing of the MHC class I region (coding units or full contigs) in several human and nonhuman primate haplotypes allowed an analysis of single nucleotide variations (SNV) across this entire segment. This diversity was not evenly distributed. It was rather concentrated within two gene-rich clusters. These were each centered, but importantly not limited to, the antigen-presenting HLA-A and HLA-B/-C loci. Rapid evolution of MHC-I alleles, as evidenced by an unusually high number of haplotype-specific (hs) and hypervariable (hv) (which could not be traced to a single species or haplotype) SNVs within the classical MHC-I, seems to have not only hitchhiked alleles within nearby genes, but also hitchhiked deleterious mutations in these same unrelated loci. The overrepresentation of a fraction of these hvSNV (hv1SNV) along with hsSNV, as compared to those that appear to have been maintained throughout primate evolution (trans-species diversity; tsSNV; included within hv2SNV) tends to establish that the majority of the MHC polymorphism is de novo (species specific). This is most likely reminiscent of the fact that these hsSNV and hv1SNV have been selected in adaptation to the constantly evolving microbial antigenic repertoire.

Alleles↗

PubMed2006

Allele frequencies for 15 STR loci in Tibetan populations from Nepal.

Samples from 105 unrelated healthy Sherpa in Namche Bazaar and 111 unrelated non-Sherpa in Kathmandu valley from Nepal were used to obtain allele frequency data for 15 short tandem repeat (STR) loci (CSF1PO, D2S1338, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D19S433, D21S11, FGA, TH01, TPOX and vWA) included in the AmpFLSTR Identifiler kit. No deviations from Hardy-Weinberg equilibrium were observed, but only after applying a Bonferroni correction in the case of D5S818 in the Sherpa population and D7S820 in the Kathmandu population. Genetic parameters of forensic interest were calculated and genetic differentiation between the two populations tested.

DNA Fingerprinting↗

PubMed2006

Genetic contribution of the endothelial nitric oxide synthase gene to high altitude adaptation in sherpas.

The Sherpas' adaptation to high altitude has been hypothesized as being due to a genetic basis since the beginning of the last century, but this has yet to be demonstrated. We randomly enrolled 105 Sherpas in Namche Bazaar (3440 m) and 111 non-Sherpa Nepalis in Kathmandu (1330 m) in Nepal. The genotypes of Glu298Asp and eNOS4b/a polymorphisms of the endothelial nitric oxide synthase (eNOS) gene were identified. The metabolites of nitric oxide (NO( x ): nitrite and nitrate) in serum were measured. The frequencies of the Glu and eNOS4b alleles were significantly higher in Sherpas (Glu: 87.5%; eNOS4b: 96.7%) than in non-Sherpas (Glu: 77.9%, p = 0.036; eNOS4b: 90.5%, p = 0.009). In addition, the combination of the wild types of Glu298Glu and eNOS4b/b was significantly greater in Sherpas (66.7%) than non-Sherpas (47.7%, p = 0.008). However, the serum NO( x ) was significantly lower in Sherpas (53.2 +/- 4.6 micromol/L) than in non-Sherpas (107.3 +/- 9.0 micromol/L, p < 0.0001). The wild alleles of the Glu298Asp and eNOS4b/a polymorphisms of the eNOS gene may be a benefit for the Sherpas' adaptation to high altitude. The nitric oxide metabolites (NO( x )) in serum vary individually, thus it is not a reliable indicator for endogenous nitric oxide production.

Acclimatization↗

PubMed2006

Autoimmune pancreatitis and complement activation system.

OBJECTIVES: Autoimmune pancreatitis is characterized by increased serum level of IgG4, but its pathogenesis has not been fully elucidated. Because this disease is occasionally associated with decreased levels of complements, we sought to clarify which complement activation system was operating in its active state. METHODS: We measured serum levels of complements, mannose-binding lectin, and circulating immune complex in patients with autoimmune pancreatitis, patients with chronic pancreatitis, and healthy controls. RESULTS: We found high serum circulating immune complex values, which decreased significantly after corticosteroid therapy. In patients with autoimmune pancreatitis, elevated levels of circulating immune complex, as determined by C1q assay, were significantly associated with increased serum levels of IgG1 and decreased levels of C4, as well as with a tendency toward decreased levels of C3. There were no significant differences in the serum levels of mannose-binding lectin or in the frequency of a mutant allele of mannose-binding lectin between patients with autoimmune pancreatitis and those with chronic calcifying pancreatitis. Furthermore, corticosteroid therapy had no effect on the level of mannose-binding lectin. CONCLUSIONS: Autoimmune pancreatitis exhibits a high serum circulating immune complex values in its active state, which links to a complement activation system with a classic pathway rather than the mannose-binding lectin pathway or alternative pathways.

Adult↗

PubMed2006

Highly sensitive HLA-DNA typing from formalin-fixed and paraffin-embedded tissue samples.

Nucleotide sequences have been determined for more than 1700 different alleles at the core of the human leukocyte antigen (HLA) system. The highly polymorphic character of these genes affects adaptive immune response and is also useful for forensic applications. HLA typing from formalin-fixed and paraffin-embedded tissue provides abundant useful information for both clinical settings and forensic investigations. This study, which investigated the potential use of DNA from formalin-fixed and paraffin-embedded tissue samples in an HLA PCR sequence-specific primer and probe (SPP) system, showed that tissue fixed in formalin for less than 3 days and embedded in paraffin can serve as a useful source of DNA for PCR-SPP typing kits.

Autopsy↗

PubMed2006

Associations of homologous RNA-binding motif gene on the X chromosome (RBMX) and its like sequence on chromosome 9 (RBMXL9) with non-obstructive azoospermia.

AIM: To investigate the associations of autosomal and X-chromosome homologs of the RNA-binding-motif (RNA-binding-motif on the Y chromosome, RBMY) gene with non-obstructive azoospermia (NOA), as genetic factors for NOA may map to chromosomes other than the Y chromosome. METHODS: Genomic DNA was extracted using a salting-out procedure after treatment of peripheral blood leukocytes with proteinase K from Japanese patients with NOA (n=67) and normal fertile volunteers (n=105). The DNA were analyzed for RBMX by expressed sequence tag (EST) deletion and for the like sequence on chromosome 9 (RBMXL9) by microsatellite polymorphism. RESULTS: We examined six ESTs in and around RBMX and found a deletion of SHGC31764 in one patient with NOA and a deletion of DXS7491 in one other patient with NOA. No deletions were detected in control subjects. The association study with nine microsatellite markers near RBMXL9 revealed that D9S319 was less prevalent in patients than in control subjects, whereas D9S1853 was detected more frequently in patients than that in control subjects. CONCLUSION: We provide evidence that deletions in or around RBMX may be involved in NOA. In addition, analyses of markers in the vicinity of RBMXL9 on chromosome 9 suggest the possibility that variants of this gene may be associated with NOA. Although further studies are necessary, this is the first report of the association between RBMX and RBMXL9 with NOA.

Adult↗

PubMed2006

Intestinal diffuse large B-cell lymphoma associated with celiac disease: a Japanese case.

Intestinal non-Hodgkin's lymphoma (NHL), especially the T-cell type, is well known to be associated with celiac disease (CD), an enteropathic disorder with a propensity for certain racial and genetic backgrounds. CD is typically characterized by gastrointestinal (GI) symptoms, anti-transglutaminase antibodies in the sera, and microscopical findings of the intestinal mucosa, which resolve with a gluten-free diet (GFD). In Asian populations, including the Japanese, CD and the associated NHL have been supposed to be quite rare, and studies concerning the frequency of CD or its relationship with NHL are scarce. We describe a Japanese middle-aged man with intestinal diffuse large B-cell lymphoma associated with CD. Following multi-combined chemotherapy, the patient's lymphoma has been in a state of complete response, and his GI symptoms have improved with a GFD. This case suggests that the possibility of CD and its association with intestinal NHL should be kept in mind, even in Asian populations.

Aged↗

PubMed2005

Human amniotic mesenchymal cells have some characteristics of cardiomyocytes.

BACKGROUND: Cellular cardiomyoplasty (CCM) is a major method for the treatment of heart failure because adult cardiomyocytes do not regenerate after ischemic injury, which results in heart failure. There is a great deal of interest in finding suitable new cell sources for use in CCM. Here, we report that human amniotic mesenchymal cells (hAMC), which are multipotent cells derived from fetal mesoderm, may be a suitable cell source for CCM. METHODS: Freshly isolated hAMC were examined to detect the expression of cardiac-specific genes by reverse-transcription polymerase chain reaction and immunocytochemistry. hAMC were cocultivated with neonatal rat heart explants and transplanted into myocardial infarcts in the rat heart. RESULTS: hAMC expressed cardiac-specific transcription factor GATA4, cardiac-specific genes, such as myosin light chain (MLC)-2a, MLC-2v, cTnI, and cTnT, and the alpha-subunits of the cardiac-specific L-type calcium channel (alpha1c) and the transient outward potassium channel (Kv4.3). After stimulation with basic fibroblast growth factor (bFGF) or activin A, hAMC expressed Nkx2.5, a specific transcription factor for the cardiomyocyte and cardiac-specific marker atrial natriuretic peptide. In addition, the cardiac-specific gene alpha-myosin heavy chain was detected after treatment with activin A. Coculture experiments confirmed that hAMC were able to both integrate into cardiac tissues and differentiate into cardiomyocyte-like cells. After transplantation into the myocardial infarcts in rat hearts, hAMC survived in the scar tissue for at least 2 months and differentiated into cardiomyocyte-like cells. CONCLUSION: The results of the present study suggest that hAMC possess some characteristics of cardiomyocytes.

Amnion↗

PubMed2005

Genetic analysis of the HLA region of Japanese patients with type 1 autoimmune hepatitis.

BACKGROUND/AIMS: Genetic predisposition to type 1 autoimmune hepatitis (AIH) is linked mainly to HLA-class II genes. The aim of this study is to scan the HLA region for additional genes which may contribute to type 1 AIH susceptibility. METHODS: We performed association analysis using HLA class I and II alleles and 18 polymorphic microsatellite markers distributed throughout the HLA region. We specifically assessed tumor necrosis factor (TNF)-alpha gene polymorphisms. RESULTS: The frequencies of HLA-DRB1*0405, DRB4 and DQB1*0401 alleles were significantly higher in AIH patients. The association study revealed the presence of three segments in the HLA region showing significantly low P (Pc) values. The first segment was located around the HLA-DR/-DQ subregion, the second was around the HLA-B54 allele, and the third was around two microsatellites near the TNF gene cluster. However, stratification analysis for the effect of DRB1*0405 eliminated association of the latter two segments. Haplotype D of the TNF-alpha promoter gene polymorphisms was weakly associated with susceptibility, but was found to be not significant after stratification analysis. CONCLUSIONS: The most influential gene on type 1 AIH pathogenesis in Japanese is the HLA-DRB1. Other genes in the HLA region, including TNF-alpha, have little or no association with type 1 AIH susceptibility.

Adult↗

PubMed2005

Monozygotic twins concordant for intestinal Behçet's disease.

Although Behçet's disease (BD) is a multisystem disorder of unknown causes, both genetic and environmental factors have been suggested. This is the second reported case of monozygotic twins concordant for Behçet's disease and the first such report of intestinal Behçet's disease. Patient 1 was a 17-year-old man with fever, recurrent oral aphthae, and skin eruptions. He developed hematochezia and was given corticosteroid empirically. One month after he was discharged, he again developed oral ulcerations, fever, and hematochezia. Colonoscopy was performed again, showing aphthous ulcerations in the entire colon, and deep oval ulcers with marginal elevation around the ileocecal valve, which are characteristics of intestinal Behçet's disease. He was treated with colchicine and azathioprine in combination with salazosulfapyridine (SASP) and prednisolone (PSL) and achieved remission. Patient 2 was the twin brother of patient 1. He was admitted because of oral aphthous ulcerations, fever, pustules on his face and body, and genital ulcers. Two weeks later he developed hematochezia. Colonoscopic and barium enema findings were similar to those of his brother. SASP, PSL, colchicines, and azathioprine were also required to achieve remission. Both of the patients were diagnosed with intestinal Behçet's disease. Their monozygosity was confirmed by detailed genetic typing, and HLA-B51 was negative.

Adolescent↗

PubMed2005

High prevalence of hypothyroidism in patients with autoimmune pancreatitis.

Autoimmune pancreatitis is a unique form of chronic pancreatitis and has been correlated with various extrapancreatic lesions. To search for a correlation between autoimmune pancreatitis and thyroid lesions, we measured thyroid functions in 41 patients with autoimmune pancreatitis and in 41 patients with chronic calcifying pancreatitis and investigated the correlation between HLA antigens and hypothyroidism. We found a significant difference in the prevalence of antithyroglobulin antibody and hypothyroidism between patients with autoimmune pancreatitis and those with chronic pancreatitis (34.1 vs. 7.3%, P = 0.005, and 26.8 vs. 0%, P = 0.0005, respectively). Patients with hypothyroidism had a significantly higher frequency of antithyroglobulin antibody (63.6%) than those without hypothyroidism but showed no differences in other findings, including serum IgG4 concentration. We could find no significant association between any HLA antigens and the hypothyroid state of autoimmune pancreatitis. One quarter of the patients with autoimmune pancreatitis have hypothyroidism that may be independent of the active state of the pancreatic lesion or systemic fibrosing disorder, and thus patients suspected of having autoimmune pancreatitis should be evaluated for possible hypothyroidism.

Adult↗

PubMed2005

Hepatic portal venous gas on postmortem CT scan.

We report on two cases involving hepatic portal venous gas (HPVG) imaging by computed tomography (CT) scans performed shortly after death. One case involved a 9-month-old infant who died of heat stroke, while the other was a 28-year-old man who died of myocarditis. Although both of these two cases were remarkable distension of the gastrointestinal tract with gas, the autopsies were unable to uncover any clinical cause for HPVG, such as necrotic bowel, ulcerative colitis, intra-abdominal abscess, bowel obstruction, or gastric ulcer. The cause of HPVG in our case is not due to organic disease, but due to gastro-intestinal distention due to emergency management using bag-valve-masking or esophageal tracheal combitube, thereby differing from the mechanisms underlying so-called clinical HPVG.

Adult↗