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Biomedical subjects

Nobuhisa Mizuki

Publications and source records attributed to Nobuhisa Mizuki.

At least 19 recordsLinked to original sources
PubMed2007

Isolation and identification of adenovirus from conjunctival scrapings over a two-year period (between 2001 and 2003) in Yokohama, Japan.

Over a 2-year period between 2001 and 2003, a total of 115 conjunctival scrapings were collected from patients with keratoconjuctivitis from several hospitals in Yokohama, Japan. Out of 115, 94 (82.4%) cases of adenoviruses were detected by polymerase chain reaction (PCR); 60 (52.1%) by cell culture isolation; and 16 (14.0%) by enzyme-linked immunosorbent assay (ELISA). The serotypes were determined by PCR- restriction fragment length polymorphism analysis (PCR-RFLP) and by the neutralization test (NT). PCR-RFLP was performed using a combination of endonucleases such as HhaI, AluI, and HaeIII. Of the 94 PCR-positive samples, the serotypes of 91 (96.8%) were identified by PCR-RFLP analysis (adenovirus 3: 50%, 4: 11%, and 8: 32%). Out of the 115 samples, 60 samples were identified by the neutralization (adenovirus 3, 4, 7, and 8). When both PCR-RFLP and the neutralization techniques were used, 53.2%, 11.7%, 1.1%, and 34% of the samples were identified as adenovirus 3, 4, 7, and 8, respectively. In contrast to the results of a nationwide surveillance report, adenovirus 3 was found as a major cause of keratoconjunctivitis in the Yokohama area. The nationwide surveillance report did not reflect accurately the epidemiological situation in the local area. In order to obtain surveillance data that would be useful for the prevention of an adenovirus conjunctivitis epidemic, it seems that local epidemiology is more important than that nationwide surveillance.

Adenovirus Infections, Human↗
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

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

Single nucleotide polymorphisms of Ficolin 2 gene in Behçet's disease.

BACKGROUND: Genetic susceptibility to Behçet's disease (BD) is well documented for HLA-B51 positivity. However, BD is not a simple hereditary disease and it is exaggerated by exogenous stimuli such as microorganisms' infections. Ficolin 2 is a lectin that binds to the surface of microbial cells and kills microbial cells through the activation of complement system. Novel single nucleotide polymorphisms (SNPs) of human Ficolin 2 gene (FCN2 gene) have been recently identified in Caucasian people. OBJECTIVE: The aim of the study was to elucidate the contribution of FCN2 gene in the pathogenesis of BD. METHODS: The frequencies of genotypes and alleles of FCN2 gene SNPs in the promoter regions (-987, -602, -557, -64, -4) and exon 8 (+6359, +6424) were examined in 83 patients with BD and 64 healthy controls by genotyping with a DNA sequencing method. RESULTS: There were no significant differences in genotype and allele frequencies of FCN2 gene SNPs between BD patients and healthy controls. No significant differences in genotype and allele frequencies of FCN2 gene SNPs were detected among different clinical subgroups in BD patients. Significant differences in allele frequencies of FCN gene SNPs at both -557 and -64 sites in the promoter regions were found between HLA-B51 positive groups and HLA-B51 negative groups of BD patients. CONCLUSION: The significant differences in allele frequencies of FCN2 gene SNPs in the promoter lesions (-557 and -64 sites) among HLA-B51 positive BD patients may reveal the possibility that ficolin may contribute to the innate immunity of BD among HLA-B51 haplotypes in BD patients.

Adult↗
PubMed2006

Role of IL-12B promoter polymorphism in Adamantiades-Behcet's disease susceptibility: An involvement of Th1 immunoreactivity against Streptococcus Sanguinis antigen.

Adamantiades-Behcet's disease (ABD) is a chronic inflammatory multisystem disorder. Although the precise etiology is unclear, high prevalence of human leukocyte antigen (HLA)-B51 predisposition and predominantly involved T-helper type 1 cells (Th1)-type proinflammatory cytokines and extrinsic Streptococcal infection suggest a substantial association with an immunogenetic basis and strengthens the hypothesis that IL-12, a potent inducer of Th-1 immune reaction, is a putative candidate in its pathogenesis. These clinicopathological findings led us to examine interleukin 12 p40 (IL-12B) promoter polymorphism, for which the 4-base pair (bp) heterozygous insertion has been shown to affect the gene transcription and subsequent protein production. We analyzed IL-12B promoter genotypes in 194 Japanese subjects (92 with ABD and 102 normal controls) by PCR-based restriction enzyme digestion. The frequency of the insertion heterozygosity was significantly higher in patients than in controls (49/92, 53.3% vs 39/102, 38.2%, respectively). Comparing these with HLA haplotype data, this trend was more significant in HLA-B51-negative patients (29/42, 69.0% vs 20/50, 40.0%; P = 0.005). As assessed by semiquantitative reverse transcription-PCR and ELISA, stimulation with Streptococcal antigens specifically increased expression of IL-12 p40 mRNA and protein, in conjunction with IL-12 p70 induction, in peripheral blood mononuclear cells from heterozygous patients. Our results provide evidence for anti-bacterial host response toward Th1-immunity mediated by IL-12 in patients with ABD, and the possible insight into the genetic susceptibility that is independent of HLA background.

Adult↗
PubMed2006

[The reevaluation of categorization for ocular manifestation of sarcoidosis in the "Guidelines for Diagnosis of Ocular Sarcoidosis"].

PURPOSE: To increase the degree of specificity for nomenclature in the current "Guidelines for Diagnosis of Ocular Sarcoidosis" published in 1990 by the Diffuse Pulmonary Disease Research Committee of Japan. SUBJECTS AND METHODS: We reviewed the records of patients with uveitis from the Uveitis Clinic in the Department of Ophthalmology at Yokohama City University. Subjects were selected from the records of uveitis patients with histologically proven sarcoidosis (78), and others with non-sarcoidosis uveitis (81). We examined the sensitivity and specificity of suspected characteristics of ocular sarcoidosis in the current "Guidelines for Diagnosis of Ocular Sarcoidosis". RESULTS: The definition specificity was improved by changing anterior uveitis to granulomatous anterior uveitis, and by simplifying to cloudy mass (snowball, string of pearls) from the previous diffused/cloudy mass vitreous opacity (snowball, string of pearls), and also by changing from retinal peripheral vasculitis (in many cases retinal periphlebitis, also at times retinal peripheral arteritis) to retinal periphlebitis. CONCLUSION: This newly proposed "Guidelines for Diagnosis of Ocular Sarcoidosis" gives a much clearer definition of sarcoidosis, as well as improved nomenclature for specific categories of ocular symptoms.

Eye Diseases↗
PubMed2005

High-throughput DNA typing of HLA-A, -B, -C, and -DRB1 loci by a PCR-SSOP-Luminex method in the Japanese population.

We have developed a new high-throughput, high-resolution genotyping method for the detection of alleles at the human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 loci by combining polymerase chain reaction (PCR) and sequence-specific oligonucleotide probes (SSOPs) protocols with the Luminex 100 xMAP flow cytometry dual-laser system to quantitate fluorescently labeled oligonucleotides attached to color-coded microbeads. In order to detect the HLA alleles with a frequency of more than 0.1% in the Japanese population, we created 48 oligonucleotide probes for the HLA-A locus, 61 for HLA-B, 34 for HLA-C, and 51 for HLA-DRB1. The accuracy of the PCR-SSOP-Luminex method was determined by comparing it to the nucleotide sequencing method after subcloning into the plasmid vector using 150 multinational control samples obtained from the International HLA DNA Exchange University of California Los Angeles. In addition, we performed the PCR-SSOP-Luminex method for HLA allele typing on DNA samples collected from 1,018 Japanese volunteers. Overall, the genotyping method exhibited an accuracy of 85.91% for HLA-A, 85.03% for HLA-B, 97.32% for HLA-C, and 90.67% for HLA-DRB1 using 150 control samples, and 100% for HLA-A and -C, 99.90% for HLA-B, and 99.95% for HLA-DRB1 in 1,018 Japanese samples. The PCR-SSOP-Luminex method provides a simple, accurate, and rapid approach toward multiplex genotyping of HLA alleles to the four-digit or higher level of resolution in the Japanese population. It takes only approximately 5 h from DNA extraction to the definition of HLA four-digit alleles at the HLA-A, HLA-B, HLA-C, and HLA-DRB1 loci for 96 samples when handled by a single typist.

DNA Primers↗
PubMed2005

Drug-induced hypersensitivity syndrome due to cyanamide associated with multiple reactivation of human herpesviruses.

Drug-induced hypersensitivity syndrome (DIHS), characterized by serious adverse systemic reactions in addition to skin rash, has unknown pathogenesis. Its association with human herpesvirus (HHV), mainly HHV-6, has been reported recently. A 46-year-old Japanese man is described in whom a generalized eruption developed about 1 month after taking cyanamide, a drug for alcoholism. This was associated with the following manifestations: high fever, lymphadenopathy, facial edema, marked leukocytosis with eosinophilia and atypical lymphocytes, lymphocytopenia, liver and renal dysfunction, and low IgG level. He was treated with 8 mg betamethasone daily and his condition improved, but he needed low-dose corticosteroid for almost 1 year because of several episodes of recurrence. HHV-6, HHV-7, herpes simplex virus (HSV), and cytomegalovirus (CMV) specific IgG titers showed more than a four-fold rise sequentially. Significant numbers of copies of HHV-6 and HHV-7 DNA were detected in the peripheral white blood cells by real-time polymerase chain reaction (PCR). HHV-6 and CMV DNA were detected in the serum by nested PCR. A patch test for cyanamide was positive. The diagnosis of DIHS due to cyanamide, which has never been reported as a causal drug of DIHS, accompanied by reactivation of not only HHV-6, but also HHV-7, CMV, and HSV, was made. Disturbance of the immune system was suggested by the persistent low level of IgG, and consecutive viral reactivation may have participated in the prolonged course in this case.

Agammaglobulinemia↗
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

Experimentally induced Vogt-Koyanagi-Harada disease in two Akita dogs.

We have investigated whether a Vogt-Koyanagi-Harada (VKH)-like disease can be induced in Akita dogs by immunizing them with tyrosinase related protein 1 (TRP1), and compared the alterations induced to those of Akita dogs with a spontaneously occurring disease that resembles human VKH disease. Two Akita dogs were immunized with a peptide mixture of human TRP1. The changes in the eyes were followed by slit-lamp biomicroscopy, ophthalmoscopy, and fluorescein angiography (FA). The eyes, skin, and brains were studied by standard histological methods at about 20 months after the first immunization in one dog (dog 1), and at 3 weeks after the second immunization in the second dog (dog 2). Both dogs developed chorioretinal disease 3-4 weeks after the first immunization. Many inflammatory cells infiltrated into the anterior chamber and anterior vitreous. The fundus showed geographic, multifocal exudative retinal detachments. Multifocal leakages of fluorescein were detected from the choroid. Histologically, exudative retinal detachment was present, and inflammatory cells were seen in the subretinal space in the eyes of dog 2 taken three weeks after the second immunization. The choroid was thickened by the infiltration of inflammatory cells in some lesions. Dalen-Fuchs nodules were seen in the eye of dog 2. Depigmentation, pigment dispersion, and infiltration of many inflammatory cells around hair follicles and vessels were seen in the skin taken three weeks post-immunization. The clinical course and changes in the eyes and skin were very similar to those seen in the Akita dogs with spontaneously occurring VKH disease. We concluded that a VKH-like disease had been induced in these dogs, and this supports the tentative conclusion that the spontaneously occurring chorioretinal disease in Akita dogs is VKH disease.

Animals↗
PubMed2005

Tolerability and efficacy of N-chlorotaurine in epidemic keratoconjunctivitis--a double-blind, randomized, phase-2 clinical trial.

The aim of this study was to assess the tolerability and efficacy of N-chlorotaurine (NCT), an endogenous antimicrobial agent, in epidemic keratoconjunctivitis. In a prospective double-blind, randomized phase 2b study, the infected eyes were treated for 7 days with eye drops containing 1% aqueous solution of N-chlorotaurine (33 subjects) or gentamicin (27 subjects, control group). Adenovirus types 3, 4, 8, 19, and 37 were detected in 39 subjects (65%), enteroviruses in 8 (13.3%), and staphylococci in 5 (8.3%). Subjective and objective symptoms were scaled and added to a subjective and objective score, respectively, on day 1 (baseline), day 4, and day 8. Analyzing the whole study population, the subjective score on day 8 was lower in the NCT group (P = 0.016), whereas there were no differences in the objective score. However, in severe infections caused by adenovirus type 8 (n = 20) both the subjective and objective score were lower in the NCT group on day 4 (P = 0.003 and 0.015, respectively), which was also true for the subjective score on day 8 (P = 0.004) in this subgroup. The frequency of subepithelial infiltrates was similar in both groups. N-chlorotaurine was well-tolerated, shortened the duration of illness, and seems to be a useful causative therapeutic approach in severe epidemic keratoconjunctivitis.

Adenoviridae↗
PubMed2005

Contact lens user statistics in Okada eye clinic.

PURPOSE: To investigate the relationships between contact lens wearers, their lens wear, and treatment to provide correct instructions for use. METHOD: A total of 55,056 consumers, who purchased contact lenses in the two institutions of Okada Eye Clinic in the 1-year period from April 1, 2002 to March 31, 2003, were analyzed with regard to age, sex, contact lens brands, treatments and lens-solution combinations purchased, and patterns of wear. RESULTS: The 2-week frequent-replacement soft contact lenses were the most popular type of contact lens, and most wearers of these lenses were those in their 20s. Saline solution was the treatment purchased most often with conventional soft contact lenses. Hard contact lens wearers tended to buy treatments of the same brand as their hard contact lenses. Hydrogen peroxide was the most purchased product with the 2-week frequent-replacement soft contact lenses and multipurpose treatment the next, especially with consumers in their 20s. There were no significant sex gaps. CONCLUSIONS: The survey was conducted on a wide age range of more than 50,000 people and can be assumed to accurately reflect the tendencies of contact lens wearers in Japan. The results clearly show the actual use of contact lenses and treatments of each age group and will be useful in instructing wearers to the correct use of their treatments.

Adolescent↗
PubMed2005

An investigation of the actual conditions of use of daily-disposable soft contact lenses and two-week disposable soft contact lenses.

PURPOSE: To investigate whether daily-disposable and 2-week disposable soft contact lenses are being used correctly. METHODS: The number of purchases made and brands selected by the 44,566 consumers who purchased daily-disposable and 2-week disposable soft contact lenses in Okada Eye Clinic institutions between April 1, 2002 and November 1, 2002 were monitored. From the 7,759 respondents to a survey conducted in the clinic between November 1, 2002 and March 31, 2003, the number of purchases made and brands selected by the 1,584 respondents, whose sales records could be traced, were analyzed in further detail. RESULTS: The total number of consumers purchasing daily-disposable soft contact lenses was 14,909, and their annual average purchase was 10.56 boxes. Most purchases were of two boxes followed by purchases of four and then six. Only 6.4% of consumers purchased 24 boxes at a time. Consumers purchasing four or fewer boxes at a time accounted for 37.8%. A total of 25,705 consumers purchased 2-week disposable soft contact lenses, with an annual average purchase of 6.37 boxes per consumer. Nineteen percent of the consumers purchased eight boxes of 2-week disposable soft contact lenses per year. Most consumers tended to purchase their contact lenses in even numbers for daily-disposable and 2-week disposable soft contact lenses. Johnson & Johnson Vision Care (Jacksonville, FL) was the most popular manufacturer. According to the survey, 86.6% of the 2-week disposable soft contact lens wearers followed instructions correctly, whereas 13.4% did not. That is, they exceeded the instructed 14 days of wear. CONCLUSIONS: Annual average purchases of daily-disposable and 2-week disposable soft contact lenses tended to be in even numbers and showed differences in their sales depending on contact lens brands. The results obtained from the survey and the actual sales records correlated.

Contact Lens Solutions↗
PubMed2004

Anti-inflammatory effects of alpha-melanocyte-stimulating hormone against rat endotoxin-induced uveitis and the time course of inflammatory agents in aqueous humor.

PURPOSE: We examined the effects of the immunosuppressive neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) on rat endotoxin-induced uveitis, and to measure the expression of inflammatory cytokines and chemokines with and without the alpha-MSH treatment over the course of the disease. METHODS: We injected Lewis rats once with Salmonella typhimurium lipopolysaccharide (LPS) to induce uveitis. The rats were given intravenous injections of 250, 500 or 1000 microg of alpha-MSH. The eyes were examined over the next 24 h for inflammation. Aqueous humor was collected 6, 12 and 24 h after endotoxin injections and the number of infiltrating cells were counted in anterior chamber. In addition, we assayed the concentration of protein, nitric oxide, TNF-alpha, IL-6, MCP-1 and MIP-2. RESULTS: Rats injected with alpha-MSH showed a significant decrease in the number of infiltrating cells in anterior chamber. Moreover, alpha-MSH-treated rats with endotoxin-induced uveitis (EIU) showed significantly lower concentrations of protein, nitric oxide, proinflammatory cytokines and chemokines in their aqueous humor. Even the early stages of EIU were suppressed by the injection of alpha-MSH. CONCLUSIONS: Our results demonstrate that the immunosuppressive neuropeptide alpha-MSH inhibits the early induction events of endotoxin-induced inflammation in the eye; therefore, suppresses the subsequent infiltration of cells and intraocular production of inflammatory cytokines and chemokines in eyes. alpha-MSH has a possibility of being a therapeutic strategy for anterior uveitis.

Animals↗
PubMed2003

Cdk5/p35 and Rho-kinase mediate ephrin-A5-induced signaling in retinal ganglion cells.

Ephrin-As are repulsive axonal guidance cues that regulate retinotectal projection. EphA tyrosine kinases, which are the receptors of ephrin-As, activate signaling cascades leading to cytosckeleton reorganization. Here, we address the role of cyclin-dependent kinase (Cdk) 5 in Eph receptor signaling induced by ephrin-A5. Ephrin-A5 induced a cell morphological response in PC-3M cells that endogenously express Cdk5 and EphA2, a receptor for ephrin-A5. This response was augmented by the transfection of p35, which is a neuronal regulator of Cdk5. While the morphological response of native PC-3M cells was not affected by olomoucine, an inhibitor of Cdk, the response was inhibited in the p35-transfected cells. In retinal ganglion cells, either olomoucine at 20 microM or Y-27632 at 10 microM, an inhibitor of Rho-kinase/ROKalpha/ROCKII, showed maximum inhibitory effect against ephrin-A5 (10 microg/ml)-induced growth cone collapse. Combined application of olomoucine and Y-27632 further suppressed the ephrin-A5-induced response. Ephrin-A5 evoked phosphorylation of Cdk5 at Tyr15 and tau, a substrate of Cdk5 in retinal growth cones. Recombinant herpes simplex virus expressing Cdk5 mutant (kinase-negative or Tyr15 to Ala) showed a dominant-negative effect on the ephrin-A5-induced growth cone collapse. These findings demonstrate that both Cdk5 and the Rho kinase pathway independently contribute to the downstream of ephrin-A-induced signaling in retinal ganglion cells.

Animals↗
PubMed2003

Effects of astaxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo.

PURPOSE: Astaxanthin (AST) is a carotenoid that is found in marine animals and vegetables. Several previous studies have demonstrated that AST exhibits a wide variety of biological activities including antioxidant, antitumor, and anti-Helicobacter pylori effects. In this study, attention was focused on the antioxidant effect of AST. The object of the present study was to investigate the efficacy of AST in endotoxin-induced uveitis (EIU) in rats. In addition, the effect of AST on endotoxin-induced nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor (TNF)-alpha production in a mouse macrophage cell line (RAW 264.7) was studied in vitro. METHODS: EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). AST or prednisolone was administered intravenously at 30 minutes before, at the same time as, or at 30 minutes after LPS treatment. The number of infiltrating cells and protein concentration in the aqueous humor collected at 24 hours after LPS treatment was determined. RAW 264.7 cells were pretreated with various concentrations of AST for 24 hours and subsequently stimulated with 10 microg/mL of LPS for 24 hours. The levels of PGE2, TNF-alpha, and NO production were determined in vivo and in vitro. RESULTS: AST suppressed the development of EIU in a dose-dependent fashion. The anti-inflammatory effect of 100 mg/kg AST was as strong as that of 10 mg/kg prednisolone. AST also decreased production of NO, activity of inducible nitric oxide synthase (NOS), and production of PGE2 and TNF-alpha in RAW264.7 cells in vitro in a dose-dependent manner. CONCLUSIONS: This study suggests that AST has a dose-dependent ocular anti-inflammatory effect, by the suppression of NO, PGE2, and TNF-alpha production, through directly blocking NOS enzyme activity.

Animals↗