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Biomedical subjects

Y Shindo

Publications and source records attributed to Y Shindo.

At least 55 records · Page 3Linked to original sources
PubMed1996

[A photoallergenicity study of prulifloxacin (NM441) in guinea pigs].

Photoallergenicity of prulifloxacin, a new antibacterial agent, was examined using guinea pigs compared with those of the other quinolone antibacterial drugs, ofloxacin (OFLX), lomefloxacin (LFLX), ciprofloxacin (CPFX), enoxacin (ENX) and nalidixic acid (NA). Prulifloxacin and other drugs were orally administered at minimal phototoxic doses 1 hr before UVA (18 J/cm2) irradiation. This photosensitization procedure was daily repeated for 5 days. On 16 days after the final sensitization, the animals were challenged with UVA (18 J/cm2) after the administration of correspondent substances at maximal non-phototoxic doses. Photoallergic reactions were induced by OFLX (40 mg/kg), LFLX (3 mg/kg), CPFX (170 mg/kg) and ENX (80 mg/kg), but were not observed in prulifloxacin (170 mg/kg) and NA (30 mg/kg). These results show that photoallergenicity of prulifloxacin were less severe than those of the other quinolone antibacterial drugs under the conditions of this study.

Animals↗
PubMed1996

[Renal toxicity of prulifloxacin (NM441) in rats].

Renal toxicity of prulifloxacin, a new antibacterial agent, was investigated in rats of both sexes. The animals were given prulifloxacin orally for 28 days at a dose of 3000 mg/kg. Tubular nephrosis in which crystalline substances appeared primarily within tubules was observed from the second day of administration, and a large number of brown circular crystals were found in the urinary sediment from the first day of administration. Electron microscopic observation revealed a close resemblance of the ultrastructural characteristics between the intratubular crystalline substance and the urinary brown circular crystal, and the tubules were occasionally occluded by the crystalline substances. Infrared spectral analysis and X-ray microanalysis indicated that the brown circular crystal consisted of NM394, an active metabolite of prulifloxacin. These results suggested that NM394, which was filtered into the primary urine, may be precipitated as crystals on the process of water reabsorption in the tubules. And then most of the crystals would be washed out as crystalluria particles, and some of crystals retained and caused the obstructive uropathy.

Administration, Oral↗
PubMed1996

[Single-dose toxicity studies of prulifloxacin (NM441) in mice, rats and dogs and the active metabolite (NM394) in rats].

Single-dose toxicity studies of prulifloxacin, a new antibacterial agent, were conducted in mice, rats and dogs. In addition, a single-dose toxicity study of (+/-)-6-fluoro-1-methyl-4-oxo-7- (1-piperazinyl)-4H-[1,3]thiazeto[3,2-a]quinoline- 3-carboxylic acid (NM394), an active metabolite of prulifloxacin, was performed in rats. Prulifloxacin was administered orally, intraperitoneally (i.p.) or subcutaneously (s.c.) to mice and rats, and orally to dogs. NM394 was administered intravenously (i.v.) to rats. When prulifloxacin was administered orally or s.c., LD50 values were more than 5000 mg/kg in both sexes of mice and rats; when it was administered i.p., LD50 values were 1757 mg/kg in male mice, 1652 mg/kg in female mice, 915 mg/kg in male rats, and 1076 mg/kg in female rats. The lethal doses of this drug were more than 5000 mg/kg in both sexes of dogs by the oral route. The LD50 values of NM394 were 226 mg/kg in male rats and 238 mg/kg in female rats by the i.v. route. In mice, the major clinical signs observed following the administration of prulifloxacin were sedation, oligopnea, abnormal gait, piloerection, closed eye and tremor by the i.p. route and a scab at the site of injection by the s.c. route; in rats, decreased spontaneous locomotor activity by any of the three routes, oligopnea, lacrimation, hypothermia, piloerection and abnormal gait by the i.p. route, and a scab at the site of injection by the s.c. route; and in dogs, vomiting, reddening of the skin, and loose stool by the oral route. When NM394 was administered i.v., rats showed clonic convulsion and dyspnea. The site of injection was hyperemic, swollen and necrotic. Mice showed a decrease in body weight or an inhibition in weight gain when prulifloxacin was administered i.p. and rats showed the same effects when prulifloxacin or NM394 was administered by any of the above-mentioned routes. Macroscopic findings detected following the i.p. administration of prulifloxacin in mice were pale color of the liver and spleen, thickening of the liver, and adhesion of intra-abdominal organs; and in rats, hydrothorax, congestion and edema of the lung, adhesion of intra-abdominal organs, swelling of the kidney accompanied by fine yellowish-white foci, and atrophy of the testis. When NM394 was administered i.v. to rats, congestion of the lung was macroscopically observed.

Administration, Oral↗
PubMed1996

[A 4-week oral toxicity study of prulifloxacin (NM441) in rats followed by a 4-week recovery test].

A repeated dose toxicity study of prulifloxacin, a new antibacterial agent, was conducted in Sprague-Dawley rats. Male and female rats were given the test material orally for 4 weeks at doses of 0 (control), 30, 300 and 3000 mg/kg. After discontinuation of the treatment, a 4-week recovery test was also conducted. There was one case of death in the 3000 mg/kg group. Grayish green and soft feces, unkempt fur, transient deep respiration and decreased body weight gain were observed in the 3000 mg/kg group. Decreased food consumption and increased water intake were seen in the 300 and 3000 mg/kg groups. Ophthalmoscopic examination failed to show any abnormalities related to the treatment. In urinalysis, crystalline substance in the urinary sediments, cloudy urine and decreased Na+ excretion were observed in the 300 and 3000 mg/kg groups. Increased urine volume, lowered urine specific gravity and decreased K+ and Cl- excretions were seen in the 3000 mg/kg group. Hematologic examination showed decreased Hb, Ht, MCV and MCH and increased WBC in the 3000 mg/kg group. Blood chemical examination revealed increased BUN and decreased K+ and Cl- in the 3000 mg/kg group, and decreased K+ and gamma-globulin in the 300 mg/kg group. Pathological changes caused by the treatment were as follows. Cecal weight was increased in all dose groups. Cecal distention and swelling of its absorptive cells were seen in the 300 and 3000 mg/kg groups. In kidney, tubular nephrosis with crystalline substance was observed in the 300 and 3000 mg/kg groups, and its organ weight was increased in the 3000 mg/kg group. The above-mentioned changes were reversible except for decreased gamma-globulin, increased BUN and urine volume, and lowered urine specific gravity. Ulcer and small cavities associated with proliferation of fibrous tissue in the femoral articular cartilage were observed in the 3000 mg/kg group at the end of recovery period of 4 weeks. Plasma levels and urinary concentrations of active metabolite of the test material were increased in all dose groups with dose-related manner, whereby no sex difference was observed. No effects caused by the repeated dosing were seen in the plasma concentrations. Increased cecal weight in the 30 mg/kg group was considered to be attributable to the pharmacological effect of the test material. The results show that the NOAEL of prulifloxacin is 30 mg/kg for 4-week repeated dose toxicity in rats.

Administration, Oral↗
PubMed1996

[A 4-week oral toxicity study of prulifloxacin (NM441) in dogs followed by a 4-week recovery test].

A repeated dose toxicity study of prulifloxacin, a new antibacterial agent, was conducted in beagle dogs. Male and female dogs were given the test material orally for 4 weeks at doses of 0 (control), 30, 150 and 750 mg/kg. After discontinuation of the treatment, a 4-week recovery test was also conducted. Feces containing white material were seen in the 150 and 750 mg/kg groups. Salivation, prone, lateral or sitting position, gait disturbance, and locomotor depression were observed in the 750 mg/kg group. In this dose group, decreased body weight and food and water consumptions were also observed. There were no treatment-related effects on survival. Ophthalmoscopic and electrocardiographic examinations and urinalysis failed to show any abnormalities related to the treatment. Hematologic examination showed decreased WBC in the 750 mg/kg group. Blood chemical examination revealed increased GPT and alpha 2-globulin in the 750 mg/kg group. Pathological changes caused by the treatment were as follows. Rarefaction of matrix, cavitations and erosions in humeral and femoral articular cartilages, and inflammatory cell infiltration in synovium were seen in the 150 and 750 mg/kg groups. Focal hemorrhage in synovium was also observed in the 750 mg/kg group. In kidney, regeneration of tubular epithelium, inflammatory cell infiltration, fibrosis and crystalline substance in the tubular lumen were observed in the 750 mg/kg group. The above-mentioned changes were satisfactorily reversible except for the changes in the humeral and femoral articular cartilages and in the kidney. Plasma levels and urinary concentrations of active metabolite of the test material were increased in all dose groups with dose-related manner, whereby no sex difference was observed. No effects caused by the repeated dosing were seen in the plasma concentrations. Toxicological findings were not observed in the 30 mg/kg group. The results show that the NOAEL of prulifloxacin is 30 mg/kg for 4-week repeated dose toxicity in dogs.

Administration, Oral↗
PubMed1996

[A 13-week oral toxicity study of prulifloxacin (NM441) in rats followed by a 5-week recovery test].

A repeated dose toxicity study of prulifloxacin, a new antibacterial agent, was conducted in Sprague-Dawley rats. Male and female rats were given the test material orally for 13 weeks at doses of 0 (control), 30, 170 and 1000 mg/kg. After discontinuation of the treatment, a 5-week recovery test was also conducted. Salivation, soft feces, reduced body weight gain and increased water consumption were seen in the 1000 mg/kg group. There were no treatment-related effects on survival and food consumption. Ophthalmoscopic and hematologic examinations failed to show any abnormalities attributable to the treatment. Urinalysis revealed increased urine volume and decreased K+ excretion in the 1000 mg/kg group. Blood chemical examination showed increased BUN, decreased triglyceride, K+, Cl- and total protein in the 1000 mg/kg group. Pathological changes caused by the treatment were as follows. Renal tubular nephrosis with crystalline substance was observed in the 170 and 1000 mg/kg groups. Renal weight was increased and crystalline substance was noted in the lumen of the urinary bladder in the 1000 mg/kg group. Cecal distention with increased its organ weight was observed in all dose groups and swelling of its absorptive cells was seen in the 170 and 1000 mg/kg groups. Swelling of jejunal goblet cells was observed in the 1000 mg/kg group. In femoral articular cartilage, focal accumulation of chondrocytes, small cavities and proliferation of fibrous tissue were seen in the 170 and 1000 mg/kg groups. The above-mentioned changes were reversible except for renal tubular nephrosis and cecal distention with its increased organ weight, of which the degree and frequency, however, were lowered. The cecal distention in the 30 mg/kg group was considered to be attributable to the pharmacological effect of the test material. The results show that the NOAEL of prulifloxacin is 30 mg/kg for 13-week repeated dose toxicity in rats.

Administration, Oral↗
PubMed1996

Mutagenicity study of the new cephalosporin antibiotic cefditoren pivoxil.

The mutagenicity of a cephalosporin antibiotic, (-)-(6R,7R)-2,2-dimethylpropionyloxymethyl 7-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-[(Z)-2- (4-methylthiazol-5-yl) ethenyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate (cefditoren pivoxil, CAS 117467-28-4, CDTR-PI), was evaluated by various mutagenicity tests as follows: the reverse mutation assay in bacteria, the chromosomal aberration test with Chinese hamster CHL cells, the micronucleus test with mice, the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus gene mutation test with L5178Y cells, the chromosomal aberration test with human lymphocytes, the unscheduled DNA synthesis test with rat stomach mucosa cells, and the cell transformation test with BALB/3T3 cells. CDTR-PI induced the structural chromosomal aberrations considered direct action in the chromosomal aberration test with CHL cells at concentrations of 150 micrograms/ml and more, but in none of the other mutagenicity tests even in excessive doses. Evaluation for clastogenicity with metabolites of CDTR-PI and checking for formaldehyde generation in the culture medium appeared to verify that the original source of the clastogenicity of this antibiotic was a formaldehyde generated from a pivoxil radical of CDTR-PI. The carcinogenicity of formaldehyde has been reported as negative in rats administered orally for 2 years. These results suggested the CDTR-PI would reveal neither mutagenicity nor carcinogenicity under clinical conditions.

3T3 Cells↗
PubMed1996

Seroepidemiological studies on Silk Road ethnic groups.

To clarify the origin of the Japanese, the Jomom and/or Yayol, we screened for HTLV-1 and -II antibodies among inhabitants of the Silk Road, the Han, Uygur and Kazaks. We also screened for HIV, HBV, and HCV. The HTLV-I, -II, HIV, and HCV antibody tests were uniformly negative in all the studied groups. In contrast, a significantly higher incidence of HBs antigen was observed in all the groups tested (Northern Han: 11.9%, Uygur: 6.0%, Kazak: 9.1%). These results indicate that these ethnic groups are not the origin of the indigenous Japanese (the Jomon), and that HBV is prevalent in the various groups along the Silk Road.

Antigens, Viral↗
PubMed1995

Antioxidant defence mechanism of the skin against UV irradiation: study of the role of catalase using acatalasaemia fibroblasts.

To clarify the role of catalase, an antioxidant enzyme, in response to UV irradiation, we compared the effects of irradiation on cytotoxicity, activities of antioxidant enzymes, total glutathione concentrations, lipid peroxidation and the rate of collagen synthesis in skin fibroblasts from a patient with acatalasaemia and in those from a normal individual. The cells were irradiated with UVA (6 and 12 J/cm2 or UVB (0.5 and 1 J/cm2). Cell survival curves after UV irradiation were similar in cells from both subjects. Although superoxide dismutase activity in acatalasaemia cells was higher than in the control cells before irradiation, after irradiation the activity decreased in acatalasaemia cells (76% with 12 J/cm2 UVA, 47% with 1 J/cm2 UVB), but remained unchanged in control cells. Total glutathione concentrations also decreased in acatalasaemia cells (60% with 12 J/cm2) in response to UVA irradiation, but remained unchanged in control cells. Lipid peroxidation did not increase significantly in either cell type. The rate of collagen synthesis decreased to a similar extent in response to UV exposure in the two cell types (60-80% with 8.2 J/cm2 UVA, 40-50% with 10 mJ/cm2 UVB). We conclude from the results of cytotoxicity and lipid peroxidation that although acatalasaemia cells were killed by hydrogen peroxide at low concentrations with a single UV exposure, catalase functions only to a small degree as an antioxidant enzyme. There remains the possibility, however, that a deficiency of catalase may chronically damage the skin resulting in a reduced defence function of superoxide dismutase and glutathione with repeated exposures to UV, which is becoming more common in our daily life.

Acatalasia↗
PubMed1995

Association of nbl gene expression and glucocorticoid-induced apoptosis in mouse thymus in vivo.

A gene of unknown biological function, nbl, was originally isolated by virtue of its abundance in a Namalwa Burkitt Lymphoma cDNA library. nbl expression was initially found to be higher in tissues which exhibited internucleosomal DNA cleavage characteristic of apoptosis, than in tissues which did not exhibit a 'DNA ladder'. nbl expression was therefore examined in mouse thymus in vivo, in which apoptosis is induced by the glucocorticoid, dexamethasone. nbl expression was markedly enhanced by dexamethasone treatment and then sharply decreased prior to the occurrence of maximal 'DNA ladder' formation. In contrast, expression of myc, which is believed to be involved in apoptosis in other cell systems, declined as thymic apoptosis increased. Thymic apoptosis was blocked by the transcriptional inhibitor actinomycin D, if administered when nbl expression was enhanced, but not before or after the peak of nbl expression. These results suggest that nbl expression is associated with thymic apoptosis.

Animals↗
PubMed1995

[Measurement of anti-acetylcholine receptor antibody using human rhabdomyosarcoma cell line].

We developed a radioimmunoassay for AChR Ab using AChR solubilized from membrane extracts of human rhabdomyosarcoma cell line (RD cell). The binding affinity of this AChR to the alpha-Bungarotoxin (alpha-BTX) was similar to that of AChR from cell surface. Lyophilized AChR was stable within two months at -20 degrees C. In our assay system, sera from patients with Myasthenia Gravis (MG) showed markedly high titers and frequency (94%) of anti-AChR Ab. On the other hand, almost all sera from normal and non-myasthenic patients such as rheumatoid arthritis and thyroid disease were negative (< 0.2nmol/l). Our assay using AChR from RD cells shows sufficient results in the intra- and inter-CV values, and recovery and dilution tests. AChR Ab titers of our assay showed good correlations with those measured by AChRs from both human ischemic muscles and TE671 cells (commercial kit). The radioimmunoassay for AChR Ab using the membrane extracts of RD cells has high sensitivity, specificity and stability. Therefore, the assay is valuable as the routine assay for the diagnosis of MG.

Autoantibodies↗
PubMed1995

A recurrent case of spontaneous mediastinal emphysema.

The first case of spontaneous mediastinal emphysema was reported by Hamman et al. in 1939. It is a rare condition that primarily occurs in young adults. In many instances, spontaneous mediastinal emphysema is caused by yelling, shouting or active exercise, but the cause is often unknown. It is rare for cases of spontaneous mediastinal emphysema to recur. Recently, we experienced a recurrent case of spontaneous mediastinal emphysema in a patient with a duodenal ulcer. Vomiting appeared to be the cause of the recurrence in our patient. Of the 58 patients with spontaneous mediastinal emphysema who have been reported in Japan so far, recurrences were documented only in our patient and two others.

Adult↗
PubMed1994

Complete association of the HLA-DRB1*04 and -DQB1*04 alleles with Vogt-Koyanagi-Harada's disease.

VKH disease is a bilateral panuveitis and has been known to be closely associated with the particular HLA class II antigens HLA-DR4 and -DQ4, defined by serologic typing. In this study, 63 Japanese VKH patients were analyzed for HLA class II alleles at the DNA level using the PCR-RFLP method. The DRB1*04 alleles encoding the serologic specificity DR4 were found in 100% of the VKH patients carrying DRB1*0405 or DRB1*0410. By statistical analysis, only DRB1*0405 was found to be significantly increased as compared to the healthy controls (RR = 46.7 and pc < 1 x 10(-5)). As to the DQB1 locus, all the patients carried DQB1*0401 or DQB1*0402 expressing the serologic DQ4 specificity, which is in a strong linkage disequilibrium with DRB1*0405 or DRB1*0410 in a Japanese population, respectively. Only DQB1*0401 showed a statistically significant increase as compared to the healthy controls (RR = 41.3 and pc < 1 x 10(-5)). Comparison of the amino acid sequences of these DRB1 and DQB1 alleles indicates that Ser at position 57 of DRB1 and/or Glu at position 70 and Asp at position 71 of DQB1 plays a crucial role in determining the susceptibility to VKH disease.

Adult↗
PubMed1994

Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin.

We measured enzymic and non-enzymic antioxidants in human epidermis and dermis from six healthy volunteers undergoing surgical procedures. Epidermis was separated from dermis by curettage and antioxidants were measured by high-performance liquid chromatography (HPLC) or standard spectrophotometric methods. The concentration of every antioxidant (referenced to skin wet weight) was higher in the epidermis than in the dermis. Among the enzymic antioxidants, the activities of superoxide dismutase, glutathione peroxidase, and glutathione reductase were higher in the epidermis compared to the dermis by 126, 61 and 215%, respectively. Catalase activity in particular was much higher (720%) in the epidermis. Glucose-6-phosphate dehydrogenase and isocitrate dehydrogenase, which provide reduced nicotinamide adenine dinucleotide phosphate (NADPH), also showed higher activity in the epidermis than the dermis by 111% and 313%, respectively. Among the lipophilic antioxidants, the concentration of alpha-tocopherol was higher in the epidermis than the dermis by 90%. The concentration of ubiquinol 10 was especially higher in the epidermis, by 900%. Among the hydrophilic antioxidants, concentrations of ascorbic acid and uric acid were also higher in the epidermis than in the dermis by 425 and 488%, respectively. Reduced glutathione and total glutathione were higher in the epidermis than in the dermis by 513 and 471%. Thus the antioxidant capacity of the human epidermis is far greater than that of dermis. As the epidermis composes the outermost 10% of the skin and acts as the initial barrier to oxidant assault, it is perhaps not surprising that it has higher levels of antioxidants.

Aged↗
PubMed1994

Dose-response effects of acute ultraviolet irradiation on antioxidants and molecular markers of oxidation in murine epidermis and dermis.

There has not as yet been an integrated, comprehensive study of the responses of dermis and epidermis in vivo to a wide range of ultraviolet (UV) doses, encompassing all major antioxidants and a sensitive marker of oxidative damage. We have irradiated hairless mice with simulated solar light at doses of 2, 5, 12.5, and 25 J/cm2 combined UVA and UVB (0.8 to 10 MED) and measured enzymic and non-enzymic antioxidants as well as lipid hydroperoxides in both epidermis and dermis to elucidate the response of cutaneous antioxidant defense mechanisms to UV stress. Among the nonenzymic antioxidants two different dose-response patterns were seen. Ascorbate was rapidly depleted at doses between 0 and 5 J/cm2 but was less affected between 5 and 25 J/cm2. In contrast, glutathione, ubiquinol/one, and alpha-tocopherol levels remained approximately equal to control levels between 0 and 5 J/cm2, then decreased to varying degrees from 5 to 25 J/cm2; ubiquinol was almost completely depleted, whereas alpha-tocopherol dropped only 30%. The concentration of lipid hydroperoxides increased throughout the dose range. These results may be explained partly by direct destruction of some antioxidants by UV light, partly by the separate antioxidant functions of the compounds, and partly by recycling of some antioxidants (e.g., alpha-tocopherol) at the expense of others (e.g., ubiquinol). Even at the lowest dose (0.8 MED) lipid hydroperoxide formation was observed. Among the enzymic antioxidants, superoxide dismutase activity decreased significantly (to 63.6% of initial activity for epidermis and 51.5% for dermis at 25 J), whereas activities of glutathione peroxidase and glutathione reductase decreased slightly. Catalase activity decreased dramatically at doses above 5 J (to 11.8% of initial activity in epidermis and 27.7% in dermis at 25 J). The dramatic loss of catalase is almost entirely accounted for by direct destruction by the simulated solar light, but superoxide dismutase was unaffected by direct exposure; hence its destruction must be due to indirect effects, either mediated by free radicals or other harmful species formed upon irradiation. At low doses of UV light many components of the cutaneous antioxidant system were damaged, whereas at high doses all components were damaged and some were almost completely destroyed.

Animals↗
PubMed1994

Effect of age on antioxidants and molecular markers of oxidative damage in murine epidermis and dermis.

This is the first study of antioxidants and oxidative-damage-related parameters in epidermis and dermis of the skin as a function of age. The four major antioxidant enzymes (catalase, superoxide dismutase, glutathione reductase, and glutathione peroxidase), hydrophilic and lipophilic antioxidants, and lipid hydroperoxides were assayed in both epidermis and dermis of young and old hairless mice. Catalase, superoxide dismutase, and glutathione reductase had similar activity levels in young and old animals. Only glutathione peroxidase from epidermis showed an activity decrease due to age. This decrease became apparent when enzyme activity was expressed per mg of total cellular protein. Hydrophilic and lipophilic antioxidants did not change as a function of age, nor did lipid hydroperoxide levels. Both the absolute level of oxidized glutathione and the ratio of oxidized to reduced glutathione were higher in dermis from old mice. These results suggest that skin aging is not accelerated in old age due to a general decrease in the antioxidant capacity of the tissue. The data are compatible, however, with the idea that continuous damage to skin tissue by free radicals occurs throughout an organism's lifetime because scavenging cannot be 100% efficient.

Aging↗
PubMed1994

HLA-DRB1 typing of Vogt-Koyanagi-Harada's disease by PCR-RFLP and the strong association with DRB1*0405 and DRB1*0410.

Vogt-Koyanagi-Harada's (VKH) disease is reported to be closely associated with the HLA class II antigen, HLA-DR4. Serologically defined DR4 is further divided into 11 alleles by molecular HLA genotyping. However, no study of HLA-DNA typing of VKH patients has been reported. To clarify molecular genetic mechanism underlying the susceptibility/resistance to VKH disease, HLA-DNA typing of DR antigens (DRB1 genotyping) by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed. It was found that DRB1*0405 showed a significant association with VKH disease compared with the healthy controls (corrected p value < 1 x 10(-5)) and that all the patients had DRB1*0405 and/or DRB1*0410. The specific amino acid residue shared only by these two alleles is Ser at position 57 which is located in the antigen binding groove and may influence the immunological function as an antigen-presenting molecule, suggesting that Ser at position 57 plays an important role in the susceptibility to VKH disease, although the possibility that the involvement of the HLA-DQ molecule, DQ4, in strong linkage disequilibrium with DRB1*0405 and DRB1*0410, cannot be excluded.

Gene Amplification↗