Association of Cw11 in Japanese patients with psoriasis vulgaris.
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Biomedical subjects
Publications and source records attributed to K Matsuki.
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HLA antigens in 104 Japanese patients and 41 families with myasthenia gravis (MG) were investigated. The frequencies of DR9 and DRw13 were significantly increased in the patients who developed MG before 3 yr of age. The DQw3 antigen was positive for all the patients that developed MG before 15 yr with only one exception. All the examined cases that developed MG before 3 yr (including this DQw3 negative patient) had the same DQA and DQB DNA restriction fragments. These HLA frequencies decreased as the age of onset increased, and no significant association was observed in adult-onset MG. No patients had B8, DR3, and DQw2. The relative risk was higher for the DR9/DRw13 heterozygotes (37.4) than for DR9 (16.4) or DRw13 (7.1) in the childhood-onset MG. Statistical analysis suggested that DR9 and DRw13 (or DQw1 and DQw3) act synergistically in the disease development. Family study revealed diverse DR9 haplotypes. The most frequent DRw13 haplotype was Bw44-BFF-C4A3B1-DRw13-DQw1, which may be evolutionarily related to the caucasian B8-DR3-DQw2 haplotype. These results showed that MG in early childhood in Japanese individuals is genetically different from that in adulthood and that in caucasians.
Takayasu's arteritis, with a strong predilection for women and particular geographic areas, has revealed significant association with human lymphocyte antigens (HLA) specificities. In the present study, the authors investigated for the first time the association of Takayasu's arteritis and HLA at the genomic level. By use of a restriction endonuclease Taq-I and a DQA cDNA probe, HLA-D region restriction fragment length polymorphism was examined in 32 Japanese patients. It was revealed that 65.6% of the patients shared a 6.6 kb fragment, although this fragment was found in 35.3% of the healthy Japanese (Chi square: 6.07, p less than 0.02). This finding suggest that HLA-D region gene variations determine susceptibility to Takayasu's arteritis.
The HLA antigens frequencies were studied in 30 Japanese patients with otosclerosis, and were compared with those of 220 randomly-selected apparently healthy unrelated Japanese. Serological HLA typing was performed by the modified two-stage complement-dependent microcytotoxicity method at the Blood Transfusion Service, Tokyo University Hospital. The results were as follows: There was no significant deviation of HLA class I antigen frequencies in the patients tested as compared with those in controls. As for HLA class II antigens, the DRw11 antigens frequency showed slight increase; however, after the correction of the P value, this was not significant.
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The association between HLA-DR4 and rheumatoid arthritis (RA) has been established in many ethnic groups. To clarify the determinant of susceptibility to RA, a polymorphic segment of the HLA-DRB gene was amplified in vitro by polymerase chain reaction and analyzed with oligonucleotide probes specific for the HLA-DR4 DNA sequences. A particular sequence encoding amino acids Gln70-Arg71-Arg72-Ala73-Ala74 showed a strong association with RA (p less than 0.005, relative risk 6.0). This amino acid sequence occurs in the DRB molecules with three RA-associated specificities, DR4/Dw14, DR4/Dw15, and DR1. DR4/Dw4, which is common in Caucasian RA patients, has a strikingly similar amino acid sequence Gln70-Lys71-Arg72-Ala73-Ala74 in terms of polarity and charge profiles. Other RA nonassociated sequences differ from this sequence by at least one amino acid substitution that causes the change of the net charge. The composition of amino acid residues at the positions 70-74 may play a crucial role in the pathogenesis of RA.
Human leukocyte antigen frequencies were examined in 40 Japanese patients with severe unilateral sensorineural hearing loss found in childhood. Human leukocyte antigen-Bw54 was significantly increased in frequency. No statistically significant deviation in the Bw54 frequency was observed among several possible subgroups studied. Although this group of patients may have various causes, and underlying mechanism is still unclear, this preliminary study suggests that childhood unilateral deafness may be associated with a genetically determined factor(s).
We investigated polymorphisms of complement components C2, C4, and factor B (BF) in Japanese patients with rheumatoid arthritis (RA). The frequencies of C4AQ0 (32.1%) and C4B5 (35.9%) among RA patients were significantly higher than among healthy control subjects. C4B5 was strongly associated with HLA-Bw54, Bw59, DR4.1, and DQw4. C4AQ0 showed no association with HLA-Bw54 or Bw59, but there was weak association with HLA-DR4.1 and DQw4. The number of persons with both C4AQ0 and C4B5 was significantly higher in the RA patient group (relative risk 13.5). C2C and BFS were the most common alleles in RA patients, as well as in healthy control subjects. These data support the existence of 2 different putative susceptibility haplotypes (HLA-Bw54 or Bw59;C2C; BFS;C4A3;C4B5;DR4.1;DQw4 and C2C;BFS; C4AQ0;C4B1 or C4B2) in Japanese patients with RA.
Narcolepsy is a sleep disorder completely associated with HLA-DR2,Dw2. We demonstrated the 100% presence of three DQ beta fragments (EcoRI 2.4-kb, BamHI 2.9-kb, and PstI 12-kb) in narcoleptic patients that were detected in healthy DR2 controls only at decreased frequencies. In this paper, we have cloned the DQ beta gene from three Japanese narcoleptic patients and sequenced their beta 1 domain in order to study the sequence polymorphisms that might exist in the DQ beta genes of patients, but no difference in sequence could be found between narcoleptic and healthy individuals, suggesting that narcolepsy is not due to mutation in the DQ beta gene. In this context, a possible role of the HLA class II antigens in narcolepsy is discussed.
As a first step of investigating male predominance of bladder cancer incidence, we have studied relationships between rat bladder carcinogenesis, induced by BBN, and changes of pituitary-testicular axis, induced by a LH-RH analogue. The rats were divided into the following five groups. The first group (Age matched control group) was given normal drinking water for 30 weeks. The 2nd group (BBN group) was given a drinking water containing 0.05% BBN for 6 weeks. The 3rd group (LH-RH group) was given subcutaneous injections of a LH-RH analogue depot every four weeks. The 4th group (LH-RH + BBN group) was given subcutaneous injections of the LH-RH analogue depot every four weeks and a drinking water containing 0.05% BBN for 6 weeks. The 5th group (castration group) was castrated and given normal drinking water. The results were summarized as follows. 1) Serum LH, FSH and testosterone levels reached their peaks one day after the LH-RH analogue injection and decreased afterwards. Testosterone marked a castration level one week after the LH-RH analogue injection. 2) There was no significant difference between the BBN and non BBN groups in serum LH, FSH and testosterone levels. Thus, BBN did not influence the pituitary-testicular axis and the action of the LH-RH analogues. 3) Incidence of cancer was higher in the group of BBN + LH-RH than in the group of BBN 8 weeks after the start of the experiment. Then, the incidence was reversed between 20 weeks and 26 weeks; finally it became almost the same at 30 weeks. This phenomenon may be explained by the experimented schedule we applied; that is, BBN and LH-RH analogue were administered simultaneously. 4) Thus, changes of the pituitary-testicular axis induced by the LH-RH analogue seemed to have influence on bladder carcinogen.
Between December 1986 and January 1978, 68 patients with bone metastases were analyzed to evaluate the effect of radiation for the relief of pain. The 68 patients, who had a total of 97 lesions, complained of pain caused by their bone metastasis. The good, fair, and poor responses were found to be 18%, 60%, and 22%, respectively. With reference to the primary neoplasms, the effective response rate was 73% in lung cancer, 100% in breast cancer, 75% in gastric cancer, 100% in hepatic cancer, 100% in bladder cancer, 25% in epipharyngeal cancer, and 70% in the other neoplasms. Depending on the cell types of the lung cancer, the effective response rate was 80% for small cell carcinomas, 72% for adenocarcinomas and 40% for squamous cell carcinomas. Our results suggest that radiotherapy for bone metastases is to be recommended, since the effective response rate was 78% for the relief of pain.
Sodium erythorbate (SE) was administered at concentrations of 0, 1.25, or 2.5% (maximum tolerated dose, MTD) in the drinking-water to groups of 50 male B6C3F1 mice respectively. Female groups, each consisting of 50 mice, received SE in the drinking-water at concentrations of 0, 2.5 or 5% (MTD). Treatment continued for 96 wks and the experiment was terminated during wk 110. Tumors were observed at various sites including the liver, hematopoietic system, lung and soft tissue. However, at any of the sites, the tumor incidence, the time to death with tumors or the histological distribution of tumors did not differ significantly from those in the untreated control group. Thus, the present study did not demonstrate a tumorigenic effect of SE on B6C3F1 mice by means of oral administration.
A case of radiation myelitis developed 1 year and 5 months after radiotherapy for lung cancer is reported. A 75-years old male was given a dose of 70 Gy to the tumor with a fraction dose of 2 Gy, 5 times per week. He developed the weakness and disturbance of sense in bilateral lower extremities, which gradually worsened in spite of a variety of treatment. Some discussions on tolerance dose, fraction dose and fraction number are made as well as technique of irradiation.
Genetic polymorphisms of the serum complement components (C2, C4, C6, and C7) and HLA-antigens were studied in Japanese patients with psoriasis vulgaris. Among these complement components, positive associations with C4A4 and C4B2 were obtained. In addition to the previously reported haplotypes HLA-Cw6-B13 and Cw6-Bw57-DR7, the extended haplotype HLA-Cw11-Bw46-C4A4. 4B2-BFS-C2C-DRw8 may be a high risk haplotype in Japanese patients with psoriasis vulgaris.
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We examined the association between HLA-DQ and refractory Behçet's disease at the genomic DNA level. Using a restriction endonuclease Taq I and a DQ beta cDNA probe, we identified the 1.9 kb DQ beta restriction endonuclease fragment tightly associated with refractory Behçet's disease. This observation indicates that genomic HLA-DQ variations affect the development of refractory Behçet's disease.
Taq I-generated HLA-DQ alpha restriction fragment length polymorphism was examined in Japanese patients with narcolepsy. All patients were DR2 positive and shared a 6.0 kb fragment, although this fragment was found only in 54% of the healthy DR2-positive Japanese. This finding added the DQ alpha gene to the list of candidates for the possible narcolepsy-susceptibility gene. In contrast, there was no complete association between narcolepsy and DX alpha restriction fragment length polymorphism. These findings suggest that a narcolepsy-susceptibility gene is located closer to the DQ locus than to the DX locus.
Segregation of narcolepsy-associated DR2/DQw1 haplotypes was studied in 19 informative Japanese families. Each family consisted of a DR2-heterozygous patient, his or her spouse, and their children. In contrast to the previous study on Caucasian narcolepsy, no segregation distortion of the DR2/DQw1 haplotype was observed. The DR2/DQw1 haplotypes were inherited by 9 of 22 offspring from fathers (41%, p = 0.54) and by 10 of 14 offspring from mothers (71%, p = 0.16). These data show that there is no significant segregation distortion of the DR2/DQw1 haplotype in Japanese patients with narcolepsy.