A new HLA-DR11 DRB1 allele found in a Korean.
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Adult↗
Biomedical subjects
K Tokunaga
Publications and source records attributed to K Tokunaga.
HLA-DR types in Japanese schizophrenics: analysis by group-specific PCR amplification.
An association of HLA-DR8 and DR1 with DSM-III schizophrenia has been reported in Japan (Miyanaga et al. (1984) Biol. Psychiatr. 19, 121-129). To further investigate this preliminary finding, we compared HLA-DR types in 44 unrelated Japanese schizophrenics (DSM-III-R) with those in 51 unrelated, healthy Japanese volunteers. Group-specific PCR amplification was used in the determination of HLA-DR in the patients. No significant difference was observed in the frequency of any DR types between patients and controls, after statistical correction for multiple testing. However, the frequency of DR1 in our patients (23%) and controls (10%) was almost the same as those in the previous report (22% vs. 10%), which means that there is a suggestive trend which could become significant if numbers were larger. It is argued that an exact determination of HLA-DR by DNA typing is important in current HLA studies of schizophrenia.
Adult↗
Do specific pockets of HLA-C molecules predispose Jewish patients to psoriasis vulgaris?
BACKGROUND: Psoriasis vulgaris was reported to be associated with a specific alanine residue at position 73 of HLA-C alleles in Japanese patients. OBJECTIVE: Our purpose was to determine the role of HLA genes in susceptibility to psoriasis vulgaris in the Israeli Jewish population. METHODS: Twenty-eight Israeli patients were analyzed for their HLA class I and II specificities by means of serologic and molecular methods. RESULTS: All patients possessed in their HLA-C antigens an alanine residue at position 73 (p < 0.002). A significantly increased frequency of HLA-Cw6 and of Cw7 was also observed among the patients (p < 0.02). CONCLUSION: Our study clearly shows that alanine in position 73 is significantly associated with psoriasis vulgaris in Jewish patients. Cw6 and Cw7 have a unique antigen-binding pocket containing both alanine at position 73 and a negatively charged aspartic acid at position 9. These residues are most probably important in determining the conformation of the C pocket and in turn the nature of the peptide bound to it. We suggest that this combination confers the highest risk of the development of psoriasis vulgaris.
Alanine↗
Sequence analysis of serological HLA-A11 split antigens, A11.1 and A11.2.
HLA-A11 has two serologically-defined splits, A11.1 and A11.2, and two alleles coding for HLA-A11, A*1101 and A*1102, have been published so far. In order to understand the relationship between the serological subtypes and the amino acid sequences, we have sequenced the alleles coding for A11.1 and A11.2. The results demonstrated that A11.1 split antigen is encoded by A*1101 and A11.2 split antigen is encoded by A*1102. Moreover, we obtained the sequences of exons 1, 5, 6, 7, and 8 of A*1102, which were not reported previously. In addition, we could distinguish A*1101 from A*1102 using a PCR-SSCP method, confirming that A11.1 carried by different HLA haplotypes has the same sequence.
Amino Acid Sequence↗
Two rare MHC haplotypes carrying DR2 in the Japanese population.
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Asian People↗
Discrimination of human HLA-DRB1 alleles by PCR-SSCP (single-strand conformation polymorphism) method.
A single-strand conformation polymorphism (PCR-SSCP) method has been adopted for discrimination of human HLA-DRB1 alleles. This method enabled the detection of DNA polymorphisms including point mutations at a variety of positions in the DNA fragments of the HLA-DRB1 gene. A total of 27 HLA-DRB1 alleles from 172 healthy donors were analysed using a combination of PCR-SSCP with group-specific amplifications. Application of a small amount of amplified and denatured DNA to non-denaturing electrophoresis followed by silver staining resulted in distinct banding patterns. Samples possessing a single allele in each amplification group showed two-band patterns which correspond to the sense and antisense strands, while heterozygotes in the same group or a mixture of two single-type samples showed four-band patterns. All of the analysed alleles were discriminated in each DRB1 group. The method described here may be somewhat complicated for routine typing of HLA-DRB1 alleles. However, it is useful in the screening of "new' alleles as well as the donor-recipient molecular matching of HLA class II genes for various purposes, e.g. selection of bone marrow transplant donors.
Alleles↗
Genetic polymorphisms in HLA-A, -B, -C and -DR antigens in Japanese patients with palmoplantar pustulosis.
Genetic polymorphisms in HLA-A, -B, -C and -DR antigens were investigated in 78 unrelated Japanese patients with palmoplantar pustulosis (PPP) and compared with a total of 472 normal persons. Only HLA-DR9 showed a significantly increased frequency among all HLA antigens investigated (chi 2 = 11.57, p < 0.001). It is suggested that major histocompatibility complex class II antigens including HLA-DR antigen may determine the susceptibility to PPP and PPP may be a distinct disease entity from psoriasis.
Adult↗
Cellulose acetate polymer thrombosis for the emergency treatment of aneurysms: angiographic findings, clinical experience, and histopathological study.
Cellulose acetate polymer solution is a liquid thrombotic material that hardens into the shape of an aneurysm into which it is injected. Therapy using this solution is a rapid technique that helps prevent the rupture of aneurysms, especially those that extravasate contrast material during angiography in the acute stage of subarachnoid hemorrhage. Using this polymer solution and an endovascular technique, we treated two patients who had aneurysms of the basilar and anterior communicating arteries with extravasation of contrast material during angiography a few hours after the initial subarachnoid hemorrhage. In one patient with an aneurysm of the anterior communicating artery, the aneurysm's wall was perforated with the catheter during neurointerventional procedures. In both patients, postoperative angiograms demonstrated obliteration of the aneurysmal dome, including the site of extravasation or perforation. The parent artery and surrounding perforating branches were preserved. Although we do not advocate aggressive therapy for patients who bleed during angiography, we pursued this therapy in these two patients because of the opportunity to introduce cellulose acetate polymer in an attempt to preserve the patients' lives. Unfortunately, both patients died. Histopathological studies performed at the time of autopsy demonstrated that the luminal surface of cellulose acetate polymer was covered with thrombus by 6 days after cellulose acetate polymer thrombosis. By 10 days, the thrombus had a prominent fibrin network, a concentrated plasma component, and few fibrocytes adhering to its luminal surface.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Effect of ischemic preconditioning on ischemia-induced contractile failure and accumulation of extracellular H+ and K+.
The present study was performed to determine whether the effects of ischemic preconditioning are mediated by a decrease in myocardial contractile activity or by a change in catabolite accumulation during the subsequent period of sustained ischemia. In ischemic preconditioning groups, crystalloid perfused rat hearts were subjected to 5 or 10 min of global ischemia before a 15-min reperfusion period and a subsequent 30 min period of ischemia, Non-preconditioned control hearts underwent a single 30-min ischemic period. In the 5-min preconditioned hearts, the onset of myocardial contracture was significantly delayed (22.0 +/- 1.6 min) compared with that in control hearts (14.7 +/- 0.7 min). Tissue ATP content of the myocardium during sustained ischemia was preserved better in 5-min preconditioned hearts than in control hearts. The time to contractile arrest during the sustained ischemic period was greater in the preconditioned hearts (3.9 +/- 0.3 and 3.1 +/- 0.2 min in PC5 and PC10 hearts respectively) than in controls (1.9 +/- 0.1 min). Thus, residual myocardial work during sustained ischemia (as estimated by the rate pressure product) was not decreased in the preconditioned hearts compared with that in control hearts. Extracellular acidosis was identical among the three groups during the subsequent period of sustained ischemia. The early rise in extracellular K+ during sustained ischemia progressively increased with the duration of preconditioning. We conclude that, in crystalloid perfused rat heart, 5 min of global ischemia had a salutary effect against cell damage caused by sustained ischemia. This "preconditioning" effect cannot be attributed to decreased myocardial work during ischemia nor to differences in extracellular H+ or K+ accumulation.
Adaptation, Physiological↗
Extracranial vertebral artery aneurysm causing spinal subarachnoid hemorrhage--case report.
A 48-year-old female presented with spinal subarachnoid hemorrhage (SAH) due to the rupture of an extracranial vertebral artery (VA) aneurysm. The aneurysm arose from the junction of the third and the fourth segments of the left VA just inside the dura mater, and was partially coated with Biobond. This is only the second such case reported. We recommend complete four-vessel angiography in evaluating patients with SAH, with special attention given to the extracranial VA if spinal SAH is suspected.
Aneurysm, Ruptured↗
Selection and combination of techniques for treating spontaneous carotid-cavernous sinus fistulas.
Twenty-eight patients with spontaneous carotid-cavernous sinus fistulas (CCFs) were treated using a variety of techniques. Three of four patients with direct CCFs underwent intravascular embolization with a detachable balloon. Embolization with polyvinyl alcohol particles through an external carotid endoarterial route was used in six patients with indirect CCFs, and with ethylene-vinyl alcohol copolymer solution in two. Patients undergoing these conventional treatments, including embolization of the meningeal branches of the external carotid artery, had less satisfactory outcomes. The transvenous approach using minicoils through the inferior petrosal sinus was successful in eight patients. One patient treated using the transvenous approach using copper wire through the ophthalmic vein had worsening of visual acuity and field. Unsuccessful transvenous embolization in four patients required direct surgical exposure and embolization with spring coils. Spontaneous cures occurred in four patients. Direct CCFs with high flow rates were best treated with the detachable balloon or coil technique through a internal carotid endoarterial route. Indirect CCFs were best treated with the minicoil through the inferior petrosal sinus. If these techniques fail, direct surgical exposure allows placement of coils into the cavernous sinus.
Adult↗
Deficiency of the fourth component of complement (C4): a family case.
In this report, an apparently healthy 38-year-old woman with a remarkably low serum C4 value is described together with other family members who had moderately low serum C4. Plasma C4 typing disclosed that the proband inherited two C4B "null" haplotypes. In addition, Southern blot analysis of the C4 gene indicated that the C4A gene was partially deleted on one of these two haplotypes in the proband. We thus concluded that a de novo deletion on the inherited half-null haplotype was the likeliest cause of the low C4 level.
Adult↗
Association of complement C4 and HLA-DR alleles with systemic lupus erythematosus in Koreans.
OBJECTIVE: To examine the association of complement C4 and HLA-DR to systemic lupus erythematosus (SLE) susceptibility in Korea. METHODS: Complement C4 protein typing was carried out by immunofixation and immunoblotting methods using EDTA-plasma from 60 patients with SLE and 72 healthy controls. Restriction fragment length polymorphism analysis of C4 genes was also carried out using TaqI or HindIII for restriction enzymes. HLA-DR was determined by polymerase chain reaction amplification with sequence specific primers using genomic DNA from 67 patients with SLE and 72 healthy controls. RESULTS: The frequency of the C4AQ0 allele was significantly higher in the patients with SLE than in controls (41.7 vs 25.0%, p < 0.05). The deletion of the C4A gene commonly found in Caucasian patients with SLE was not observed in any patients. For HLA-DR, a significant increase of the haplotype DRB1*1501 was observed in the patients (26.9 vs 12.5%, p < 0.05) and DR9 was also significantly increased (23.9 vs 11.1%, p < 0.05). An increase in each DR2 and DR9 was independent of an increase in C4AQ0. The frequencies of DR2 and DR9 were significantly decreased in patients with renal involvement and alopecia, respectively. CONCLUSION: Our data suggested that the presence of C4AQ0 allele, DRB1*1501-DRB5*0101 haplotype and DR9 contributed to susceptibility to SLE in Koreans and that Korean SLE is based on a different genetic background from Caucasian patients.
Adult↗
Cellular kinetics of posttransfusion graft-versus-host disease after heart operations.
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Aged↗
Sexual dimorphism of age-related changes in whole-body fat distribution in the obese.
We performed a cross-sectional study using whole-body computerized tomographic (CT) scans in order to clarify age-related changes in whole-body fat distribution in both genders. The subjects were 66 men and 96 women, whose body mass index (BMI) was over 25 kg/m2. CT scans were performed at seven levels (head, fore-arms, upper arms, chest, abdomen, thighs and calves), and the fat volumes of the segments were calculated from the cross-sectional areas of the fat tissues. After calibrating to the total fat volumes, the relationship between age and the relative segmental fat volumes was analysed. In both genders, the relative intra-abdominal visceral fat volume increased and that of the legs decreased with age. The relative abdominal subcutaneous fat volume decreased with age only in male subjects. The increase in the relative visceral fat volume with age was about 2.6 times larger in males than in pre-menopausal females, while post-menopausal females showed the same increase as male subjects. These data suggest that there is a definite gender difference in the age-related changes in whole-body fat distribution, especially in the abdominal fat tissues. In addition, the accumulation of visceral fat is markedly accelerated by menopause in women.
Abdomen↗
Association of HLA-DR with progressive systemic sclerosis in Japanese.
OBJECTIVE: To clarify the contribution of HLA-DR genes to the susceptibility to progressive systemic sclerosis (PSS). METHODS: HLA-DR typing was carried out in 36 Japanese patients with PSS, 42 with systemic lupus erythematosus and 104 healthy subjects by polymerase chain reaction (PCR) method using specific primers and by PCR-SSCP (single-standard DNA conformation polymorphism) method. RESULTS: A haplotype DRB1*1502-DRB5*0102 was significantly increased in PSS (50.0%, p < 0.00004, pc < 0.001), especially in antitopoisomerase I antibody (a-Scl-70) positive patients (62.5%, p < 0.00003, pc < 0.001) and PSS with diffuse scleroderma (75.0%, p < 0.00001, pc < 0.0001). In addition, DRB1*0802 was also increased in DRB1*1502 negative patients with a-Scl-70, (50.0%, p = 0.033, pc = not significant) and in DRB1*1502 negative patients with diffuse scleroderma (75.0%, p = 0.008, pc = not significant). Thus, 81.3% of a-Scl-70 positive patients, and 93.8% of patients with PSS with diffuse scleroderma showed either HLA-DRB1*1502 or 0802. CONCLUSIONS: Our observations show the extreme difference of genetic background of a-Scl-70 positive PSS, with regard to HLA-DR, between Japanese and other ethnic groups including Caucasian and American black persons. The increase in DRB1*1502-DRB5*0102 haplotype supported the hypothesis of Reveille, et al that uncharged polar amino acid residue at position 30 of HLA-DQB1 allele was important for a-Scl-70 positive PSS because close association of the haplotype with DQB1*0601 was well established in Japanese; listed as a hypothetical candidate of PSS susceptible DQB1 allele. DRB1*0802 were also associated with hypothetical candidates of DQ alleles. Furthermore, the sharing of the particular amino acid sequence: valine38 and phenylalanine67-lysine68-glutamic acid69-asparic acid70-arginine71, by DRB5*0102, DRB1*0802 and DR11 (associated with Caucasian PSS) also suggests a contribution of the sequence in HLA-DR molecules to the pathogenesis of PSS according to the shared epitope hypothesis.
Adult↗
Tumor necrosis factor-alpha mRNA expression in lipopolysaccharide-stimulated rat kidney. Chronological analysis of localization.
To study the time course of lipopolysaccharide-induced production of tumor necrosis factor-alpha (TNF-alpha) in the kidney, we utilized a highly sensitive non-radioisotopic in situ hybridization with 1-nm gold-conjugated anti-digoxigenin for localization of TNF-alpha mRNA expression after lipopolysaccharide administration. TNF-alpha mRNA expression localized by in situ hybridization showed a peak increment in proximal tubular epithelial cells and glomeruli at 2 hours and returned to almost normal levels at 6 hours. The intensity of the signal was much stronger in proximal tubules than in glomeruli. These findings were confirmed by the demonstration of similar kinetics in the increase of TNF-alpha message, measured by using amplification of the third and fourth exons of TNF-alpha gene by reverse transcription-polymerase chain reaction of microdissected proximal tubular segments and isolated glomeruli. Reverse transcription-polymerase chain reaction of cultured rat mesangial and glomerular epithelial cells demonstrated that mesangial cells, not glomerular epithelial cells, were responsible for the observed glomerular signals.
Animals↗
Recognition of human insulin in the context of HLA-DRB1*0406 products by T cells of insulin autoimmune syndrome patients and healthy donors.
Our recent study indicated that all the insulin autoimmune syndrome (IAS) patients had specific HLA class II alleles, the DRB1*0406, DQA1*0301, and DQB1*0302, which allowed T cells to proliferate when autologous APC were exposed to human insulin. The study implied that gene products of DRB1*0406, DQA1*0301, and/or DQB1*0302 may be involved in the presentation of human insulin to T cells. We therefore examined T cell response of healthy donors with different HLA phenotypes to human insulin using an autologous MLR system. The T cells from not only IAS patients but also healthy donors were able to proliferate after exposure of human insulin to autologous APC with DRB1*0406, DQA1*0301, and DQB1*0302 products. The class II molecules are considered to be involved in the recognition of human insulin by T cells. The proliferative response of T cells was completely blocked by anti-HLA-DR mAb and not by anti-HLA-DQ mAb or other mAb. Furthermore, human insulin-specific CD4-positive T cell clones were established from blast cells in autologous MLR of PBMC from two healthy donors with DRB1*0406 in the presence of human insulin. Using DRB1*0406-transfected L cells as APC, we confirmed that these T cells clones recognize human insulin in the context of gene products of DRB1*0406. These results provide the first evidence that HLA-DRB1*0406 products act as the dominant restriction element for the presentation of human insulin to T cells, and suggest that this particular class II gene, HLA-DRB1*0406, contributes to the development of IAS.
Antibodies, Monoclonal↗