HLA-A26 subtype A pockets accommodate acidic N-termini of ligands.
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Alleles↗
Biomedical subjects
K Tokunaga
Publications and source records attributed to K Tokunaga.
Founder-haplotype analysis in Fukuyama-type congenital muscular dystrophy (FCMD).
Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal recessive, severe muscular dystrophy associated with brain anomalies. After our initial mapping of the FCMD locus to 9q31-33, we performed linkage disequilibrium analysis, which led us to suspect that the FCMD gene lay within a region of less than 100 kb containing D9S2107. In the present study, we developed two new microsatellites (D9S2170 and D9S2171) in close vicinity to D9S2107 and examined haplotypes of FCMD chromosomes by using four markers (cen-D9S2105-D9S2170-D9S2171-D9S2107-tel). As 82% of the FCMD chromosomes that we examined shared the founder haplotype (138-192-147-183) and 94% of the FCMD patients in our panel carried founder haplotypes on one or both chromosomes, the data supported the hypothesis of a single founder of this disease in the Japanese population. Eight haplotypes different from the founder's were observed in FCMD chromosomes, indicating that eight different FCMD mutations in addition to the founder's have occurred in Japan. Moreover, we have detected several historical recombinations that have disrupted the founder haplotype at D9S2105 or D9S2170 and conclude that the FCMD gene is probably located just centromeric to D9S2170.
Chromosomes, Human, Pair 9↗
Cardioprotective effect of succinate against ischemia/reperfusion injury.
We investigated the protective effects of succinate, which is a respiratory substrate and a potential antioxidant, on myocardial ischemia/reperfusion injury with the whole heart. Isolated rat hearts were loaded with 25-min normothermic global ischemia followed by 30-min reperfusion in a working heart model. Succinate administered either before reperfusion or added to the cardioplegic solution improved the postischemic cardiac function significantly. The hearts arrested with succinate-supplemented cardioplegic solution replenished high-energy phosphates and maintained the total adenine nucleotides during the reperfusion period, whereas those arrested with succinate-nonsupplemented cardioplegic solution replenished the high-energy phosphates less, and also lost total adenine nucleotides during that period. We thus conclude that succinate administered before reperfusion may decrease the degree of mitochondrial damage during reperfusion and thereby reduce the amount of myocardial ischemia/reperfusion injury.
Animals↗
A nested PCR-RFLP method for high-resolution typing of HLA-A alleles.
We developed a nested polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method for high-resolution typing of HLA-A alleles. HLA-A alleles can be identified by this method without the need for other information such as serological type. The first PCR was performed using outer primers, ASP5 and ASP3, specific for the HLA-A gene, and a 991-bp DNA fragment extending from exon 1 through exon 3 was amplified. In the second PCRs, exon 2 and exon 3 of the HLA-A gene were amplified separately from the diluted first PCR product using nested primers. Computer analysis of cleavage patterns for 78 HLA-A alleles showed that 31 RFLP patterns could be obtained by digestion of the exon 2 PCR product using eight restriction endonucleases and 42 RFLP patterns by digestion of the exon 3 PCR product using 11 restriction endonucleases, and all alleles could be discriminated based on combinations of these RFLP patterns except for nine allele groups or pairs: A*0201/0207/0215N/0220/0222, A*0205/0208/0214, A*0206/0221, A*0212/0213, A*2402/2405, A*2406/2413, A*2601/2605, A*2603/2606 and A*7401/7402. Thus, 65 PCR-RFLP patterns were predicted from the results of analysis of digestion patterns of 78 HLA-A alleles. Among 2145 possible homozygous and heterozygous combinations of the 65 distinguishable PCR-RFLP patterns, 82 combinations were predicted to have the same PCR-RFLP patterns. In PCR-RFLP analysis, although the nested primers were not specific for the HLA-A gene, clear RFLP banding patterns were obtained because specificity was guaranteed by the use of the outer primers, ASPS and ASP3 in the first PCR. A*0201 and A*0207 occur relatively frequently in the Asian populations among indistinguishable allele groups or pairs using the present PCR-RFLP method. We also developed a PCR sequence-specific primers (PCR-SSP) method for distinguishing between A*0201/0220/0222 and A*0207/0215N. We could identify 39 alleles (groups) upon HLA-A typing of 50 Japanese individuals, 40 cell lines of the Fourth Asia-Oceania Histocompatibility Workshop, and 80 cell lines of the UCLA International Cell Exchange Program using the present PCR-RFLP and PCR-SSP methods.
Alleles↗
Partial thrombosis of canine carotid bifurcation aneurysms with cellulose acetate polymer.
OBJECTIVE: To investigate the usefulness of a cellulose acetate polymer (CAP) solution for partial thrombosis of aneurysms. METHODS: We created 14 canine cervical carotid bifurcation aneurysms, 11 of which were subsequently thrombosed partially with CAP solution. We then conducted angiographic and histological investigations. RESULTS: Nine aneurysms were thrombosed 50 to 70% by volume, although a significant crescent crevice between the aneurysmal sac and the CAP mass was left in four of the aneurysms. In the remaining two aneurysms in which a crescent crevice had been seen in the initial stage of CAP injection, 80% and more than 95% thrombosis were needed to occlude the crevice, respectively. Follow-up angiograms of the seven aneurysms with no crescent crevice revealed no shifts of position of the CAP mass toward the bottom of the aneurysm sac, but slight ballooning of the remnants was observed in two of them. The angiograms of the other four aneurysms with significant crescent crevices demonstrated rupture with a massive hematoma in one and shifts of the CAP mass with marked enlargement of remnants in three. Histologically, the seven aneurysms with no enlarged remnants had newly developed membranes consisting of endothelium, infiltrated spindle-shaped cells, collagen, and elastic fibers. In contrast, in the three markedly enlarged aneurysms, there were only recent clots between the CAP mass and the aneurysm lumen and no development of endothelium. CONCLUSION: Partial thrombosis with CAP solution is useful to keep aneurysms in a stable configuration, unless a crescent crevice has been left.
Aneurysm↗
Enhancement of human immunodeficiency virus type 1 infectivity by Nef is producer cell-dependent.
The growth kinetics of wild-type and nef mutant viruses of human immunodeficiency virus type 1 were comparatively analysed in several human CD4+ cell lines. Delayed replication of nef mutant virus was observed in all cell lines examined. To determine the stage in the virus replication cycle that is affected by Nef, a single-round replication assay was performed. Initially, the expression of marker genes in transfected cells was examined in order to study the role of Nef in the late phase of infection. The results obtained indicated that Nef is dispensable during the transcription to virion production stage. Next, the effect of Nef on the early phase was investigated with a single-round infection. It was demonstrated that Nef is required in the early phase of the virus replication cycle, from virion adsorption to integration. Finally, the infectivity of virus stocks prepared from four cell lines was determined. The relative infectivity of the nef mutant from the four cell lines differed. Taken together, we conclude that Nef acts via modulation of viral particles to enhance virus infectivity in a cell-dependent manner.
Gene Products, nef↗
HLA haplotypes in Koreans based on 107 families.
There are marked differences in the distribution of HLA haplotypes among different populations, and multilocus HLA haplotypes can best be studied by family analysis. In the present study, 107 Korean families were analyzed for HLA-A, B, C, DR, and DQ antigens and haplotypes. Allele frequencies of more than 10% for class I antigens were A2, A24, A33, B44, B62, Cwl, Cw7, Cw9, Cw10, and C blank (CBL) and those for class II antigens were DR4, DR8, DR13, DR15, DQ1, DQ3, DQ4 and DQ7. In the analysis of HLA haplotypes, 18 kinds of A-B-DR and 11 kinds of A-C-B-DR-DQ haplotypes occurred at frequencies of more than 1%, comprising 34% and 24% of the total theoretical haplotypes, respectively. The five most common A-B-DR haplotypes were exclusively related with the five most common A-C-B-DR-DQ haplotypes (frequency>2%). These remarkably conserved five-locus haplotypes in Koreans were A33-CBL-B44-DR13-DQ1 (5.4%), A24-Cw7-B7-DR1-DQ1 (3.5%), A33-Cw7-B44-DR7-DQ2 (3.0%), A33-Cw10-B58-DR13-DQ1 (2.3%), and A30-Cw6-B13-DR7-DQ2 (2.3%). Comparison of the distribution of A-B-DR haplotypes among East Asian populations revealed that Koreans are closest to Japanese, but show a higher degree of polymorphism in the distribution of HLA haplotypes compared to Japanese. The results obtained in this study will be useful as basic data on Koreans for anthropology and organ transplantation.
Alleles↗
Diversity of HLA-B61 alleles and haplotypes in East Asians and Spanish Gypsies.
The distribution of HLA-B61 alleles and their association with HLA-C and DRB1 alleles were investigated in six East Asian populations (South Korean, Chinese Korean, Man (Manchu), Northern Han, Mongolian and Buryat) and Spanish Gypsies and compared to our previous report on the Japanese population. The alleles were identified using a group-specific polymerase chain reaction (PCR) and genomic DNA followed by hybridization with sequence-specific oligonucleotide probes (SSOP). Both HLA-B*4002 and B*4006 were commonly detected in the South Korean, Chinese Korean, Man, Northern Han and Japanese populations, while HLA-B*4002 was predominant in the Mongolian and Buryat populations. Strong associations of B*4002 with Cw*0304 and of B*4006 with Cw*0801 were commonly observed in these East Asian populations. In contrast, in Spanish Gypsies, only HLA-B*4006 was found and the allele exhibited a strong association with Cw*1502. HLA-B*4003 was also identified in the South Korean, Chinese Korean, Northern Han, Mongolian and Japanese populations at relatively low frequencies, and exhibited an association with Cw*0304. Moreover, the association of these B61 alleles with the DRB1 alleles revealed considerable diversity among the different populations. HLA-B*4004 and B*4009 were not observed in these populations. Consequently, the frequencies of the B61 alleles varied among the different East Asian populations, but the individual B61 alleles were carried by specific haplotypes often regardless of the ethnic differences.
Alleles↗
Cw*0103, a new allele encoding for a novel HLA-Cw1 split in the Japanese population.
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Alleles↗
Polymorphism of TAPASIN and its linkage disequilibria with HLA class II genes in the Japanese population.
Tapasin plays an important role in HLA class I assembly. The gene has been mapped on the human MHC region. We identified two alleles of TAPASIN in the Japanese population and analyzed the association of the alleles with HLA-DPB1, -DQB1 and -DRB1 alleles. The allele frequencies of TAPASIN*01 and *02 were estimated to be 0.37 and 0.63, respectively, in the Japanese population. TAPASIN showed strong linkage disequilibrium with the HLA-DPB1 locus. Several frequent four-locus haplotypes were identified, including DRB1*0901-DQB1*0303-DPB1*0501-TAPASIN*02, DRB1*0901-DQB1*0303-DPB1*0201-TAPASIN*02 and DRB1*1302-DQB1*0604-DPB1*0401-TAPASIN*02.
Antiporters↗
Human lymphocytes obtained from decidual tissue express killer activatory receptors as well as killer inhibitory receptors: analysis using a single strand conformation polymorphism method.
PROBLEM: The objective was to clarify whether lymphocytes in decidual tissue express only killer inhibitory receptors (KIRs) or both KIRs and killer activatory receptors (KARs). METHOD OF STUDY: A polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis method, using cDNA as a template, was applied to detect as many natural killer receptors (NKRs) expressed on natural killer (NK) cells as possible and to distinguish between KIRs and KARs. Using this method, we analyzed NKRs on lymphocytes in decidual tissue and maternal peripheral blood mononuclear cells (PBMCs) (n = 10) from the same individuals. RESULTS: More than 20 SSCP bands were detected for NKRs on both the lymphocytes in decidual tissue and the maternal PBMCs. The SSCP band patterns were different for each individual. KARs mRNA was detected in lymphocytes in decidual tissue according to the SSCP analysis results. CONCLUSION: Lymphocytes in decidual tissue express not only KIRs but also KARs; this finding suggests their roles in placentation and the maintenance of pregnancy.
Abortion, Induced↗
Inhibition of human immunodeficiency virus type 1 virion entry by dominant-negative Hck.
To study the role of Src family tyrosine kinases in infection with human immunodeficiency virus type 1 (HIV-1), we constructed an Hck mutant, HckN, that hinders signaling from wild-type Hck. HIV-1 produced in HckN-expressing cells was significantly less infectious to HeLa-CD4-LTR-beta-gal (MAGI) cells than HIV-1 produced in mock-transfected cells. The inhibitory effect of HckN was compensated for by the expression of vesicular stomatitis virus G protein. Finally, we found that the HIV-1 produced in the HckN-expressing cells entered into the cells less efficiently than did the control HIV-1. These results suggest that the Src family tyrosine kinases regulate entry of HIV-1 into target cells.
Gene Products, nef↗
Reference typing report for complement components C6, C7 and C9 including mutations leading to deficiencies.
The results of the present (VIIth Complement Genetics Workshop and Conference, Mainz, May 1998) and past reference typing workshops for the terminal complement components C6, C7 and C9 are compiled and discussed both on the protein level and on the DNA level. This report also focuses on the molecular bases of expressed and silent polymorphisms and reviews the molecular bases of subtotal and complete deficiencies of these proteins and their associations with protein and DNA markers. The results of the protein typing for C6 are published in the following paper of this issue.
Alleles↗
Contribution of HLA genes to genetic predisposition in diffuse panbronchiolitis.
Diffuse panbronchiolitis (DPB) in East Asia is a distinctive chronic obstructive pulmonary disease of unknown etiology. We hypothesize that the disease susceptibility is due to genetic predisposition unique to Asians. Association between human leukocyte antigen (HLA)-Bw54 and the disease was previously reported. In the present study, using newly developed polymerase chain reaction (PCR)- based methods, we directly analyzed HLA class I and II alleles in 76 Japanese patients. HLA-A, -B, and -C antigens were screened by the conventional typing method, and then B22-group alleles including HLA-B54 were genotyped by single-strand conformation polymorphism analysis. Alleles of HLA-DRB1 gene were fully determined by the microtiter plate hybridization method. Thirty-seven percent of the patients possessed HLA-B*5401 allele conserved predominantly in East Asians, as compared with 15% of 110 healthy volunteers (chi2 = 12.4, p = 0.0004). In addition, 4% of the patients possessed B*5504 also unique to Asians but a rare allele which was not found in normal control subjects in this study. Typing of HLA-DRB1 class II gene did not demonstrate strong positive association with the disease. A33, B44, and DRB1*1302 showed negative association with the disease. We conclude that distinctive molecular structure of HLA-B alleles or a closely linked gene in the HLA region contributes to genetic predisposition in diffuse panbronchiolitis. This may partly explain why this disorder is found primarily in Asians.
Alleles↗
Association of HLA class I and class II alleles with myositis in Japanese patients.
OBJECTIVE: To investigate the correlation of HLA class I and class II antigens and alleles with various forms of myositis in Japanese patients. METHODS: Eighty-four Japanese patients with myositis [22 with polymyositis (PM), 46 with dermatomyositis (DM), 16 with myositis overlapping with other collagen vascular diseases] were typed serologically for HLA-A, B, C antigens. HLA-DRB1, DQA1, and DQB1 alleles were determined by polymerase chain reaction dependent DNA typing methods. Fifty-eight Japanese controls were typed serologically while HLA-DRB1, DQA1, and DQB1 allele typing was carried out in 175, 95, and 104 controls, respectively. RESULTS: HLA-B7 was higher in patients than controls [20.2 vs 6.9% in controls: p=0.02, odds ratio (OR)=3.4]. The increase of HLA-B7 was largely dependent on the increase in overlap patients (37.5%; p=0.005, OR=8.1). HLA-A24 and B52 were significantly decreased in PM as compared to DM, while CW3 was significantly increased in PM versus DM. DRB1*08 alleles were significantly increased in patients (36.9 vs 20.5% in controls; p=0.004, OR=2.3), especially in PM and DM. DQA1*0501 and DQB1*0301 were significantly decreased in patients [4.8 vs 13.7% in controls; p=0.04, OR=0.32, and 8.3 vs 20.2% in controls; p=0.02, OR=0.36, respectively]. CONCLUSION: HLA-class I and class II alleles associated with Japanese patients with myositis may be different from those associated with Caucasian patients.
Alleles↗
Different alleles cause an imbalance in A2 and A2B phenotypes of the ABO blood group.
BACKGROUND AND OBJECTIVES: In several populations, including the Japanese, the frequency of the A2B phenotype is significantly higher than expected based on the A2 phenotype frequency. To understand the genetic basis of this 'excess' of A2B, we examined ABO alleles in individuals with A2-related phenotypes. MATERIALS AND METHODS: ABO alleles were identified by means of polymerase chain reaction single-strand conformation polymorphism (SSCP) and nucleotide sequence analyses. RESULTS: The frequencies of A2-related alleles (*A105, *A106, *A107, *A111 and *R101) were clearly different between the A2 and A2B phenotypes. In particular, a putative recombinant allele, *R101, was uncommon in the A2 but common in the A2B phenotype individuals. This allele was also detected in 4 of 401 (1%) unrelated A1 phenotype (AO genotype) individuals. CONCLUSION: *R101 is presumably expressed as phenotype A1 in *R101/*O heterozygous individuals, but as phenotype A2 in *R101/*B heterozygotes, thus giving rise to a high A2B phenotype frequency.
ABO Blood-Group System↗
[Lipid peroxide and antioxidants in the elderly].
Aging is associated with changes in physical characteristics and decline of many physiological functions. The aging process have been described by various theories, in particular the free radical theory of aging has received widespread attention. It has been accepted that the oxidative stress or damage induced by free radicals is related to aging. In this study, we determined the serum concentration of lipid peroxide and antioxidant as biomarker for aging. Healthy subjects were classified into 3 groups, elderly (65-), middle-aged (40-64) and young group (20-39). Findings in the elderly were as follows: 1. Lipid peroxides in the elderly group were significantly higher than those in the young group. 2. Preventive antioxidant concentrations of superoxide dismutase, glutathione peroxidase and albumin were lower than those in the young group, but ceruloplasmin values increased and catalase activity was unchanged. 3. The total antioxidant capacity of serum was slightly decreased. 4. Superoxide generation by neutrophils while resting was significantly higher in the young group.
Adult↗
Characteristics of coronary artery disease and lipoprotein abnormalities in patients with heterozygous familial hypercholesterolemia associated with diabetes mellitus or impaired glucose tolerance.
Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of serum low density lipoprotein (LDL) cholesterol and premature coronary atherosclerosis. In order to elucidate the influence of abnormal glucose metabolism on the development of coronary artery disease (CAD) in FH patients, we examined the prevalence of CAD and characteristics of lipoprotein abnormalities in patients with heterozygous FH who were accompanied by diabetes mellitus (DM) or impaired glucose tolerance (IGT). The subjects of the present study were 150 patients with heterozygous FH, all over 40 years of age. Oral glucose tolerance tests demonstrated that 15 patients had DM and 27 had IGT. The combination of DM or IGT with FH was associated with a further increase in the prevalence of CAD (DM:IGT:normal glucose tolerance (N), 87:59:43%). Furthermore, the prevalence of the stenoses in the distal coronary arteries was significantly higher in the DM group than in the N group, while there was no significant difference in the prevalence of proximal and middle lesions. Serum triglyceride levels were significantly higher in the DM and IGT groups than in the N group (P < 0.01, DM versus N group; P < 0.01, IGT versus N group), while total cholesterol levels were not significantly different. When lipoproteins were analyzed by polyacrylamide gel electrophoresis, the frequency of midband appearance, which implies an increase in remnant lipoproteins, was significantly higher in the DM and IGT groups than in the N group (DM:IGT:N, 87:72:29%, P < 0.01, DM versus N group; P < 0.01, IGT versus N group). Ultracentrifugation analysis of lipoproteins revealed that intermediate density lipoprotein cholesterol was increased in DM and IGT groups compared with the N group. These data suggest that abnormal glucose metabolism may accelerate the development of CAD in FH patients due to an increase in atherogenic remnant lipoproteins in addition to high concentration of LDL. Special attention should be paid in the treatment of FH patients with impaired glucose metabolism, to avoid the advancement of coronary atherosclerosis.
Adult↗