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Biomedical subjects

K Tokunaga

Publications and source records attributed to K Tokunaga.

At least 289 records · Page 16Linked to original sources
PubMed1995

Distribution of HLA antigens and haplotypes in the Buryat population of Siberia.

Polymorphisms of HLA-A, B, C, DR, and DQ antigens were investigated in a Mongoloid population named Buryat living in Siberia. HLA gene and haplotype frequencies were calculated from the population data obtained from 141 unrelated healthy Buryat adults. Gene frequencies of class I antigens A2, A24, A1, B61, Cw10, and Cw6 were estimated to be more than 10%. For class II, DR4, DR7, DR13, DQ7, and DQ1 antigens were predominant. A phylogenetic tree was constructed based on HLA gene frequencies, and the Buryat population was clustered with the Mongoloid groups in Northeast Asia. In the analysis of HLA-A, C, B, DR, and DQ five-locus haplotype frequencies, seven kinds of haplotypes were calculated to occur at frequencies of more than 2%. Five of the seven common haplotypes have also been described in the other human populations thus far. Some of the haplotypes have been described in European populations, while the others were shared with Northeast Asian Mongoloids as well as Amerindians. Similar situation was also found in the analysis of class I (HLA-A, C, B) three locus haplotypes. These observations suggest the unique genetic background of this Buryat population.

Ethnicity↗
PubMed1995

Determination of HLA class II alleles by genotyping in a Manchu population in the northern part of China and its relationship with Han and Japanese populations.

The genetic polymorphism of the HLA class II loci was investigated in a Manchu population resident in the northern part of China and compared with those of other Asian populations including Japanese and Han. In 8 DQA1 alleles, the most frequent allele was DQA1*03 with the gene frequency of 25.5%. Of 15 DQB1 alleles tested, 11 were observed and the most common allele was DQB1*0301 with the gene frequency of 24.5%. Among 19 DPB1 alleles, 11 were detected and DPB1*0501 (43.8%) was the most frequent allele as observed in other Asian populations such as Japanese, Chinese and Korean. Of 43 DRB1 alleles tested, 21 were detected and DRB1*0901 (14.0%), *1501 (11.0%), *1201 (11.0%), *07 (9.0%) and *1401 (9.0%) were highly predominant and account for the high frequencies of DR9, DR2, DR5, DR7 and DR6. In the DRB3 gene (DR52), DRB3*0202 (18.0%) was the most frequent. With respect to the DRB4 gene (DR53), the gene frequency of DRB4*0101 was 35.0%. Of 3 DRB5 alleles detected, DRB5*0101 (11.0%) was highly predominant. Comparison of HLA class II allele frequencies in Manchu with those in Japanese and Han Chinese populations (South & North) detected some significant differences and genetic divergence between these Oriental populations. The dendrogram constructed by the neighbor-joining (NJ) method based on the allele frequencies of DQA1, DQB1, DPB1 and DRB1 of 10 representative populations over the world suggested that Manchu is the closest, but at the same genetic distance to both Northern and Southern Han Chinese.

Alleles↗
PubMed1995

DNA-based typing of human platelet antigen systems by polymerase chain reaction-single-strand conformation polymorphism method.

Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method has been established to discriminate genotypes for the human platelet antigen (HPA) systems HPA-1, HPA-2, HPA-3, HPA-4, and HPA-5. Gene fragments which contain polymorphic sequences corresponding to the HPA-1, HPA-2, HPA-3, HPA-4, and HPA-5 systems were PCR-amplified with specific primers. The amplified DNA was denatured and subjected to non-denaturing polyacrylamide gel electrophoresis followed by silver staining. The results obtained by the PCR-SSCP method were in good agreement with those of the allotypes determined by serological typing. Furthermore, the results agreed with those obtained by other DNA-based typing methods such as PCR-allele-specific restriction enzyme analysis and PCR-sequence-specific primer. These results indicate that PCR-SSCP is a simple and sensitive method for determining HPA genotypes and identifying unknown polymorphisms.

Antigens, Human Platelet↗
PubMed1995

Establishment of a T-cell line from lymphocytes presumably implicated in posttransfusion graft-versus-host disease.

Posttransfusion graft-versus-host disease (PTGVHD) is known to develop in immunocompetent patients exhibiting clinical symptoms such as erythroderma, fever, liver dysfunction, diarrhea and pancytopenia. It is speculated that transfused blood donors' lymphocytes might recognize the recipients' HLAs as alloantigens. The thus stimulated lymphocytes might proliferate, expand and finally attack the host's immune system or tissues. However, details regarding these expanded donor cells such as: (1) whether they represent one clone or more, (2) the composition of lymphocyte subsets, and (3) the target HLA antigens of recipients, are not clear, since T-cell lines derived from PTGVHD patients have not yet been obtained. The aim of this study is to characterize T-cells responsible for PTGVHD and to identify their target molecules. For that purpose, we attempted to establish T-cell lines derived from a PTGVHD patient. We show that the established T-cell line, proven to be derived from donor lymphocytes, showed a CD4+ phenotype and had cytotoxic activities. Furthermore, we describe that the target of the cytotoxic T-cell line (CTL) is an HLA-DRB1*0405-related molecule of the patient.

Base Sequence↗
PubMed1995

Multiplex ARMS-PCR-RFLP method for high-resolution typing of HLA-DRB1.

A reliable method for high-resolution HLA-DRB1 typing using the combination of group-specific amplification and RFLP analysis is described. Group-specific PCR amplification (multiplex ARMS-PCR) was carried out under the same conditions for all groups using seven different primer pairs divided into four groups: (1) DR1 and DR10; (2) DR2, DR7 and DR9; (3) DR3 DR5, DR6 and DR8, and (4) DR4. The subsequent polyacrylamide gel electrophoresis was used to determine the group(s) contained in each sample. DR1, DR2/7, DR3/5/6/8, DR4, DRB1*0901 and DRB1*1001 could be distinguished easily using this system. Computer analysis of the various restriction enzyme cleavage sites was carried out on 105 DRB1 allele sequences. It was shown that all DRB1 alleles, except for five allele pairs and some alleles possessing silent mutations, could be distinguished with commonly available restriction endonucleases. Computer analyses on the discrimination of the heterozygous and homozygous combinations were also carried out. Although some heterozygous combinations could no be distinguished with single digestion, double digestion using two restriction enzymes could distinguish most of such heterozygotes. The results of the typing of 100 Japanese individuals using this method showed good agreement with those obtained by other methods.

Alleles↗
PubMed1995

Naturally occurring accessory gene mutations lead to persistent human immunodeficiency virus type 1 infection of CD4-positive T cells.

Proviral DNA from cells surviving severe but transient cytopathic effects, mediated by infection with recombinant human immunodeficiency virus type 1 (HIV-1) carrying a single gene mutation at vif, vpr, or vpu, was characterized by use of HIV-1-specific primer pairs in a two-step PCR. Deletion mutations were detected in a region that spanned the vif and vpr open reading frames. Cloning and sequencing of the amplified DNA from this region revealed frequent large deletions in a limited number of nucleotide positions. Analyses of the deletions suggested that (i) genetic recombination, (ii) template-primer slippage, and (iii) misalignment of the growing point during reverse transcription of the HIV-1 genome might be the mechanisms that generated the mutations. Apart from the large deletions, smaller deletions that gave frameshift mutations in vif and/or vpr prevailed. In addition, cells infected with a triple mutant defective in vif, vpr, and vpu did not show any cytopathic effect. Thus, mutations generating multiple accessory gene defects during HIV-1 replication correlate with viral persistence and loss of cytopathogenicity.

Base Sequence↗
PubMed1995

Marked hypocholesterolemia in a case with adrenal adenoma--enhanced catabolism of low density lipoprotein (LDL) via the LDL receptors of tumor cells.

A 16-yr-old girl was hospitalized because of amenorrhea and virilism, and was diagnosed with an adrenal tumor on the right side. Her serum androgen levels were markedly elevated, and severe hypocholesterolemia (total cholesterol, 0.59 mmol/L) was observed. After resection of the tumor, her serum cholesterol level dramatically rose to normal, suggesting a role of this tumor in her marked hypocholesterolemia. To investigate the mechanism of hypocholesterolemia in this case, we examined the effects of dehydroepiandrosterone and dehydroepiandrosterone sulfate on the low density lipoprotein (LDL) receptor activity of fibroblasts. These hormones did not have any effect on LDL receptor activity. Northern blot analysis demonstrated that the LDL receptor messenger ribonucleic acid level of this tumor tissue was increased about 8-fold compared with that of normal adrenal cortex. The LDL receptor activity of the cultured cells established from this tumor was 2-fold higher than that of Hep G2 cells. Furthermore, the LDL receptor activity could not be down-regulated by an excessive dose of 25-hydroxycholesterol. These results suggest that increased LDL receptor activity and unrestricted uptake of LDL by the adrenal tumor may have caused the marked hypocholesterolemia in this patient.

Adenoma↗
PubMed1995

Prophylactic thrombosis to prevent new bleeding and to delay aneurysm surgery.

Six aneurysms in five patients with acute aneurysmal subarachnoid hemorrhages were treated with direct thrombosis using cellulose acetate polymer within 4 hours of rupture. The aneurysms involved the internal carotid and posterior communicating arteries (two patients), the anterior choroidal artery (one patient), the bifurcation of the basilar artery (one patient), and the middle cerebral artery (two patients). Four patients underwent aggressive volume expansion after direct thrombosis with cellulose acetate polymer. The aneurysms remained thrombosed until operations on the necks were performed 2 to 7 weeks after the subarachnoid hemorrhages. Three patients were given intrathecal tissue plasminogen activator. One patient, who remained at neurological Grade V, was not treated surgically and died from cardiac failure. Five aneurysms in the remaining four patients were successfully clipped. These preliminary data suggest that immediate aneurysmal thrombosis, then aggressive preoperative prophylactic volume expansion and/or administration of intrathecal tissue plasminogen activator, can help prevent new bleeding and reduce delayed cerebral ischemia in patients after aneurysmal subarachnoid hemorrhages.

Aged↗
PubMed1995

Differential immunogenetic determinants of polyclonal insulin autoimmune syndrome (Hirata's disease) and monoclonal insulin autoimmune syndrome.

The insulin autoimmune syndrome (IAS), or Hirata's disease, is characterized by the combination of fasting hypoglycemia, high concentration of total serum immunoreactive insulin, and presence of autoantibodies to native human insulin in serum. Autoantibody production is classified as monoclonal or polyclonal, with the majority of IAS cases classified as polyclonal. Previously, we observed a striking association between the human leukocyte antigen (HLA) class II alleles DRB1*0406/DQA1* 0301/DQB1*0302 and Japanese IAS patients with polyclonal insulin autoantibodies (IAAs) and T-cell recognition of human insulin in the context of DRB1*0406 molecules. Because of such a strong HLA association in IAS, we performed intra- and interethnic studies on IAS-associated DRB1 alleles and searched for the critical amino acid residue(s) for IAS pathogenesis. Glutamate at position 74 in the HLA-DR4 beta 1-chain was presumed to be essential to the production of polyclonal IAA in IAS, whereas alanine at the same position of the HLA-DR beta 1-chain might be important in the production of monoclonal IAA.

Adult↗
PubMed1995

Early treatment of subarachnoid hemorrhage after preventing rerupture of an aneurysm.

Twelve patients with Hunt and Hess neurological Grades III to V underwent thrombosis of aneurysms using cellulose acetate polymer within 23 hours of aneurysm rupture. On computerized tomography (CT), nine of these patients had difuse or localized thick subarachnoid blood clots, two had diffuse thin clots and one had intraventricular clots. Immediately after thrombosis, all patients were administered tissue plasminogen activator (TPA) through spinal or ventricular catheters. The pressure of the lumbar cerebrospinal fluid was maintained at 100 to 150 mm H2O. The TPA was given as multiple injections of 2 mg on Day 0 and 1 to 2 mg on the following 1 to 2 days. In two patients the second injection of TPA was not given because of severe brain damage resulting from the initial subarachnoid hemorrhage. Ten patients showed complete clearance of the cisternal clot on CT within 72 hours after thrombosis. Seven partially thrombosed aneurysms and five multiple aneurysms were clipped during delayed surgery. Only one patient experienced mild vasospasm as shown on the follow-up angiogram. Eight patients improved clinically and had a good recovery, two had severe disability, and two died. Urgent thrombosis of a ruptured aneurysm followed by immediate postthrombotic administration of TPA may be a safe and reasonable means of preventing vasospasm and improving patient outcome.

Aged↗
PubMed1995

Direct thrombosis of experimental aneurysms with cellulose acetate polymer (CAP): technical aspects, angiographic follow up, and histological study.

Experimental aneurysms were created using a microsurgical technique to produce anastomosed venous pouches in the bilateral common carotid arteries of 12 dogs. The 24 aneurysms were then thrombosed via an endovascular approach with injection of a cellulose acetate polymer (CAP) solution that the authors have developed for use as a liquid thrombotic material. Angiography performed 1 to 4 weeks after CAP injection revealed complete thrombosis of the aneurysm with patency of the parent artery in 16 aneurysms. Histological analysis disclosed that the aneurysmal orifice in these cases was completely covered with newly formed endothelial cells 2 weeks after CAP thrombosis. Three other aneurysms exhibited parent artery occlusion caused by protrusion of the CAP mass through the aneurysmal orifice into the parent artery; this was thought to be caused by over-injection of the CAP solution. Histological analysis of the remaining five aneurysms, initially shown to have incomplete occlusion, revealed that they each possessed a residual neck that was partially covered with endothelial cells. No rupture of the aneurysms or migration of CAP into the distal arteries was observed. These results suggest that using an endovascular approach, direct thrombosis of cerebral aneurysms with CAP is safe and effective. This technique may prove to be an alternative treatment for such aneurysms. However, there is a potential risk of regrowth or rupture of aneurysms that retain a residual neck and long-term follow-up studies will be required to evaluate this issue.

Animals↗
PubMed1995

Increased proportion of plasma apoB-48 to apoB-100 in non-insulin-dependent diabetic rats: contribution of enhanced apoB mRNA editing in the liver.

To assess the alteration of apolipoprotein (apo) B mRNA editing in non-insulin-dependent diabetes mellitus (NIDDM), we measured plasma apoB-100 and apoB-48 levels and apoB mRNA editing efficiency in the liver and intestine from GK (Goto-Kakizaki) rats, a genetically NIDDM animal. Male GK rats and control littermates, aged 25 weeks, were used in this study. Ventromedial hypothalamus (VMH)-lesioned control rats were used as hyperinsulinemic models. VMH-lesioned GK rats (GK+VMH) were treated as an insulin-exhausted NIDDM model. Plasma cholesterol and triglyceride levels were increased in GK rats. Very low density lipoprotein (VLDL)-triglyceride and low density lipoprotein (LDL)-cholesterol concentrations were significantly higher in GK rats than in controls. The increase of VLDL-triglyceride was most marked in GK+VMH rats. Plasma apoB-48 levels, quantified by immunoblot, were increased in GK rats. However, apoB-100 levels were minimally elevated in GK rats. Therefore, the apoB-48/apoB-100 ratio was remarkably increased in GK rats. ApoB mRNA editing was analyzed by reverse transcriptase-polymerase chain reaction coupled with dideoxynucleotide chain termination assay. The ratio of apoB-48-type cDNA to apoB-100-type cDNA was significantly increased in the liver from GK rats compared with controls. Although the development of the VMH lesion increased plasma apoB-48 levels, it had no effect on the proportion of apoB-48-type to apoB-100-type cDNA in the liver from both GK and control littermates. ApoB mRNA in the intestine was almost totally edited (approximately 95%). Intestinal apoB-48/apoB-100 cDNA ratio showed no significant difference among the four groups. In conclusion, an enhanced apoB mRNA editing was indicated in the non-insulin-dependent diabetic rats, which might contribute to the increase of plasma apoB-48 levels.

Animals↗