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Biomedical subjects

T Juji

Publications and source records attributed to T Juji.

At least 91 records · Page 5Linked to original sources
PubMed1999

Analysis of 500 bone marrow transplants from unrelated donors (UR-BMT) facilitated by the Japan Marrow Donor Program: confirmation of UR-BMT as a standard therapy for patients with leukemia and aplastic anemia.

In December 1991, the Japan Marrow Donor Program (JMDP) was established with the cooperation of the Japanese Red Cross and Japan Marrow Donor Foundation under the auspices of the Ministry of Health and Welfare in Japan. By December 1998, 122365 HLA-A,B typed volunteer marrow donors and 7207 patients had been cumulatively registered in the JMDP. The results of HLA-matching between donors and patients revealed that 5684 out of 7207 (78.9%) patients could have at least one HLA-A,B,DR serologically matched donor. Among these matched pairs, 1829 unrelated bone marrow transplants (UR-BMT) were performed. The initial 500 UR-BMT transplanted from January 1993 to October 1995 were analyzed as of July 1998. Engraftment was achieved in 95% of cases. Probability of the occurrence of grade III and IV acute GVHD was 18.4%. The rate of disease-free survival (DFS) of the patients who had standard-risk leukemia and did not suffer from grade III or IV acute GVHD (n = 154) was 60-71% and the rate of survival of patients with aplastic anemia was 56%. It can be stated that UR-BMT is a modality of treatment which is as effective as related BMT if the occurrence of grade III or IV acute GVHD is predicted and prevented.

Acute Disease↗
PubMed1999

Association of Fc gamma receptor IIIB, but not of Fc gamma receptor IIA and IIIA polymorphisms with systemic lupus erythematosus in Japanese.

Human Fc gamma receptor (Fc gamma R) genes form a clustered gene family on chromosome 1q21-24. Although the association of Fc gamma R polymorphisms with systemic lupus erythematosus (SLE) has been extensively studied, the results are often contradictory. In this study, Fc gamma RIIA-131H/R, Fc gamma RIIIA-176F/V and Fc gamma RIIIB-NA1/2 genotypes were determined in the Japanese patients with SLE (n = 81) or rheumatoid arthritis (RA, n = 115) as well as in healthy individuals (n = 217), and possible association with the disease was tested using case-control analysis. Unlike in other populations, significant difference was not observed in the frequencies of Fc gamma RIIA and Fc gamma RIIIA genotypes between patients with SLE and healthy individuals. However, significant difference was detected in the frequencies of Fc gamma RIIIB genotypes between SLE and healthy individuals (P = 0.008). The odds ratio [OR] of the Fc gamma RIIIB-NA2/NA2 homozygotes for the development of SLE was 2.52 (95% confidence interval [CI]: 1.33-4.79). Among the patients with SLE, individuals with NA2/2 were significantly more likely to have lupus nephritis (P = 0.007). No association was observed between any of the Fc gamma R polymorphisms and RA. Significant linkage disequilibrium was detected between Fc gamma RIIIA and IIIB, but neither between IIA and IIIA, nor between IIA and IIIB. These observations may underscore the relevance of defective immune complex handling in the pathogenesis of SLE, or may suggest the presence of primarily associated gene(s) in linkage disequilibrium with Fc gamma R genes.

Adolescent↗
PubMed1999

A search for a mutation in the tumour necrosis factor-alpha gene in narcolepsy.

The discovery of almost 100% association of narcolepsy with human leukocyte antigens (HLA) DR2 antigen prompted molecular biological research of this disorder. In the HLA class II gene cluster, the gene for tumour necrosis factor-alpha (TNF-alpha), which plays a role in the regulation of normal human sleep, is located. The present study searched for a mutation in the TNF-alpha gene by single-strand conformation polymorphism analysis (SSCP) in patients with narcolepsy. No mutation was detected in exons and introns of the TNF-alpha gene by SSCP and sequencing.

DNA Mutational Analysis↗
PubMed1999

Possible association of human leucocyte antigen DR1 with delayed sleep phase syndrome.

The study investigated the human leucocyte antigen (HLA), types A, B and DR, of 42 patients with delayed sleep phase syndrome (DSPS) and compared the frequencies of the antigens with those in 117 healthy controls. The comparison revealed that the gene frequencies and positivities of HLA-A, -B and -DR, except for DR1, had no significant differences between the patients and controls. The frequency of HLA-DR1 was increased in the DSPS patients as compared with that in the healthy controls (P = 0.0069 in positivity). Although the corrected P-value (0.069) for multiple comparisons almost reached the significance level, the results indicated a possible association of the HLA-DR1 antigen with DSPS. This study suggests that there are genetic predispositions to DSPS.

Adolescent↗
PubMed1999

Analysis of human leukocyte antigen-G polymorphism including intron 4 in Japanese couples with habitual abortion.

PROBLEM: The purpose of this study was to clarify whether there is a difference between the allele frequency of human leukocyte antigen (HLA)-G in healthy Japanese people and that of Japanese couples with habitual abortion. METHOD OF STUDY: Exons 2, 3, 4, and intron 4 of the HLA-G gene were analyzed in 20 couples with habitual abortion, using polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. Intron 4 of the HLA-G gene was also analyzed in 54 healthy individuals. The nucleotide sequence of the PCR product of intron 4 was further determined by direct sequencing. RESULTS: Two kinds of nucleotide sequence were identified in intron 4 of the HLA-G gene, one of which was identical to that of HLA-G*01011, and the other was identical to that of HLA-G*01012, G*01013, and G*0104. The frequency of each allele in affected women and their husbands did not significantly differ from that of healthy individuals, and no mutation was found in any affected couple. CONCLUSION: HLA-G allelic abnormality seemed to have little, if any, implication in the pathogenesis of habitual abortion.

Abortion, Habitual↗
PubMed1999

Treatment of post-transfusion graft-versus-host disease with nafmostat mesilate, a serine protease inhibitor.

BACKGROUND: Cytotoxic T lymphocytes from donors are thought to injure the target organs in post-transfusion graft-versus-host disease (PT-GVHD) through perforin-granzyme- and Fas-dependent cell killings. The protease involved is a serine protease, and nafmostat mesilate (NM), a serine protease inhibitor, has been found to inhibit the in vitro allocytotoxicity of the T cell clone established from a patient with PT-GVHD, thus suggesting the usefulness of NM for treatment of PT-GVHD. CASE REPORT: A 47-year-old male with esophageal cancer, who received 3 units of packed red cells and 20 units of platelet concentrates from 5 unrelated donors, was diagnosed as having PT-GVHD on the basis of typical clinical features, HLA typing of the patient and the responsible donor, and a mixed chimera of CD8+ lymphocytes on microsatellite DNA polymorphism analysis. NM was administered to inhibit the activity of the serine proteases, thought to be granzymes; a liver dysfunction and thrombocytopenia with leukocytopenia simultaneously improved. Subsequently, a high-dose methylprednisolone pulse therapy and monoclonal anti-CD3 were administered to reduce the donor's proliferating lymphocytes, which resulted in lymphopenia accompanied by elimination of the donor's lymphocytes and normalization of the CD4/CD8 ratio. However, recurrence of the proliferation of the responsible donor's lymphocytes developed after cessation of NM administration, probably because of excessive immunosuppression caused by steroids and the monoclonal anti-CD3. CONCLUSION: This case indicates that administration of a serine protease inhibitor may improve PT-GVHD symptoms by inhibiting cytotoxic T-cell-mediated killing of target cells in fatal PT-GVHD. Steroids and monoclonal anti-CD3 were probably responsible for the transient clinical improvements. More studies are required, however, on mechanisms to eliminate the donor's lymphocytes.

Benzamidines↗
PubMed1999

Determination of granulocyte-specific antigens on neutrophil FcA receptor IIIb by PCR-preferential homoduplex formation assay, and gene frequencies in the Japanese population.

BACKGROUND AND OBJECTIVES: Granulocyte-specific antigens play an important role in provoking immune neutropenia and transfusion reactions. We developed a new DNA-typing method, PCR-preferential homoduplex formation assay (PHFA), to determine granulocyte-specific antigens on the neutrophil Fcgamma receptor IIIb (FcgammaRIIIb, CD16b), namely, the NA1, NA2, and SH antigens and their gene frequencies in the Japanese population. MATERIALS AND METHODS: Four hundred unrelated healthy Japanese blood donors were typed using PCR-PHFA. To confirm the accuracy of the results of FcgammaRIIIB genotyping using PCR-PHFA, PCR-sequence-specific primer (SSP) typing and PCR-restriction fragment length polymorphism (RFLP) typing were carried out in another 20 samples for comparison. RESULTS: The results of PCR-PHFA typing agreed well with other methods. The frequencies of the FcgammaRIIIB alleles were 62.2, 37.8, 0 and 0% for NA1, NA2, SH, and 'NA-null', respectively. CONCLUSION: The PCR-PHFA method can be semi-automated easily with computer-based assignment and is suitable for typing both small and large numbers of samples. In the Japanese population, the frequency of NA1 is about double that in Caucasians (32.5%), and the SH allele is rare.

Alleles↗
PubMed1999

Splice acceptor site mutation of the transporter associated with antigen processing-1 gene in human bare lymphocyte syndrome.

Expression of histocompatibility leukocyte antigen (HLA) class I molecules on the cell surface depends on the heterodimer of the transporter associated with antigen processing 1 and 2 (TAP1 and TAP2), which transport peptides cleaved by proteasome to the class I molecules. Defects in the TAP2 protein have been reported in two families with HLA class I deficiency, the so-called bare lymphocyte syndrome (BLS) type I. We have, to our knowledge, identified for the first time a splice site mutation in the TAP1 gene of another BLS patient. In addition, class I heavy chains (HCs) did not form the normal complex with tapasin in the endoplasmic reticulum (ER) of the cells of our patient.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Suppression of arthritic bone destruction by adenovirus-mediated csk gene transfer to synoviocytes and osteoclasts.

Rheumatoid arthritis (RA) is characterized by a chronic inflammation of the synovial joints resulting from hyperplasia of synovial fibroblasts and infiltration of lymphocytes, macrophages, and plasma cells, all of which manifest signs of activation. Recent studies have revealed the essential role of osteoclasts in joint destruction in RA. Src family tyrosine kinases are implicated in various intracellular signaling pathways, including mitogenic response to growth factors in fibroblasts, activation of lymphocytes, and osteoclastic bone resorption. Therefore, inhibiting Src activity can be a good therapeutic strategy to prevent joint inflammation and destruction in RA. We constructed an adenovirus vector carrying the csk gene, which negatively regulates Src family tyrosine kinases. Csk overexpression in cultured rheumatoid synoviocytes remarkably suppressed Src kinase activity and reduced their proliferation rate and IL-6 production. Bone-resorbing activity of osteoclasts was strongly inhibited by Csk overexpression. Furthermore, local injection of the virus into rat ankle joints with adjuvant arthritis not only ameliorated inflammation but suppressed bone destruction. In conclusion, adenovirus-mediated direct transfer of the csk gene is useful in repressing bone destruction and inflammatory reactions, suggesting the involvement of Src family tyrosine kinases in arthritic joint breakdown and demonstrating the feasibility of intervention in the kinases for gene therapy in RA. off

Adenoviridae↗
PubMed1999

HLA genes and haplotypes in Ryukyuans suggest recent gene flow to the Okinawa Islands.

Polymorphism of HLA genes was investigated in a population sample of Ryukyuans living on the main island of Okinawa (n = 197), in the southwestern islands of Japan. Serological typing was applied to class I loci (HLA-A, -B, and -C) and to HLA-DRB1; nucleotide sequence-level typing was performed using PCR microtiter plate hybridization and PCR single-strand conformation polymorphism methods. Ryukyuans showed a higher frequency of DRB1*0405 and lower frequencies of DRB1*1502 and DRB1*1302 compared with Hondo Japanese living on main islands. Principal components and phylogenetic analyses of 12 East Asian populations, including Ryukyuans, were performed based on the allele frequencies of HLA-A, -B, and -DRB1. In the principal components analysis 3 Japanese populations (Ryukyuans, Hondo Japanese, and Ainu) formed a cluster and showed the highest affinity to 2 Korean populations. In the phylogenetic tree Ryukyuans and Ainu were neighbors, but the genetic distance between them was larger than the distances between Ryukyuans and Hondo Japanese and between Ryukyuans and Korean populations. The geographic cline of the predominant haplotype in Ryukyuans, A*24-B*54-DRB1*0405, suggests that an ancestral population possessing A*24-B*54-DRB1*0405 moved into the Okinawa Islands after the divergence of Ryukyuans from the Ainu. Such a recent gene flow, probably from South China to the Okinawa Islands, is considered the major cause of difference in genetic characteristics between Ryukyuans and the Ainu.

Adult↗
PubMed1999

Typing for human platelet alloantigens.

Antibodies to platelet alloantigens, and sometimes to isoantigens, induce severe clinical problems such as neonatal alloimmune thrombocytopenia (NAIT), post-transfusion purpura (PTP) and refractoriness to platelet transfusions (PTR). For example, NAIT affects approximately 1 in 5,000 live births. It is essential, therefore, to screen pregnant women for platelet antibodies in order to save babies' lives. Almost 40 years ago, two platelet alloantigen systems were discovered using relatively simple methods, namely the platelet agglutination test and the complement fixation test. However, these methods were not sensitive enough to identify all antibodies in mothers and patients, even in those with severe clinical problems. Tremendous effort has been devoted to establish more sensitive and reliable methods. In recent years, excellent new serological and immunochemical methods have been established and several new platelet antigen systems have been discovered. Simultaneously, newly developed molecular genetic techniques have been introduced for the typing and analysis of human platelet alloantigen systems. These methods allow DNA typing for cases in which serological typing is not available. In this article, the history of studies on human platelet alloantigen systems and isoantigens, the nomenclature of platelet alloantigen systems and their alleles, the present status of antibody detection and typing techniques and, finally, ethnic variations in platelet antigen profiles are reviewed.

Alleles↗
PubMed1998

Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. Japan Marrow Donor Program.

BACKGROUND: The requirements with respect to HLA compatibility and the relative importance of matching for individual class I and class II HLA alleles in the transplantation of hematopoietic stem cells from unrelated donors have not yet been established. METHODS: We performed retrospective DNA typing of alleles at 11 polymorphic loci of HLA genes in 440 recipients of hematopoietic stem cells from unrelated donors who were serologically identical with their respective recipients for HLA-A, B, and DR antigens. Of these recipients, 80 percent had leukemia; the rest had lymphoma, marrow failure, or a congenital disorder. RESULTS: Multivariate analysis showed that incompatibility for HLA-A alleles and incompatibility for HLA-C alleles were independent risk factors for severe acute graft-versus-host disease (GVHD) (HLA-A, P=0.006; HLA-C, P=0.001). Mismatching of HLA-A, but not of HLA-C, alleles was an independent risk factor for death (P<0.001). Matching [corrected] of HLA-C alleles was a significant risk factor for relapse of leukemia (P=0.035). HLA-B disparity was a significant risk factor for both GVHD and death in the univariate analysis, but not in multivariate analysis. Disparities in class II HLA alleles of the DRB1, DQA1, DQB1, DPA1, and DPB1 loci were not identified as significant risk factors for acute GVHD or death in the multivariate analysis. CONCLUSIONS: Genomic typing of class I HLA alleles adds substantially to the success of transplantation of hematopoietic stem cells from unrelated donors, even if the donors are serologically identical to their recipients with respect to HLA-A, B, and DR antigens.

Adolescent↗
PubMed1998

Highly efficient recovery of functional single-chain Fv fragments from inclusion bodies overexpressed in Escherichia coli by controlled introduction of oxidizing reagent--application to a human single-chain Fv fragment.

An improved and efficient refolding system for a single-chain antibody fragment (scFv) from inclusion bodies expressed in Escherichia coli was developed. Stepwise removal of denaturing reagent and controlled addition of oxidizing reagent were found to be the most effective conditions to achieve for almost complete recovery of functional monomeric scFv from inclusion bodies. Adding L-arginine to the refolding solution also increased the yield of refolded functional scFv. The single-chain Fv fragments of both a mouse anti-lysozyme monoclonal antibody, HyHEL10, and a human monoclonal antibody against the D antigen of the Rh blood group, D10, in solubilized inclusion bodies could be refolded under these conditions with yields of up to 95%. The refolding procedures developed in this study will contribute to providing a stable supply of large amounts of human single-chain Fv fragments.

Animals↗
PubMed1998

Evidence that CD31, CD49b, and CD62L are immunodominant minor histocompatibility antigens in HLA identical sibling bone marrow transplants.

Despite complete matching of siblings for the HLA loci, after bone marrow transplantation (BMT), approximately 20% develop graft-versus-host disease (GVHD). This is presumably due to incompatibility of minor histocompatibility antigens (mHa). We investigated the polymorphisms of 14 adhesion molecules (CD2, CD28, CD31, CD34, CD36, CD42, CD44, CD48, CD49b, CD54, CD62L, CD86, CD102, and CD106) in Japanese subjects and their association with the occurrence of GVHD after allogeneic HLA identical BMT. Six molecules (CD2, CD31, CD42, CD49b, CD54, and CD62L), which were found to be polymorphic, were then examined in 118 HLA identical sibling donors and recipients who had undergone BMT. Association of the incompatibility of the polymorphic molecules with the presence or absence of GVHD was examined. In these six, we observed a significant correlation between acute GVHD and the compatibility of CD31 (codons 563/670) (Pcorrected = .018), and CD31 (codons 563/670) + CD62L (Pcorrected = .018) in patients with the HLA-B44-like superfamily. In patients with the HLA-A3-like superfamily, the compatibility of CD62L (Pcorrected = .03) and CD62L + CD49b (P = . 004, Pcorrected = .078) was associated with acute GVHD. Therefore, CD31, CD49b, and CD62L might be candidates for immunodominant mHa.

Adolescent↗
PubMed1998

Guillain-Barré and Fisher's syndromes subsequent to Campylobacter jejuni enteritis are associated with HLA-B54 and Cw1 independent of anti-ganglioside antibodies.

The frequencies of human leukocyte antigens (HLA)-class I (A, B and Cw) were determined serologically and those of HLA-class II (DRB1 and DQB1) at the genomic level in 35 Japanese patients with Guillain-Barré syndrome (GBS), 58 with Fisher's syndrome (FS), and 112 healthy controls. HLA-B54 and -Cw1 antigens were found in GBS and FS patients from whom Campylobacter jejuni had been isolated more often than found in the healthy controls. No HLA types were related to GBS or FS as a whole, except for the B54 antigen which often was significant in the entire GBS group. This relation, however, may depend on the high population of C. jejuni-isolate patients in our GBS group. There were no relationships between the frequencies of HLA types and the presence of serum IgG antibodies to GM1, GQ1b, GD1a, or GalNAc-GD1a. Our findings suggest that HLA types are associated with the onset of GBS and FS after C. jejuni enteritis and that the HLA types in distinct GBS and FS subgroups of a single etiological origin need to be examined.

Antibodies↗