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Biomedical subjects

T Juji

Publications and source records attributed to T Juji.

At least 235 records · Page 13Linked to original sources

Anti-idiotypic antibody to T-cell receptor in multiply transfused patients may play a role in resistance to graft-versus-host disease.

Most patients who receive multiple blood or platelet transfusions do not develop graft-versus-host disease (GVHD) in spite of the transfusion of donor white cells--cells that are capable of engraftment and subsequent GVHD. The object of this study was to search for the factors responsible for resistance to GVHD in such patients. Some sera from patients who have received multiple platelet transfusions inhibit the proliferation of alloreactive T-cell clones that function as an in vitro model of donor-derived proliferating T cells recognizing recipient alloantigens. The humoral factor in such sera was capable of binding to the T-cell clones, but not to stimulator cells. Further analysis revealed that the humoral factor in such sera was IgG, which specifically bound to membrane molecules of the T-cell clones. The antibody competed with WT31, a monoclonal antibody (MoAb) to T-cell receptor (TCR), in binding to TCR of the T-cell clones. It did not compete with CD3 or CD2 MoAb. These observations strongly favor the view that the antibody against TCR exists in the sera of multiple transfusion recipients. It is suggested that the TCR antibody binds to TCR of the T-cell clones, thus blocking the interaction of the T-cell clone with alloantigens of stimulator cells and resulting in inhibition of the proliferation of T-cell clones. Furthermore, in view of T-cell clone-specific binding of the antibody in sera, it might be concluded that the antibody is anti-idiotypic.

Antibodies, Anti-Idiotypic↗

Genetic polymorphisms in the fourth component of complement (C4) and in properdin factor B (BF) in Japanese patients with palmoplantar pustulosis.

Genetic polymorphisms in the fourth component of complement (C4) and in properdin factor B (BF) were investigated in 49 and 32 Japanese patients with palmoplantar pustulosis (PPP), respectively. C4B2 was significantly increased in frequency, whereas no significant deviations were detected in BF compared with the controls. These results may indicate that complement polymorphisms are involved in the pathogenesis of PPP.

Adult↗

Study of HLA class I, class II and complement genes (C2, C4A, C4B and BF) in Japanese psoriatics and analysis of a newly-found high-risk haplotype by pulsed field gel electrophoresis.

Genetic polymorphisms of HLA antigens and HLA-linked serum complement components (C2, C4A, C4B and BF) were investigated in 79 Japanese patients suffering from psoriasis. HLA typing revealed increased frequencies of HLA-A1, A2, B39, Bw46, Cw6, Cw7 and Cw11. Among complement components, positive associations were obtained with C4A4 and C4B2 and a negative association with BFF. The major histocompatibility complex haplotype (supratype), HLA-A2-Cw11-Bw46-C2C-BFS-C4A4-C4B2-DRw8 is purported to be a new high-risk haplotype in Japanese patients with psoriasis. Analysis of patients with this supratype via pulsed field gel electrophoresis showed the existence of specific, extensive DNA deletions near HLA-DR genes, but no disease-specific patterns could be observed by means of this technique. The newly-found high-risk haplotype indicates racial and ethnic differences among psoriatic patients.

Alleles↗

Specific nucleotide sequence of HLA-C is strongly associated with psoriasis vulgaris.

The association of specific HLA-C nucleotide sequences with psoriasis vulgaris was investigated in 75 Japanese patients by the polymerase chain reaction method, followed by slot-blot hybridization using two specific oligonucleotide probes. The synthesized nucleotide primers were C180P, 5'-GACCGGGAGACACAGAAGTACAAG-3' (coding for amino acid residues 61 to 68 of the alpha 1 domain of the HLA-C molecule) and C243PR, 5'-GCTCTGGTTGTAGTAGCCGCG-3' (residues 82 to 88), respectively. The amplified sequence detected with the probe C208A (5'-AGGCACAGGCTGACCGA-3'), including the coding region for alanine at position 73, was significantly increased in frequency in the patients compared with the healthy individuals (81% versus 48%, relative risk = 4.7, chi 2 = 15.3, p less than 0.0001). This specific nucleotide sequence is common to Cw6 and Cw7, but some other HLA-C alleles including Cw4 and C blank (Cx52) also proved to have this sequence. It is suggested that alanine at position 73 of HLA-C molecules can be a good marker for psoriasis vulgaris and that this residue may play an important role in determining susceptibility to this disease.

Alanine↗

Interleukin-4 gene expression and IgE responsiveness.

Interleukin-4 (IL-4) gene expression by stimulation with concanavalin A (Con A) in murine spleen cells was examined. The amount of IL-4 mRNA induced by Con A was greatest in spleen cells obtained from IgE high responder strains of mice. A trace amount of IL-4 mRNA was induced in spleen cells from IgE low responder (SJL) mice. The amount of IL-4 mRNA induced in spleen cells from an IgE intermediate responder (C57BL/6) was smaller than that from high responders, but significantly greater than that from low responders. Spleen cells from IgE nonresponders (SJA/9) developed only a negligible amount of IL-4 mRNA. IL-4 mRNA was detected in human peripheral blood mononuclear cells (PBMC) stimulated with Con A. The IL-4 gene expression seemed to be greater in PBMC obtained from highly atopic patients and was decreased in PBMC from individuals showing hypo-IgE immunoglobulinemia (less than 10 IU/ml). The results obtained in the present study may indicate that high and low IgE responder traits are determined depending on their levels of IL-4 mRNA expression.

Animals↗

[DNA typing of HLA].

Recent advance of molecular biology and genetic engineering has made a profound influence on clinical and laboratory medicine. In this article we will review present aspects of DNA typing of HLA-class II alleles. The HLA system is characterized by its highly genetic polymorphisms. HLA -class I (A, B, C) molecule consists of alpha 1, alpha 2, alpha 3, and beta 2-microglobulin domain, and HLA-class II (DR, DQ, DP) molecule consists of alpha 1, alpha 2, beta 1, and beta 2 domain. Differences of amino acid sequences determining polymorphisms of HLA-class II molecule are located mainly on the beta 1 domain, while alpha 1 chain of DQ molecule is also polymorphic. Polymerase chain reaction (PCR) has enabled us to make great progress in DNA typing of HLA, in place of RFLP (restriction fragment length polymorphisms) analysis. One of the most important and valuable advantages is to make us non-radioisotopic detection method available. There are several methods for the further analysis of products of PCR amplification; 1) dot-blot hybridization, 2) PCR-RFLP, 3) PCR-SSCP (single strand conformation polymorphism), 4) DGGE (denaturing gradient gel electrophoresis), 5) direct sequencing. As for dot-blot hybridization, there are also several methods for detecting hybridization; 1) radioactive detection with 32P - labelled probes, 2) colorimetric reaction and 3) chemiluminescent assay. Newly developed chemiluminescent assay yields as high sensitivity just as radioactive probes. HLA-D and -DP specificities have been typed cytologically by mixed lymphocyte culture (MLC) or primed lymphocyte test (PLT) method. Cytological typing will be replaced by PCR analysis in near future.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

Analysis of human leukocyte antigen HLA-DR beta amino acid sequence in Vogt-Koyanagi-Harada syndrome.

Vogt-Koyanagi-Harada syndrome (VKH) is a systemic disorder involving many organ systems, including the eye, the ear, the skin, and the meninges. One of the important clinical features of the disease is its strong association with histocompatibility antigens HLA-DR4 and HLA-Dw15. To investigate this association at the DNA level, the polymerase chain reaction technique was used. The DR beta 1 DNA sequence was analyzed to determine which part played the most significant role in the disease process. Although the number of patients studied was small, these data showed that these probes were useful in investigating the HLA-DR subtypes related to VKH. All but one patient (19 of 20) had a specific sequence encoding amino acids 70 and 71 of the HLA-DR beta 1 molecule. The data suggest that the sequence that encodes for amino acids 70 and 71 and adjacent ones of the HLA-DR beta 1 molecule could contribute to disease susceptibility.

Amino Acid Sequence↗

Functional expression of HLA-C blank antigens on human blood lymphocytes.

The surface expression of two HLA-C blank Ag (Cb-1 and Cb-2) on PBL was investigated with Cb-1- and Cb-2-specific CTL clones generated by the stimulation of the HLA-C blank Ag on transfected Hmy2CIR cells. The Cb-1- and Cb-2-specific CTL clones could lyse EBV-transformed B cells and PHA-induced T cells from which the HLA-C blank genes were derived. Furthermore, the reactivity of these CTL clones with PHA-induced T cells was blocked by HLA class I monomorphic mAb. These results demonstrated that the HLA-C blank Ag are expressed on the surfaces of PBL. Thus, despite the fact that the HLA-C blank Ag are expressed on normal PBL, they are incapable of generating corresponding alloantibodies. On the other hand, the present study demonstrated that these Ag on normal PBL are able to induce specific CTL and that the capacity of these Ag to induce allogeneic CTL is almost identical to that of HLA-B Ag, indicating that they may function as alloantigens in vivo and play a significant role in the rejection of organ grafts and in the graft-versus-host reaction in bone marrow transplantation.

B-Lymphocytes↗

Association of a particular amino acid sequence of the HLA-DR beta 1 chain with HTLV-I-associated myelopathy.

Analyses of HLA-DRB1 gene using polymerase chain reaction and sequence-specific oligonucleotide probes reveal that the amino acid sequence Glu-Gln-Arg-Arg-Ala-Ala-Val at positions 69-75 of the third hypervariable region (HVR) of HLA-DR beta 1 chain is significantly associated with HTLV-I-associated myelopathy (HAM). Since the frequency of this sequence in HTLV-I carriers is almost the same as that in controls from Kagoshima (an endemic area of HTLV-I), this sequence may be related to susceptibility to HAM rather than to susceptibility to HTLV-I infection. Since this third HVR functions as putative antigen-binding sites and T cell recognition sites, the amino acid sequence of positions 68-73 was analyzed in detail. The analysis reveals that Gln70 and Arg71 are relevant to the occurrence of HAM.

Alleles↗

Recombinant human erythropoietin corrects anemia of blood loss: a study in the dog.

In order to evaluate the possibility of using recombinant human erythropoietin (rhEpo) for the prevention and correction of anemia due to blood loss and as an adjuvant for autologous blood transfusion, its preventive and therapeutic effects were evaluated in beagles in which anemia was induced by repeated phlebotomies. Two hundred U/kg of rhEpo were administered i.v. four or nine times every two weeks for six weeks. Phlebotomies (25 ml/kg of body weight) were conducted three times at two-week intervals. rhEpo was found to successfully prevent and correct anemia caused by the phlebotomies. Concurrent administration of iron increased efficacy. The findings obtained in the present study suggest that rhEpo is useful both for the treatment of anemia caused by blood loss due to surgery and as an adjuvant therapy for pre-deposit autologous blood transfusion.

Anemia↗

Direct sequencing of a HLA-DRB gene by polymerase chain reaction: sequence variation in DRw8 specificity.

The nucleotide sequence of a HLA-DRB gene with a predominant subtype of DRw8 specificity in Japanese (DR8.1) was determined with single-stranded DNA enzymatically amplified by polymerase chain reaction (PCR). The sequence differs at a single amino acid from both of the published DRw8/Dw8.1 and DRw8/Dw8.2 sequences: isoleucine67(AUC) instead of phenylalanine67(TTC) in DRw8/Dw8.1 and serine57(AGC) instead of aspartic acid57(GAT) in DRw8/Dw8.2. On the other hand the DR8.1 and DRw8/Dw8.3 have the same amino acid sequence although one silent nucleotide substitution has occurred between the two sequences. These results indicate that Japanese DR8.1 specificity corresponds to DRw8/Dw8.3. Furthermore, an oligonucleotide probe specific for this sequence was synthesized and hybridized with 33 HLA-typed controls. This probe clearly distinguished the particular subtype from other DRw8 subtypes and specificities.

Amino Acid Sequence↗