Biomedical subjects
Publications and source records attributed to K Takabayashi.
An IgM antibody cytotoxic to normal human lymphocytes was found in 46.2% (male: 61.5%; female: 30.8%) of sera from chronic schizophrenics by means of a complement-dependent cytotoxicity test. The relationship between this antibody and the immunological manifestations of schizophrenia is discussed.
A 43-year-old man with pancytopenia and circulating blast cells was found to have acute megakaryoblastic leukemia. Bone marrow biopsy disclosed reticulin fibrosis with infiltration of blast cells. Cytogenic study showed 48,XY,+15,+18. The megakaryocytic origin of blast cells was confirmed by platelet peroxidase reaction at ultrastructural level. The spleen which had not been felt on admission increased in size rapidly and ruptured abruptly. This appears to be the first reported case of a splenic rupture associated with acute megakaryoblastic leukemia.
We analyzed the surface phenotypes of infiltrated cells in pancreases of nonobese diabetic (NOD) mice with monoclonal antibodies to mouse lymphocytes. Most of the infiltrated cells were Thy1+ and Ly1+ T-lymphocytes, and most of them were L3T4+ helper T-lymphocyte subsets. To elucidate the role of L3T4+ T-lymphocytes in the development of insulitis and diabetes in NOD mice, we treated the animals with injections of monoclonal anti-L3T4 antibody. Administration of this antibody prevented the insulitis and diabetes in NOD mice. These results lead to conclusions that the L3T4+ helper T-lymphocytes may play an essential role in the pathogenesis of type I diabetes and that the manipulation of the OKT4+ (Leu3+) T-lymphocyte subset, the human homology of L3T4, with monoclonal antibodies may provide effective therapy for human type I diabetes.
IgG antilymphocyte antibodies preferentially reacting with phytohemagglutinin (PHA) activated peripheral blood lymphocytes (PBL) and an adult T cell leukemia cell line were detected in 70.6% sera from patients with systemic lupus erythematosus (SLE), using a fluorescence activated cell sorter (FACS). In the sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, 2 major peaks with an apparent molecular weight 60,000 to 65,000 Da and about 40,000 Da were observed in the membrane glycoprotein fractions of both PHA activated PBL and an adult T cell leukemia cell line. From the result of sequential coprecipitation analysis of SDS-PAGE between SLE serum, antiinterleukin-2 (IL-2) receptor antibody (anti-Tac antibody) and anti-Ia antibody, the reactive antigen on the activated PBL and an adult T cell leukemia cell line proved to be an identical molecule of the IL-2 receptor on these cells. The role of this autoantibody in the modulation of T cell mediated immunity in patients with SLE is discussed.
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FAS1, the structural gene of the pentafunctional fatty acid synthetase subunit beta in Saccharomyces cerevisiae has been sequenced. Its reading frame represents an intron-free nucleotide sequence of 5,535 base pairs, corresponding to a protein of 1,845 amino acids with a molecular weight of 205,130 daltons. In addition to the coding sequence, 1,468 base pairs of its 5'-flanking region were determined. S1 nuclease mapping revealed two transcriptional initiation sites; 5 and 36 base pairs upstream of the translational start codon. Within the flanking sequences two TATATAAA boxes, several A-rich and T-rich blocks and a TAG...TATGTT...TATGTT...TTT sequence were found and are discussed as transcriptional initiation and termination signals, respectively. The order of catalytic domains in the cluster gene was established by complementation of defined fas1 mutants with overlapping FAS1 subclones. Acetyl transferase (amino acids 1-468) is located proximal to the N-terminus of subunit beta, followed by the enoyl reductase (amino acids 480-858), the dehydratase (amino acids 1,134-1,615) and the malonyl/palmityl transferase (amino acids 1,616-1,845) domains. One major inter-domain region of about 276 amino acids with so far unknown function was found between the enoyl reductase and dehydratase domains. The substrate-binding serine residues of acetyl, malonyl and palmityl transferases were identified within the corresponding domains. Significant sequence homologies exist between the acyl transferase active sites of yeast and animal fatty acid synthetases. Similarly, a putative sequence of the enoyl reductase active site was identified.
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It has been anticipated that type C oncornaviruses, which participate in the pathogenesis of murine systemic lupus erythematosus (SLE), would be found to have a role in the development of SLE in humans. In studies of tissues from SLE patients, type C-related proteins have been identified. Using information obtained on the recent isolation of the human T cell leukemia virus (HTLV), together with that from studies of murine SLE, we attempted to clarify the role of antibodies to HTLV in the pathogenesis of human SLE. Using a solid-phase enzyme-linked immunosorbent assay and sodium dodecyl sulfate-polyacrylamide gel electrophoretic techniques, we were unable to find evidence of the participation of antibodies to HTLV proteins in the development of human SLE.
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A specific surface change of mouse thymocytes induced by treatment with anti-Thy-1 antibody was ultrastructurally demonstrated by a rapid-freezing and deep-etching technique. Round elevations, 30 nm in diameter, were found on the exoplasmic surface (ES) face of the cell membrane of BALB/c mouse thymocytes (expressing Thy-1.2 on the cell surface) after treatment with non-labelled monoclonal anti-Thy-1.2 antibody, whereas the ES face without the treatment gave a smooth appearance. Immunological studies indicated that the elevation was induced by the specific antigen-antibody reaction. Further, the elevation was demonstrated to be located at the site of antigen-antibody reaction by the results of the protein A-gold test. It was also supported by the fact that the elevations showed cluster formations under capping conditions. Accordingly, the elevations were assumed to be antibody molecules or antigen-antibody complexes.
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Albumin with and without a free sulfhydryl group (mercapt-albumin and nonmercapt-albumin) has low and high amounts of fatty acids, respectively. It was found that this difference was brought about by the following two mechanisms: (a) the binding of fatty acids increases the rate of oxidation of the sulfhydryl group, (b) the oxidation of the sulfhydryl group of the protein enhances the binding of fatty acids. The incubation of the protein with fatty acids enhanced reversibly the reaction rate of the free sulfhydryl group with 5,5'-dithiobis(2-nitrobenzoic acid). This effect of fatty acids depends on the kind of fatty acid added. Among saturated long-chain fatty acids tested, the shortest fatty acid, lauric (dodecanoic) acid, had the strongest effect. Oleic (cis-9-octadecenoic) acid, which has a long chain but also one cis-double bond, however, was as effective as lauric acid in enhancing the reactivity of the sulfhydryl group on the protein. Analyses with palmityl-Sepharose and equilibrium partitioning of palmitic acid between heptane and aqueous protein solutions have shown that nonmercapt-albumin has higher affinity to the fatty acid than mercapt-albumin. These results imply that the binding of fatty acids and the oxidation of sulfhydryl groups of the protein are intimately coupled.
A nephelometric method is described for determination of plasminogen and two types of plasmin inhibitors in human plasma having different affinity toward plasmin. This method is based on the kinetic analysis of effects of whole plasma and plasmin inhibitor fraction obtained from plasma on the activity of exogenously added plasminogen which was determined by measuring the decrease of light scattering of fibrin suspension. With this method we have determined the activity of plasminogen and two types of inhibitors in the plasma of normal subjects and patients with high fibrinogen degradation product values. They include patients with various malignant tumors with DIC, chronic renal failure, sepsis, vascular diseases, and liver cirrhosis with hepatoma.
The I-J and antigen-binding chains with constant region determinant (Ct) that compose an antigen-specific suppressor T cell factor were found on the surface of suppressor T cell hybridomas, serologically and morphologically demonstrated by a fluorescence-activated cell sorter (FACS) and immunoelectron microscopic analyses. Moreover, the surface expression of the I-J and Ct-bearing chains fluctuating with the same kinetics depended entirely upon the cell cycle. The maximum expression of these two chains was observed in the early stage of the M phase, and the minimum in the S phase. Similarly, the magnitude of the suppressor activity was maximal in the late stage of the M phase, and was minimal in the S phase. The results therefore demonstrated that there exists good correlation between the cell surface expression of the I-J and Ct-bearing chains and the magnitude of the suppressor activity produced. The antigen recognition units on suppressor T cell hybridomas have serologically and morphologically been characterized by using radiolabeled antigens or monoclonal antibodies against the I-J or Ct on the antigen-binding molecule. Cell-binding assay and radioautographic analysis demonstrated that the suppressor T cell hybridoma possesses the capacity to bind native antigen in an antigen-specific fashion as does the hybridoma-derived, antigen-specific suppressor factor composed of the I-J and the Ct-bearing chains, indicating that the recognition unit on the cell surface is composed of a structure similar to the factor.
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In two children with hepatoblastoma, response to chemotherapy permitted subsequent surgical resection. Initially, in both patients, the tumor was thought to be unresectable because of size and/or extent. Chemotherapy with vincristine sulfate and cyclophosphamide resulted in substantial reduction in tumor size, and laparotomy for excision was performed after nine months and four months of therapy, respectively. In case 1, the tumor was localized in the right hepatic lobe and the right hepatic lobectomy was performed. In case 2, the tumor was located in both right and left lobes, but was encapsulated and it was possible to enucleate the tumor with complete gross excision. Both children are living and well without evidence of recurrence of tumor 11 and 23 months after operation.
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