Specific decrease in T3 antigen density in adult T-cell leukaemia cells: I. Flow microfluorometric analysis.
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Biomedical subjects
Publications and source records attributed to K Takatsuki.
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The genome of human T-cell leukemia virus (HTLV) was surveyed in fresh tumor cells of 163 patients with lymphoma and leukemia from the southwest part of Japan where adult T-cell leukemia (ATL) is endemic. Leukemic cells of all 88 cases of ATL tested so far were found to contain the provirus genome and also found to be monoclonal with respect to the integration site of provirus genome. In most cases of ATL, leukemic cells contained one or two copies of the complete HTLV provirus genome, and it was shown that the single species of HTLV with a fully determined sequence is typical in ATL. Some cases of T-cell malignancies, diagnosed as chronic lymphocytic leukemia or non-Hodgkin lymphoma, also had the provirus genome in their tumor cells, whereas some cases with the same diagnosis did not. No cases of other types of lymphoma or leukemia contained the provirus genome in their tumor cells. Monoclonal integration of the HTLV provirus genome in all primary tumor cells of ATL not only indicates that HTLV directly interacts with target cells, which become leukemic, and that integration of the provirus genome is a prerequisite for development of ATL and possibly other related diseases but also indicates that the virus is not associated with other types of lymphoma or leukemia.
A homologous radioimmunoassay specific for amino-terminal portion of human parathyroid hormone(PTH) was developed in order to study the clearance of biologically active species of the hormone in the circulation in man. Characterization of the assay system with synthetic analogues of human PTH (1-34) indicated that the carboxyl-terminal region of human PTH(1-34) is an important recognition site. Plasma amino-terminal PTH levels were less than 0.3 ng/ml in all of 35 normal subjects. The levels were elevated above 0.3 ng/ml in 15 of 24 patients with primary hyperparathyroidism. In 5 patients in whom the levels were determined before and after parathyroidectomy, the elevated levels were all normalized within 60 minutes after the removal of adenomata. The disappearance of exogenous human PTH(1-34) was studied after intravenous administration in 17 patients with hypoparathyroidism. A graphical analysis of the data disclosed two major components of the disappearance curve with estimated half-disappearance time of 3 and 28 minutes respectively, suggesting that multiple mechanisms are involved in the clearance of the peptide from the circulation. These results demonstrate usefulness of homologous radioimmunoassay for human PTH(1-34) in diagnosis and management of hyperparathyroidism, as well as in studying the clearance of amino-terminal portion of PTH which is known to represent biological activity.
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We screened serum samples from patients with various hematological disorders and healthy individuals for the presence of adult T-cell leukemia/lymphoma associated antigen (anti-ATLA) antibodies. These antibodies were detected not only in all patients with ATL but frequently in those diagnosed as T-cell malignant lymphoma or T-cell chronic lymphocytic leukemia; the positivity rate of anti-ATLA antibody was lower in B- and null-cell-type lymphoma, B-cell chronic lymphocytic leukemia, and multiple myeloma. Patients with aplastic anemia or acute leukemia who had received frequent and massive blood transfusions also possessed anti-ATLA antibodies. About 5.5% of the healthy individuals over 40 years of age in the endemic area (Kumamoto) were carriers. The rate of positivity gradually increased with age, and was higher in females than in males. In addition, the peripheral blood mono-nuclear cells and/or lymph node cells from patients with various hematological disorders, including ATL, were examined. The presence of human T-cell leukemia/lymphoma virus type I (HTLV-I) proviral DNA was confirmed in all patients with ATL and in some with T-cell-type malignant lymphomas. However, in HTLV-I carriers or other patients with hematological disorders without ATL, proviral DNA was not detected. In endemic areas, detection of proviral DNA is essential for the classification and diagnosis of T-cell malignancies.
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Adult T cell leukemia virus (HTLV or ATLV) proviral DNA integrated in the cellular DNA was examined by a modified Southern blotting method in the peripheral blood mononuclear cells and/or lymph node cells from 61 patients with adult T cell leukemia (ATL) and other hematologic diseases. Serum antibodies against ATL-associated antigens (ATLA) were also examined. The presence of human T cell leukemia virus (HTLV) proviral DNA was confirmed in all 20 patients with overt ATL and in 3 patients with T cell malignant lymphoma, who were seropositive but did not show clinical features characteristic of prototypic ATL. However, it was not detected in 6 antibody-positive healthy individuals and 8 seropositive patients with various hematologic disorders. Thus, the detection of proviral DNA by the method described here seems to be useful for the diagnosis of ATL in the endemic area and may provide a powerful tool for the classification of T cell malignancies.
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Adult T-cell leukemia-associated antigen (ATLA) and adult T-cell leukemia virus (ATLV) antigens were localized in the MT-2 cell system by the immunocolloidal gold method using 71 human sera having various anti-ATLA titers and rabbit anti-ATLV antisera. In the thin-section method with anti-ATLA-positive human sera and rabbit antisera, protein A-gold particles were preferentially observed on and around sectioned adult T-cell leukemia (ATL) virions located in pericellular aggregates and within the cytoplasmic vacuoles but nowhere else in a significant number. The number of gold particles per ATL virion was statistically well correlated with the anti-ATLA titers of human sera applied (p less than 0.005). The preembedding method showed that pericellular ATL virions were specifically tagged with protein A-gold, but the antigens in question were not expressed on the plasma membrane of MT-2 cells. The absence of ATLA and ATLV antigens on the plasma membrane constitutes a unique pathobiological feature of ATL and ATLV as compared with other retrovirus systems.
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This study was conducted as a multicenter trial in 12 institutions in the Kyushu region of Japan. The clinical effects of cefoperazone were evaluated in 101 patients with 112 infections complicated by hematological disease. In about half of the patients, the baseline neutrophil count was below 1,000/mm3. Results were excellent in 23 of 101 cases and good in 48, with an efficacy rate of 70.3%. Cefoperazone alone or in combination with other antibiotics was effective in 60.7% of patients who had not responded to previous antibiotic therapy. No serious side effects attributable to cefoperazone were noted. The results indicate that cefoperazone is a useful antibiotic for the treatment of severe infections in patients with hematological diseases.