Immunohistological study on the graft following all O- and xenotransplantation in recipients with preformed antibody.
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Biomedical subjects
Publications and source records attributed to Y Tomonaga.
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Isolation of cell lines that display various degrees of transformed phenotypes may be very useful to clarify multistep mechanisms of oncogenesis, but malignant transformation of human diploid fibroblasts in culture is a very rare event. We attempted to isolate variously transformed cell lines from human diploid fibroblasts (RB) of a patient with hereditary retinoblastoma. The RB cells exhibited normal karyotypes with the exception of one copy of chromosome 13, which contained a large deletion at the q14-22 region, where the RB1 gene is located. By transfection with SV40 early genes and repeated passage, we succeeded in obtaining SV40-transfected mortal, immortalized, anchorage-independent, and tumorigenic RB cell lines. DNA fingerprinting showed that these cell lines were not contaminants, but derivatives of the original RB cells. The remaining RB1 allele may be wild-type even in the malignant cell lines, because the expression and the LT-binding ability were normal. Furthermore, we did not find any homozygous loss in 16 polymorphic markers located in the 13q14-22 region in the transformed cell lines. However, introduction of a copy of a normal chromosome 13 into the anchorage-independent cell line suppressed its anchorage-independent growth ability. All these data, together with the fact that the RB cells containing the deletion progressed to a tumorigenic state spontaneously, but normal fibroblasts did not, raise the possibility that a new tumor suppressor gene, located at 13q14-22, may play a critical role in neoplastic transformation. We conclude that these RB cell lines provide an excellent system for identification of genes involved in malignant transformation of human cells. Genes Chromosomes Cancer 26:47-53, 1999.
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The chromosomes of leukemic blood cells in eight Japanese patients with acute adult T-cell leukemia (ATL) were examined by a direct method or short-term culture method without any mitogens. Six patients showed a chromosome 14 anomaly with a break at band q11-13: inv(14)(q11q32) in two patients, t(11;14)(p13;q13) in one patient, t(14;14)(q11;q32) in addition to del(14)(q11q13) in another, and only del(14)(q11q13) in two patients. Thus, a proximal 14q rearrangement exists in ATL as in other types of T-cell malignancies. Based on these facts, the pathogenesis of ATL is discussed in reference to the literature.
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A case of adult T-cell leukemia (ATL) with an unusual phenotype is presented. Leukemia cells of this patient reacted with anti-Leu-2a monoclonal antibody, although most of ATL cases are reported to show the phenotype of helper/inducer T-cell. It is indicated that the surface phenotype of ATL is rather heterogeneous.
We report phenotypic and functional characterization of lymph node cells from 27 patients with T lymphoma from the Nagasaki district of Japan. Nagasaki is one of several areas where adult T-cell leukemia is endemic, and sera from 18 of 23 patients examined (78.3%) were positive for antibody to adult T-cell leukemia-associated antigen. The majority of cases (24 of 27) showed the Leu-2a-, 3a+, MASO36c- phenotype similar to adult T-cell leukemia, but seemed to be subdivided into four groups according to the presence or absence of Leu-1 antigen and the receptor for sheep erythrocytes (SRBC). Eleven cases had both Leu-1 antigen and the receptor for SRBC (E-RFC+, Leu-1+, 2a-, 3a+), but 6 cases lacked Leu-1 antigen (E-RFC+, Leu-1-, 2a-, 3a+), 4 cases lacked receptors for SRBC (E-RFC-, Leu-1+, 2a-, 3a+), and 3 cases lacked both of these markers (E-RFC-, Leu-1-, 2a-, 3a+). The effects of lymph node T cells on pokeweed mitogen (PWM)-induced normal B-cell differentiation was studied in 10 cases. Lymph node T cells of 5 cases showed helper activity without any suppressor activity, and 2 cases showed suppressor activity with almost no detectable helper activity, similar to adult T-cell leukemia cells. Two other cases lacked particular functional effects. These results suggest the possibility that Leu-3a+ T-cell lymphoma may be functionally subdivided into at least two types, a helper type and a suppressor (adult T-cell leukemia) type.
The gene for erythrocyte glutathione reductase (E-GR) activity has been assigned to chromosome #8. In the present series, we examined the E-GR activity in 14 cases with chronic myelodysplastic syndrome (CMS, preleukemia), atypical acute myelogenous leukemia (AML), or chronic myelogenous leukemia (CML), with and without acquired trisomy #8. No difference in the incidence of high levels of this enzyme was found between two groups, i.e., those with and without trisomy #8 suggesting the existence of a complex regulatory system in addition to chromosome #8.
Serial haematopathological and cytogenetic studies disclosed three distinct clinical phase in a case of refractory anaemia (RA), a subtype of myelodysplastic syndrome (MDS; FAB group, 1982): first, chronic MDS phase (1 year 10 months) with karyotypic abnormality (45, XY, --7) (Clone I); second, hypo-aplastic phase concurrent with first clonal evolution (45, XY, --7, 12p--) (Clone II); third, acute myelomonocytic leukaemia phase (6 months) with second clonal evolution (45, XY, --7,t (1q --; Bq+), Bq --, 12p --) (Clone III). In the second phase the bone marrow became almost aplastic as Clone II expanded progressively, indicating simultaneous occurrence in Clone II stem cells of growth advantage for self-renewal function over Clone I and normal stem cells, and arrest of differentiation. These observations support the hypothesis that leukaemic change in MDS, at least in RA, occurs by stepwise clonal evolution(s), not by progressive arrest of differentiation in original MDS clone.
An enzyme immunoassay for polyamines is described which uses beta-galactosidase labeled spermine and antiserum raised in rabbits against spermine-bovine serum albumin synthesized by coupling spermine to mercaptosuccinylated bovine serum albumin with a bifunctional cross-linker, N-(gamma-maleimidobutyryloxy)-succinimide. The lower limit of detection by this assay, which involves a double antibody technique for the separation of antibody-bound and free antigen, was 1 ng of spermine per tube. The anti-spermine serum showed 88% cross-reaction with spermidine but only 0.13% with putrescine, 0.08% with 1,3-diaminopropane, and 0.04% with cadaverine. The method has been used to measure serum polyamine levels in healthy subjects and cancer patients, in whom mean concentrations of 58.1 ng/ml and 94.8 ng/ml (as spermine), were respectively noted. This enzyme immunoassay is specific, accurate and easy to perform, and appears suitable for routine clinical use.
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Described here is an autopsy case of a 30-year-old woman with systemic hemangiomatosis accompanied by coagulopathy and microangiopathic hemolytic anemia. She had hepato-splenomegaly, anemia, thrombocytopenia, prolonged prothrombin time and partial thromboplastin time, and fibrinogenopenia. A splenectomy was performed and a diffuse angioma of the spleen was found. Postmortem examination revealed cavernous hemangiomas and hemangioendotheliomatous lesions in the liver, bone marrow, intestine, and lymph nodes. Coagulation studies suggested that exacerbation of coagulopathy occurred due to Liniac (10MV X-ray) irradiation. Our observation raised the possibility that the irradiation might lead to chronic localized consumption coagulopathy, which was confined to the hemangioma, to acute disseminated types of intravascular coagulation.
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