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Biomedical subjects

F Maruyama

Publications and source records attributed to F Maruyama.

At least 55 records · Page 3Linked to original sources

[Rearrangement of immunoglobulin light chain and heavy chain constant region genes in multiple myeloma].

We analysed immunoglobulin (Ig) gene rearrangements in 28 patients with multiple myeloma by Southern hybridization method. We used 5 probes which cover C kappa and kappa de loci of Ig light chain kappa gene, and JH, 5'S mu and S gamma 3 loci of Ig heavy chain gene. In 11 out of 12 patients with kappa-producing myeloma, DNA rearrangements were observed using C kappa probe. Among them, kappa de region was rearranged in 7 patients and kept germline configuration in 4 patients. In all of 14 patients with lambda-producing myeloma, C kappa region was deleted and kappa de region was rearranged. 5'S mu-probe was very useful for detecting class switch recombination, and furthermore by using S gamma-probe together, S mu-S gamma joining could be detected. In all of 10 patients with gamma-producing myeloma, 5'S mu and S gamma-probes detected the rearranged band of the same size on at least 1 allele, which suggested the presence of S mu-S gamma joinings. In 8 of 10 patients with Bence-Jones myeloma, 5'S mu-probe detected rearranged bands and the presence of class switch recombinations were suggested as observed in other Ig secretory myelomas. In other 2 patients with Bence-Jones myeloma, non-functional class switch recombinations were detected. The results of this study indicated that genotypes corresponded well to phenotypes in multiple myeloma, and further analysis in other types of B cell malignancies will be interesting.

Gene Rearrangement, B-Lymphocyte, Heavy Chain↗

Mixed lymphocyte-autologous tumor cell reaction in hematological malignancies--effect of interferon-beta and correlation with the expression of MHC class I antigen on tumor cells.

The mixed lymphocyte-autologous tumor cell reaction (MLTR) was performed in 15 patients with hematological malignancies. Lymphocyte proliferative response and generation of cytotoxic cells against autologous tumor cells were evaluated and as was the effect of interferon-beta (IFN-beta) (750 IU/ml). Lymphocytes from patients during complete remission had sufficient functions in mixed lymphocyte culture with normal lymphocytes. Tumor cells stimulated allogeneic lymphocytes, although to a generally lesser extent as compared with remission lymphocytes from the same patients. Increased [3H]TdR uptake was observed in 5 patients and was suppressed by the addition of IFN-beta. Autologous tumor cell kill activity was induced by MLTR in 3 patients; IFN-beta-enhanced killing activity was present in these patients as well as in 3 other patients. Tumor cells from the 3 patients with positive autologous tumor cell kill activity had almost the same stimulating capacity as lymphocytes. The expression of MHC class I antigen and IFN-beta-enhanced expression was observed in all tumor cells studied by indirect immunofluorescence. These data suggest that some factors on tumor cells, in addition to MHC class I antigen, participate in the generation of cytotoxic cells against autologous tumor cells and its enhancement by IFN-beta.

Cytotoxicity, Immunologic↗

[Alternating non-cross resistant multi-drug chemotherapy against malignant lymphoma (CAMBO-VIP)--consideration of the dose intensity].

Dose intensity defined as the amount of drug used per unit time, expressed as mg/m2/week, was reported to be a significant determinant of antitumor activity of single or combined drugs in cancer chemotherapy. We formulated a 12 week high dose intensity chemotherapy (CAMBO-VIP) for the treatment of advanced non Hodgkin's lymphoma with aggressive histology. The treatment consists of weekly alternate administration of myelosuppressive and non-myelosuppressive agents. Doxorubicin was administered every other week in combination with either cyclophosphamide, etoposide or ifosfamide. On the weeks in between, non-myelosuppressive vincristine was given with either methotrexate with leucovorin rescue or bleomycin. Prednisolone was given for the first and the last 4 weeks. Dose reduction and treatment delay were kept minimal for the purpose not lowering dose intensity. As of February 1990, 32 patients (pts), median age 52, entered the study, 29 of whom completed the treatment. There were 3 incomplete cases, in which 2 were due to interruption of the treatment at 5 and 6 weeks, respectively and 1 due to a half dose given because of the old age. CR was obtained in 29 pts (90.6%). Relapse occurred in 3 (10.4%) with the median follow-up of 12 months. Two year disease-free survival (DFS) was estimated to be 76.0% for all the patients and 83.9% for CR patients. Toxicity of CAMBO-VIP was moderate with no chemotherapeutic death. Myelosuppression was severe but of short duration, requiring virtually no dose reduction. Treatment delay was 3 days, median, and maximally 28 days. The average actual dose intensity calculated from given amount of drugs and treatment duration was as high as 90% of the protocol dose intensity. Dose intensity of CAMBO-VIP protocol is highest, equaling to that of MACOP-B, among representative series of reported lymphoma protocols. A highly significant correlation was observed between 9 drug relative dose intensity and DFS of the patients treated with each protocol. Significance of dose intensity as an independent prognostic factor, however, should be determined, by a prospective carefully designed stratified randomized studies.

Aged↗

T-cell malignancy following B-cell lymphoma in remission.

A T-cell malignancy developed in a 64-year-old man with recurrent B-cell lymphoma after one and a half years of remission. Immunophenotypic and DNA analyses confirmed clonality and cell lineage of both lymphoid malignancies. Sequential development of B- and T-cell malignancies in this patient may be an example of biclonal lymphoma or treatment-related secondary lymphoma. However, another possibility would be the existence of a transformed lymphoid stem cell that underwent intraclonal conversion from B- to T-cell lines.

Antibodies, Viral↗

[Clinicopathologic analyses of eleven patients with Hodgkin's disease].

Clinicopathologic analyses were performed on 11 patients with histopathologic diagnosis of Hodgkin's disease which was confirmed immunohistochemically with the use of anti-Leu M 1 which is known to be specific to Reed-Sternberg cells. Patients with clinical stage II developed infradiaphragmatic involvement after Mantle field irradiation and should have been treated with extended field irradiation or combined modality therapy because of the possibility of PSIII1. Maintenance VENP therapy seemed to sustain remission but may have caused opportunistic infections. There were no rearrangements in either immunoglobulin or T cell receptor genes studied in two patients.

Adolescent↗

[Lymphocyte cytotoxicity against autologous tumor cells and the effect of interferon-beta on their activities. (2) Evaluation of large granular lymphocytes (LGL)].

Large granular lymphocytes (LGL) were obtained by Percoll density gradient centrifugation of peripheral mononuclear cells from 15 patients with hematological malignancies (10 acute leukemias and 5 non-Hodgkin's lymphomas). Five-hour 51Cr-release cytotoxic assay by LGL was performed against frozen autologous tumor cells in these patients. Mean percentage cytotoxicity by LGL was 5.6%, and this was enhanced to 15.0% by the addition of IFN-beta to the culture medium. A decrease of cytotoxicity was observed when LGL was treated with anti-Leu 11b antibody plus complement, or when LGL was pretreated with the unlabelled K562 as a competitive inhibition assay. The addition of monocytes also induced a decrease of cytotoxicity, suggesting that monocytes may act as a suppressive agent in autologous tumor cell killing by LGL.

Antigens, Differentiation, T-Lymphocyte↗

[Lymphocyte cytotoxicity against autologous tumor cells and the effect of interferon-beta on their activities. (1) Evaluation by modification of target tumor cells].

IFN is known to enhance NK activity against cultured cell lines such as K562, but not against frozen autologous tumor cells. In order to obtain increased NK cytotoxicity using IFN-beta, various modifications were performed on autologous tumor cells. IFN-beta induced more enhanced NK cytotoxicity of normal lymphocytes when frozen tumor target cells were cultured for 4-5 days in the medium, or when these cells were treated with Vibrio cholerae neuraminidase (VCN). However, in an autologous setting, IFN-beta did not enhance NK cytotoxicity against either cultured autologous tumor cells or VCN-treated tumor cells. Also, IFN-beta did not enhance cytotoxic T cell activity against autologous tumor cells induced by mixed lymphocyte-tumor cell culture, although IFN-beta was able to induce enhancement of allospecific cytotoxic T cells mediated by mixed lymphocyte culture.

Cells, Cultured↗