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Biomedical subjects

M Shimoyama

Publications and source records attributed to M Shimoyama.

At least 199 records · Page 11Linked to original sources
PubMed1988

ADP-ribosylation of bradykinin and effects on its biological activities.

We investigated the ADP-ribosylation of bradykinin by hen liver nuclear ADP-ribosyltransferase. Two Arg residues of the peptide were modified by this enzyme. Arg1 was preferentially modified as compared to Arg9; the Vmax/Km for Arg1 was 3 times higher than that for Arg9. These results were given support by data observed in experiments with des-Arg1 and des-Arg9 bradykinin; the Vmax/Km for des-Arg9 bradykinin was 3 times that for des-Arg1 bradykinin. ADP-ribosylation suppressed the biological activity of bradykinin, as related to both binding and contractile activities. The extent of ADP-ribosylation-induced suppression of both activities was higher in the case of the modification of Arg1 than that of Arg9. In view of the observation of ADP-ribosyltransferase activity in skeletal, cardiac, and smooth muscles (Soman, G. et al. (1984) Biochem. Biophys. Res. Commun. 120, 973-980; Shimoyama, M. et al. (1987) in The 8th International Symposium on ADP-Ribosylation, Texas, abstract p. 13), bradykinin functioning in the contraction of smooth muscle may be modified in this way in vivo.

ADP Ribose Transferases↗
PubMed1988

A soluble-factor(s) secreted by a human skin cancer cell line supports clonal growth of adult T-cell leukemia cells.

Leukemic cells from four out of eight patients with adult T-cell leukemia (ATL) were successfully grown by cocultivation with HSC-I cells, a human skin cancer cell line, in the presence of interleukin-2. Three of these four cultures of growing cells showed rearrangement of the T-cell receptor beta-chain gene like the original leukemic cells in vivo, and also showed conservation of the patterns of HTLV-I integration of the original leukemic cells in vivo. Cell-to-cell contact between HSC-I cells and leukemic cells was not necessary for growth of the leukemic cells. The results indicate that some soluble growth factor secreted by HSC-I cells and interleukin-2 are required for the in vitro growth of leukemic cells from some patients with adult T-cell leukemia.

Adult↗
PubMed1988

Non-Hodgkin lymphoma of the skin excluding mycosis fungoides and cutaneous involvement of adult T-cell leukemia/lymphoma.

Forty-nine cases of cutaneous malignant lymphoma were reviewed in order to analyze the clinicopathological features of these neoplasms. Excluding 13 cases of mycosis fungoides and 4 cases of cutaneous involvement of proven adult T-cell lymphoma/leukemia, the remaining 32 cases were further classified according to their pathological and clinical features. There were 12 primary cutaneous lymphomas, 15 cases of secondary cutaneous involvement of systemic lymphoma, and 5 cases of concurrent skin and lymph node involvement. Histologically, large cell lymphoma predominated in both primary and secondary cutaneous lymphomas. Immunohistochemical study using monoclonal antibodies reactive with B- and T-cells in paraffin sections revealed the cellular lineage in 30 cases. Nineteen cases were of T-cell origin and 11 cases were of B-cell derivation. The prognosis of these patients was rather poor; 25 patients died within 5 years. The predominance of T-cell lymphoma contrasts with a higher frequency of cutaneous B-cell lymphoma in Western countries. As the clinicopathological features of cutaneous lymphomas are diverse, it is suggested that cutaneous lymphomas should be classified and studied in a similar way to their nodal counterparts.

Adolescent↗
PubMed1988

Chemotherapeutic results and prognostic factors of patients with advanced non-Hodgkin's lymphoma treated with VEPA or VEPA-M.

One hundred sixty-three patients with advanced non-Hodgkin's lymphoma including adult T cell leukemia/lymphoma (ATL) were treated from 1981 to 1983 with VEPA (vincristine, cyclophosphamide, prednisolone, and doxorubicin) or VEPA-M (VEPA plus methotrexate) in randomized fashion after stratification by surface marker. The complete response (CR) rate and the 4-year survival rate of patients treated with VEPA-M was 62.2% and 36.9%, respectively, while for those treated with VEPA the rates were 51.9% and 26.6, respectively. The difference was not statistically significant, but pretreatment characteristics predictive for response and survival were interesting. Three factors, leukemic change, poor performance status (PS), and T cell marker, were negatively associated with both CR and survival rates, and high-grade pathology was adversely associated with survival rate in a multivariate analysis. These prognostic factors are somewhat different from those in Western lymphomas. This may be reflection of major differences in patients' characteristics between Japanese and Western lymphomas: in this study, there was a high incidence of T cell lymphoma/leukemia (50%) including ATL (33%), leukemic manifestation (34%), poor PS (34%), and a low incidence of follicular lymphoma (9%). The statistically significant three factors for both CR and survival rates were used to construct a model containing eight categories of patients at increasing risk for poor response and shortened survival. These categories were divided into four groups, with respective CR and 4-year survival rates of 91% and 73%, 67% and 35%, 27% and 7%, and 10% and 5%. Ninety-three patients in whom CR was induced by VEPA or VEPA-M therapy were evaluated for prognostic factors predictive for disease-free survival. A shorter period (less than 28 days) required to achieve CR, a clinical diagnosis of ATL, and a lower hemoglobin level were found to affect disease-free survival adversely. These results have important implications for both the design of prospective randomized therapeutic trials and the determination of optimal therapy for individual patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Major prognostic factors of adult patients with advanced T-cell lymphoma/leukemia.

Eighty-one adult patients with advanced T-cell lymphoma/leukemia including 54 with adult T-cell leukemia/lymphoma (ATL), who were treated between 1981 and 1983 with vincristine, cyclophosphamide, prednisolone, and doxorubicin (VEPA) or VEPA plus methotrexate (VEPA-M) in randomized fashion, were evaluated for pretreatment characteristics. The overall complete response (CR) and the 4-year survival rates were 39.5% and 19.4%, respectively, and 69% of 32 CR patients had relapses, indicating the need for development of new effective regimens for the disease. In a multiple logistic regression analysis, only three factors, leukemic manifestation, poor performance status (PS), and a high lactate dehydrogenase (LDH) level, were significantly associated with the poor response rate. In a Cox proportional hazards model analysis, shortened survival was again significantly associated with poor PS and a high LDH level, but not with a clinical diagnosis of ATL. The two factors, PS and LDH level, that were found to be significantly associated with both CR and survival rates, were used to construct a model containing six categories of patients at increasing risk for poor response and shortened survival. These categories divided the patients into three groups with respective CR and 4-year survival rates of 75% and 53% for low-risk, 45% and 15% for moderate-risk, and 15% and 0% for high-risk. The results indicate that PS and LDH levels were the most important in predicting the response and survival of an adult patient with advanced T-cell lymphoma/leukemia. The prognosis of patients with usual peripheral T-cell lymphoma, excluding ATL, was comparable with that of advanced B-cell lymphoma. These results have important implications for the design of new prospective therapeutic trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

[Detection of multidrug resistant phenotype in leukemia and lymphoma by monoclonal antibodies].

Two monoclonal antibodies, MRK16 and MRK20 that recognize P-glycoprotein and P-85 kd protein on the surface of adriamycin (ADM) resistant cells, respectively, were tested for the reactivity with 40 cultured leukemia/lymphoma cell lines. F(ab')2 form is essential to avoid false reaction through Fc gamma-R. Drug sensitivity of 19 representative cell lines were also examined in vitro. From this study, it was found that these cell lines were classified into 4 groups. Group 1 (4 cell lines) was insensitive to ADM, mitoxantron (MXT), etoposide (VP-16) and vincristine (VCR), and reactive to MRK16 and MRL20. Group II (1 cell line) was insensitive to the 4 drugs, but not reactive to both antibodies. Group III (3 cell lines) was insensitive to ADM, MXT and VP-16, but sensitive to VCR, and reactive to MRK20, but not to MRK16. Group IV (all other cell lines) was sensitive to these drugs, and not reactive to both antibodies. From these results, MRK16 detects P-glycoprotein-associated multidrug resistance (MDR), while MRK20 does P 85-kd-associated another type MDR (cross resistance to ADM, MXT and VP-16, but not to VCR). MRK20 reacted with monocytes, but MRK16 did not with any WBC type. One hundred and ninety eight clinical samples obtained from blood cancer were tested for the reactivity with MRK16. MRK16 did not react with any of 98 samples obtained before treatment, but did with 9 of 100 obtained at relapse or refractory stage after chemotherapy. The results indicate that MRK16 is useful to detect drug resistance phenotype of leukemia and lymphoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1988

[Recent progress in non-Hodgkin's lymphoma study in Japan].

Great progress has been made in clinical research on non-Hodgkin's lymphoma during the last 15 years. Surface marker and DNA analyses of immunoglobulin and T-cell receptor genes are essential for new classification of the disease according to the cellular origin of tumor cells. This approach resulted in the establishment of new disease entities such as adult T-cell leukemia/lymphoma(ATL), immunoblastic lymphoadenopathy (IBL)-like T-cell lymphoma, and the pleural B-lymphoma occurring in long-standing pyothorax. New retrovirus, HTLV-I, was found during studies on ATL. Prevention of HTLV-I infection is an important project. HTLV-I negative ATL was also found and is of particular interest in understanding leukemogenesis of ATL. An oncogen such as bcl-2 is important for characterization of follicular lymphoma. Prognostic factors of patients with T-lymphoma are completely different from those of B-lymphoma. Risk grouping by combination of major prognostic factors is useful for the selection of the best treatment modality and the accurate estimation of prognosis of patients at initial presentation. The effect of combination chemotherapy should be evaluated separately between T- and B-lymphomas because of the difference in response rate and prognostic factors.

B-Lymphocytes↗
PubMed1988

Clinicopathologic, immunophenotypic, and immunogenotypic analyses of immunoblastic lymphadenopathy-like T-cell lymphoma.

Immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma is a distinct peripheral T-cell lymphoma, which closely resembles angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) and/or IBL, but is characterized by focal or sheet-like proliferation of immunoblasts and pale cells of T-cell nature. In this report, 36 patients with IBL-like T-cell lymphoma were analyzed. The disease is clinically characterized by generalized lymph node swelling, hepatosplenomegaly, fever, skin rash, polyclonal hypergammaglobulinemia, marked male predominance, predilection for the elderly, and poor prognosis. There was no association with human T-cell leukemia virus type I or human immunodeficiency virus. IBL-like T-cell lymphoma may be divided into two categories (CD4+ type and CD8+ type) by surface marker analysis. It can also be divided into three categories on the basis of the histologic findings of distribution of morphologically recognizable tumor cells: nine cases of "inconspicuous type," six cases of "patchy type," and 21 cases of "diffuse type." Two cases of "inconspicuous type" converted later to "diffuse type." DNA hybridization analyses in the ten recent cases revealed that three of four "inconspicuous types" and five of six "diffuse types" showed clonal rearrangement of T-cell receptor-beta chain gene without rearrangement of immunoglobulin heavy chain gene, providing strong evidence for clonal proliferation of T cells.

Adult↗
PubMed1988

Molecular genetic and immunohistochemical analyses of a case of multicentric Castleman's disease.

Whether Castleman's disease is primarily hyperplastic or neoplastic in nature is a matter of controversy; however, the classical localized form has been thought clinically benign in itself, because it can be cured by local therapy. Recently, a multicentric form of the disease has been reported and has received attention because of its aggressive clinical course and high incidence of developing malignant lymphoma. Here, we describe a case of multicentric Castleman's disease which occurred in a 24-year-old Japanese man. To ascertain whether a monoclonal population was present or not, we performed a molecular genetic analysis of the genes encoding the T-cell receptor and the immunoglobulin, as well as a conventional immunohistochemical analysis. Using these sensitive methods, no monoclonal population could be found. The findings suggest that our case represents a reactive rather than a neoplastic disorder.

Adult↗
PubMed1988

[Combined chemo-radiation therapy in adult patients with B-cell lymphoma in stage I and II].

155 adult patients with B-lymphoma in stage I and II who were treated in National Cancer Center Hospital between 1975 and 1986 were analyzed for treatment outcome. 5-year survival rates were about 66% in these patients and almost equal in the patients treated with radiation alone, doxorubicin-containing combination chemotherapy alone, or combined chemo-radiation therapy. However, when analysis was limited to patients in stage I, patients treated with chemotherapy alone seemed to have better survival rate than those treated with radiation alone. In the patients who were in stage III or more and had bulky mass more than 10 cm in diameter, small residual tumor was sometimes detected by restaging procedure after achieving apparent remission by multi-drug chemotherapy. In these patients, additional radiation therapy was quite usefull to eradicate residual tumor cells to cure.

Adolescent↗
PubMed1988

Effects of 3-methyl-1-(5-oxohexyl)-7-propylxanthine on the in vivo release of monoamines studied by intracerebral dialysis.

The effect of a xanthine derivative, 3-methyl-1-(5-oxohexyl)-7-propylxanthine (HWA 285, 10 mg/kg i.p.), on the release of endogenous monoamines and their metabolites from the rat striatum and hippocampus are examined in vivo by intracerebral dialysis technique. Using this method, which is based on the dialysis principle, a small-calibered (0.5 mm) dialysis tube is inserted into the striatum or hippocampus transversally and is perfused with Ringer solution. The amounts of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the perfusates are measured by high performance liquid chromatography system with electrochemical detection. HWA 285 (10 mg/kg) decreased monoamine levels in hippocampal perfusates after its i.p. administration. However, there were no consistent changes in monoamine release in striatal perfusates after the drug administration. These findings suggest that HWA 285 exerts an inhibitory influence on hippocampal dopaminergic and serotonergic systems.

Animals↗
PubMed1988

Major prognostic factors of adult patients with advanced B-cell lymphoma treated with vincristine, cyclophosphamide, prednisone and doxorubicin (VEPA) or VEPA plus methotrexate (VEPA-M).

Eighty-two adult patients with advanced B-lymphoma, treated between 1981 and 1983 with VEPA (vincristine, cyclophosphamide, prednisolone and doxorubicin) or VEPA-M (VEPA plus methotrexate) in a prospective randomized fashion, were evaluated for pretreatment characteristics. The overall complete response (CR) and the 4-year survival rates were 74% and 45%, respectively. The relapse rate was 51%. Stage of disease only was negatively associated with the CR rate in a multivariate analysis. The primary extranodal tumor site other than upper gastrointestinal (GI) tract and high grade pathology were found to affect disease-free survival adversely in a Cox proportional hazards model. Poor performance status, advanced stage, primary extranodal tumor site other than upper GI tract, advanced age, high grade pathology and prior therapy by either surgery or radiation, were significantly associated with shortened survival in a Cox proportional hazards model. These results indicate advanced B-lymphoma in Japan to be generally similar to advanced non-Hodgkin's lymphoma in the West in terms of prognostic factor characteristics, but the importance of the primary site in predicting survival has not been reported in the West. Also, the lack of a survival plateau in patients with diffuse large cell lymphoma indicates more intensive chemotherapy regimens than VEPA or VEPA-M to be needed. It was also found that the significant prognostic factors in patients with advanced B-lymphoma were very different from those with T-lymphoma. The five factors: pathology, stage, primary site, age, prior therapy by surgery or radiation, for which the risk ratio was more than 2.3, were used to construct a model containing 23 categories of patients running an increasing risk of shortened survival; this divided patients into three groups. The CR and 4-year survival rates of low-, moderate- and high-risk groups were 90% and 74%, 74% and 58%, and 50% and 5%, respectively. The risk-grouping provides indications for determining optimal therapy for individual patients and the need for new therapeutic trials in patients at high risk.

Adult↗