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Biomedical subjects

M Shimoyama

Publications and source records attributed to M Shimoyama.

At least 253 records · Page 14Linked to original sources

[Coexisting malignant lymphoma and advanced adenocarcinoma of the colon--a case report].

Although it is not uncommon to find multiple malignant neoplasms in the same organ, the incidence of synchronous malignant lymphoma and colonic adenocarcinoma has been very rare. This a case report involving a 52-year-old woman in whom malignant lymphoma actually arose within the same segment in which colonic adenocarcinoma was present. Under the diagnosis of advanced adenocarcinoma, she had been treated by right hemicolectomy. However, she developed intestinal obstruction about a month later. At the second surgery for this latter condition, cytologic examination of ascitic fluid revealed many malignant lymphoma cells. In spite of antilymphoma chemotherapy, the patient's condition became progressively worse during the subsequent five-month period, and she died of recurrent malignant lymphoma.

Adenocarcinoma↗

Time-dependent cytotoxic action of human recombinant alpha-interferon (Ro22-8181) in vitro and the sensitivity of various cultured leukemia and lymphoma cell lines to it.

The growth inhibitory activity of human recombinant leucocyte A interferon (Ro22-8181: alpha-interferon) against 23 human cultured cell lines derived from leukemias and lymphomas was measured quantitatively by regrowth assay. Daudi cells were the most sensitive to it. Two T-cell lines (RPMI-8402, HUT78), three B-cell lines (Raji, Ly16, A3/Kawakami), one non-T, non-B acute lymphoblastic leukemia (ALL) cell line (KOPN-1) and three myelomonocytoid cell lines (U937, THP-1, ML-1) were moderately or slightly sensitive. Although the levels of sensitivity of these cell lines were different, cells could be killed by the recombinant alpha-interferon. Morphological changes in the sensitive cells treated with it were decreases in mitosis, pyknosis and fragmentation of the cells. Thirteen other cultured cell lines were not sensitive. The results indicated that the growth inhibitory activity of recombinant alpha-interferon is not always cell lineage-specific. There were only three cell lines whose sensitivity, expressed by the concentration required for 90% growth inhibition, was less than the several hundred units per milliliter that has usually been obtained as blood levels in clinical trials. These three included one of 10 T-cell lines and two of seven B-cell lines; none of six non-T, non-B ALL and myelomonocytoid cell lines were that sensitive. Among virus-associated cell lines, only Epstein-Barr virus-associated B-cell lines were sensitive to the interferon; adult T-cell leukemia virus-associated T-cell lines were not sensitive. It was demonstrated that recombinant alpha-interferon has a time-dependent, but not a concentration-dependent cytocidal action, indicating that optimal therapeutic schedules of recombinant alpha-interferon for cancer may be daily long-term treatment, not single or short-term large-dose therapy.

Antineoplastic Agents↗

Second primary malignancies in lymphoma patients.

We evaluated the occurrence and the type of second malignancies among 74 patients with Hodgkin's disease (HD) and 407 patients with non-Hodgkin's lymphoma (NHL) who were treated at the National Cancer Center Hospital for more than one year. Fifteen patients developed a second malignancy. In 10 of these patients the second cancer was gastric cancer, but no cases of acute nonlymphocytic leukemia were encountered. The observed number of second cancers in females among the HD patients was significantly (p less than 0.005) greater than the expected incidence based upon the number of age-adjusted person-years both for all cancers and for stomach cancer. However, no significant differences between males and females in the NHL patients were found. Furthermore, no significant differences were seen in any of the groups between the observed and expected numbers of second malignancies according to the treatment.

Adult↗

[The significance of reinduction chemotherapy with adriamycin for relapsed non-Hodgkin's lymphoma of Waldeyer's ring].

Of those patients with localized (CS I-II) non-Hodgkin's lymphoma of Waldeyer's ring who were treated with radiotherapy or radiotherapy plus chemotherapy and who suffered relapses at the National Cancer Center Hospital over the past 22 years, 24 cases were analyzed on the basis of their response rate and duration of remission with reinduction chemotherapy, and survival time after recurrence. The group [ADM (+)], treated with regimens including adriamycin, was compared with the group [ADM (-)] treated with regimens excluding adriamycin. Complete response was seen in 9 out of 11 cases (81.8%) and in 8 out of 13 cases (61.5%) for the ADM (+) group and the ADM (-) group, respectively (p greater than 0.1). The period of complete response of the ADM (+) and ADM (-) groups was compared using the logrank method. The prognosis of the former was significantly (p less than 0.01) better than that of the latter and the median duration of remission was 30 months and 7 months, respectively. When the survival after recurrence of the ADM (+) and ADM (-) groups was compared, the median survival time was 38 months for the ADM (+) group and 12 months for the ADM (-) group, but no significant difference was observed between the two groups (0.05 less than p less than 0.1).

Adult↗

Prognostic factors and therapeutic results in multiple myeloma.

Prognostic factors in 68 consecutive patients with myeloma treated at the National Cancer Center Hospital from 1962 to 1984 were analyzed. Median survival time from onset was 100 months for stage I, 72 months for stage II, and 26 months for stage III of the Durie and Salmon's clinical staging system. It was 55 months in patients with normal renal function and 18 months in those with abnormal renal function. All early deaths occurred in patients with stage III disease. Hemoglobin level, bone lytic lesions and presence of Bence Jones protein were also significant prognostic factors. On the other hand, heavy chain as well as light chain subtypes of monoclonal immunoglobulin (M-component) and M-component production rate did not influence the survival of myeloma patients. The analysis of chemotherapeutic responses and survival curves according to the chemotherapy used in this study (alkylating agent vs Vinca-alkaloid plus alkylating agent) did not disclose any significant difference between the two groups. The overall response rate was 67%. The survival time from the initial chemotherapy of responding patients was significantly longer than that of nonresponders.

Adult↗

Immortalization of peripheral blood lymphocytes of cats by human T-cell leukemia virus.

Peripheral blood lymphocytes of domestic cats were co-cultivated with lethally irradiated MT-2 cells, which produced human T-cell leukemia virus type 1 (HTLV-I). Two cat lymphoid cell lines, CaL-1 and CaL-2, established and maintained without exogenously added T-cell growth factor, were characterized after more than 6 months of cultivation. These cells grew in suspension, had a chromosome number of 38 and lacked cytoplasmic and surface immunoglobulins. CaL-2 cells formed E-rosettes. Both cell lines harbored HTLV genomes but not human Alu family sequences, which are highly repetitious in the human genome, suggesting that transfer of human DNA fragments was not necessary for their immortalization or transformation. HTLV antigens were detected in CaL-1 and CaL-2 cells by indirect immunofluorescence assay. CaL-1 and CaL-2 cells both expressed viral proteins with apparent molecular weights of 53 kd, 24 kd and 19 kd, and CaL-2 cells also expressed 28 kd and 20 kd proteins. Reverse transcriptase activity was detected in culture fluid of CaL-2 cells, but not of CaL-1 cells. CaL-2 cells but not CaL-1 cells had syncytium-induced activity. These findings indicated that lymphocytes of cats, especially T lymphocytes, were susceptible to infection with HTLV and to immortalization by HTLV.

Animals↗

Possible participation of Ca2+, Mg2+-dependent endonuclease in liver DNA fragmentation after N-methyl-N-nitrosourea treatment.

We examined the fragmentation of DNA treated with N-methyl-N-nitrosourea under conditions in which Ca2+, Mg2+-dependent endonuclease is active. The molecular mass of DNA found in mouse liver slices treated with methylnitrosurea in the presence of Ca2+ plus Mg2+ was 4 X 10(5) Da. Similar results were obtained with a reconstituted system containing partially purified Ca2+, Mg2+-dependent endonuclease and methylnitrosurea-treated DNA. The enzyme extensively cleaved methylnitrosurea-treated DNA, compared with non-treated DNA. The methylnitrosurea-treated nuclear proteins obtained from mouse liver nuclei had no effect on the DNA fragmentation by the enzyme. Using closed-circular DNA treated with methylnitrosurea, the enzyme produced single-strand cuts in the DNA, as was seen in non-treated, closed-circular DNA, however, the rate of hydrolysis was increased. Ca2+, Mg2+-dependent endonuclease thus warrants further investigation, with regard to the precise mechanism of extensive degradation of DNA in cells treated with carcinogenic alkylating agents.

Animals↗

ADP-ribosyltransferase from hen liver nuclei. Purification and characterization.

Chromatin-bound ADP-ribosyltransferase from adult hen liver nuclei was purified to a homogeneous state through salt extraction, gel filtration, hydroxyapatite, phenyl-Sepharose, Cm-cellulose, and DNA-Sepharose. The ADP-ribosyltransferase has a pH optimum at 9.0 and does not require DNA for reaction. The purified enzyme has a molecular weight of 27,500 +/- 500. Agmatine sulfate, arginine methyl ester, histones, and casein proved to be effective acceptors for the ADP-ribose molecule. Among histones, H3 was most active, followed by H2a, H4, and H2b, in that order, the lowest activity seen with H1. With all the acceptors tested, the rate of nicotinamide release was in excess of the ADP-ribosylation. However, changes in the ratio of nicotinamide release to ADP-ribosylation seemed to depend on concentrations of the acceptor used. ADP-ribose-whole histones X adducts formed by ADP-ribosyltransferase served as initiators for poly(ADP-ribose) synthesis when these adducts were incubated in the presence of NAD, DNA, Mg2+, and the purified poly(ADP-ribose) synthetase, in which poly(ADP-ribose) formation can occur.

Animals↗

Immunologic characterization of Reed-Sternberg cells and other cell components in lymph nodes with Hodgkin's disease.

Seven lymph nodes from patients with Hodgkin's disease were immunologically studied. Histologically these cases consisted of 3 lymphocyte predominance, 2 mixed cellularity, and 2 nodular sclerosis. Positive staining of mononuclear Hodgkin- and multinuclear Reed-Sternberg (RS) cells were obtained with anti-Ia like antigens and OKT9 (anti-transferrin receptor) monoclonal antibodies. No supportive data for discussing similarity of RS cells with ordinary histiocytes, B-lymphocytes or T-lymphocytes were obtained from the study of surface phenotype, although some analogy was present with histiocytes. Small lymphocytes around RS cells were helper/inducer T-lymphocytes, and the relationship between these T lymphocytes and RS cells was discussed.

Adult↗

Ribosome-lamella complex of the lymphocytes in a case of plasmacytic lymphadenopathy with polyclonal hypergammaglobulinemia.

A case of lymphoid hyperplasia with prominent plasmacytic proliferation histologically and with polyclonal hypergammaglobulinemia and anemia clinically was reported. This condition in a 54-year-old Japanese male was probably a type of plasma cell dyscrasia similar to a plasma cell variant of Castleman's disease. About 19% of apparently nonatypical lymphocytes in the biopsy material of this case were found to have ribosome-lamella complexes (RLC) similar to those previously described in patients with hairy cell leukemia and some other hematologic disorders. An intimate association with the rough endoplasmic reticulum of these structures suggested aberrant protein synthesis by B-lymphocytes.

Anemia↗

Clinical implications of anti-HTLV antibody titer, abnormal lymphocytes in HTLV carriers and HTLV genome negative adult T-cell leukemia-lymphoma.

Abnormally large lymphocytes with Pelger-like nuclear lobulation have been found in peripheral blood of smoldering adult T-cell leukemia-lymphoma (ATL) patients. They are also found in quite low percentage in peripheral blood of healthy HTLV carriers. Therefore, it has become difficult to discriminate smoldering ATL having only abnormal lymphocytes from a healthy human T-cell leukemia virus (HTLV) carrier only by morphology and serology. We found that patients with smoldering ATL with visceral organ involvement such as skin or lung lesions had much higher titer (about 1 : 1,000) of anti-HTLV antibodies than those with other subtypes of ATL (about 1 : 250); the difference was highly significant (p less than 0.001). In addition, the period of survival of patients with smoldering ATL having antibody with high titer was much longer than that of patients with other subtypes of ATL, suggesting the role of a host immune response. Four cases of HTLV-negative ATL were found to have the same chromosomal abnormality as that has been seen in HTLV-positive typical ATL; the situation was quite similar to Burkitt's lymphoma. Since it has been considered that HTLV does not include oncogenes, a common oncogenic mechanism, ATL specific cellular oncogenes, might exist: they might be activated by HTLV or a mechanism other than a virus.

Antibodies, Viral↗

Growth-inhibitory activity of human recombinant beta-interferon (GKT-beta) in vitro.

Growth-inhibitory activity of human recombinant beta-interferon (GKT-beta) against 20 human cultured cell lines derived from leukemias and lymphomas was measured quantitatively by regrowth assay. Daudi cells were the most sensitive to GKT-beta. Two T-cell lines (RPMI-8402, HUT78), three B-cell lines (Raji, P3HR-1, A3/Kawakami), one non-T, non-B acute lymphoblastic leukemia (ALL) cell line (KOPN-1) and one monocytoid cell line (U937) were moderately sensitive to GKT-beta. Although the levels of sensitivity of these cell lines to GKT-beta were different, the cells could be killed by GKT-beta. Morphological changes of the sensitive cells treated with GKT-beta were decrease in mitosis, pyknosis and segmentation of cells. Twelve other cultured cell lines, comprising four T-cell lines, four B-cell lines, one non-T, non-B ALL cell line and three myelomonocytoid cell lines, were not sensitive to GKT-beta. The results indicated that the growth-inhibitory activity of GKT-beta was not always cell lineage-specific or differentiative stage-specific. GKT-beta was instable in vitro and its antiviral activity was reduced to about 10% during the first 24 hr of incubation in culture medium with or without cells. This instability was reflected in a similar reduction of its growth-inhibitory activity. It was demonstrated that GKT-beta had a time-dependent, but not a concentration-denpendent antiproliferative action. This suggests that, in the clinical use of the interferon, direct antiproliferative activity of GKT-beta may be expected only through the use of therapeutic schedules which are suitable for its time-dependent action, such as through daily long-term treatment, but not through a single large-dose therapy.

Cell Division↗