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Biomedical subjects

M Shimoyama

Publications and source records attributed to M Shimoyama.

At least 271 records · Page 15Linked to original sources
PubMed1984

[Screening test of antitumor agents by human tumor cell lines in nude mice in ascitic form].

Two kinds of, serially transplantable human tumor cell lines were established in nude mice in ascitic form. One is breast cancer cell line, poorly differentiated adenocarcinoma, Hattori strain, and the other is acute lymphocytic leukemia cell line, T-cell type, Ichikawa strain. There exists a distinct correlation between the survival time of nude mice and the number of tumor cells transplanted. Clinically established antitumor agents which showed over 200% increase in life span were MMC, ADM and 5FU in Hattori strain, and VCR, VLB, VDS, ADM and BH-AC in Ichikawa strain. These results were considered to be consistent with the clinical effect of these drugs in breast cancer or in acute lymphocytic leukemia. Both strains can serve as the reliable screening system of antitumor agents.

Adenocarcinoma↗
PubMed1984

A novel human myelomonocytoid cell line, P39/Tsugane, derived from overt leukemia following myelodysplastic syndrome.

A novel human cultured cell line, P39/Tsugane, was established from leukemic cells in the peripheral blood of a 69-year-old male with overt leukemia following myelodysplastic syndrome (MDS). P39/Tsugane cells were characterized by blastic appearance, presence of NaF-sensitive alpha-naphthyl butylate esterase activity, Fc gamma-receptor, C3-receptor, capacity to phagocytize sensitized erythrocytes, and reactivity with monoclonal antibodies such as OKT4, My4, VIMD5, MCS-2 and My7. These data indicate that P39/Tsugane cells are of myelomonocytoid nature. P39/Tsugane had a hypodiploid chromosome constitution with a gain of a consistent marker, 6q+, the presence of less consistent markers 9q+ and rcp(14;16), and random and non-random losses of autosomes: in accordance with the reported cytogenetic profiles of MDS, a representative karyotype of the present cell line is 45,XY,+del(6)(q15),9q+, t(14;16)-(q24;q21),-16,-17. P39/Tsugane cells were transplantable intraperitoneally into nude mice, and produced abdominal tumors and hemorrhagic ascites. These results indicate that P39/Tsugane is the first cultured cell line of myelomonocytoid nature to be derived from overt leukemia following MDS. Therefore, P39/Tsugane cells should be useful for studies on the differentiation of leukemia cells, the pathogenesis of MDS and in vitro-in vivo experimental chemotherapy.

Aged↗
PubMed1983

ADP-ribosylation regulates the phosphorylation of histones by the catalytic subunit of cyclic AMP-dependent protein kinase.

Phosphorylation of whole histones from calf thymus by the catalytic subunit of cyclic AMP-dependent protein kinase was markedly reduced when the histones were ADP-ribosylated. NAD, nicotinamide or free ADP-ribose molecule did not suppress the phosphorylation. Urea gel electrophoretic analyses of the phosphorylated histones which had already been ADP-ribosylated revealed that the suppression of phosphorylation occurred in both H1 and core histones. Therefore, the possibility that ADP-ribosylation may regulate the phosphorylation of histones phosphorylation in nuclei warrants further investigation.

Adenosine Diphosphate Ribose↗
PubMed1983

Mg2+-dependent/poly(ADP-ribose)-sensitive endonuclease.

A novel endonuclease from adult hen liver nuclei has been purified to a homogeneous state through salt extraction, ammonium sulfate fractionation, gel filtration, acetone fractionation, and successive chromatography of 1) hydroxyapatite and DNA Sepharose and 2) hydroxyapatite and isoelectric focusing. The endonuclease has a pH optimum at 9.0 and requires Mg2+ for activity. The enzyme hydrolyzes more rapidly in the order of polynucleotide: denatured DNA = rRNA greater than poly(dA) = poly(dT) greater than poly(dC) = poly(dG) greater than native DNA. This endonuclease degrades denatured DNA about 20 times more rapidly than does the native DNA. The products contain 5'-phosphoryl and 3'-hydroxyl termini and all four deoxynucleotides are present while dGMP is predominant. The enzyme cleaves the circular duplex PM2 DNA, endonucleotically, via single strand scission. The isoelectric point is 10.2 +/- 0.2 and the molecular weight is 43,000 +/- 2,000, determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration. Pyridoxal 5'-phosphate and 2,3-butanedione inhibit the catalytic activity, respectively. The inhibition of DNA binding activity was also seen with former, but not with the latter. Purified Mg2+-dependent alkaline endonuclease was used to investigate the nature of poly(ADP-ribose) inhibition of the enzyme. In contrast to the Ca2+/Mg2+-dependent endonuclease (Yoshihara, K., Tanigawa, Y., Burzio, L., and Koide, S. S. (1975) Proc. Natl. Acad. Sci. U. S. A. 72, 289-293), ADP-ribosylation of the endonuclease protein was not observed. When 100 ng of the poly(ADP-ribose) having four to five ADP-ribose units per molecule were added to the nuclease assay system (total volume of 0.2 ml) 14% inhibition was observed, and increase in the chain length increased the inhibition. When 100 ng of poly(ADP-ribose) consisting of 20 or more units of the ADP-ribose per mol were added, the inhibition was over 95%. The possible role of the poly(ADP-ribose)-sensitive endonuclease is discussed.

Animals↗
PubMed1983

Mono (ADP-ribosyl)ation of hen liver nuclear proteins suppresses phosphorylation.

The phosphorylation of nuclear proteins from hen liver nuclei was suppressed under conditions of incubation with NAD. The reconstituted protein kinase assay system containing heat-treated and subsequently ADP-ribosylated nuclei and NI type protein kinase revealed that the ADP-ribosylated nuclear proteins are poor acceptors for the phosphorylation reaction. Therefore, mono(ADP-ribosyl)ation may contribute to the regulation of phosphorylation reaction in nuclei.

Adenosine Diphosphate Ribose↗
PubMed1983

Establishment and characterization of 10 cell lines derived from patients with adult T-cell leukemia.

By using human T-cell growth factor (TCGF), 10 cell lines were established from tissue samples of 10 patients with adult T-cell leukemia (ATL). Three cell lines were adapted to growth in medium lacking TCGF. The surface markers of all cell lines were characteristic of inducer/helper T cells, i.e., OKT3+, OKT4+, OKT6-, OKT8-, OKIa1+, and human Lyt2+ and Lyt3+, except that one cell line was OKT3-. The expression of the viral antigen was examined during establishment of 8 of the 10 cell lines. The viral antigen was not expressed in leukemic cells before cultivation. In 5 lines, the viral antigen was detected by immunofluorescent staining after a short period of cultivation. However, 3 cell lines, ATL-6A, ATL-9Y, and ATL-1K did not express the viral antigen during short-term culture: the ATL-6A and ATL-9Y cell lines became positive for the viral antigen after 5 and 2 months of cultivation, respectively; the ATL-1K cell line remained antigen-negative throughout a culture period of 13 months. Southern blot hybridization assay showed that all of the cell lines, including the viral antigen-negative ATL-1K cell line, contained the viral genome. Thus, the retrovirus was associated with all 10 cell lines established from ATL patients, but there was a heterogeneity in the expression time of the retroviral antigen in leukemic cells maintained in vitro. Our findings suggested that the expression of the viral antigen was not required for maintenance of the leukemic state in vivo and for growth of leukemic cells in vitro.

Antigens, Surface↗
PubMed1983

Detection of lymphocytes producing a human retrovirus associated with adult T-cell leukemia by syncytia induction assay.

Recently 10 T-cell lines were established from patients with adult T-cell leukemia (ATL). During establishment of these cell lines, it was found that when T-cell lines expressing the ATL-associated retroviral antigen were cocultivated with 8C cat cells, multinucleated syncytia were formed. Retroviral antigen-negative T-cell lines did not induce syncytia. Peripheral blood lymphocytes obtained from ATL patients did not express the retroviral antigen before cultivation in vitro but became positive for the retroviral antigen after cultivation for a short period; these retroviral antigen-positive lymphocytes, but not retroviral antigen-negative lymphocytes, induced syncytia upon cocultivation with 8C cells. Peripheral blood lymphocytes isolated from patients with chronic lymphocytic leukemia of T-cell origin or Sézary syndrome or from normal adults and lymph node cells from a patient with immunoblastic lymphadenopathy-like T-cell lymphoma did not express the retroviral antigen even after cultivation in vitro and did not induce syncytia upon cocultivation with 8C cells. Thus, there was complete agreement between the presence of the retroviral antigen in established T-cell lines or freshly isolated peripheral blood lymphocytes and their ability to induce syncytia. Syncytia formation was enhanced 5- to 20-fold by the presence of Polybrene and inhibited by addition of plasma of ATL patients to the cocultures. Syncytia were detected within 4 hr on cocultivation of 8C cells with the retroviral antigen-positive T-cells, indicating that most syncytia were formed by early polykaryocytosis. After cocultivation, a clone of 8C cells that harbored the ATL virus genome and had syncytia-inducing activity was isolated. These findings indicate that the retrovirus associated with ATL has syncytia-inducing activity. Syncytia induction assay using 8C cells will be useful for detection and characterization of human retrovirus associated with T-cell malignancies.

Adult↗
PubMed1983

[Antitumor activity of human interferons: their direct cytotoxic activity and clinical effects].

It was found that both interferon-beta and interferon-alpha had a direct cytotoxic action against a few sensitive cultured cell lines. The action was not concentration dependent, but time dependent. Interferons expressed their maximum effect when they were given daily for long time to nude mice bearing transplantable ascitic human cancer cell lines, indicating that interferons had schedule dependency. In preliminary phase II study of interferons (3-9 X 10(6) U daily im, iv or local use) to 40 patients with various malignancies, only one patient with B-cell lymphoma responded to systemic use of both interferons and two out of five patients with pleural malignant effusion of breast cancer also responded to intrapleural use of interferons. Side effects were usually mild, but included fever, weakness, gastrointestinal, hematopoietic, liver and kidney function disturbances.

Animals↗
PubMed1983

[The clinical effects of a new antiviral 9-(2-hydroxyethoxymethyl) guanine (aciclovir) against herpes virus infections].

The clinical effects of a new anti-viral 9-(2-hydroxymethoxymethyl) guanine (Aciclovir) against Herpes virus infections have been investigated. The patients had malignant tumours or auto-immune disease complicated by shingles and chicken pox due to Vaicella zoster virus (VZV) (43 cases), Herpes simplex virus (HSV) (10 cases) and 9 cases which were clinically diagnosed as Herpes, though the virus was not confirmed as the causative agent. As a general principle the dosage of Aciclovir was 5 mg/kg, t. i. d. for 5 days by slow intravenous infusion. The clinically effective rate against VZV was 93%, being excellent in 42% and against HSV it was 80%, being excellent in 40% and when the results of the cases of unknown origin were included it was excellent in 40% and the cumulative effective rate was 88%. Concerning the efficacy in reduction of pain, swelling, disappearance of vesicles and new scab formation, the effect was most noticeable after the third day of treatment. Treatment given early in the disease is likely to provide better results. Concerning side effects, one of 62 patients had proteinuria and the other had a drug rash and an abnormal liver function test. It is likely that the combination of treatment and the primary disease had some influence, but the cause/effect relationship to Aciclovir treatment is not clear.

Acyclovir↗
PubMed1983

Monoclonal antibody studies in B(non-T)-cell malignancies.

Tumor cells suspensions prepared from 129 B- or non-T cell malignancies were investigated with a panel of 10 monoclonal antibodies and conventional surface marker techniques. Surface immunoglobulin (sIg) and B1 antigen proved to be the most useful markers for B-cell lineage. Six major subtypes of acute lymphoblastic leukemia (ALL) of non-T cell nature are now recognized by these immunological techniques, including null-ALL, Ia-ALL, lymphoid stem cell ALL, pre-pre-B ALL, pre-B ALL and B-ALL. In cases of chronic leukemias and lymphomas of non-T cell nature, 80% of the tumor was defined by sIg and 88% by B1 antigen as definitely of B-cell lineage. The clonal character was also defined in 68% of the tumor on the basis of the detection of predominant single light chain in sIg. Ia-like antigen was detected in almost all cases (96%). Leukemic cells from all cases of chronic lymphocytic leukemia (CLL), chronic lymphosarcoma cell leukemia (CLsCL) and hairy cell leukemia (HCL) reacted with OKIa1 and anti-B1, and leukemic cells from most of them with anti-pan T monoclonal antibody (10.2). In more than half of CLL and CLsCL, leukemic cells were reactive with J5, OKM1, 9.6 and OKT8, but not with OKT3, OKT4 and OKT6. HCL cells had almost the same reactivity with these monoclonal antibodies as CLL and CLsCL cells except that J5 remained unreactive. These results indicated that Japanese CLL, CLsCL and HCL were different from Western ones at least with respect to surface marker characteristics. In cases of lymphomas, heavy chains of sIg were expressed in polyclonal fashion, especially in follicular lymphoma and diffuse lymphomas of medium sized cell type and large cell type, indicating that lymphomas of these types may originate from follicular center cells of the heavy chain switching stage. Anti-T monoclonals were also reactive with lymphoma cells. In about half of follicular lymphomas and diffuse lymphomas of the medium sized cell type, lymphoma cells reacted with 10.2, and less frequently with 9.6, OKT4 and OKT3. On the other hand, only in one or two cases of diffuse lymphoma of the large cell type and of immunoblastic sarcoma (IBS), did tumor cells react with 10.2 and 9.6, but this was exceptional. In more than 25% of IBS, tumor cells also reacted with OKT8, but not with OKT4 and OKT3. These results indicated that anti-T monoclonals are no longer specific for T-cell lineage.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1983

Two novel cultured cell lines, A3/Kawakami and A4/Fukuda, derived from malignant lymphoma of B(non-T)-cell nature of the gastrointestinal tract.

A3/Kawakami was derived from ascitic lymphoma cells of a 68-year-old female patient with malignant lymphoma (non-Hodgkin's lymphoma, diffuse, large cell type) of the stomach and A4/Fukuda was derived from ascitic lymphoma cells of a 52-year-old female patient with double cancer of the colon (well-differentiated papillary adenocarcinoma and non-Hodgkin's lymphoma, diffuse, large cell type). The fresh ascitic lymphoma cells in the case of A3/Kawakami were surface immunoglobulin-positive, but the cultured A3/Kawakami cells no longer expressed any distinct markers. In the case of A4/Fukuda, the fresh ascitic lymphoma cells and cultured cells did not express any specific surface markers. Only 20% of A4/Fukuda cells were reactive with OKI1. However, a small amount of IgM could be detected in the cell extract and concentrated culture supernate of A4/Fukuda. In addition, A4/Fukuda cells heterotransplanted into anti-thymocyte sera-treated newborn hamster or athymic nude mice with a BALB/c genetic background were found to have weak surface immunoglobulin and distinct cytoplasmic immunoglobulin (gamma, mu). These data suggest that A4/Fukuda cells share the characteristics of the late differentiation stage of B-cell lineage (intermediate between mature B-cells and plasma cells). It was found that monoclonal antibodies, OKT4 and anti-Leu 3a, which are known to react specifically with inducer/helper T-cells, reacted to both A3/Kawakami and A4/Fukuda cells. The karyotypes of both A3/Kawakami and A4/Fukuda cells were very complicated but included some marker chromosomes such as 14q+.

Aged↗