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J Nishimura

Publications and source records attributed to J Nishimura.

At least 289 records · Page 16Linked to original sources
PubMed1988

Regulation of biosynthesis and phosphorylation of P210bcr/abl protein during differentiation induction of K 562 cells.

The changes of P210bcr/abl and other tyrosine phosphorylated proteins in K562 cells during growth and differentiation were studied by metabolic labeling with 32PO4 and immunoprecipitation with anti-phosphotyrosine sera. The anti-phosphotyrosine sera recognized P210bcr/abl and other phosphoproteins with mol wt of 150, 115, 100, 70 and 64 kD. The 2-day incubation of K562 cells with inducers for differentiation, hemin, sodium butyrate and TPA, decreased the level of P210bcr/abl protein and other phosphoproteins. Inhibitors of tyrosine protein kinase, amiloride and genistein, also reduced the phosphorylation of P210bcr/abl protein and other substrates, but did not induce differentiation of the cells. Although most of these additives inhibited the cell growth, cytotoxic agents such as adriamycin, vincristine and Ara-C did not affect the level of P210bcr/abl protein. The experiments using 35S-methionine labeled cells and the immunoprecipitation with anti-abl sera suggested that reduced biosynthesis but not dephosphorylation of P210bcr/abl protein mainly accounted for the reduction of P210bcr/abl protein reacting to anti-phosphotyrosine sera in differentiation-induced cells. These results indicate that the reduction of P210bcr/abl protein synthesis plays some roles in cellular differentiation of K562 cells.

Cell Differentiation↗
PubMed1988

Difference of bone marrow adipocyte colony-forming capacity between aplastic anemia and iron deficiency anemia.

The bone marrow adipocyte colony-forming capacity (Adipo-CFC) in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS) and iron deficiency anemia (IDA) was studied. Before treatment, Adipo-CFC in IDA was higher than that in AA and MDS. After treatment, Adipo-CFC decreased in IDA, but it increased in AA and MDS only at the responsive stage. In this context, it is suggested that increase of Adipo-CFC occurs during not only regenerating hemopoiesis but also accelerated erythropoiesis such as severe IDA. Colony-stimulating activity (CSA) production by marrow stromal cells (MSC) in AA was lower than that in normal subjects. Low Adipo-CFC and defective CSA production by MSC may explain in part the pathogenesis of microenvironmental defect in AA.

Adipose Tissue↗
PubMed1988

Hematopoietic growth factors (BPA and Epo) induce the expressions of c-myc and c-fos proto-oncogenes in normal human erythroid progenitors.

We investigated serial expressions of eight proto-oncogenes during in-vitro differentiation of normal human burst-forming unit, erythroid (BFU-E), and found that c-myc and c-fos are expressed in progenies of BFU-E. The expressions of the two proto-oncogenes correlated to the replating efficiency and adversely to erythroid differentiation. The absence of hematopoietic growth factors decreased the expressions, but the addition of erythropoietin together with burst promoting activity induced a re-expression of the c-myc and c-fos after 2 h of incubation. These observations suggest that the c-myc and c-fos proto-oncogenes have a physiological role in the proliferation of erythroid progenitors and that activations of the two proto-oncogenes are early cellular events after the stimulation by hematopoietic growth factors.

Cell Differentiation↗
PubMed1988

Specific phosphorylation of 22-kD proteins by various inducers for granuloid differentiation in myeloid leukemic cells.

We studied the changes of protein phosphorylation in human leukemic cells by granuloid inducers, using two-dimensional electrophoresis. The phosphorylation of 22 kD, pI 6.0 and 5.8 proteins (pp22) in HL-60 cells or myeloid leukemic cells from patients, was enhanced by treatment with granuloid inducers such as retinoic acid, dimethyl sulfoxide or G-CSF, in common with prostaglandin E2 and theophylline, or dibutyryl c-AMP, which increased intracellular c-AMP. In contrast, pp22 phosphorylation was not induced by the monocytes/macrophages inducer in HL-60 cells, or by the granuloid inducers in lymphoid cells. This phosphorylation occurred within 30 min and continued for more than 48 h. These pp22 proteins were present in the cytosol and phosphorylated on the serine residues. We now present a possibility that granuloid differentiation in myeloid cells is closely linked with these pp22 phosphorylation.

Cell Differentiation↗
PubMed1988

Possible mechanism of ineffective erythropoiesis by an altered transferrin receptor cycle in erythroleukemia.

Involvement of the transferrin receptor cycle was noted in erythroblasts from a patient with erythroleukemia (FAB classification M6). The kinetics of transferrin receptor cycle in bone marrow erythroblasts was obtained by pulse-chase experiments before the initiation of therapy. Internalization of transferrin was impaired and resulted in a delayed peak of internalized transferrin, as compared with the kinetics pattern seen in healthy subjects. The subsequent exocytosis of the internalized ligand was also delayed. Thus, transferrin receptor cycle seems to be influenced all along the transferrin pathway, hence transferrin travels more slowly in erythroblasts in erythroleukemia. The altered transferrin receptor cycle led to a diminished iron uptake per surface transferrin receptor (approximately 30% of that in healthy subjects), and the incorporation of iron into heme was greatly reduced. Our observations suggest a possible role for the altered transferrin receptor cycle in the pathogenesis of defective heme synthesis and ineffective erythropoiesis in erythroleukemia.

Endocytosis↗
PubMed1988

Hydrocortisone modulates colony-stimulating activity produced by human bone marrow-derived adherent cells.

In an attempt to clarify the significance of hydrocortisone (HC) in human long-term bone marrow cultures, the production of colony-stimulating activity (CSA) and colony-enhancing activity (CEA) by human bone marrow-derived adherent cells (MDAC) and the modulation by HC were examined. The CSA production by MDAC was demonstrated using bilayer agar cultures. After treatment of MDAC with 10(-6) mol/l HC, the CSA production was markedly enhanced, and after treatment of macrophages with 10(-6) mol/l HC, the CSA production was inhibited. When added to a granulocyte-macrophage precursor cells (CFU-GM) assay system, HC inhibited colony formation. These results suggest that HC treatment directly stimulates CSA production by nonmacrophage cells of MDAC. The conditioned medium of the confluent layer of MDAC contained CEA, which was not influenced by the HC treatment of MDAC. Thus, HC plays an essential role in granulopoiesis in vitro, enhancing the CSA production by MDAC and inhibiting the differentiation of CFU-GM.

Bone Marrow↗
PubMed1988

Regulation of erythropoietin and burst-promoting activity production in patients with aplastic anemia and iron deficiency anemia.

To clarify the control mechanism of production of erythropoietic growth factors in anemic states, we compared erythropoietin (Epo) and burst-promoting activity (BPA) in patients with aplastic anemia and iron deficiency anemia, using in vitro erythroid progenitor assays. Although serum levels of Epo activity increased in the presence of anemia, the rise was more marked in patients with aplastic anemia. BPA was high only in the sera of aplastic anemia patients. Serum levels of BPA of patients with aplastic anemia negatively correlated with hemoglobin concentrations, while those of patients with iron deficiency anemia did not correlate. In 2 patients with aplastic anemia who responded well to androgen therapy, serum levels of Epo activity and BPA decreased after the hemopoiesis had recovered. These results suggest that serum levels of BPA do not rise in response to anemia only. The elevated BPA levels in sera in cases of aplastic anemia are probably related to a reduction in the number of hemopoietic stem cells. Moreover, we observed that BPA in bone-marrow-conditioned medium (BMCM) from patients with severe aplastic anemia increased more than in the BMCM from patients with severe iron deficiency anemia. Therefore, our findings suggest that the enhanced BPA production depends on a decrease in hemopoietic precursors rather than the anemic state.

Adolescent↗
PubMed1988

Quin2 microfluorometry and effects of verapamil and diltiazem on calcium release from rat aorta smooth muscle cells in primary culture.

We investigated the effects of the Ca2+ antagonists diltiazem and verapamil on release of Ca2+ from intracellular store sites of rat aorta vascular smooth muscle cells in primary culture. Using the microfluorometry of Ca2+-indicator dye quin2, relative changes in cytosolic Ca2+ concentration could be measured. In the presence of 1 mM extracellular Ca2+, both diltiazem (IC50, 0.31 microM) and verapamil (IC50, 0.47 microM) dose-dependently inhibited elevations in the cytosolic Ca2+, as induced by depolarization of the plasma membrane with high extracellular K+. In the absence of extracellular Ca2+, caffeine and high extracellular K+ induced transient and dose-dependent elevations of the cytosolic Ca2+, and these elevations were not inhibited by either diltiazem or verapamil. Norepinephrine also induced a transient and dose-dependent elevation of cytosolic Ca2+ in the absence of extracellular Ca2+. However, this elevation was inhibited by verapamil and diltiazem (when the norepinephrine concentration was 10(-5) M, IC50 for verapamil and diltiazem was 4.0 and 24.9 microM, respectively). Thus, while verapamil and diltiazem may have no direct effect on the release of Ca2+ from the depolarization- and the caffeine-sensitive intracellular Ca2+ storage sites, the agents do seem to inhibit the adrenoceptor-mediated Ca2+ release mechanism in vascular smooth muscle cells.

Aminoquinolines↗
PubMed1988

[Improved survival rates in Hodgkin's disease].

Results of treatment of 25 Hodgkin's disease patients at Kyushu University Hospital from 1981 to 1985 were reviewed. Total nodal irradiation or MOPP chemotherapy was used mainly. The actuarial 5-year survival rate, 87.2%, was significantly better than the 41.0% of 61 patients treated between 1966 and 1980 (P less than 0.01). However, 12 of the 24 patients in remission eventually relapsed. To further improve the survival rates of patients with Hodgkin's disease, technical improvements in total nodal irradiation and altering Adriamycin-containing chemotherapy protocol from MOPP chemotherapy are advisable.

Adult↗
PubMed1988

A novel leukemia cell line, MR-87, with positive Philadelphia chromosome and negative breakpoint cluster region rearrangement coexpressing myeloid and early B-cell markers.

We developed a Philadelphia chromosome (Ph) positive cell line, designated MR-87, from a 4-year-old boy with Ph+-acute leukemia. MR-87 cells grew in single cell suspensions with a doubling time of 120 to 144 hours. Both MR-87 and original leukemia cells were positive for myeloperoxidase (MPO) and myeloid antigen CD13. These cells exhibited the early B-cell phenotype, ie, terminal deoxynucleotidyl transferase+, Ia+, CD19+, and CD10+. Rearrangement of the immunoglobulin heavy chain was confirmed in both. Approximately 80% of MR-87 cells coexpressed CD13 and lymphoid antigens CD10 or CD19, as confirmed by a two-color analysis. Simultaneous expression of MPO and CD19 on a single MR-87 cell was demonstrated at ultrastructural level. Thus, MR-87 is a Ph+ leukemia cell line exhibiting a hybrid phenotype. The breakpoint cluster region (bcr) was not rearranged in the MR-87 cells and subsequent analysis using antisera revealed that these cells expressed a novel protein, P190c-abl, which was immunoprecipitated with anti-abl and anti-phosphotyrosine antibodies. The MR-87 line will be most useful for investigating the biology and pathogenesis of Ph+ bcr- acute leukemia.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1988

Immunodeficiency in preclinical smoldering adult T-cell leukemia.

We treated two Japanese patients with Pneumocystis carinii pneumonia. Inclusion bodies in both adrenal glands of patient no. 1 indicated a herpesvirus infection. The patient no. 2 recovered from the pneumonia upon sulfametoxazole-trimethoprim medication and high-dose methylprednisolone therapy. In both patients, anti-human T-cell leukemia virus type I (HTLV-I) antibodies were positive and anti-human immunodeficiency virus antibodies were negative. Peripheral leukocytes in patient no. 1 numbered 13.6 X 10(3)/microliter with 25% morphologically normal lymphocytes and 4% abnormal. Lymphocyte surface markers were 72.6%, CD4+, 13.6% CD8+ and 46.4% CD3+. In patient no. 2, leukocytes numbered 13.8 X 10(3)/microliter, including 18% lymphocytes, although no morphologically abnormal lymphocyte was evident. Lymphocyte markers were 36.6% CD4+, 16.8% CD8+ and 46.6% CD3+. Monoclonal integration HTLV-I proviral DNA in lymphocytes of patient no. 2 was demonstrated by Southern blotting. Thus, both patients must have had smoldering adult T-cell leukemia (ATL) without any cutaneous involvement, whereas the morphological diagnosis from peripheral blood smears was one of HTLV-I carrier status with a few atypical lymphocytes, i.e., the preclinical state of smoldering ATL. Pneumocystis carinii infections, a viral infection of the adrenals (no. 1), negative purified protein derivatives of the tuberculin reaction and suppressed blastogenesis of the peripheral lymphocytes indicated HTLV-I-induced impairment of the immune mechanism to have already occurred in both patients without there being a vast proliferation of ATL cells.

Adult↗
PubMed1987

Ketanserin blocks alpha 1-adrenoceptors of porcine vascular smooth muscle cells.

The effect of ketanserin on alpha-adrenoceptors was studied in membrane preparations of the porcine aorta using [3H]prazosin and [3H]yohimbine binding assays to identify alpha 1- and alpha 2-adrenoceptors. Ketanserin bound to alpha-adrenoceptors and the Ki value of ketanserin for alpha 1-adrenoceptors was 8.3 nM, a value practically equal to that of phentolamine (Ki = 7.2 nM). The Ki value of ketanserin for alpha 2-adrenoceptors was 3.3 microM. Thus, at the doses prescribed clinically, ketanserin blocks alpha 1- but not alpha 2-adrenoceptors of porcine vascular smooth muscle.

Adrenergic alpha-Antagonists↗
PubMed1987

Erythroblast transferrin receptors and transferrin kinetics in iron deficiency and various anemias.

To clarify the role of transferrin receptors in cases of altered iron metabolism in clinical pathological conditions, we studied: number of binding sites; affinity; and recycling kinetics of transferrin receptors on human erythroblasts. Since transferrin receptors are mainly present on erythroblasts, the number of surface transferrin receptors was determined by assay of binding of 125I-transferrin and the percentage of erythroblasts in bone marrow mononuclear cells. The number of binding sites on erythroblasts from patients with an iron deficiency anemia was significantly greater than in normal subjects (p less than 0.01). Among those with an aplastic anemia, hemolytic anemia, myelodysplastic syndrome, and polycythemia vera compared to normal subjects, there were no considerable differences in the numbers of binding sites. The dissociation constants (Kd) were measured using Scatchard analysis. The apparent Kd was unchanged (about 10 nmol/L) in patients and normal subjects. The kinetics of endocytosis and exocytosis of 125I-transferrin, examined by acid treatment, revealed no variations in recycling kinetics among the patients and normal subjects. These data suggest that iron uptake is regulated by modulation of the number of surface transferrin receptors, thereby reflecting the iron demand of the erythroblast.

Anemia↗
PubMed1987

Effect of guanosine triphosphate on the release of Ca2+ from intracellular store sites of saponin-treated human peripheral lymphocytes.

The effects of guanosine triphosphate (GTP) on the release and uptake of Ca2+ in nonmitochondrial intracellular store sites of human peripheral lymphocytes were examined. GTP in the presence of 3% polyethylene glycol released Ca2+ from the intracellular store sites of lymphocytes in a dose-dependent manner, and the maximal release was obtained at 10 microM GTP. GDP and 5'-GMP also enhanced the release of Ca2+. On the other hand, Ca2+ uptake in the presence of oxalate by saponin-treated lymphocytes was stimulated by GTP and this stimulation was abolished when polyethylene glycol was concomitantly present. The dose dependence of the stimulated Ca2+ uptake by GTP was much the same as that of the Ca2+ released by GTP. These results indicate that GTP has an inherent activity to release Ca2+ as well as to stimulate the uptake of Ca2+ in nonmitochondrial intracellular store sites of saponin-treated lymphocytes. The stimulatory effect of polyethylene glycol on GTP-mediated Ca2+ release may occur by inhibiting functions of the Ca2+ pump.

Biological Transport, Active↗