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Biomedical subjects

J Nishimura

Publications and source records attributed to J Nishimura.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1987

A stimulator of mouse stem cell proliferation produced by human regenerating bone marrow.

We examined CFU-S proliferation stimulator, which recruits stem cells in DNA synthesis, in conditioned media prepared from bone marrow cells of patients with regeneration hemopoiesis after chemotherapy induced hypoplasia. This activity was estimated by hydroxyurea sensitivity of CFU-S in mice, under conditions of incubation with human bone marrow conditioned medium (BMCM). We found that CFU-S proliferation stimulator was present to a considerable extent in human regenerating BMCM, but less so in normal BMCM and that the production fluctuated with change of hemopoietic states, in the same patient. This stimulator was heat-labile, trypsin-sensitive and mainly produced by adherent cells. This factor may possibly be involved in regulation of proliferation of stem cells in regenerating bone marrow in humans.

Animals↗
PubMed1987

Pancreatic carcinoma associated with marked eosinophilia: a case report.

A case of pancreatic carcinoma associated with marked eosinophilia is reported. A 71-yr-old man was admitted to hospital because of melena and abdominal pain. The systematic examinations revealed pancreatic adenocarcinoma with multiple metastases (rectum, lung and brain). The leukocyte count was gradually increased and reached up to 81.7 X 10(9)/l, of which 54% consisted of eosinophils. Colony-stimulating factor (CSF) was detected both in the patient's serum and in the tumor extracts by a normal human bone marrow culture system. The colonies which were stimulated with patient's serum largely consisted of granulocyte, granulocyte/macrophage and eosinophil types. These results suggest that blood leukocytosis and eosinophilia were due to a high concentration of plasma CSF, which was probably produced by the tumor cells.

Adenocarcinoma↗
PubMed1987

Characteristics of adrenoceptors and [3H]nitrendipine receptors of porcine vascular smooth muscle: differences between coronary artery and aorta.

Characteristics of the bindings of [3H](-)dihydroalprenolol, [125I](-)iodocyanopindolol, [3H]prazosin, [3H]yohimbine, and [3H]nitrendipine to porcine coronary membranes were investigated and the results compared with studies of porcine aortic membranes. In the equilibrium binding study carried out in sarcolemma-enriched fractions, there were no major differences in the Kd values of these radioligands between coronary artery and aorta. However, the densities of beta-, alpha 1-, and alpha 2-adrenoceptors and [3H]nitrendipine receptors of coronary artery were 258, 12, 12, and 561 fmol/mg protein, respectively, while those of aorta were 37, 525, 1,000, and 215 fmol/mg protein. beta-Adrenergic agonists competed with [3H](-)dihydroalprenolol binding sites in coronary artery, the order of potency being (-)isoproterenol greater than (-)norepinephrine greater than (-)epinephrine greater than (+)isoproterenol. In case of aorta, the order was (-)isoproterenol greater than (-)epinephrine greater than (-)norepinephrine. The competition by (+/-)bisoprolol (beta 1-selective antagonist) and ICI 118,551 (beta 2-selective antagonist) for [125I](-)iodocyanopindolol binding sites in coronary artery resulted in nonlinear Hofstee plots (beta 1:beta 2 = 90%:10%). In case of aorta, linear Hofstee plots were obtained. From these results, we conclude that coronary beta-receptors in pigs are predominantly of beta 1-type, while those of aorta are of beta 2-type; regarding the relative population of adrenoceptors, coronary artery is beta-dominant (beta/alpha = 11), while aorta is alpha-dominant (beta/alpha = 0.02); compared with alpha-adrenoceptors, coronary artery has a greater number of [3H]nitrendipine binding sites (nitrendipine/alpha-adrenoceptor = 23) than aorta (nitrendipine/alpha-adrenoceptor = 0.14).

Animals↗
PubMed1987

[Conversion of 5'-deoxy-5-fluorouridine to 5-FU by pyrimidine nucleoside phosphorylases in normal and tumor tissues from rodents bearing tumors and cancer patients].

Enzyme levels of pyrimidine nucleoside phosphorylase, which is an essential enzyme for the phosphorolysis of 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil (5-FU), in normal and tumor tissues were investigated. In all mouse strains tested, the enzyme level was found to be higher in the small intestine and stomach than other tissues, while in rats a higher level of the enzyme in the lung was also observed additionally. The enzyme levels of tumor tissues varied in tumor cell lines transplanted. P388 leukemia, Ehrlich ascites carcinoma, sarcoma 180, colon 26 carcinoma, and Lewis lung carcinoma cells contained high levels of the enzyme and the mice bearing these tumors responded well to the therapy with 5'-DFUR than its active metabolite 5-FU, while 5'-DFUR did not show clear advantage over 5-FU against L1210 or LSTRA leukemia, in which the enzyme levels were low. These results indicate that there is some correlation between the enzyme level and antitumor efficacy of 5'-DFUR. In human specimens, the enzyme levels were 2-6 times higher in tumors than those of the corresponding normal tissues and those adjacent to the tumors. These results predict that 5'-DFUR seemed to be converted efficiently to 5-FU also in human tumors.

Animals↗