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Biomedical subjects

N Katayama

Publications and source records attributed to N Katayama.

At least 181 records · Page 10Linked to original sources

Activity of the ligand for c-mpl, thrombopoietin, in early haemopoiesis.

We examined the role of the ligand for c-mpl. thrombopoietin (TPO). in murine early haemopoiesis. using a serum-free culture system. TPO in combination with the ligand for c-kit (SF) or interleukin-3 (IL-3) supported colony formation by marrow cells of 5-fluorouracil (5-FU)-treated mice whereas TPO alone yielded no colony. When blast cell colonies grown in the presence of TPO plus SF or TPO plus IL-3 were individually replated in suspension cultures containing serum and several growth factors, various combinations of myeloid lineages were seen, indicating that the progenitors supported by TPO plus SF or TPO plus IL-3 are multipotential. Delayed addition experiments demonstrated that TPO has the potential to effectively support the survival of haemopoietic progenitors. We then studied the effects of TPO on proliferative kinetics of cycling progenitors. TPO hastened IL-3-dependent growth of progenitors by shortening the time required for cell cycling. These results suggest that TPO as a single factor, can support the survival of haemopoietic progenitors and TPO synergizes with SF or IL-3 to act on early multipotential haemopoietic progenitors.

Animals↗

DMI-2 and DMI-3, DNA methyltransferase inhibitors produced by Streptomyces sp. strain no. 560.

Streptomyces sp. strain No. 560 produces several types of DNA methyltransferase inhibitors in the culture filtrate. Two of them, DMI-2 and DMI-3, were distinguished from the previously reported DMI-1 by their inhibitory spectrum and inhibition characteristics against DNA methyltransferase. The molecular weights of DMI-2 and DMI-3 were 854 and 435, respectively. The structure of DMI-2 was determined to be 4"'R,6aR,10S,10aS-8-acetyl-6a, 10a-dihydroxy-2-methoxy-12-methyl-10-[4'-[3"-hydroxy-3",5"-dimethyl-4" (Z-2"',4"'-dimethyl-2"'-heptenoyloxy) tetrahydropyran-1"-yloxy]-5'-methylcyclohexan-1'-yloxy ]-1,4,6, 7,9-pentaoxo-1,4,6,6a,7,8,9,10,10a,11-decahydronaphthacene. The chemical structure of DMI-2 was established as a tautomer of dutomycin which is an antitumor antibiotic produced by Streptomyces sp. 1725. DMI-2 and DMI-3 showed strong inhibition against N6-methyladenine-DNA methyltransferase (M. Eco RI). DMI-2 inhibited M. Eco RI in a competitive manner with respect to plasmid pUC19 used as DNA substrate and in an uncompetitive manner with respect to S-adenosylmethionine (SAM) used as methyl donor. DMI-3 inhibited M. Eco RI in a competitive manner with respect to plasmid pUC19 and SAM. The inhibitory activities of both inhibitors depended upon the pH and temperature in the assay media.

DNA Methylation↗

Inhibition of DNA methyltransferase by microbial inhibitors and fatty acids.

Streptomyces sp. strain No. 560 produces four kinds of DNA methyltransferase inhibitors in the culture filtrate. One of them, DMI-4 was distinguished from DMI-1, -2 and -3 previously reported with respect to certain properties, DMI-4 is considered to be a triglyceride consisting of the fatty acids anteisopentadecanoic acid (C15:0), isopalmitic acid (C16:0) and isostearic acid (C18:0) from the results of gas chromatography analysis. Since DMI-4 contains three molecules of fatty acid, and the previously reported DMI-1, 8-methylpentadecanoic acid, is analogous to a fatty acid, the inhibitory activity has been examined of various fatty acids and their methyl esters against Eco RI DNA methyltransferase (M. Eco RI). Oleic acid (C18:1) was found to be a potent inhibiton of M. Eco RI. The inhibitory activity of oleic acid was shown to be pH- and temperature-dependent and inhibited M. Eco RI in a noncompetitive manner with respect to DNA or S-adenosylmethionine (SAM). The number of carbon atoms and double bonds in the fatty acid molecule affected the inhibitory activity, but their methyl esters were not inhibitors. Our results suggest that the length of the carbon chain, the number of double bonds and the presence of a carboxyl group and branched methyl group in the fatty acid molecule may play an important role in the inhibition of DNA methyltransferase.

DNA Modification Methylases↗

[Evaluation of efficacy for Japanese cedar pollen-specific immunotherapy by lymphocyte proliferation test].

Peripheral mononuclear cells from 47 patients suffering from Japanese cedar pollinosis were stimulated with crude pollen extract of Cryptomeria Japonica (CJ) to evaluate the effect of CJ-specific immunotherapy. The stimulation index (SI) with crude pollen extract of CJ in the patients with excellent and good clinical outcome was significantly lower than those with poor outcome. The SI increased with the increasing symptoms in a dose dependent manner. In the patients under immunotherapy for long period, the good clinical outcome and low SI were gained. These results suggest that peripheral lymphocyte proliferation test should be a good objective indicator for allergen-specific immunotherapy.

Adult↗

Accelerated cell-cycling of hematopoietic progenitor cells by growth factors.

Recent advances in molecular biology have led to the identification of hematopoietic growth factors that support and influence the proliferation of hematopoietic progenitor cells in vitro and in vivo. Although these factors have been extensively studied, little is known of their role in the regulation of cell-cycling of hematopoietic progenitors, especially in the early stage of hematopoiesis. In the present study, we examined the effects of early acting growth factors on proliferative kinetics of hematopoietic progenitors by monitoring the number of cells in individual developing colonies, using an in vitro clonal assay. Interleukin-11 (IL-11) or steel factor (SF), alone or in combination, shortened the time for the size of IL-3-dependent colonies to double. Consecutive replating experiments provided evidence for direct action of growth factors on the growth rate of hematopoietic progenitor cells. Shortening of the time for the total cell number in the colonies to double was due to a reduction in time for each single cell within the respective colonies to become two daughter cells, and there was no alteration in the incidence of cells with a proliferative capacity. Cell-cycle analysis demonstrated that IL-11 has the potential to induce a shortened time for cell-cycle of hematopoietic progenitor cells without affecting distribution of each fraction of the cell-cycle, whereas SF has the potential to reduce cell-cycle time mainly by decreasing the time required for hematopoietic progenitor cells to go through the G1 phase. These results suggest that growth factors may modulate cell-cycling of hematopoietic progenitor cells.

Animals↗

Insulin secretion from islets of GK rats is not impaired after energy generating steps.

Insulin secretory responses of intact and electrically permeabilised islets of Goto-Kakizaki (GK) rats, a novel model of non-insulin dependent diabetes mellitus, and Wistar (control) rats were compared to investigate the mechanism of the impairment of insulin secretion from pancreatic islets of GK rats. Insulin secretion from intact islets in response to glucose, glyceraldehyde, succinate monomethylester and tetramethyl p-phenylenediamine, which reduces cytochrome c directly, was significantly impaired in GK rats compared to control rats (P < 0.05, P < 0.01, P < 0.05 and P < 0.05, respectively). However, Ca(2+)-induced insulin release from electrically permeabilised islets of GK rats was higher than that of control rats. Moreover, insulin secretion from intact islets in response to 50 mM KCl, which depolarises islet cells, was not impaired in GK rats. These results indicate that insulin secretion from islets of GK rats is not impaired after energy generating steps of metabolism.

Animals↗

Ganglioside GM3 inhibits interleukin-3-dependent bone marrow-derived mast cell proliferation.

To investigate the modulated proliferation of an interleukin-3(IL-3)-dependent cell by exogenous ganglioside GM3, mouse bone marrow-derived mast cells (BMMC) were cultured with various concentrations of GM3 in the presence of IL-3. By 4 weeks of culture, most of the nonadherent cells were alcian blue-positive mast cells. Culturing 2-week-cultured BMMC with GM3 for 1 week reduced the number of alcian blue-positive cells, but the increased total histamine content of BMMC was observed. To examine the effect of GM3 on the synergistic response by IL-3 and interleukin-4 (IL-4), 3-week-cultured BMMC were cultured with GM3 in the presence of IL-3 and IL-4 for 1 week. Although the addition of IL-4 to culture medium increased the number of BMMC, treatment with GM3 reduced its proliferative activity. Concerning the effect of GM3 on cell membrane, there are no changes in the expression of IgE receptors on BMMC treated with GM3 though a low concentration of GM3 increased it. However, the production of tumor necrosis factor-alpha from BMMC treated with GM3 was significantly suppressed. These results indicate that in vitro treatment with exogenous GM3 inhibited the proliferative response of IL-3-dependent mast cell populations and modulated its characteristics.

Animals↗

Preliminary X-ray crystallographic studies of photosynthetic reaction center from a thermophilic sulfur bacterium, Chromatium tepidum.

A membrane protein complex, photosynthetic reaction center purified from the thermophilic purple sulfur bacterium, Chromatium tepidum has been crystallized from a phosphate buffer containing a detergent, n-octyl-beta-D-glucopyranoside and a precipitant, polyethylene glycol 4000. The crystals diffracted X-rays beyond 3A resolution with synchrotron radiation and are suitable for high-resolution X-ray crystallographic studies. The crystals belong to the orthorhombic space group P2(1)2(1)2(1) with unit-cell dimensions of a = 136A, b = 197A, and c = 82A. Assuming that they contain one reaction center complex in the asymmetric unit, VM was calculated to be 4.3 A3/Da, which agrees with the values obtained in the membrane protein complexes.

Chromatium↗