PubMed Health⌕ Search

Biomedical subjects

H Nakane

Publications and source records attributed to H Nakane.

At least 91 records · Page 5Linked to original sources
PubMed1988

Differential inhibition of various mammalian DNA polymerase activities by ammonium 21-tungsto-9-antimoniate (HPA23).

The 21-tungsto-9-antimoniate ammonium salt (HPA23), known as an antiviral agent, has been shown to be a potent inhibitor of both human and murine DNA polymerase alpha and murine DNA polymerase gamma. HPA23 inhibited the activity of DNA polymerase alpha in noncompetitive fashion with respect to either deoxynucleotide substrate or nucleic acid template.primer. The Ki of murine DNA polymerase alpha for HPA23 was determined to be 24 nM. The activity of mouse DNA polymerase gamma also was strongly inhibited by HPA23 (Ki, 20 nM), and the mode of inhibition was competitive with respect to the template.primer, (rA)n.(dT)12-18, and noncompetitive to substrate, dTTP. DNA polymerase beta and terminal deoxynucleotidyltransferase, however, were relatively resistant to inhibition by HPA23. The observed inhibitions by HPA23 seem to be closely related to the polyanionic property of this drug.

Animals↗
PubMed1988

Differential inhibition of various deoxyribonucleic and ribonucleic acid polymerases by suramin.

The inhibitory effects of hexasodium sym-bis(m-aminobenzoyl-m-amino-p-methylbenzoyl-1-naphthylamino-4,6, 8-trisulfonate)carbamide (trivial name: suramin) on the activities of various deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) polymerases from mammalian cells, bacteria and retrovirus were examined and compared with each other. Among the various DNA and RNA polymerases tested, the activities of DNA primase, DNA polymerase alpha, reverse transcriptase and Escherichia coli RNA polymerase were strongly inhibited by suramin, while the activities of other enzymes including DNA polymerases beta and gamma, terminal deoxynucleotidyl-transferase and DNA polymerase I were relatively resistant to inhibition by this drug. The inhibition by suramin of DNA polymerase alpha from KB cells and Rauscher murine leukemia virus (RLV) reverse transcriptase was due to competition with the respective template primer (activated DNA for alpha polymerase and (rA)n.(dT)12-18 for reverse transcriptase) for the template.primer-binding site of the enzyme, while the inhibition of DNA primase and E.coli RNA polymerase was due to competition with the ribonucleoside triphosphate substrate. The inhibition constants (Ki) of suramin were determined to be 2.6 microM, 0.35 microM, 0.54 microM and 0.70 microM for DNA primase, DNA polymerase alpha, RLV reverse transcriptase and E. coli RNA polymerase respectively. The observed inhibitions of these polynucleotide-synthesizing enzymes by suramin seem to explain, at least in part, an as yet unknown mechanism of trypanocidal action of this drug.

DNA Primase↗
PubMed1988

Establishment and characterization of a transplantable erythroblastic leukemia in C3H mice.

A disease with the characteristics of an erythroblastic leukemia was induced by X-ray irradiation of 300 Rads in C3H mice. The leukemia is transplantable in syngeneic mice by i.v. injection of the spleen cells. The mice show almost pure erythroid cells of various differentiation stages in peripheral blood. The number of total nucleated cells in the peripheral blood increased, but hematocrit and platelet number decreased. Reverse transcriptase activities were measured in spleen and liver of the mice and the data suggested that the leukemia was not induced by retrovirus infection. This leukemia is distinguishable, in this respect, from diseases reported by Friend or Rauscher. The leukemia will offer a good animal model for the studies on non-viral leukemogenesis and disorders of erythropoiesis.

Animals↗
PubMed1988

Stromal cell-dependent growth of leukemic cells from murine erythroblastic leukemia.

Transplantable erythroblastic leukemia was induced by 300-rad irradiation of C3H mice. Conditions for in vitro growth of the leukemic cells were studied. None of interleukin-3, granulocyte/macrophage colony-stimulating factor and erythropoietin could support the growth of the cells in vitro. In contrast, the leukemic cells grew into a stroma-dependent cell line, ELM-D, in close contact with the stromal cell layer of 900-rad-irradiated long-term bone marrow culture. A stroma-independent cell line, termed ELM-I-1, was further established from the non-adherent population in the co-culture of the leukemic cells, ELM-D, with stromal cells. Reverse transcriptase activity was not detectable in ELM-D or ELM-I-1 cells. Studies on binding and cross-linking of 125I-erythropoietin showed that ELM-I-1 cells had erythropoietin receptors, and two major radiolabeled protein products with molecular weights of 120 kDa and 140 kDa were detected on sodium dodecyl sulfate/polyacrylamide gel electrophoresis under reducing conditions.

Animals↗
PubMed1987

Effects of atrial natriuretic peptide on renal function and renin release in the isolated perfused rat kidney.

The effects of synthetic atrial natriuretic peptide (ANP) on the renal hemodynamics, glomerular filtration rate (GFR), fluid and electrolyte excretion and renin release were studied in the isolated perfused rat kidney (IPK). When 10(-9) mol of ANP was administered in 75 ml of perfusate, the renal vascular resistance (RVR) was transiently decreased for 3 to 5 min, thereafter increased for 30 min and then tended to return to the control level. ANP increased the GFR (0.55 +/- 0.08 to 0.71 +/- 0.07 ml/min), urine flow (UV) (0.018 +/- 0.002 to 0.194 +/- 0.028 ml/min), absolute Na excretion (UNaV) (1.83 +/- 0.03 to 17.93 +/- 2.71 microEq/min) and absolute K excretion (UKV) (0.67 +/- 0.13 to 2.33 +/- 0.18 microEq/min). The addition of indomethacin or mefenamic acid to the perfusate before the administration of ANP exerted no influence on any of the effects of ANP. Renin release was inhibited by approximately 50% compared to the ANP-free control group. With the administration of ANP, UV and UNaV reached a peak 15-20 min after the GFR reached a peak and remained elevated after the GFR fell below the control level. These findings suggest that 10(-9) mol of ANP causes natriuresis and renin suppression in the IPK, and that the natriuresis is prostaglandin-independent and cannot be explained only by an increase in GFR.

Animals↗
PubMed1987

Suppressive effects of various antitumor prostaglandin derivatives on the activity levels of DNA polymerases in human cultured tumor cells.

Some PG derivatives have been shown to be inhibitory for tumor cell growth. To elucidate the underlying mechanism(s) for this, we examined various DNA polymerase activities in PG-treated cultured cells. Human KBIII cells were exposed for one day to each of PGJ2, delta 7-PGA1 and delta 12-PGJ2 at a concentration of 5 micrograms/ml. The cells were harvested and homogenized, and the cell-free extracts were analyzed by phosphocellulose column chromatography for separation, identification, and quantification of each of the DNA polymerases. The results obtained were as follows: The activity of DNA polymerase alpha, which is responsible for DNA replication, has remained almost unchanged by any of the PG derivatives tested (77-87%), whereas the activity of DNA polymerase beta (repair enzyme) was found to dramatically decrease to 13 to 20% of that of the nontreated control cells by treatment with any of these PG derivatives. The results indicate that (a) these PG derivatives inhibit, either directly or indirectly, the synthesis of DNA polymerase beta in the KBIII cell, and (b) DNA polymerase beta may also participate in DNA replication other than DNA repair.

Antineoplastic Agents↗
PubMed1986

Inhibition of reverse transcriptase activity by 2',3'-dideoxythymidine 5'-triphosphate and its derivatives modified on the 3' position.

Inhibitory effects of 2',3'-dideoxythymidine 5'-triphosphate (ddTTP) and its three derivatives modified on the 3' position of ribose moiety [3'-azido-2',3'-dideoxythymidine 5'-triphosphate (3'-N3-ddTTP), 3'-amino-2',3'-dideoxythymidine 5'-triphosphate (3'-NH2-ddTTP) and 2'-deoxyxylo-furanosylthymine 5'-triphosphate (dXTP)] on the activity of the reverse transcriptase purified from Rauscher murine leukemia virus were examined and compared with each other. When (rA)n X (dT)12-18 was used as the template X primer in the presence of manganese ion, all these compounds except 3'-NH2-ddTTP inhibited the reverse transcriptase activity in competitive fashion with respect to the dTTP substrate. The inhibition potentials of these compounds are ordered as follows: 3'-N3-ddTTP (Ki = 1.8 microM) greater than ddTTP (Ki = 9.3 microM) greater than dXTP (Ki = 16.3 microM), and the Ki values of these inhibitors are smaller than the Km of dTTP (30 microM). The observed inhibitions were mainly due to competition between the dTTP substrate and inhibitor rather than chain-termination of the elongating DNAs caused by incorporation of these dideoxy compounds.

Binding, Competitive↗
PubMed1986

Biochemical and immunological characterization of Suncus murinus mammary tumor virus DNA polymerase.

Enzymological properties of the RNA-directed DNA polymerase associated with the Suncus murinus mammary tumor virus (Sm-MTV) was investigated and its antigenic relatedness to other retroviral DNA polymerases was examined. The enzyme exhibited higher activity in the presence of Mg2+ than in the presence of Mn2+ with endogenous RNA as well as with almost all of the synthetic template X primers tested. Mg2+ was also effective with poly(2'-O-methylcytidylate) X oligodeoxyguanylate which was known to be specific for Mn2+. To examine the immunological relatedness of this enzyme with other retroviral DNA polymerases, remaining Sm-MTV DNA polymerase activity was measured after treatment of this enzyme with various antisera prepared against each of the reverse transcriptases of Mason-Pfizer monkey virus (MPMV), murine mammary tumor virus (MuMTV), simian sarcoma virus-simian sarcoma associated virus (SSV/SSAV), and Rauscher murine leukemia virus (RLV). No inhibition of the Sm-MTV enzyme activity was observed when treated with the latter three antisera with which the DNA polymerase activities of the corresponding retroviruses were fully inhibited. Only the antiserum against MPMV-enzyme, however, was found to slightly inhibit the Sm-MTV enzyme activity. These results indicate that Sm-MTV DNA polymerase has similar enzymological properties to those of MPMV and MuMTV and shares some common antigenic determinant group(s) with MPMV DNA polymerase.

Animals↗
PubMed1986

Metabolism of bradykinin in isolated perfused rat kidney. Measurement of kininase activity in perfusate and urine.

The effect of bradykinin and kininase on renal function and the metabolism of bradykinin in the kidney were examined in isolated perfused rat kidney. In this experimental system, exogenous bradykinin did not affect the water and electrolyte handling by the kidney. Most of bradykinin and kininase in urine were derived from kidney but not from circulating medium. Kininase II may not have a major role in bradykinin destruction by the kidney.

Animals↗
PubMed1986

Differential inhibitory effects of Evans blue on various DNA polymerases.

Evans Blue, an anionic dye which has been found to inhibit the replication of human immunodeficiency virus, proved also inhibitory to the DNA polymerases alpha and beta. The mode of inhibition was competitive with respect to the template X primer, and noncompetitive with respect to the deoxynucleoside triphosphate substrates. The inhibitory effect of Evans Blue on DNA polymerases is discussed in relation to that of suramin.

Azo Compounds↗
PubMed1985

Effect of the angiotensin converting enzyme inhibitor, captopril (SQ14,225), on orthostatic sodium and water retention in patients with idiopathic edema.

Captopril (SQ14,225), an orally administered angiotensin converting enzyme inhibitor, was given to 8 patients with idiopathic edema, in order to study the role of the renin-angiotensin-aldosterone system in orthostatic sodium and water retention. Compared to 5 normal subjects, patients with idiopathic edema showed significantly greater reduction in water and sodium excretion, and greater increment in plasma aldosterone and plasma renin activity, in the upright posture. Captopril significantly restored water and sodium excretion, attenuated the increment in plasma aldosterone, and enhanced the rise in plasma renin activity in patients with idiopathic edema. The effects of captopril on these variables were not remarkable in normal subjects. These results suggest that an enhanced response of the renin-angiotensin-aldosterone system to standing plays an important role in the pathophysiology of idiopathic edema.

Adult↗
PubMed1985

Inhibition of the activities of DNA primase-polymerase alpha complex from KB cells by hexasodium sym-bis(m-aminobenzoyl-m-amino-p-methylbenzoyl-1-naphthylamino-4 ,6,8-trisulfonate)carbamide.

A trypanocidal drug suramin [hexasodium sym-bis(m-amino-benzoyl-m-amino-p-methylbenzoyl-1-naphthylamino-4, 6, 8-trisulfonate)carbamide] was found to be a potent inhibitor of the activities of DNA primase and polymerase alpha from human KB cells. The mechanism of the inhibition by suramin was, however, quite different by these two polymerases. In the case of DNA primase, suramin inhibited competitively the incorporation of a nucleotide substrate, GTP, on the template polydeoxycytidylate, while the polymerase alpha was inhibited competitively by the drug with respect to the template primer (activated DNA). The observed inhibitory effect of suramin on nucleic acid synthesis seems to explain yet unknown mechanism of trypanocidal action of the drug.

Binding, Competitive↗
PubMed1984

Induction of cellular DNA polymerases in a Burkitt lymphoma-derived cell line by treatment with 5-iododeoxyuridine.

Cellular DNA polymerases of a Burkitt lymphoma-derived cell line (P3HR-1) were found to be greatly induced by treatment of the cells with 5-iododeoxyuridine (IUdR) at a concentration which induces Epstein-Barr virus (EBV) early antigen (EA) expression. The activities of all the DNA Polymerases alpha, beta and gamma in P3HR-1 cells increased 7-9 fold by exposure of the cells to IUdR (25 micrograms/ml) for 3 days, while the EBV-coded DNA polymerase activity in the cell remained undetectable under the assay conditions employed. Under the same culture conditions with IUdR, EA-positive P3HR-1 cells increased to 16.6% which was much higher than that of the non-treated control cells (0.32%). On the other hand, another Burkitt lymphoma cell line, Raji, had very low incidence (1.27%) of EA induction by IUdR-treatment and the level of DNA polymerase activities remained almost unchanged. From these results it seems that the increase in DNA polymerase activity during the treatment of P3HR-1 cells with IUdR is closely related to high incidence of EA expression in these Burkitt lymphoma cells. Also, the finding has revealed yet unknown effect of IUdR on cultured cells and provides a useful tool to obtain a large quantity of the induced cellular DNA polymerases from the P3HR-1 and KB cells.

Burkitt Lymphoma↗
PubMed1984

The enhancement of tumor cell susceptibility to macrophage binding and cytolysis by p-aminobenzoic acid-N-xyloside sodium salt (K-247).

The enhancement of tumor cell susceptibility to macrophage binding and cytolysis by the pretreatment of tumor cells by p-aminobenzoic acid-N-xyloside sodium salt (K-247) was investigated in the C3H/He mouse-syngeneic tumor system. Binding and cytolytic activities of Corynebacterium parvum-activated macrophages were significantly enhanced when target MM-102 and MH-134 cells were pretreated with K-247 at doses of 200 or 400 micrograms/ml, while thioglycollate-elicited macrophages showed much lower binding and lytic activities against K-247 pretreated target cells. No enhancement of these activities were observed when target cells were pretreated with D-xylose, which had no anti-tumor activity. Furthermore, in a binding assay a significant reduction of macrophage binding to target cells by the K-247 pretreated cold competitors was observed. It is suggested that target cell susceptibility to macrophage cytolytic activity might be enhanced by pretreatment with K-247, involving an initially increased target binding.

4-Aminobenzoic Acid↗
PubMed1984

Excretion and metabolism of dopa and dopamine by isolated perfused rat kidney.

The renal metabolism and handling of dopa and dopamine were studied with the use of the isolated perfused rat kidney to elucidate the source of urinary dopamine. Dopa added to the perfusate was rapidly metabolized, and a significant amount of urinary dopamine excretion was observed, whereas dopa was not detected in the urine. When the perfusate dopa concentration was near the plasma dopa concentration in normal rats, urinary dopamine excretion was comparable with physiological values. Carbidopa, a dopa decarboxylase blocker, added to the perfusate markedly reduced the urinary excretion of dopamine. When the physiological concentration of dopamine was added to the medium, the perfusate dopamine rapidly decreased and urinary dopamine excretion was much less than that seen in normal rats. In studies with nonfiltering kidneys, a marked decrease of dopa and slight increase of dopamine in the perfusate were observed. It is suggested that the process of glomerular filtration and tubular reuptake of dopa is not essential for renal dopamine formation. These data indicate that urinary free dopamine is mainly derived from plasma dopa, which is converted by dopa decarboxylase in the kidney.

Animals↗
PubMed1984

Inhibition of DNA polymerase alpha activity by ammonium 21-tungsto-9-antimoniate (HPA23).

Ammonium 21-tungsto-9-antimoniate (HPA23), an inorganic condensed ion, was shown to be a potent inhibitor for DNA polymerase alpha but not for beta. It inhibited the activity of mammalian DNA polymerase alpha in noncompetitive fashion with respect to either of deoxynucleotide substrate and template X primer, indicating the presence of a specific binding site for HPA23 on DNA polymerase alpha molecule. The Ki of the alpha polymerase for HPA23 was 24 nM. A possible interaction of HPA23 with DNA polymerase alpha is discussed.

Animals↗