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Biomedical subjects

H Nakane

Publications and source records attributed to H Nakane.

At least 109 records · Page 6Linked to original sources
PubMed1984

Inhibition of DNA polymerase alpha by 2',3'-dideoxyribonucleoside 5'-triphosphates: effect of manganese ion.

Inhibitory effects of 2',3'-dideoxyribonucleoside 5'-triphosphates (ddNTP's) on the activity of mouse myeloma DNA polymerase alpha were examined. In contrast to the widely accepted conclusion that DNA polymerase alpha was not inhibited by ddNTP, our results showed that all 4 ddNTP's (ddATP, ddCTP, ddGTP, ddTTP) exhibited strong inhibitory power to this enzyme in the presence of Mn2+. The observed inhibitions by ddNTP's were neither due to chain termination of growing DNA nor to enzyme inactivation by these compounds, but due to competition with deoxynucleoside triphosphate with the same base. The inhibition constant (Ki) varied depending on the combination of template-primer, substrate and inhibitor. The results suggest that Mn2+ plays a role in increasing affinity of the dideoxynucleotides to DNA polymerase alpha by interacting with anyone or more of the dideoxynucleotide, enzyme and template-primer.

Animals↗
PubMed1984

[Four gastrectomized cases associated with chronic leukemia].

We reviewed 4 gastrectomized cases associated with chronic leukemia. Three patients had chronic myelogenous leukemia, one had hairy cell leukemia. Subtotal gastrectomy was performed in all cases; two operations were for gastric cancer and two for bleeding gastric ulcers. The spleen was removed in three patients without any trouble. There were no difficulties in managing the patients during and after surgery and their leukemia was not aggravated during these periods.

Aged↗
PubMed1983

Concanavalin A-induced and spontaneous suppressor cell activities in peripheral blood lymphocytes and spleen cells from gastric cancer patients.

In 173 gastric cancer patients, activities of Concanavalin-A-induced suppressor cells (Con-AS) and spontaneous suppressor cells (SpS) in peripheral blood lymphocytes (PBL), splenic vein lymphocytes (SVL), and spleen cells (SCs) were investigated. Suppressions by Con-AS in PBL were significantly effective in patients of Stages III and IV, while suppressions by SpS were effective in patients with recurrent tumors. Thus, in PBLs of cancer patients, suppressor precursors, which are considered to be activated in vitro by Concanavalin-A, seemed to appear with the advances of the disease, and SpS activities, which could be already activated in vivo, seemed to increase in the terminal stage. In SCs, increased activities of Con-AS, but normal activities of SpS, were observed, and these suppressor-cell populations consisted of glass nonadherent cells. Suppressor activities of SCs would be due to suppressor T-cells, not to other types of cells. Furthermore, Con-AS existed in the medium-sized lymphocytes, which were fractionated on the basis of cell size, while SpS in the large-sized lymphocytes. A higher proportion of T-cells, bearing Fc receptors for IgG, was observed in the larger-sized lymphocyte fractions. Cell numbers in the large-sized lymphocyte fraction tended to increase with the advances of tumors. From these results, it is suggested that higher presence of suppressor precursors and the increase of SpS activities may occur in cancer patients, depending on the tumor advancing.

Adult↗
PubMed1983

Effects of angiotensin I converting enzyme inhibitors on the renal excretory function, hemodynamics and renin release in isolated perfused rat kidney.

Direct renal effects of angiotensin I converting enzyme inhibitors (CEIs), captopril, SA446 and MK421, were examined in isolated rat kidneys perfused with a renin-substrate-free medium. Among three CEIs, only captopril induced a significant natriuresis, whereas SA446 and MK421 did not. UKV, renal vascular resistance and creatinine clearance were not affected by any of these CEIs. Renin release from perfused rat kidneys were not influenced by CEIs under the present experimental conditions. These results suggest that among three different types of CEIs, only captopril possesses natriuretic action in the isolated perfused rat kidney and that this action may be independent of its inhibitory action on angiotensin converting enzyme. It is also suggested that these three CEIs themselves do not have a direct effect on the renal vascular bed.

3-Mercaptopropionic Acid↗
PubMed1983

[Enhancement of antitumor activity of Propionibacterium avidum in combined with neurotropin in tumor bearing mice].

The enhancement of antitumor activity of Propionibacterium avidum (P. avidum) in combination with Neurotropin (NSP) was investigated in C3H mice-MH 134 tumor system. P. avidum (0.5 mg) and NSP (20 mg/kg) were administered on day 2 and from day 1 to 7 after tumor inoculation, respectively. When mice were treated with P. avidum in combination with NSP, a significant prolongation in survival days was observed (P less than 0.01). Treatment with P. avidum alone produced prolongation in survival days, but NSP did fail. Increase of Con-A induced suppressor cell activity and depressed proliferative response of spleen cells were observed by the treatment with P. avidum. However, recovery of proliferative response to normal level and disappearance of suppressor cell activity were observed when NSP was combined. Thus, treatment by P. avidum in combination with NSP produced a significant prolongation in survival days and it may be depending on macrophage activation by P. avidum and on the restoration of T cell functions by NSP.

Animals↗
PubMed1983

[Analysis of suppressor cell activities in spleen cells from gastric cancer patients and the effect of splenectomy on prognosis of gastric cancer].

In gastric cancer patients, activities of Concanavalin-A induced suppressor cells ( ConAS ) and spontaneous suppressor cells (SpS) in spleen cells (SC), peripheral blood lymphocytes (PBL) and splenic vein lymphocytes (SVL) were comparatively investigated. Suppressions by ConAS in PBL were significantly increased in patients of Stages III and IV, while suppressions by SpS were increased in patients with recurrent tumors. Elevated activities of ConAS and SpS were observed in SCs and SVLs , respectively. ConAS activities were mostly indicated in the medium sized lymphocyte fractions which were fractionated on the basis of cell size, while SpS activities in the larger sized fraction. Cell numbers in the large sized lymphocyte fraction which contained higher proportion of Tg cells and OKT8 reactive T cells, tended to increase with advances of the disease. These results suggest that spleen contained much higher proportion of suppressor precursors which might be activated to become suppressor cells with advances of the disease. Furthermore, the effect of splenectomy on the prognosis of gastric cancer was investigated in randomized controlled trial. The patients who underwent total gastrectomy and had main location of the tumor on lesser curvature region were divided into two groups at random; splenectomy (+) and splenectomy (-) groups. A suggestive prolongation of survival time was observed in splenectomy (+) group. Thus, spleen seems to contribute to the immunosuppression in gastric cancer patients and splenectomy may lead to better prognosis.

Adult↗
PubMed1983

[Enhancement of in vitro lymphocyte proliferative response by vitamin B compounds].

The effects of Vitamin B compounds consisting of B1, B6 and B12 on the in vitro lymphocyte proliferative (LP) response were investigated. Vitamin B compounds failed to enhance the LP response of healthy controls but did enhance that of cancer patients, suggesting the recovery of depressed LP response to normal level by the treatment employing the compounds. The addition of Vitamin B compounds in the generation phase of Concanavalin-A induced suppressor cells significantly abrogated the activities. However, Vitamin B compounds produced no effect to neutralize the inhibitory effect of cancer sera on LP response.

Concanavalin A↗
PubMed1983

Inhibition of terminal deoxynucleotidyltransferase by (E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-triphosphate.

(E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-triphosphate (BVdUTP), known as a specific inhibitor of herpes simplex virus (type 1)-DNA polymerase, was found to be a potent inhibitor of the activity of terminal deoxynucleotidyltransferase (TdT) from calf thymus. BVdUTP was not an efficient substrate of TdT, but it inhibited the incorporation of normal deoxynucleotide substrates in competitive fashion at the nucleotide binding site of TdT molecule. The Ki value for BVdUTP (5 microM) was much less than the Km value for dGTP (83 microM), indicating stronger affinity of the inhibitor to TdT than that of the substrate. These results indicate the usefulness of BVdUTP as a potent inhibitor of TdT for elucidation of the reaction mechanism of this enzyme.

DNA Nucleotidylexotransferase↗
PubMed1983

Inhibition of terminal deoxynucleotidyltransferase by various 5-alkylated derivatives of 1-beta-arabinofuranosyluracil 5'-triphosphate: substituent effects on inhibitory action.

Inhibitory effects of 1-beta-D-arabinofuranosyluracil 5'-triphosphate (ara-UTP) and its 5-alkylated derivatives [1-beta-D-arabinofuranosylthymine 5'-triphosphate (ara-TTP): 1-beta-D-arabinofuranosyl-5-ethyluracil 5'-triphosphate (ara-EtUTP); 1-beta-D-arabinofuranosyl-5'-propyluracil 5'-triphosphate (ara-PrUTP); 1-beta-D-arabinofuranosyl-5-butyluracil 5'-triphosphate (ara-BuUTP)] on the activity of terminal deoxynucleotidyl-transferase (TdT) from calf thymus were examined. All these compounds inhibited TdT activity by competition with the natural substrate dTTP for the same substrate-binding site of the enzymes. The extent of inhibition by the inhibitor, however, decreased by introducing an alkyl group on the 5-position of the uracil nucleus, indicating the importance of inductive and steric effects of the 5-substituents on TdT. Of the four 5-alkylated ara-UTP's, ara-EtUTP was less inhibitory to TdT than the other compounds, and the potency of inhibition was restored by replacing 5-ethyl group with longer propyl or butyl group, suggesting that the hydrophobic effects of these 5-alkyl side chains are involved in the inhibitory action of the compounds. The results are compared and discussed with those of our previous report on the inhibition of DNA polymerase alpha and beta by these 5-alkylated ara-UTP's (Ono et al., 1981).

Alkylation↗
PubMed1982

Direct renal action of captopril (SQ 14225): dissociation of natriuretic and vascular actions in isolated perfused rat kidney.

Direct effects of captopril on renal function were examined in isolated perfused rat kidneys. Captopril induced a significant increase in urinary volume and urinary sodium excretion (1.8- and 1.7-fold, respectively; both p less than 0.005), whereas urinary potassium excretion and renovascular resistance were not significantly changed. Because the perfusion medium lacks angiotensinogen, kininogen and aldosterone, the natriuretic action in perfused kidneys may not be related to its inhibitory action on angiotensin I converting enzyme or kininase II. Because the natriuresis was not accompanied by changes in renovascular resistance, it is suggested that captopril possesses a direct natriuretic action and that this property may partly explain the mechanism of captopril-induced natriuresis clinically observed.

Animals↗
PubMed1982

Allosteric inhibition by aphidicolin of the activity of DNA polymerase alpha from mouse myeloma.

The mechanism of inhibition by aphidicolin of the activity of purified DNA polymerase alpha was studied. In the presence of aphidicolin and activated DNA, DNA polymerase alpha from mouse myeloma did not show Michaelis kinetics with respect to changes in nucleotide substrate concentration (i.e., dGTP & dTTP). A plot of the reaction velocity versus dGTP or dTTP concentration was hyperbolic with an intermediary plateau. The double reciprocal plot was concave downwards, and the Hill plot gave Hill coefficients of less than 1.0 over most of the curve. These results indicate that aphidicolin acts as an allosteric inhibitor for DNA polymerase alpha and that DNA polymerase alpha functions as a multisite enzyme that exhibits negative cooperativity among at least 3 binding sites of the nucleotide substrates (dGTP & dTTP).

Animals↗
PubMed1982

Inhibitory effects of diadenosine polyphosphates and diguanosine polyphosphates on terminal deoxynucleotidyltransferase from calf thymus.

The effects of diadenosine 5', 5"'-polyphosphates (ApnA's, n = 2-6) and diguanosine 5', 5-polyphosphates (GpnG's, n = 2-6) on the activity of terminal deoxynucleotidyltransferase (TdT) from calf thymus were investigated. Both ApnA's and GpnG's (n greater than or equal to 3) were found to inhibit TdT activity. The inhibitory effects were the strongest when TdT activity was measured by determining the incorporation of dCTP. The inhibition by ApnA's and GpnG's was due to competition with the substrate deoxynucleoside triphosphate(s). The inhibition constant (Ki) varied depending on the triphosphate substrate used, but in most cases Ki value decreased by increasing the number of the phosphoryl group of the dinucleotide inhibitors.

Adenine Nucleotides↗
PubMed1981

Effect of adrenalectomy and aldosterone on the modulation of mineralocorticoid receptors in rat kidney.

Adrenalectomized rat kidney is commonly used for the study of mineralocorticoid mechanism of action in mammals. In this model, aldosterone is known to bind to two classes of binding sites: type I (mineralocorticoid) and type II (glucocorticoid). The study of the aldosterone binding in normal rat kidney requires the elimination of endogenous hormones bound to each type of receptor. Thus, a suitable technique was developed using in situ perfusion of the kidneys. The efficacy of this method was of about 85 to 90% at the level of both cytoplasm and nucleus. Aldosterone binding capacity was checked in normal rat kidney after in situ perfusion and was found to be 300 to 500% lower than in adrenalectomized rat kidney, both in cytoplasm and nuclei. Computer analysis of aldosterone binding parameters in the cytoplasm (30,000 X g supernatant) of rat kidney suggested that adrenalectomy might induce an important rise in the number of mineralocorticoid receptors (congruent to 260%). An increase in the number of glucocorticoid receptors was also observed but appeared to be lower. Aldosterone, when perfused during 24 h in adrenalectomized rats, lowered the number of type I sites to the same level as observed in normal rat kidney. This effect was fully reversible after interruption of aldosterone perfusion. These results suggested an aldosterone-induced down regulation of mineralocorticoid receptors.

Adrenalectomy↗
PubMed1980

Sodium balance and renin regulation in rats: role of intrinsic renal mechanisms.

Renin secretion was compared in vivo and in vitro among five groups of rats, each group subjected to a different sodium balance for 10 to 14 days. The state of the renin-angiotensin system in vivo was evaluated by measuring the renal renin (RR) and the plasma renin concentration (PRC) in both anesthetized and nonanesthetized animals. The in vitro renin secretion rate (RSR) was determined in isolated perfused kidneys. RR was reduced (-48%) by sodium loading and deoxycorticosterone (DOCA) and increased (+27%) by sodium deprivation and furosemide. Sodium loading and DOCA reduced both the PRC and the RSR to less than 20% of control values. By contrast, sodium deprivation and furosemide induced a more than fourfold rise in the PRC but only a small increase in the RSR (+37%). These results indicate that changes in fractional renin release are induced by sodium balance variation, and these changes are preserved in vitro only in sodium-loaded states. The inability of sodium-deprived kidneys to maintain high renin release in vitro suggests that high plasma renin levels in these rats depend on mechanisms that are not preserved in vitro. There was no evidence supporting the participation of inactive renin secretion in the regulation of fractional renin release under varying sodium balance.

Animals↗
PubMed1980

A comparison of multiple forms of renin in rat renal perfusate with those in renal extract.

1. Physicochemical properties of renin secreted by isolated perfused rat kidney were examined and the results compared with those obtained for the renin in renal extract. 2. In renal extract, two high-molecular-weight renins (molecular weight 65 000 and 55 000) and one low-molecular-weight renin (molecular weight 39 000) were found. Their relative proportion varied depending on extraction conditions. By acidification, high-molecular-weight renins were converted into low-molecular-weight renin without marked changes in activity. 3. In renal perfusate only low-molecular-weight renin was found after renin stimulation by isoprenaline or anoxia. Inactive renin was not found. 4. Renin in renal extract and perfusate samples were both found to consist of at least four isoenzymes having different isoelectric points (pI). The pI patterns were identical in renal extract and perfusate samples: pI 5.7 (60-70%), 5.5 (15-25%), 5.3 (5-10%) and 5.0-5.2 (2-5%). 5. These results indicate that the native renin secreted by rat kidney consists entirely of the low-molecular-weight and active form comprising multiple isoenzymes with a stable pI pattern.

Animals↗
PubMed1980

Effects of selective and nonselective beta adrenergic agents on renin secretion in isolated perfused rat kidney.

The effects of selective and nonselective beta adrenergic drugs on the renin secretion rate (RSR) in isolated perfused rat kidneys were studied. Both isoproterenol (Ipr) (nonselective agonist) and salbutamol (Salb) (beta-2 selective agonist) stimulated RSR in a dose-dependent manner. The lowest doses able to induce a significant RSR increase were 5 nM for Ipr and 50 nM for Salb. A 5-fold increase in RSR was induced by 500 nM Ipr and a 3.2-fold increase by 5 microM Salb. Renin stimulation by both agonists was suppressed by propranolol (nonselective) and by acebutolol and its derivative M&B 16,942 (beta-1 selective antagonists). Thus, renin release was stimulated or inhibited effectively by all the drugs tested, regardless of the beta selectivity of agonists and antagonists. There were no consistent relationships observed between changes in renal hemodynamics and in RSR, suggesting that the used drugs affected renin release from in vitro-perfused rat kidney through their direct effects on juxtaglomerular cells. These results indicate that renal beta adrenoreceptors involved in renin release do not fall into two distinct beta subtypes.

Acebutolol↗
PubMed1979

Assessment of the clinical usefulness of serum ribonuclease assays: an indicator for the detection of pancreatic cancer.

To evaluate diagnostic usefulness for pancreatic cancer, serum ribonuclease (RNase) level was determined in three groups of subjects; 1) normal volunteers as control, 2) patients with histologically determined pancreatic cancer, and 3) patients with miscellaneous diseases other than pancreatic cancer. A small increase of RNase values was recognized with age in the normal subjects and in the patients with nonpancreatic diseases, if renal function was normal. The mean RNase level in the control subjects was 97 +/- 41.2 units. A marked elevation of serum RNase level was demonstrated in the patients with pancreatic cancer (p less than 0.001) and in the patients with renal dysfuction, but no significant rise was noticed in the patients with pancreatitis. Mean values of RNase in the patients with pancreatic cancer and renal dysfuncton were 368 +/- 146 units and 342 +/- 78.1 units respectively. RNase values above 300 units were recognized in 15(71%) out of 21 patients with pancreatic cancer. Seven cases with elevated RNase over 300 units other than non-pancreatic malignancy and renal dysfunction were noticed in 6 instances of obstructive jaundice and in one instance of early gastric cancer (an 84-year-old male). The above-stated findings indicate that serum RNase determinations can be utilized as a diagnostic indicator for pancreatic cancer.

Adult↗