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Biomedical subjects

N Watanabe

Publications and source records attributed to N Watanabe.

At least 1,045 records · Page 58Linked to original sources
PubMed1987

[The synergistic effect of human recombinant TNF in combination with various anti-cancer drugs].

The synergistic effect of human recombinant TNF in combination with various anti-cancer drugs was examined in vitro. In vitro treatment of L-M cells with TNF and mitomycin C (MMC), adriamycin (ADM), cytosine arabinoside (Ara-C), actinomycin D (ACD), daunorubicin (DM), cisplatin (CDDP), vincristine (VCR), or 5-fluorouracil (5-FU) revealed a synergistic cytotoxicity. However, the combination of TNF with bleomycin (BLM) failed to show such a synergistic effect.

Animals↗
PubMed1987

Nifedipine suppressed atherosclerosis in cholesterol-fed rabbits but not in Watanabe heritable hyperlipidemic rabbits.

We studied the effects of nifedipine, a calcium antagonist, on atherosclerosis in cholesterol-fed rabbits and Watanabe heritable hyperlipidemic rabbits (WHHL rabbits). Japanese White rabbits were fed 120g of 2% cholesterol rabbit chow daily, and WHHL rabbits were fed standard rabbit chow. In each experiment, the rabbits were divided into two groups. Twenty milligrams of nifedipine was given orally twice a day to the nifedipine group, and the control group was given a placebo in the same way. The rabbits were sacrificed at the end of the 12th week in the case of cholesterol-fed rabbits, and the 20th week in the case of WHHL rabbits. Among the cholesterol-fed rabbits, the percentage of aortic intimal surface area covered by atherosclerotic lesions (AS%) was 25.9 +/- 7.6% (mean +/- S.D.) in the nifedipine group (n = 7), and 55.6 +/- 22.8% in the placebo group (n = 8) (p less than 0.01). The cholesterol content of thoracic and abdominal aorta in the nifedipine group was lower than those in the placebo group (p less than 0.05). Among the WHHL rabbits, the AS% was 33.4 +/- 14.1% in the nifedipine group (n = 5), and 27.0 +/- 11.7% in the placebo group (n =6) (n.s.). The aortic cholesterol and calcium contents also showed no significant differences between the two groups. We concluded that nifedipine suppressed atherosclerosis in cholesterol-fed rabbits but not in WHHL rabbits. The different responses suggest that the effect of nifedipine could be mediated by low density lipoprotein receptors or that the early exposure to hyperlipidemic serum from birth might affect cell functions of WHHL rabbits.

Administration, Oral↗
PubMed1986

Replication timing: histone genes replicate during early S phase in cleavage-stage embryos of sea urchin.

Newly synthesized DNA was separated from the bulk of the DNA by pulse-labeling with BUdR and centrifugation in an alkaline CsCl buoyant density gradient. The content of histone gene in the newly synthesized DNA was determined by DNA dot hybridization. The gene contents in DNA replicated during the early half of S phase and during the whole S phase were compared. Results showed that histone genes were replicated during the first half of the S phase in embryos in the early cleavage stage.

Animals↗
PubMed1986

Cytotoxic effects of paraquat and inhibition of them by vitamin E.

Paraquat causes failure of multiple organs including the liver in humans. The kinetics and mechanism of paraquat intoxication were studied using cultured rat hepatocytes. Paraquat induced time- and dose-dependent lactate dehydrogenase release, lipid peroxidation, and cell death, estimated as decrease in protein in cells attached to culture dishes. However, the increase in lipid peroxidation occurred after lactate dehydrogenase release had reached a plateau. Vitamin E inhibited the inductions of all these cytotoxic effects of paraquat. Kinetic studies showed that lipid peroxidation was a better indicator of cell death than lactate dehydrogenase release, because vitamin E inhibited the induction of cell death even when added 6 h after paraquat, when lactate dehydrogenase release had reached a plateau but lipid peroxidation had not. The present results strongly suggest that paraquat exerts its cytotoxicity by a mechanism involving oxidation reactions.

Animals↗
PubMed1986

Effects of carbamazepine and valproic acid on brain immunoreactive somatostatin and gamma-aminobutyric acid in amygdaloid-kindled rats.

Somatostatin and gamma-aminobutyric acid (GABA) concentrations were evaluated in the brain of kindled rats treated chronically with carbamazepine and valproic acid. Kindled seizures were almost completely blocked by treatment with carbamazepine, whereas the effect of valproic acid was partial, suppressing only generalized seizures. The duration of after-discharge in amygdala was suppressed by carbamazepine not by valproic acid. Carbamazepine induced a decrease in immunoreactive somatostatin concentration and an increase in GABA concentration in the temporal cortex of kindled rats. Valproic acid induced only an increase in GABA concentration. The results suggest that somatostatin may be associated with the suppression of focal seizure in amygdala and GABA may have a role in the suppression of generalized seizures.

Amygdala↗
PubMed1986

An immunochemical study of delta-aminolevulinate synthase and delta-aminolevulinate dehydratase in liver and erythroid cells of rat.

The relationship between erythroid delta-aminolevulinate (ALA) synthase and hepatic ALA synthase in rat was analyzed immunochemically, using antibodies directed against rat liver ALA synthase and against chicken liver ALA synthase. Rat erythroid ALA synthase showed no cross-reactivity with anti-liver ALA synthase antibodies, but hepatic ALA synthases from rat, mouse, and chicken share substantial cross-reactivity with one another. These results clearly distinguish the isozyme relationship between erythroid ALA synthase and hepatic ALA synthase in rat and suggest that there may be at least two different ALA synthase genes in rat. ALA dehydratase in rat liver, on the other hand, could not be immunochemically distinguished from ALA dehydratase in rat erythroid cells when antibody against rat erythroid ALA dehydratase was used. The finding that erythroid ALA synthase is an entity different from hepatic ALA synthase may provide a clue to understanding the different features in hepatic and erythropoietic porphyrias.

5-Aminolevulinate Synthetase↗
PubMed1986

[Studies on plasma insulin-like growth factor (IGF)-I levels in normal subjects and in patients with various endocrine and metabolic diseases using radioimmunoassay for synthetic IGF-I (26-46)].

Determination of plasma IGF-I concentrations is not easily accessible to clinical use at present because of extremely limited supply of purified natural IGF-I essential for its assay system. Thus, an alternative method has recently been introduced by the development of a specific radioimmunoassay (RIA) for IGF-I (26-46). We examined the specificity and sensitivity of this assay system, and then investigated the changes in plasma concentrations of IGF-I in normal children, adults and in patients with various endocrine and metabolic diseases. Each plasma sample was subjected to acid-ethanol treatment before assay to separate IGF-I from its binding protein. The recovery rate of known amount of IGF-I (26-46) added to untreated plasma sample was more than 90%. The coefficients of variation of intra- and interassay were 9.0% and 13.6%, respectively. This assay system was able to detect IGF-I as low as 10 pg/tube. When plasma sample of a patient with active acromegaly was applied to Sephadex G-75 column, immunoreactive IGF-I was eluted at the position of 7,000 molecular weight. An inhibition curve of plasma extract from an acromegalic patient was parallel to that of IGF-I (26-46), indicating that the RIA could detect IGF-I. There was no remarkable difference between IGF-I values of plasma and serum from the same individual. The value of IGF-I concentration of cord plasma was considerably low (144 +/- 6.7 pg/ml, M +/- SEM) as compared with that of sera of 49 normal children aged 7-12 12 years (320 +/- 14.3 pg/ml). The highest value (460 +/- 54 pg/ml) was attained at the age of 13 years, followed by gradual decrease toward adult age. Plasma IGF-I concentration of normal adults between 20 and 69 years of age was 290 +/- 10 pg/ml. When plasma IGF-I values of adult males and females were separately plotted against age group of each decade, the value declined gradually with age in males while in females there was a remarkable increase in plasma IGF-I concentration at 4th and 5th decades, suggesting the effect of hormonal change at menopause on plasma IGF-I levels. There was a good correlation between disorders of GH secretion and plasma IGF-I concentrations. In 10 cases of active acromegaly the level was 506 +/- 67 pg/ml (285-970 pg/ml). On the other hand in 20 patients with pituitary dwarfism it was only 180 +/- 15 pg/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1986

Effect of duration of diabetic state on insulin action in isolated rat soleus muscles.

We studied the effect of the duration of diabetic state on insulin action in skeletal muscle by measuring insulin binding, 2-deoxyglucose uptake, and intracellular glucose metabolism in isolated soleus muscles from streptozotocin-induced diabetic rats. Insulin binding to soleus muscles from diabetic rats was increased over that from controls. Glucose transport activity was determined by measuring the 2-deoxyglucose uptake at the concentration of 1 mmol/L at 25 degrees C. In the rats with diabetes of one week duration, insulin-stimulated 2-deoxyglucose uptake was not impaired, whereas basal 2-deoxyglucose uptake was decreased. However, the diabetic rats with two weeks duration revealed a 35.6% decrease in the insulin-stimulated 2-deoxyglucose uptake. Furthermore, four week duration of diabetic state led to a 60% decrease both in basal and insulin-stimulated 2-deoxyglucose uptake. Total glucose utilization was estimated as the total amount of glucose incorporated into muscle and lactate released into the medium following incubation at 37 degrees C, with 5 mmol/L glucose. The diabetic rats with one week duration did not demonstrate any changes in total glucose utilization both in basal and insulin-stimulated state. However more than two weeks duration of diabetes led to a 30% to 35% decrease both in basal and insulin-stimulated total glucose utilization, similar to the findings in the 2-deoxyglucose uptake study. We concluded that prolonged insulinopenia led to decreased glucose transport and intracellular glucose metabolism and resulted in insulin resistance in skeletal muscles.

Animals↗
PubMed1986

A primary defect in insulin receptor in a young male patient with insulin resistance.

We studied insulin binding to cells from an insulin-resistant patient, a 5-year-old boy with clinical Rabson-Mendenhall syndrome. Decreased insulin binding was observed in three different cells: erythrocytes (37.4% of normal), cultured fibroblasts (53.3% of normal), and transformed lymphocytes (9.8% of normal). Decreased insulin binding in the cultured cells suggested that the patient had a primary defect in insulin receptors. In addition, insulin binding to the transformed lymphocytes from the patient was relatively high at lower pH compared with those in normal subjects. The cultured fibroblasts from the patient showed decreased glucose incorporation at the low insulin concentration with normal maximal stimulation, and the insulin dose response curve was shifted to the right. These results suggested that the defect resided in the receptor binding but not in the postreceptor steps. This was one of the rare cases showing decreased insulin binding clearly demonstrated in three different cells from a young male patient with extreme insulin resistance.

Child↗
PubMed1986

Release of tumor necrosis factor (TNF) into mouse peritoneal fluids by OK-432, a streptococcal preparation.

A cytotoxic factor was induced in peritoneal fluid by injection of OK-432 in mice which had been primed with OK-432. Two-step stimulation (priming and eliciting) was always necessary to induce the cytotoxic factor. OK-432-primed mice did not produce soluble cytotoxic factor spontaneously and no cytotoxic activity was detected in the mice treated by a single injection of OK-432 as an eliciting agent. This observation was also confirmed by in vitro experiments. Only when activated macrophages were incubated with OK-432 (or with lipopolysaccharide) was cytotoxin released into medium supernatant. High doses of OK-432 were required to prime mice for the production of cytotoxic factor, whereas a small amount was enough to elicit. The peritoneal cytotoxic factor obtained by OK-432 injection appears to be identical to tumor necrosis factor in the serum for the following reasons: The two factors are similar in mode of cytotoxic action. Both are produced from macrophages. They are similar in physicochemical characteristics. The cytotoxicity of the peritoneal cytotoxic factor was totally abolished by anti-TNF serum.

Animals↗
PubMed1986

Characterization of a cytotoxic factor induced in mouse peritoneal fluid by OK-432.

A cytotoxic factor (peritoneal cytotoxic factor, PCF) was strongly induced by the injection of LPS into the peritoneal fluids of mice which had been previously primed with OK-432. In order to clarify characteristics of PCF, physicochemical and immunological studies were conducted. When incubated with LPS, the macrophages from mice primed with OK-432 induced PCF whereas the lymphocytes did not. These results indicate that PCF is different from lymphotoxin. PCF appears to be quite similar to tumor necrosis factor (TNF) in the serum for the following reasons: The two factors are similar in the mode of cytotoxic action in vitro; both factors have a tumor necrotizing effect when injected into tumor bearing mice; both are produced from macrophages; they are similar in physicochemical characteristics; and the cytotoxic activity of PCF is totally abolished by anti-TNF serum.

Animals↗
PubMed1986

The effects of caerulein on nocturnal sleep.

Caerulein, a decapeptide chemically related to cholecystokinin octapeptide, was examined polysomnographically for its effect on nocturnal sleep in healthy volunteers. The subjects were 6 males (20-24 years of age). Either a placebo (saline) or caerulein 0.6 microgram/kg was administered intramuscularly to volunteers at 23:00. Polysomnograms were then recorded from 23:00 till 06:30. Little variation in sleep period time, total sleep time, sleep efficiency index, sleep latency, or REM sleep latency in the drug night were found as compared to the control night values. The percentage of REM stage sleep increased significantly (P less than 0.01) on the drug administered night, whereas the change in the percentages of each of the other stages was not significant. The REM density of the vertical eye movements tended to increase on the drug night, but the density of the horizontal eye movements showed no change. There were no changes in the spontaneous GSRs in either vola or dorsum manus. As caerulein shows alpha-1 adrenergic receptor blocker activity, it is suggested that caerulein may increase REM sleep by affecting the central noradrenergic neurons.

Adult↗
PubMed1986

Effect of sixth component of complement on the prostaglandin E1 stimulated adenyl cyclase activity in rat calvaria.

Human serum enhanced the PGE1 stimulated adenyl cyclase activity in membrane rich fraction of rat calvaria, but heated serum did not. Human C6 enhanced the PGE1 stimulated adenyl cyclase activity. C6 did not enhance the PTH stimulated adenyl cyclase activity. The enhancement of the PGE1 stimulated adenyl cyclase activity with C6 was due to increasing Vmax. The enhancement of the enzyme activity with C6 was significantly inhibited with anti-C6 antibody. Adenyl cyclase was not activated with C6 alone.

Adenylyl Cyclases↗