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Biomedical subjects

A Kitahara

Publications and source records attributed to A Kitahara.

At least 55 records · Page 3Linked to original sources
PubMed1983

Molecular forms of glutathione S-transferase and UDP-glucuronyltransferase as hepatic preneoplastic marker enzymes.

Changes in molecular forms of glutathione S-transferase (GST) and UDP-glucuronyltransferase (UDP-GT) as hepatic detoxicating enzymes were investigated during chemical hepatocarcinogenesis in the rat. The activity and the protein amount (formula; see text) itself of the GST-A form, which has fetal characteristics and is separable from other forms by CM-Sephadex column chromatography and by immunologic techniques, was much increased in gamma-glutamyl transpeptidase (gamma-GTP)-positive foci or hyperplastic nodules (HNs) induced by diethylnitrosamine and 2-fluorenylacetamide or 3'-methyl-4-dimethylaminoazobenzene. The activity of enzyme 1 (late fetal form) of UDP-GT assayed with o-aminophenol (o-GT) also increased with increased number of the foci or HNs, while the activity of enzyme 2 (neonatal form) assayed with phenolphthalein (p-GT) changed but little. The foci and HNs were stained more strongly than the nonnodular areas immunohistochemically using the antibody against purified GST-A or o-GT. The two activities were also increased in well-differentiated hepatomas, but they were decreased in moderately and poorly differentiated hepatomas, and activating enzymes such as cytochrome P-450 were markedly decreased from HN. GST-A and o-GT differ from fetal enzymes such as those of carbohydrate metabolism in that they are inducible in the short-term by drugs, including carcinogens, and they show the highest activities in HNs, and so they may be considered as hepatic preneoplastic (PN) antigens.

Animals↗
PubMed1983

Changes in activities of glutathione peroxidase and glutathione reductase during chemical hepatocarcinogenesis in the rat.

Changes in the activities of rat hepatic glutathione (GSH) peroxidase (GSH-Px) and GSH reductase (GR) were investigated during the induction of preneoplastic gamma-glutamyltransferase (gamma-GT)-positive foci and hyperplastic nodules by the administration of diethylnitrosamine followed by N-2-fluorenylacetamide. Activities of GSH-Px towards both cumene hydroperoxide (cumene-OOH) and hydrogen peroxide markedly decreased at an early stage of the above hepatocarcinogenesis, but the activity towards cumene-OOH again increased with the appearance of the foci and nodules, which were detectable as an increased gamma-GT activity. It was demonstrated by CM-Sephadex column chromatography and immunochemically that the increased activity towards cumene-OOH alone is due to the increased GSH-Px activity of GSH S-transferase B. GR activity and the total glutathione content in the liver also increased with increased preneoplastic foci and nodules. These results are discussed in connection with the protection mechanism(s) of these cell populations against damage by active oxygen and lipid peroxides produced in chemical hepatocarcinogenesis.

Animals↗
PubMed1981

Effects of azelastine hydrochloride, a novel anti-allergic drug, on the central nervous system.

The effects of 4-(p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1-(2H)-phthalazinone hydrochloride (azelastine hydrochloride), a new anti-allergic drug, on the central nervous system were studied in mice, rats and rabbits in comparison to clemastine, chlorpheniramine and diphenhydramine. In mice, azelastine showed a definite central action with the same dose range (10--40 mg/kg p.o.) as the reference drugs. However, the central action profile of azelastine was considerably different from those of the reference antihistaminics. Clemastine and diphenhydramine produced potent anti-tremorine and anti-pilocarpine activities, while azelastine was less active than the two drugs. Chlorpheniramine and diphenhydramine produced a marked anti-reserpine activity and a marked potentiation of the caffeine-induced hypermotility, while clemastine had little effect in this animal model; on the contrary, 40 mg/kg of azelastine suppressed the caffeine-induced hypermotility. In rats, a high dose of 100 mg/kg azelastine produced a slight suppression of the paradoxical sleep. But the drug affected neither the rectal temperature nor the conditioned avoidance response at oral doses up to 100 mg/kg. In unanesthetized and restrained rabbits, azelastine in a dose of 0.5 to 8 mg/kg i.v. showed no significant change in the spontaneous EEG activity and in the susceptibility of the ascending reticular activating system, whereas an i.v. dose of 2 mg/kg clemastine produced a marked high voltage and slow wave pattern in EEG activity and suppressed the reticular activating system.

Aggression↗
PubMed1978

Effects of hexapeptide, a compound analogous to insulin B chain fragment B-21-26(DP-432) on the glucose uptake into the perfused hind limb of rats.

DP-432 is a synthetic new peptide analogous to insulin B-chain fragment B21-26. It has been reported that this hexapeptide shows insulin potentiating action besides insulin-like activities in adipose tissue and diaphragm of rats. The perfusion of the hind limb of rats was performed according to the procedure of Ruderman with some modifications. The medium was Krebs-Ringer bicarbonate buffer containing 0.5% bovine albumin and 8.3 mM glucose. The erythrocytes were omitted from the medium. In this experimental procedure it was shown that the glucose uptake into the hind limb of rats increased by infusion of DP-432 (100 microgram/ml). The amount of glucose uptake into the hind limb responded to insulin doses (50, 100, 1000 muU/ml). DP-432 had insulin-like activity of 100 muU/ml. However, DP-432 itself did not have any potentiation of insulin activity on the muscle.

Animals↗
PubMed1978

Activities of hepatic enzymes in spontaneous diabetes rats produced by selective breeding of normal Wistar rats.

Acitivites of the hepatic enzymes were determined in spontaneous diabetes rats. The activities of the enzymes were compared with those in normal rats and in streptozotocin diabetic rats. In the spontaneous diabetes rats, glycogen phosphorylase and glycogen synthase were 14.6 +/- 0.6 and 1.73 +/- 0.15 U respectively. The activities of both the enzymes were significantly increased. In the spontaneous diabetes rats glucokinase was 3.82 +/- 0.5 U showing a significant increase. On the contrary, the activity of the enzyme was decreased in the streptozotocin diabetic rats. Glucose-6-phosphatase was increased both in the spontaneous diabetes rats and in the streptozotocin diabetic rats. Fructose-1,6-diphosphatase was increased in the spontaneous diabetes rats. Glucose-6-phosphate dehydrogenase was increased in the spontaneous diabetes rats and decreased in the streptozotocin diabetic rats. In the spontaneous diabetes rats phosphofructokinase showed a reduction of the activity and glucose-6-phosphate dehydrogenase was elevated. These findings are consistent with the results of activities of the hepatic enzymes in adult-onset diabetic patients. These patterns of the hepatic enzymes in the spontaneous diabetes rats were different from those in the streptozotocin diabetic rats. From these patterns of activities of the hepatic enzymes, the spontaneous diabetes rats produced by repetition of selective breeding according to Goto et al. (1975,1976) are an excellent model of human adult-onset diabetes.

Animals↗
PubMed1977

Enzyme alteration in skeletal muscle of mice with muscular dystrophy.

1. Developmental enzyme alterations were investigated in skeletal muscle of the hereditary progressive muscular dystrophy (PMD) mice of C57BL/6J strain. 2. Enzymes examined were classified into three groups according to changes of activities in dystrophy muscle during ageing. Activities of creatine kinase (EC 2.7.3.2), pyruvate kinase (EC 2.7.1.40), glycogen phosphorylase (EC 2.4.1.1), and fructose-biphosphate aldolase (EC 4.1.2.13), each of which had the respective muscle specific isoenzyme of extremely high activity in normal adult skeletal muscle, decreased rapidly in dystrophy muscle from the early stage of the disease with ageing. Activities of glycogen synthase (EC 2.4.1.11) and hexokinase (EC 2.7.1.1) were higher in dystrophy muscle in the early stage but decreased gradually to lower levels than those in the control with ageing. Activities of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) were always much higher in dystrophy muscle than in the control, with no relation to ageing. 3. Isoenzymes of creatine kinase, pyruvate kinase and phosphorylase in dystrophy muscle were mainly the muscle types, indicating that muscle differentiation was not blocked profoundly even in dystrophy muscle. In limited cases, especially in the early stage of the disease, very weak activities of the non-muscle fetal type isoenzymes of creatine kinase and phosphorylase were detected, apparently associated with partial muscle regeneration in dystrophy muscle.

Aging↗
PubMed1976

[Pharmacological studies on degeneration and regeneration of peripheral nerves. (1) Effects of methylcobalamin and cobamide on EMG patterns and loss of muscle weight in rats with crushed sciatic nerve].

Experiments were performed to investigate the effects of Vitamin B12, i.e., methylcobalamin and cobamide, on the neural degeneration and regeneration. Male Wistar rats (140 to 150 g) under conditions of experimental unilateral sciatic nerve crushing were treated consecutively with methylcobalamin (50 and 500 mug/kg/day i.p.), cobamide (50 and 500 mug/kg/day i.p.) or saline. EMG recordings were periodically carried out and rats of each group were sacrificed to determine the weight-loss of denervated muscles 1, 2, 3 and 4 weeks after crush. Neither methylcobalamin nor cobamide exerted any significant effect on body-weight gain of the nerve-crushed rats with a daily injection of 50 and 500 mug/kg i.p.. The EMG pattern of the denervated biceps femoris muscle showed a total lack of fibrillation for 2 days after the nerve-crush. Thereafter, the fibrillation appeared and continued for 10 to 14 days until the nerve had regenerated, as evidenced by the appearance of a complex NMU voltage. The occurrence of fibrillation voltage was slightly delayed in methylcobalamin group (500 mug/kg/day) as compared with the saline control group. The re-appearance of normal NMU voltage was more rapid in the methylcobalamin 500 mug/kg group than in controls and other experimental groups. Neither methylcobalamin nor cobamide had any significant effect on the weight-loss of the gastrocnemius and tibialis anterior muscles following crush of the sciatic nerve. However, a daily injection of 500 mug/kg of methylcobalamin produced a significant increase in the weight of the soleus muscle which recovered to the extent of being the same weight of the contralateral 4 weeks after the nerve-crush. These results suggest that methylcobalamin may have an inhibitory effect on Wallerian degeneration and also a facilitatory effect on the neural regeneration of the crushed sciatic nerve of rats.

Animals↗