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Biomedical subjects

M Arai

Publications and source records attributed to M Arai.

At least 523 records · Page 29Linked to original sources
PubMed1989

Lack of modifying effects of 2,2'-[(4-aminophenyl) imino] bisethanol sulfate on induction of preneoplastic gamma-glutamyl transpeptidase-positive foci in a medium-term bioassay system using F344 rats.

The modifying effects of 2,2'-[(4-aminophenyl) imino] bisethanol sulfate (4APE) on liver carcinogenesis were investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given 4APE at dietary levels of 1,000, 330 and 110 parts per million (ppm), or 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) at 600 ppm as a positive control for 6 weeks. At week 3 following DEN administration, all animals were subjected to partial hepatectomy. No adverse effects on survival and body weight were seen in rats treated with 4APE, even at the highest dietary levels. Marked growth retardation and significant increase of relative liver weight were found in animals treated with the known hepatocarcinogen 3'-Me-DAB, which demonstrated marked promoting activity as evidenced by significantly increased values for gamma-glutamyl transpeptidase (gamma-GT) positive foci as compared with the controls given DEN alone. In contrast, 4APE did not significantly increase the level of gamma-GT positive foci over that induced by DEN initiation alone. From these results, it is concluded that 4APE does not possess promoting activity for liver carcinogenesis.

Animals↗
PubMed1989

Identification of glutathione conjugate formed from loxistatin in rats.

1. The metabolic fate of loxistatin, ethyl-(+)-(2S,3S)-3-[(S)-3-methyl-1-(3-methyl- butylcarbamoyl)butylcarbamoyl]-2-oxiranecarboxylate, was studied in rats. 2. Following oral administration of 14C-loxistatin the major part of radioactivity was eliminated via the bile into the faeces. 3. The major metabolites in bile were isolated and identified as glutathione and cysteine conjugates of loxistatin acid, by chromatography, proton n.m.r. spectroscopy and mass spectrometry and comparison with those of the authentic reference compounds. 4. Formation of the glutathuone conjugate was also demonstrated in vitro by incubation of 14C-loxistatin acid with rat liver cytosol and glutathione.

Administration, Oral↗
PubMed1989

[Comparisons of bioavailability of various calcium salts. Utilization incisor dentin in parathyroidectomized rats].

In the present study, we compared the bioavailability of various calcium salts in the diet such as calcium lactate, calcium carbonate and calcium phosphate by examining the effects of these calcium salts on serum calcium concentration and on the mineralization of incisor dentin in parathyroidectomized (PTXed) rats. Each rat was given daily 12 g of a low calcium (0.1% Ca) diet beginning from 3 days before the operation and continuing for 11 days after. Then the diet was changed to those containing various calcium salts (1.5% Ca). The serum calcium and phosphorous concentrations were examined every three days, just before feeding time and 6 hours after. The degree and site of the mineralization of incisor dentin were examined histologically by a time marking method using lead acetate. In the PTXed rats maintained on a low calcium diet, the serum calcium concentration decreased to about 4.5 mg/dl and the mineralization of incisor dentin was inhibited. On the 11th day, just before feeding on diets containing various calcium salts, the serum calcium concentrations were very similar for each group, but at 6 hours after feeding, concentration was 7.6 mg/dl in the calcium lactate group, 6.2 mg/dl in the calcium carbonate group and 4.8 mg/dl in the calcium phosphate group. On the 17th day following administration of the high calcium diets, the serum calcium concentrations were 9.8 mg/dl in the calcium lactate group, 8.4 mg/dl in the calcium carbonate group and 4.4 mg/dl in the calcium phosphate group. Mineralization of the incisor dentin was best in the calcium lactate group, moderate in the calcium carbonate group and poor in the calcium phosphate group. We also examined the effects of dietary phosphorus contents on serum calcium concentrations and on the mineralization of incisor dentin using PTXed rats. On the 17th day following the administration of diets (1.5% Ca, with calcium lactate) containing various amounts of phosphorus, the serum calcium concentrations in the calcium lactate group were 8.8 mg/dl (0.4% P), 6.9 mg/dl (0.8% P) and 4.2 mg/dl (1.6% P) respectively. Mineralization of incisor dentin was also inhibited in rats fed a high phosphorus diet. These results suggest that in PTXed rats, absorption of calcium from the intestines and mineralization of the incisor dentin is best by the administration of calcium lactate, moderate by calcium carbonate and poor by calcium phosphate, and that phosphorus in the diet inhibits calcium absorption from the intestines.

Animals↗
PubMed1989

[Alteration of prostaglandin metabolism in alcoholic liver disease: its association with platelet dysfunction after chronic alcohol ingestion].

Recently, hepatic microcirculation has been focused on as an important pathogenic factor in progression of alcoholic liver disease (ALD). Therefore, blood levels of several prostaglandins, which are associated with organ microcirculation, were determined in various liver diseases, including ALD. Blood thromboxane B2 (TXB2) level was significantly increased in ALD, when compared to other types of liver diseases, whereas both 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) and prostaglandin E were not changed. These consequences resulted in the imbalance of 6-keto PGF1 alpha to TXB2, which might promote platelet aggregation and blood vessel contraction. Indeed, the increase of beta-thromboglobulin and platelet factor 4 in blood was observed in ALD. Furthermore, in ALD, the rate of arachidonate-induced platelet aggregation was prominently enhanced, and malondialdehyde production in platelet, which was well correlated with blood TXB2 levels, significantly increased. Thus, the present study may indicate that, in ALD, hyper-aggregability of platelet is produced, because of the derangement of prostaglandin metabolism and platelet dysfunction.

Adult↗
PubMed1989

[A case of sarcoidosis presenting ataxic hemiparesis as an initial clinical manifestation].

A case of sarcoidosis presenting ataxic hemiparesis was reported. A 25-year-old man was admitted to Kanto Teishin Hospital because of slight weakness and dysesthesia in the right side of his body. His physical findings were normal. Neurological findings disclosed mild right hemiparesis (MMT 4+), cerebellar signs and mild dysesthesia in the same side. Laboratory findings were within normal limits except for elevated serum ACE and lysozyme. Chest roentgenogram showed bilateral hilar lymphadenopathy and TBLB disclosed sarcoid granuloma. Though brain CT, brain MRI and cerebral angiography were within normal limits, the neurological features were thought to be due to sarcoidosis. They disappeared along with the decrease of ACE and lysozyme. This is the first report of ataxic hemiparesis due to sarcoidosis, and it is interesting in that ataxic hemiparesis, which is one of signs of diseases in central nervous system, is the first manifest clinical feature of sarcoidosis.

Adult↗
PubMed1989

A method for measuring contact pressures instantaneously in articular joints.

A method whereby instrumented pipes are inserted part of the way into articular cartilage from the underlying subchondral bone has been developed for measuring instantaneous contact pressures acting within articular joints. Contact pressures developed between two specimens cut from fresh cadaveric knee joints were measured with this technique and then subsequently with pressure-sensitive paper. Average contact pressures (load/contact area) were also calculated. Comparisons of the three sets of data show that contact pressures measured with the pressure pipe system are linearly related (p less than 0.001) to both the contact pressures measured with the pressure-sensitive paper and the calculated average contact pressures.

Cartilage, Articular↗
PubMed1989

[An experimental study on the severe type of alcoholic liver disease--a pathogenetic role of potentiated activation of complement system by endotoxin after chronic ethanol consumption].

Endotoxemia frequently appears in severe type of alcoholic liver disease. However, we have little knowledge how endotoxin influences the progression of alcoholic liver injury. Thus, to study the causal mechanism for the progression to the severe type of alcoholic liver diseases, endotoxin (0.2 mg/100 g BW, E. Coli O26:B6) was intravenously injected in chronic ethanol-fed rats and controls, and then, rats were sacrificed after 16 hours of endotoxin treatment. The elevation of serum GOT and GPT activities induced by endotoxin was significantly higher in chronic ethanol-fed rats than controls, and these biochemical changes were well correlated with the grade of necrosis of liver histology. Furthermore, in chronic ethanol-fed rats, endotoxin treatment tremendously increased blood BUN and creatinine levels and produced the degeneration of renal tubuli with neutrophil infiltration into glomerulus. These experimental findings are very similar to the severe type of alcoholic liver disease. On the other hand, endotoxin significantly decreased serum values of CH50 in chronic ethanol-fed rats, but not in controls. Such alterations of CH50 induced by endotoxin were well correlated with the several parameters indicating the injury of liver and kidney. Therefore, the present study may indicate that chronic ethanol ingestion aggravates endotoxin-induced organ injury, and that the activation of complement system may associate with such progression of organ injury.

Animals↗
PubMed1989

[Diagnosis and treatment of dysplasia of the uterine cervix].

The accuracy of diagnosis and the results of treatment for dysplasia of the uterine cervix are analyzed. Three hundred and thirty-seven cases of mild, 231 of moderate and 200 of severe dysplasias have been treated at Kitasato University Hospital. By cytology 40.4% of mild, 74.5% of moderate and 89.0% of severe dysplasias were judged suspicious or positive, and the accurate cytopathological detection rate was 19.8%, 16.1% and 60.1%, respectively. Abnormal colposcopic findings such as M, P and W were observed in more than 95% of cases with dysplasia. The area of abnormal findings tends to be large as the lesion becomes more severe. Mild dysplasia progressed to cervical cancer in 1.5%, moderate dysplasia in 2.4% and severe dysplasia in 9.4%. Conservative therapy by laser vaporization or conization was used for 31 mild, 96 moderate and 114 severe dysplasias. The cure rate of each dysplasia was 100%, and pregnancy following laser therapy was encountered in 28 cases without abnormal course. It is concluded that colposcopy is more useful in diagnosis of mild and moderate dysplasia than cytology, and conservative laser treatment is an effective method for dysplasia.

Adult↗
PubMed1989

[Radiation therapy of adult cerebral glioblastoma:].

For the past twenty years, 85 adult patients with cerebral glioblastoma were treated with postoperative radiation therapy (RT). Hypofractionated RT (5 Gy twice a week) was performed in 31 patients. The survival rate of the hypofractionated RT was superior to the conventionally fractionated RT, especially in the patients involved mainly in the frontal lobe. In the hypofractionation group, misonidazole proved of benefit to the survival. In future, hyperfractionation of RT seems reasonable to be explored for improving CNS tolerance.

Adult↗
PubMed1989

Changes in production of interleukin-1 and interleukin-2 associated with obstructive jaundice and biliary drainage in patients with gastrointestinal cancer.

Increased susceptibility to infection in patients with obstructive jaundice has been well documented in vitro and in vivo. Nevertheless, an underlying mechanism for immunocompromise in these patients has not been identified. This study was undertaken to evaluate the production of two important immunoregulatory molecules, interleukin-1 (IL-1) and interleukin-2 (IL-2), by peripheral blood mononuclear cells in cancer patients with obstructive jaundice before and after percutaneous transhepatic biliary drainage (PTBD). After decompression with PTBD, IL-1 and IL-2 production was significantly increased (IL-1: from 7.9 +/- 4.9 to 13.9 +/- 4.9 U/ml, p less than 0.05; IL-2: from 8.8 +/- 4.9 to 14.1 +/- 6.5 U/ml, p less than 0.05). There was a positive correlation between IL-1 and IL-2 production (r = 0.424, p less than 0.05). The production of both interleukins correlated negatively with serum total bilirubin level (IL-1 r = -0.478, p less than 0.05; IL-2: r = -0.482, p less than 0.05) and positively with high-density lipoprotein cholesterol in serum (IL-1: r = 0.505, p less than 0.01; IL-2: r = 0.494, p less than 0.05). IL-2 production also correlated positively with serum albumin levels (r = 0.511, p less than 0.01). These results suggest that hyperbilirubinemia and abnormal lipid metabolism may be associated with impaired interleukin production, which may result in an increased susceptibility to infection during obstructive jaundice.

Bile↗
PubMed1988

Preventive effect of pravastatin sodium, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on coronary atherosclerosis and xanthoma in WHHL rabbits.

In this paper, we examined whether the development of atherosclerosis in the Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model of familial hypercholesterolemia in man, could be prevented by the reduction of serum cholesterol levels. Pravastatin sodium (the generic name of CS-514), a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was used as a cholesterol-lowering drug. The drug was administered orally to 12 WHHL rabbits (2-3 months old) at a dose of 50 mg/kg per day for 24 weeks, and 13 animals were given water as control. In the treated group, serum cholesterol, phospholipid and triacylglycerol levels were significantly reduced by 28%, 32% and 16%, respectively, as compared with those of the control group. Although the prevention of development of the aortic atherosclerosis was not significant, the progression of coronary atherosclerosis was significantly prevented. The incidence of atherosclerosis in four main coronary arteries was reduced from 42% (control group) to 19% (treated group, P less than 0.01), and the development of lesion of coronary arteries evaluated by area of lesion was reduced from 19.7% (control group) to 9.1% (treated group, P less than 0.05). Histopathological findings supported the above observations. In addition, development of xanthoma in digital joints was also reduced from 90.4% (control group) to 58.3% (treated group, P less than 0.005). These results suggest that the development of coronary atherosclerosis and xanthoma in WHHL rabbit was reduced by continuous reduction of serum cholesterol levels treated with pravastatin sodium.

Animals↗
PubMed1988

A determination of the positions of disulphide bonds in Paim I, alpha-amylase inhibitor from Streptomyces corchorushii, using fast atom bombardment mass spectrometry.

Paim I, a protein alpha-amylase inhibitor, is a single-chain polypeptide which consists of 73 amino acids, including 4 half-cystine residues. The positions of disulphide bonds in Paim I have been determined with the combination of enzymatic digestion and fast atom bombardment (FAB) mass spectrometry. Denatured Paim I was digested to peptides with Staphylococcus aureus V8 protease. These peptides were subjected to FAB mass spectrometry, with or without isolation by high-performance liquid chromatography. The positions of disulphide bonds in Paim I were determined from the relative molecular masses of the peptides containing a disulphide bond and by the enzyme specificity of S. aureus V8 protease. It is deduced that Paim I has two disulphide bridges at Cys(8)--Cys(24) and Cys(42)--Cys(70).

Amino Acid Sequence↗