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Biomedical subjects

M Arai

Publications and source records attributed to M Arai.

At least 487 records · Page 27Linked to original sources
PubMed1990

Effect of interleukin 1 (IL-1) on the levels of cytochrome P-450 involving IL-1 receptor on the isolated hepatocytes of rat.

In the present study, the expression of IL-1 receptor (IL-1 R) on the primary cultured hepatocytes was determined and the effect of IL-1 on the intracellular amount of cytochrome P-450 was investigated. The kinetics of IL-1R on the hepatocytes was studied by [125I]-IL-1 alpha and revealed that 5,000 molecules of IL-1 bound to a hepatocyte with a Kd of 4.0 x 10(-9) M. Incubation of the hepatocytes with IL-1 for 18 hrs decreased the contents of cytochrome P-450 in a dose-dependent manner. These findings suggest that IL-1 potentially depresses the drug metabolism involving IL-1R which is expressed on hepatocytes.

Animals↗
PubMed1990

Characterization of a thrombin cleavage site mutation (Arg 1689 to Cys) in the factor VIII gene of two unrelated patients with cross-reacting material-positive hemophilia A.

The molecular defect responsible for moderate and severe hemophilia A has been identified for two unrelated patients with the CRM-positive form of this disorder (factor VIII activity of 0.02 and 0.05 U/mL with factor VIII antigen of 0.87 and 2.20 U/mL). In both cases, the immunopurified dysfunctional factor VIII protein is abnormal, in that the 80 Kd light chain is not cleaved by thrombin at arginine-1689. The basis for this failure was identified by polymerase chain reaction amplification of exon 14 of the variant factor VIII genes and direct sequencing of the amplified products. In both cases, a single base substitution (C to T) was identified that produces an arginine to cysteine substitution at amino acid residue 1689. These data identify the molecular defects of the two identical factor VIII variant proteins. The dysfunctional factor VIII has been designated "Factor VIII-East Hartford," the residence of the patient in whom the defect was first identified.

Arginine↗
PubMed1990

Cloning and sequence analysis of a cDNA for cellulase (FI-CMCase) from Aspergillus aculeatus.

We have cloned and characterized the cDNA coding for a major component of cellulase, endoglucanase (FI-CMCase), produced by Aspergillus aculeatus. The cDNA was isolated from a A. aculeatus cDNA library using synthetic oligonucleotide mixtures that correspond to the internal amino acid sequence of the mature FI-CMCase protein. Nucleotide sequence analysis of the cloned cDNA insert revealed a 711 bp open reading frame that encoded a protein of 237 amino acid residues. The primary structure of FI-CMCase deduced from the nucleotide sequence of cDNA agreed with that found by amino acid sequencing of peptide fragments obtained by digestion with several proteinases and cyanogen bromide cleavage. There may be a signal peptide sequence of 16 amino acid residues at the N-terminus. The molecular mass of the mature protein calculated from the cDNA is 24002 daltons, which compares favorably with molecular mass estimates of purified FI-CMCase obtained from SDS-PAGE (25000 Da). No distinct homology was found between the amino acid sequence of FI-CMCase and known cellulase sequences of other microorganisms. This study is the first example of cDNA cloning of an endoglucanase from the genus Aspergillus.

Amino Acid Sequence↗
PubMed1990

Divergence paralysis associated with the ingestion of diazepam.

A case of divergence paralysis associated with diazepam ingestion is reported. The cerebrospinal fluid findings and the computed tomographic scan of the brain were unremarkable. The time of ingestion of diazepam and the occurrence of diplopia were so closely related that it is likely that diazepam caused the divergence paralysis an association which is thought not to have been reported previously.

Aged↗
PubMed1990

Comparative studies on the expression of gastrointestinal-cancer-associated antigen, PA8-15, CA19-9 and the blood-group antigens in non-malignant and malignant human pancreatic tissues.

The expression of PA8-15 antigen and the blood-group-related antigens A, B, O, Le(a), Le(b), Le(x), and Le(y), as well as CA19-9, were examined in the normal pancreas and in specimens from benign and malignant pancreatic tissue by the avidin-biotin-immunoperoxidase technique. A correlation was found between the expression of PA8-15, Le(a), and CA19-9 in some cases. However, in the cancer tissues in which neither Le(a) nor CA19-9 could be demonstrated, strong expression of PA8-15 was observed. The reactivity of monoclonal antibody (mAb) PA8-15 with pancreatic cancer tissue was not inhibited by the preincubation of the sections with the mAb anti-Le(a) (CO514) and mAb CA19-9 (CO19-9) indicating that the epitope recognized by PA8-15 is different from that detected by the other two antibodies. Moreover, unlike Le(a) and CA19-9, PA8-15 was also expressed in cancer cells of patients of the Le(a-b-) type. The results suggest that mAb PA8-15 recognizes a sialylated molecule related to Le(a) but different from CA19-9, and seems to be an additional useful marker for pancreatic cancer.

Adenocarcinoma↗
PubMed1990

Electrophoresis of phosphoglycerate kinase-2 to determine testicular damage induced by ethylene glycol monomethyl ether and sterility associated with chromosomal abnormality.

Phosphoglycerate kinase (PGK, EC 2.7.2.3), which is expressed specifically in sperm and spermatids, is an enzyme in the Embden-Meyerhof pathway that converts glucose to pyruvate. We developed an electrophoresis method to determine relative PGK-2 quantity and applied it to evaluate spermatogenesis activity. In the ethylene glycol monomethyl ether (EGME)-induced testicular toxicity, relative PGK-2 quantity had not decreased until 4 weeks of exposure. Mean relative PGK-2 quantities, defined as PGK-2 quantity over PGK-1 quantity in a pooled spleen sample (+/- SD) were: 1.43 +/- 0.32 for control animals (N = 10); 1.67 +/- 0.24 for the group exposed at 500 mg/kg for 5 days (N = 6); 1.85 +/- 0.58 for the group exposed at 500 mg/kg for 2 weeks (N = 6); 0.09 +/- 0.06 for the group exposed at 500 mg/kg for 4 weeks (N = 6); not detectable in animals exposed at 500 mg/kg for 5 weeks (N = 7); 0.208 +/- 0.103 for the group exposed at 250 mg/kg for 5 weeks (N = 6); and 1.35 +/- 0.38 for the group exposed at 125 mg/kg for 5 weeks (N = 6). These relative quantities showed a good correlation with sperm/spermatid counts (r = 0.823, p less than 0.01) and histological findings. These findings suggest that EGME has toxicity on primary spermatocytes and spermatogonia. In the case of sterility associated with a chromosomal abnormality (chromosomal translocation between chromosome X and 16), relative PGK-2 quantity was not detected in any of the seven adult (12 weeks of age) mice, although many primary spermatocytes were detected by histological examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Suppression of established atherosclerosis and xanthomas in mature WHHL rabbits by keeping their serum cholesterol levels extremely low. Effect of pravastatin sodium in combination with cholestyramine.

We investigated the possibility that established atherosclerosis and xanthomas in mature WHHL rabbits could be suppressed or even regressed when their serum cholesterol levels were kept extremely low. Ten-month-old WHHL rabbits were divided into 3 groups, i.e. control rabbits, sacrificed at age 10 months, and placebo and treated rabbits, sacrificed at age 18 months. The treated rabbits were given pravastatin sodium (50 mg/kg/day), an HMG-CoA reductase inhibitor, in combination with cholestyramine (2% in diet), a bile acid sequestrant, for 36 weeks. The serum cholesterol levels and atherogenic lipoproteins in the treated group were markedly reduced, by about 60% (P less than 0.005 and P less than 0.001). Consequently, the degrees of both coronary and aortic atherosclerosis in the treated group were significantly reduced compared with the placebo group, and were almost the same as in the control group. The histopathological findings supported the above results. In addition, the incidence and degree of xanthomas in digital joints in the treated group were significantly reduced. These results suggest that established atherosclerosis and xanthomas in mature WHHL rabbits could be suppressed by keeping their serum cholesterol levels extremely low by the combination drug treatment.

Animals↗
PubMed1990

An epoxysuccinic acid derivative(loxistatin)-induced hepatic injury in rats and hamsters.

Loxistatin is a possible therapeutic agent of muscular dystrophy. A single oral administration of loxistatin to male rats caused focal necrosis of the liver with inflammatory cell infiltration. The severity of the lesions was dose-dependent up to 200 mg/kg and also manifest by an increase in serum alanine aminotransferase and aspartate aminotransferase activities. Hepatic glutathione (GSH) levels decreased with a maximum 20% depletion within 5 hr after the oral administration of loxistatin. Pretreatment with diethyl maleate did not potentiate the loxistatin-induced hepatic injury. On the other hand, the hepatoprotective effect of cysteamine was observed when cysteamine was administered 24 hr before loxistatin dosing, but the effect was not observed when the antidote was administered concomitantly with loxistatin. Pretreatment of rats with phenobarbital or trans-stilbene oxide provided partial protection against the hepatotoxic effect of loxistatin. Pretreatment with SKF-525A resulted in increased hepatic injury, while pretreatment with piperonyl butoxide, cimetidine, or 3-methylcholanthrene had no effect on hepatic damage by loxistatin. Five hours after [14C]loxistatin administration to rats, the covalent binding of the radioactivity to proteins was greatest in the liver, followed by the kidney, then muscle and blood to a lesser extent. [14C]Loxistatin acid, the pharmacologically active form of loxistatin, irreversibly bound to rat liver microsomal proteins; more binding occurred when the NADPH-generating system was omitted and when the microsomes were boiled first. GSH did not alter the extent of irreversible binding, whereas N-ethylmaleimide decreased the binding of [14C]loxistatin acid to rat liver microsomal proteins by 75%. Unlike the rat, administration of loxistatin to hamsters caused neither hepatic injury nor hepatic GSH depletion even at a high dose (500 mg/kg). Both the distribution and covalent binding of radioactivity in the hamster liver were one-third of those in rats following [14C]loxistatin dosing. These results suggest that loxistatin causes species-specific hepatotoxicity and that, at least in part, some of the toxic effects of loxistatin are mediated by the nonenzymatic covalent binding of loxistatin acid to thiol residues on cellular macromolecules.

Alanine Transaminase↗
PubMed1990

Acute effect of parathyroid hormone-(1-34) fragment on blood pressure in rats fed a low calcium diet.

1. Acute effects of human PTH-(1-34) fragment on blood pressure were examined in rats fed a low or normal calcium diet. 2. Plasma biochemistry showed that a low calcium diet evoked hyperparathyroidism as well as hypocalcemia in rats. 3. Subcutaneous administration of human PTH-(1-34) caused a significant decrease in tail-cuff systolic blood pressure in rats fed a normal calcium diet, but not in rats fed a low calcium diet. 4. Intravenous administration of human PTH-(1-34) reduced the arterial blood pressure in rats, dose-dependently. The reduction of blood pressure was more pronounced in rats fed a normal calcium diet than that in the rats fed a low calcium diet. 5. It is suggested that the hypotensive action of human PTH-(1-34) was more pronounced in the rats fed a normal diet than in the rats fed a low calcium diet, and that PTH has different cardiovascular consequences under chronic hyperparathyroidism and/or hypocalcemia.

Animals↗
PubMed1990

Lack of modifying effects of p-phenylenediamine on induction of gamma-glutamyl transpeptidase-positive foci in a medium-term bioassay system using F344 rats.

The modifying effects of p-phenylenediamine (p-PD) 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 p-PD at dietary levels of 1000, 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. Slight retardation of body weight was observed in rats treated with p-PD at all dietary levels. Significant increases in relative liver weight were found in animals treated with 1000 ppm p-PD. Remarkable growth retardation and increased liver weight were found in rats given 3'-Me-DAB. p-PD did not significantly increase the level of gamma-glutamyl transpeptidase (gamma-GT) positive foci observed after DEN initiation. In contrast, 3'-Me-DAB demonstrated marked enhancing activity as evidenced by significantly increased values for gamma-GT positive foci as compared with the controls given DEN alone. The results demonstrate that p-PD does not modify liver carcinogenesis in our in vivo medium-term bioassay system.

Animals↗
PubMed1990

Detection of tumor associated antigen, PA8-15, in sera from pancreatic and gastrointestinal carcinoma patients.

A sandwich enzyme immunoassay was set up to measure tumor associated antigen (antigen PA8-15) detected by monoclonal antibody PA8-15. The cut-off value was set at 55 U/ml. Tests on 437 sera samples from patients with malignant or benign diseases yielded the following positive percentages: esophageal cancer, 9.1%; gastric cancer, 23.1%; colorectal cancer, 44.8%; hepatoma, 32.6%; biliary tract cancer, 47.5%; pancreatic cancer, 84%; lung cancer, 30.8%; breast cancer, 16%; benign diseases, 13.2%. Positive antigen PA8-15 levels in patients with gastric, colorectal and pancreatic cancers, increased with the progression of clinical stage. When antigen PA8-15 was monitored in 11 various cancer cases before and after surgery, a decrease in PA8-15 value was revealed in all resected patients postoperatively, whereas a more than 100% increase in PA8-15 values was noted in non-resected patients. Compared with CEA and CA19-9, the highest positive PA8-15 rate was seen in pancreatic cancer patients. By combining the rates of positive sera obtained with each tumor marker, the overall percentage increased. These results suggest that measuring serum PA8-15 levels will aid in serological cancer diagnoses, particularly pancreatic cancer.

Adolescent↗
PubMed1990

Effect of lithium on deoxyribonucleic acid synthesis and iodide uptake in porcine thyroid cells in culture.

We investigated the direct effect of lithium on porcine thyroid cells in culture to exclude the secondary regulatory factors. First we have studied the effect of lithium on TSH-induced iodide uptake. Significant suppression was seen at 0.1 mmol/liter, and half-maximal suppression was obtained at the pharmacological concentration reported in patient serum. The suppression was dose dependent and reversible. Besides the suppression of cAMP production stimulated by TSH, lithium also inhibited iodide uptake stimulated by forskolin or 8-bromo-cAMP. These results demonstrated that lithium inhibits TSH-induced iodide uptake not only by reducing cAMP production, but also by acting on the steps of post-cAMP production. Next, we studied the effect of lithium on DNA synthesis of the cultured porcine thyroid cells. Lithium stimulated [3H]thymidine incorporation of the thyroid cells in the basal condition (0.5% fetal calf serum) as well as those stimulated by insulin-like growth factor-I (100 micrograms/liter). The minimal concentrations for the significant increase were 0.5 and 0.1 mmol/liter, respectively. These results suggest that lithium might contribute to the formation of the goiter directly at the cellular levels in patients treated with the agent.

Animals↗
PubMed1990

Metabolic fate of loxistatin in rat.

1. The urinary and plasma metabolites of 14C-loxistatin, a new thiol protease inhibitor, were studied after oral administration to rats. 2. The major metabolites in urine were identified as loxistatin acid (M-1), a pharmacologically active form, and its hydroxy metabolites (M-4a and M-4b). These metabolites were also shown to be the major metabolites in plasma. 3. The inhibitory activity of the synthetic metabolite, M-4b, on papain was almost the same as that of loxistatin acid.

Administration, Oral↗
PubMed1990

[Comparisons of effects of vitamin D3 metabolites on mineralization: utilization of incisor dentin in parathyroidectomized rats].

The rat incisor is continuously growing throughout the animal's life recording the state of mineralization within its dentin at all times. Therefore, it was assumed that the incisor dentin was suitable material for studying the effects of various drugs on such mineralization. The present study set out to examine the effects of vitamin D3 metabolites on the remineralization of dentin and the serum calcium level in parathyroidectomized (PTX) rats. Male Wistar rats weighing about 200-250 g were parathyroidectomized. Each rat was given daily 12 g of a synthetic diet containing 0.1% Ca and 0.4% P (normal P) or 0.06% P (P deficient) without vitamin D. Exp. I: Three groups of rats given a normal P diet were orally administered vehicle, 25 (OH) D3 (50 IU/rat) or 1,25 (OH)2D3 (5 IU/rat) for 5 days from the 28th day after PTX, respectively. Exp. II: Two groups of rats given a normal P diet or a P deficient diet were further divided into 4 sub-groups and intramuscularly administered 0, 5,000, 10,000 or 20,000 IU of vitamin D3 on the 9th day after PTX, respectively. The active vitamin D3, 1,25 (OH)2D3 restored the mineralization of the dentin which had been suppressed following PTX, and elevated the serum calcium level to about 9 mg/dl. However, the 25 (OH) D3 neither restored the mineralization of the dentin nor elevated the serum calcium level in the PTX rats. At doses below 1,000 IU, vitamin D3 could not restore the mineralization of the dentin. However, at massive doses above 5,000 IU, the mineralization was restored in proportion to the dose. The serum calcium levels also increased in proportion to the dose. It is assumed that the increase of the serum calcium level was mainly due to the enhancement of calcium absorption from the intestine by vitamin D3. Both remineralization of the incisor dentin and increase of the serum calcium level were more marked in groups of rats given a P deficient diet than in those given a normal P diet. In all cases in the present experiments, the degree of mineralization of the dentin seemed to correspond with the degree of elevation of the serum calcium levels. These results suggest that the remineralization of the dentin in the PTX rats was attributable to the effect of the vitamin D3 metabolites on serum calcium regulation. Relative biological activities of 1,25 (OH)2D3, 25 (OH) D3 and vitamin D3 on the remineralization of dentin were estimated to be 1, less than 0.02 and less than 0.001, respectively.

Animals↗
PubMed1990

[A case of Becker muscular dystrophy with schizophrenic symptoms].

A 23-year-old male patient with Becker muscular dystrophy (BMD) who showed schizophrenic symptoms was reported. He tumbled easily and was poor at running since age at 8 years. He had difficulty in climbing stairs and was idle away all day long since age at 21 years. Although his premorbid personality was not schizoid, he showed auditory hallucinations and delusions without any psychogenetic moment at the age of 23. At first, he seemed to be schizophrenic, but after the treatment with antipsychotics, he always had an insight into his disease and exhibited natural emotional communication. He showed no autism and character changes. According to the Wechsler Adult Intelligence Scale (WAIS), intellectual impairment was notified (total IQ58). Neurological examinations revealed weakness and atrophy of muscles in the proximal part of his lower extremities, and pseudohypertrophy of calves. In the serum enzyme, serum creatine kinase (CK) level was elevated (700 U/L). Abnormal Q waves appeared in the leads, II, III, aVF, V5, V6 on the electrocardiogram (ECG), and the finding of the echocardiography suggested dilated cardiomyopathy. The electroencephalogram (EEG) revealed the basic rhythm of 9-10 Hz with 0 activities of 6-7 Hz which were predominant in frontparietal and central leads. The electromyogram (EMG) revealed a myopathic pattern with low voltage and short duration. A muscle biopsy from right biceps brachii disclosed the abnormal immunofluorescent staining pattern of dystrophin which is consistent with BMD patient, i.e., "patchy," discontinuous and faint immunoreaction at surface membrane of the fiber. Both molecular weight (380 kd: n = 400) and amount (30%; n = 100) of dystrophin were reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[CT of gold pneumonitis].

We experienced five cases of gold pneumonitis. CT findings of four cases and pathological findings of an autopsy case were discussed. CT findings of gold pneumonitis could be classified as follow; (1) high density shadow of subpleural zone-BOOP suspected- (2) high density shadow along the broncho-vascular bundle (3) small cystic shadow of subpleural zone-UIP. Histological findings of an autopsy case revealed the fibrosis along the broncho-vascular bandle. A variety of radiologic and pathologic feature on the gold pneumonitis were seen.

Adult↗