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Biomedical subjects

M Arai

Publications and source records attributed to M Arai.

At least 307 records · Page 17Linked to original sources
PubMed1995

Ontogeny of immunoreactive and bioactive microsomal steroidogenic enzymes during adrenocortical development in rats.

The functional development of the neonatal rat adrenal cortex is characterized by a triphasic response to adrenocorticotropic hormone (ACTH), with a nadir in responsiveness around neonatal day 10 (d10). In this study, the hypothesis was tested that hyporesponsiveness to ACTH partly results from deficiencies in steroidogenic enzyme content. Immunoreactive (ir) levels of mitochondrial cytochrome P450 enzymes (side chain cleavage (P450scc) and 11 beta-hydroxylase (P450c11)) did not change during neonatal development. Immunoreactive levels of microsomal 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD), however, were significantly and comparably lower in both day 1 (d1) and d10 neonates compared to adult rats. Activity of 3 beta-HSD did not parallel changes in ir 3 beta-HSD content. Enzyme activity was low on d1 (approximately 39% of adult activity), but by d10 was statistically equivalent to that of microsomes from adult adrenal glands. Immunoreactive levels of microsomal cytochrome P450 21 alpha-hydroxylase (P450c21) were significantly lower in d1 glands than in adult glands (by approximately 50%), but by d10 were statistically indistinguishable from adults. On the other hand, P450c21 activity was equivalent on d1 and d10 and both were significantly lower compared to adults (approximately 62% of adult activity). ACTH injections from d3-d10 facilitated the adrenocortical steroidogenic response to ACTH on d10. This treatment increased levels of ir 3 beta-HSD, but not ir P450c21. The results suggest that rat adrenocortical 3 beta-HSD and P450c21 are developmentally and differentially regulated, and that ir levels of the proteins are not correlated with enzyme activity during the neonatal period. One possible explanation for these observations is that multiple isoforms of the two enzymes, with different antigenic and enzymatic properties, may be expressed during development at different times. In addition, the combined decreased activities of these two enzymes can almost entirely account for the decreased steroidogenic output of rat adrenocortical cells on d1, but not during the later neonatal period.

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

Blood coagulation equilibrium in rat liver microcirculation as evaluated by endothelial cell thrombomodulin and macrophage tissue factor.

The regulatory mechanisms of microcirculation might differ in the liver from other organs, because macrophages are resident in the hepatic sinusoids and sinusoidal endothelial cells are unique in shape and function. Thrombomodulin expression in endothelial cells and tissue factor activity in isolated macrophages were studied in the liver and lung of rats. In normal rats, the thrombomodulin expression was minimal in hepatic sinusoids, but prominent in pulmonary capillaries, while the tissue factor activity in the presence of endotoxin was higher in pulmonary macrophages than in Kupffer cells, although the levels in the absence of endotoxin were comparable in both cells. The tissue factor activity in hepatic macrophages was increased after priming of the cells with Corynebacterium parvum or after induction of liver necrosis or cirrhosis with carbon tetrachloride. In the necrotic or cirrhotic liver, increased thrombomodulin expression was seen along capillaries extending in necrotic areas and regenerating nodules, but this increase was minimal in the Corynebacterium parvum-treated rat liver. Blood coagulation equilibrium in microcirculation regulated by endothelial cells and macrophages may differ between the liver and lung. Such equilibrium in the liver may vary depending on pathological status.

Animals↗
PubMed1995

Physiological basis of myocardial contrast enhancement in fast magnetic resonance images of 2-day-old reperfused canine infarcts.

BACKGROUND: Contrast-enhanced fast magnetic resonance (MR) images of acute, reperfused human infarcts demonstrate regions of hypoenhancement and hyperenhancement. The relations between the spatial extent and time course of these enhancement patterns to myocardial risk, infarct, and no-reflow regions have not been well characterized. METHODS AND RESULTS: The proximal left anterior descending coronary artery was occluded in 11 closed-chest dogs for 90 minutes followed by 2 days of reperfusion. Regional blood flow was determined by use of radioactive microspheres. The animals were studied at the 2-day time point with contrast-enhanced fast MRI (Signa 1.5 T, General Electric). Thioflavin-S was administered to demarcate no-reflow regions. The hearts were then excised, sectioned into five base-to-apex slices, stained with 2,3,5-triphenyltetrazolium chloride (TTC), and photographed under room light (for TTC) and ultraviolet light (for thioflavin). The spatial extents of thioflavin-negative, TTC-negative, and risk regions were compared planimetrically with MRI hypoenhanced and hyperenhanced regions. The spatial locations of subendocardial hypoenhancement in MR images correlated closely with those of thioflavin-negative regions. Microsphere blood flow in these regions was significantly reduced compared with remote regions (0.37 +/- 0.09 versus 0.88 +/- 0.10 mL/min per gram, respectively, P < .001) and with baseline (0.37 +/- 0.09 versus 0.87 +/- 0.15 mL/min per gram, P < .01). The spatial extent of hyperenhancement was smaller than the risk region (r = .64, slope = 0.48, P < .001) but highly correlated with TTC-negative regions and were, on average, 12% larger (r = .93, slope = 1.12, P = .035). CONCLUSIONS: In contrast-enhanced MR images of 2-day-old reperfused canine infarcts, myocardial regions of hypoenhancement are related to the no-reflow phenomenon. Approximately 90% of the myocardium within hyperenhanced regions is nonviable.

Animals↗
PubMed1995

ICAM-1 expression in hepatocytes following dissociation of cell-to-cell contact in rats.

ICAM-1 was not detected immunohistologically in hepatocytes in normal rats, but detectable in centrilobular degenerative hepatocytes in carbon tetrachloride-intoxicated rats. ICAM-1 expression was observed even in normal hepatocytes following liver perfusion with Hank's balanced salt solution at a flow rate of 4.2 mL/g liver weight/min or with the same solution containing collagenase or EGTA at the physiological flow rate (1.4 mL/g liver weight/min). Such expression was also observed when liver perfusion was performed after pretreatment of rats with cycloheximide. On electron microscopy, ICAM-1 was exclusively stained on hepatocyte plasma membrane that was detached from the plasma membrane of adjacent hepatocytes. ICAM-1 mRNA and ICAM-1 protein were detected in hepatocytes freshly isolated from normal rats. Thus, ICAM-1 expression in degenerative hepatocytes as well as in hepatocytes following liver perfusion can be assumed to result from dissociation of cell-to-cell contact.

Animals↗
PubMed1995

Cloning and sequencing of beta-mannanase gene from Bacillus subtilis NM-39.

A gene encoding beta-mannanase from Bacillus subtilis NM-39 was cloned into Escherichia coli DH5 alpha by using pUC 18 and its nucleotide sequence was determined. The beta-mannanase gene was 1080 base pairs long and encoded a mature protein of 336 amino acids and a signal peptide of 24 amino acids. The deduced amino acid sequence of the cloned mannanase showed sequence homology with mannanase from alkalophilic Bacillus sp. strain AM-001 (about 50%).

Amino Acid Sequence↗
PubMed1995

In vivo transfection of genes for renin and angiotensinogen into the glomerular cells induced phenotypic change of the mesangial cells and glomerular sclerosis.

Locally activated renin angiotensin system plays an important role in the progression of the glomerular diseases. In order to understand the local effect of overexpressed angiotensin II in the glomerulus in situ, we introduced human genes for renin and angiotensinogen into the rat kidney by hemagglutinating virus of Japan-liposome procedure. Three days after transfection human renin was detected in the glomeruli by immunohistochemistry. Seven days after transfection, extracellular matrix was expanded in the glomeruli and alpha-smooth muscle actin was expressed in the mesangial cells. These results suggest that locally activated renin angiotensin system induces glomerular sclerosis and a phenotypic change in mesangial cells.

Actins↗
PubMed1995

Autoantibody to factor VIII that has less reactivity to factor VIII/von Willebrand factor complex.

To determine the difference in reactivity of factor VIII (FVIII) inhibitor to FVIII/von Willebrand Factor (vWF) complex and FVIII free of vWF, an autoantibody to FVIII light chain was tested. A patient (1-3) suffered from autoimmune hemolytic anemia with autoantibody to FVIII. Epitope specificity of the patient's IgG (I-3 IgG) was shown to be the C2 domain of FVIII light chain (2170-2332) by Western blotting using recombinant FVIII deletions expressed in Escherichia coli. The inhibitory effect on FVIII procoagulant activity (VIII:C) of I-3 IgG was tested against a conventional FVIII concentrate; Haemate P, a monoclonal antibody-purified FVIII concentrate; Hemofil M, and a recombinant FVIII (rFVIII); Kogenate. I-3 IgG showed only 1.3 BU/mgIgG for Haemate P, in contrast to 20 BU/mgIgG for both Hemofil M and Kogenate. The ratio of VIII:C/vWF:Ag in Haemate P and Hemofil M was 1/3.43 and 1/0.01, respectively, while Kogenate did not contain vWF. The inhibitory effect of the I-3 IgG was then compared with Kogenate and its complex with vWF. The inhibitory effect was decreased against the rFVIII by forming a complex with vWF from 22 BU/mgIgG to 0.5 BU/mgIgG. Fab from the I-3 IgG had the same effect. In addition, vWF showed a protective effect on FVIII inactivation by the I-3 IgG in a dose dependent manner. Fifty-nine percent of residual VIII:C was retained in the presence of 8 U/ml of vWF after 1 hr incubation with I-3 IgG. These results suggested that vWF could compete with the I-3 IgG for binding to FVIII.

Adult↗
PubMed1995

Role of neutrophil-mediated inflammation in aspirin-induced gastric mucosal injury.

The objectives of this study were to determine the roles of neutrophil-endothelial cell interactions and oxygen-derived free radicals in the pathogenesis of aspirin-induced gastric mucosal injury in rats. Oral administration of acidified aspirin (200 mg/kg) resulted in linear hemorrhagic erosions and an increase in myeloperoxidase activity, an index of neutrophil infiltration, in the gastric mucosa. Aspirin-induced gastric damage and the increase in myeloperoxidase activity were significantly inhibited by the injection of anti-CD11a, anti-CD11b, anti-intercellular adhesion molecule-1 monoclonal antibodies, and the combination of superoxide dismutase and catalase, which are scavengers of active oxygen species. These results suggest that neutrophil-endothelial adhesive interactions, which occur via CD11a/ CD18- and CD11b/CD18-dependent interactions with intercellular adhesion molecule-1, and oxygen-derived free radicals produced by neutrophils are implicated in the production of aspirin-induced gastric mucosal injury.

Animals↗
PubMed1995

Use of prostaglandin I2 analog in treatment of massive hepatic necrosis associated with endothelial cell injury and diffuse sinusoidal fibrin deposition.

Endothelial cell damage causes massive hepatic necrosis as a result of fibrin deposition in the hepatic sinusoids. When a stable analog of prostaglandin I2, beraprost sodium, was administered to rats given either dimethylnitrosamine, carbon tetrachloride, or endotoxin following Corynebacterium parvum administration, the hepatic necrosis produced in each was attenuated, but to a greater extent in the dimethylnitrosamine and endotoxin/Corynebacterium parvum models, where fibrin deposition in the hepatic sinusoids occurs, as compared to the carbon tetrachloride model, where such fibrin deposition does not occur. Beraprost sodium reduced the expected increase of portal venous pressure in the endotoxin/Corynebacterium parvum model without affecting plasma thrombin-antithrombin III complex levels. Beraprost sodium also significantly reduced cell killing of both isolated rat hepatocytes and hepatic sinusoidal endothelial cells exposed to tert-butyl hydroperoxide when compared to controls. Beraprost sodium could prove to be a therapeutic candidate for the treatment of hepatic necrosis, particularly in cases associated with fibrin deposition in the hepatic sinusoids because of its fibrin clot-clearing action.

Animals↗
PubMed1995

Wound healing of acetic acid-induced gastric ulcer in rats and the effects of cimetidine and calcitonin, with special reference to prolylhydroxylase and collagenase enzyme activity.

The healing of acetic acid-induced gastric ulcer in rats and the effects of cimetidine and calcitonin were investigated with reference to the enzyme activity of both prolylhydroxylase and collagenase as related to histological findings. The rats were observed by endoscopy on the 3rd day after the subserosal injection of acetic acid; rats with ulcers were divided into three groups: non-treated, and cimetidine- and calcitonin-treated. The latter two groups were treated for 7 days. Prolylhydroxylase activity in active ulcers in the non-treated group was slightly higher on the 3rd day and significantly higher on the 10th day than the activity in control rats that had received subserosal injections of physiological saline solution on the respective days. In non-treated rats, the healed ulcer on the 10th day showed lower prolylhydroxylase activity than that in the active ulcer on the same day. Cimetidine did not affect prolylhydroxylase activity, but, with calcitonin, there was higher prolylhydroxylase activity in the healed than in the active ulcer, although the difference was not significant. Interstitial collagenase showed the highest activity on the 3rd day and decreased on the 10th day in non-treated rats. Collagenase activity was higher in the cimetidine-treated group, than that in the non-treated group, and numerous peroxidase-positive granulocytes were seen in the mucosa and submucosa. Calcitonin did not affect collagenase activity. The participation of both enzymes is indispensable in the healing process and the effects of anti-ulcer agents on these enzymes must be considered.

Acetates↗
PubMed1995

Acute hepatitis in an adult with acquired rubella infection.

We report a case of acute hepatitis in a 28-year-old male with acquired rubella infection. Serological tests revealed acute rubella virus infection and ruled out infection by other common viruses, including type A and type B hepatitis viruses. The patient showed not only marked increase of lactate dehydrogenase (LDH) activity, with only slight liver dysfunction, but also platelet and kidney injury, suggesting systemic rubella virus infection. Because the liver dysfunction was slight, liver biopsy was not performed. When a patient has mild, transient hepatitis accompanied by high LDH activity in comparison with both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, we should take a common viral infection such as rubella into consideration when making a diagnosis.

Acute Disease↗
PubMed1995

Changes in immunoreactive insulin, C-peptide immunoreactivity, and immunoreactive glucagon in acute viral hepatitis.

Insulin and glucagon are thought to play important roles as hepatotrophic factors in acute viral hepatitis (AVH); however, few reports have investigated the responses and relationships of each of these hormones to liver damage in detail. We studied insulin and glucagon responses during the acute and recovery phases of AVH. We performed a glucose tolerance test (GTT) and an insulin sensitivity test (IST) in each phase in 11 patients with AVH. In 8 additional patients in the acute phase (total n = 19), were compared immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR) levels with transaminase levels. In the acute phase, IRI concentrations were normal from fasting to 60 min, despite an increased CPR level. In the recovery phase, IRI and CPR levels increased significantly. Immunoreactive glucagon levels in both phases did not differ significantly from those in controls. During the IST, the insulin sensitivity index in both phases was significantly lower than that in the controls. Fasting IRI and sigma IRI showed significant negative correlations with transaminase levels. We found enhanced insulin secretion and a decrease in plasma insulin in the acute phase of AVH. The discrepancy between IRI and CPR responses in the acute phase suggests an increase in the degradation or consumption of insulin in the liver.

Acute Disease↗
PubMed1995

Factor VIII inhibitor developed in a 60-year-old patient with mild hemophilia A after surgery for colon cancer.

Most factor VIII inhibitors are developed at an early age and in patients with severe type of hemophilia A. We report a case of newly developed factor VIII inhibitor in a 60-year-old patient with mild hemophilia A who had been treated with several kinds of factor VIII concentrates. The patient was treated with a total of 103,580 units of recombinant factor VIII concentrate by continuous and bolus infusions for the open surgery of sigmoid colon cancer. On the 95th postoperative day, the patient had right low limb muscle bleeding and was infused with 1,000 units of recombinant factor VIII concentrate for three days. Subsequently, the level of factor VIII inhibitor in the patient's plasma was 2 Bethesda units (BU)/ml. Since then numerous subcutaneous hemorrhages developed, but an adequate hemostatic effect was not obtained even with the administration of a high dose of recombinant factor VIII concentrate. The patient was switched to bypass therapy using human plasma-derived factor VIIa concentrate, which showed a favorable hemostatic effect.

Adenocarcinoma↗
PubMed1995

Molecular cloning and functional expression of a cDNA for rat phospholipid hydroperoxide glutathione peroxidase: 3'-untranslated region of the gene is necessary for functional expression.

A full-length cDNA clone for phospholipid hydroperoxide glutathione peroxidase (PHGPx) was isolated from a rat brain. The cDNA was 0.761 kb in length and encoded 170 amino acids, which included a TGA-encoded selenocysteine at residue 46. The protein has a calculated molecular mass of 19,473 Da. We succeeded in the transient functional expression of a full-length cDNA for PHGPx, which includes the 3'-UTR, in COS-7 cells at the first attempt. Deletion of the 3'-UTR prevented the expression of the PHGPx activity and the incorporation of [75Se]selenious acid into the monomeric 19.7 kDa PHGPx protein. Thus, the 3'-UTR of the cDNA for PHGPx was required for the functional expression of PHGPx. Northern blot analysis demonstrated that the mRNA for PHGPx was widely expressed in normal rat tissues, especially in the testis. The mRNA levels of PHGPx in the cultured cells such as hepatomas, neuronal cells, nephroblastoma, and mammary myo-epithelial cells were higher than those of the tissues. The ratio of PHGPx to cytosolic glutathione peroxidase (cGPx) was significantly high in the testis and relatively high in the cultured cells. The mRNA levels of PHGPx in tissues were lower than those of cGPx.

Amino Acid Sequence↗