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Biomedical subjects

K Ichihara

Publications and source records attributed to K Ichihara.

At least 235 records · Page 13Linked to original sources
PubMed1986

Effect of peroxisomal proliferators on microsomal prostaglandin A omega-hydroxylase.

Earlier, we reported the isolation of a cytochrome P-450 highly active in prostaglandin A (PGA) omega-hydroxylation (PGA omega-hydroxylase) from rabbit kidney cortex, small intestine, and colon microsomes. In the present studies, the effects of peroxisomal proliferating agents on the PGA omega-hydroxylase have been examined. Administration of clofibrate or di(2-ethylhexyl)phthalate (DEHP) resulted in a significant increase in the PGA1 omega-hydroxylase activity of kidney cortex, liver, and small intestine microsomes. Similar findings were also obtained for laurate hydroxylase activity in kidney and liver microsomes. Kidney PGA omega-hydroxylase (designated cytochrome P-450ka) was isolated and highly purified from clofibrate- or DEHP-treated rabbits, with a yield 3 times higher than that from untreated, or phenobarbital- or 3-methylcholanthrene-treated rabbits. Cytochrome P-450ka from clofibrate- or DEHP-treated rabbits exhibited the same properties as those from untreated rabbits. Guinea pig antiserum against cytochrome P-450ka strongly inhibited the omega-hydroxylation of PGA1 by kidney cortex microsomes from clofibrate-treated rabbits. The PGA1 omega-hydroxylase activity of clofibrate-treated liver microsomes was also inhibited by this antiserum, suggesting that a PGA omega-hydroxylase immunochemically related to cytochrome P-450ka exists in liver microsomes.

Animals↗
PubMed1986

Asymptomatic hyperprolactinaemia and prolactinoma in the general population--mass screening by paired assays of serum prolactin.

A total of 10,550 'normal' adults (8450 men and 2100 women) in the general population were screened by a paired assay method for serum PRL and 40 subjects with hyperprolactinaemia (greater than 75 micrograms/l) were detected. Of these, five patients (three men and two women) with pituitary prolactinoma, one man with empty sella syndrome, 10 cases of 'big' prolactinaemia, seven pregnant women and 13 subjects with drug-induced hyperprolactinaemia were found. The patients with prolactinoma had few if any complaints (asymptomatic prolactinoma).

Female↗
PubMed1986

Reduced serum carnosinase activity in hypothyroidism.

Carnosinase hydrolyses carnosine in muscle, and its deficiency is associated with extensive neuromuscular abnormalities. We measured serum carnosinase activity in patients with thyroid dysfunction which often involves neuromuscular systems. In hyperthyroidism, the carnosinase activity was not significantly different from that in normal subjects. In hypothyroidism, however, it was significantly lower than that in normal subjects. The activity examined in five patients with hypothyroidism returned to normal after replacement therapy. In hypothyroidism, the carnosinase activity showed significant correlation with concentration of serum thyroxine and negative correlation with serum creatine kinase activity. This finding may be of practical importance in the differential diagnosis of disorders causing carnosinase deficiency.

Clinical Enzyme Tests↗
PubMed1986

Functional and metabolic responses to ischemia in the perfused heart isolated from normotensive and spontaneously hypertensive rats.

The difference between normotensive rats (WKY) and spontaneously hypertensive rats (SHR) in functional and metabolic responses to ischemia was studied. Systolic arterial blood pressure of SHR (171.2 +/- 2.9 mmHg) was significantly higher than that of WKY (135.3 +/- 1.2 mmHg), and the left ventricular mass of SHR was larger than that of WKY. Hearts isolated from either WKY or SHR were perfused by the working heart technique. Ischemia was induced by lowering the afterload pressure of the working heart. Ischemia produced cardiac arrest, and decreased the tissue levels of adenosine triphosphate and creatine phosphate in both WKY and SHR. Recovery of mechanical function of the heart during reperfusion following ischemia in SHR was better than that in WKY, while recovery of the high-energy phosphates level in SHR was less prominent than in WKY. It is postulated that hypertension has a deleterious effect on myocardial energy metabolism in ischemic heart, even when cardiac mechanical function is maintained.

Adenosine Triphosphate↗
PubMed1986

[Ischemic myocardial metabolism and antianginal drugs].

The effect of several kinds of antianginal drugs: nitrates, coronary vasodilators, beta-adrenergic blocking agents and calcium entry blocking agents on the myocardial metabolism and myocardial acidosis during ischemia was studied in the dog heart in vivo. Ischemia was induced by ligating the left anterior descending coronary artery. Ischemia accelerated anaerobic metabolism in the myocardium, in which glycogen breakdown, accumulation of glycolytic intermediates, loss of high energy phosphate and tissue acidosis occurred. Nitroglycerin, beta-adrenergic blocking agents such as propranolol, and some calcium entry blocking agents such as diltiazem and flunarizine prevented the myocardial metabolism from shifting to an anaerobic metabolism in spite of ischemia. However, coronary vasodilators and the dihydropyridine type of calcium entry blocking agents were not capable of reducing changes in the myocardial metabolism and myocardial acidosis during ischemia. The author makes a point in the present review that all the drugs which dilate coronary artery are not always effective on the ischemic myocardium.

Angina Pectoris↗
PubMed1986

Antiulcer effect of (-)-cis-2,3-dihydro-3-(4-methylpiperazinylmethyl) -2-phenyl-1,5-benzothiazepin-4-(5H)-one hydrochloride (BTM-1086) in experimental animals.

Effects of (-) cis-2,3-dihydro-3-(4-methylpiperazinylmethyl)-2-phenyl-1,5-benz othiazepin-4-(5H ) -one hydrochloride (BTM-1086) on various experimental gastric and duodenal ulcers were studied in rats. In the pylorus-ligated ulcer, restraint and water immersion stress ulcer, and drug-induced ulcer (indomethacin, aspirin, reserpine, serotonin, cysteamine), BTM-1086 prevented the development of ulcer at a dose of 0.1 to 1 mg/kg, p.o., but only weakly inhibited the histamine-induced gastric ulcer. The inhibitory activities of BTM-1086 were significantly higher than those of atropine sulfate. In the healing experiment with the acetic acid-induced stomach ulcer, BTM-1086 (1 mg/kg/day, p.o., X 14) showed a significant healing effect, which was higher than that of propantheline bromide. BTM-1086 at a dose of 0.2 mg/kg, i.d., remarkably inhibited the gastric secretion 6 hr after pylorus ligation. The aspirin-induced reductions of the total acid and K+ as well as the increments of the volume and Na+ in the gastric secretion were prevented dose-dependently by pretreatment with BTM-1086.

Animals↗
PubMed1986

Hypercalcemia in glucocorticoid withdrawal.

We found severe hypercalcemia in the course of hydrocortisone withdrawal in a patient who had undergone unilateral adrenalectomy to resect a cortisol-hypersecreting adenoma. Serum calcium gradually but progressively increased after unilateral adrenalectomy. Severe hypercalcemia developed on the 77th postoperative day (the 15th day after discontinuing hydrocortisone replacement). The serum concentration of calcium, PTH, 25(OH)D, and 1,25(OH)2D were 8.0 mEq/l, less than 100 pg/ml, 10.1 ng/ml and 29.6 pg/ml, respectively. This hypercalcemia was accompanied by marked urinary hydroxyproline excretion and less calcium excretion in the urine than the prevailing level of serum calcium. Serum concentrations of 25(OH)D, 1,25(OH)2D and PTH were not elevated during the severe hypercalcemia. We concluded that the hypercalcemia in this patient was due in part to enhanced bone resorption and increased renal tubular reabsorption of calcium as a result of glucocorticoid withdrawal, but not to the elevation of serum PTH or serum 25(OH)D and serum 1,25(OH)2D.

Adenoma↗
PubMed1986

Myocardial ischemia stimulates catecholamine synthesis and catabolism in the dog adrenal medulla.

The effects of regional ischemia of the myocardium upon metabolism and catabolism of catecholamines were studied in the dog adrenal medulla. Regional ischemia was induced by ligating a small branch of the left anterior descending coronary artery for 1 or 24 hours. Sham-operated controls were run in parallel. Coronary ligation for 24 hours resulted in a decrease in the level of epinephrine and an increase in the level of dopamine in the adrenal medulla, and also resulted in an increase in the activities of the phenylethanolamine-N-methyltransferase (PNMT), monoamine oxidase, and catechol-O-methyltransferase. The results after coronary ligation for 1 hour were essentially the same as those after coronary ligation for 24 hours, except that the activity of PNMT decreased. These results suggest that both synthesis and catabolism of catecholamines in the adrenal medulla are accelerated during coronary ligation for a period of 1 to 24 hours.

Adrenal Medulla↗
PubMed1986

A method for evaluating antianginal drugs in experimental animals: assessment of myocardial ischemia by myocardial pH.

This paper describes a method by which antianginal drugs can be evaluated in the dog heart in situ. Myocardial pH was measured continuously by a micro glass pH electrode inserted in the left ventricular endocardial layers of the dog anesthetized with pentobarbital. Occlusion of the left anterior descending coronary artery (LAD) decreased myocardial pH, and release of the LAD restored the pH. The myocardial acidosis induced by ischemia was metabolic in nature and accompanied by a decrease in the levels of adenosine triphosphate and creatine phosphate and an increase in the levels of lactate in the myocardium. Drugs were injected intravenously 30 min after incomplete (partial) occlusion ot the LAD, lasting until 60 min after drug injection. Propranolol, atenolol, and sotalol markedly attenuated the myocardial pH that had been decreased by LAD occlusion. Nitroglycerin, diltiazem, and nicorandil also attenuated the pH, but these drugs were less active in attenuating myocardial acidosis. Dipyridamole, nifedipine, and beta-2 adrenoceptor antagonists were least active in this regard. It is concluded that myocardial pH can be used as an indicator of myocardial regional ischemia and utilized for evaluation of antianginal drugs.

Acidosis↗
PubMed1986

Hyperphosphatemia as a detectable laboratory manifestation of glucocorticoid withdrawal syndrome.

We found hyperphosphatemia in five patients who had undergone unilateral adrenalectomy (ADX) for resection of cortisol-producing adenomas. The mean (+/- SEM) serum inorganic phosphorus level, theoretical renal phosphorus threshold and percent tubular phosphorus reabsorption rose from the preoperative level of 3.3 +/- 0.2 mg/dl, 2.6 +/- 0.2 mg/dl and 82.1 +/- 0.6%, to 6.0 +/- 0.2 mg/gl, 7.4 +/- 0.4 mg/dl and 95.9 +/- 1.0%, respectively, after ADX (P less than 0.001, P less than 0.001, P less than 0.001). Urinary phosphorus excretion decreased from 549 +/- 40 to 294 +/- 108 mg/day after ADX (P less than 0.05). Changes in serum calcium, serum sodium, serum potassium, serum chloride and creatinine clearance were not significant after ADX. Hyperphosphatemia may be the only abnormality found in serum electrolytes in glucocorticoid deficiency. It thus seems that hyperphosphatemia may be regarded as one of the clinical manifestations of the glucocorticoid withdrawal syndrome.

Adenoma↗
PubMed1986

Effect of nifedipine and niludipine on myocardial pH in the ischemic canine heart.

The effect of nifedipine and niludipine on ischemic myocardial pH was studied. To make the myocardium ischemic (60% reduction of coronary flow), the left anterior descending coronary artery (LAD) was partially occluded 30 min before either vehicle (1% ethanol solution) or drugs were injected intravenously. In the non-occlusion group, nifedipine (10 micrograms/kg) and niludipine (10 micrograms/kg) increased coronary flow, decreased blood pressure, and did not change myocardial pH appreciably. In the partial occlusion group, reduction of coronary flow decreased the myocardial pH, increased ST segment, and did not change heart rate and blood pressure. Vehicle was injected 30 min after the occlusion, but did not change any of the parameters. A small dose (1 microgram/kg) and a large dose (10 micrograms/kg) of nifedipine, and niludipine (10 micrograms/kg) did not exert any beneficial effect on the myocardial pH, coronary flow and the ST segment during coronary occlusion.

Animals↗
PubMed1986

Decreased activity of carnosinase in serum of patients with chronic liver disorders.

We measured the activity of carnosinase, a prominent hepatic peptidase, in sera from 69 patients with liver disorders. Mean values (and SDs) for those with liver cirrhosis (17 cases) and hepatoma (seven cases) were 0.51 (0.28) and 0.68 (0.21) mumol/mL per hour, respectively--clearly less than for normal adults: 4.19 (0.95) mumol/mL per hour. Samples from 17 cases of chronic hepatitis also showed moderately decreased activity, 1.41 (0.97) mumol/mL per hour. In contrast, 14 cases of acute hepatitis generally showed values falling within the normal limits: 3.41 (1.97) mumol/mL per hour. Our results for carnosinase correlated with those for cholinesterase (r = 0.70) and with the concentration of albumin in serum (r = 0.59), but not with the activity of either creatine kinase, aspartate aminotransferase, or alanine aminotransferase in serum. Carnosinase values differed more among groups of disorders than did the values for cholinesterase or albumin. Measurement of serum carnosinase activity may be of clinical value in assessing the severity of chronic liver-cell damage, but not in differentiating liver disease from nutritional, muscle, or endocrine disorders.

Adult↗
PubMed1985

Separation of two constitutive forms of cytochrome P-450 active in aminopyrine N-demethylation from rabbit intestinal mucosa microsomes.

Two constitutive forms of cytochrome P-450, designated P-450ib and P-450ic, were purified from intestinal mucosa microsomes of untreated rabbits. P-450ib and P-450ic have minimal molecular weights of 56 000 and 49 000, respectively, as determined by calibrated sodium dodecyl sulphate polyacrylamide gel electrophoresis. The CO-reduced difference spectral maximum of cytochrome P-450ib is at 450 nm and P-450ic is at 451 nm. Both the cytochromes preferentially demethylate aminopyrine, benzphetamine and N,N-dimethylaniline in the presence of NADPH-cytochrome P-450 reductase. Cytochrome P-450ib has absorption maxima at 417, 535 and 573 nm in the oxidized form, indicating that this cytochrome is in a low-spin state. Ouchterlony double-diffusion studies show that cytochrome P-450ib does not cross-react with antisera against liver cytochrome P-450LM2 purified from phenobarbital-treated rabbits, but P-450ic cross-reacts with spur formation. Unlike cytochrome P-450ib, P-450ic is very similar, if not identical, to liver cytochrome P-450LM2 on the basis of its molecular weight, spectral properties, catalytic activities and immunochemical properties.

Aminopyrine N-Demethylase↗
PubMed1985

Diagnosis, treatment and postoperative results of Cushing's disease.

One hundred patients with Cushing's disease were operated on in Nagoya University Hospital between January 1977 and January 1984. Pituitary adenomas were found and resected in 93 cases and complete clinical remissions were observed in 89 treated by operation alone and in two additional cases by operation followed with radiotherapy. The clinical features, pre-operative endocrine data, radiological findings including high resolution CT with coronal and sagittal reconstructions, data of selective venous sampling, operative findings, tumour pathology, postoperative clinical course, postoperative endocrine results and follow-up findings are presented and discussed.

Adenoma, Basophil↗
PubMed1985

Fractionation of polyclonal antibody by isoelectric focusing and chromatofocusing: separation of high-affinity rabbit clonotype anti-thyroxine antibody.

Immunoglobulin G fractions prepared from conventional rabbit anti-thyroxine (T4) antisera were fractionated by agarose gel isoelectric focusing (IEF) in the range of pH 3 to 10, and by chromatofocusing using a Fast Protein Liquid Chromatography (FPLC) system. The clonotype antibodies were recovered from the fractions and subjected to Scatchard plot analysis. The highest affinity constants of the initial antibody (shown in parentheses) and those of the antibodies recovered were IEF, 1.8 X 10(9) to 8.3 X 10(9) M-1 (2.2 X 10(9) M-1); FPLC, 2.4 X 10(9) to 6.0 X 10(9) M-1 (2.5 X 10(9) M-1). A sensitive radioimmunoassay of T4 was achieved with the isolated high-affinity anti-T4 antibody. The minimum detectable concentration of T4 was 6.3 X 10(-15) to 1.5 X 10(-14) mol/tube, which was three to five times lower than detectable with the initial antibodies.

Animals↗