Search PubMed⌕ Search

Biomedical subjects

K Ichihara

Publications and source records attributed to K Ichihara.

At least 199 records · Page 11Linked to original sources
PubMed1989

A possible involvement of oxygen free radicals in the development of myocardial acidosis during coronary occlusion in dogs.

The present study was designed to examine whether free radical scavengers attenuate myocardial acidosis induced by partial occlusion of the coronary artery in dogs. The myocardial pH was determined by a micro glass pH electrode inserted in the endocardial layers of the left ventricular wall perfused by the left anterior descending coronary artery. The left anterior descending coronary artery was occluded for 90 min incompletely so that the flow would be 1/2-1/3 the original flow. The myocardial pH before partial occlusion was 7.54-7.55. Partial occlusion decreased the flow in the left anterior descending coronary artery by 49.3-64.9% and the myocardial pH by 0.71-0.76, and increased the ST segment (surface electrocardiogram) by 6.3-9.3 mV. Saline (0.5 ml/kg), recombinant human superoxide dismutase (70,000 or 210,000 U/kg), or catalase (55,000 or 165,000 U/kg) was injected intravenously 30 min after partial occlusion. The injection of recombinant human superoxide dismutase or catalase alone did not restore the myocardial pH that had been decreased by coronary occlusion. The combined injection of recombinant human superoxide dismutase (70,000 U/kg) + catalase (55,000 U/kg), however, restored the myocardial pH without restoration of ST segment. In conclusion, recombinant human superoxide dismutase + catalase attenuated myocardial acidosis during ischaemia, suggesting a possible involvement of oxygen free radicals in the development of myocardial acidosis (especially in the endocardial layers) during ischaemia.

Acidosis↗
PubMed1989

Partial characterization of testosterone 5 alpha-reductase solubilized from rat testicular microsomes.

Testosterone 5 alpha-reductase was successfully solubilized by the use of digitonin from rat testicular microsomes and then partially purified by polyethylene glycol fractionation and DEAE-Sephacel column chromatography. The 5 alpha-reductase activity of the partially purified preparation was significantly stimulated by addition of phosphatidylserine (bovine brain). Synthetic dilauroylphosphatidylcholine also increased the reductase activity to a somewhat lesser extent than did phosphatidylserine, whereas natural phosphatidylcholine from bovine liver did not exhibit any stimulation. When synthetic phosphatidylcholines with varying acyl chain lengths were tested for their stimulatory effects on the reductase activity, dilauroylphosphatidylcholine was most active; dimyristoylphosphatidylcholine was less active; dioleoylphosphatidylcholine was almost inactive.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1989

Progesterone metabolism in the gastric mucosa microsomes of guinea pig.

The microsomes from guinea pig gastric mucosa were found to convert [4-14C]progesterone to two major metabolites in the presence of NADPH. The gastric metabolizing activity was the highest among the gastrointestinal tissues of guinea pig. 5 alpha-Pregnane-3,20-dione and 3 beta-hydroxy-5 alpha-pregnan-20-one were identified as the major metabolites by thin-layer chromatography and crystallization to constant specific activity, suggesting the presence of steroid 5 alpha-reductase and 3 beta-hydroxysteroid dehydrogenase activities in the gastric mucosa microsomes. Furthermore, time course of progesterone metabolism and analysis of 5 alpha-pregnane-3,20-dione metabolites suggest that the gastric progesterone metabolism is initiated by 5 alpha-reductase and followed by 3 beta-hydroxysteroid dehydrogenase. The progesterone-metabolizing activity was strongly inhibited by SKF 525-A and disulfiram. The activity was also inhibited by methyrapone to a somewhat lesser extent than the above inhibitors. From gastric mucosa microsomes, the progesterone-metabolizing activity was successfully solubilized with 2% digitonin using 0.1 M potassium chloride and 1 mM dithiothreitol, 0.4 mM NADPH and 20% glycerol as stabilizers for the solubilized activity. Among these stabilizers, glycerol was found to be most effective for stabilizing the activity of the solubilized microsomes.

17-Hydroxysteroid Dehydrogenases↗
PubMed1989

Microsomal phosphatidate phosphatase in maturing safflower seeds.

An assay system comprising sodium phosphatidate, phosphatidylcholine, and bovine serum albumin has been developed for the reproducible determination of phosphatidate phosphatase activity in maturing seeds of safflower (Carthamus tinctorius L.). The activity was detected in both membrane and soluble fractions, and the microsomal phosphatidate phosphatase was characterized. The optimum pH for Pi release was 6.7, and the activity depended on the concentration of Mg(2+). Phosphatidylcholine and bovine serum albumin stimulated the phosphatase reaction. This phosphatase was highly specific for phosphatidate; lysophosphatidate, and water-soluble phosphate esters did not serve as substrate. The specific activity was approximately 20 nanomoles per minute per milligram of protein, which was close to that of glycerol-phosphate acyltransferase and higher than that of diacylglycerol acyltransferase. Furthermore, the activity per seed was enough to account for the rate of triacylglycerol accumulation in vivo. The step of diacylglycerol formation by phosphatidate phosphatase does not appear to be rate-limiting for triacylglycerol synthesis during seed maturation.

Journal Article↗
PubMed1989

Evaluation of TSH receptor antibody by 'natural in vivo human assay' in neonates born to mothers with Graves' disease.

Neonatal thyrotoxicosis induced by transferred TSH receptor antibody (TRAb) is the ideal human in-vivo experimental system for the evaluation of TRAb. The clinical significance of circulating TRAb in Graves' disease was evaluated by this 'natural in-vivo human assay'. TRAb activity in vitro was measured by radioreceptor assay (thyrotrophin-binding inhibitor immunoglobulin, TBII) and sensitive cAMP accumulation assay using FRTL-5 cells (thyroid-stimulating antibody, TSAb). Further, the binding-stimulation index (B-S index) was newly introduced, which was the most useful indicator for prediction of neonatal thyrotoxicosis, calculated as the product of TBII and TSAb (Tamaki et al., 1988a). Maternal serum TRAb indices showed highly significant correlations with the serum free T4 index (FT4I) and free T3 index (FT3I) in neonates (5-10 days after birth) born to 20 mothers with Graves' disease who had positive TBII and/or TSAb (FT4I: r = 0.825 for TBII, r = 0.908 for TSAb, r = 0.944 for the B-S index, P less than 0.001; FT3I: r = 0.622 for TBII, P less than 0.01, r = 0.812 for TSAb, r = 0.791 for the B-S index, P less than 0.001; n = 20). In contrast, in 57 untreated adult patients with hyperthyroid Graves' disease, the FT4I and FT3I levels were not correlated with any of the TRAb indices. The linear regression relationship between the B-S index and FT4I found in neonates was applied to values in adult patients with Graves' disease, and the patients were divided into three groups on the basis of the 95% confidence limit: high, normal, and low responders of thyroid hormone (FT4I) secretion to the B-S index. FT4I and the ratio of FT4I to the B-S index were highest and the TRAb indices were lowest in the high responders, while FT4I and the FT4I/B-S index ratio were lowest and the TRAb indices were highest in the low responders. The FT4I/B-S index ratio was inversely correlated with the titres of antithyroid microsomal antibody in all the adult patients with untreated Graves' disease (r = -0.288, P less than 0.05). The results suggest that in-vitro assays using animal thyroid cells and cAMP as an index of response are suitable for detecting circulating thyroid stimulating activity in vivo. Secretion of thyroid hormones in Graves' disease may be regulated not only by circulating thyroid-stimulating antibodies but also by intrathyroidal stimulatory factors or by inhibitory or destructive factors.

Antibodies↗
PubMed1989

Attenuation of ischaemia-induced regional myocardial acidosis by bevantolol, a beta 1-adrenoceptor antagonist, in dogs.

In dogs anaesthetized with pentobarbital, the left anterior descending coronary artery (LAD) was occluded for 90 min. so that about 1/2 of the original flow was allowed to flow (partial occlusion). Bevantolol (a beta 1-adrenoceptor antagonist) or propranolol (a reference drug) was injected intravenously 30 min. after partial occlusion. Regional myocardial pH was measured by a micro glass pH electrode inserted in the LAD area. Partial occlusion decreased myocardial pH by 0.62 to 0.74. Bevantolol (1.0 mg/kg) or propranolol (1.0 mg/kg) significantly increased myocardial pH, that had been decreased by partial occlusion, within 60 min. after the injection. Restoration of myocardial [H+] (defined as return towards a lower [H+] to the preocclusion level) (calculated from the pH data) induced by bevantolol and that induced by propranolol were 64.0 and 66.4% (measured 60 min. after the injection), respectively. Bevantolol or propranolol decreased heart rate also. Even in the paced heart, bevantolol restored the myocardial [H+] that had been increased by partial occlusion. These results suggest that bevantolol has a favorable effect on the ischaemic myocardium as has propranolol, and that the pH effect of bevantolol is not primarily due to a decrease in heart rate.

Acidosis↗
PubMed1989

Analysis of overall pathophysiological relationships between serum levels of TSH and thyroid hormones using a large laboratory database.

Factors associated with the basal level of serum thyrotropin (TSH) were analyzed over a wide range of pathophysiological conditions by means of a large laboratory database on thyroid function. When data were analyzed two-dimensionally, serum TSH showed significant inverse correlations with total triiodothyronine (T3), free T3 index (FT3I), total thyroxin (TT4) and free T4 index (FT4I) in the order of increasing intensity. The three-dimensional analysis, however, revealed that 1) total hormone levels were actually unrelated to serum TSH when the levels of free hormone indices were held constant, 2) the relation between FT3I and TSH became obscure when the influence of FT4I was similarly removed. On the other hand, 3) the relation of FT4I with TSH was unaffected by the level of FT3I. These results suggest that free T4 is the main determinant of the serum TSH level. This study also implies that it is possible to use large amounts of laboratory data to elucidate the overall profile of a given patho-physiological system, whose structure is only partially revealed by conventional clinical or animal studies.

Data Interpretation, Statistical↗
PubMed1989

Marked increase of CD5 + B cells in hyperthyroid Graves' disease.

We examined the proportions of B lymphocytes bearing CD5 cell surface antigen (CD5+ B cells), which are capable of making autoantibodies, in peripheral blood from patients with various thyroid diseases. The level of CD5+ B cells was markedly increased (>9.0%) above the normal range (0.5-7.7%) in untreated, hyperthyroid patients with Graves' disease, although about 10% of the patients had no detectable serum thyroid-stimulating hormone (TSH) receptor antibody (TRAb). However, the levels of CD5+ B cells were normal in untreated patients with destructive thyrotoxicosis due to aggravation of Hashimoto's thyroiditis or subacute thyroiditis. In patients with stimulated hyperthyroid Graves' disease the levels of CD5+ B cells were correlated with those of thyroid hormones and TRAb, all significantly increased. However, once hyperthyroidism was controlled by anti-thyroid drugs, CD5+ B cells were decreased, followed in turn by reduction of TRAb. We conclude that the proportion of CD5+ B cells is useful as a therapeutic index and for diagnosis of Graves' disease and its differentiation from destruction-induced thyrotoxicosis.

Adult↗
PubMed1989

Cellular immunity as a valuable factor for prognostic prediction in patients with Graves' disease under antithyroid drug therapy.

Studies were performed on 42 unselected clinically euthyroid patients with Graves' disease under maintenance doses of antithyroid drugs for various clinical parameters to determine the remission rate and to investigate which parameters carry weight in determining the outcome of the disease and could be good predictive factors. T3 suppression test was performed in all patients, after which antithyroid drugs were discontinued and outcome of drug therapy was evaluated for 18-24 months. Patients were divided into two groups; group A, 12 patients, who stayed in remission and group B, 30, who had recurrence during the first year (0.5-9 months) after discontinuation of therapy. Duration of clinical history was not different between group A (mean 62.3 months) and group B (59.6 months), nor euthyroid periods before the test (15.5 months for group A and 17.6 months for group B). For thyroid specific parameters T4, T3, RT3U, TSH, thyroglobulin (Tg), thyroid suppressibility after T3 administration and goiter size; and anti-thyroglobulin antibody (TGHA), anti-thyroid microsomal antibody (MCHA), TSH-binding inhibitor immunoglobulins (TBII), thyroid-stimulating antibodies (TSAb), peripheral lymphocytes count and lymphocyte subsets [CD3, CD4, CD8, Leu7 and CD20 (B1)], as immunological parameters were analysed by linear discriminant analysis method to observe the significance in discriminating patients with or without remission and to evaluate the validity for predictive factors. (ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Nipradilol, a beta-adrenoceptor antagonist having a vasodilatory action, attenuates myocardial acidosis induced by coronary artery occlusion in dogs.

In dogs anesthetized with pentobarbital, the anterior descending coronary artery (LAD) was partially occluded to reduce LAD flow to about half of the original flow (partial occlusion). Myocardial pH (MpH) was measured by the use of a micro glass pH electrode. MpH decreased from 7.5-7.63 to 6.82-6.86 30 min after partial occlusion of the LAD. Nipradilol (0.3 mg/kg) was injected intravenously 30 min after partial occlusion, which continued for a further 60 min after nipradilol injection. Nipradilol decreased blood pressure and heart rate, and significantly increased myocardial pH which had been decreased by partial occlusion, within 60 min after injection. Nipradilol-induced restoration of the myocardial [H+] (calculated from the pH data), that had been increased by partial occlusion, was 48.5%. Bradycardia induced by nipradilol was not a determinant factor in the pH effect of nipradilol, because even in the paced heart, nipradilol restored the myocardial [H+] that had been increased by partial occlusion. These results indicate that nipradilol attenuates ischemia-induced myocardial acidosis, suggesting the favorable effect of nipradilol on ischemic myocardium. The favorable effect of nipradilol may be due to the beta-adrenoceptor antagonistic effect rather than the vasodilating effect.

Acidosis↗
PubMed1988

Effects of haloperidol, sulpiride and SCH 23390 on passive avoidance learning in mice.

The main purpose of the present study was to examine the effect of dopamine blockers on memory processes by means of a one-trial passive avoidance (PA) task with ddY mice. Haloperidol (0.025-0.4 mg/kg i.p.) did not affect the PA response when it was given before the training or retention test. Sulpiride (10-80 mg/kg i.p.) had different effects, depending on the doses employed: A lower dose (20 mg/kg) of sulpiride, which is thought to block presynaptic receptors, impaired the PA response but higher doses (40 and 80 mg/kg i.p.) did not affect it when sulpiride was given before the training or retention test. SCH 23390 (0.025-0.1 mg/kg i.p.) impaired the PA response only when it was given before the training. These results suggest that blocking of postsynaptic D-2 receptors does not impair memory processes but blocking of presynaptic D-2 receptors impairs both acquisition and retrieval stages of memory processes following an increase in dopamine release. The involvement of D-1 receptors in memory processes involved in the PA response may be essentially different from that of D-2 receptors, since the blocking of D1 receptors impaired only memory acquisition.

Animals↗
PubMed1988

Diacylglycerol acyltransferase in maturing safflower seeds: its influences on the fatty acid composition of triacylglycerol and on the rate of triacylglycerol synthesis.

Diacylglycerol acyltransferase in a particulate preparation from maturing safflower seeds showed no strict selectivity for acyl-CoA when acyl-CoA substrates were administered as mixtures. This suggested that the fatty acid composition of position 3 in safflower triacyl-sn-glycerol exclusively depends on the acyl-CoA composition in the cell. The specific activity of the acylation was approximately 3 nmol/min per mg protein of the preparation under the optimum assay conditions. This low activity and other data appeared to indicate that the diacylglycerol acyltransferase reaction may be the rate-limiting step in triacylglycerol synthesis in vivo.

Acyltransferases↗
PubMed1988

Cardiac metabolism as an indicator of oxygen supply/demand ratio.

We evaluated the anti-ischemic effect of drugs by using the inhibition of glycolytic flux at the level of the phosphofructokinase (PFK) reaction, caused by ischemia, as an indicator of the oxygen supply/demand ratio in the ischemic myocardium. Ischemia was induced by ligating the left anterior descending coronary artery in the open-chest dog. After 3 min of coronary ligation, the ischemic myocardium was removed. The endocardial portion of the myocardial sample was used to determine the levels of glucose-6-phosphate (G6P), fructose-6-phosphate (F6P) and fructose-1,6-diphosphate (FDP), and the ratio of [( G6P] + [F6P])/[FDP] was calculated in order to assess the rate of glycolytic flux at the PFK stage. Either saline or drug (propranolol, 1 mg/kg; carteolol, 100 micrograms/kg; nadolol, 1 mg/kg; nifedipine, 10 micrograms/kg; diltiazem, 100 micrograms/kg; verapamil, 100 micrograms/kg; and flunarizine, 1 mg/kg) was injected intravenously 5 min before coronary ligation. In the saline-treated heart, ischemia increased the levels of G6P and F6P, whereas it decreased the level of FDP. The ratio of ([G6P] + [F6P])/[FDP] was increased by ischemia from 2.2 to 23.6, suggesting the inhibition of glycolytic flux at the level of the PFK reaction. In the drug-treated heart, ischemia increased the levels of G6P and F6P, but the increases were smaller than those in the saline-treated heart. Pretreatment with propranolol, nadolol, diltiazem, verapamil, flunarizine attenuated the increase in the ratio of ([G6P] + [F6P])/[FDP] caused by ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Opposite effects induced by low and high doses of apomorphine on single-trial passive avoidance learning in mice.

The effects of apomorphine (0.0125-1 mg/kg, SC), a dopamine (DA) agonist, on passive avoidance learning were assessed in mice which received brief and long foot-shocks in a training test. At low doses, apomorphine stimulates DA autoreceptors. With a shock of brief duration, apomorphine at a low dose (0.05 mg/kg), enhanced the avoidance learning when it was administered 20 min before the training test or the retention test. At high doses, apomorphine stimulates postsynaptic DA receptors. With a shock of long duration, apomorphine at a high dose (1 mg/kg), impaired the avoidance learning when it was administered 20 min before the training test or the retention test. However, apomorphine (0.05 and 1 mg/kg) given immediately after the training test did not have any effect on the avoidance behavior with shocks of either brief or long durations. Apomorphine-induced enhancement of passive avoidance learning was antagonized by sulpiride, but not by haloperidol. These results show that apomorphine induced the opposite effects on the passive avoidance learning depending on the dose or on the reinforcement intensity and suggest that the central DA system may play an important role in modulating memory processes.

Animals↗
PubMed1988

Clinical, biochemical and ultrastructural study on the pathogenesis of hyperornithinemia-hyperammonemia-homocitrullinuria syndrome.

A 10-year-old boy with the hyperornithinemia, hyperammonemia and homocitrullinuria (HHH) syndrome is described. With dietary restriction of protein intake and supplementary administration of L-ornithine and L-arginine, the high concentration of ammonia decreased and the clinical signs of truncal ataxia and lethargy improved. A deficiency of ornithine transport into liver mitochondria was demonstrated biochemically, and glycogen granules and smooth surface endoplasmic reticulum were increased, but mitochondria showed normal construction ultrastructurally. Cranial computed tomography (CT) showed diffuse white matter low density and cerebellar vermis atrophy. The impairment of ornithine transport and energy production in the central nervous system may be related to the cranial CT findings and neurological signs.

Amino Acid Metabolism, Inborn Errors↗
PubMed1988

Hereditary hemorrhagic telangiectasia with malignant lymphoma. An autopsy case.

A 60-year-old Japanese woman was diagnosed at autopsy as having had hereditary hemorrhagic telangiectasia (HHT) associated with systemic hemangiomas. In her reproduction period, premenstrual epistaxis frequently occurred. At the age of 60, the patient died of malignant lymphoma. At autopsy, multiple telangiectatic spots were noted on the face, limbs and trunk. The paraaortic lymph nodes, which were enlarged and irregularly conglomerated, were histologically diagnosed as malignant lymphoma of the diffuse large cell type. Submucosal telangiectatic lesions were found in the gastrointestinal system from the oral cavity to the rectum. Cavernous hemangiomas were present in various visceral organs including the liver, spleen, small and large intestines, rectum, appendix, uterus, and jejunal and colonic mesenteries. There was an arteriovenous fistula in the left lung. Examination of her family pedigree showed that the patient had an autosomal dominant trait of inheritance. The pathogenesis of the systemic visceral hemangiomas observed in this patient was considered to be similar to that of harmartoma.

Female↗
PubMed1988

[Effects of cibenzoline on myocardial ischemia].

The effect of cibenzoline, an antiarrhythmic drug, on myocardial ischemia was studied in the anesthetized open-chest dog. Ischemia was induced by completely ligating or partially occluding the left anterior descending coronary artery. The levels of ATP and creatine-phosphate decreased, and the ADP and AMP levels increased during ischemia. The level of glycogen was also decreased, and that of lactate was increased by ischemia, resulting in myocardial acidosis. Pretreatment with either 2 mg/kg or 8 mg/kg of cibenzoline prevented the decrease in ATP level and the increase in lactate level. These results suggest that cibenzoline reduces the influence of ischemia on the myocardium.

Adenosine Diphosphate↗