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Biomedical subjects

K Hirota

Publications and source records attributed to K Hirota.

At least 451 records · Page 25Linked to original sources
PubMed1985

Precocious induction of tryptophan dioxygenase by glucocorticoid in suckling rats and correlation with change in glucocorticoid receptor.

When young rats (less than 14 days old) were treated once a day for 2 days with 100 micrograms/100 g body weight of dexamethasone, their liver cytosol showed a sharp new peak of glucocorticoid binding protein (peak C) eluted with 0.14 M NaCl on DEAE-cellulose chromatography. When the young rats were given a single injection of the hormone, the chromatogram showed a dominant peak of binding protein (peak B), eluted with 0.07 M NaCl, which was similar to that in untreated rats. The appearance of peak C on two treatments of young rats with hormone was confirmed by both in vivo and in vitro labeling and also studies on the nuclear fraction. Peaks B and C were specific hormone-binding proteins as shown with excess unlabeled hormone. The appearance of peak C was concomitant with the precocious induction of tryptophan dioxygenase in the liver of the young rats, and pretreatment with two injections of dexamethasone were necessary for maximal enzyme induction. On the other hand, in adult rats a single injection of dexamethasone (of 20 micrograms/100 g body weight or more) was enough to cause the appearance of peak C and induce tryptophan dioxygenase activity maximally; an additional injection of the hormone did not change the chromatographic pattern of the specific binding or the enzyme activity. For this effect in young rats, dexamethasone could not be replaced by other hormones such as glucagon, growth hormone, thyroid hormones, insulin, sex steroids or short-acting glucocorticoid.

Aging↗
PubMed1985

Urinary excretion of isomers of biliverdin after destruction in vivo of haemoproteins and haemin.

The amount and isomeric composition of urinary biliverdin in rabbits were analysed by h.p.l.c. Physiological values were maintained after the injection of haemin. On the other hand, when haemoglobins from several mammalian species were injected into rabbits, the excretion of biliverdin-IX alpha and biliverdin-IX beta were increased 6-18-fold and 32-66-fold respectively over physiological excretion. Injection of myoglobin resulted in a 44-fold increase in excretion of the IX alpha-isomer. Coupled oxidation with ascorbate of haemoglobin and myoglobin by oxygen produced mainly the IX alpha- and IX beta-isomers from haemoglobin and the IX alpha-isomer from myoglobin. The destruction of part of the haem from injected haemoproteins by non-enzymic chemical degradation would account for the observed respective increases in the excretion of biliverdin isomers. The excretion of biliverdin isomers after the injection of phenylhydrazine into rabbits was similar to that after the injection of haemoglobin.

Animals↗
PubMed1985

Hormone-induced redistribution of calcium-activated phospholipid-dependent protein kinase in pituitary gonadotrophs.

The distribution of calcium-activated, phospholipid-dependent protein kinase (protein kinase C) between cytosol and membrane fractions was analyzed in cultured pituitary gonadotrophs during treatment with gonadotropin-releasing hormone (GnRH). In pituitary cells purified by centrifugal elutriation, the extent of protein kinase C redistribution during GnRH stimulation was correlated with the enrichment of gonadotrophs. GnRH-stimulated release of luteinizing hormone (LH) from gonadotroph-enriched cells was accompanied by a rapid and dose-dependent decrease in cytosolic protein kinase C and by a corresponding increase in protein kinase C activity in the particulate fraction. Retinal directly inhibited the activity of cytosolic protein kinase C and also attenuated the release of LH from GnRH-stimulated gonadotrophs. These findings, and the ability of GnRH to cause rapid translocation of cytosolic protein kinase C to a membrane-associated form, suggest that hormonal activation of protein kinase C is an intermediate step in the stimulation of pituitary LH secretion by GnRH.

Animals↗
PubMed1985

Sepharose derivatives containing citric acid as affinity ligand. Purification of fumarase.

Six Sepharose derivatives, in which citrate was immobilized via methylene carbons, were prepared by coupling of the alpha- and beta-isomers of citrylpolymethylenediamine to Sepharose. The purification of fumarase from pig heart was dependent on the length of the spacer arm, but not on the isomeric configuration of the immobilized citrate. Gels having six methylene carbons had the largest adsorption capacity for the enzyme and therefore were the most suitable for use in affinity columns for its purification. Affinity chromatography with these gels was followed by hydrophobic interaction chromatography on an octamethylenediamine-Sepharose column.

Animals↗
PubMed1985

Combination of short-term prednisolone and adenine arabinoside in the treatment of chronic hepatitis B. A controlled study.

The efficacy of adenine arabinoside (Ara-A) alone or in combination with prednisolone utilizing its withdrawal effect was studied in 43 patients with deoxyribonucleic acid polymerase- and hepatitis B e antigen-positive chronic hepatitis. Ten patients were treated with 10 mg/kg body wt of Ara-A alone for 4-8 wk. In 9 cases, prednisolone (40 mg/day) was given at a constant dosage for 4 wk before Ara-A treatment. Fourteen patients received oral prednisolone alone for 4 wk, and 10 patients served as untreated controls. Six of 9 patients (67%) undergoing the combination therapy became seronegative for hepatitis B e antigen, whereas only 4 of 24 patients (17%) treated either with Ara-A alone or prednisolone alone lost the antigen. Two of the 10 untreated patients became seronegative for hepatitis B e antigen during the same follow-up period of 9 mo. This prospective controlled study suggests that the combination of immunomodulation by steroid withdrawal and subsequent Ara-A is more effective in the treatment of patients with chronic liver disease and active hepatitis B virus replication than treatment with Ara-A alone.

Adult↗
PubMed1985

GnRH receptors and actions in the control of reproductive function.

The hypothalamic control of reproductive function is expressed through the receptor-mediated actions of GnRH on the pituitary gonadotroph. GnRH receptors in the pituitary gland exhibit prominent variations in number during the ovarian cycle and after changes in steroid feedback, and are modulated by the rate of GnRH secretion from the hypothalamus. In cultured pituitary cells, GnRH receptors undergo down-regulation during exposure to GnRH agonists, followed by a subsequent elevation of sites that is dependent on protein synthesis. GnRH antagonists do not cause receptor down-regulation, but high-affinity antagonist analogs bind for extended periods to cause receptor occlusion and prolonged inhibition of GnRH action. Analysis of the rat pituitary GnRH receptor by photoaffinity labeling reveals two binding subunits of mol. wt 53,000 and 42,000. The receptor-activated processes leading to gonadotropin secretion are highly calcium-dependent, and are initiated by rapid phospholipid hydrolysis with production of arachidonic acid metabolites, diacylglycerol, and inositol phosphates. The role of protein kinase C in gonadotropin secretion is indicated by the ability of phorbol esters and synthetic diacylglycerols to stimulate LH release, the inhibition of protein kinase C and LH release by retinal, and the redistribution of protein kinase C between cytosol and membrane fractions during stimulation of pituitary gonadotrophs by GnRH. It is likely that the effects of arachidonate metabolites are integrated with those of calcium-calmodulin and calcium, phospholipid-dependent protein kinases during the immediate and sustained phases of GnRH-induced gonadotropin secretion.

Animals↗
PubMed1985

Appearance of new hepatic glucocorticoid binding proteins under various stressful conditions: relation to endogenous glucocorticoid secretion.

When rats were subjected to the stress of burns, tumors, or partial hepatectomy, a notable new peak of glucocorticoid binding protein appeared on DEAE-cellulose chromatography. This peak accompanied the original peak, which was the only dominant peak in intact rats. The appearance of the new binding protein was concomitant with a high rise in serum corticosterone levels. The new peak was eluted with 0.12-0.14 M NaCl and another, small new peak with 0.02-0.03 M NaCl, while the original peak of intact rats was eluted with 0.05-0.08 M NaCl. In rats adrenalectomized prior to the stress, the new peaks did not appear. To mimic these stressful conditions which provoked a burst of endogenous glucocorticoid, rats were administered with an exogenous high dose of dexamethasone (100 micrograms/100 g B.W.) in vivo. The new peak eluted with 0.12-0.14 M NaCl was again observed and was more dominant in the hormone-treated rats than the stressed rats. These three peaks eluted with 0.02-0.03 M, 0.05-0.08 M, and 0.12-0.14 M NaCl are called here Peak A, B, and C, respectively. This is the first demonstration of the effect of physiological changes in serum levels of glucocorticoid hormone on the nature of glucocorticoid binding protein by DEAE-cellulose chromatography.

Adrenalectomy↗
PubMed1985

A new glucocorticoid receptor species: relation to induction of tryptophan dioxygenase by glucocorticoids.

When rats were treated with a high dose (greater than or equal to 20 micrograms/100 g BW) of dexamethasone, their liver cytosol showed a predominant peak of specific binding protein of glucocorticoid eluting with 0.13-0.14 M NaCl on diethylaminoethyl cellulose chromatography. On the other hand, when rats were treated with a low dose (approximately 2 micrograms/100 g BW) of dexamethasone, the cytosol showed only the same peak as that of untreated rats, which is widely thought to be that of the typical glucocorticoid receptor. The appearance of the new binding peak depended both on the dose of hormone and the time (from 30 min to 20 h) after dexamethasone treatment; it disappeared 40 h after treatment. A peak similar to that in the cytosol also appeared in the nuclear fraction after treatment with a high dose of hormone. The glucocorticoid-inducible enzymes, tryptophan dioxygenase [(TO) EC 1.13.11.11] and tyrosine aminotransferase (EC 2.6.1.5) were assayed as physiological markers of receptor function. TO induction correlated well with the appearance of the new binding peak in terms of dose- and time dependence on glucocorticoid, whereas tyrosine aminotransferase induction did not. The new peak of glucocorticoid-binding protein detected in the cytosol and nuclear fractions may thus represent the glucocorticoid receptor species involved in TO induction, physiological changes under stress, and pharmacological changes after therapy with high doses of glucocorticoid hormones.

Animals↗
PubMed1985

[Left ventricular function in essential hypertension during isoproterenol infusion].

The left ventricular function of 23 patients with essential hypertension was investigated during infusion of isoproterenol (ISP). These patients consisted of 13 without cardiac hypertrophy (Group NH) and 10 with cardiac hypertrophy (Group HH). Ten normotensive subjects served as normal controls. To assess left ventricular functions, M-mode echocardiograms were recorded at rest and after ISP infusion for 5 minutes (0.005 and 0.01 microgram/kg/min). There were no significant differences in peak negative dD/dt in all groups at rest. But peak negative dD/dt of Group HH significantly decreased after an infusion of 0.005 microgram/kg/min ISP (Group N: 3.43 +/- 0.69, Group NH: 3.15 +/- 0.61, and Group HH: 2.49 +/- 0.48 cm/sec, respectively). The peak negative dD/dt of Group HH was also significantly decreased after a dose of 0.01 microgram/kg/min. Among all patients with hypertension, peak negative dD/dt correlated inversely with left ventricular mass (LVM) after the infusion of ISP (0.005 microgram/kg/min: r = -0.64, p less than 0.001, 0.01 microgram/kg/min: r = -0.68, p less than 0.001). The peak positive dD/dt of Group HH was significantly decreased only when compared with that of Group N at rest (Group N: 3.15 +/- 0.75, Group NH: 3.02 +/- 0.86, and Group HH: 1.92 +/- 0.68 cm/sec, respectively). The difference between the peak positive dD/dt of Group HH and that of Group N was more prominent after the infusion of ISP than at rest. Among all patients with hypertension, the peak positive dD/dt was inversely related to LVM at rest (r = -0.64, p less than 0.002). There was a similar relation between the two indexes after the infusion of ISP. Peak positive dD/dt was related to peak negative dD/dt after a dose of 0.01 microgram/kg/min in Group HH (r = 0.67, p less than 0.05). There was no significant difference in heart rate, change in blood pressure, or total peripheral vascular resistance after the infusion of ISP. It is concluded that diastolic left ventricular dysfunction and latent systolic left ventricular dysfunction are related to increased LVM in Group HH. It seems that after the infusion of ISP severe diastolic left ventricular dysfunction is related to latent systolic left ventricular dysfunction.

Adult↗
PubMed1985

[Analysis of CA 125 assay system and its diagnostic significance in gynecologic tumors].

CA125 antigen levels were measured in patients with ovarian cancer (54 cases) by the RIA method using a monoclonal antibody OC125 and were examined as a marker for ovarian cancer. The upper normal limit of CA125 of 35 U/ml was derived from the mean value (15.7 U/ml)+2SD (9.3 U/ml) of CA125 in healthy controls. The mean value for CA125 in patients with ovarian cancer (1160 +/- 1850 U/ml) was statistically (p less than 0.001) higher than those of healthy controls, benign ovarian tumors (28 +/- 20 U/ml) and cervical cancers (226 +/- 526 U/ml). Elevated CA125 levels were also found in the early pregnant stage and endometriosis, but these cases showed not so high CA125 values as those of ovarian cancers. In addition, CA125 levels were not clearly affected by the menstrual cycle. Among ovarian malignancies, the elevated CA125 values were specifically demonstrated in serous cystadenocarcinoma (positivity 89%) and markedly low in mucinous cystadenocarcinoma (positivity 16%). No positive correlation of CA125 values with the clinical stage (FIGO) were found in any ovarian cancer patients. The rise and fall of CA125 levels corresponded closely with progression and regression of cancer patients with positive CA125 levels. In conclusion, serum CA125 determinations may be useful in patients with ovarian cancer (except for mucinous type) for diagnosis and for monitoring the results of the treatment.

Antigens, Neoplasm↗
PubMed1985

[Findings of computed tomography in vascular parkinsonism].

CT findings in the patients with vascular Parkinsonism were discussed. We investigated 26 patients who were clinically diagnosed as vascular Parkinsonism aged from 55 to 77 years old (mean 66.4), and compared with 27 controls aged from 54 to 78 years old (mean 69.1). In order to evaluate the ventricular size, we measured the following A-F. A: The ratio of the ventricle-caudate nucleus distance to the maximum transverse inner diameter of skull on 4.0 cm above orbitomeatal plane. B: The ratio of the largest width of the anterior horn of the lateral ventricle to the maximum transverse inner diameter on the same level as A. C: The ratio of the maximum width of the third ventricle to the maximum transverse inner diameter of skull on the same level as A. D: The ratio of the minimal width of both cellae mediae to the maximum transverse inner diameter on 6.0 cm above orbitomeatal plane. E: The ratio of the area of both the anterior horn to the intracranial area on the same level as A. F: The ratio of the area of both the body of the lateral ventricle to the intracranial area on the same level as D. C was only statistically significant compared with controls. The enlargement of cerebral cortical sulci in patients was more prominent than that in controls. The degree of periventricular lucency in patients was more severe than that in controls. The number of small low density area in basal ganglia in patients was more than that in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗