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Biomedical subjects

H Kuroda

Publications and source records attributed to H Kuroda.

At least 325 records · Page 18Linked to original sources

An endogenous inhibitor of GABA receptor binding.

An endogenous inhibitor of GABA receptor binding was prepared from synaptic membrane of rat brain with 0.05% Triton X-100. The endogenous inhibitor was competitive with GABA for GABA binding sites. The inhibition of GABA receptor binding by the endogenous inhibitor was blocked by the allosteric effect of diazepam. In the presence of diazepam, specific [3H]GABA binding was greater in a medium containing the endogenous inhibitor than in one containing an equal inhibitory potency of GABA, whereas there was no difference in the absence of diazepam. This indicated that the endogenous inhibitor was not GABA itself.

Animals↗

Augmentation of aromatase activity by FSH in ovaries of fetal and neonatal mice in organ culture.

The stimulative effect of FSH on aromatase activity was investigated in ovaries of fetal (on days 17 and 18 of gestation) and neonatal mice (on days 0, 3, 6 and 9 after birth). Two to six ovaries, were cultured for 48 h in 2 ml of Medium 199 supplemented with insulin (5 micrograms/ml) and [1 alpha, 2 alpha, 6 alpha, 7 alpha, beta-3H]4-androstene-3,17-dione (0.35 microM) in the presence or absence of porcine FSH (0.5 units/ml) and the amount of [3H]oestradiol-17 beta and [3H]oestrone produced was estimated. In the presence of FSH, aromatase activity per ovary, which was found in all fetal and neonatal ovaries examined, increased with age. In the absence of FSH, however, the production of oestrogens could be demonstrated only in ovaries from 3- to 9-day old mice. FSH increased the aromatase activity by up to 10-fold. In spite of the stimulative effect of FSH on aromatase activity, FSH exerted no significant effect on DNA synthesis of the ovaries. The formation of primordial follicles could not be observed histologically in ovaries of fetal mice on day 17 of gestation, although the ovaries of 6- and 9-day old mice contained multilayered follicles. These results show that FSH stimulates the aromatase activity of the mouse ovary even before the formation of primordial follicles and that the stimulative effect of FSH on ovarian aromatase is not due to the proliferation of ovarian cells.

Androstenedione↗

Effects of transition metals on TRH-receptor interaction.

The interaction of TRH receptors and metal ions was investigated. Although the addition of a physiological serum concentration (20 microM) of Zn2+ or Cu2+ to the TRH radioreceptor assay reaction mixture significantly increased the binding capacity, pretreatment of crude synaptic membranes with Ni2+, Zn2+, Cu2+ or Pd2+ resulted in a significant loss of binding activity. The receptor preparation was bound to [3H]TRH in the presence of 10 mM Ni2+ and was solubilized by Triton X-100. Gel filtration was carried out with cold Tris-HCl-Triton buffer without Ni2+. The molecular weight of the solubilized TRH-macromolecular complex was about 300,000 daltons, and Ni2+ was found in the same fraction as the solubilized TRH-receptor. These results suggest that metal ions have inverse effects in different steps of TRH-receptor interaction and that a TRH-receptor molecule indicates a Ni-binding molecule.

Animals↗

Growth hormone response to thyrotropin releasing hormone in a pellagrin.

An abnormal hyperresponse of GH to intravenous injection of TRH in a 66-year-old female pellagra patient with typical 3'D's was reported. Diagnosis of pellagra was mainly based on her clinical course and manifestations, although serum levels of nicotinic acid and serotonin were within the normal range. Serum vitamin A and B2 levels were low. However, these findings did not exclude the diagnosis. The abnormal GH response to TRH observed in this patient was decreased at 2 months and thoroughly disappeared at 10 months after admission. GH response to arginine showed an exaggerated and sustained response on admission, decreased at 2 months and showed an almost normal pattern at 10 months after admission. TSH and prolactin response to TRH were normal throughout the clinical course. LH and FSH response to LH-RH were exaggerated, suggesting post-menopausal hypogonadism. Cortisol response to ACTH showed slightly sustained reactions at both times of the provocation. Oral glucose tolerance test revealed a slight impairment in this patient. These results suggest that pellagra is one of the disorders which exhibit an abnormal hyperresponse of GH to intravenous administration of TRH.

Aged↗

Cardiac performance and coenzyme Q10 in thyroid disorders.

To investigate the relationship between serum levels of Coenzyme Q10 and cardiac performance in thyroid disorders, we studied the cardiac performance and assessed serum levels of thyroid hormones and Coenzyme Q10 in 20 patients with hyperthyroidism, 5 patients with hypothyroidism and 10 normal subjects. A significant inverse correlation between thyroid hormones and Coenzyme Q10 levels was found by performing partial correlation analysis. Because low serum levels of Coenzyme Q10 were found in thyrotoxic patients and congestive heart failure may occur as a result of severe hyperthyroidism, 120 mg of Coenzyme Q10 was administered daily for one week to 12 hyperthyroid patients and the change in cardiac performance was assessed. Further augmentation of cardiac performance was found in hyperthyroid hearts, which were already augmented, after the administration of Coenzyme Q10. It appears, therefore, that the Coenzyme Q10 dose actually has a therapeutic value for congestive heart failure induced by severe thyrotoxicosis.

Adolescent↗

Improvement in freezing phenomenon of Parkinson's disease after DL-threo-3, 4-dihydroxyphenylserine.

A 77-year-old man with Parkinson's disease of long standing, under treatment with L-DOPA and benserazide, was administered DL-threo-3, 4-dihydroxyphenylserine (DL-threo-DOPS), a precursor of norepinephrine, for 10 days. With this administration the patient's freezing phenomenon was remarkably improved, and his dysarthria also showed improvement. When DL-threo-DOPS was suspended, the frozen gait returned on the third day to almost the former level, even though he continued to receive L-DOPA and benserazide. After administration of DL-threo-DOPS, the CSF level of 3-methoxy-4-hydroxyphenylglycol (MHPG), a major metabolite of norepinephrine, was 127.5% of the pretreatment level. These observations suggest that DL-threo-DOPS can pass through the blood-brain barrier and change to norepinephrine, and that DL-threo-DOPS may be beneficial in the treatment of the freezing phenomenon of Parkinson's disease.

Aged↗

Production of androgens and estrogens by tubular adenomas which developed in ovaries of mutant mice of Sl/Slt genotype.

Bilateral tubular adenomas develop spontaneously in ovaries of WB X C57BL/6 F1-Sl/Slt mice after exponential loss of oocytes. We investigated the ability of this tumor to produce sex steroids. Incubation of tubular adenoma tissue with [3H] progesterone resulted in production of [3H]androstenedione and [3H]-testosterone. The amount of androgens produced by the tumor tissue was much greater than that produced by the normal ovarian tissue. The concentration of testosterone in the serum of the Sl/Slt mice bearing tubular adenomas, measured by radioimmunoassay, was about five times as high as the value in the serum of the congenic +/+ mice. Although incubation of the tumor tissue with [3H]androstenedione resulted in production of 3H-estrogens, the aromatase activity of the tumor tissue was about one-fifth of that of the normal ovarian tissue. Therefore, the major sex steroid secreted by tubular adenomas seemed to be testosterone. These endocrinological features of tubular adenomas were consistent with the following pathological features of the Sl/Slt mice with the tumors: (a) although the weight of uterus of the Sl/Slt mice was about one-half of the value observed in the +/+ mice, it decreased markedly after oophorectomy; and (b) submandibular glands of the Sl/Slt mice were significantly heavier than those of the +/+ mice.

Adenoma↗

[Breast cancer--topics from basic research].

The measurement of estrogen and progesterone receptors in human breast cancer provides useful markers for predicting response to endocrine therapy. In human breast cancer, about 90% of unresponsive tumors and 60-80% of tumors responsive to endocrine therapy can be predicted by receptor measurement. Hormone-dependency of breast cancer easily disappears, and endocrine therapy for hormone-dependent cancer markedly encourages disappearance. Since very useful non-steroidal antiestrogens have been synthesized recently, the usefulness of drug-based endocrine therapy for breast cancer has become more important compared with brought about by surgical therapy. To improve the effectiveness of endocrine therapy for hormone-dependent cancer, the proliferation of hormone-independent cancer cells developing from hormone-dependent cancer cells during endocrine therapy should be inhibited. For inhibition, chemotherapy combined with the endocrine therapy and adjuvant endocrine therapy seem to be useful methods for the future.

Animals↗

Detection of mitochondria in bile canaliculi in early stage primary biliary cirrhosis cases.

Biopsy specimens of liver obtained from patients with early stages of primary biliary cirrhosis were examined by electron microscopy with special attention being paid to changes in bile canaliculi, as well as bile ducts and hepatocytes. Ultrastructural alterations of hepatocytes were minimal and non-specific. In bile canaliculi mitochondria were noted to be normal or slightly lack uniformity. These findings varied according to each case. This alteration was strongly considered to be specific in early stage primary biliary cirrhosis cases.

Adult↗

Sero-epizootiological study on swine influenza in a prefecture of Japan.

A total of 1799 swine sera collected in Toyama prefecture in the central part of Japan during the years 1978-82 were tested for antibody against swine influenza virus (SIV), A/New Jersey/8/76 (H1N1). A high prevalence of antibody was observed in the years after the severe epizootic of SI, 34.5% in 1979 and 51.7% in 1982. In other years, the percentages of positive sera were low and ranged from 1.7 to 12.4%. Regional variations were seen in relation to a small scale epizootic. No antibody to SIV was detected in any of the sera collected during the warm season. In the following dry and cold winter, however, a severe epizootic occurred among the swine populations.

Animals↗

Isoniazid effects on choreiform movement and on GABA, HVA, and 5-HIAA in CSF.

Isoniazid was administered in 4-week open trial in patients with choreiform movement. Gamma-aminobutyric acid (GABA), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in CSF were measured before and after treatment. Isoniazid did not improve choreiform movement. CSF GABA levels were significantly increased after treatment, but HVA and 5-HIAA levels were not significantly altered. The findings suggest that isoniazid influenced brain GABA metabolism but did not influence dopamine and serotonin metabolism in patients with chorieform movement.

Aged↗

Characteristics of gamma-aminobutyric acid (GABA) receptors in the rat central nervous system.

Characteristics of gamma-aminobutyric acid (GABA) were investigated in the rat central nervous system by radioreceptor assay (RRA). Scatchard analysis revealed that the rat brain had two distinct GABA binding sites with an apparent dissociation constant (Kd) of 11.7 nM and 34.7 nM. The highest level of specific [3H]-GABA binding was found in the rat cerebellum. Imidazole acetic acid, a potent GABA agonist, was effective in displacing [3H]-GABA binding but beta-alanine was slightly effective in inhibiting [3H]-GABA binding. Muscimol, the most potent GABA agonist, has been used as a ligand to characterize the postsynaptic GABA receptors. However, the maximal binding capacity (Bmax) of muscimol-RRA was about 3 times larger than that of GABA-RRA, suggesting that muscimol might label not only GABA receptors but other unknown receptors as well. An endogenous inhibitor of GABA receptor binding was purified from the P2 fraction of rat brain with 0.05% Triton X-100. The endogenous inhibitor was competitive with GABA on GABA binding sites. The inhibition by the endogenous inhibitor of GABA receptor binding was blocked by the allosteric effect of diazepam. In the presence of diazepam, [3H]-GABA binding with the endogenous inhibitor was larger than that with GABA, whereas there was no difference in the absence of diazepam. This indicated that the endogenous inhibitor was not GABA itself. The molecular weight of the endogenous inhibitor was estimate by gel filtration to be less than 3,000 daltons.

Animals↗