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Biomedical subjects

N Sakamoto

Publications and source records attributed to N Sakamoto.

At least 505 records · Page 28Linked to original sources

Gastric carcinoid with ectopic production of ACTH and beta-MSH.

A 51-year-old woman with typical Cushing's syndrome of about 9 years duration was shown to have a gastric carcinoid tumor. Plasma levels of ACTH and cortisol were elevated and lacked the normal diurnal rhythm. Urinary excretion of steroids was unaffected by the administration of either metyrapone or dexamethasone. Fluctuation in urinary steroid excretion, as well as transient hypokalemic alkalosis and glycosuria suggested periodic hormonogenesis. The extirpated gastric carcinoid was shown to contain immunoreactive ACTH and beta-MSH. However, the biologic ACTH activity was undetectable by in vivo steroidogenic assay. By gel filtration, it was demonstrated that both tumor and plasma ACTH was predominately "big" ACTH. Although postoperatively she developed hypoadrenocorticism severe enough to require ACTH treatment, her pituitary-adrenal function was gradually restored. This is the first documented case of ectopic ACTH syndrome caused by gastric carcinoid in which successful cure was achieved by surgery.

Adrenal Cortex Function Tests↗

Biological activity of synthetic corticotrophin with short chain lengths in the rabbit.

The andrenocorticotrophic effect of a synthetic substituted adrenocorticortophic hormone (ACTH), alpha-1-18NH2-D-Ser1-Lys17, 18-ACTH (CIBA 47, 795-Ba) has been compared with that of alpha1-24-ACTH (tetracosactide), alpha1-24-ACTH depot (tetracosactide depot) and alpha1-18NH2-Gly1-ACTH (giractide) in the rabbit. Plasma corticosteroid levels after salin injection were higher in the afternoon than in the morning. The highest value was observed at 3 p.m. 41,795-Ba, either given intravenously or intramuscularly, was shown to be the most potent peptide followed by tetrocosactide depot and was 15 times more potent than tetracosactide and giractide in steroidogenic activity in the rabbit. The intravenous administration of 41,795-Ba caused more sustained stimulation of the adrenal cortex than the intramuscular injection. These results reveal the diurnal variation pattern of the pitutitary-adrenal axis of the rabbit similar to that of the rat and also confirm the finding that alpha1-18NH2-Dser1-Lys17, 18-ACTH is a potent adrenocorticotrophic peptide without the addition of any agent to delay its absorption in the rabbit.

Adrenal Cortex Hormones↗

[Metabolism of tetrachloroethylene in guinea pigs (author's transl)].

Tetrachloroethylene oxide was chemically prepared from tetrachloroethylene, and the metabolites of the oxide in guinea pigs were analyzed by gaschromatography and Fujiwara reaction. The results obtained are as follows: 1) Trichloroacetic acid appeared in gaschromatogram after injection of tetrachloroethylene oxide, but trichloroethanol did not. 2) The metabolites analyzed by Fujiwara reaction after injection of tetrachloroethylene oxide were composed of large proportion of trichloroacetic acid and small proportion of trichloroethanol. 3) The ratio of trichloroacetic acid to trichloroethanol in the urine in case of tetrachloroethylene oxide was relatively similar to that of tetrachloroethylene. 4) The effects of pH (2.0 and 10.0) and temperature (4 degrees C and 37 degrees C) on the urinary metabolites suggest that the substance equivalent to trichloroethanol by Fujiwara reaction in metabolites may not be a real one. 5) Toxicity of tetrachloroethylene oxide seems to be much higher as compared with that of tetrachloroethylene in consideration of the maximum allowable dose in guinea pigs. 6) It is supposed from our experiments that tetrachloroethylene oxide is an intermediary metabolite of tetrachloroethylene.

Animals↗

Radioimmunoassay for 11-deoxycortisol using iodine-labeled tracer.

A simple and sensitive radioimmunoassay for 11-deoxycortisol was developed. The antiserum produced in rabbits by immunizing with a complex of 11-deoxycortisol-3-oxime and bovine serum albumin (BSA) has little cross-reactivity with other endogenous steroids. The immunoassay procedure requires only one-step ethanol denaturation of binding proteins in plasma and extraction by an organic solvent can be omitted. Furthermore, use of 125I-labeled tracer significantly simplify the counting procedure. The method is sensitive enough to detect 1 microng/100 ml of 11-deoxycortisol. Plasma 11-deoxycortisol levels measured by this method after the administration of a single dose of metyrapone ranged from 5.0 to 19.2 microng/100 ml, whereas they were 0 to 4.0 microng/100 ml in hypopituitary patients. It is concluded that this simple method is useful for the routine assay of plasma 11-deoxycortisol as a parameter of the metyrapone tests.

17-Hydroxycorticosteroids↗

Glutamate dehydrogenase from Escherichia coli: purification and properties.

Glutamate dehydrogenase (L-glutamate:NADP+ oxidoreductase [deaminating], EC 1.4.1.4) has been purified from Escherichia coli B/r. The purity of the enzyme preparation has been established by polyacrylamide gel electrophoresis, ultracentrifugation, and gel filtration. A molecular weight of 300,000 +/- 20,000 has been calculated for the enzyme from sedimentation equilibrium measurements. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate and sedimentation equilibrium measurements in guanidine hydrochloride have revealed that glutamate dehydrogenase consists of polypeptide chains with the identical molecular weight of 50,000 +/- 5,000. The results of molecular weight determination lead us to propose that glutamate dehydrogenase is a hexamer of subunits with identical molecular weight. We also have studied the stability and kinetics of purified glutamate dehydrogenase. The enzyme remains active when heat treated or when left at room temperature for several months but is inactivated by freezing. The Michaelis constants of glutamate dehydrogenase are 1,100,640, and 40 muM for ammonia, 2-oxoglutarate, and reduced nicotinamide adenine dinucleotide phosphate, respectively.

Ammonia↗

Plasma levels of beta-MSH and ACTH during acute stresses and metyrapone administration in man.

Simultaneous measurements of both beta-melanocyte stimulating hormone (beta-MSH) and adrenocorticotropic hormone (ACTH) in extracted plasma were performed by specific radioimmunoassays. During insulin-induced hypoglycemia, there was a marked increase of plasma ACTH levels and a slight but significant increase of plasma beta-MSH levels. Lysine-vasopressin on the other hand, caused a significant rise of plasma ACTH levels without corresponding response of plasma beta-MSH. Following glucagon administration, neither hormone rose significantly. However, metyrapone infusion caused a significant increase of both ACTH and beta-MSH levels, and frequent blood sampling revealed that both hormones were secreted episodically, and that peaks generally coincided with each other. These data suggest that the secretion of these two hormones can occur together in most instances, and that the same mechanism is involved in the secretion of both hormones under the negative feedback control.

Adrenocorticotropic Hormone↗

Diabetes insipidus and galactorrhea caused by histiocytosis X.

A 44-year-old woman with diabetes insipidus of 3 years duration was found to have histiocytosis X. This was based on clinical, radiological and pathological findings consistent with the diagnosis. Furthermore, she developed spontaneous galactorrhea during the course. Endocrine studies of hypothalamic-pituitary function revealed completely impaired secretion of gonadotropin, growth hormone and anti-diuretic hormone, and possible partial impairment of adrenocorticotropic hormone secretion, while thyroid stimulating hormone secretion remained intact. Persistently elevated plasma levels of human prolactin were also demonstrated, which were unaffected by administration of either thyrotropin releasing hormone, l-DOPA or water loading, but suppressed significantly by CB-154, an ergot alkaloid. These results suggest that abnormalities of the patient's endocrine function may be mainly accounted for by a single hypothalamic lesion.

17-Hydroxycorticosteroids↗