[Hypothalamic (tertiary) hypothyroidism].
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Biomedical subjects
Publications and source records attributed to M Sakoda.
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Insulin secretion induced by leucine and leucine plus glucose from rat pancreatic islets was enhanced by prior treatment with somatostatin antiserum as compared with normal rabbit serum in vitro. The results provide evidence that somatostatin plays an important role in insulin secretion in rats.
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The hypothalamic content and concentration of thyrotropin-releasing hormone (TRH) were determined by radioimmunoassay in normal, thyroidectomized, hypophysectomized and cold-exposed rats with or without thyroxine. In normal animals, the single administration of thyroxine (1,5 and 20 microgram/100 g B.W.) altered neither the content nor the concentration of TRH in the hypothalamus. However, seven days' administration of this hormone resulted in the dose-dependent increase in the hypothalamic TRH levels. In thyroidectomized rats the hypothalamic TRH levels were slightly reduced in spite of the marked increase of plasma TSH levels and decrease of pituitary TSH levels. In the animals given thyroxine (10 microgram/100 g B.W.) for 7 days in addition to thyroidectomy, however, the TRH levels exceeded that in the animals which underwent throidectomy alone. The hypothalamic TRH levels were markedly reduced in hypophysectomized rats. Conversely, in hypophysectomized rats given 7 days' thyroxine (1 and 5 microgram/100 g B.W.), the levels were increased dose-dependently. In cold-exposed rats, the plasma TSH levels roughly doubled, but the TRH levels remained unchanged. These findings strongly suggest that the feedback site of thyroxine extends not only to the pituitary gland but also to the hypothalamus, and that thyroxine has an increasing effect of the hypothalamic TRH level, though the mechanism(s) remain to be clarified.
In order to clarify the physiologic role of somatostatin in insulin release, rat pancreatic islets treated by somatostatin antiserum were incubated in media containing various concentrations of glucose. Insulin release from antiserum-treated islets was significantly elevated above that from nontreated ones at 3.3 and 8.3 mM glucose, while the former was not different from the latter at 16.7 mM glucose. It is suggested that somatostatin plays an important role in the regulation of insulin release in the physiologic range of glucose concentration.
The best-fit values of the Michaelis constant (Km) and the maximum velocity (V) in the Michaelis-Menten equation can be obtained by the method of least squares with the Taylor expansion for the sum of squares of the absolute residual, i.e., the difference between the observed velocity and the corresponding velocity by calculation. This method makes it possible to determine the values of Km and V not in a trial-and-error manner but in a deductive and unique manner after some iterative procedures starting from arbitrary approximate values of Km and V. These values can be said to be uniquely determined for a set of data as the finally converged values are no longer dependent upon the initial approximate values of Km and V. It is also very important to obtain initial approximate values of parameters for the application of the method described above. A simple method is proposed to estimate the approximate values of parameters involved in fractional functions. The method of rearrangement after canceling of denominator of a fractional function can be utilized to obtain approximate values, not only for cases of two unknown parameters such as the Michaelis-Menten equation, but also for cases with more than two unknowns.
A novel method is proposed to determine deductively and uniquely the values of three parameters, a, b, and c in a fractional function of the form, y=a+bx/(c+x) where x and y are experimentally obtainable variables. This type of equation is frequently encountered in chemistry and biochemistry involving relaxation kinetics. The method of least squares with the Taylor expansion is employed for direct curve fitting of observed data to the fractional function. Approximate values of the parameters, which are always necessary prior to commending the above procedure, can be obtained by the method of rearrangement after canceling the denominator of fractional functions. This procedure is very simple, but very effective for estimating provisional values of the parameters. Deductive and unique determination of the parameters involved in the fractional function shown above can be accomplished for the first time by the combination of these two procedures. This method is extended to include the analysis of relaxation kinetic data such as those of temperature-jump method where the determination of equilibrium concentrations of reactants in addition to the three parameters is also necessary.
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Urine TRH was estimated by the radioimmunoassay which was accomplished according to the method of Bassiri and Utiger. Minimum detectable dose of TRH was 25 pg and recovery of TRH ranged from 72% to 112% in our laboratory. Intraassay coefficients of variation were 5.4% to 14.0% and interassay variations were 10.6% to 15.0%. Of the TRH analogues tested, only two (Ser-His-Pro-NH2, Thr-His-Pro-NH2) had potent reactivity to anti-TRH serum in large dose of 100 ng/tube. Urine samples were kept at -20 degrees C after adjusted to pH 3.0 because the inactivation of TRH in urine was markedly dependent on temperature and pH value. Using this radioimmunoassay, diurnal variation of the urinary TRH excretion at regular intervals in normal subjects was observed. Peak TRH excretion occurred around early morning, while minimum of the excretion was observed around noon. Total urinary TRH excretion of 24 hours was 817-1579 ng (M+/-SE: 1241+/-89 ng) in normal subjects. In patients with chronic renal failure, urinary excretions of TRH was obviously lower than those of normal subjects.
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