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Biomedical subjects

T Hachiya

Publications and source records attributed to T Hachiya.

At least 199 records · Page 11Linked to original sources

Effect of sodium loading and depletion on cyclic nucleotides in plasma and aorta. Interaction between prostacyclin and cyclic nucleotides.

The present study evaluated the effect of sodium loading and sodium depletion on cAMP and cGMP content of rat aorta. Enhanced generation of prostacyclin (PGI2) in aorta was noticed in sodium loading and sodium-depletion. As PGI2 is potent vasoactive agent, the interaction between PGI2 generation in the aorta and cyclic nucleotide accumulation in the aorta was investigated. Sodium depletion of rats induced the elevation of both cAMP and cGMP in the aorta and of cAMP in plasma. No change in cyclic nucleotides was noticed following sodium loading. These changes in cyclic nucleotides were felt to reflect the fluctuation of vasoactive agents under various sodium metabolism conditions. These observations may indicate that PGI2 is not a major factor in the regulation of cyclic nucleotide metabolism under sodium loading and sodium depletion. The increased accumulation of cAMP and cGMP in rat aorta in sodium depletion may be due to the cumulative effects of PGI2, catecholamine and probably angiotension II which are induced by sodium depletion.

Aldosterone↗

Measurement of serum thyroxine binding prealbumin in various thyroidal states by radioimmunoassay.

Serum thyroxine binding prealbumin (TBPA) levels in various thyroidal states were examined by radioimmunoassay (RIA). This technique is highly sensitive, accurate and reproducible. The normal mean (+/- 2SD) level of serum TBPA is 26.9 +/- 8.0 mg/dl (29.4 +/- 5.2 in men and 24.9 +/- 7.6 mg/dl in women). Serum TBPA levels in pregnant women were significantly lower than in normal females (P less than 0.05). Serum TBPA levels in patients with untreated hyperthyroidism were 12.9 +/- 4.0 mg/dl (mean +/- SD) and in patients with untreated hypothyroidism were 25.2 +/- 4.7 mg/dl (mean +/- SD). The mean TBPA concentrations in untreated hyperthyroidism were significantly lower than that for normal population (P less than 0.01), but untreated hypothyroidism was almost within normal range. The changes in TBPA levels in hyperthyroidism and hypothyroidism were similar to those in TBG levels. In untreated hyper- and hypothyroidism, restoration to euthyroidism by treatment was uniformly accompanied by a normalization of serum TBPA and TBG levels. A negative correlation between serum thyroid hormone binding protein (TBG and TBPA) and free thyroxine was observed in patients with hyperthyroidism. The coefficient of correlation between TBPA and free thyroxine was -0.80 (P less than 0.01) and between TBG and free thyroxine -0.58 (P less than 0.01). From these experiments it appears that not only TBG but also TBPA may play an important role in the regulation of the free thyroxine concentration in response to various thyroidal states.

Female↗

Clinical study on increased serum thyroxine-binding globulin in cancerous state.

Serum thyroxine-binding globulin (TBG) in 169 patients with various cancers was determined by radioimmunoassay (RIA). Eleven patients showed a high serum TBG level (greater than 35 micrograms/ml). Two of them had been treated with estrogen for prostate cancer. One patient had high serum TBG with serum hepatitis. Another 8 cases had normal liver function and also normal levels serum estrogen. Thus, about 4.7% (8/169) of the cancer patients had high serum TBG and mild hyperthyroxinemia caused by unknown mechanisms. The high TBG level in these patients continued until just before death, or in some cases decreased to normal after removal of cancer tumors by operation. Cancer is occasionally associated with an increase in serum TBG. Although the mechanism is not clear, the increased TBG in the cancerous state in interesting and has significance as a tumor marker.

Adult↗

[Measurement of regional cerebral blood flow by 133Xe inhalation method -experimental system and its evaluation of data analysis by simulation study (author's transl)].

Noninvasive measurement of regional cerebral blood flow (rCBF) by 133Xe inhalation and simulation studies of the errors in analyzing 133Xe clearance curves were reported. Our system was based on Obrist's 10 minutes desaturation method after 1 minute inhalation of 185 approximately 222 MBq (5 approximately 6 mCi)/l of 133Xe gas mixed in the air. Clearance curves were simultaneously measured at six location in each hemisphere. End-tidal 133Xe curve used for correction of recirculation was generated from respired air curve. Values for rCBF were calculated by two compartment analysis of the head curves. We evaluated the experimental errors with computer simulation studies. The synthetic head curves were generated with a three compartmental model representing the fast and slow component in the brain and the extracerebral component. The arterial input function used was the end-tidal curves of a typical control subject. The results of computer simulation studies were obtained as follows: F1 that is the flow of the fast compartment in brain and adequate reliability; statistical errors for normal value of F1 (80 ml/100 g/min) were 5% at 30 kcpm; the optimum end point of curve-fitting was 10 approximately 11 minutes after 1 minute inhalation of 133Xe gas; the error due to remaining activities of repreceding study was 3% at the interval of 25 minutes between inhalation.

Cerebrovascular Circulation↗

Urinary excretion of LATS in a patient with Graves' disease complicated by nephrotic syndrome.

A case report of a female patient with Graves' disease complicated by nephrotic syndrome with high LATS activity in urinary gamma-globulin is presented. When in the hyperthyroid state with high LATS activity in the serum, she was treated with antithyroid drugs, excess iodine, and finally radioisotopes. Mild hypothyroidism occurred transiently without any significant change in serum LATS activity. Nephrotic syndrome suddenly appeared. Urinary IgG was purified by salting out with ammonium sulfate, DEAE and protein A-Sepharose, and LATS activity in the purified urinary IgG fraction was demonstrated. The specific activity of LATS activity in urinary IgG protein was slightly lower than that of the serum. This case is the first demonstration of LATS activity in urine from a patient with hyperthyroidism and nephrotic syndrome.

Female↗

An attempt to analyze various thyroid stimulators by the receptor assay using hTSH radioimmunoassay.

In an attempt to analyze thyroid stimulators in serum we developed an assay procedure using hTSH radioimmunoassay (RIA) in combination with receptor competition. The principle of this method is the determination by RIA of hTSH displaced by other thyroid stimulators from a thyroidal receptor preparation which previously bound unlabelled hTSH. Practically 4 microunits of hTSH were bound with human or bovine receptor, and then hTSH displaced by addition of test serum (0.1 ml) or samples dissolved in serum (0.1 ml) was measured by RIA. This assay can determine the thyroid stimulators other than hTSH in serum that has the displacement activity of 0.5-4.0 microunits of hTSH in the useful range, such as mU/ml level of bovine TSH or rat TSH. Cholera toxin that has the thyroid stimulating activity like TSH also showed the displacement of the bound hTSH. This assay is not applicable for the human serum with more than 5 microunits/ml of TSH, because the assay value is over estimated by the free hTSH derived from the test serum. On the other hand, eighteen sera with high LATS activity and 42 sera with negative LATS activity from patients with untreated hyperthyroidism did not show any displacement. This might be due to the lower binding activity of LATS with hTSH receptor or the lower sensitivity of this assay method. Although it is difficult to use this assay clinically because of its low sensitivity, increased TSH in animal serum can be determined by this assay. The principle of this method may be also useful for examining the receptor binding of other peptide hormone that can be determined by an RIA method.

Animals↗

Effect of prostaglandin E1 on renin and aldosterone in hypertensive patients.

The effect of prostaglandin E1 (PGE1) on plasma renin activity (PRA) and plasma aldosterone concentration (PAC) was studied in the hypertensive subjects treated with or without 75 mg indomethacin or 60 mg propranolol for a week. Subsequent to the treatment with indomethacin for a week, PRA and PAC levels were decreased as compared to the control, without changes in the blood pressure and heart rate. During the infusion of PGE1, the blood pressure was decreased and the pulse rate was increased. PRA and PAC levels were also elevated. These changes of parameters were not different between the control and the indomethacin-treated subjects. PRA and PAC were suppressed after the treatment with propranolol. With the infusion of PGE1, the level of PRA was not significantly elevated, while, PAC was significantly increased by the infusion of 100 ng/Kg/min of PGE1. During the infusion of PGE1, the blood pressure was decreased while the pulse rate was increased in the subjects treated with propranolol. However, the elevation of the pulse rate was less remarkable than the control. These data indicate that PGE1 have important roles in the regulation of the release of renin and aldosterone. These findings also suggest that PGE1 may act to stimulate the secretion of aldosterone in man.

Adult↗

Demonstration of antibody for glutamic pyruvic transaminase (GPT) in chronic hepatic disorders.

The present paper describes the detection of an autoantibody for glutamic pyruvic transaminase (GPT) in sera of patients with chronic hepatic disorders. In 16 out of 500 patients, the existence of an antibody for pig GPT was demonstrated by the double antibody method, gel filtration and radioimmunoelectrophoresis. The antibody was demonstrated as an immunoglobulin G (IgG) with either polyclonal or monoclonal type (kappa or lambda). The binding portion of IgG with GPT was determined as the fragment Fab, but not Fc of IgG. Because the binding of 125I-pig GPT with the patient's antibody was displaced by human GPT, this antibody may have the characteristic of cross reacting with both pig and human GPT. Although the mechanism of production of the antibody for GPT and the pathological significance of the antibody in chronic hepatic disorders remained obscure, possible inhibition of GPT activity in serum is suggested in the presence of this antibody.

Alanine Transaminase↗

Changes in the cyclic nucleotides of rat thyroid, pituitary and plasma caused by methylthiouracil treatment.

Changes in the content of cyclic nucleotides (cAMP and cGMP) and related enzyme activities were observed in the rat thyroid, pituitary and plasma during the prolonged increase of endogenous TSH produced by treatment with methylthiouracil (MTU). Experiments were performed after 4 weeks treatment with MTU. The wet weight and cAMP content per wet weight of the thyroid increased 3 and 1.4 times respectively, but cGMP showed a slight decrease. Pituitary weight increased 1.3 times, but cAMP and cGMP content did not change. The cAMP level in plasma also increased about 1.3 times, but cGMP did not increase. The cAMP-phosphodiesterase activity in the thyroid, pituitary and plasma was increased 1.9, 1.4 and 1.3 times respectively after MTU treatment, while cGMP-phosphodiesterase showed no significant change. ATPase activity in the thyroid and pituitary was also increased more than 1.5 times after MTU treatment, while 5'-nucleotidase activitity decreased remarkably. These data indicate that the metabolism of the cyclic nucleotide system in the thyroid is stimulated by TSH.

Adenosine Triphosphatases↗

Changes in cyclic nucleotides of rat thyroid by chronic administration of LATS and TSH.

The effects of LATS and TSH on the cyclic nucleotide content and enzymatic activity in rat thyroid was observed during the continuous administration of LATS or TSH for 6 days. Serum T4 and T3 levels were increased significantly compared with the saline controls. The cyclic nucleotide (cAMP and cGMP) levels and enzyme activities per wet weight of tissue were determined. The thyroid weight in both the LATS and TSH groups increased approximately two-fold, but cAMP and cGMP content per wet weight did not significantly change. Neither cyclic nucleotide showed any significant change in plasma. The cAMP-PDE activity in the thyroid significantly increased in both the LATS and TSH groups, but the cGMP-PDE activity was unchanged. Neither was cyclic nucleotide-PDE activity changed in the plasma. The ATPase activity in the thyroid increased markedly in both the LATS and TSH groups, while 5'-nucleotidase activity did not change. These data suggest that LATS and TSH appear to have a stimulatory effect on the metabolism of cAMP, but do not affect the metabolism of cGMP.

Adenosine Triphosphatases↗

Methods for separation of long-acting thyroid stimulator (LATS) from sera containing LATS and TSH.

Methods were devised for separation of long-acting thyroid-stimulator (LATS) from TSH in serum containing both thyroid stimulators by using Rivanol, concanavalin A (con A), or staphylococcal protein A. When 3-5 volumes of 0.5% Rivanol solution were mixed to serum containing TSH or LATS activity, LATS activity remained mainly with IgG in the supernatant fraction. On the contrary, TSH activity was precipitated. When 10 mg con A was added to 1 ml test serum, almost all TSH activity was precipitated, but LATS activity remained in the supernatant fraction, which consisted mainly of IgG and albumin. Almost all LATS activity and part of the TSH activity were precipitated by addition of more than 7.5% polyethylene glycol (PEG), which was therefore not useful for separation of the stimulators in serum. Affinity chromatography on staphylococcal protein A-Sepharose was also found to separate the two thyroid stimulators in serum. By this method LATS-immunoglobulin bound to the protein A column, but no binding of the biologic and immunologic activity of TSH was observed. The protein A method seems the most useful of these four methods for complete separation of both stimulators.

Bacterial Proteins↗