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Biomedical subjects

H Mashiba

Publications and source records attributed to H Mashiba.

At least 163 records · Page 9Linked to original sources

Three patients who spontaneously developed persistent hypothyroidism during or following treatment with antithyroid drugs for Graves' hyperthyroidism.

Three patients with Graves' disease who spontaneously developed hypothyroidism after treatment with antithyroid drugs are described herein. Patient 1 developed a painful tender thyroid enlargement with a fever and accelerated erythrocyte sedimentation rate when she was receiving maintenance therapy with methimazole, and she progressed to persistent hypothyroidism with increased titers of antithyroglobulin and antimicrosomal antibodies and marked reduction of goiter size within the subsequent 2 months. Thyroid-stimulating hormone-binding inhibitory immunoglobulins (TBIIs) and thyroid stimulation-blocking antibody (TSBAb) were absent when she was hypothyroid. Hypothyroidism probably resulted from autoimmune thyroid destruction due to subacute aggravation of Hashimoto's thyroiditis. During the clinical course of patient 2, accelerated erythrocyte sedimentation rate and later transient increases of antimicrosomal and antithyroglobulin antibody titers were observed repeatedly (four times), and she finally fell into overt hypothyroidism. She also had negative results of tests for TBII and TSBAb. Her hypothyroidism appeared to result from repeated thyroid destruction due to aggravation of Hashimoto's thyroiditis. Patient 3 fell into hypothyroidism when receiving a small dosage of methimazole. The TBII and TSBAb were strongly active when she developed hypothyroidism, which thus seemed to be due to blocking antibody. Patients with Graves' hyperthyroidism may eventually progress to hypothyroidism later by several different mechanisms. Severe and sudden or slowly repeated thyroid destruction due to aggravation of Hashimoto's thyroiditis is one mechanism. Another may be the appearance of a blocking antibody to the TSH receptor.

Adult↗

Augmented antiproliferative effect of tumor necrosis factor (TNF), lymphotoxin and glycyrrhizin in combined use with diethyldithiocarbamate on Meth A tumor cells in vitro.

Role of oxygen free radicals in inhibition of proliferation of Meth A tumor cells was studied. Diethyldithiocarbamate (DDC), a chelator which inactivates superoxide dismutase, was used to examine the effect of tumor necrosis factor (TNF), lymphotoxin preparation derived from a human lymphoid cell line (c-LT) and glycyrrhizin (GL) on in vitro proliferation of Meth A tumor cells. High degree of antiproliferative effect was observed when DDC was added simultaneously with TNF to target cells. Similar effect was obtained by the addition of GL. However, augmentation of antiproliferative effect was not observed when c-LT was added. However, augmentation of antiproliferative effect was observed when the target cells had been treated with DDC in advance of the addition of TNF, GL or c-LT. Roles of oxygen free radicals in inhibition of tumor cell proliferation were discussed.

Antineoplastic Combined Chemotherapy Protocols↗

Augmented inhibition of tumor cell proliferation in the combined use of disulfiram with ascorbic acid and the involvement of oxygen free radicals.

To examine the roles of oxygen free radicals in the inhibition of tumor cell proliferation, we have used disulfiram (DS), a metal-chelator, to inactivate superoxide dismutase and ascorbic acid (AsA) to inhibit catalase. Simultaneous addition of DS and AsA to Meth A tumor cells or Ehrlich ascites tumor cells induced marked inhibition of the cell proliferation assessed by [3H]thymidine uptake and trypan blue dye exclusion method. Similar augmented inhibition of Meth A tumor cell proliferation was observed when the cells were pretreated with DS and AsA. However, the addition of catalase (2000 u/ml) nullified the augmentation of anti-proliferative effect which can be induced in the combined use of DS and AsA. These results suggest that the steady-state increase of intracellular oxygen free radicals within tumor cells could be induced in the combined use of DS and AsA.

Animals↗

[Augmentation of TNF- and lymphotoxin-mediated cytotoxic effect in the combined use of ACNU and involvement of oxygen free radicals].

Roles of oxygen free radicals in recombinant human TNF- and human lymphotoxin (LT)-mediated cytotoxicity have been examined. Nimustine (ACNU), which inhibits glutathione reductase, and buthionine sulphoximine (BSO), an inhibitor of glutathione (GSH) synthesis, were used to modify the steady-state level of intracellular H2O2. TNF-mediated cytotoxicity was augmented when ACNU was added simultaneously to target L cells or Meth A tumor cells. Similar augmented effect was observed when TNF or LT was added to ACNU-treated target cells. However, the addition of GSH nullified the augmentation of TNF-mediated cytotoxicity to ACNU-treated Meth A tumor cells. Meth A tumor cells were pretreated with BSO for 24 hr, and thereafter TNF or LT was added in the presence or the absence of BSO. The cytotoxic effect of TNF and LT was augmented by the treatment of the cell with BSO or simultaneous addition of BSO. High degree of the augmentation was obtained when the pretreatment with BSO and further addition of BSO were combined. These results suggest that oxygen free radicals are closely involved in TNF- and LT-mediated cytotoxicity and the modulation of intracellular GSH level alters the degree of the cytotoxicity of these cytotoxins.

Animals↗

Effect of thyroid hormone on somatomedin-C release from perfused rat liver.

The effect of thyroid hormone on plasma somatomedin-C (SmC) level and on SmC release from perfused rat liver was investigated. Plasma SmC levels and liver tissue SmC were significantly increased in thyroxine-treated rats. Physiological doses of triiodothyronine increased SmC release and SmC concentration in the perfused rat liver. These results indicate that thyroid hormone directly enhances the synthesis and release of SmC in the rat.

Animals↗

Positive inotropic effect of somatostatin in guinea-pig ventricular muscles.

We investigated the effect of somatostatin (SS) in guinea-pig ventricular muscles using a force transducer and a conventional microelectrode method. Instead of a negative inotropic effect in atrial muscles, SS (10(-11) to 10(-7) M) elicited a positive inotropic effect in ventricular muscles in a concentration-dependent fashion, without changing the time course of contraction. The positive inotropic effect of SS was accompanied by a significant enhancement of the slow action potentials and was suppressed by diltiazem and phentolamine. An increase of extracellular Ca2+ concentration or stimulation frequency enhanced the positive inotropic effect of SS. The positive inotropic effect of SS was not suppressed in the presence of propranolol, metoclopramide, cimetidine or indomethacin, and it appeared even under cold conditions. These results suggest that SS has a positive inotropic effect in guinea-pig ventricular muscle, which is at least partly due to an increase in the slow inward Ca2+ current.

Action Potentials↗

Glucose tolerance and gastric emptying in thyrotoxic rats.

To clarify the contribution of gastrointestinal function to impaired oral glucose tolerance in hyperthyroidism, gastric emptying rate and portal and peripheral blood glucose responses to intragastric or intraduodenal glucose administration were investigated in experimental thyrotoxic rats. Glucose absorption from perfused intestine of thyrotoxic rats was also examined. Thyrotoxicosis was induced by subcutaneous (SC) thyroxine injection (50 micrograms/kg/d) for seven days. In intragastric glucose tolerance test, although insulin and glucagon responses were not significantly altered, increments in portal and peripheral blood glucose were significantly higher in thyrotoxic rats than in controls at 30 minutes. This phenomenon was almost normalized by the preadministration of phentolamine (2 mg/kg SC). In intraduodenal glucose tolerance test, blood glucose, insulin, and glucagon responses were similar in thyrotoxic and control rats. Gastric emptying rate in thyrotoxic rats was significantly higher than that in controls at 30 minutes, and that was also normalized by phentolamine administration. Absorption of glucose from perfused intestine was similar in thyrotoxic and control rats. These results suggest that an altered glucose tolerance to intragastric glucose load in thyrotoxic rats may primarily be due to rapid gastric emptying induced by increased alpha-adrenoceptor responses, and that glucose absorption from small intestine was not increased in short-term thyrotoxic rats.

Animals↗

Effect of luteinizing hormone-releasing hormone on the mechanical activity of the guinea-pig cardiac muscle.

1. The inotropic effect of physiological concentrations of luteinizing hormone-releasing hormone (LH-RH) in isolated guinea-pig cardiac muscles was studied. 2. LH-RH increased the contractile force elicited by either fast and slow responses in a dose-dependent manner. 3. These effects of LH-RH were affected by phentolamine and diltiazem but not by propranolol and cold condition. 4. This study showed the positive inotropic effect of LH-RH on myocardium through the affection to intracellular Ca, and the difference from the effect of cardiotonic steroids.

Animals↗

Significance of coronary artery tone in patients with vasospastic angina.

To investigate the relation between basal coronary artery diameter and development of coronary artery spasm, the diameters of the proximal, middle and distal segments of the three major coronary artery branches, together with that of the left main trunk, were measured on a control angiogram and after ergonovine and nitrate administration in 30 patients with vasospastic angina without significant organic stenosis, and in 35 patients without ischemic heart disease. The percent change in coronary diameter after ergonovine and nitrate administration compared with the control diameter was used as an index of coronary vasoreactivity. In patients with vasospastic angina, coronary artery responses to both ergonovine and nitrate were greater in the spastic segments than in the other segments (p less than 0.05), and those of the coronary arteries without spasm were greater than those of the coronary arteries in patients without ischemic heart disease (p less than 0.01). There were no significant differences between the coronary artery diameters in the two groups after nitrate administration, and the control diameters were less in patients with vasospastic angina than in patients without ischemic heart disease. These observations indicate that a coronary vasomotion disorder, which involves increased basal coronary artery tone and hypersensitivity to vasoconstrictive stimuli, not only at a localized segment but also in the entire coronary artery tree, is present in patients with vasospastic angina. Clinically, evaluation of basal coronary artery tone may be useful for predicting the occurrence and location of coronary artery spasm.

Adult↗

Thyroidal dependence of glucose-induced insulin secretion in starved rats.

To elucidate the possible role of thyroid hormone in insulin secretion during starvation, we investigated the glucose-induced insulin release in T3-administered starved rats. The rats were fasted for 72 hr, and one-half of the starved rats were administered subcutaneous 3,5,3'-triiodothyronine (5.0 micrograms/kg) at 12, 36, and 60 hr. In an intravenous glucose (0.5 g/kg) infusion test, insulin response was significantly lower in starved rats than in fed controls. This decreased insulin was restored by T3 administration. These results suggest the thyroidal dependence of insulin response to glucose in short-term starvation.

Animals↗

Decreased plasma C-peptide to insulin molar ratio after oral glucose in elderly subjects.

To evaluate the effect of aging on hepatic extraction of insulin, peripheral plasma insulin and C-peptide levels after an oral glucose ingestion were measured in 39 non-obese healthy subjects with normal glucose tolerance test. The subjects were divided into two groups. One age group was below 30 years (n = 17) and another was above 50 years (n = 22). Blood glucose level was significantly higher in elderly subjects than in young at 30 and 60 min, and insulin level was also significantly higher in elderly subjects than in young subjects at 60 min after glucose ingestion. C-peptide response after glucose ingestion was similar in both groups. The molar ratio of C-peptide to insulin after glucose ingestion in elderly subjects was slightly lower than that in young subjects, and the difference between the incremental areas of C-peptide and insulin divided by the incremental area of C-peptide were significantly lower in elderly subjects. These results suggest that hepatic insulin extraction after glucose loading is decreased in elderly subjects and this may partly be responsible for the slightly altered glucose metabolism in elderly subjects with normal glucose tolerance test.

Administration, Oral↗

Effect of glucagon on glucose output from bivascularly perfused rat liver.

Glucose output was investigated in bivascularly perfused rat liver. Flow rate was 1 ml/min/g from hepatic artery and 2 ml/min/g from portal vein. Basal glucose output (130 +/- 30 microM/min) from bivascularly perfused liver was significantly (p less than 0.02) higher than that (80 +/- 20 microM/min) from usual monovascularly perfused (3 ml/min/g from portal vein) liver. However, glucagon-induced (1 ng/ml) increment in glucose output from bivascularly perfused liver 589 +/- 127 microM/30 min) was not significantly different from that (630 +/- 127 microM/30 min) of monovascularly perfused liver. These results suggest that glucagon-dependent glucose output was similar in monovascularly and bivascularly perfused rat liver, and that arterial blood supply may have some role in glycogenolysis in the perfused rat liver.

Animals↗

Urinary N-acetyl-beta-D-glucosaminidase in the patients with hyperthyroidism.

Urinary N-acetyl-beta-D-glucosaminidase (NAG) was measured in patients with hyperthyroidism. The value of urinary NAG in these patients was higher than that in normal subjects and diabetic patients without diabetic nephropathy. This high level of urinary NAG in patients with hyperthyroidism decreased to the level of normal subjects after treatment of hyperthyroidism. Why urinary NAG increases in the patients with hyperthyroidism remains unknown. On the occasion of estimating the significance of the high level of urinary NAG, however, the possibility of the existence of hyperthyroidism has to be considered in addition to renal damage or hyperglycemia which have already been found to increase urinary NAG.

Acetylglucosaminidase↗

Hypouricaemia with acute viral hepatitis.

We report five female cases of hypouricaemia accompanied by acute viral hepatitis (serum urate 101 +/- 12 mumol/l, mean +/- SD). Their urate clearance was increased to 14.2 +/- 3.4 ml/min during hyperbilirubinaemia but 24-h urate excretion was not elevated (2.09 +/- 0.64 mmol/24 h). No other renal tubular abnormalities were detected. Comparing urate metabolism with that of four cases of inborn renal hypouricaemia, the degree of uricosuria was lower. One patient showed elevation of serum and urinary oxypurine, which normalized with return of a normal blood uric acid level. In all cases, the serum urate returned to normal after improvement of liver function. We suggest that renal uricosuria due to an isolated renal defect of urate transport might contribute to hypouricaemia in these cases but that inhibition of xanthine oxidase activity might also contribute to this phenomenon.

Acute Disease↗

Effect of bile acid on electrophysiological properties of rabbit sino-atrial node in vitro.

1 In order to examine the action of bile acid on cardiac pacemaker activity, the effect of sodium taurocholate (NTC) was studied on the membrane potential and current of rabbit sino-atrial node preparations by means of a double microelectrode voltage clamp technique. 2 In spontaneously beating sino-atrial node preparations, NTC (above 30 microM) decreased the maximum rate of rise of the action potential. Above 100 microM, the compound also exerted a bradycardiac effect and decreased the rate of diastolic depolarization significantly. 3 On the current systems, NTC produced dose-related decreases in the slow inward Ca2+ current and the time-dependent outward K+ current. 4 It is concluded that NTC depresses the spontaneous discharge of the sino-atrial node through decreases in both inward and outward current systems.

Animals↗

Membrane actions of ethanol on rabbit sino-atrial node studied by voltage clamp method.

Electrophysiological effects of ethanol on rabbit sino-atrial node were studied by means of the double-microelectrode voltage clamp method. In spontaneously beating preparations, ethanol (above 1%) decreased the maximum rate of depolarization of the action potential. Furthermore, 3% ethanol produced a significant decrease in the action potential amplitude, the action potential duration at 50% repolarization and the rate of the diastolic depolarization. Of the current systems, voltage clamp studies showed that ethanol reduced the slow inward current, the time-dependent potassium outward current and the hyperpolarization activated inward current. These observations indicate that ethanol does not have an effect on a single current system, but directly modifies the spontaneous discharge of sino-atrial node pacemaker cells due to a reduction of the time-dependent current systems.

Action Potentials↗

Effects of trimebutine maleate on electrical activities of isolated mammalian cardiac preparations.

The effects of trimebutine maleate on electrical activity in guinea-pig isolated papillary muscles and rabbit sino-atrial nodes have been studied by means of a standard microelectrode method. In papillary muscles, trimebutine (above 10 microM) decreased the maximum rate of rise (Vmax) and the action potential duration at 90% repolarization (APD90), whereas the resting potential was not significantly altered. As to a decrease in Vmax, trimebutine produced a negative shift of the curve relating Vmax to the resting potential along the voltage axis. Trimebutine also depressed the slow action potentials of papillary muscles produced by 27 mM K and 0.2 mM Ba. In spontaneously beating sino-atrial node preparations, trimebutine (above 10 microM) decreased the heart rate, Vmax and the rate of diastolic depolarization. These results indicate that trimebutine maleate possesses a depressant action on the electrical activities of the fast- and slow-response fibres of the heart mainly due to inhibitions of both fast Na+ and slow Ca2+ channels.

Action Potentials↗