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Biomedical subjects

H Mashiba

Publications and source records attributed to H Mashiba.

At least 145 records · Page 8Linked to original sources

Possible role of the stomach in enteroinsular axis in rats.

To elucidate the possible role of the stomach in enteroinsular axis, rats had both an inflow gastric cannula and an outflow diversion cannula and a duodenal inflow cannula. The effects of intragastric infusion of glucose (1 mL in 10% solution) or mannitol (1 mL in 10% solution) on blood and plasma insulin responses to subsequent intraduodenal glucose (1.5 g/kg in 10% solution) or amino acids (1.0 g/kg in 10% solution) infusion were investigated. Blood glucose and plasma insulin responses to intraduodenal amino acids were not altered by intragastric infusion of glucose or mannitol. However, higher blood glucose and lower plasma insulin responses to intraduodenal glucose were observed in the rat with intragastric infusion of glucose or mannitol compared with controls (intragastric infusion of distilled water). This phenomenon was abolished in the rat with preadministration of phentolamine. These results suggest that intragastric tonicity may suppress glucose-induced insulin secretion, probably through the alpha-adrenergic mechanism in the rat.

Amino Acids↗

An electrophysiological study of 9-amino-1,2,3,4-tetrahydroacridine (THA) on sino-atrial node preparations of rabbits.

1. The electrophysiological effect of 9-amino-1,2,3,4-tetrahydroacridine (THA) on the rabbit sino-atrial node was studied using double-microelectrode voltage clamp methods. 2. THA (above 10 microM) caused statistically significant decreases in the maximum rate of rise, the action potential amplitude, the rate of diastolic depolarization, and increases in the spontaneous cycle length, the action potential duration at 50% repolarization. 3. On the current systems, THA obviously depressed the time-dependent outward K+ current. The compound also decreased the slow inward Ca2+ current and the hyperpolarization-activated inward current. 4. These findings indicate that THA exerts an inhibitory action on the automaticity of sino-atrial node via effects on both outward and inward current systems.

Action Potentials↗

Effect of corticotropin-releasing factor on the electrical and mechanical activities of the guinea-pig ventricular myocardium.

1. The effects of the physiological levels of corticotropin-releasing factor (CRF) on isolated guinea-pig ventricular myocardium were studied using a force transducer and standard microelectrode techniques. 2. CRF increased the contractile force of muscles concentration-dependently in normal Tyrode and a high-K+ (27 mM) solution. The positive inotropic effect of CRF was associated with a significant enhancement of the slow action potentials of partially depolarized muscles in high-K+ solution. CRF potentiated the effect of increasing Ca2+ concentration of Tyrode solution. 3. The inotropic effect of CRF was reduced in the presence of diltiazem, and suppressed by phentolamine, metoclopramide, and cimetidine, but was not affected by propranolol and cold condition. 4. It is suggested that an increase in the slow inward Ca2+ current induced by CRF plays an important role in its positive inotropic effect and that its effect differs from that of cardiotonic steroids.

Action Potentials↗

Effect of long-term administration of insulin and glibenclamide on pancreatic A and B cell function.

To investigate the effects of insulin and sulfonylurea drug administration on islet A and B-cell functions, insulin and glucagon response was studied in normal rats treated with insulin (4 U/day subcutaneously) or glibenclamide (0.03 mg/kg intraperitoneally) for 8 weeks. In intravenous glucose tolerance test (0.5 g/kg), lower insulin response and impaired glucose tolerance were observed in insulin-treated rats and higher insulin response and impaired glucose tolerance were observed in glibenclamide-treated rats. In perfused pancreas, insulin response to glucose and arginine was significantly lower in insulin-treated rats and that was significantly higher in glibenclamide-treated rats. Glucagon response was not altered by insulin or glibenclamide treatment. These results suggest that hyperinsulinisation and glibenclamide administration strongly influence pancreatic B-cell function but not influence pancreatic A-cell function.

Animals↗

Inhibitory effect of 9-amino-1,2,3,4-tetrahydroacridine (THA) on the potassium current of rabbit sinoatrial node.

STUDY OBJECTIVE - To examine the effect of 9-amino-1,2,3,4-tetrahydroacridine (THA), a compound similar to the K+ blocker 4-aminopyridine, on potassium channels in the sinoatrial node. DESIGN - The pacemaking portion of rabbit sinoatrial nodes was studied using the double microelectrode voltage clamp method in the presence of THA at various concentrations. MEASUREMENTS AND RESULTS - Above 1 mumol.litre-1, THA prolonged the spontaneous cycle length and the transmembrane action potential duration at 50% repolarisation. Above 10 mumol.litre-1, the compound also decreased the maximum rate of rise, the action potential amplitude, and the rate of diastolic depolarisation. Under voltage clamp conditions, THA reduced the time dependent K+ current (IK) in a dose dependent manner. Neither the decay process of IK nor its activation process were altered by THA. CONCLUSIONS - THA depresses sinoatrial node IK without changing its kinetics. Thus it may inhibit the open state of the potassium channels.

Alzheimer Disease↗

Development of postpartum spontaneously resolving transient Graves' hyperthyroidism followed immediately by transient hypothyroidism.

A 25-year-old woman with a history of Graves' disease, in remission for 8.5 years following 6 months of methimazole therapy, first came to our attention 5 months after her first delivery with clinical and biochemical hypothyroidism, markedly elevated titre of anti-thyroid microsomal antibody (MCHA; 1:102400) and mildly elevated activity of thyrotropin-binding inhibitory immunoglobulins (TBII; 29.5%). After short-term (3 months) treatment with L-thyroxine therapy, the development of hyperthyroidism in the first trimester of the second pregnancy, which remitted through the second and third trimesters, was observed. TBII showed a peak value (93.1%) 1 month after the onset of hyperthyroidism, and a normal value (12.4%) 6 d after delivery. One month after the second delivery, the patient developed hyperthyroidism, with an elevation of 99mTc thyroid uptake (5.58%; normal range 0.5-2.5%), which was immediately followed by transient clinical and biochemical hypothyroidism. Concomitant increases in MCHA titre and TBII activity were observed after delivery, and both reached peak levels (1:409600 and 81.0%, respectively) one and a half months after the onset of hypothyroidism. Thyroid-stimulating antibody (TSAb), measured using FRTL-5 thyroid cells, was detected at a weakly positive level (161%) on initial examination, and the serial change in TSAb was almost identical to that in TBII. Patients with Graves' disease may develop Graves' type hyperthyroidism, followed immediately by transient hypothyroidism due to coexisting destructive autoimmune thyroiditis during the early postpartum period, despite increasing TSAb activity.

Adult↗

Use-dependent effects of pirmenol on Vmax and conduction in guinea-pig ventricular myocardium.

1. The use-dependent effects of pirmenol, a new antiarrhythmic drug, on the maximal rate of rise (Vmax) of the action potential, conduction velocity, and their corresponding recovery kinetics were studied in isolated papillary muscles of guinea-pig. Standard microelectrode techniques were used to monitor the conduction and action potential characteristics of the muscles. 2. Pirmenol decreased Vmax and the overshoot of action potentials in a dose-dependent fashion. Also, doses of pirmenol greater than 1 mM abolished the generation of action potentials. Low concentrations of pirmenol (3 and 10 microM) prolonged the action potential duration, while concentrations greater than 0.1 mM shortened it markedly. 3. The resting block of Vmax in the presence of 10 and 30 microM pirmenol was 9.48 +/- 3.12 and 20.36 +/- 3.61%, and that of conduction velocity 2.87 +/- 1.52 and 6.58 +/- 2.09%, respectively. 4. The degree of use-dependent block induced by 10 and 30 microM pirmenol during 0.2, 1, 2 and 3 Hz stimulations was dose- and rate-dependent. 5. In the presence of 30 microM pirmenol, mean values of time constants for the onset of the use-dependent inhibition of Vmax and conduction velocity during a 2 Hz stimulation were 1.32 +/- 0.15 and 1.28 +/- 0.09 s, respectively. The recovery time constants averaged 15.83 +/- 2.14 (for Vmax) and 27.80 +/- 8.74 (for conduction velocity) s in the presence of 30 microM pirmenol. 6. These results showed that the characteristics of the use-dependent inhibition of Vmax and conduction velocity induced by pirmenol are similar to those of slow kinetic drugs such as disopyramide rather than of fast ones.

Action Potentials↗

Sympathetic nervous system response to dynamic exercise in complete AV block patients treated with AV synchronous pacing with fixed AV delay or with auto-AV delay.

To investigate the sympathetic nervous system (SNS) responses and circulatory responses to exercise in eight patients (five male and three female) with complete atrioventricular block (CAVB) treated with atrioventricular (AV) synchronous pacing, a symptom-limited, multistaged treadmill stress test was performed, and plasma norepinephrine (NE) and circulatory parameters were measured at rest, at peak exercise, and in the recovery period. The eight patients were tested using the fixed AV interval (150 or 156 msec). Their exercise tolerance was generally poor. In all measured points, plasma NE levels were significantly higher in the eight study patients than those in the 12 normal subjects (eight male and four female). Systolic blood pressure (SBP) of CAVB patients elevated significantly after exercise compared to that at peak exercise. Heart rate (HR) responses of CAVB patients were characterized by their poor increase at peak exercise. These results suggest that some latent cardiac dysfunction continues in the CAVB patients however satisfactorily the AV synchronous pacing might perform. AV synchronous pacing with three different kinds of auto-atrioventricular delay (auto-AVD) was applied to three of the eight patients. In each AVD mode, a treadmill stress test was performed repeatedly according to the same protocol. Plasma NE concentrations under the condition with fixed AVD at peak exercise increased compared to those under the other two conditions with auto-AVD. These findings suggest that AV synchronous pacing with auto-AVD was better than that with fixed AVD during exercise. Plasma NE response to exercise seems to be a useful indicator for evaluating the condition of patients treated with DDD pacemakers and their adaptation for cardiac function.

Aged↗

Effect of pinacidil on the electrophysiological properties in guinea-pig papillary muscle and rabbit sino-atrial node.

The electrophysiological effect of the antihypertensive drug pinacidil has been examined in preparations of guinea-pig papillary muscle and rabbit sino-atrial node using a standard microelectrode method. In papillary muscle preparations, pinacidil (greater than 30 microM) shortened the action potential duration (APD), whereas it did not affect the maximum rate of rise (Vmax). Pinacidil (greater than 1 microM) also decreased APD of slow action potentials evoked by high K+ (27 mM) solution containing 0.2 mM Ba2+. At 30 microM, the drug reduced the Vmax of slow action potentials. In the spontaneously beating sino-atrial node, pinacidil (greater than 30 microM) shortened APD. At 100 microM, it also decreased the heart rate, Vmax, action potential amplitude and the rate of diastolic depolarization. It is concluded that pinacidil modifies the electrical activity of myocardial cells probably due to an increase in the potassium conductance although in high concentrations the compound might also reduce Ca2+ influx through the cell membrane, which would contribute to an obvious negative chronotropic action.

Action Potentials↗

Excess purine degradation caused by an imbalance in the supply of adenosine triphosphate in patients with congestive heart failure.

To evaluate purine degradation in patients with congestive heart failure concentrations of serum hypoxanthine, lactate, and noradrenaline were measured before and after submaximal treadmill exercise in 12 patients with chronic congestive heart failure and nine healthy volunteers. In four patients the concentration of hypoxanthine was significantly higher than in the controls or in the remaining eight patients with congestive heart failure. Venous lactate and noradrenaline in the four patients with high concentrations of hypoxanthine were also significantly higher than those in the eight patients with normal concentrations of hypoxanthine. Patients who responded normally were also more likely to have been treated with vasodilators and angiotensin converting enzyme inhibitors. Exercise induced arrhythmias were more common in the patients with high concentrations of hypoxanthine. These results suggest that the excess purine degradation in patients with congestive heart failure might be the result of a "relative" disturbance in the supply of adenosine triphosphate caused by the shift of cellular metabolism from aerobic glycolysis to anaerobic glycolysis during submaximal exercise and that hypoxanthine (a substrate for xanthine oxidase and a source of free radicals) was increased after submaximal exercise in some patients with congestive heart failure.

Adenosine Triphosphate↗

Possible role of thyroid hormone in decreased somatomedin-C levels in diabetic and starved rats.

To elucidate the possible role of thyroid hormone in somatomedin-C (SmC)/insulin-like growth factor I regulation in diabetes mellitus and starvation, plasma SmC, liver SmC, and kidney SmC concentrations were measured in streptozotocin-induced (60 mg/kg) diabetic and starved (for 72 h) rats. Triiodothyronine (T3, 5.0 micrograms/kg every 24 h) was subcutaneously injected into diabetic rats for 7 days and into starved rats at 12, 36, and 60 h after starvation. Plasma T3, plasma SmC, liver SmC, and kidney SmC concentrations were significantly decreased in diabetic and starved rats. T3 administration restored plasma T3 levels to the normal value in diabetic and starved rats. Plasma SmC and kidney SmC concentrations were significantly increased in T3-treated starved rats, while they were not increased in T3-treated diabetic rats. These results suggest that thyroid hormone may have some role in SmC regulation during starvation, but may have no role in diabetes mellitus in the rat.

Animals↗

Effects of anoxia and low free fatty acid on myocardial energy metabolism in streptozotocin-diabetic rats.

To investigate anaerobic glycolysis and glucose oxidation in the diabetic heart, we studied the effects of anoxia and low exogenous free fatty acid (FFA) on myocardial adenosine triphosphate (ATP) content in the isolated perfused heart from streptozotocin-diabetic rats. The perfusate consisted of Krebs-Ringer buffer (pH 7.4) containing 5 mM glucose and 0.30 mM or 0.05 mM FFA, equilibrated with 95% O2 + 5% CO2 or 95% N2 + 5% CO2 gas. Under aerobic conditions, glucose uptake, lactate production and glucose oxidation by the diabetic heart were reduced by 68, 57 and 53% of the control, respectively, and FFA oxidation by the diabetic heart was increased by 67% of the control. Under anoxic conditions, the increments in glucose uptake and lactate production by the diabetic heart were much smaller than those by the control (2.6 and 9.5 mumol/g/30 min vs. 11.4 and 40 mumol/g/30 min, respectively). The ATP content in the diabetic myocardium was decreased more rapidly in the anoxic perfusion than that in the control. In the aerobic perfusion, the ATP content in the control myocardium was maintained for 60 min at low FFA (0.05 mM) in the perfusate. The ATP content in the diabetic myocardium was reduced after 40 min at low FFA but was well maintained for 60 min by the addition of 0.30 mM FFA. Thus the ATP content in aerobic diabetic myocardium was not well maintained when exogenous FFA supply was depleted. These results suggest that diabetic hearts have a primary defect in the stimulation of glycolysis and glucose oxidation, which does not result from increased FFA utilization.

Adenosine Triphosphate↗

The mechanism involved in the conversion of thyrotropin receptor-bound blocking-type immunoglobulin G (IgG) to the stimulating-type by anti-human IgG antibodies.

It has been reported that the addition of antibody (Ab) against human immunoglobulin G (IgG) converts TSH receptor-bound blocking-type IgG to stimulating-type IgG. However, the detail of converting mechanism remains unclear. In this study we examined the mechanism involved in this conversion using FRTL-5 cells. Blocking-type IgG was obtained from a patient with hypothyroidism. FRTL-5 cells were first incubated with IgG solution, then washed with PBS and exposed to antihuman IgG Ab. The effect of antihuman IgG Ab on converting activity was dose dependent. Maximal stimulation of cAMP was achieved with an antiserum dilution of 1:75. It seems likely that antimicrosomal Ab does not interfere with cAMP production, since IgG with a high anti-hemagglutination antibody titer did not show converting activity. Of the several kinds of antibodies tested, Ab against human IgG-Fab fragment was the most effective in converting ability, while the least effective were those against human IgG-Fc fragment. Although the divalent F(ab')2 fragment of antihuman IgG was significantly more effective in its converting ability than the monovalent Fab fragment, the Fab fragment itself also converted blocking IgG to the stimulating type in a dose-dependent manner. Accordingly, receptor cross-linking or aggregation does not play a major role in promoting this converting phenomenon. When cells were first exposed to blocking-type IgG and then to both antihuman IgG Ab and bovine TSH, cAMP production was much greater than the sum of each alone. However, anti-IgG Ab alone did not affect the binding of blocking-type IgG to receptor. These results suggest that the addition of antihuman IgG Ab not only converts blocking-type IgG to the stimulating type but also recovers TSH activity via a postreceptor step. Forskolin, like TSH, showed an additive effect on cAMP stimulatory action with antihuman IgG. In contrast, cholera toxin and antihuman IgG Ab were not additive. The reason for this discrepancy remains unknown. In summary, our observation indicates that 1) the converting phenomenon is induced via IgG-TSH receptor complexes; 2) the mechanism aside from receptor aggregation, i.e. the recognition of a critical domain in TSH receptor molecule, seems necessary for promoting converting phenomenon; and 3) the addition of antihuman IgG Ab affects a postreceptor step via TSH receptor structures that differ from the TSH-binding site.

Adult↗

Chronic thyroiditis with painful tender thyroid enlargement and transient thyrotoxicosis.

Clinical and laboratory findings and long term outcome (1.5-9 yr) in 7 women and 1 man with chronic thyroiditis (CT) who had painful tender thyroid enlargement were evaluated and compared with those in 11 women with subacute thyroiditis (SAT). Histological features consistent with SAT were not demonstrable, and various forms of CT (fibrous variant, diffuse, or focal lymphocytic thyroiditis) were observed. There were no differences in mean age, duration of symptoms, erythrocyte sedimentation rate, and C-reactive protein values in the 2 diseases. Seven patients had a history of goiter, and none had a history of a preceding upper respiratory tract infection. The mean white blood cell count was significantly lower in CT than in SAT patients. Six CT patients had transient thyrotoxicosis with a marked depression of radioactive iodine uptake. Mean serum T4 and T3 levels and T3 to T4 ratio in these 6 patients did not differ from those in the SAT patients. Five (all with high antimicrosomal antibody titers) of 8 CT patients developed persistent hypothyroidism. In contrast, none of the SAT patients became permanently hypothyroid. TSH binding inhibitory immunoglobulins and thyroid stimulation-blocking antibody at recent examination were negative in these 5 patients. Patients with this disorder present with transient thyrotoxicosis, with a marked depression of the thyroid radioactive iodine uptake, and often develop goitrous or atropic persistent hypothyroidism. This disorder may represent acute exacerbation of an underlying immunological process during the course of CT. To differentiate this syndrome from SAT, thyroid biopsy is necessary.

Adult↗

Diagnostic value of R-wave amplitude increase during treadmill exercise testing for detecting coronary artery disease.

To evaluate the diagnostic value of an exercise-induced increase in R-wave amplitude (RWA) for detecting coronary artery disease (CAD), treadmill testing using the modified Bruce protocol was performed on a CASE II computerized system (Marquette) in 10 healthy young men, 35 patients (pts) with CAD, 22 subjects with normal coronary arteries, and 11 pts with aortic or mitral regurgitation. Based on the analysis of the patterns of serial changes in RWA in lead V5, we proposed new RWA criteria for detecting CAD. (1) During exercise, RWA increases in stage 1 and subsequently increases further or remains unchanged. (2) During exercise, RWA decreases in the early phase of exercise and subsequently increases. (3) In the recovery period, RWA shows a gradual and excessive increase. A combination of the above RWA criteria showed a sensitivity, specificity and accuracy of an equal value of 86%. We conclude that an exercise-induced RWA increase is a useful indicator for detecting CAD, especially when taking the patterns of serial changes into consideration, and that the abnormal RWA increase may be related to an increase in left ventricular (LV) end-diastolic volume due to exercise-induced LV dysfunction.

Adult↗

A case of secundum atrial septal defect combined with aortic stenosis and coronary artery disease showing a single second heart sound.

We describe an extremely rare case of secundum atrial septal defect with aortic stenosis and coronary artery disease showing a single second heart sound throughout the respiratory cycle by echocardiogram with simultaneous phonocardiogram. Aortic valve closure corresponded to the single second heart sound. We were unable to detect pulmonary valve closure (PVC) on echocardiogram. Because of the presence of pulmonary hypertension, the pulmonary component of the second heart sound (P2) was presumed to be increased in intensity, and the PVC-P2 interval was thought to be abbreviated. Carotid pulse tracing showed a prolongation of the left ventricular ejection time. We concluded that the single second heart sound was due to both prolongation of left ventricular systole and pulmonary hypertension.

Aortic Valve Stenosis↗

Effect of intestinal osmolality on insulin secretion to subsequent intravenous glucose or arginine in the rat.

To elucidate the effect of intestinal osmolality on insulin secretion, we investigated insulin response to a subsequent intravenous infusion of glucose or arginine after intragastric or intraduodenal mannitol or NaCl instillation in the rat. After anesthesia with intraperitoneal pentobarbital sodium, mannitol solution (10% or 20%) or 2.7% NaCl was instillated into the stomach or duodenum for 5 min at a flow rate of 0.5 ml/min, and 20% glucose (0.5 g/kg) or 10% L-arginine (0.5 g/kg) was infused bolus into the femoral vein 45 min after intestinal instillation. Insulin response to intravenous glucose was significantly higher in the rat with intragastric or intraduodenal mannitol or NaCl infusion than in control rats with intragastric or intraduodenal instillation of distilled water. Insulin response to intravenous arginine was almost the same in all groups. Subcutaneous preadministration of propranolol (0.4 mg/kg), atropine (1.2 mg/kg), or phentolamine (0.8 mg/kg) did not alter the present phenomenon. These results suggest that intestinal osmolality may enhance insulin release to intravenous glucose, but not to arginine in the rat.

Animals↗

In vitro augmentation of macrophage-activating-factor release from peripheral blood cells of cancer patients by a DNA fraction from Mycobacterium bovis BCG.

Effect of a DNA-rich fraction from Mycobacterium bovis BCG (MY-1) on the macrophage-activating-factor (MAF)-activity release from peripheral blood lymphocytes (PBL) of patients with benign diseases and patients with gastric cancer or colorectal cancer was studied in vitro. The MAF activity was augmented by the addition of 10 micrograms/ml of MY-1 in many cases. Augmentation of the MAF activity in benign disease, gastric cancer and colorectal cancer in stages I to III was observed in five of six cases, eight of 10 cases and five of eight cases, respectively. The activity of MY-1-induced MAF was partially abolished by the treatment with monoclonal anti-interferon-gamma (IFN-gamma) antibody. These results suggest that MY-1 augments MAF-activity release from PBL by inducing IFN-gamma and other MAF-like substances.

DNA, Bacterial↗