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Biomedical subjects

T Shishido

Publications and source records attributed to T Shishido.

At least 127 records · Page 7Linked to original sources
PubMed1995

Gastrin receptor antagonist YM022 prevents hypersecretion after long-term acid suppression.

Female rats were treated orally for 13 wk with YM022 (300 mumol.kg-1.day-1) and with omeprazole (400 mumol.kg-1.day-1) or famotidine (900 mumol.kg-1.day-1) with or without YM022. At 2 h after the last dose, YM022 and omeprazole markedly inhibited basal and pentagastrin-induced acid secretion. Famotidine was less potent than YM022 and omeprazole against both secretions. The degree of increase in plasma gastrin level in the three groups was parallel to the antisecretory potencies of the drugs. At 14 days after the cessation of omeprazole treatment, the secretory response to pentagastrin increased above that of the control. This hyperresponse lasted for > or = 56 days. In the famotidine-treated group, a small increase in secretory response to pentagastrin was observed but was not statistically significant. The increase in secretory response to pentagastrin was paralleled by an increase in mucosal cell mass. In contrast, YM022 not only exhibited a long-lasting inhibition of pentagastrin-induced acid secretion but also prevented the hyperresponse to pentagastrin caused by omeprazole. These results indicate that the hypergastrinemia caused by long-term administration of antisecretory drugs increases mucosal secretory response to pentagastrin through a gastrin/cholecystokinin B receptor-mediated pathway in rats.

Animals↗
PubMed1995

Explorations into development of a neurally regulated cardiac pacemaker.

Although the artificial cardiac pacemaker has contributed to the management of patients with serious arrhythmias, its rate-responsive function is not sufficient to provide physiological regulation of heart rate (HR). To achieve truly physiological rate response in any given patient, we propose a framework to develop a pacemaker directly regulated by sympathetic nerve activity (SNA). In eight anesthetized rabbits, we quantified the dynamic transduction characteristics from SNA to HR as a transfer function. We then characterized the decoding rule as an impulse response, that is the transfer characteristics in the time domain. The transfer function was approximated by a first-order, low-pass filter with lag time (corner frequency: 0.024 +/- 0.013 Hz, lag time: 0.98 +/- 0.09 s). Predicted HR correlated well with measured HR (r = 0.80-0.98). The standard error of the prediction relative to mean HR was only 1.2 +/- 0.7%, indicating that the prediction was reasonably accurate. Direct decoding of SNA to predict instantaneous HR is possible through this analysis. This framework should enable development of a neurally regulated artificial pacemaker.

Animals↗
PubMed1994

Phosphorylation, high ionic strength, and calmodulin reverse the binding of MARCKS to phospholipid vesicles.

The myristoylated alanine-rich protein kinase C substrate (MARCKS) is a major cellular substrate of protein kinase C (PKC), and PKC phosphorylation produces translocation of MARCKS from membrane to cytoplasm in many cells. Our working hypothesis is that binding of MARCKS to biological membranes requires both hydrophobic insertion of its myristoyl chain into the lipid bilayer and electrostatic interaction of its basic domain with acidic lipids. We tested this hypothesis by measuring the binding of murine MARCKS to large unilamellar phospholipid vesicles (LUVs). We estimated the partition coefficient of the myristoyl moiety of MARCKS (KH) by measuring the binding of MARCKS to electrically neutral LUVs (KH = 3 x 10(3) M-1). We examined the effect of electrostatic interactions by measuring the binding of MARCKS to LUVs containing 20% acidic lipid and obtained four results. First, incorporating 20% acidic lipid into the LUVs increased binding of MARCKS about 100-fold. Second, PKC phosphorylation, which added 3 negatively charged phosphate groups to the basic domain, reduced 20-fold the binding of MARCKS to these negatively charged vesicles. Third, increasing the KCl concentration from 0.1 to 0.5 M reduced the binding 15-fold. Fourth, Ca(2+)-calmodulin reduced the binding 20-fold. We present a simple theoretical model that explains these results, which are all consistent with the working hypothesis.

Animals↗
PubMed1994

The role of superoxide anions in the pathogenesis of cerebral vasospasm.

BACKGROUND AND PURPOSE: To determine the role of superoxide anions in the pathogenesis of cerebral vasospasm after aneurysmal subarachnoid hemorrhage, we studied the preventive effect of human recombinant copper-zinc superoxide dismutase (h-r SOD) in a rabbit subarachnoid hemorrhage (SAH) model. METHODS: Forty-five rabbits receiving intracisternal injection of 3 mL autologous nonheparinized blood or 3 mL saline were divided into four groups as follows: (1) saline injected and no treatment (control group, n = 6); (2) blood injected and no treatment (SAH group, n = 20); (3) blood injected and treated by multiple intracisternal injections of 30,000 U of h-r SOD in 0.5 mL saline (SOD group, n = 9); and (4) blood injected and treated by multiple intracisternal injections of 0.5 mL saline (saline group, n = 10). Serial angiograms were performed after the blood injection, and the diameter of the basilar artery was measured. Three animals from the control group and five animals from the SAH and SOD groups each were killed 2 days after SAH, and their basilar arteries were processed for transmission electron microscopic observations. RESULTS: In the SAH and saline groups, the diameter of the basilar arteries was significantly reduced (28 +/- 14% and 27 +/- 9%, respectively) at 2 days after the blood injection, then recovered to pre-SAH levels until 11 days. In the SOD group, the diameter of the basilar artery was only minimally changed during the follow-up period. Transmission electron microscopy revealed endothelial injury in all basilar arteries in the SAH group, whereas endothelial injury was minimal in the SOD group. CONCLUSIONS: We determined that h-r SOD prevents the occurrence of vasospasm, possibly as a result of preventing endothelial injury initiated by superoxide anions.

Animals↗
PubMed1993

Physiological characteristics of spontaneously developed diabetes in male WBN/Kob rat and prevention of development of diabetes by chronic oral administration of synthetic trypsin inhibitor (FOY-305).

The male WBN/Kob rats spontaneously develop diabetes mellitus with age. In this study, we examined how glucose tolerance, potency of insulin release, and histology of the pancreas were changed with age in this model. Furthermore, we examined the effect of FOY-305, a synthetic trypsin inhibitor, on this model. Male WBN/Kob rats were divided into two groups: one group fed on standard pellet diet (STD group) and the other on pellet containing 0.1% FOY-305 (FOY group) for 56 weeks after age 4 weeks. Oral glucose (2 g/kg) tolerance test, histology of the pancreas, and glucose (8.3 mM)- and arginine (10 mM)-stimulated insulin release from the isolated perfused pancreas were examined at 8, 20, 40, and 60 weeks of age in both groups. Pancreatic insulin content was examined at 60 weeks. In the STD group, impairment of glucose tolerance and destruction and fibrosis of pancreatic tissues progressed with age. Glucose-stimulated insulin release was remarkably reduced with age, while arginine-stimulated insulin release was preserved. By contrast, in the FOY group, development of glucose intolerance was delayed and the pancreas showed fewer pathologic changes compared with the STD group. Insulin releases in response to both glucose and arginine were preserved at all ages examined. Total pancreatic insulin content at 60 weeks of age was significantly greater than that of the STD group. The male WBN/Kob rat is a new type of diabetic model that shows a similar pattern of insulin release to that in rat with non-insulin-dependent diabetes mellitus and also shows unique histopathological changes in exocrine pancreas. FOY-305 was effective in preventing the development of diabetes in this model, although its mechanism is still unknown.

Administration, Oral↗
PubMed1993

[Evaluation of left ventricular early diastolic function by first pass radionuclide angiocardiography after dipyridamole infusion in patients with coronary artery disease--comparison with exercise test].

To evaluate the left ventricular early diastolic function after dipyridamole infusion or during exercise, the first pass radionuclide angiocardiography (FPRA) by a multicrystal gamma camera (SIM-400) was performed in 32 patients with coronary artery disease (CAD) and 14 normal subjects. Dipyridamole was administered intravenously (0.56 mg/kg in 4 min). The first third filling fraction (FF 1/3) and the first third mean filling rate (MFR 1/3) were calculated from the time-activity curve. FF 1/3 decreased and MFR 1/3 increased in both normal subjects and patients with CAD during exercise. After dipyridamole infusion, FF 1/3 and MFR 1/3 unchanged in normal subjects, in contrast, FF 1/3 and MFR 1/3 decreased in patients with CAD. Thus, dipyridamole infusion FPRA is more sensitive method to detect early diastolic dysfunction in patients with CAD than FPRA during exercise.

Aged↗
PubMed1993

Very low calorie diet-induced weight loss reverses exaggerated insulin secretion in response to glucose, arginine and glucagon in obesity.

To examine the cause of hyperinsulinemia in obesity, we determined plasma glucose, insulin, and C peptide responses to glucose (75g), arginine (0.5 g/kg body weight), and glucagon (1mg) in seven normal subjects and 20 obese subjects before and after weight loss by very low calorie diet therapy (Optifast, 240 kcal/day for 8 to 12 weeks). Integrated insulin and C peptide secretion in response to three different stimuli were markedly increased before weight loss and were significantly decreased following weight loss in response to glucose (mean +/- s.e. 36.6 +/- 6.4 vs. 18.4 +/- 2.6; 148.2 +/- 12.0 vs. 113.1 +/- 8.7 pmol/ml/h; P < 0.01), arginine (13.8 +/- 2.2 vs. 8.2 +/- 2.1; 94.8 +/- 11.2 vs. 66.0 +/- 6.1 pmol/ml/h; P < 0.01), and glucagon (16.5 +/- 2.7 vs. 10.7 +/- 1.5; 89.0 +/- 6.0 vs. 68.7 +/- 4.8 pmol/m/h; P < 0.01). The molar ratio of integrated C peptide to integrated insulin in response to all three stimuli was markedly decreased before, and this ratio significantly increased following weight loss (mean +/- s.e., 5.01 +/- 0.41 vs. 7.45 +/- 0.65; P < 0.01), and to arginine (7.78 +/- 0.61 vs. 10.97 +/- 1.28; P < 0.05), but not to glucagon (6.72 +/- 0.60 vs. 7.47 +/- 0.66). These findings suggest that both increased insulin secretion and decreased insulin clearance contribute to hyperinsulinemia in obese subjects. Improvement in these abnormalities to all three stimuli after weight loss also suggests that hyperinsulinemia in obesity is a consequence of the obesity itself rather than a pre-existing disorder.

Adolescent↗
PubMed1992

Spontaneous coronary artery dissection after a natural course for 10 years--a case report.

We encountered a patient with spontaneous coronary artery dissection complicated by acute inferior myocardial infarction. A 58-year-old male was admitted to our hospital due to acute inferior myocardial infarction in 1979. Coronary angiography performed 4 weeks after the onset showed a double lumen divided by a linear intimal flap in the right coronary artery, suggesting coronary artery dissection, but no apparent occlusion. Subsequently, he had been medicated with nitrates without any recurrent infarction. In February, 1989, 10 years after the first examination, coronary angiography was again performed and showed that the dissection had remained unchanged. Acetylcholine infusion into the right coronary artery induced coronary spasm. The prognosis of this condition seems to be better than has been generally considered, particularly in patients such as ours in whom the involvement of coronary spasm in the development of coronary artery dissection and myocardial infarction is suggested. When coronary spasm in controlled by treatment with nitrates or calcium antagonists, an uneventful course may be expected.

Acetylcholine↗
PubMed1992

[A case of monoblastic crisis of CML beginning with extramedullary tumor formation in a rib].

A patient with CML showed monoblastic crisis which started with extramedullary tumor formation in a rib before medullary involvement. She was diagnosed as having CML in 1984 at the age of 57. In February 1990, she was admitted to Furukawa City Hospital because of extramedullary blastic crisis beginning at the right 5th rib. At that time, the bone marrow revealed 4.6% blasts. On March 5, after one course of chemotherapy, she was transferred to our hospital for radiotherapy. Hematological findings were WBC 10,100/microliter with 10% blasts, Hb 10.9 g/dl, platelet 3.7 x 10(4)/microliters. Bone marrow aspiration was unsuccessful. The blasts in the peripheral blood were negative for peroxidase and chloroacetate esterase; but positive for naphtylbutyrate esterase. The leukemic cells were positive for CD13, CD33, and had phagocytic activity. Chromosomal analysis revealed 46XX with Ph1 chromosome and some additional anomalies. Southern blot analysis of tumor cells shows BCR rearrangement. These findings suggest that the blasts were immature monocytic cells, and we conclude that this is a rare case of extramedullary monoblastic crisis of CML.

Bone Neoplasms↗
PubMed1992

[Differentiating effect of oral administration of retinol palmitate (Chocola-A) for an aged AML (M3) with severe complications].

A 74 year-old woman, who had been diagnosed as AML (M3) in poor condition, was treated with Retinol Palmitate (Chocola-A, 150,000 unit/m2 per os, after informed consent. An increase of white blood cells (neutrophil) counts was observed after 7 days. After 4 weeks, WBC counts were increased to 20,700/microliters (neutrophil counts 6,400/microliters) Maturation tendency of leukemic cells was also proved in the bone marrow. In vitro studies showed that morphological differentiation was recognizable in cultured leukemic cells treated with 10(-6)M all-trans retinoic acid after 6 days, but not in controls. Responses in the NBT reduction test were slightly less than in the clinical study. The administration of Retinol Palmitate may be a new regimen to treat AML (M3) in aged patients in poor condition.

Administration, Oral↗
PubMed1991

Age-related decrease in plasma growth hormone: response to growth hormone-releasing hormone, arginine, and L-dopa in obesity.

Aging is associated with a reduction in plasma growth hormone (GH) secretion in non-obese subjects. To determine whether or not age-related changes in plasma GH secretion exist in obese subjects, we measured (a) plasma GH response to growth hormone-releasing hormone (GRH; 1 microgram/kg body wt), arginine (0.5 g/kg body wt), L-dopa (500 mg), and (b) plasma glucose, insulin, and free fatty acids (FFAs) in 26 fasted obese subjects of various ages ranging from 16 to 71 years. Only subjects with a body mass index (BMI; kg/m2) between 30.0 and 39.0 were studied. Six subjects were adolescents, 9 were in their 20s, and 11 were 30 years or older. The mean peak levels of plasma GH in response to GRH, arginine, and L-dopa in obese subjects were 11.3 +/- 2.1, 21.9 +/- 4.4, and 5.2 +/- 0.3 ng/mL in adolescents, 8.2 +/- 1.6, 9.1 +/- 1.5, and 3.1 +/- 0.6 ng/mL in those in their 20s, and 4.5 +/- 0.4, 7.3 +/- 1.4, and 2.8 +/- 0.3 ng/mL in those 30 years or older, respectively, showing a significant decrease in peak GH level with advancing age (P less than .05 to P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Marked growth of a cerebral arteriovenous malformation: case report and review of the literature.

A case demonstrating the marked growth of an angiographically occult arteriovenous malformation is presented. A review of 58 cases in which an increase in the size of an arteriovenous malformation occurred suggested that the patient's initial age may have had an important role in such growth and that both the age and the duration of follow-up were related to the extent of growth. Follow-up neuroradiological examinations are thought to be necessary for patients who have had an episode of intracranial hemorrhage of unknown cause during childhood, even if the initial angiograms revealed no vascular lesion.

Adolescent↗
PubMed1990

Formation and resolution of white matter oedema in various types of brain tumours.

Following infusion of 200 ml of Iopamidol for 1 hour the propagation of extravasated contrast medium around different types of 12 brain tumours was examined and imaged via CT. Increasing volume of expanding peritumoural contrast enhanced brain tissue was measured by integrating volumes of planimetrically measured enhanced area on CT slice of 0.5 cm in thickness. So far our data failed to demonstrate differences in the peritumoural contrast expansion between the different types of tumours. Formation and resolution as well as the speed of oedema propagation were determined by calculation of the increasing volume of the enhanced peritumoural brain tissue. Average formation rate of oedema fluid from 1 cm3 of tumour was 0.06 ml/hr, and was lower in larger tumours, while formation rate of oedema fluid from whole tumour was higher in larger tumours. Average resolution rate of oedema fluid during the passage through 1 cm3 of the peritumoural white matter was 0.03 ml/hr, and was not affected by tumour size. Average speed of oedema propagation was 0.59 mm/hr, and was higher in larger tumours. The main therapeutic effect of steroid in peritumoural oedema was a reduction in formation rate of oedema fluid.

Brain Edema↗