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Biomedical subjects

M Shiomi

Publications and source records attributed to M Shiomi.

At least 55 records · Page 3Linked to original sources
PubMed1997

Zonisamide monotherapy in newly diagnosed infantile spasms.

PURPOSE: We determined the short-term efficacy of zonisamide (ZNS) monotherapy in newly diagnosed patients with infantile spasms (IS). METHODS: Eleven hospitals participated in this open, prospective trial. ZNS 3-10 mg/kg/day was administered as the second-choice drug to 11 newly diagnosed patients with IS (cryptogenic 3, symptomatic 8) who failed to respond to high-dose vitamin B6. RESULTS: Four infants with symptomatic IS had cessation of spasms and disappearance of the hypsarrhythmia. In these responders, the spasms ceased after a few days (1-5 days) of treatment at a dose of ZNS 4-5 mg/kg/day which produced plasma ZNS concentrations ranging from 5.2 to 16.3 microg/ml (mean 9.8 microg/ml). There were two relapses (50%) 4-6 weeks after cessation of seizures, however. Relapse was predicted by effects of ZNS on EEG; the 2 infants in whom an abnormal EEG persisted had relapses, whereas the 2 whose EEG normalized remained seizure-free (follow-up 20 and 26 months). No adverse reactions were noted. CONCLUSIONS: ZNS may be effective in the initial treatment of selected patients with IS.

Adrenocorticotropic Hormone↗
PubMed1997

Endogenous carbon monoxide suppression stimulates bile acid-dependent biliary transport in perfused rat liver.

This study aimed to investigate whether carbon monoxide (CO), a product of heme oxygenase that degrades protoheme IX, serves as an endogenous modulator for biliary transport. To that end, effects of zinc protoporphyrin IX (ZnPP), a heme oxygenase inhibitor, on the biliary transport were tested in perfused rat liver. Perfusion of 1 microM ZnPP abolished detectable levels of CO in the venous perfusate and increased bile acid-dependent bile output accompanying an increased secretion of bile salts. The ZnPP-induced choleresis coincided with a reduction of tissue guanosine 3',5'-cyclic monophosphate (cGMP) levels and a decrease in vascular conductance. On administration of 2.5 microM CO, ZnPP-elicited choleresis, decreases in vascular conductance, and cGMP levels were all attenuated. Treatment with 1 microM 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) partly attenuated the ZnPP-induced choleresis in concert with repression of vascular conductance. Furthermore, treatment of the liver with methylene blue, a guanylate cyclase inhibitor, evoked a choleresis similar to that induced by ZnPP. Thus endogenous CO suppression stimulates the biliary transport in part through a cGMP-dependent mechanism.

Animals↗
PubMed1997

[Sporadic cases of hemolytic uremic syndrome and hemorrhagic colitis with serum IgM antibodies to lipopolysaccharides of enterohemorrhagic Escherichia coli O157].

In 1994-1996 summer, eight patients with hemolytic uremic syndrome(HUS) and 3 patients with hemorrhagic colitis, whose fecal specimens yielded no Enterohemorrhagic Escherichia coli(EHEC) because of the antibiotic therapies before presentation, showed serum IgM antibody responses to lipopolysaccharide(LPS) of O157. Although early bacteriological examination is essential for diagnosis, serological testing of patients with HUS or HC for antibodies to the LPS of EHEC provides evidence of infection with EHEC. We also presented successful fluoroquinolones(SPFX and NFLX) therapies of another 15 HC inpatient cases from Sakai outbreak of O157 infections due to school lunch in summer 1996. In these 15 HC patients, 12 EHECs of serotype O157:H7 with VT1 and VT2 and phage type 32 were obtained, but no growths of EHECs after fluoroquinolones therapy and no progressions to HUS resulted. The MICs of SPFX is 0.025 microgram/dl, NFLX 0.1, NA 3.13, FOM 12.5, ST 0.39, KM 3.13, ABPC 1.56-3.13.

Anti-Infective Agents↗
PubMed1996

A case of bronchial cast.

We report a case of bronchial cast in a boy 1 year and 5 months old. Bronchial casts often obstruct the main bronchi, causing dyspnea and hypoxia. The bronchial cast was studied pathologically, with findings of eosinophilia and neutrophilic infiltration; the cast seemed to involve an allergic reaction. Such casts can be removed during bronchoscopy, but we used aspiration.

Airway Obstruction↗
PubMed1996

A novel de novo mutation in HPRT gene responsible for Lesch-Nyhan syndrome (HPRT OSAKA).

A virtually complete deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT) causes Lesch-Nyhan syndrome. A novel mutation of HPRT gene in a Japanese Lesch-Nyhan family has been identified using mRNA and genomic DNA from peripheral blood cells. A single nucleotide substitution of T to C in exon 3 resulted in a mis-sense mutation, CTC (Leu) to CCC (Pro), at codon 65. Utilizing an Mn/I restriction site which was lost in the mutation as an indicator, a family study showed that the mother was normal not having the mutant gene. The mutation was a de novo event that had occurred in the germ cells of the mother or in the proband during the early phase of fetal development.

DNA↗
PubMed1996

General pharmacological properties of the new angiotensin II receptor antagonist (+/-)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate. Part I: Effects on central nervous system and other properties.

The effects of TCV-116 ((+/-)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate, CAS 145040-37-5), a nonpeptide angiotensin II receptor antagonist, on the central nervous and autonomic nervous systems, isolated smooth muscle and digestive system were investigated in various experimental animals. TCV-116 at 1000 mg/kg (p.o.) produced a slight decrease in body tone in mice, but at 300 mg/kg did not affect spontaneous locomotor activity, skeletal muscle coordination, tonic extensor convulsions, pentobarbital-induced sleeping time, frequency of acetic acid-induced writhing, or body temperature in mice or rats. TCV-116 (at 300 mg/kg p.o.) did not affect the spontaneous EEG in conscious, unrestrained cats, or (at 100 mg/kg i.d.) the spinal reflex in anesthetized cats. CV-11974, the active metabolite of TCV-116, did not inhibit neuromuscular transmission in isolated rat phrenic nerve-diaphragm preparations (10(-5) mol/l and 10(-4) mol/l). In anesthetized cats, TCV-116 at 100 and 300 mg/kg (i.d.) slightly reduced the pressor response to carotid occlusion, but had no effect on the bradycardic response to stimulation of the cervical vagus nerve, contraction of the nictitating membrane induced by electrical stimulation of the cervical sympathetic preganglionic nerve, or the changes in blood pressure in response to acetylcholine, histamine, norepinephrine, or bradykinin. CV-11974 had no effect on agonist-induced contraction of guinea pig ileum. In isolated smooth muscle preparations, CV-11974 even at 10(-4) mol/l did not affect the spontaneous motility of the rabbit ileum or the rat uterus, or KCl-induced tension in guinea pig trachea. TCV-116 at 300 mg/kg (p.o.) had no significant effect on gastric emptying or intestinal transport of a semisolid meal in rats, or on gastric secretion in pylorus-ligated rats. TCV-116 (30-300 mg/kg p.o.) had no effect on carrageenin-induced paw edema in rats. The results suggest that TCV-116 exerts no notable pharmacological effects on the central nervous system, autonomic nervous system, gastrointestinal function or smooth muscle function.

Analgesics↗
PubMed1996

General pharmacological properties of the new angiotensin II receptor antagonist (+/-)-1-(cyclohexyloxycarbonyloxy) ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl] methyl]-1 H-benzimidazole-7-carboxylate. Part II: Effect on cardiovascular system and renal functions.

The effects of TCV-116 ((+/-)-1-(cyclohexyloxycarbonyloxy) ethyl 2-ethoxy-1-[[2'-(1 H-tetrazol-5-yl)biphenyl-4-yl] methyl]-1 H-benzimidazole-7-carboxylate, CAS 145040-37-5) on the cardiovascular system and renal function were investigated in rats, guinea pigs, and dogs. TCV-116 at doses of 3 mg/kg (i.d.) and higher markedly increased renal blood flow in anesthetized dogs. TCV-116 at 30 mg/kg (i.d.) had no effect on heart rate, left ventricular systolic pressure, its dp/dtmax, or cardiac output in anesthetized dogs. Furthermore, TCV-116 at 10 and 30 mg/kg (p.o.) had little effect on cardiac output, right atrial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure or respiration in conscious dogs. In isolated guinea pig perfused heart, CV-11974 even at a dose of 0.1 mg/ heart had no effect on cardiac function. In isolated guinea-pig atria, CV-11974, the active metabolite of TCV-116, even at 10(-4) mol/l had no effect on the spontaneous beating rate of the right atria or the contractile force of electrically-paced left atria. No significant effect of TCV-116 on urinary volume or urinary excretion of sodium and potassium was observed in rats (at 30, 100 or 300 mg/kg p.o.). These findings suggest that TCV-116 exerts no any additional pharmacological effects on cardiac and respiratory functions in dogs or on renal function in rats, other than an increase in renal blood flow in anesthetized dogs thought to be due to its inhibitory effect on the renin-angiotensin system.

Angiotensin II↗
PubMed1996

Expression of very low density lipoprotein receptor mRNA in rabbit atherosclerotic lesions.

The expression of very low density lipoprotein (VLDL) receptor mRNA in atherosclerotic lesions in rabbits was investigated. To examine the expression of the VLDL receptor in the vascular wall, poly(A)+ RNA was isolated from whole aortas of cholesterol-fed New Zealand White (NZW), Watanabe heritable hyperlipidemic (WHHL), and normal NZW rabbits, and then Northern blot analysis was performed. The VLDL receptor mRNA was detected in aortas from both NZW rabbits fed 0.5% cholesterol for 16 weeks and 12-month-old WHHL rabbits, whereas no expression was seen in normal NZW rabbit aortas. To further determine the localization of the VLDL receptor mRNA, in situ hybridization using digoxigenin-labeled riboprobes and immunohistochemistry using monoclonal antibodies against each cell component were performed. Early atherosclerotic lesions, termed fatty streaks, in the NZW rabbits fed 0.5% cholesterol for 4 weeks demonstrated strong expression of the VLDL receptor mRNA by macrophages. The VLDL receptor mRNA was also expressed in more advanced atherosclerotic lesions from both atherogenic animal models. The predominant origin of the VLDL receptor mRNA-positive cells was macrophages, and some intimal smooth muscle cells appeared to express a weak but significant signal in these advanced lesions. Our findings suggest that the VLDL receptor expression may play a role in the development of atherosclerosis.

Animals↗
PubMed1995

High dose of fluvastatin sodium (XU62-320), a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, lowers plasma cholesterol levels in homozygous Watanabe-heritable hyperlipidemic rabbits.

The effects of fluvastatin sodium (XU62-320), a new type of inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on plasma cholesterol and triacylglycerol levels were investigated using homozygous Watanabe-heritable hyperlipidemic (WHHL) rabbit, an LDL-receptor-deficient animal which expresses a hepatic LDL receptor activity less than 5% that of control rabbits. Plasma levels of total, VLDL- and LDL-cholesterol were decreased profoundly after oral administration of fluvastatin at a dose of 50 mg/kg per day for 4 weeks. Plasma triacylglycerol levels were not affected by fluvastatin. Hepatic HMG-CoA reductase activity increased by 3-fold and hepatic LDL receptor activity increased by only 3.7-fold, as calculated by Scatchard plot analysis, with fluvastatin administration for 4 weeks, and the hepatic mRNA level for the rabbit LDL receptor was increased by 3-fold. Combined administration of fluvastatin (50 mg/kg per day) and cholestyramine, a bile acid sequestrant resin, at a level of 2% of the diet for 4 weeks more profoundly decreased plasma total, VLDL- and LDL-cholesterol levels with induction of hepatic cholesterol 7 alpha-hydroxylase and no further induction of the hepatic LDL receptor. Plasma triacylglycerol levels were increased by the combination treatment. These results suggest that high dose of fluvastatin sodium is effective in lowering plasma cholesterol levels in homozygous WHHL rabbits through the shared mechanisms involving decrease in production and secretion of cholesterol from the liver and the induction of hepatic LDL receptor. Additional effect of cholestyramine on decrease in plasma cholesterol levels seems to be due to the further decrease in hepatic cholesterol secretion by up-regulation of hepatic cholesterol 7 alpha-hydroxylase.

Animals↗
PubMed1995

Reduction of serum cholesterol levels alters lesional composition of atherosclerotic plaques. Effect of pravastatin sodium on atherosclerosis in mature WHHL rabbits.

We examined whether serum cholesterol reduction alters the lesional composition of atherosclerotic plaques. To reduce serum cholesterol levels, we gave pravastatin sodium, a 3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitor, to mature Watanabe heritable hyperlipidemic rabbits, an LDL receptor-deficient animal model, for 48 weeks. Atherosclerotic lesions were immunohistochemically and conventionally stained and each lesional component area was measured by a color image analyzer. Compared with those of a placebo group, serum LDL cholesterol levels were reduced by 22% (P<.05). Data for atherosclerosis indicated a significant decrease in percent of surface lesion area (26% reduction) and in intimal thickening (30% reduction) in the abdominal aorta, as well as in coronary stenosis (29% reduction). Data for lesional composition indicated a significant decrease in the percent area of macrophage plus extracellular lipid deposits in aortic lesions (32% reduction) and coronary lesions (45% reduction). A significant increase was observed in the percent area of collagen in aortic lesions and in the percent area of smooth muscle cells in coronary lesions. The plaques seemed to become stable lesions as a result of pravastatin treatment. In conclusion, a long-term reduction of serum LDL cholesterol reduced lipid-related lesional components, in addition to suppressing the progression of established atherosclerosis.

Animals↗
PubMed1995

Effects of the non-peptide angiotensin II receptor antagonist TCV-116 on systemic and renal hemodynamics in dogs with renal hypertension.

The effects of TCV-116, a new non-peptide angiotensin II receptor antagonist, on systemic and renal hemodynamics were studied in conscious normotensive and renal hypertensive (2-kidney, 1-clip Gold-blatt type) dogs. When orally administered at 0.03 to 1.0 mg/kg, TCV-116 inhibited the pressor response to angiotensin II in conscious normotensive dogs in a dose-dependent fashion. The IC50 and IC100 values were 0.06 mg/kg and 0.86 mg/kg, respectively. TCV-116 at doses of 0.3 mg/kg and 1.0 mg/kg dose-dependently and persistently decreased systolic and diastolic blood pressure in both dogs with acute renal (hyperreninemic) and those with chronic renal (normoreninemic) hypertension. Even a high dose of TCV-116 (10 mg/kg, p.o.) increased effective renal plasma flow without affecting blood pressure or glomerular filtration rate in normotensive dogs. Furthermore, even at this high dose, TCV-116 did not reduce effective renal plasma flow or glomerular filtration rate in dogs with renal hypertension despite marked reduction in systemic blood pressure. The angiotensin converting enzyme inhibitor enalapril (10 mg/kg, p.o.) had renal hemodynamic effects similar to those of TCV-116. These findings indicate that TCV-116 has potent hypotensive effects not only in dogs with acute renal hypertension but also in those with chronic renal hypertension, but does not appear to adversely affect renal hemodynamics.

Angiotensin II↗
PubMed1994

Involvement of LDL receptor in the proliferation of vascular smooth muscle cells.

To study the involvement of the low-density lipoprotein (LDL) receptor in the growth of vascular smooth muscle cells (VSMC), we compared the proliferation of cultured VSMC from Watanabe heritable hyperlipidemic (WHHL) rabbits, which lack the LDL receptor, and VSMC from normal Japanese white rabbits in response to platelet derived growth factor (PDGF). The increase in the number of VSMC from WHHL rabbits in response to PDGF (10(-8) M) was significantly lower than that of VSMC from normal rabbits. PDGF stimulated the synthesis of DNA in VSMC from both normal rabbits and WHHL rabbits, but the response was significantly lower in the latter. To determine the involvement of the LDL receptor in the decreased mitogenic response of WHHL rabbit VSMC, we used an anti-LDL receptor monoclonal antibody (MAb) to normal rabbit VSMC; DNA synthesis of VSMC was stimulated by PDGF, but the effect was significantly blocked by the anti-LDL receptor MAb. Mitogen-activated protein (MAP) kinase activity in normal rabbit VSMC was increased by exposure to PDGF, but the effect was significantly suppressed in the presence of the MAb. The anti-LDL receptor MAb markedly inhibited LDL binding to the surface of normal rabbit VSMC. These results suggest that the LDL receptor influences the proliferation of VSMC and thus might be involved in the pathogenesis of atherosclerosis.

Animals↗
PubMed1994

Relation of N-glycosylation of apolipoprotein B-100 to cellular metabolism of low density lipoprotein.

We studied the functional role of N-linked sugar chains of apolipoprotein (apo) B-100 of low density lipoprotein (LDL) in cholesterol metabolism. The N-linked sugar chains of apo B-100 of LDL obtained from four homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits were liberated by hydrazinolysis, followed by NaB3H4 reduction and were fractionated by paper electrophoresis and column chromatography. They consisted of one neutral (N) and two acidic (A1, A2) fractions. The ratio of apo B-100 acidic fractions (A1+A2) varied among 4 WHHL rabbits. Serial measurements of serum cholesterol levels showed that they decreased with aging in each of 4 WHHL rabbits. We investigated the relation of the ratio of acidic sugar chains of apo B-100 to the serum cholesterol levels. Reciprocals of the serum cholesterol levels were significantly correlated with the ratio of acidic sugar chains of apo B-100 (r = 0.901, P < 0.001). To elucidate the role of N-linked sugar chains of apo B-100, we investigated cellular uptake of LDL in normal rabbit skin fibroblasts. The amounts of association, degradation and cholesteryl esterification of LDL with a lower ratio of acidic sugar chains at 37 degrees C were greater than those of LDL with a higher ratio of acidic sugar chains. These results suggest that N-glycosylation of apo B-100 may be related with serum cholesterol levels and N-linked sugar chains of apo B-100 may play an important role in cellular metabolism of LDL.

Aging↗
PubMed1994

Dextran sulfate, a competitive inhibitor for scavenger receptor, prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits.

Dextran sulfate competes with binding of modified LDL to the scavenger receptor in macrophages. To elucidate the role of dextran sulfate in the atherosclerotic process, 100 mg of dextran sulfate in drinking water was given to 5 Watanabe heritable hyperlipidemic (WHHL) rabbits for 12 months starting at age 4 months. During the experimental period, there were no significant differences in plasma cholesterol levels between dextran sulfate-treated and untreated rabbits. After 12 months' treatment, accumulation of cholesterol ester in total aorta was significantly suppressed in dextran sulfate-treated rabbits as compared with untreated rabbits (71.4 +/- 22.3 vs. 42.7 +/- 16.5 mg/g dry weight, P < 0.05). Furthermore, lesion area with atherosclerotic plaques in treated rabbits was significantly less than that in untreated rabbits (59.7 +/- 24.5 vs. 30.4 +/- 14.4%, P < 0.05). These results indicate that dextran sulfate might prevent the progression of atherosclerosis by competitively inhibiting the binding of modified LDL to scavenger receptors.

Animals↗
PubMed1994

Quantitative characterization of insulin-glucose response in Watanabe heritable hyperlipidemic and cholesterol-fed rabbits and the effect of cilazapril.

A great deal of evidence suggests that insulin resistance, via hyperinsulinemia, contributes to hyperlipoproteinemia and coronary atherosclerosis. When Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model of familial hypercholesterolemia (FH), are compared with normolipidemic Japanese White (JW) rabbits, an elevated fasting plasma insulin level and a heightened plasma insulin response to an intravenous (i.v.) glucose challenge are found. To elucidate the mechanism behind this phenomenon, a two-compartment model of the glucose/insulin system was fitted to empirical time courses of glucose and insulin concentrations during an i.v. glucose tolerance test (IVGTT) by nonlinear least-square regression, and the model parameters such as the glucose utilization rate constant, insulin degradation rate constant, and pancreas sensitivity were determined. WHHL rabbits showed decreased values of glucose utilization and insulin degradation rate constants and slightly higher values of pancreas sensitivity. This suggests that insulin resistance occurs in extrapancreatic tissues, and that this may be attributable to insulin receptor and/or post-insulin receptor abnormalities. Cholesterol feeding did not significantly change glucose tolerance or insulin action in JW rabbits. The effects of an angiotensin-converting enzyme (ACE) inhibitor, cilazapril, on insulin resistance were also examined in WHHL and JW rabbits. A decreased insulin response to an i.v. glucose challenge and increased glucose utilization and insulin degradation rate constants were observed in WHHL rabbits that had been treated with cilazapril, indicating that cilazapril improved insulin resistance in WHHL rabbits, possibly by increasing the number of insulin receptors. No significant differences were found in glucose tolerance and insulin action in JW rabbits before and after cilazapril administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Pravastatin sodium, a competitive inhibitor of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase, decreases the cholesterol content of newly secreted very-low-density lipoprotein in Watanabe heritable hyperlipidemic rabbits.

We examined the secretion of very-low-density lipoprotein (VLDL) when hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme of cholesterol biosynthesis, was inhibited. To inhibit HMG-CoA reductase in liver, pravastatin sodium, a competitive inhibitor of HMG-CoA reductase, was administered to homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits, a low-density lipoprotein receptor-deficient animal model, at a dosage of 50 mg/kg per day for 5 weeks. Although triglyceride levels were not changed, total cholesterol levels of sera and each atherogenic lipoprotein were decreased by approximately 30%. As a result, the percentage of cholesterol concentration in newly secreted VLDL was significantly decreased by 24%. The VLDL secretion rate was determined by intravenous injection of Triton WR-1339. The VLDL secretion rate was significantly decreased by 23% using cholesterol as an index, but it did not change using triglyceride, phospholipid, or protein as an index. It is concluded that one of the mechanisms of serum total cholesterol decrease due to reduction of the putative cholesterol pool of the liver in homozygous WHHL rabbits is caused by a decrease of cholesterol content in newly secreted VLDL particles.

Animals↗
PubMed1994

[Thirty seven cases of respiratory syncytial virus infection hospitalised and 7 severe cases with apneic attacks].

We studied 37 cases of respiratory syncytial virus infection hospitalized during the period January 1, 1989 and March 31, 1993. 37 patients were 0-4 years old on admission. Fever, positive CRP and elevation of BSG were frequent in patients aged 8 months-4 years old. Patient more than 8 months of age didn't need supplementation of oxygen. Of the 37 patients, we had one case who had hyponatremia and six cases who were admitted with severe apneic attacks required incubation. Of the six cases, one patient had delayed neurological deterioration after anoxia due to apneic attacks. He, followed up for 4 years, have serious residual deficits including spastic quadriplegia, delayed development and epilepsy. Variety of factors, including premature birth, young postnatal age and milk feeding appeared to be significant risk factors for sever infections of RSV. In RSV infection, apneic attacks can cause near-miss SIDS. So, we stress the importance of careful and rapid diagnosis for all infants less than 8 months of age.

Apnea↗