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Biomedical subjects

N Izumi

Publications and source records attributed to N Izumi.

At least 19 recordsLinked to original sources
PubMed1992

Clinical significance of elevated plasma endothelin concentration in patients with cirrhosis.

Endothelin is a newly discovered potent vasoconstrictor peptide. To explain the clinical significance of endothelin in patients with chronic liver diseases, we measured the plasma concentration of endothelin in patients with chronic hepatitis (n = 15), cirrhosis with ascites (n = 8) and cirrhosis without ascites (n = 12), and we compared the findings with the plasma concentration of endothelin in normal controls (n = 14). The plasma endothelin concentration was significantly higher in patients with cirrhosis with ascites than in normal controls (8.3 +/- 2.3 pg/ml vs. 3.3 +/- 1.4 pg/ml, mean +/- S.D., p less than 0.001), whereas no significant difference was observed between normal controls and the other groups of patients (cirrhosis without ascites = 5.0 +/- 1.3 pg/ml; chronic hepatitis = 3.8 +/- 1.2 pg/ml). In patients with cirrhosis, the plasma endothelin concentration showed a significant negative correlation with creatinine clearance (r = -0.73, p less than 0.01), but no significant correlation was observed between plasma endothelin concentration and fractional excretion of filtered sodium. Furthermore, plasma endothelin levels were significantly higher in patients with endotoxemia than in those without (10.1 +/- 2.1 pg/ml vs. 4.9 +/- 1.2 pg/ml, p less than 0.001). From these results, elevated plasma endothelin, which has a close relation to endotoxemia, may play a contributory role in kidney dysfunction in patients with cirrhosis.

Aldosterone↗
PubMed1992

V1-receptor mediated GSH efflux by vasopressin from rat hepatocytes.

Vasopression increases sinusoidal efflux of GSH in the perfused rat liver. The mechanism of this effect was studied in the perfused rat liver and in isolated rat hepatocytes. Vasopressin stimulated GSH efflux in both systems and a V1-receptor antagonist (OPC-21268) significantly inhibited the effect of vasopressin suggesting that vasopressin stimulates GSH efflux from rat hepatocytes via V1-receptor.

Angiotensin Receptor Antagonists↗
PubMed1992

Possible involvement of protein kinase C and calcium in GSH efflux from Hep G2 cells.

We investigated the effects of protein kinase C modulations and calcium mobilization on GSH efflux in Hep G2 cells. GSH efflux from Hep G2 cells was increased by a phorbol ester. Staurosporine, an inhibitor of protein kinase C, diminished phorbol ester-stimulated GSH efflux from the cells. GSH efflux was negatively correlated with extracellular calcium concentrations. Verapamil enhanced GSH efflux, whereas ATP decreased GSH efflux. The latter effect was diminished in the absence of extracellular calcium. Protein kinase C and calcium mobilization may be crucial factors in GSH efflux from human hepatocytes.

Adenosine Triphosphate↗
PubMed1992

Formation of cholic acid from 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid in human skin fibroblasts.

Whether 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid (THCA) was converted into cholic acid in human skin fibroblasts was examined. THCA was incubated with subcellular fractions of cultured skin fibroblasts in the presence of NAD+, ATP, CoA, and Mg2+. The reaction products were analyzed by thin-layer chromatography and high-performance liquid chromatography after p-bromophenacyl ester derivatization. The highest specific activity was found in the light mitochondrial fraction (2.71 nmol/mg protein/h). The specific activity was about 9-fold higher than that in heavy mitochondrial fraction. The peroxisomal fraction prepared from the light mitochondrial fraction by sucrose gradient centrifugation was also able to catalyze the conversion of THCA into cholic acid. The specific activity in this fraction was a further 2.2-fold higher than that in the light mitochondrial fraction. These results suggest that cultured human skin fibroblasts are able to convert THCA into cholic acid, and that the activity exists in peroxisomes.

Catalase↗
PubMed1992

Methacholine inhalation challenge in children with idiopathic chest pain.

Bronchial reactivity to inhaled methacholine (MCH) was evaluated in 32 patients with 'idiopathic' chest pain. Each pain was recurrent in nature. The incidence of cases with a provocative concentration causing a 20% fall in the forced expiratory volume in 1 sec (PC20) of 10 mg/ml or less was 62.5% (20 cases), while it was only 11.1% (three cases) in 27 healthy controls. Seventeen patients had no personal history of allergic diseases, elevated serum IgE level or positive house dust mite-specific IgE antibody. Among these 17, eight (47.1%) had a PC20 of 10 mg/ml or less, the incidence of which was also higher than that of the healthy controls. During the challenge, eight patients complained of chest pain similar to that experienced before. The present results indicate that bronchial hyper-reactivity is an important cause of 'idiopathic' chest pain. Patients with unexplained chest pain should be considered for inhalation challenge.

Adolescent↗
PubMed1990

Red blood cell aluminum in patients with renal failure and effect of desferrioxamine infusion.

Red blood cell (RBC) aluminum (Al) in patients with renal failure on different treatments was studied. Nondialyzed renal failure patients had high levels of RBC Al, but low serum Al levels. However, their RBC Al levels were lower than those of patients on hemodialysis (HD) and continuous ambulatory peritoneal dialysis. In addition, HD patients who were not given Al-containing medications showed high levels of RBC Al, which suggests that there may be a source of Al other than medications. When desferrioxamine (DFO) was administered to these HD patients, the changes in RBC Al levels after DFO infusion were independent of those in serum Al levels and blood hemoglobin levels. In an in vitro study, RBC Al was removed using an ultrafiltration membrane, which showed that RBC Al exists in a bound form. These results suggest that Al accumulates in RBCs of renal failure patients independently of serum Al levels, and that the improvement of anemia by DFO may not be due to the direct removal of RBC Al.

Adult↗
PubMed1990

[A clinical trial of transarterial chemoembolization for hepatocellular carcinoma using 4'-0-tetrahydropyranyladriamycin].

A clinical trial of transarterial chemoembolization for hepatocellular carcinoma using pirarubicin (4'-0-tetrahydropyranyladriamycin, THP) was performed. Although adriamycin has been widely utilized for chemoembolization on the hepatocellular carcinoma, myocardial toxicity has been occasionally observed as its serious side effect. THP has an advantage that myocardial and gastrointestinal complications are less frequent than adriamycin. Ten patients with hepatocellular carcinoma were included in this study. Emulsion of 30-60 mg of THP and lipiodol was administered through a catheter inserted into the right or left hepatic artery, and thereafter, transarterial embolization was performed. PR was observed in seven of the ten patients and MR in two. Only one patient showed NC. Serum alpha-fetoprotein levels decreased in nine of the ten patients, and PIVKA II in the peripheral blood disappeared in all five patients that had been positive before the chemo-embolization four weeks after the treatment. Side effects included nausea in two patients just after administration of THP, but leukopenia below 2,000/cmm, was not observed in any of the patients. No other serious side effect was observed. From these results, THP was suggested to be a useful chemotherapeutic agent for hepatocellular carcinoma.

Aged↗
PubMed1990

Urinary polyamine excretion measured by a simple enzymatic method is clinically useful as an expression of hepatic regeneration in liver diseases.

Polyamines have been known to play an important role in hepatic regeneration. In the present study, we measured the amount of urinary polyamine excretion in various liver diseases using a simple enzymatic method. Urinary polyamine excretion was elevated above the normal range in 21 out of 47 cases with fulminant hepatic failure, acute hepatitis, chronic active hepatitis, and liver cirrhosis. No change, however, was observed in 11 patients with chronic inactive hepatitis. In fulminant hepatic failure, two patients with urinary polyamine concentrations above 100 mumoles/g.cr. recovered, while two patients with concentrations of 56.2 and 26.7 mumoles/g.cr., died. In acute hepatitis, urinary polyamine excretion was significantly less in the recovery stage compared with the acute stage. When insulin and glucagon infusion therapy was performed in patients with liver cirrhosis without ascites, urinary polyamine excretion was significantly elevated after three days. These results suggest that measuring the amount of polyamine in urine is clinically useful for monitoring hepatic regeneration.

Biogenic Polyamines↗
PubMed1989

Clinical significance of serum antibodies against alcohol-altered hepatocyte membrane in alcoholic liver disease.

The clinical significance of serum antibodies against alcohol-altered rabbit hepatocytes was evaluated in 91 patients with alcoholic liver disease. Patients were divided into two groups according to the presence or absence of those antibodies at the time of first admission, and their clinical, biochemical, and histological findings were compared. In 38 seropositive patients, the total amount of ethanol consumption as well as serum activity of glutamate-oxaloacetate transaminase, serum levels of total bilirubin, gamma-globulin, IgG, and IgA were all significantly higher than in 53 seronegative patients. In addition, the extent of fibrosis, alcoholic hyalin, cholestasis, and lymphocytic and polymorpholeukocytic infiltrations in the liver were all significantly greater in the seropositive patients. Histological changes were compared in the 16 patients who continued to drink alcohol and who received repeated liver biopsies. Seven out of eight patients who were seropositive at the time of the first liver biopsy showed histological deterioration, whereas one of the eight seronegative patients showed a slight progression. These results suggest that the presence of serum antibodies against alcohol-altered liver cell membrane delineates a group of alcoholic patients with severe, advanced liver disease characterized by a tendency to progress with continued alcohol ingestion.

Alanine Transaminase↗
PubMed1989

Mechanism of increased hepatotoxicity of acetaminophen by the simultaneous administration of caffeine in the rat.

The simultaneous administration of caffeine has been shown to potentiate acetaminophen-induced hepatotoxicity. In the present study, the mechanisms of this effect were studied. Male Sprague-Dawley rats, fasted for 18 hr, were given acetaminophen (0.5 g/kg) and/or caffeine (0.1 g/kg) i.p. Two hours later, the depletion of hepatic reduced glutathione (GSH) induced by acetaminophen was more pronounced by the concomitant administration of caffeine, although the effect of caffeine alone on the hepatic GSH content was minimal at this dose. Covalent binding of a reactive metabolite of acetaminophen to hepatic proteins was increased by caffeine although the free acetaminophen content in the liver was not affected. In isolated rat hepatocytes prepared from normal animals, caffeine enhanced acetaminophen-induced GSH depletion and potentiated covalent binding of the reactive metabolite to cellular proteins. The extracellular release of GSH + oxidized glutathione was decreased by acetaminophen, and this decrease was potentiated further by the addition of caffeine. In the cells, the production of acetaminophen-GSH conjugate also was increased in the presence of caffeine, whereas that of glucuronide conjugate was decreased. In microsomes, NADPH-dependent production of acetaminophen-GSH conjugate was increased in the presence of caffeine. Thus, caffeine appears to potentiate acetaminophen-induced hepatotoxicity mainly by enhancing the production of a reactive metabolite of acetaminophen by mixed function oxidases. To what extend caffeine-induced GSH depletion plays a role is to be clarified.

Acetaminophen↗
PubMed1988

Brain protection against oxygen deficiency by nizofenone.

The cerebral protective effect of nizofenone against tissue oxygen deficiency was investigated in mice. Treating mice with nizofenone resulted in a dose-dependent decrease in the rate of KCN-induced mortality and significant protection was observed at a dose as low as 0.3 mg/kg (i.p.). The cerebroprotective action of nizofenone was also demonstrated biochemically: Nizofenone (10 mg/kg i.p.) ameliorated KCN-induced anoxic disorder of cerebral energy metabolism, characterized by irreversible depletions of cerebral high energy phosphate stores and glucose concentrations and a marked accumulation of lactate, while keeping the cerebral energy charge potential (ECP) close to its normal value. Nizofenone showed similar effects in another experiment in which cerebral metabolic disorder was induced by complete ischemia following decapitation. These findings suggest that nizofenone has a considerable cerebroprotective action against oxygen deficiency.

Animals↗
PubMed1988

Differences of liver membrane antibody frequency in alcoholic liver disease. Detection of IgG and IgA classes using radioimmunoassay.

The presence of liver membrane antibody in IgG and IgA was investigated by radioimmunoassay using isolated rabbit hepatocytes as target cells. This technique was more sensitive than the immunofluorescent method. IgG liver membrane antibodies were positive in 24% of patients with alcoholic liver disease. IgA liver membrane antibodies were detected in 58% of patients with alcoholic liver disease, whereas they were detected only in 21% of those with nonalcoholic liver disease, except for cases of autoimmune chronic active hepatitis. In alcoholic liver disease, IgA liver membrane antibodies were detected at a high frequency in a group of patients with alcoholic hepatitis and active cirrhosis (94%) as compared with that of fatty liver, hepatic fibrosis, and inactive cirrhosis (42%). These results suggest that alcoholic liver disease is characterized in part by a humoral immune response of IgA liver membrane antibodies.

Cell Membrane↗
PubMed1986

Protection against hepatic injury by a novel spiropiperidine derivative.

The evaluation of a novel hepatoprotective agent, Y-8845 (8(2-dimethylaminoethyl)-3-oxo-4-phenyl-1-thia-4,8-diazaspiro [4,5]decane dihydrochloride monohydrate), against carbon tetrachloride (CCl4)- and endotoxin-induced acute and chronic hepatic injury was carried out in rats. This compound, in a dose-dependent way, markedly reduced the increases in serum transaminase activities, the extent of liver cell necrosis, and the delay in indocyanine green (ICG) disappearance produced by a single toxic dosage of CCl4. This protective effect was observed even at doses of Y-8845 lower than 10 mg/kg po. It was also shown to protect the liver against injury induced by endotoxin. Furthermore, in the chronic liver injury induced by repeated administrations of CCl4 for 12 weeks, significant reductions of the increases in serum enzyme activities, liver fibrosis, and liver enlargement, and improvement in the ICG retention rate, were recognized in the Y-8845-treated groups at 10 mg/kg po or less. These findings indicate that this new agent has a remarkable protective effect, and possibly a therapeutic effect on liver injury.

Alanine Transaminase↗
PubMed1986

Inhibition of lymphocyte DNA synthesis by plasma from patients with Kawasaki disease.

Plasma obtained from patients with Kawasaki disease during the acute phase markedly inhibited DNA synthesis in autologous peripheral blood lymphocytes (PBLs) stimulated by phytohaemagglutinin-P (PHA-P) or concanavalin A (Con A). The inhibition became less marked with the progression of the disease and there was no effect on DNA synthesis in PBLs stimulated by pokeweed mitogen (PWM). The plasma also inhibited DNA synthesis in PBLs obtained from healthy adults. The postulated suppressors markedly inhibited DNA synthesis in PBLs from healthy adults stimulated by PHA-P, Con A, purified protein derivative (PPD) or mixed lymphocyte culture reaction (MLR) but they had little effect on the DNA synthesis stimulated by PWM or protein A. With respect to the mechanism, the suppression was found to be potentiated by an increase in the concentration of the patients' plasma, and not to be associated with cytotoxicity nor with a deficiency of factor(s) indispensable for PBL proliferation. It was also evident that the suppression was not related to the concentration of the stimulant, to the lengths of the culturing period nor to the presence of prostaglandins.

Adult↗
PubMed1986

Purification and characterization of cytotoxic factors in the venom of the Okinawa habu (Trimeresurus flavoviridis).

Two cytotoxic factors in the venom of Okinawa habu (Trimeresurus flavoviridis), a crotalid, have been purified and characterized. They had cell monolayer-disrupting activity against cells cultivated in vitro, but no proteolytic, hemorrhagic or direct hemolytic activity nor lethal toxicity. They were heat labile acidic proteins (isoelectric points 5.2 and 5.4) having similar molecular weights (approx. 14,000) and amino acid compositions. They were indistinguishable immunologically.

Amino Acids↗
PubMed1986

[Pharmacological studies on Y-8894. (IV). Ameliorative effect on a cerebral energy metabolism disorder induced by KCN].

The amelioration of energy metabolic disturbance in cerebral anoxia is valuable for the treatment of various cerebral ischemic diseases and insufficiency. In this study, the effect of Y-8894 on the cerebral energy metabolism was investigated using a KCN-induced cerebral anoxia model with mice. The intravenous injection of a lethal dose of KCN (2.5 mg/kg) induced rapid and marked decreases of brain glucose, phosphocreatine and ATP contents, with a remarkable enhancement of lactate and AMP levels, indicating a severe disorder of the cerebral energy metabolism. This phenomenon was also shown by an irreversible deterioration of the energy charge potential (ECP), an index of the cerebral energy state. The treatment with Y-8894 (30 mg/kg, i.p.) remarkably ameliorated this KCN-induced energy metabolic disturbance: markedly reducing the changes in brain phosphocreatine, glucose and lactate contents, while keeping ATP, AMP and ECP at nearly their normal levels. In addition, these changes in the Y-8894 treated group recovered promptly to normal, whereas those in the control group were irreversible. In normal mice, Y-8894 induced a significant increase in the cerebral glucose content without affecting either the cerebral glycolytic metabolism or the energy state. The present findings suggest that Y-8894 has an ameliorative effect on the cerebral energy metabolic disturbance, and this effect likely plays an important role in the improvement of amnesia and other neurological deficits related to cerebral anoxia.

Animals↗