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Biomedical subjects

N Inoue

Publications and source records attributed to N Inoue.

At least 19 recordsLinked to original sources
PubMed1992

Identification and quantitative analysis of urinary metabolites of dichloropropanols in rats.

Urinary metabolites of dichloropropanols in rats were analyzed by gas chromatography-mass spectrometry (GC/MS). Solutions of dichloropropanols consisting of 1, 3-dichloro-2-propanol (DC2P) and 2, 3-dichloro-1-propanol (DC1P) were diluted in a saline at the concentration of 100 mg/ml, and 0.1 ml of the solutions were subcutaneously injected into male Wistar rats weighing about 160g. The urine samples were collected over a period of 24 hours after the injections. DC2P and DC1P in the urine were extracted with ethylacetate and analyzed by a GC/MS. The derivatization procedure with 4-bromophenylboric acid after acetonitril extraction was applied for the analyses of diols in the urine. By the GC/MS analysis, 3-chloro-1, 2-propanediol (3CPD), 2-chloro-1, 3-propanediol (2CPD) and 1, 2-propanediol (PPD) were identified as the hydroxylated metabolites of dichlorpropanols. Based on the analytical results, the metabolic pathways of dichlorpropanols forming 3CPD and 2CPD, and then hydroxylating to PPD were elucidated.

Animals↗
PubMed1992

[Effects of ethylene oxide inhalation on mice].

Male ddY mice were exposed to ethylene oxide (EO) at a concentration of 400 ppm, 6 hours a day, 3 days a week for 13 weeks and the effects of EO on the hepatic drug metabolizing enzymes were investigated. The liver and spleen weight per body weight did not change. Compared to the control group, the kidney weight of the exposed group increased while the testis weight decreased significantly. Hematological examination showed macrocytic anemia in the exposed group. Contents of microsomal cytochrome P-450 in the exposed group increased twice as much as that in the control group, while microsomal protein, cytochrome b5, protoheme and NADPH-cytochrome C reductase activity did not change. NADH-ferricyanide reductase activity of the exposed group increased significantly. Among the glutathione related enzymes in the liver, glutathione reductase and glutathione peroxidase activities in the exposed group decreased but glutathione-S-transferase activity increased significantly.

Administration, Inhalation↗
PubMed1992

[Fulminant hepatitis after the inhalation of dichloropropanols].

A fatal case of acute fulminant hepatitis following exposure to dichloropropanols is reported. A 59-year-old male worker in a chemical plant developed general malaise, nausea and vomiting several hours after cleaning a tank that had contained dichloropropanols. He had no previous history of hepatic dysfunction. On admission, hepatomegaly was prominent. Because of highly elevated levels of GOT and GPT in the serum, reduced prothrombin time and a lowered consciousness level, a diagnosis of fulminant hepatitis was made. Significant decreases of leukocytes and platelets were also observed. Serum creatinine and BUN were slightly elevated. Although plasma exchanges were conducted on the third and fourth day, the liver functions continued to deteriorate. The patient died on the fifth day. Because dichloropropanols could be detected in the blood specimens obtained at the time of admission, we considered that fulminant hepatitis in this case was attributed to dichloropropanols exposure. To our knowledge, this is the first case of fulminant hepatitis after dichloropropanols-exposure.

Administration, Inhalation↗
PubMed1992

[Toxicity of dichloropropanols--changes in hematological findings and serum chemistry].

We investigated the toxicity of dichloropropanols (DCPs) in hematological findings and serum chemistry. The solutions of two isomers of DCPs, 1,3-dichloro-2-propanol (DC2P) and 2,3-dichloro-1-propanol (DC1P) were dissolved in saline at the concentration of 100 mg/ml, and 0.1 ml of each solution was subcutaneously injected into male Wistar rats weighing about 200 g. At 6 hours after the injections, in the DC2P group, the number of white blood cells and platelets showed a significant decrease. Transaminases, alkaline phosphatase and lactate dehydrogenase were greatly elevated. Blood urea nitrogen and creatinine also showed a significant increase. There were no changes in the measurements in the DC1P group. These results indicate that there is a prominent hepatotoxicity in DC2P, and that there is a considerable difference in the toxicity present in DC2P and DC1P. Furthermore, in the workplace where DCPs, especially DC2P, is used, the monitoring of the working environment and biological monitoring should be mandatory.

Alkaline Phosphatase↗
PubMed1992

[Effects of methylmercury chloride on creatine kinase activity in the rat brain].

The effects of methylmercury chloride (MMC) on creatine kinase (CK) activity in the rat brain were studied. Male Wistar rats were injected subcutaneously with 10 mg MMC/kg body weight/day for 7 consecutive days, and sacrificed on the 15th day when all rats showed a crossing phenomenon of the hind limbs. CK activity was mildly inhibited in the anterior, mid and posterior cerebral cortex. Aspartate aminotransferase and lactate dehydrogenase activities were also inhibited in some parts of the cerebral cortex, almost to the same extent as the CK activity. No definite inhibition of the enzyme activity was found in the striatum and the cerebellum. From this study we concluded that the mild inhibition of CK activity does not seem to play an important role in the genesis of neurotoxicity of MMC.

Animals↗
PubMed1992

Activation of human natural killer cells by the protein-bound polysaccharide PSK independently of interferon and interleukin 2.

The protein-bound polysaccharide PSK was tested for the ability to activate human natural killer (NK) cells. When blood lymphocytes and purified CD3-CD16+ large granular lymphocytes (LGL) were treated in vitro overnight with PSK, they demonstrated enhanced NK cell activity against K562. The PSK-activated killer cells also lysed NK-resistant targets and freshly isolated autologous and allogeneic tumor cells. The PSK effect was observed with concentrations that could be obtained in the blood of cancer patients receiving oral administration of PSK. PSK-induced enhancement of NK activity was not abrogated by monoclonal antibodies (mAb) that neutralized interferon (IFN) alpha, IFN gamma, or interleukin-2 (IL-2). In addition, mAb reactive with p55 (alpha chain) or p75 (beta chain) glycoproteins of IL-2 receptors had no effects on PSK-enhanced NK activity even when used simultaneously. These results indicate that the PSK could activate human NK cells independently of IFN and IL-2/IL-2R systems.

Adenocarcinoma↗
PubMed1992

Effects of megadoses of pyridoxine on spermatogenesis and male reproductive organs in rats.

Although it has been indicated that many neurotoxicants also cause reproductive toxicity, the reproductive toxicity of megadoses of pyridoxine, which is a neurotoxicant, has not been studied. In this paper, we studied the effects of megadoses of pyridoxine on male reproductive organs. Pyridoxine hydrochloride, 125 mg/kg, 250 mg/kg, 500 mg/kg or 1000 mg/kg, daily, was intraperitoneally injected into Wistar male rats 5 days a week for 2 or 6 weeks, and its effects on the male reproductive organs were investigated. After 2 weeks of administration, absolute weights of the testis in the 500 and 1000 mg/kg epididymis in all the exposed groups and prostate gland in the 1000 mg/kg group decreased, and mature spermatid counts in the testis decreased in the 1000 mg/kg group. After 6 weeks administration, the absolute and relative weights of the testis, epididymis, prostate gland and seminal vesicle decreased in the 500 mg/kg and 1000 mg/kg groups, and mature spermatid counts in the testis and sperm counts in the epididymis decreased in these groups. Among the marker enzymes of the testicular cells, LDH-X activity decreased, and beta-glucuronidase activity, cytochrome P-450 content and cytochrome b5 content increased in the 1000 mg/kg group. Plasma testosterone concentration did not significantly alter in all the exposed groups. From these results, it was concluded that megadoses of pyridoxine affected the spermatogenesis and decreased reproductive organ weights in the rat.

Animals↗
PubMed1992

Selective cerebral perfusion during operation for aneurysms of the aortic arch: a reassessment.

Thirty-two consecutive patients with thoracic aortic aneurysms who required aortic arch reconstruction were operated on with the aid of extracorporeal circulation and selective cerebral perfusion between January 1986 and August 1990. For selective cerebral perfusion, blood was infused into both the innominate and left common carotid arteries at a rate of 10 mL.kg-1.min-1 using a single roller pump separately from the systemic circulation. In 9 patients treated before March 1987, the operations were performed without open aortic anastomosis (group 1), whereas in 23 patients treated from March 1987 onward we used open aortic anastomosis (group 2). The extracorporeal circulation and cardiac arrest times were significantly longer in group 2, but there was no significant difference in the cerebral perfusion time. Early death occurred in 1 patient in group 1 and 2 in group 2. No serious cerebrospinal neurological complications occurred in either group, and there were similar rates of postoperative hepatic and renal dysfunction in both groups. The present data suggest that selective cerebral perfusion and open aortic anastomosis are useful methods for thoracic aortic aneurysm operation requiring complex repair of the aortic arch.

Adult↗
PubMed1992

Regression of coronary atherosclerosis by combined LDL-apheresis and lipid-lowering drug therapy in patients with familial hypercholesterolemia: a multicenter study. The LARS Investigators.

The purpose of the LDL-Apheresis Regression Study (LARS) group, which included 13 institutions in Japan, was to investigate the effects on coronary atherosclerosis of LDL-apheresis combined with cholesterol-lowering drugs. Changes in coronary artery stenosis were assessed angiographically in 37 patients with familial hypercholesterolemia (7 homozygotes and 25 heterozygotes) and hypercholesterolemia which had not been defined as familial hypercholesterolemia (5 patients) by visual judgement and computer analysis. Definite regression was observed in 14 cases, including 4 homozygotes and 10 heterozygotes and others. Regression occurred as often in patients with severe coronary artery disease (2 or more vessel disease) as in those having less severe disease. Our results encourage initiation of aggressive cholesterol-lowering therapy to produce regression of coronary atherosclerosis in FH patients at high risk for cardiovascular events.

Adult↗
PubMed1992

Effects of dimethylformamide on hepatic microsomal monooxygenase system and glutathione metabolism in rats.

The effects of repeated exposure to N,N-dimethylformamide (DMF) on hepatic microsomal monooxygenase system and glutathione metabolism were investigated. DMF was administered to Wistar male rats by subcutaneous (s.c.) injection at 0.5 ml/kg body weight daily for 1 week. Macroscopically, mild liver swelling was observed and liver weights significantly increased after 1 week of exposure to DMF. Hematological changes were not detected. In exposed rats, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, cholinesterase and total cholesterol significantly increased. Hepatic microsomal cytochrome P-450 and protoheme decreased by 34% and 24%, respectively, while microsomal protein and cytochrome b5 were not affected. NADH-ferricyanide reductase activity decreased by 24% while NADPH-cytochrome c reductase activity showed no change. Glutathione reductase (GR) activity showed a significant decrease after the first injection and remained depressed throughout the study, with no change in glutathione peroxidase (GPx) activity. Glutathione S-transferase (GST) activity showed a significant increase at 3 days after DMF treatment and gradually increased by 66% at 1 week. In a subsequent experiment with a single administration of DMF (4 ml/kg), reduced glutathione (GSH) in the liver was decreased by 28% at 8 h, but recovered to control levels by 24 h. These results indicate that DMF alters the hepatic microsomal monooxygenase system and glutathione metabolism. These findings may greatly contribute to the elucidation of the pathogenesis of DMF hepatotoxicity.

Animals↗
PubMed1992

Distribution and possible origins of substance P-containing nerve fibers in the rat liver.

The distribution and possible origins of substance P-containing nerve fibers in the rat liver were investigated by immunohistochemistry and nerve transection. Nerve fibers with substance P-like immunoreactivity formed a more complex network than previously known in the walls of portal vein branches. Substance P-immunoreactive fibers were seen not only in and around the walls of the hepatic artery, but also in close association with the hepatic veins and bile ducts. Transection of the greater splanchnic nerves and/or the vagus nerves indicated that substance P-immunoreactive fibers in the walls of the portal and hepatic veins enter the liver via both nerves, and that those associated with the hepatic artery and bile ducts stem from the greater splanchnic nerves. The widespread distribution of hepatic substance P and its complex innervation pattern within the liver suggest that it is involved in a variety of physiological processes in this organ.

Animals↗
PubMed1992

Use of enzyme-linked immunosorbent assays with chimeric fusion proteins to titrate antibodies against Epstein-Barr virus nuclear antigen 1.

Two new enzyme-linked immunosorbent assays (ELISAs) with chimeric fusion polypeptides for the detection of human antibodies specific to Epstein-Barr virus nuclear antigen 1 (EBNA-1) are described. One is an indirect ELISA with affinity-purified beta-galactosidase-EBNA-1 fusion protein as the antigen. The other is a "sandwich" assay based on the use of anti-beta-galactosidase antibody to capture beta-galactosidase-EBNA-1 fusion proteins in bacterial extracts. A good correlation was shown between antibody titers determined by the ELISA with the EBNA-1 fusion proteins and those determined by a conventional anticomplement immunofluorescence test which is being widely performed with Raji cells for the purpose of research and clinical diagnosis. The advantage of the ELISAs for seroepidemiologic studies on Epstein-Barr virus was demonstrated by sensitive detection of marginal immunoglobulin G antibody to the EBNA-1 domain in serum samples from patients with infectious mononucleosis.

Antibodies, Viral↗
PubMed1992

Comparative sequence analyses of Epstein-Barr virus nuclear antigen-2 and -3B genes of a fresh Epstein-Barr virus-2 isolate.

The nucleotide sequence of Epstein-Barr virus (EBV) nuclear antigen (EBNA)-2 and EBNA-3B regions of an EBV-2 isolate in Japan was analyzed. The deduced amino acid sequences of EBNA-2 and EBNA-3B of the isolate and a prototype EBV-2 strain AG876 were identical, but the number of the repeated sequence in EBNA-3B was variable as that of IR-3 in EBNA-1. The remarkably well-conserved sequence seems to suggest that the structure of the EBNA-2 and EBNA-3B genes of EBV-2 is crucial for their function in virus replication.

Antigens, Viral↗
PubMed1992

Lysophosphatidylcholine inhibits bradykinin-induced phosphoinositide hydrolysis and calcium transients in cultured bovine aortic endothelial cells.

Vascular endothelium, which produces endothelium-derived relaxing and constricting factors, plays an important role in regulating the vascular tone. We recently demonstrated that oxidized low density lipoprotein inhibited endothelium-dependent relaxation and that lysophosphatidylcholine accumulated during the oxidative modification of low density lipoprotein was the essential substance for the inhibition of endothelium-dependent relaxation. To clarify the mechanisms of the inhibitory effect of lysophosphatidylcholine, we used a bioassay system to investigate the effect of lysophosphatidylcholine on the production and/or release of endothelium-derived relaxing factor and its effect on the cytosolic Ca2+ level ([Ca2+]i) and phosphoinositide hydrolysis in cultured bovine aortic endothelial cells. [Ca2+]i was monitored by the fura 2 method, and the accumulation of inositol phosphates in cells labeled with myo-[2-3H]inositol was measured. Bioassay experiments showed that lysophosphatidylcholine inhibited the production and/or release of endothelium-derived relaxing factor from cultured endothelial cells. Lysophosphatidylcholine (5-20 micrograms/ml) induced a biphasic increase in [Ca2+]i, which consisted of a rapid increase followed by a sustained increase, and the initial component was a result of mobilization from intracellular Ca2+ stores without detectable synthesis of inositol 1,4,5-trisphosphates. Furthermore, lysophosphatidylcholine (5-20 micrograms/ml) dose-dependently inhibited both phosphoinositide hydrolysis and the increases in [Ca2+]i evoked by bradykinin. These results indicate that the impairment of endothelium-dependent relaxation induced by lysophosphatidylcholine is due to the inhibition of phosphoinositide hydrolysis and the subsequent increases in [Ca2+]i in endothelial cells. Lysophosphatidylcholine that accumulates in oxidized low density lipoprotein and atherosclerotic arteries may play an important role in the modification of endothelial function.

Animals↗
PubMed1992

[Recovery study from anemia and alterations of glutathione metabolism in erythrocytes induced by chronic inhalation of ethylene oxide].

A study was made on the recovery from anemia induced by chronic exposure of ethylene oxide. When rats were exposed to ethylene oxide at a concentration of 500 ppm, 6 h a day, 3 d a week for 13 wk, macrocytic normochromic anemia with a high reticulocyte count was observed. The hematological values were also evaluated 4 and 13 wk after the end of exposure and the values were found to have already recovered at 4 wk. We reported previously that anemia induced by ethylene oxide was accompanied with a decrease in glutathione reductase activity and instability of glutathione. In this study, alterations of glutathione redox cycle after the end of exposure were examined. The recovery in the decrease of glutathione reductase was slow and the speed of recovery seemed to be dependent on the life span of erythrocytes of the rats. The decrease in glutathione content completely recovered at 4 wk after the exposure. It was concluded from these observations that anemia induced by ethylene oxide is reversible.

Administration, Inhalation↗