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Biomedical subjects

Y Hori

Publications and source records attributed to Y Hori.

At least 145 records · Page 8Linked to original sources
PubMed1998

Impaired transport of lipopolysaccharide across the hepatocytes in rats with cerulein-induced experimental pancreatitis.

Hepatic dysfunction is one of the critical complications in acute pancreatitis but this mechanism is poorly understood. In patients with acute pancreatitis, hypoalbuminemia is often recognized, suggesting possible disturbance of hepatic transport of proteins and hepatic metabolites. The present study was undertaken to elucidate hepatic function in cerulein-induced pancreatitis from the viewpoint of intrahepatic vesicular transport. We examined the biliary excretion of lipopolysaccharide (LPS), whose pathway in the hepatocyte has been shown to be microtubule dependent. In vivo studies and ex vivo studies using isolated perfused rat liver (IPRL) showed that cumulative excretion of LPS in each period was significantly reduced, by 49 and 25%, respectively, compared with that in control rats. But studies of biliary secretion in vivo and ex vivo studies indicated statistical insignificance between the two groups. Moreover, biliary excretion of LPS was inhibited to 60% of the control by colchicine pretreatment, without affecting bile flow in IPRL, but gadolinium chloride had no effect. We conclude that transport of LPS across the hepatocyte from blood to bile is impaired in rats with cerulein-induced pancreatitis without being affected by Kupffer cell function. These results suggest that a disturbance of vesicular transport in hepatocyte may also occur in exocytosis and endocytosis via the sinusoidal membrane, cause impairment of hepatic transport of proteins and hepatic metabolites, and result in hepatic dysfunction in acute pancreatitis.

Animals↗
PubMed1998

Immune thrombocytopenia due to Tranilast (Rizaben): detection of drug-dependent platelet-associated IgG.

Tranilast (Rizaben)-induced thrombocytopenia occurring in a 17-year-old man was reported. After withdrawal of the drug, he recovered within a week with oral prednisolone administration. Serological examination revealed no anti-platelet antibody, but platelet-associated IgG (PAIgG) was found. After incubation of peripheral blood of the patient with the drug in vitro, the level of PAIgG was significantly increased. These findings suggest the presence of a drug-dependent anti-platelet IgG in the patient's serum. This is the first report of immune thrombocytopenia caused by Tranilast. Our method for detecting drug-dependent platelet antibody in vitro is safe and useful for diagnosing drug-induced thrombocytopenia.

Adolescent↗
PubMed1998

Differentiation of the inhibitory effects of calcium antagonists on abnormal behaviors induced by methamphetamine or phencyclidine.

The abnormal behaviors induced by methamphetamine (MAP: 1 mg/kg) or phencyclidine (PCP: 10 mg/kg) were measured using behavioral analysis following the microinjection of one of three calcium (Ca) antagonists (nifedipine: Nif, nicardipine: Nic and flunarizine: Flu) into the rat caudate putamen or amygdala. The intraperitoneal administration of MAP or PCP induced abnormal behaviors in a time-dependent manner; the maximum locomotor activity was measured 30-45 min after the administration of MAP or PCP. This hyperactivity was sustained for more than 2 h. Following microinjection of these Ca antagonists into the caudate putamen, each showed a different pattern of inhibition on MAP- or PCP-induced abnormal behaviors. Nic and Flu were effective at reducing these abnormal behaviors, in contrast, Nif was ineffective. In particular, the inhibitory effect of Nic was stronger than that of Flu. Microinjection of these Ca antagonists into the amygdala did not show any reductive effect on the hyperactivity induced by MAP or PCP. These results demonstrate that these Ca antagonists have different pharmacological properties and that both L- and T-type Ca2+ channels modulate the dopamine release in the rat caudate putamen. These results further lead us to suggest the presence of a subtype of L-type Ca2+ channels in the caudate putamen.

Amygdala↗
PubMed1998

Intracellular calcium changes and chemosensitivities of human epidermoid carcinoma cell lines after exposure to cisplatin.

In order to elucidate the mechanisms of cisplatin (cis-diamminedichloroplatinum; CDDP)-resistant tumor cells, we previously established a CDDP-resistant KB cell line (KBrc cells) from a parental KB cell line derived from epidermoid carcinoma (KB cells). The KBrc cells were resistant to 5 kinds of platinum (Pt) drugs. Intracellular Pt concentrations in KBrc cells were lower than in KB cells. Decrease of intracellular Pt concentrations was one of the CDDP-resistant mechanisms. When we measured changes of intracellular calcium ion concentration ([Ca2+]i) during exposure to high-dose CDDP, a sustained elevation of the [Ca2+]i level was observed in the KB cells. These results suggest that the mechanisms underlying CDDP resistance involve changes in calcium channels and an alteration of calcium homeostasis in the tumor cell line.

Antineoplastic Agents↗
PubMed1998

Determination of free fatty acids in human bile by high-performance liquid chromatography.

We developed a high-performance liquid chromatography (HPLC) method for free fatty acids (FFAs) analysis in bile. In this method, FFAs were extracted from bile in a single step using an Isolute ODS cartridge, derivatized with 9-anthryldiazomethane (ADAM). ADAM was chosen because of its high reactivity with carboxylic acid at room temperature. Then, HPLC was used for separating and quantifying FFAs. This method proved to be simple and time-saving. The mean recovery of FFA added to human gallbladder bile was 97.6%, and the detection limit was 100-250 pg. Using this method, we determined FFA concentrations in the gallbladder bile of 11 gallstone patients. The mean concentration of total FFA was 0.61 (SD = 0.41) mmol/L, and there was wide variation in the individual FFAs.

Adult↗
PubMed1998

Production of superoxide and nitric oxide by alveolar macrophages in the bleomycin-induced interstitial pneumonia mice model.

To elucidate the potential role of superoxide (O2-) and nitric oxide (NO) in the pathogenesis of interstitial pneumonia, the quantity of O2- and NO produced by the alveolar macrophages (AM) were determined in the bleomycin (BLM)-induced interstitial pneumonia mouse model. The production of O2- and NO increased on days 7, 14 and 21 after BLM injection. Strong expression of peroxynitrite (ONOO-) was seen in AM by using immunostaining for nitrotyrosine. The hydroxyproline contents increased on day 21 after BLM injection. O2- and NO are thought to play an important role in the pathology of fibrosis.

Animals↗
PubMed1998

Significant decreased insulin secretion in a diabetic patient with clinically probable multiple sclerosis.

A 39-year-old man with chief complaints of aphasia, disorientation and acalculia was admitted to our hospital. He was diagnosed as a clinically probable case of multiple sclerosis (MS) and his symptoms improved while on steroid pulse therapy. The patient had been diagnosed as having diabetes mellitus 16 years before the onset of MS and his insulin secretion further decreased with time. Slight insulin resistance was observed during a euglycemic hyperinsulinemic clamp study. These results suggested that this patient developed diabetes mellitus mainly due to the decrease of insulin secretion.

Adrenal Cortex Hormones↗
PubMed1998

The risk of hepatitis C virus infection among blood donors in Osaka, Japan.

To estimate the risk of hepatitis C virus (HCV) infection among blood donors, we conducted a retrospective cohort study with 448,020 HCV-seronegative donors who donated blood more than once between February 1992 and July 1997 in Osaka (a total of 2,676,738 allogeneic blood donations). The donors were divided into four age groups according to the age at the initial donation: Group A (16-24 years), Group B (25-34 years), Group C (35-49 years) and Group D (50-64 years). Fifty-nine donors became infected with HCV among the 448,020 HCV-seronegative donors who donated blood more than once within a period of approximately five years. In a total of 1,095,668 person-years of observation (PYO), the incidence rate was 5.38 per 105 PYO, with the 95% confidence interval (95% C.I.) being 4.10 to 6.95. There was no significant difference in the incidence rate between males and females. Young donors between the ages of 16 and 24 (8.89; 95% C.I., 6.04 to 12.61) had a significantly higher incidence rate of HCV infection than donors between the ages of 35 and 49 (1.81; 0.67 to 3.95). The cumulative risk of HCV infection among donors between the ages of 16 and 64 was estimated to be 0.27% (95% C.I., 0.16 to 0.39) for males and 0.27% (95% C.I., 0.15 to 0.38) for females. Based on the recent age-specific incidence rate, the cumulative risk of HCV infection among blood donors was estimated to be about 0.3% in the Osaka district of Japan. The incidence rate differed among age groups, indicating that HCV infection is associated with age-related behaviors and the need for further epidemiological research towards the eradication of community-acquired HCV infection.

Adolescent↗
PubMed1998

Blood glucose and ischemic brain damage.

The effect of hyperglycemia on ischemic brain damage was studied in a rat model of incomplete ischemia. Incomplete ischemia was produced by permanent occlusion of one (either left or right) common carotid artery (CCA). Hyperglycemia was induced by intraperitoneal injection of 50% glucose, and same volume of physiological saline was injected in the controls 40 min before CCA ligation. Serum glucose level, at the time of vessel ligation, was 33.3 mMol/L. After CCA ligation, the rats were allowed to wake up and survive for upto 1 month. Perfusion-fixed brains were embedded in paraffin, subserially sectioned, and stained with haematoxylin-eosin/cresyl violet. Brain from sham-operated animals showed no damage neurons. Only mild neuronal damage was observed in saline pre-treated rats in CA1 area. Histological examination 24 h after CCA occlusion revealed ischemic neuronal cell damage to be more extensive in hyperglycemic rats. Neuronal damage was found in the major brain structures vulnerable to several insults. Some of those damaged neurons recovered well, but presence of some damaged neurons at 1 month of recovery suggesting delayed recovery. The results indicate that increased blood glucose level (hyperglycemia) during brain ischemia exaggerates structural alterations and leads to delay in recovery.

Animals↗
PubMed1998

[Evaluation of 99mTc-DTPA-HSA abdominal imaging of protein-losing gastroenteropathy].

Abdominal images were obtained after the intravenous injection of 99mTc-HSA-D in 8 patients with protein-losing gastroenteropathy (PLG). Six neck images and 7 abdominal images were obtained in 11 patients with ischemic heart disease as a control study. We evaluated all the images with respect to visualization, initial appearance time, and movement of abnormal radioactivity. In 7 of 8 patients with PLG, abnormal radioactivity in the intestine appeared from 10 min to 4 hours after injection, and moved 6 hours after injection. In 6 of 7 abdominal images of control cases, slight activity was observed in the alimentary tract 6 hours or 24 hours after injection. The thyroid was not visualized in any of the 6 cases. In conclusion, if radioactivity in the alimentary tract was first observed 6 hours or later after injection, the diagnosis of PLG may be difficult by this method alone. It still may be necessary to perform the alpha 1-antitrypsin test for the correct diagnosis of PLG.

Abdomen↗
PubMed1997

Co-mutagenicity of glyco- and tauro-deoxycholic acids in the Ames test.

Mutagenicity and co-mutagenicity of glyco- and tauro-deoxycholic acids (GDCA and TDCA), which are abundant in human bile, were examined by the Ames test. The two chemicals were not mutagenic for themselves to Salmonella typhimurium TA98 and TA100, with and without S9 mix. They enhanced, however, the mutagenic activities of the pro-mutagens, 2-aminoanthracene (2AA) and benzo[a]pyrene (BaP), for both TA98 and TA100 with S9 mix. They were more co-mutagenic for the pro-mutagens on TA98 than on TA100. On TA98, the mutagenic activities of 2AA with GDCA (5 mumol/plate) and with TDCA (5 mumol/plate) were 9.7-fold and 11.8-fold as high as that of the corresponding control (2AA only), respectively. BaP with GDCA (2.5 mumol/plate) and with TDCA (2.5 mumol/plate) showed 2.8-fold and 3.0-fold increases over the corresponding control level (BaP only), respectively. It is hence concluded that GDCA and TDCA may enhance the activity of some mutagens existing in bile.

Animals↗
PubMed1997

Synthesis and evaluation of novel fluorinated methotrexate derivatives for application to rheumatoid arthritis treatment.

An ongoing search for new antifolate drugs useful against rheumatoid arthritis (RA) led us to prepare new methotrexate (MTX) derivatives containing enantiomerically pure L-erythro- or L-threo-gamma-fluoroglutamic acid. The derivatives in which the phenyl ring was replaced by a 3'-substituted phenyl or methylthiophene ring showed potent immunosuppressive activities, including in vitro inhibition of mitogen responses to both T and B cells and in vivo inhibition of antibody production in mice. These compounds also exhibited inhibitory activity in adjuvant arthritis in rats. Their toxicity was lower than that of MTX, which was probably due to the strong electronegativity of fluorine, which increases the acidity of the gamma-carboxyl group and thereby decreases polyglutamylation in normal cells. These results revealed the potential of the fluorinated MTX derivatives as candidate drugs for the treatment of RA.

Animals↗
PubMed1997

Extracellular sodium concentration has diverse effects on the hypoxia-induced increase in intracellular Ca2+ in rat hippocampal slices.

The intracellular free Ca2+ concentration ([Ca2+]i) in the CA1 pyramidal cell layer was measured using fura-2-loaded hippocampal slices prepared from adult rats. Hypoxia (oxygen-glucose deprivation) elicited a gradual increase in [Ca2+]i in normal Krebs solution. With a high extracellular sodium concentration ([Na+]o), the hypoxia-induced response was attenuated, its onset-latency was longer and the time constant of its decay phase was shorter than in controls. In contrast, hypoxia in low [Na+]o elicited a significantly enhanced response with a short onset-latency and delayed decay phase. This exaggerated response to hypoxia in low [Na+]o was reversed by pre-incubation of the slice in low [Na+]o prior to the hypoxic insult. Some possible mechanisms and the functional significance of the observed effects of [Na+]o on the hypoxia-induced increase in [Ca2+]i are discussed, with particular emphasis on the putative participation of the glutamate transporter and the sodium-calcium exchanger in hypoxia-induced neuronal injury.

Animals↗
PubMed1997

Inhibitory action of sphingosine or ceramide on amylase secretion from isolated rat pancreatic acini.

Sphingosine and ceramide, products of sphingomyelin hydrosis by sphingomyelinase, have recently been regarded as second messengers for cell biological actions. On the other hand, exocrine pancreas is a typical organ to perform regulatory secretion of digestive enzymes, depending upon extracellular signals. We investigated the effects of sphingosine or ceramide on amylase secretion from isolated rat pancreatic acini. Either sphingosine or cell-permeable ceramide inhibits CCK8- or carbachol-induced enzyme secretion from isolated rat pancreatic acini in a dose-dependent manner. Sphingosine or ceramide itself does not affect basal amylase secretion from the acini. Ceramide also inhibits NaF-induced amylase secretion, indicating that it acts post the activation of receptor-linked GTP-binding protein. In our experiments, ceramide inhibited Ca2+ ionophore-induced amylase secretion, but not phorbol ester-induced secretion. These results indicate that ceramide affects secretory processes post intracellular Ca2+ mobilization in the exocrine pancreas.

Amylases↗
PubMed1997

Molecular cloning of the human methylthioadenosine phosphorylase processed pseudogene and localization to 3q28.

Human methylthioadenosine phosphorylase (MTAP) is a purine and methionine metabolic enzyme present ubiquitously in all normal tissues, but often deleted in many types of cancer. The gene for this enzyme maps to chromosome 9 at band p21 where the cyclin-dependent kinase inhibitor genes for p16 and p15 also reside. During our efforts to clone this gene we also isolated a phage clone containing a processed pseudogene of MTAP. The sequence is 92% homologous to the MTAP cDNA, is flanked at its 3' end by a repetitive element, but does not possess a poly(A) stretch. We localized this processed pseudogene to band 28 on the long arm of chromosome 3 by fluorescence in situ hybridization. All 22 malignant cell lines with deletions at 9p21 screened possessed the pseudogene.

Amino Acid Sequence↗
PubMed1997

Hepatocyte growth factor in assessment of acute pancreatitis: comparison with C-reactive protein and interleukin-6.

Serum levels of hepatocyte growth factor (HGF), C-reactive protein (CRP), and interleukin-6 (IL-6) were determined at the time of admission in 38 patients with acute pancreatitis. The clinical utility of HGF for the detection of severe pancreatitis and for predicting prognosis, bacterial infection (infected pancreatic necrosis or sepsis), and organ dysfunction (liver, kidney, and lung) during the clinical course of acute pancreatitis was compared with the clinical utility of CRP and IL-6 by analysis of receiver operator characteristic (ROC) curves. The optimum cutoff levels of HGF for severity, prognosis, infection, hepatic dysfunction, renal dysfunction, and respiratory dysfunction were 0.9, 1.1, 1.0, 1.1, 1.1, and 1.0 ng/ml, respectively. HGF was as useful as CRP and more useful than IL-6 for detection of severe pancreatitis and for predicting hepatic dysfunction. Moreover, HGF was more useful than CRP or IL-6 for predicting prognosis, renal dysfunction, and respiratory dysfunction. However, for predicting infection, CRP was more useful than HGF. These results suggest that serum HGF levels on admission may be a useful new clinical parameter for determining the prognosis of acute pancreatitis and that HGF may be closely related to the organ dysfunction of acute pancreatitis.

Acute Disease↗
PubMed1997

Protective effect of the intravenous administration of ursodeoxycholic acid against endotoxemia in rats with obstructive jaundice.

This study was undertaken to elucidate the effect of the intravenous administration of ursodeoxycholic acid (UDCA) on endotoxemia in rats with obstructive jaundice from the viewpoint of the biliary excretion of lipopolysaccharide (LPS) through hepatocytes. In rats with obstructive jaundice, fluorescein isothiocyanate-labeled LPS was administered via the portal vein and then its biliary excretion was examined. A significant increase in the LPS excretion was thus noticed in UDCA-treated rats at a dose of 0.1 micromol/100 g body wt. per min. In place of UDCA, sodium taurocholate at the same dose also enhanced the biliary excretion of LPS. Secondly, we also examined whether or not UDCA protects against endotoxemia. In this experiment, nonlabeled LPS was administered via the portal vein and its peripheral concentration was then measured. In UDCA-treated rats, the endotoxin concentration was significantly lower. Finally, to elucidate the effect of UDCA on Kupffer cells, serum tumor necrosis factor (TNF-alpha) was measured. But UDCA had no effect on the TNF-alpha level. These findings thus demonstrate that the intravenous administration of UDCA protects against endotoxemia by enhancing the transport of LPS across the hepatocytes from blood to bile without affecting Kupffer cells, and that this biliary excretion of LPS is dependent on bile acids.

Analysis of Variance↗