Acute hepatitis type C co-infected with GBV-C treated with interferon.
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Acute Disease↗
Biomedical subjects
M Sata
Publications and source records attributed to M Sata.
Prognostic factors for short-term survival in alcoholic hepatitis in Japan: analysis by logistic regression.
Prognostic factors for the outcome of patients with alcoholic hepatitis were identified by logistic regression analysis. To predict the outcome immediately after admission, clinical data from 97 patients with alcoholic hepatitis on admission were introduced to multivariate analysis. Independent prognostic factors for favorable outcome were hepaplastin time, peripheral white blood cell count, age (40 to 60 years), and serum creatinine level (below 1.4 mg/dl). Sensitivity, specificity, positive predictive value, negative predictive value, and predictive accuracy were 0.78, 0.89, 0.78, 0.89, and 0.86, respectively. The resultant equation for the death rate was applied to another set of patients with alcoholic hepatitis as a validation study. Predictive accuracy estimated 0.95 in validation. The prognostic index derived was simple, accurate, and useful in the prediction of the outcome in patients with alcoholic hepatitis. Furthermore, it provides the clinician with an indication of the necessity for the intensive care of patients in a critical condition.
Adult↗
Enhanced interaction between tubulin and microtubule-associated protein 2 via inhibition of MAP kinase and CDC2 kinase by paclitaxel.
Paclitaxel, an anti-mitotic anti-cancer agent, is active against solid tumors. The inhibition of depolymerization and promotion of microtubular assembly are essential for the anti-tumor activity of paclitaxel. Microtubule-associated proteins (MAPs) co-polymerize with tubulin and play some roles in microtubular dynamics. We examined the effect of paclitaxel on the interaction between tubulin and MAPs. Human lung-cancer cells, PC-14, were synchronized to G1/S border by the thymidine-double-block technique. After release from exposure to thymidine, the cells were treated briefly with 2 nM paclitaxel and the levels of alpha and beta tubulins and MAPs were examined after various times. Immunoblot analysis of paclitaxel-treated cells showed no changes in the overall expression of alpha and beta tubulins, microtubule-associated protein 2 (MAP2) or MAPs in comparison with controls. The samples were immunoprecipitated with anti-alpha- and anti-beta-tubulin antibodies and reblotted with an anti-MAP2 antibody, which showed that the amount of co-immuno-precipitated MAP2 in the synchronized cells, were increased by the brief paclitaxel treatment. These results suggest that paclitaxel treatment enhances the interaction between alpha and beta tubulins and MAP2. Since the phosphorylation state of MAP2 regulates the affinity of MAP2 for tubulins, and mitogen-activated protein (MAP) kinase is considered to be one of the kinases responsible for MAP2 phosphorylation, the effect of paclitaxel treatment on the MAP-kinase activity of synchronized PC-14 cells was examined. Two bands with molecular masses of 42 and 44 kDa were detected by an "intra-gel" MAP-kinase assay using myelin basic protein as the substrate. Paclitaxel treatment inhibited the MAP-kinase activity of PC-14 cells and inhibition was maximal at the G2/M phase of the cell cycle. Similar, concentration-dependent inhibition by paclitaxel of cellular MAP kinase of human synchronized small-cell lung carcinoma, H69, was observed. No inhibition of the MAP kinase of the paclitaxel-resistant sub-line H69/Txl by paclitaxel was observed, suggesting that some change of the MAP-kinase cascade had occurred in these cells. No direct inhibition of MAP-kinase activity by paclitaxel was observed in the cell-free assay (in vitro), suggesting that paclitaxel did not inhibit MAP kinase directly. Since it has been speculated that p34cdc2 kinase is also a kinase that phosphorylates MAP2, the effect of paclitaxel treatment on the p34cdc2-kinase activity of synchronized PC-14 and PC-9 cells was examined. Paclitaxel inhibited p34cdc2-kinase activation at the G2/M phase. These results suggest that paclitaxel inhibited MAP kinase and p34cdc2 kinase in vivo indirectly. These actions of paclitaxel may be responsible for the increased affinity between MAP2 and tubulins that it induces.
Amino Acid Sequence↗
Gamma-glutamylcysteine synthetase gene overexpression results in increased activity of the ATP-dependent glutathione S-conjugate export pump and cisplatin resistance.
The ATP-dependent glutathione S-conjugate export pump (GS-X pump) has been suggested to play a role in the mechanism of cisplatin resistance. The purpose of this study was to determine the relationship between intracellular glutathione (GSH) levels and GS-X pump activity and whether GS-X pump overexpression results in cisplatin resistance. We transfected the human gamma-glutamylcysteine synthetase (gamma-GCS) gene into a human small-cell lung cancer cell line, SBC-3, producing SBC-3/GCS. The intracellular GSH content of SBC-3/GCS was twice that of the parental line, its GS-X pump activity was significantly enhanced and cellular cisplatin accumulation decreased. SBC-3/GCS showed higher resistance (relative resistance value of 7.4) to cisplatin than the parental line SBC-3. These data indicate that gamma-GCS gene overexpression induces cellular cisplatin resistance associated with increases in both the GSH content and GS-X pump activity, resulting in reduced cisplatin accumulation. In conclusion, GS-X pump expression is related to cellular GSH metabolism and involved in cisplatin resistance.
Adenosine Triphosphate↗
Force-velocity relations of rat cardiac myosin isozymes sliding on algal cell actin cables in vitro.
The difference in kinetic properties between two myosin isozymes (V1 and V3) in rat ventricular myocardium was studied by determining the steady-state force-velocity (P-V) relations in the ATP-dependent movement of V1 and V3-coated polystyrene beads on actin cables of giant algal cells mounted on a centrifuge microscope. The maximum unloaded velocity of bead movement was larger for V1 than for V3. The velocity of bead movement decreased with increasing external load applied by the centrifuge microscope, and eventually reached zero when the load was equal to the maximum isometric force (P0) generated by the myosin heads. The maximum isometric force P0 was less than 10 pN, and did not differ significantly between V1 and V3. The P-V curves consisted of a hyperbolic part in the low force range and a non-hyperbolic part in the high force range. The critical force above which the curve deviated from the hyperbola was much smaller for V1 than for V3. An analysis using a model with an extremely small number of myosin heads involved in the bead movement suggested a marked difference in kinetic properties between V1 and V3.
Actins↗
Pimobendan directly sensitizes reconstituted thin filament to slide on cardiac myosin.
To elucidate the mechanism of the Ca(2+)-sensitizing action of pimobendan, cardiac thin filaments were reconstituted from actin and tropomyosin-troponin complex and made to slide on a myosin layer. Although filaments showed Brownian movement with a low Ca2+ concentration, they slid at a constant velocity above a certain level of Ca2+ concentration, showing that the sliding was regulated by Ca2+ within a narrow pCa range. Acidosis, addition of inorganic phosphate, and phosphorylation of troponin I increased the threshold Ca2+ concentration. Addition of pimobendan reversed these desensitization effects. These results clearly demonstrated that pimobendan directly increases the Ca2+ sensitivity of thin filament.
Animals↗
A new in vitro motility assay technique to evaluate calcium sensitivity of the cardiac contractile proteins.
We attempted to introduce calcium regulation into in vitro motility assay. Cardiac thin filament was reconstituted from actin and tropomyosin-troponin complex purified from rat myocardium separately. Double staining of the filaments showed tropomyosin-troponin complex was integrated along actin filaments homogeneously. The reconstituted thin filaments were made to slide on cardiac myosin fixed on a glass coverslip in the presence of MgATP while varying free Ca2+ concentration of the medium ([Ca2+]). Filaments showed only Brownian motion when [Ca2+] was below 10(-6.4) M. However, filaments slid at a constant velocity when [Ca2+] exceeded 10(-6.4) M, showing that the sliding was regulated in an on-off manner. The threshold [Ca2+] increased to 10(-5.0) M under acidic conditions, indicating a decrease in Ca2+ sensitivity of the contractile proteins. Simple actin filaments slid at a constant velocity independently of [Ca2+], demonstrating that the regulatory proteins were responsible for this on-off manner regulation. This new assay technique may be a powerful tool to directly evaluate the Ca2+ sensitivity of the contractile apparatus and to investigate how cardiac contraction is regulated by Ca2+.
Animals↗
Functional liver imaging with asialoglycoprotein receptors and serum hyaluronate in a patient with amyloidosis.
A 47-year-old man with primary amyloidosis was admitted with abdominal pain. A new radionuclide liver imaging technique using Technetium-99m diethylenetriamine-pentaacetic acid-galactosyl human serum albumin, was performed and the serum hyaluronate concentration was measured. Although ordinary laboratory tests revealed only slight abnormalities, the uptake of the radiolabelled ligand for hepatocyte asialo-glycoprotein receptors was decreased, and marked hepatomegaly was revealed. Furthermore, the serum hyaluronate level was elevated. Histological examination of a hepatic needle biopsy specimen revealed a marked deposition of amyloid in the hepatic perisinusoidal spaces. These results indicate that this new radionuclide liver imaging technique (using Technetium-99m diethylenetriamine-pentaacetic acid-galactosyl human serum albumin) and the measurement of serum hyaluronate may be useful supplementary tools for identifying amyloid deposition in the hepatic perisinusoidal spaces in patients with amyloidosis.
Amyloidosis↗
Effects of exercise on plasma level of brain natriuretic peptide in congestive heart failure with and without left ventricular dysfunction.
This study was designed to determine whether plasma brain natriuretic peptide (BNP) increases in response to exercise in patients with congestive heart failure and to show what kind of hemodynamic abnormalities induce increased secretion of BNP during exercise. Plasma levels of atrial natriuretic peptide (ANP) and BNP and hemodynamic parameters were measured during upright bicycle exercise tests in seven patients with dilated cardiomyopathy and nine with mitral stenosis. At rest, there were no intergroup differences in cardiac output or pulmonary capillary wedge pressure; however, the group with dilated cardiomyopathy had higher left ventricular end-diastolic pressures and lower left ventricular ejection fractions than did the group with mitral stenosis. Plasma ANP levels were comparable between the dilated cardiomyopathy group (170 +/- 77 [SE] pg/ml) and the mitral stenosis group (106 +/- 33 pg/ml) (p, not significant), whereas BNP was significantly higher in the dilated cardiomyopathy group (221 +/- 80 pg/ml) than in the other group (37 +/- 10 pg/ml) (p < 0.05). The plasma concentration of BNP but not of ANP significantly correlated with left ventricular end-diastolic pressure and volume. Exercise increased plasma ANP and BNP in the two groups. The dilated cardiomyopathy group had a larger increment in BNP (+157 +/- 79 pg/ml) than did the mitral stenosis group (+17 +/- 5 pg/ml) (p < 0.05), although the increase in pulmonary capillary wedge pressure was greater in the mitral stenosis group. Thus exercise increases plasma levels of BNP, and impaired left ventricular function may be a main factor in the greater increment in BNP during exercise in patients with congestive heart failure.
Atrial Natriuretic Factor↗
Role of hepatocytes in direct clearance of lipopolysaccharide in rats.
BACKGROUND & AIMS: The liver is the clearance organ for lipopolysaccharide (LPS). The aim of this study was to investigate the biliary excretion of LPS using fluorescein isothiocyanate (FITC)-labeled LPS. METHODS: After FITC-LPS was injected intravenously into rats, the cellular localization of fluorescence in the liver was examined and the biliary excretion of fluorescence was measured. The effects of gadolinium chloride, a blocker of Kupffer cells, and colchicine, an inhibitor of microtubules, on the biliary excretion of fluorescence was investigated, and bile was analyzed using high-performance liquid chromatography. RESULTS: Laser scanning confocal microscopy showed that fluorescence was taken up by hepatocytes 5 minutes after injection of FITC-LPS into the portal vein. When FITC-LPS was injected into the portal vein, fluorescence was rapidly secreted into bile, peaking at 20 minutes, and 25.1% of the injected dose appeared in bile within 60 minutes. When the same dose of FITC-LPS was injected into the tail vein, 15.8% appeared in bile within 60 minutes. Chromatography showed that FITC-LPS was excreted into bile in an unchanged form over a period of 20 minutes after injection. Colchicine significantly reduced the biliary excretion of fluorescence, but gadolinium chloride had no effect. CONCLUSIONS: LPS was directly and effectively processed by hepatocytes and secreted into the bile canalicular system via a microtubule-dependent vesicular pathway.
Animals↗
The roles played by the D2 and D3 domains of recombinant human thrombomodulin in its function.
Thrombomodulin (TM) is composed of five domains. We investigated the roles of the sixth epidermal growth factor (EGF)-like structure (E6) in the second domain (D2) and of an O-glycosylation site rich domain (D3) in the function of TM in more detail using deletion analysis. Two soluble mutants of TM, TMD123 and TMD12, and three deletion mutants lacking respectively 6, 16, and 38 C-terminal residues of the E6 portion, TMD12 delta 6, TMD12 delta 16, and TMD12 delta 38, were expressed in COS cells and purified. The results of protein C-activating cofactor assay showed that TMD12 delta 6, TMD12 delta 16, and TMD12 delta 38, which lack the C-terminal region, had remarkably weak cofactor activities in comparison with TMD123 (9.1, 1.4, and 1.1% of TMD123 activity, respectively). Similar findings were obtained for anticoagulant activity. These findings indicate that the last loop structure in E6 is required for full activity of recombinant human TM. We also determined in vivo stabilities of TMD12, TMD123, and TMD12 delta 6 in a pharmacokinetic study in rats. TMD12 and TMD12 delta 6, which lack the D3 domain, exhibited increased clearance (about twice that of D123). This finding suggested that the D3 domain of TM plays an important role in stabilizing TM in vivo.
Anticoagulants↗
Lichen planus and hepatitis C virus in the northern Kyushu region of Japan.
Oral lichen planus (OLP) is a common oral disorder that manifests a mucosal reaction to a variety of aetiological factors, including liver disorder. This study investigated the relationship between OLP and hepatitis C virus (HCV) infection by studying the prevalence of hepatitis B and C virus infection or liver disease in 45 patients with OLP in the Northern Kyushu region of Japan where the prevalence of HCV infection is the highest in the country. Serum hepatitis B virus surface antigen (HBsAg) was positive in only four patients. Serum anti-HCV or serum HCV RNA was positive in 28 (62%) and 27 (60%) of 45 OLP patients, respectively. The majority (35 of 45, 78%) of OLP patients suffered from liver disease, including chronic hepatitis C (22/45, 49%), HCV-related liver cirrhosis (two), and HCV-related hepatocellular carcinoma (two). These results suggest that HCV is a major cause of OLP.
Adolescent↗
A histopathological study of alcoholics with chronic HCV infection: comparison with chronic hepatitis C and alcoholic liver disease.
To clarify the relationship between hepatitis C virus infection and excessive alcohol intake, we carried out histological examination of the liver in 46 alcoholics with chronic hepatitis C virus infection and compared the findings in 55 patients with chronic hepatitis C, 38 with alcoholic liver disease, and 27 with chronic hepatitis B. The majority of alcoholics with chronic hepatitis C virus infection displayed virus-related histological changes very similar to those in chronic hepatitis C, including frequent lymphoid follicles (34.7%) or aggregates (93.3%) in the portal tracts, mild necroinflammatory change (76.1%) in the parenchyma, and lymphocytosis in sinusoids (83.7%). Liver cell dysplasia and irregular regenerative activity of hepatocytes were rarely observed. The effects of alcohol on the liver were found to be minimal in the majority. These findings could suggest that the hepatic injury in the majority of alcoholics with chronic hepatitis C virus infection in Japan is due to persistent hepatitis C virus infection rather than to alcoholic injury. In addition, our study disclosed that the perivenular fibrosis which is designated as a histological characteristic of alcoholic liver disease is frequently observed in chronic hepatitis C. These similarities suggest that a similar fibrogenesis is present in chronic hepatitis C and alcoholic liver disease.
Adult↗
High prevalence of hepatitis C virus antibody and RNA in patients with oral cancer.
We have investigated the correlation between the prevalence of hepatitis C virus (HCV), which is detectable in saliva, and oral cancer and other digestive tract cancers in the Northern Kyushu region of Japan. Anti-HCV antibodies were detected in sera from 24 of the 100 patients with oral cancer (24%, p < 0.05 vs the control group, p < 0.01 vs the stomach cancer group), in 11 of 104 patients with non-malignant diseases receiving dental treatment (the control group, 10.6%), and in 12 of 113 patients with stomach cancer (10.6%). HCV-RNA was detected in sera from 17 of 100 oral cancer patients (17%, p < 0.05 vs the control group) and 4 of 104 patients of the control group (3.9%). These results indicate a high prevalence of HCV infection in oral cancer patients, which warrants a systematic study of etiological associations between oral cancer and HCV.
Adolescent↗
Decrease of interferon-induced 2',5'-oligoadenylate synthetase activity in cirrhotic rat liver.
We evaluated the effect of hepatic fibrosis on the induction of hepatic 2',5'-oligoadenylate synthetase (2-5AS) by interferon (IFN) in a rat model of liver cirrhosis, induced with thioacetamide. Although there was no difference in serum 2-5AS activity between the control and cirrhotic rats given murine IFN, 2-5AS activity in the liver homogenates of cirrhotic rats was significantly lower than in the controls (105 +/- 18.5 vs. 171 +/- 10.2 pmol/micrograms, p < 0.01). These results suggested that hepatic fibrosis attenuated the effect of IFN and one of the reasons for this may be the decreased induction of hepatic 2-5AS activity after IFN administration in the presence of a cirrhotic liver.
2',5'-Oligoadenylate Synthetase↗
A case of oral lichen planus with chronic hepatitis C successfully treated by glycyrrhizin.
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Anti-Inflammatory Agents, Non-Steroidal↗
Evaluation of intestinal permeability in patients with inflammatory bowel disease using lactulose and measuring antibodies to lipid A.
This study looked at the intestinal permeability and the immune response to enteric bacterial antigens in patients with inflammatory bowel disease (IBD). They were evaluated by using a lactulose tolerance test and measuring blood anti-lipid A antibody concentrations, respectively. The lactulose tolerance tests were performed 22 times in 14 patients with Crohn's disease (CD), 19 times in 12 patients with ulcerative colitis (UC), and 12 times in 12 healthy controls. Blood lactulose concentrations were measured after oral administration every two hours for eight hours, also blood C reactive protein concentrations and anti-lipid A antibody concentrations were measured just before lactulose administration. Blood lactulose concentrations were significantly higher in patients with CD than in the controls from two to eight hours after administration, while in UC they were significantly higher than in the controls from six to eight hours. Maximum blood lactulose concentrations in each tolerance test in patients with the active phase significantly exceeded those in the inactive phase of either CD or UC. A significant correlation was also seen between the maximum blood lactulose concentrations and the C reactive protein concentrations. Blood anti-lipid A antibody concentrations in patients with CD were significantly higher than in the controls as well as in patients with UC in immunoglobulin (Ig) A class and IgG class. In UC they were significantly higher than in the controls in IgA class. But, they were not related to the severity of the disease of either CD or UC, and not correlated significantly with the maximum blood lactulose concentrations in either CD or UC. The intestinal permeability and the immune response to enteric bacterial antigens in patients with inactive CD were significantly increased over those in the controls as well as in patients with inactive UC. These findings suggest that an increase of the intestinal permeability and that of producing antibodies to enteric bacterial antigens are both important for the pathogenesis of IBD, and that the characteristics of CD and UC differ.
Adolescent↗
Structural and functional characteristics of peripheral pulmonary parenchyma in golden hamsters.
Mechanical properties of the peripheral pulmonary parenchyma of freshly excised hamster lung tissue were examined to evaluate determinants of displacement-tension relationships with regard to structural constituents of the alveolar wall. A tissue segment measuring 50 x 50 x 400-600 microns and consisting mostly of the alveolar wall was prepared from the lung parenchyma adjacent to the pleura. By use of a constant speed maneuver for extension and relaxation of this minute preparation, displacement-tension relationships of peripheral pulmonary parenchyma were examined in a bath filled with 37 degrees C physiological buffer solution. The specimen was repeatedly extended up to 20-40 mg, a little above a point resembling "yield" in displacement-tension relationships. Analyses of displacement-tension relationships constantly showed double exponential relations. The first component at the lower strain was approximated by sigma 1 = A1(e alpha 1 epsilon - 1) and the second component beyond the inflection (yield) point was sigma = s1 + s2 = A1(e alpha 1 epsilon - 1) + A2(e alpha 2 epsilon - 1), where sigma, A, alpha, and epsilon represent stress, constant determined by tissue quantity, elasticity constant, and strain, respectively. Immersion of the lung specimen into elastase resulted in decreases of only alpha 1, and collagenase reduced alpha 2 but not alpha 1. Hyaluronidase, acetylcholine, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and norepinephrine did not alter alpha 1 or alpha 2. These observations suggest that alpha 1 and alpha 2 of the peripheral pulmonary parenchyma are mechanical indexes of elastin and collagen characters, respectively.
Acetylcholine↗