Hepatitis C in hospital employees with needlestick injuries.
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Accidents, Occupational↗
Biomedical subjects
E Tanaka
Publications and source records attributed to E Tanaka.
Characterization of liver microsomal cytochrome P450 from rats treated with muscone (3-methylcyclopentadecanone).
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Animals↗
A high prevalence of antibody to the hepatitis C virus in patients with hepatocellular carcinoma in Japan.
In Japan, hepatocellular carcinoma (HCC) is one of the most prevalent cancers, with a reported fatality rate showing a consistent and significant increase in the last decade. At most, only 25% of HCC cases are positive for the hepatitis B surface antigen (HBsAg). To investigate a potential role for hepatitis C virus (HCV) in the development of HCC, sera from 105 HBsAg-negative HCC patients were collected from five districts of Japan and assayed for antibody to HCV antigen (HCVAb). A large number of these patients (76.2%) were found to be positive for the HCVAb in comparison with the reported prevalence in sera from blood donors (1.1%). A history of blood transfusion was found in 39.6% of the cases positive for HCVAb, which was significantly different to the lower rate (4.7%) observed in HCC patients who were both positive for HBsAg and negative for HCVAb (P less than 0.001).
Blood Transfusion↗
The effect of diltiazem on hepatic drug oxidation assessed by antipyrine and trimethadione.
The effect of pretreatment for 3 days with diltiazem 60 mg three times a day on the pharmacokinetics of 500-mg antipyrine and 250-mg trimethadione was studied in six healthy male subjects. Diltiazem decreased the total body clearance from 34.0 +/- 8.0 to 28.6 +/- 6.1 mL/min (P less than .01), and prolonged the elimination half-life from 12.6 +/- 3.0 to 14.3 +/- 2.5 hours (P less than .01) of antipyrine without any changes in volume of distribution. The cumulative renal excretion (% dose) of antipyrine was significantly increased from 2.23 +/- 0.73 to 2.78 +/- 0.83% (P less than .05). Clearances of production for three major antipyrine metabolites, norantipyrine (4.31 +/- 1.64 to 3.50 +/- 1.28 mL/min, P less than .01), 3-hydroxymethylantipyrine (4.67 +/- 1.63 to 3.82 +/- 1.34 mL/min, P less than .01) and 4-hydroxyantipyrine (10.47 +/- 3.41 to 8.16 +/- 2.82 mL/min, P less than .01) were reduced significantly by diltiazem. On the other hand, diltiazem did not produce any significant changes in pharmacokinetic parameters of trimethadione and plasma concentration ratio, oxidative major metabolite of trimethadione to trimethadione itself. These results suggest that other drugs metabolizing the same hepatic oxidative pathways as antipyrine, may be influenced by diltiazem.
Adult↗
Intrafamilial transmission of hepatitis C virus in Japan.
To clarify the intrafamilial transmission of hepatitis C virus (HCV), the prevalence of antibody to HCV (anti-HCV) in 107 index patients with type C chronic liver disease was studied and compared with the prevalence of anti-HCV antibody in their 296 family members. Of the 85 index patients who were positive for anti-HCV, 15 (8%) of 196 of their family members were also HCV antibody positive, whereas of the 22 index patients who were anti-HCV antibody negative, none of the family members of the 100 evaluated was positive for anti-HCV antibody, a statistically significant difference between groups (P less than 0.02). No specific relative (spouse, child, parent, and sibling) was linked to HCV positivity in the index cases making it difficult to identify the route of infection that is believed to occur via the parenteral route in the home or community.
Adolescent↗
Significance of antibody to hepatitis C virus in Japanese patients with viral hepatitis: relationship between anti-HCV antibody and the prognosis of non-A, non-B post-transfusion hepatitis.
In a retrospective study, antibody to hepatitis C virus (anti-HCV antibody) was measured in 80 patients with acute viral hepatitis (type A, 18; type B, 21; type non-A,non-B, 41). Anti-HCV antibody was found in 12 of 20 patients (60%) with non-A,non-B post-transfusion hepatitis (NANB-PTH) and in 9 of 21 patients (43%) with sporadic NANB hepatitis (NANB-SPO). Patients with acute hepatitis type A or type B did not have anti-HCV antibody. The number of patients who developed chronic hepatitis was greater in the group with anti-HCV antibody than in the anti-HCV negative group in both NANB-PTH and NANB-SPO. The difference was significant in those with NANB-PTH (P less than 0.05). To investigate the relationship between the long-term prognosis of NANB-PTH and the course of anti-HCV, we studied anti-HCV antibody in 12 patients who developed chronic type C hepatitis (C-CH) after PTH and followed them for more than 5 years after the development of PTH. One year after the development of PTH, all 12 had anti-HCV antibody. Five lost anti-HCV antibody (group 1) while 7 remained positive (group 2) at the final examination. Four of the 5 patients in group 1 had normal serum transaminases; however, abnormal transaminase persisted in all 7 patients in group 2 until the end of follow-up (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Identification of amino acid residues modified by two ATP analogs in Bacillus subtilis glutamine synthetase.
Bacillus subtilis glutamine synthetase was modified by two ATP analogs, 5'-p-fluorosulfonylbenzoyladenosine (FSBA) and 8-azidoadenosine 5'-triphosphate (8-N3-ATP), each one containing either Mg2+ or Mn2+. The FSBA labeled peptide was monitored by measuring the characteristic absorbance of the 4-carboxybenzenesulfonyl (CBS) part at 243 nm. The 8-N3ATP photolabeled peptide could also be monitored by measuring its absorption at 310 nm. A single CBS-labeled tryptic peptide was obtained, spanning residues 89-91 from the N-terminal of the subunit polypeptide chain, and sequence analysis by Edman degradation revealed that CBS-arginine was at position 91. The amino acids photolabeled by 8-N3ATP at the ATP-binding site in B. subtilis GS were His-186, His-187, and Trp-424. These results suggested that these four amino acids constitute an ATP-binding active site located at the interface between two subunits. The region surrounding Trp-424, which varies among different prokaryotic enzymes, was considered to be involved in a catalytic or regulatory role in B. subtilis GS. Since the same amino acids were labeled when B. subtilis GS was modified with FSBA or 8-N3ATP in the presence of Mn2+ or Mg2+, no conformational difference between B. subtilis GS binding Mn(2+)-ATP and that binding Mg(2+)-ATP was detected by affinity labeling with ATP analogs.
Adenosine↗
The effects of diltiazem on hepatic drug metabolizing enzymes in man using antipyrine, trimethadione and debrisoquine as model substrates.
Six healthy male subjects were given single oral doses of antipyrine (7 mg kg-1), trimethadione (4 mg kg-1) and debrisoquine (10 mg) before and during diltiazem treatment (30 mg three times daily orally for 8 days). Antipyrine clearance decreased from 33.7 +/- 9.1 to 22.5 +/- 4.9 ml min-1 (P less than 0.05, mean +/- s.e. mean) after diltiazem treatment without any significant change in apparent volume of distribution (0.59 +/- 0.06 to 0.60 +/- 0.04 1 kg-1), resulting in an increase in antipyrine elimination half-life from 13.4 +/- 4.8 to 19.7 +/- 3.2 h (P less than 0.05). The formation clearance of antipyrine to 4-hydroxyantipyrine was decreased significantly from 10.8 +/- 2.7 to 6.6 +/- 2.7 ml min-1 (P less than 0.05), while that to 3-hydroxymethylantipyrine and norantipyrine was not altered by diltiazem. The metabolic ratio of debrisoquine (urinary excretion of debrisoquine/4-hydroxydebrisoquine) was increased significantly from 0.70 +/- 0.05 to 1.95 +/- 0.20 (P less than 0.05), while that of trimethadione (serum concentration of dimethadione/trimethadione) was not changed significantly (0.48 +/- 0.08 vs 0.41 +/- 0.06) after diltiazem treatment. Diltiazem selectively inhibits cytochrome P-450 isoenzymes.
Adult↗
Antibody to the hepatitis C virus in acute hepatitis and chronic liver diseases in Japan.
In a 6-month follow-up study of acute hepatitis in Japan, 31 out of 41 (75.6%) cases of post-transfusion non-A and non-B hepatitis (NANB-PTH) and 14 out of 40 (35.0%) cases of sporadic non-A non-B hepatitis (NANB-SPO) were found to be positive for antibody to the hepatitis C virus (HCVAb). After 12 months of follow-up, 30 cases (81.1%) became chronic among 37 HCVAb positive acute NANB hepatitis cases. This figure shows a significantly higher rate of chronicity as compared with HCVAb negative acute NANB hepatitis. The prevalences of HCVAb in hepatitis B surface antigen (HBsAg) negative cases of chronic hepatitis and liver cirrhosis were 76.3% (200/262) and 66.7% (106/159), respectively, which were significantly different from the values of 5.1% (13/255) and 10.6% (13/123) observed in HBsAg positive cases. Of chronic liver disease cases positive for HCVAb, 45.8% (152/332) had a history of blood transfusion, in contrast to the value of 3.7% (13/352) observed in HBsAg positive cases of chronic liver disease that were negative for HCVAb.
Enzyme-Linked Immunosorbent Assay↗
Expression of hepatitis B surface antigen subtypes in liver of patients with hepatocellular carcinoma; comparison of subtypes in serum and liver.
To clarify the discrepancy in hepatitis B surface antigen (HBsAg) subtypes present in the serum and liver, as well as among hepatocytes, liver specimens which were resected from 37 HBsAg-positive patients with hepatocellular carcinoma (HCC) were examined. We evaluated HBsAg and the subtypic determinants of HBsAg and hepatitis B core antigen (HBcAg) using the peroxidase-antiperoxidase (PAP) staining method. Hepatitis B antigens were more frequently detected in small tumors (HBsAg in 67%. HBcAg in 40%) than in large ones (HBsAg in 36%, HBcAg in 14%). The prevalence of each subtypic determinant in the HBsAg positive non-tumorous vs. tumorous areas was 100% vs. 67% in a, 100% vs. 57% in d, 100% vs. not tested in y, 100% vs. 53% in r and 25% vs. 0% in w (a, d, y, r and w represent subtypic determinants). There was virtually no difference in a set of subtypic determinants between the serum and liver. However, there were some variations in a set of subtypic determinants among the hepatocytes. On the other hand, liver tissue of compound subtype adyr in serum contained both cells with a,d,r and with a,y,r as well as a few cells with a,d,y,r. These findings suggest that HBV genomes in hepatocytes of type B chronic liver disease may differ genetically among cells even in the same liver tissue.
Adult↗
Detection of elastase production in Escherichia coli with the elastase structural gene from several non-elastase-producing strains of Pseudomonas aeruginosa.
The elastase structural gene from Pseudomonas aeruginosa IFO 3455 has been cloned and sequenced. Using this gene as a probe, we cloned the DNA fragments (pEL3080R, pEL10, and pEL103R) of the elastase gene from non-elastase-producing strains (P. aeruginosa IFO 3080, N-10, and PA103 respectively). These three Pseudomonas strains showed no detectable levels of elastase antigenicity by Western blotting (immunoblotting) or by elastase activity. When elastase structural genes about 8 kb in length were cloned into pUC18, an Escherichia coli expression vector, we were able to detect both elastase antigenicity and elastolytic activity in two bacterial clones (E. coli pEL10 and E. coli pEL103R). However, neither elastolytic activity nor elastase antigenicity was detected in the E. coli pEL3080R clone, although elastase mRNA was observed. The partial restriction map determined with several restriction enzymes of these three structural genes corresponded to that of P. aeruginosa IFO 3455. We sequenced the three DNA segments of the elastase gene from non-elastase-producing strains and compared the sequences with those from the elastase-producing P. aeruginosa strains IFO 3455 and PAO1. In P. aeruginosa N-10 and PA103, the sequences were almost identical to those from elastase-producing strains, except for several nucleotide differences. These minor differences may reflect a microheterogeneity of the elastase gene. These results suggest that two of the non-elastase-producing strains have the normal elastase structural gene and that elastase production is repressed by regulation of this gene expression in P. aeruginosa. Possible reasons for the lack of expression in these two strains are offered in this paper. In P. aeruginosa IFO 3080, the sequence had a 1-base deletion in the coding region, which should have caused a frameshift variation in the amino acid sequence. At present, we have no explanation for the abnormal posttransciptional behavior of this strain.
Amino Acid Sequence↗
Membrane properties of guinea pig cingulate cortical neurons in vitro.
1. The passive and active membrane properties of guinea pig cingulate cortical neurons were studied in vitro using the slice preparation. Results were reported for intracellular recordings made from neurons that were penetrated in layers V/VI of the anterior cingulate cortex areas 1 and 3. 2. The neurons had an average resting potential of -71 mV, an input resistance of 71 M omega, a spike amplitude of 93 mV, and a spike duration of 1.6 ms. The firing occurred regularly at an average rate of 13 spikes/s at the membrane potential of -55 mV, suggesting that they are probably regular spiking pyramidal cells. 3. The voltage decay following a hyperpolarizing current pulse could always be fitted by two exponentials in most cells. The slope of the charging function was analyzed to estimate the two cable theory parameters of the neurons, based on a simple Rall model: the electrotonic length (LN) of the equivalent dendritic cylinder and the conductance ratio (rho) of the dendrites to that of the soma. There were no significant differences in the LN (0.9-1.1) and the rho (2.8-3.0) of neurons in normal media and solutions containing tetrodotoxin (TTX), Cs+ and low Ca2+, indicating that the neurons may be electrically compact. 4. In most cells the steady-state current-voltage (I-V) relationship revealed three distinct types of rectification: an anomalous inward rectification in the hyperpolarizing direction, a subthreshold inward rectification, and a delayed outward rectification in the depolarizing direction. 5. The anomalous rectification was increased in high K+ solutions and was decreased in low K+ solutions. Analysis of the Ba2+ and Cs+ sensitivity confirmed that the anterior cingulate neurons had two distinct types of anomalous rectification, one that was time dependent and Ba2+ insensitive and the other that was fast and Ba2+ sensitive. Ionic analyses indicated that the time-dependent anomalous rectification was due to an increased permeability to both Na+ and K+, whereas the fast, Ba(2+)-sensitive rectification was probably only K+ dependent. 6. The subthreshold inward rectification was depressed by TTX, lidocaine, or Co2+, as well as the reduction of extracellular Na+, whereas it was augmented by extracellular Ba2+. This persistent Na(+)-Ca2+ conductance triggered the generation of Na(+)-dependent action potentials. 7. The delayed outward rectification was recorded in the potential range between -65 and -20 mV.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Synaptic responses of guinea pig cingulate cortical neurons in vitro.
1. Intracellular recordings were made from layer V/VI neurons of the guinea pig anterior cingulate cortex to investigate postsynaptic potentials (PSPs) evoked by electrical stimulation of the subcortical white matter (forceps minor). 2. Four distinct types of PSPs were recorded (at the resting potential) under normal physiological conditions; 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive excitatory postsynaptic potentials (EPSPs) were followed by bicuculline- or picrotoxin-sensitive depolarizing or hyperpolarizing inhibitory postsynaptic potentials (IPSPs), which were further followed by phaclofen-sensitive, long-lasting hyperpolarizing postsynaptic potentials (LPSPs). The average times-to-peak for the EPSP, depolarizing and hyperpolarizing IPSPs, and LPSP were 10, 22, 28, and 146 ms, respectively. 3. In the presence of CNQX and bicuculline, high-intensity electrical stimulation elicited a longer lasting EPSP with a time-to-peak of 21 ms. The amplitude and duration of the EPSP decreased with membrane hyperpolarization and increased with membrane depolarization. The EPSP was reversibly abolished by D,L-2-amino-5-phosphonovaleric acid (D,L-APV). 4. The bicuculline- or picrotoxin-sensitive depolarizing and hyperpolarizing IPSPs and the phaclofen-sensitive LPSP were markedly suppressed by CNQX, suggesting that glutamate (Glu) and/or aspartate nerve terminals project to GABAergic interneurons, and that the GABAergic interneurons are activated mainly by non-N-methyl-D-aspartate (non-NMDA) receptors. 5. In the presence of picrotoxin, the average reversal potential for the compound EPSP was 0 mV, which was similar to that (-6 mV) for the Glu-induced depolarization. In a solution containing D,L-APV at low concentrations, the average reversal potentials for the depolarizing and hyperpolarizing IPSPs and for the early and late components of the gamma-aminobutyric acid (GABA)-induced responses were -62, -72, -70, and -61 mV, respectively. Thus the value for the depolarizing IPSP was similar to that for the late response to GABA, whereas the value for the hyperpolarizing IPSP was almost the same as that for the early response to GABA. The average reversal potential of -90 mV for the LPSP was similar to -93 mV for the baclofen-induced hyperpolarization and to -94 mV for the spike afterhyperpolarization. 6. Application of phaclofen decreased the interspike interval of the spontaneous firing and reversed the increase in the interspike interval after subcortical stimulation. This result indicates that, even in a slice preparation, the anterior cingulate neurons are under tonic inhibitory control exerted by spontaneously active GABAergic interneurons.(ABSTRACT TRUNCATED AT 400 WORDS)
2-Amino-5-phosphonovalerate↗
The elastic modulus of the temporomandibular joint disc from adult dogs.
The present study was designed to measure the elastic properties of temporomandibular joint (TMJ) discs from six adult dogs. Each disc was divided mediolaterally into medial, middle, and lateral parts. Under tension, the articular disc exhibited a non-linear stress-strain relationship, which could be represented as two lines (two moduli of elasticity) connected at a point of stress around 1.5 MPa. These two elastic moduli of the disc were approximately 44 MPa and 92 MPa in the lower- and higher-stress regions, respectively. Elastic moduli of the articular disc in the middle area were significantly different from that in the lateral area of the disc. The reaction to external force appeared to be different in the medial, middle, and lateral regions of the disc.
Animals↗
Influence of liver damage on antipyrine metabolite formation in rats.
1. The effects of three types of liver damage induced by carbon tetrachloride (CCl4), D-galactosamine (Ga1N) and alpha-naphthylisothiocyanate (ANIT) on antipyrine (AP) metabolism was studied in rats. 2. The serum half-life (t1/2) of AP (50 mg/kg, i.p.) was increased and total body clearance (CL) decreased in all three types of liver damage; the apparent volume of distribution (Vd) was relatively unchanged. 3. Rates of formation of AP metabolites (CLm) were lower than those in the control group in all three types of liver damage. 4. Rates of urinary excretion (% dose) of AP metabolites, 3-hydroxymethylantipyrine (HMA) and 3-hydroxymethyl-3-norantipyrine (NORA) were decreased in all three types of liver damage. However, the rate for 4-hydroxyantipyrine (OHA) was lower only in the Ga1N-treated rats. 5. The percentage conjugation of HMA was higher in the ANIT-treated rats than in the control group, and percentage conjugation of NOR was lower only in the Ga1N-treated rats. 6. These results indicate that the pathways of oxidation and conjugation of AP metabolism are not affected to the same extents by different types of liver damage.
1-Naphthylisothiocyanate↗
Murine monoclonal anti-Ba antibody that enhances haemolytic activity of factor B.
A murine monoclonal antibody (mAb 20-ET) (IgG1, kappa) was selected from a panel of stable hybridomas produced by fusion of P3-X-63-Ag8-U1 (P3UI) myeloma cells with spleen cells from a BALB/c mouse immunized with human factor B. This antibody was shown by the immune blotting method to be directed against the Ba domain of factor B. The haemolytic activity of factor B was enhanced dose-dependently by mAb 20-ET when it was incubated with factor B and EAC4b, 3b cells (sensitized erythrocytes bearing complement fragments C4b and C3b). However, when the antibody was added after factor B had been bound to EAC4b,3b cells and the cells had been washed, it caused little enhancement of the haemolytic activity. The enhancing effect of this antibody was not due to its stabilization of the C3b-B complex, because EAC4b,3b dissociated from mAb 20-ET-bound factor B complexes rather more readily than from uncomplexed factor B. The presence of mAb 20-ET in the reaction mixture caused and maintained a much higher steady-state level of binding of factor B with EAC4b,3b cells than that in its absence. Factor P caused delayed dissociation of mAb-bound factor B from EAC4b,3b cells, thus enhancing the haemolytic activity of factor B bound with the mAb.
Animals↗
Trimethadione tolerance test for one-point estimation of the severity of liver damage in cirrhotic patients.
We evaluated the adequacy of the trimethadione (TMO) tolerance test (the method of estimation from the serum dimethadione [DMO]/TMO ratio, DMO is only one metabolite of TMO, at 4 hours after oral administration of TMO) for estimating the severity of liver damage in 40 cirrhotic patients with and without hepatic encephalopathy. Serum dimethadione (DMO)/TMO ratios in a single blood sample after oral administration of TMO were significantly lower in cirrhotic patients with (0.07 +/- 0.02, p less than 0.05) or without (0.29 +/- 0.12, p less than 0.05) hepatic encephalopathy than in normal subjects (0.63 +/- 0.04). Serum DMO/TMO rations showed a good correlation with the following laboratory data: plasma indocyanine green retention at 15 minutes (r = -0.857, p less than 0.001), serum choline-esterase activity (r = 0.844, p less than 0.001), and albumin (r = 0.736, p less than 0.001). In cirrhotic patients with hepatic encephalopathy, the serum DMO/TMO ratio was found to be below 0.10, which was 16% of the normal level, by the TMO tolerance test. These findings suggest that the TMO tolerance test is a useful indicator of the hepatic parenchymal function in cirrhotic patients.
Dimethadione↗
[Infection route of non-transfused type C hepatitis].
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Cross Infection↗