[Secondary biliary cirrhosis].
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Cholestasis↗
Biomedical subjects
T Aramaki
Publications and source records attributed to T Aramaki.
Characterization of the calcium-sensitive voltage-gated delayed rectifier potassium channel in isolated guinea pig hepatocytes.
The voltage-dependent K+ channel was examined in enzymatically isolated guinea pig hepatocytes using whole-cell, excised outside-out and inside-out configurations of the patch-clamp technique. The resting membrane potential in isolated hepatocytes was -25.3 +/- 4.9 mV (n = 40). Under the whole-cell voltage-clamp, the time-dependent delayed rectifier outward current was observed at membrane potentials positive to -20 mV at physiological temperature (37 degrees C). The reversal potential of the current, as determined from tail current measurements, shifted by approximately 57 mV per 10-fold change in the external K+ concentration. In addition, the current did not appear when K+ was replaced with Cs+ in the internal and external solutions, indicating that the current was carried by K+ ions. The envelope test of the tails demonstrated that the growth of the tail current followed that of the current activation. The ratio between the activated current and the tail amplitude was constant during the depolarizing step. The time course of growth and deactivation of the tail current were best described by a double exponential function. The current was suppressed in Ca(2+)-free, 5 mM EGTA internal or external solution (pCa > 9). The activation curve (P infinity curve) was not shifted by changing the internal Ca2+ concentration ([Ca2+]i). The current was inhibited by bath application of 4-aminopyridine or apamin. alpha 1-Adrenergic stimulation with noradrenaline enhanced the current but beta-adrenergic stimulation with isoproterenol had no effect on the current. In single-channel recordings from outside-out patches, unitary current activity was observed by depolarizing voltage-clamp steps whose slope conductance was 9.5 +/- 2.2 pS (n = 10). The open time distribution was best described by a single exponential function with the mean open lifetime of 18.5 +/- 2.6 ms (n = 14), while at least two exponentials were required to fit the closed time distributions with a time constant for the fast component of 2.0 +/- 0.3 ms (n = 14) and that for the slow component of 47.7 +/- 5.9 ms (n = 14). Ensemble averaged current exhibited delayed rectifier nature which was consistent with whole-cell measurements. In excised inside-out patch recordings, channel open probability was sensitive to [Ca2+]i. The concentration of Ca2+ at the half-maximal activation was 0.031 microM. These results suggest that guinea pig hepatocytes possess voltage-gated delayed rectifier K+ channels which are modified by intracellular Ca2+.
4-Aminopyridine↗
Characterization of the calcium-activated chloride channel in isolated guinea-pig hepatocytes.
Macroscopic and unitary currents through Ca(2+)-activated Cl- channels were examined in enzymatically isolated guinea-pig hepatocytes using whole-cell, excised outside-out and inside-out configurations of the patch-clamp technique. When K+ conductances were blocked and the intracellular Ca2+ concentration ([Ca2+]i) was set at 1 microM (pCa = 6), membrane currents were observed under whole-cell voltage-clamp conditions. The reversal potential of the current shifted by approximately 60 mV per 10-fold change in the external Cl- concentration. In addition, the current did not appear when Cl- was omitted from the internal and external solutions, indicating that the current was Cl- selective. The current was activated by increasing [Ca2+]i and was inactivated in Ca(2+)-free, 5 mM EGTA internal solution (pCa > 9). The current was inhibited by bath application of 9-anthracenecarboxylic acid (9-AC) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) in a voltage-dependent manner. In single channel recordings from outside-out patches, unitary current activity was observed, whose averaged slope conductance was 7.4 +/- 0.5 pS (n = 18). The single channel activity responded to extracellular Cl- changes as expected for a Cl- channel current. The open time distribution was best described by a single exponential function with mean open lifetime of 97.6 +/- 10.4 ms (n = 11), while at least two exponentials were required to fit the closed time distributions with a time constant for the fast component of 21.5 +/- 2.8 ms (n = 11) and that for the slow component of 411.9 +/- 52.0 ms (n = 11). In excised inside-out patch recordings, channel open probability was sensitive to [Ca2+]i. The relationship between [Ca2+]i and channel activity was fitted by the Hill equation with a Hill coefficient of 3.4 and the half-maximal activation was 0.48 microM. These results suggest that guinea-pig hepatocytes possess Ca(2+)-activated Cl- channels.
Algorithms↗
Effect of long-term therapy with nipradilol on esophageal varices in patients with compensated cirrhosis. Results of a multicenter open study.
The effect of long-term administration of nipradilol (NIP, Hypadil Kowa, CAS 81486-22-8), a beta-blocker with a vasodilatory action, on esophageal varices was studied in 66 patients with compensated liver cirrhosis. Administration of NIP (6-12 mg/d) for 3-12 months produced progressive improvement of endoscopic findings over time (30% for C, 25% for F, and 40% for the R-C sign after 12 months). At the last examination (mean: 9 +/- 4 months), the improvement rates were 16.7%, 16.7% and 22.7%, respectively. No significant relationship was found between endoscopic improvement and the Child-Pugh score or the dose of NIP. Gastrointestinal bleeding occurred in five patients: one had bleeding esophageal varices, three had bleeding gastric varices, and one had a bleeding gastric ulcer. The systolic blood pressure was decreased significantly (4.6-12.3%) at 2 weeks as well as 1 and 2 months, and the heart rate showed a significant decrease throughout the study (10-18.4%). With the exception of the patients who had gastrointestinal bleeding, no symptoms of decompensation appeared, and there was no deterioration of laboratory parameters including ammonia. Adverse effects occurred in about 10% of the patients, most of which were related to bradycardia and/or hypotension, and they improved when the drug was withdrawn or the dose reduced. These results suggest that long-term administration of NIP is useful in the treatment of esophageal varices.
Adult↗
[Congestive (cardiac) cirrhosis].
As the incidence of cardiac cirrhosis at autopsy today is much lower than that from decades ago, true cardiac cirrhosis is a rare finding. With the decline in incidence of valvular disease, cardiomyopathy, in the etiology of congested liver, has increased. The pathophysiology of congestive heart failure consists of two components: forward failure with decreased hepatic blood flow and backward failure with congestive liver. Both lead to hepatocellular hypoxia. Increased serum transaminases and serum bilirubin correlate with reduction in cardiac output and elevation of venous pressure. Even when cardiac cirrhosis develops, it is difficult to diagnose clinically.
Heart Failure↗
Pathophysiological characteristics of cutaneous microcirculation in patients with liver cirrhosis: relationships to cardiovascular hemodynamics and plasma neurohormonal factors.
To elucidate pathophysiological characteristics of the peripheral circulation in liver cirrhosis, cutaneous microcirculation was analyzed at the finger, palm, toe, and arch of the foot using laser Doppler spectroscopy in 19 patients with liver cirrhosis, and the results were correlated with cardiovascular hemodynamics (n = 10) and plasma neurohormonal factors (n = 8). Cutaneous blood flow at each area was all significantly reduced (P < 0.001, < 0.05, < 0.01, < 0.001, respectively) in patients with liver cirrhosis compared to those in normals (n = 20). Cutaneous blood mass was also significantly reduced (P < 0.05, < 0.01, < 0.001, respectively) except at the arch of foot in patients with liver cirrhosis. There were significant correlations between finger cutaneous blood flow and systemic vascular resistance (r = -0.73, P < 0.05), plasma norepinephrine level (r = -0.84, P < 0.01), plasma renin activity (r = -0.77, P < 0.01), plasma concentrations of aldosterone (r = -0.76, P < 0.05) and angiotensin II (r = -0.76, P < 0.05), between palm blood flow and plasma vasoactive intestinal polypeptide concentration (r = 0.83, P < 0.05). From these results and our previous data demonstrating increased forearm muscular blood flow in patients with liver cirrhosis, increases in arteriovenous anastomotic flow and the contribution of neurohormonal factors will represent pathophysiological mechanisms for these changes.
Adult↗
(D-Ala, D-Leu) enkephalin reduces the binding of GTP in hippocampal membranes.
The effect of (D-Ala, D-Leu) enkephalin (DADLE) on the binding of GTP in hippocampal preparations was studied. It was observed that treatment of hippocampal slices with 10(-5) -5 x 10(-5) M DADLE followed by the preparation of membrane fractions reduced the binding of 35S-GTP-gamma-S. There was no change in the affinity of the binding. This decrease of 35S-GTP-gamma-S binding was reversed when 5 x 10(-5) M naltrindole was included. The effect was not observed when the membrane fractions were incubated with DADLE. Photoaffinity labeling with the use of 32P P3-(4-azidoanilido)-P1 5'-GTP followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed the incorporation of radioactivity into molecular mass of the 43 kDa and 33-34 kDa proteins. 32P Photolabeling of both the 43 kDa and 33-34 kDa bands decreased following treatment of hippocampal slices with 10(-4) M DADLE. These results suggested that DADLE reduces the GDP-GTP exchange in hippocampal membranes.
Affinity Labels↗
Plasma volume contraction in portal hypertension.
The effect of blood volume contraction induced by a 4-week regimen of spironolactone (100 mg/day) or furosemide (40 mg/day) on the hepatic venous pressure gradient (HVPG), an indicator of portal hypertension, was evaluated in patients with cirrhosis and no ascites. In the spironolactone group (n = 15), HVPG decreased significantly from 16.5 +/- 0.9 mmHg (mean +/- S.E.M.) to 12.9 +/- 1.0 mmHg (P < 0.005) and total blood volume contracted significantly from 4338 +/- 231 ml to 4006 +/- 203 ml (n = 14, P < 0.01). Although the HVPG changes did not correlate significantly with changes in measured total blood volume or in simultaneously determined systemic haemodynamics, a significant inverse correlation (r = -0.74, P < 0.01, n = 12) was found between the HVPG change and posttreatment plasma aldosterone levels, attesting to the effectiveness of spironolactone therapy in lowering HVPG. In the furosemide group (n = 10), neither HVPG (13.7 +/- 0.3 mmHg vs. 13.6 +/- 0.9 mmHg) nor total blood volume (4961 +/- 153 ml vs. 4964 +/- 162 ml) declined significantly. These results show that long-term administration of spironolactone to patients with cirrhosis and no ascites produced a significant reduction in HVPG that may have been due to gradual, sustained volume contraction. Thus, spironolactone may prove to be an effective treatment for portal hypertension in cirrhosis without ascites.
Aged↗
Hyperthyroidism in a patient with chronic hepatitis C during alpha-interferon therapy.
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Antithyroid Agents↗
[Studies on the treatment of chronic hepatitis C with interferon. Assessment of treatment regimens and response to treatment].
The difference in response rate to interferon (IFN) among several treatment regimens was assessed retrospectively in 48 HCV-RNA positive patients with chronic hepatitis C. The study focused on patients' pretreatment profiles and response to treatment, histological findings before and after the treatment and the significance of HCV-RNA detection in evaluating the outcome. A complete response (CR) evaluated by the outcome of alanine aminotransferase (ALT) was obtained in 16 of 25 patients (64.0%) treated with IFN in doses of 3 to 6 million units daily for the first 4 or 8 wks and subsequent dosing twice or three times weekly for the following 8 to 146 wks. In contrast, CR was obtained in only 7 of 16 patients (43.8%) treated with the regimen in which patients received IFN in doses of 1 to 6 million units daily for 4 to 8 wks and no subsequent IFN. In comparing the responders to IFN (25 cases) and the non responders (19 cases), there were no significant differences regarding patients' age, sex, the presence or absence of history of blood transfusion, pretreatment ALT values or histological magnitude, or total doses of IFN administered. When the basal and final biopsy samples were compared, Knodell's index of histological activity had decreased significantly in the responders but not in the non responders. In 24 of the 25 responders, HCV-RNA had disappeared from their serum at the end of treatment, and in 23 it remained undetectable 6 months after treatment. In contrast, in 6 of the 19 non responders HCV-RNA had become negative at the end of treatment but was detectable in all cases 6 months after treatment. Thus, it is concluded that (1) a regimen of daily administration for the first 4 or 8 wks with subsequent dosing twice or three times weekly was preferable in terms of obtaining frequent CR, (2) response to IFN cannot be predicted by a patient's pretreatment profile, (3) in responders, histological activity decreases, and (4) in responders, HCV-RNA becomes undetectable not only at the end of treatment but also 6 months after treatment.
Adult↗
Primary biliary cirrhosis associated with multiple myeloma.
An association between autoimmune disease and malignancy, in particular lymphoproliferative neoplasms, has been reported, as has an increased incidence of extrahepatic malignancy in primary biliary cirrhosis (PBC). Monoclonal immunoglobulin elevations in PBC are rare, and there have been only three cases in the literature of PBC associated with multiple myeloma. We describe a patient who was concurrently diagnosed as having PBC and multiple myeloma, and emphasize the need to consider myeloma when evaluating monoclonal gammopathy in PBC. We also discuss the possible mechanisms for the association of the two conditions.
Aged↗
Purification and properties of a decapping enzyme from rat liver cytosol.
A decapping enzyme has been purified about 2400-fold from rat liver cytosol. The decapping enzyme was shown to be fairly homogeneous by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The enzyme had an apparent molecular weight of 110,000 and consisted of two equal subunits. The enzyme hydrolyzed m7Guo5'PPP5'Ado to m7GMP and ADP. Analysis of the products produced from radioactively capped oligonucleotides and intact mRNA having 3H-cap suggests that the enzyme can hydrolyze capped mono- to pentanucleotides (m7Guo5'PPP5'N (where N = 1-5 nucleotides)) but not intact mRNA. The existence of methyl group at the N7 position of guanosine moiety of cap structure was necessary for the action of the decapping enzyme. This was confirmed by the comparison of the rates of hydrolysis of m7Guo5'PPP5'Ado by the enzyme in the presence of various nucleotides. The activity of enzyme was slightly stimulated by Na+, K+, NH4+, Ca2+ and polyamines. Mg2+ and Mn2+ were without effect on the enzyme activity.
Animals↗
Pollution due to volatile halocarbon compounds in biota.
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Animals↗
Long-term haemodynamic effects of a 4-week regimen of nipradilol, a new beta-blocker with nitrovasodilating properties, in patients with portal hypertension due to cirrhosis. A comparative study with propranolol.
To study the long-term effects of pharmacological combination therapy, a comparison was made of the haemodynamic changes in patients with cirrhosis and portal hypertension following a 4-week treatment of propranolol or nipradilol, a new nonselective beta-blocker with nitrovasodilating effect. Nipradilol (12 mg/dag, n = 12) significantly diminished wedged hepatic venous pressure (WHVP, 25 +/- 16%), the hepatic venous pressure gradient (HVPG, 20 +/- 12%), and estimated hepatic blood flow (EHBF, 18 +/- 16%). Propranolol (30 mg/day, n = 11) also caused a significant reduction in WHVP (22 +/- 21%) and HVPG (24 +/- 21%), but not in EHBF. The percentage of portal pressure reduction and the frequency of nonresponders did not differ between the nipradilol and propranolol groups. Both agents reduced heart rate by approx. 20%. Nipradilol, however, did not cause a significant reduction in cardiac index (CI) versus a 14% reduction by propranolol. Pulmonary capillary wedge pressure and central venous pressure, an index of preload, were decreased slightly in the nipradilol group. When nonresponders were excluded, there was a significant correlation of the percentage of reduction between WHVP and CI or systemic vascular resistance, in the nipradilol group. These results indicate that nipradilol may have potent hypotensive effects on portal hypertension, similar but not superior to propranolol. Nipradilol, at the dosage used in the present study, did not appear to exert a nitrovasodilating effect to enhance the portal pressure reduction induced by beta-blocking action.
Adrenergic beta-Antagonists↗
Formation of PhIP in a mixture of creatinine, phenylalanine and sugar or aldehyde by aqueous heating.
A mixture of 100 mM creatinine and 100 mM L-phenylalanine was heated at 60 or 37 degrees C in the presence of sugar or aldehyde. A mutagen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) formed in the model system was determined by reversed-phase HPLC. Any sugars tested induced the formation of PhIP when heated at 60 degrees C, though PhIP was not detected in a mixture without sugar. Among the sugars tested, D-erythrose and D-glyceraldehyde were more productive than pentose (D-arabinose and D-ribose) and hexose (D-glucose and D-galactose) in the yield of PhIP. Moreover, PhIP was formed even when a mixture of creatinine, L-phenylalanine and D-glucose or D-ribose was incubated at 37 degrees C for a long time. Both formaldehyde and acetaldehyde also induced the formation of PhIP, though PhIP was not detected in a mixture without sugar or aldehyde even when heated at 100 degrees C. These results indicate that PhIP can be formed at low-temperature heating and that either sugar or aldehyde is essential for PhIP formation in the model system. Our data also suggest that aldehydes may be a key reactant in the formation of PhIP in aqueous heating of the mixture of creatinine and L-phenylalanine.
Acetaldehyde↗
Long-term status of antibody to hepatitis C virus and the relation to the outcome of hepatitis: a retrospective study using stored sera from patients with Sashima epidemic hepatitis.
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Follow-Up Studies↗
Detection of a carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), in cigarette smoke condensate.
A carcinogenic heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), was measured in condensate of cigarette mainstream smoke by HPLC. PhIP was detected in all brands of filter-tipped cigarettes analyzed. The mean level of PhIP in the cigarette mainstream smoke was 16.4 ng/cig.
Chromatography, High Pressure Liquid↗
[The effect of extract from human tubercle bacilli (SSM) on HBeAg positive type B chronic hepatitis].
UNLABELLED: The effect on the HBeAg/anti-HBe system of SSM (specific substance Maruyama), an extract from human tubercle bacilli, was evaluated in patients with HBeAg positive type B chronic hepatitis. SUBJECTS AND METHODS: Twenty-five (25) HBeAg positive patients with biopsy-proven chronic hepatitis were injected subcutaneously with SSM solution twice a week for two years. Fifteen (15) comparable patients served as untreated controls for one year. HBeAg and anti-HBe were measured by the RIA method. RESULTS: (1) In the group receiving SSM injections, HBeAg disappeared in 8 out of 25 patients (32.0%) one year after the treatment and in 15 out of 23 (65.2%) within two years. Seroconversion from HBeAg to anti-HBe occurred in 5 of the 25 patients (20.0%) after one year and in 7 out of 23 (30.4%) within two years. Of the 15 untreated controls, HBeAg disappeared in 3 patients (20%), and seroconversion from HBeAg to anti-HBe occurred in 1 (6.7%) within one year. (2) In the SSM group, the HBeAg cut off index decreased significantly (p less than 0.01), from 5.2 +/- 1.9 during the pretreatment period to 2.7 +/- 2.3 twelve months after the treatment. (3) In the SSM group, a transient rise in sGOT and sGPT was observed in some patients three to nine months after starting the treatment. HBeAg disappeared in all these patients. (4) No notable side effects were observed in any of the patients treated with SSM. CONCLUSION: These results indicate that SSM treatment improves the HBeAg/anti-HBe system in patients with HBeAg positive chronic hepatitis.
Adolescent↗