bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversal of Ethanol and Indomethacin–Induced Suppression of Hepatic Dna Synthesis by 16,16–Dimethyl Prostaglandin E2
Authors: McNeil Gloria E. , Chen Thomas S. , Leevy Carroll M. 
Published: March 2007

Investigations were undertaken to determine effectiveness of 16,16–dimethyl prostaglandin E2 (dmPGE2) in overcoming the suppressive effects of ethanol and/or indomethacin on hepatic DNA synthesis. Adult litter mate Sprague–Dawley rats were subjected to sham operation or partial hepatectomy. Immediately after partial hepatectomy, and at 8–hr intervals for 24 hr, the rats were given: (a) ethanol with and without dmPGE2 or (b) indomethacin with and without ethanol and/or dmPGE2. DmPGE2 produced a significant increase in DNA synthesis in sham–operated (p < 0.001) and untreated partially hepatectomized animals (p < 0.025). Ethanol and indomethacin caused a 6– and 18–fold reduction, respectively, in hepatic DNA synthesis following partial hepatectomy. DmPGE2 overcame the inhibitory effect of ethanol (p < 0.005) and indomethacin (p < 0.0005) in partially hepatectomized animals. Mitoses were decreased concomitantly with ethanol and/or indomethacin–induced reduction in DNA synthesis and increased with administration of dmPGE2.
It is concluded that dmPGE2 increases hepatic DNA synthesis and regeneration in normal rat liver and overcomes their inhibition when ethanol and/or indomethacin is given after partial hepatectomy. Timing of dmPGEz administration is crucial. When given 30 min before ethanol, it completely inhibits suppression of regenerative activity; omission of this “priming” dmPGE2 dose results in only 44% of DNA synthesis obtained in control animals.
Liver Plasma Membrane: the Source of High Molecular Weight Alkaline Phosphatase in Human Serum
Authors: De Broe Marc E. , Roels Frank , Nouwen Etienne J. , Claeys Lutgarde , Wieme Roger J. 
Published: March 2007

This study presents biochemical, histochemical, morphological and immunological evidence that part of the high molecular weight alkaline phosphatase observed in the serum of patients with liver disease and particularly in cases of intrahepatic cholestasis or focal–, extrahepatic obstruction originates from the liver plasma membrane.
The high molecular weight protein alkaline phosphatase complex contains several plasma membrane enzymes and behaves like a plasma membrane fragment after isopycnic density gradient ultracentrifugation in sucrose, cesium chloride and metrizamide. Electron microscopic examination revealed a triple–layered vesicle which retained alkaline phosphatase activity. Incubation of human liver cells with anti–serum against purified high molecular weight multienzyme complex resulted in fixation of antibodies on the plasma membrane as shown by positive plasma membrane fluorescence. These plasma membrane fragments in the serum are not of biliary origin.
Aldehyde Dehydrogenase in Alcoholic Subjects
Authors: Palmer Kelvin R. , Jenkins William J. 
Published: March 2007

Hepatic aldehyde dehydrogenase activity is depressed in alcoholic liver disease and may account for the observation that alcoholics develop high blood acetaldehyde concentrations following ethanol. To determine whether this is a specific defect in alcoholics, aldehyde dehydrogenase was studied in liver tissue obtained from three groups of subjects. Group I comprised 30 patients with alcoholic liver disease, Group II consisted of eight subjects with liver disease unrelated to alcohol abuse and Group III was a control group of 10 individuals with no significant liver disease. Mean hepatic aldehyde dehydrogenase activity was significantly lower in Group I than in Groups II or III [4.9 ± 0.6 (mean ± S.E.), compared to 10.2 ± 1.8 and 12.4 ± 1.1 nmoles of acetaldehyde oxidized per min ± mg of protein, respectively]. Aldehyde dehydrogenase activity in Group II was relatively well maintained.
Aldehyde dehydrogenase activity was found in cytosolic and mitochondrial fractions of liver homogenates. In alcoholic subjects, cytosolic aldehyde dehydrogenase activity was not more depressed than was mitochondrial aldehyde dehydrogenase. Isoelectric focusing demonstrated a single mitochondrial isoenzyme and a single cytosolic isoenzyme in most cases in Group III. In contrast, multiple cytosolic isoenzymes were consistently found in liver tissue from Group I subjects.
These findings suggest that depressed aldehyde dehydrogenase activity in alcoholic subjects is not a consequence of liver disease.
Age–Related Changes in the Endocytic Capacity of Rat Liver Kupffer and Endothelial Cells
Authors: Brouwer Adriaan , Barelds Roel J. , Knook Dick L. 
Published: March 2007

There are many indications that the functional capacity of the reticuloendothelial system (RES) declines with age. The aim of this study was to investigate the cellular basis of age–related changes in the clearance function of the RES. The experiments were focused mainly on Kupffer and endothelial cells of the liver which represent a major part of the RES and are primarily responsible for clearance of colloidal material from the circulation. The clearance capacity of the RES was tested clinically and experimentally by intravenous injection of colloids, such as radiolabeled heataggregated colloidal albumin.
Age–related changes in the endocytosis of 125I–labeled colloidal albumin (CA) in rats were determined by clearance and organ distribution of different doses of intravenously injected CA, uptake of CA by Kupffer and endothelial liver cells in vivo as determined after isolation of the cells from injected rats and kinetic studies on CA uptake by Kupffer cells in culture.
The results show that, at a low dose, the clearance of CA is primarily determined by liver blood flow. At a higher saturating dose, plasma clearance and uptake by the liver are not significantly decreased with age. Endocytosis by endothelial cells, which accounts for about 60% of that of the whole liver, is also unchanged with age. In contrast, a significant decrease in endocytic capacity was observed for Kupffer cells in vivo. This age–related functional decline was also observed in Kupffer cells which were isolated from rats of different ages and maintained in culture. It is concluded that the overall capacity of the liver to clear the circulation of colloidal material is not necessarily affected by age. However, the Kupffer cell–specific decrease in endocytic capacity with advancing age may be important in the increased sensitivity to agents which are exclusively removed by Kupffer cells.
Hepatic Clearance of Rat Liver Aspartate Aminotransferase Isozymes: Evidence for Endocytotic Uptake Via Different Binding Sites on Sinusoidal Liver Cells
Authors: Horiuchi Seikoh , Kamimoto Yukio , Morino Yoshimasa 
Published: March 2007

Rat liver aspartate aminotransferase (AAT) (EC 2.6.1.1) exists in two isozymic forms, cytosolic (c–AAT) and mitochondrial (m–AAT). The previous study (Kamimoto, Y. et al., Hepatology an accompanying paper in this issue) demonstrated that these isozymes were cleared from blood at different half–lives via adsorptive endocytosis by sinusoidal liver cells. To understand the cellular mechanism for the differential uptake of the isozymes, we have further studied in vivo uptake of 125I–labeled AAT isozymes by sinusoidal cells. The results indicated that the uptake of the isozymes occurred via a typical endocytotic pathway: the initial binding, internalization and subsequent degradation in the lysosomes. Quantitation of the isozymes bound to the cell surface prior to internalization either by binding at 4°C or by a combined use of anti–AAT antibody and 125I–protein A at 37°C revealed that the differential plasma clearance of AAT isozymes could be attributable to the isozymic difference in capacity of surface membranes to bind the isozymes. The uptake of 125I–c–AAT was inhibited by unlabeled c–AAT more significantly than by m–AAT, but not by other ligands known to be taken up by sinusoidal cells via receptor–mediated pathways. Similarly, the uptake of 125I–m–AAT was inhibited predominantly by unlabeled m–AAT. Similar ligand specificity was also demonstrated in the binding study at 4°C. The binding of 125I–m–AAT and c–AAT followed saturation kinetics with an apparent Kd of 1.3 × 10-6
M and 1.7 × 10-6
M, respectively.
These findings indicate that differential uptake of AAT isozymes results from the presence on the surface membrane of two binding sites with a definite specificity for each isozyme.
Portal Pressure, Presence of Gastroesophageal Varices and Variceal Bleeding
Authors: Garcia-Tsao Guadalupe , Groszmann Roberto J. , Fisher Rosemarie L. , Conn Harold O. , Atterbury Colin E. , Glickman Morton 
Published: March 2007

This study was performed to examine the relationships between portal pressure measurements and the presence of esophagogastric varices, the size of varices and the occurrence of hemorrhage from varices in 93 patients with alcoholic cirrhosis, using standardized measurements of portal pressure by hepatic vein catheterization.
The mean hepatic vein pressure gradient (HVPG) was significantly higher in 49 patients who had bled from varices than in 44 cirrhotic patients who had not (20.4 ± 5.1 vs. 16.0 ° 5. 2; p < 0.001). None of the 49 patients who had bled from varices had an HVPG <12 mm Hg. Among the 87 patients who had been examined by endoscopy for varices, all 72 with varices had an HVPG > 12 mm Hg. Six of 15 cirrhotic patients without varices had HVPG < 12 mm Hg.
The mean HVPG in the 15 patients without varices (15.1 ± 6.8 mm Hg) was lower than the 72 patients with varices (19.3 ± 4.8 mm Hg; p < 0.01).
Of the 72 patients with varices, 40 had large varices, 28 had small varices, and in four patients variceal size coukt not be assessed adequately. The mean HVPG was similar in the patients with large or small varices (19.8 ± 4.8 vs. 18.3 ± 5.0 mm Hg; p < 0.10).
There was a positive relationship between the presence of large varices and the occurrence of bleeding from varices. Thirty–three of the 46 patients who had bled from varices had large varices (72%) compared to 7 of the 22 who had not bled from varices (32%) (p < 0.01).
The mean HVPG was similar in groups with large varices who had bled (20.3 ± 4.9) and in the group with small varices who had bled (20.2 ± 6.2 mm Hg) (p > 0.10). The mean HVPG in the groups of patients with large varices who had not bled was similar to those with small varices who had not bled (17.3 ± 3.1 vs. 16.7 ± 3.2 mm Hg) (p > 0.10). In both groups, the pressure was lower in those who had not bled.
We confirm previous observations that an HVPG > 12 mm Hg is necessary for the occurrence of variceal hemorrhage. We note in addition that this pressure gradient is necessary for the appearance of gastroesophageal varices. Elevated portal pressure plays a major role in the development of esophageal varices, but other factors contribute to the precipitation of hemorrhage from varices. All of these factors, which include size of the varix, thickness of the wall and transmural pressure are integrated in the wall stress formula, which is based on the LaPlace formula. Risk factors are multiple and variable and may interact in the individual patient to precipitate variceal hemorrhage.
Immunofluorescent Determination of the Lobular Distribution of A Constitutive Form of Hepatic Microsomal Cytochrome P–450
Authors: Moody David E. , Taylor Lorna A. , Smuckler Edward A. 
Published: March 2007

We have used an immunohistochemical approach to study the lobular distribution of constitutive liver microsomal cytochrome P–450. Cytochrome P–450 isolated (10.3 nmoles per mg protein) from hepatic microsomes from untreated, mature male Sprague–Dawley rats was used to produce antisera in rabbits. The IgG fraction produced single precipitin lines of identity with liver microsomes after double immunodiffusion, precipitated 80% of the total microsomal cytochrome P–450 and inhibited three cytochrome P–450–dependent enzyme activities. By these criteria, the IgG appeared to be specific for a constitutive form (or immunochemically related family) of liver microsomal cytochrome P–450.
The pattern of fluorescence after indirect immunofluorescent labeling of liver sections depended on the route of tissue preparation and the concentration of primary antibody. In frozen sections, the labeling was uniform throughout the lobule, whereas in “antigen–depleted” paraffin–embedded sections it was heaviest in the centrilobular and midzohal regions. Increasing the concentration of primary antibody to 500 μg per ml inhibited the centrilobular labeling in frozen sections in a concentration–dependent manner. When specific isozymes of cytochrome P–450 were induced with phenobarbital or 3–methylcholanthrene, the constitutive cytochrome P–450 was localized predominantly in the periportal region. Decreases in cytochrome P–450 in rats treated with carbon tetrachloride or 1,2–dibromo–3–chloropropane were associated with antigen loss only in necrotic cells. Regional differences in the loss of antigen in paraffin sections and the inhibition of fluorescence in frozen sections establish that the lobular distribution of constitutive hepatic microsomal cytochrome P–450 is qualitatively heterogeneous and may be altered during hepatocellular responses to chemical treatment.
Transferrin Metabolism in Alcoholic Liver Disease
Authors: Potter Barry J. , Chapman Roger W.G. , Nunes Rosa M. , Sorrentino Dario , Sherlock Sheila 
Published: March 2007

The metabolism of transferrin was studied using purified 125I–labeled transferrin in 11 alcoholic patients; six with fatty liver and five with cirrhosis. Six healthy subjects whose alcohol intake was les than 40 gm daily were studied as a control group.
There were no significant differences in the mean fractional catabolic rate and plasma volume in the alcoholic groups when compared with control subjects. A significantly decreased mean serum transferrin concentration was found in the alcoholic cirrhotic patients (1.8 ± 0.3 gm per liter vs. 2.9 ± 0.2; p < 0.01), resulting from diminished total body synthesis (0.9 ± 0.2 mg per kg per hr vs. 1.8 ± 0.2; p < 0.01). In contrast, in the patients with alcoholic fatty liver, the mean total body transferrin synthesis (2.4 ± 0.3 mg per kg per hr) was significantly increased when compared with controls (p < 0.05).
For all the alcoholic patients, the serum transferrin correlated with transferrin synthesis (r = +0.70; p < 0.01) but the serum iron did not.
These results suggest that, in alcoholic cirrhosis, transferrin synthesis is decreased, probably reflecting diminished synthetic capacity by the liver. In contrast, in patients with alcoholic fatty liver, transferrin turnover is accelerated.
Function of the Autonomic Nervous System in Patients With Hepatic Encephalopathy
Authors: Lenz Kurt , Hörtnagl Heide , Magometschnigg Dieter , Kleinberger Gunter , Druml Wilfred , Laggner Anton 
Published: March 2007

To obtain further pathophysiological details concerning the development of cardiovascular disturbances in severe liver disease, the state of the autonomic nervous system, the function of the baroreceptor reflex pathway and the responsiveness of the cardiovascular system to noradrenaline, angiotensin II and isoprenaline were investigated in 11 patients with hepatic encephalopathy and in 10 healthy control subjects. Increased plasma levels of noradrenaline and adrenaline and an attenuated increase in heart rate in response to atropine were found in patients with hepatic encephalopathy. These changes and the hemodynamic disturbances tended to be more pronounced in patients with hepatic encephalopathy Grades III-IV as compared to hepatic encephalopathy Grades I-II.
The increase in systolic blood pressure induced by infusion of noradrenaline (400 ng per kg per min) and angiotensin II (20 ng per kg per min) was higher in the patients than in healthy control subjects (hepatic encephalopathy Grades I-II: p < 0.001; hepatic encephalopathy Grades III-IV: p < 0.02). The changes in mean and diastolic blood pressure in response to angiotensin II were more pronounced in hepatic encephalopathy grades I-II than in hepatic encephalopathy Grades III-IV (p < 0.02). The decrease of heart rate in response to blood pressure increase in patients with hepatic encephalopathy was not different from control subjects except a smaller decrease during angiotensin II infusion in hepatic encephalopathy grades III-IV (p < 0.05). The responsiveness to isoprenaline was diminished (p < 0.001).
The present results indicate that the increased activity of the sympathetic nervous system in hepatic encephalopathy is associated with decreased parasympathetic tone. In addition, patients with hepatic encephalopathy have normal function of the baroreceptor reflex and excellent responsiveness of vascular tissue to endogenous vasoconstrictors.
Reticuloendothelial System Fc Receptor–Mediated Clearance of Igg–Tagged Erythrocytes From the Circulation of Patients With Idiopathic Ulcerative Colitis and Chronic Liver Disease
Authors: Minuk Gerald Y. , Hershfield Noel B. , Lee Weng Y. , Maccannell Keith L. , Preshaw Roy , Price Lorne M. , Shaffer Eldon A. , Sutherland Lloyd R. 
Published: March 2007

Immune complexes may be important in the pathogenesis of the liver disease associated with idiopathic ulcerative colitis. In the present study, we documented Fc receptor–mediated clearance by the reticuloendothelial system of immune complex–like material from the systemic circulation of 25 healthy control subjects, 19 patients with ulcerative colitis alone, 9 patients with ulcerative colitis and elevated liver enzyme tests and 8 patients with various other formsof chronic liver disease. Following an intravenous infusion of IgG–tagged 51Cr–labeled autologous erythrocytes, serial blood samples were drawn over a 2–hr period of time, and computer–generated clearance curves were obtained. The time required for clearance of 50% of infused erythrocytes (T1/2) was then calculated. Serum immunoglobulin (IgA, IgG and IgM), complement (C3 and C4) and immune complex–like activity (IgG and IgM types) were also determined. Sixteen of 19 (84%) ulcerative colitis patients and 7 of 8 (88%) chronic liver disease patients had normal clearance T1/2's (when compared to 25 healthy controls). Conversely, only 1 of 9 (11%) ulcerative colitis + chronic liver disease patients demonstrated normal clearance function. Aside from serum IgM levels, the results of serum immunoglobulin, complement and immune complex–like determinations were similar in ulcerative colitis and ulcerative colitis + chronic liver disease patients. Serum IgM levels, however, were significantly decreased in ulcerative colitis patients and increased in ulcerative colitis + chronic liver disease patients (p < 0.001).
These results indicate that the reticuloendothelial system of patients with ulcerative colitis and chronic liver disease is impaired in its ability to clear immune complex–like material from the systemic circulation. This finding tendsto support the hypothesis that immune complexes are of pathogenic importance in the liver disease associated with idiopathic ulcerative colitis.
Hemagglutination and Immunofluorescence Studies on Polymerized Human Serum Albumin Binding Activity in Chronic Hepatitis B Virus Infection
Authors: Mora Ignacio , Porres Juan Carlos , Guio Carlos Hernández , Gutiez Julia , Carreño Vicente 
Published: March 2007

The binding activity of polymerized human serum albumin was determined in 202 HBsAg carriers. The presence of polymerized human serum albumin receptor sites was tested by hemagglutination and differentiated from antihuman albumin antibodies by immunofluorescence, isolation of IgG and IgM fractions and testing of HBsAg anti–HBs immune complexes. A granular pattern with anti–HBs was specific for polymerized human serum albumin receptor sites as demonstrated with purified HBsAg. In addition, a linear pattern with fluoresceinated antihuman immunoglobulins might suggest the presence ofantihuman albumin antibodies (which was generally due to an IgG antibody). However, a granular pattern with fluoresceinated antihuman immunoglobulins may indicate the presence of HBsAg anti–HBs immune complexes. A weak linear pattern was also observed simultaneously in these cases, probably due to IgM antihuman albumin antibodies or an antipolymerized human serum albumin receptor site antibody.Of 202 HBsAg–positive patients, 71 showed polymerized human serum albumin receptor sites activity. The highest percentage of polymerized human serum albumin receptor sites was found among patients showing HBeAg and hepatitis B virus DNA polymerase positivity (96%), followed by HBeAg positivity and hepatitis B virus DNA polymerase negativity (48%), and anti–HBe positivity and hepatitis B virus DNA polymerase negativity (17%). In addition, a significant correlation between polymerized human serum albumin titers and hepatitis B virus DNA polymerase was found (r = 0.573, p <0.01). However, at a similar HBeAg titer, patients who were positive for hepatitis B virus DNA polymerase had a higher polymerized human serum albumin receptor sites titer than those who were negative for hepatitis B virus DNA polymerase.The presence of a granular pattern with anti–HBs or fluoresceinated antihuman immunoglobulins means a positivity to polymerized human serum albumin receptor sites or the presence of HBsAg anti–HBs immune complexes, respectively. Furthermore, polymerized human serum albumin receptor sites titers correlate with hepatitis B virus DNA polymerase concentrations and may serve as indicators of viral replication.
Effects of Immunosuppressive Therapy With Prednisolone on B and T Lymphocyte Function in Patients With Chronic Type B Hepatitis
Authors: Hanson Reginald G. , Peters Marion G. , Hoofnagle Jay H. 
Published: March 2007

B and T lymphocyte function was studied in 10 patients with chronic type B hepatitis before, during and after a 28–day course of prednisolone therapy. Lymphocyte function was assessed by measuring the in vitro synthesis of immunoglobulin by peripheral blood mononuclear cells stimulated with pokeweed mitogen and by assaying lymphocyte proliferation in response to B and T cell mitogens. During high dose prednisolonetherapy, there was a decrease in immunoglobulin synthesis by peripheral blood mononuclear cells and in lymphocyte proliferation to all mitogens. Studies using separated B and Tcells showed that prednisolone treatment led to a decrease in both helper and suppressor T cell function but an enhancement of primary B cell function. When prednisolone was withdrawn, lymphocyte function rapidly returned to baseline levels.
During prednisolone therapy, serum aminotransferase activities decreased by an average of 50%. In all patients, there was a subsequent rebound increase in serum aminotransferase activities 4 to 10 weeks after withdrawal of prednisolone. This was accompanied by a striking increase in suppressor T lymphocyte activity without significant changes in either helper T cell or B cell function. The close correlation between changes in helper and suppressor T lymphocyte function and serum aminotransferase activities during andafter immunosuppressive therapy suggests that immunoregulatory T lymphocytes may play an important role in the pathogenesis of chronic type B hepatitis.