bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial Antibodies in Primary Biliary Cirrhosis: Species and Nonspecies Specific Determinants of M2 Antigen
Authors: Lindenborn-Fotinos Jutta , Baum Harold , Berg Peter A.
Published: March 2007

Sera from patients with primary biliary cirrhosis reacted with four major bands in beef heart mitochondria and ATPase extract when analyzed by immunoblot after sodium dodecyl sulfate–polyacrylamide gel electrophoresis. These four immunologically reactive bands corresponded to protein bands with molecular weights of about (a) 80,000; (b) 63,000; (c) 56,000; and (d) 43,000 to 46,000. An additional immunoreactive band was found with some high–titered primary biliary cirrhosis sera at 36,000. No association with any ATPase subunits was found, except for band c which migrated between the α– and β–subunit of ATPase. Most ATPase fractions did not contain this band c, indicating that M2 determinants, as defined by immunoblot, are not identical with any ATPase subunit.

Species and nonspecies–specific determinants of M2 were identified using mitochondria from rat liver and human heart and liver. Antigenic bands a, c and d were nonspecies–specific. Band b and e occurred only in beef heart. An additional determinant at about 38,000 was detected using human heart and liver mitochondria. Primary biliary cirrhosis sera showed a typical reaction with two protein bands of Escherichia coli, one at about 85,000 to 90,000 and the other at 60,000. Antibodies against both determinants could be absorbed with submitochondrial particles of beef heart showing that E. coli shares cross–reacting determinants with mitochondria.

Sera from 56 primary biliary cirrhosis patients were tested using beef heart mitochondria. Fifty–four sera reacted positively with the M2 antigen in the ELISA, and these sera reacted with at least 1 of the 4 major antigenic bands: 85% were positive with band a and/or band b; 15% detected exclusively band c and none of the latter fixed complement. Antimitochondrial antibodypositive sera possessing other specificities (anti-M1, -M3, -M5, -M6 and -M7) were negative. A correlation with the precipitating antimitochondrial antibody system was not found.
Hepatitis B Virus Dna, Hbeag and Delta Infection During the Course From Acute to Chronic Hepatitis B Virus Infection
Authors: Krogsgaard Kim , Aldershvile Jan , Kryger Peter , Andersson Poul , Nielsen Jens Ole , Hansson Bengt Göran
Published: March 2007

The presence of hepatitis B virus DNA in serum was determined in 57 unselected patients during the course from acute to chronic hepatitis B infection. Forty–six (81%) patients were hepatitis B virus DNA–positive in the first available serum sample. Generally, hepatitis B virus DNA was cleared before or at the same time as HBeAg, but in two patients (4%), hepatitis B virus DNA could be demonstrated after HBeAg clearance. One of the latter patients had hepatitis B virus DNA in the presence of anti–HBe. Both patients became hepatitis B virus DNA–negative. Seven of the hepatitis B virus DNA–positive patients received long–term treatment with prednisone, and three of them continued to be hepatitis B virus DNA positive for more than 10 years. Among the untreated patients hepatitis B virus DNA could be detected for up to 7 years, and 10 patients were hepatitis B virus DNA–positive for three years or more.

Twenty–four patients (42%) showed serological signs of delta agent infection. Hepatitis B virus DNA clearance was observed in a significantly higher proportion (87%) of delta–infected patients as compared to patients with no delta infection (45%) (p < 0.05). In addition patients with delta infection had a significantly increased hepatitis B virus DNA clearance rate as compared to patients without delta markers in their serum (p < 0.01). In one (8%) delta–infected patient, hepatitis B virus DNA clearance was followed by a fall in transaminases into the normal range as opposed to results in 86% of patients with pure hepatitis B (p < 0.002).
Hepatic Mitochondrial Oxidative Metabolism in Rats With Chronic Dietary Iron Overload
Authors: Bacon Bruce R. , Park Chanho H. , Brittenham Gary M. , O-Neill Rosemary , Tavill Anthony S.
Published: March 2007

We examined the effects of chronic dietary iron overload on hepatic mitochondrial oxidative metabolism. Experimental iron overload was produced by feeding rats a chow diet supplemented with carbonyl iron over a 7–week period. Biochemical and histologic evaluations of liver tissue confirmed moderate degrees of hepatic parenchymal iron overload. Electron microscopy showed no abnormalities in hepatic mitochondrial ultrastructure in blocks of tissue or in mitochondrial fractions from iron–loaded liver. Studies of mitochondrial oxidative metabolism revealed a consistent and progressive decrease in state 3 (ADP–stimulated) respiration and in respiratory control ratios at hepatic iron concentrations above 1,000 μg per gm for all three substrates studied, glutamate, β–hydroxybutyrate and succinate. Changes in state 4 (ADP–limited) respiration and ADP/O ratios were not progressive with increasing hepatic iron concentrations. At hepatic iron concentrations at which there were decreases in state 3 respiration and respiratory control ratios, there was also evidence of lipid–conjugated diene formation, indicative of mitochondrial lipid peroxidation. There were no changes in mitochondrial function when iron as either ferritin or hemosiderin or as a combination of ferritin, hemosiderin and ferric nitrilotriacetate was added in vitro to normal liver homogenates. Use of density gradient centrifugation to reduce iron and lysosomal contamination of mitochondrial fractions failed to prevent the reduction in mitochondrial function. We conclude that moderate degrees of chronic hepatic iron overload in vivo result in an inhibitory defect in the mitochondrial electron transport chain as evidenced by a decrease in state 3 respiration and respiratory control ratios.
Measurement of Fibrosis in Needle Liver Biopsies: Evaluation of A Colorimetric Method
Authors: Jimenez Wladimiro , Parés Albert , Caballería Joan , Heredia Daniel , Bruguera Meguel , Torres Miguel , Rojkind Marcos , Rodés Joan
Published: March 2007

Collagen content was measured in 38 needle liver biopsies (8 steatosis, 8 chronic hepatitis, 7 fibrosis and 15 cirrhosis) by a new colorimetric method based on the selective capacity of Sirius red and Fast green to bind to collagen and noncollagenous proteins, respectively. The values were compared with those obtained after determination of the degree of fibrosis by morphometry in the same tissue.

In biopsies with cirrhosis and fibrosis, there was a higher amount of collagen than in biopsies with chronic hepatitis and steatosis. Furthermore, there was a highly significant direct correlation between the collagen content measured colorimetrically and the degree of fibrosis determined morphometrically (r = 0.77, p < 0.001), suggesting that this new colorimetric method is useful in measuring the degree of fibrosis in needle liver biopsies.
Improved Survival Following Injection Sclerotherapy for Esophageal Varices: Final Analysis of A Controlled Trial
Authors: Westaby David , Macdougall Brian R.D. , Williams Roger
Published: March 2007

Long–term follow–up (median: 37 months; range: 19 to 68) of the 116 patients (56 sclerotherapy, 60 control group) entered into a controlled trial of endoscopic variceal sclerotherapy has shown a total of 18 deaths in the sclerotherapy group, including five from variceal bleeding compared with 32 deaths in the control group (p < 0.01), of which 25 were from variceal hemorrhage (p < 0.001). Survival as assessed by cumulative life analysis was significantly better in those treated by sclerotherapy (p < 0.001). Both the cumulative proportion of patients rebleeding and the total number of episodes of variceal hemorrhage were also significantly less in the sclerotherapy group (p < 0.01). Recurrence of varices was observed in 27 of 45 patients in whom variceal obliteration was initially observed at a median of 11 months (range: 2 to 27) later, although in only 12 of these did bleeding recur and was the cause of death in one.
Pathogenesis of Steatorrhea in Primary Biliary Cirrhosis
Authors: Lanspa Stephen J. , Chan Albert T.H. , Bell Sumner J. , Go Vay Liang W. , Dickson Rolland E. , Dimagno Eugene P.
Published: March 2007

To investigate the pathophysiology of steatorrhea in primary biliary cirrhosis, the severity of steatorrhea, small bowel histology and function, cholestasis, exocrine pancreatic secretion and liver histology were studied. Twenty–four primary biliary cirrhotic patients had a quantitative stool fat collection, serum bilirubin and alkaline phosphatase and liver biopsies. From this group, ten had further studies: a small bowel biopsy (n = 7); a D–xylose test (n = 9); measurement of pancreatiobiliary concentrations and outputs after intravenous cholecystokinin (n = 10); essential amino acid perfusion of the duodenum (n = 9), and eating a test meal (n = 7).

D–xylose absorption was normal, and only one patient had a minimal small bowel mucosal abnormality. Pancreatic lipase outputs in response to cholecystokinin were low in two primary biliary cirrhotic patients, but were greater than 10% of normal. Postprandial lipase outputs were normal except in one patient who had abnormal duodenal acidification. Mean enzyme outputs in primary biliary cirrhotic patients were normal in response to essential amino acid perfusion; but 6 had low lipase and 5 had low trypsin outputs which were associated with decreased bile acid outputs (p < 0.03). Severity of steatorrhea was associated with reduced bile acid outputs and concentrations (r = 0.82; p < 0.0001), degree of cholestasis (serum bilirubin; r = 0.88; p < 0.001) and advanced histologic stages (p < 0.005). Severe intraluminal bile acid deficiency combined with a submaximal intraluminal stimulus (essential amino acids) may be associated with decreased exocrine pancreatic secretion in primary biliary cirrhosis. However, mild and severe steatorrhea is explained by severely reduced intraluminal bile acid content rather than decreased lipase secretion.
Polycythemia and the Budd–Chiari Syndrome: Study of Serum Erythropoietin and Bone Marrow Erythroid Progenitors
Authors: Levy Victor Georges , Ruskone Agnès , Baillou Claude , Thierman-Duffaud Diana , Najman Albert , Boffa Georges Albert
Published: March 2007

The mechanism of polycythemia associated with the Budd–Chiari syndrome is unknown. Erythropoiesis in 10 patients with Budd–Chiari syndrome was studied in an attempt to distinguish prior unrecognized polycythemia vera from secondary polycythemia.

Serum erythropoietin was assayed using a mouse fetal liver erythroblast assay. High concentrations of serum erythropoietin were observed in 6 of 7 patients with acute primary Budd–Chiari syndrome. Levels were normal in four patients who were investigated during the chronic phase and were increased in one with persisting polycythemia. In one patient, erythropoietin concentration in the hepatic vein was twice the level measured in peripheral, caval and renal venous blood.

Bone marrow erythroid progenitors developed in vitro in the absence of exogenous erythropoietin in all polycythemia vera cases studied in acute and chronic phases, whether polycythemia persisted or not.

These findings indicate that hepatic erythropoietin production occurs in the acute phase of Budd–Chiari syndrome and suggest that, in some cases of Budd Chiari syndrome, polycythemia which resolves after the acute phase may be secondary to liver disease.
Prognostic Value of Thyroid Hormone Levels in Patients Evaluated for Liver Transplantation
Authors: Van Thiel David H. , Udani Mahendra , Schade Robert R. , Sanghvi Agit , Starzl Thomas E.
Published: March 2007

The thyroid hormones T4, T3, rT3 and TSH were assayed in 134 adult patients evaluated and accepted as potential liver transplant candidates at the Universty of Pittsburgh from March, 1981 to December, 1983. The subsequent course of these patients was evaluated with respect to the levels of these hormones obtained at the time of acceptance for transplantation. T4 levels were increased significantly while their T3 levels were reduced (both p < 0.01) in those who survived and were discharged home as compared to either those who died waiting to be transplanted or died following the procedure. As a result, the ratio of T3/T4 was reduced markedly (p < 0.01) in those who were transplanted and survived as compared to those not transplanted or dying following transplantation. Importantly, the rT3 levels clearly separated (p < 0.01) those who would die prior to transplantation from those who would survive to be transplanted. Finally, the ratio rT3/T3 even more clearly separates those who will die prior to transplantation (p < 0.01) from the other two groups.

These data suggest that thyroid hormone levels, particularly rT3 levels, might be useful in setting priorities for which patients referred for a transplantation evaluation should be accepted into the program and in determining who among accepted patients should be operated upon in preference to others also accepted and waiting to be transplanted.
The Effect of 3–Palmitoyl–(+)–Catechin on Kupffer Cells in Guinea Pig Liver
Authors: Piazza Marcello , Borgia Guglielmo , Crowell Jane , Nappa Salvatore , Lambiase Alberto , Perrissoud Daniel , Schreil Werner
Published: March 2007

We report a morphometric study on the effect of 3–palmitoyl–(+)–catechin on phagocytic activity of latex particles by Kupffer cells in guinea pig liver. We found an increase in the density of latex particles in Kupffer cells of animals treated with 3–palmitoyl–(+)–catechin. The volume and density of Kupffer cells of treated animals increased (p < 0.01); there was no significant difference in surface density of the plasma membrane. None of the parameters measured was altered in endo–thelial cells. These results show that 3–palmitoyl–(+)–catechin produces morphological and functional changes in Kupffer cells.
Chronic Alcoholism Enhances Hepatocarcinogenicity of Diethylnitrosamine in Rats Fed A Marginally Methyl–Deficient Diet
Authors: Porta Eduardo A. , Markell Nalani , Dorado Russell D.
Published: March 2007

To determine whether the chronic consumption of ethanol was capable of enhancing the hepatocarcinogenic activity of diethylnitrosamine per se, or through the accentuation of a methyl deficiency, two groups (A and B) of Sprague–Dawley female rats were fed for 10 months either a 20% casein basal diet marginally deficient in methyl, or the same diet supplemented with choline (1 gm per 100 gm) and folic acid (0.54 mg per 100 gm). Both groups were offered a drinking ethanol solution, while two other nonalcohol control groups (C and D) were isocalorically pair–fed to Groups A and B, and received diets in which the alcohol consumed by the corresponding groups was replaced by isocaloric amounts of sucrose. A baseline nonalcohol Group E, isocalorically pair–fed to Group A, received the intact basal diet of Group A and water. One day before the initiation of the experiment, and again 2 months later, all rats from the five groups were injected with a single i.p. dose of diethylnitrosamine (100 mg per kg). The growth attained by all groups was statisticlly similar. Hepatic triglycerides in Group A were significantly higher than in all the other groups. While in Group A primary hepatocellular carcinomas and renal tumors were encountered at the end of the experiment in 3 of 6 and in 2 of 6 rats, respectively, no malignancies were observed in any of the other groups. These results indicate that chronic ethanol consumption enhances the hepatocarcinogenic and renal tumorigenic activity of diethylnitrosamine, and strongly suggest that this action is mediated through the accentuation of methyl deficiency.
Effects of Dietary Selenium on Hepatic and Renal Tumorigenesis Induced in Rats by Diethylnitrosamine
Authors: Dorado Russell D. , Porta Eduardo A. , Aquino Therese M.
Published: March 2007

Seven groups of female Sprague–Dawley rats (˜200 gm initial body weight) were injected i.p. with a single subcarcinogenic dose of diethylnitrosamine (40 mg per kg body weight) between 8 to 10 hr after partial hepatectomy, and after a recovery period of 3 weeks (herein called induction stage) received 0.05% phenobarbital in the diet for the rest of the experiment (promotion stage). The rats were fed a 20% casein–based diet containing 0.16 ppm of selenium or the same diet supplemented with 4 or 6 ppm of selenium as sodium selenite. The effects of these three dietary regimens were tested when administered 9 to 11 days before and during induction, 1 week before and during promotion or during the entire experiment. Pair–feeding conditions were used to minimize influences due to differences in food intake and growth. Despite similarities in food intakes, the growth rates in groups receiving the 6 ppm–selenium diet during promotion or during the entire experiment were in general significantly lower than in rats fed the 4 ppm–selenium diet or the 0.16 ppm–selenium basal diet. Survival rates were also significantly reduced in rats fed the 4 and 6 ppm–selenium diets during promotion or during the entire experiment. In rats killed at the 19th week for interim assessment of the experiment's progress, the stereologically analyzed numerical and volumetric densities of hepatic premalignant hyperplastic nodules did not differ significantly between groups. All the remaining rats were killed at the 46th week. The statistical analysis of the total incidence of hepatic carcinomas and renal tumors encountered in rats during the course of the experiment and in those killed at the end of the study showed no significant differences between groups. Toxic effects of selenium on liver structure were quite conspicuous in rats under prolonged treatment with 4 and 6 ppm–selenium diets.
Liver Biopsy Immunotyping to Characterize Lymphoid Malignancies
Authors: Verdi Christopher J. , Grogan Thomas M. , Protell Robert , Richter Lynne , Rangel Catherine
Published: March 2007

To determine the feasibility of liver biopsy immunotyping to characterize hepatic lymphoid malignancies, we employed a panel of monoclonal antibodies on snapfrozen hepatic tissue from 18 patients. Six patients proved to have a histologic diagnosis of lymphoid malignancy. By using free avidin and biotin–blocking reagents to block endogenous biotin, followed by standard immunochemistry, immunotyping was successful in all six cases. Serial section typing allowed delineation of complex B cell phenotypes. Furthermore, architecture was preserved allowing discernment of disease patterns (e.g.), sinusoidal, hairy cell leukemia vs. portal, follicular small–cleaved cell lymphoma. Unexpectedly, we found striking expression of common ALL antigen in normal bile canaliculi, which may prove of diagnostic or therapeutic relevance. This study establishes the utility of immunohistochemical techniques applied to hepatic biopsies as a valuable adjunct to histologic diagnosis as well as a tool in revealing the immunobiology of the liver.
Prognostic Significance of Serum Bile Acids in Cirrhosis
Authors: Mannes Gerd A. , Thieme Christian , Stellaard Frans , Wang Tiancai , Sauerbruch Tilman , Paumgartner Gustav
Published: March 2007

The value of serum bile acid concentrations for predicting prognosis in cirrhotics was compared with the prognostic significance of clinical and laboratory findings in a prospective 1–year study of 76 patients with cirrhosis. A commercial radioimmunoassay for total serum–conjugated primary bile acids was used. Of 76 patients, 16 died within the follow–up period. The concentration of bile acids in serum more closely correlated with mortality in cirrhosis than the commonly used clinical and laboratory parameters such as the Number Connection Test, ascites, albumin, pseudocholinesterase, bilirubin, prothrombin time and nutritional state. Serum bile acids alone yielded a prediction of mortality comparable to the Child classification. When logistic regression analysis was performed, optimal prediction of prognosis was achieved with the combination of serum bile acids and the Number Connection Test. Serum bile acid levels alone or in combination with the Number Connection Test may be a clinically useful prognostic index in cirrhosis.
Periductal Fibrosis and Lipocytes (Fat–Storing Cells or Ito Cells) During Biliary Atresia in the Lamprey
Authors: Yamamoto Kazuhide , Sargent Patricia A. , Fisher Murray M. , Youson John H.
Published: March 2007

Transmission and scanning electron microscopy were utilized to follow the degeneration of bile ducts of lampreys (Petromyzon marinus L.) during metamorphosis. The convoluted bile ducts of larval lampreys are surrounded by rich sinusoids, but this intimate biliovascular relationship is lost during metamorphosis because the bile duct degeneration is accompanied by the development of thick periductal fibrosis. Lipocytes, which are present not only in the parenchyma but also in the interstitial tissue of the liver, increase in number in the periductal fibrous tissue, and their processes are directly opposed to collagen fibrils. Fibrillar materials in the dilated cisternae of the rough endoplasmic reticulum andthe nuclear envelope of lipocytes are believed to be excreted by exocytosis in a manner similar to such excretion by fibroblasts. The findings suggest that lipocytes are responsible for the periductal fibrosis during biliary atresia in lampreys. This animal might prove to be an interesting model in which to study the biology and fibrogenic potential of lipocytes.
Transport and Intracellular Distribution of Copper in A Human Hepatoblastoma Cell Line, Hepg2
Authors: Stockert Richard J. , Grushoff Phyllis S. , Morell Anatol G. , Bentley Glenn E. , O'Brien Harold A. , Scheinberg Herbert I. , Sternlieb Irmin
Published: March 2007

The uptake of radiocopper by HepG2 cells is a saturable, temperature–dependent and cellular energy–independent process with a Vmax of 7.1 ± 0.2 pmoles min-1 mg protein-1 andan estimated Km of 3.3 ± 0.5 μM. The rate of copper uptake is reduced at an equimolar concentrationof albumin and is unaffected by zinc at a 10–fold molar excess. Approximately 70% of the newly incorporated radiocopper binds to membranes and organelles, while 30% is recovered in the cytosol. The soluble fraction can be resolved intotwo copper–binding protein peaks. Incubation of HepG2 with nonisotopic copper results in displacement of radiocopper associated with the proteins contained in the lower molecular weight peak. Exposure of the cells to cycloheximide inhibits the incorporation of the isotope into this fraction.
A Comparative Study of the Effects of Insulin/Glucagon Infusions, Parenteral Amino Acids and High Dose Corticosteroids on Survival in A Rabbit Model of Acute Fulminant Hepatitis
Authors: Minuk Gerald Y. , Sherman Thomas A. , Shaffer Eldon A. , Kelly Seamus K.
Published: March 2007

Acute fulminant hepatitis was induced in 55 healthy adult male rabbits with the potent hepatotoxin galactosamine hydrochloride (3.75 mmoles per kg i.v.). Control rabbits (n = 27) were divided into three groups: Group I (n = 10) underwent sham surgery for placement of an indwelling central venous catheter; Group II (n = 9) received 5% dextrose and water via an indwelling central venous catheter, and Group III (n = 8) received daily intramuscular injections of 0.9% sodium chloride. Treated rabbits (n = 28) also consisted of three groups: Group IV (n = 9) received 12–hr intravenous infusions of insulin (0.029 units per kg per hr) and glucagon (2.86 μg per kg per hr) daily; Group V (n = 10) received a continuous infusion of parenteral amino acids (Travasol), and Group VI (n = 9) received daily intramuscular methylprednisolone (0.69 mg per kg). In each case, treatment was initiated 16 hr following galactosamine injection. Serum aminotransferase activity was determined on Days 0, 1, 4 and 10 of the 10–day study. Liver histology was obtained immediately after death and graded under code on a scale of 1 to 4 for severity of hepatitis. Rabbits surviving 10 days were sacrificed on Day 10 for histologic examination.

The extent of galactosamine–induced hepatic injury was similar in all six groups as manifest by peak mean SGPT(range: 2,662 to 3,568 IU per liter), SGOT (range: 4,435 to 5,625 IU per liter) levels and hepatic histologic findings. The overall survival rate in controls was 6/27 (22%); in insulin/glucagon–treated animals 2/9 (22%), and in the amino acid–treated group 2/10 (20%). The corticosteroid–treated group, however, had significantly improved survival: 6/9 (67%, p < 0.05, Fisher's exact test). No difference between groups was observed in the mean survival times of animals dying prior to Day 10 (range: 30.7 ± 2.7 — 55.5 ± 13.0 hr, mean ± S.E., p > 0.05). In conclusion, the results of this study indicate that in this animal model of acute fulminant hepatitis and withthese doses, insulin/glucagon infusions and parenteral amino acids have no beneficial effect, while high dose corticosteroids significantly enhance survival. On the basis of these results, a reappraisal of the use of high dose corticosteroidsin the treatment of nonviral forms of acute fulminant heptitis in humans would appear to be indicated.
Terlipressin in Bleeding Esophageal Varices: A Placebo–Controlled, Double–Blind Study
Authors: Walker Siegfried , Stiehl Adolf , Raedsch Richard , Kommerell Burkhard
Published: March 2007

The effect of terlipressin (N–α–triglycyl–8–lysinevasopressin) in bleeding esophageal varices was evaluated in a prospective placebo–controlled study. Fifty bleeding episodes from esophagealvarices in 34 patients were randomized. Standard therapy with transfusions, fluid and electrolyte correction, and lactulose was performed in both groups. Balloon tamponade was used in 20 bleeding episodes in the terlipressin group and in 19 bleeding episodes in the control group.

In the terlipressin group, hemorrhage was controlled in all bleeding episodes (25/25) whereas in the placebo group, only 20 of 25 bleeding episodes could be stopped within 36 hr (p < 0.05). Sclerotherapy was performed in five bleeding episodes in the terlipressin group and in seven bleeding episodes in the placebo group. Treatment failures, including patients who required sclerotherapy, occurred in five bleedings in the terlipressin group and in 12 in the control group (p < 0.05). The hospital mortality rate was 12% (3/25) in the terlipressin group and 32% (8/25) in the control group. Patients in the terlipressin group required fewer transfusions, the balloon needed to be inflated for a shorter time and theduration of bleeding was shorter than in the control group. However, these differences were not significant.

These data do not allow conclusions concerning monotherapy with terlipressin, but they indicate that the addition of terlipressin to standard therapy may increase the control rate in acute variceal hemorrhage.
Assessment of Short–Term Prognosis After Variceal Bleeding in Patients With Alcoholic Cirrhosis by Early Measurement of Portohepatic Gradient
Authors: Vinel J. P. , Cassigneul J. , Levade M. , Voigt J. J. , Pascal J. P.
Published: March 2007

Seventy–two consecutively admitted patients with biopsy–proven alcoholic cirrhosis and a bleeding episode endoscopically proven to originate from ruptured esophageal varices were studied. Hemodynamic assessment was performedwithin 48 hr of admission using the transjugular approach.

Mean portal pressure was found to be significantly greater in the group of patients who died than in those who survived for 1 week, 2 weeks or 1 month after admission.

We conclude that: The portohepatic pressure gradient and portal pressure have short–term prognostic value in patients with alcoholic cirrhosis bleeding from ruptured esophageal varices. Owing to a high early mortality, any delay between the occurrence of a bleeding episode and the measurement of portal pressure appears to select a sample of survivorswith a significantly lower mean level of portal pressure than in those measured earlier. When evaluating portal pressure, the time of study is one of the most important variables which may affect the conclusions.
Effect of Volume Expansion on Hemodynamics, Capillary Permeability and Renal Function in Conscious, Cirrhotic Rats
Authors: Caramelo Carlos , Fernandez-Muñoz Dolores , Santos Juan C. , Blanchart Alicia , Rodriguez-Puyol Diego , López-Novoa José M. , Hernando Luis
Published: March 2007

General and splanchnic hemodynamics (radioactive microspheres), renal function, spontaneous and histamine–mediated vasopermeability and albumin distribution space were studied in conscious control and nonascitic cirrhotic rats, before and after a moderate and sustained saline infusion (3% of body weight per 30 min + repletion of urinary losses). In basal conditions, cirrhotic rats showed lower fractional sodium excretion than did control rats (0.09 ± 0.01 vs. 0.15 ± 0.01%, p < 0.005). In addition, cirrhotic animals showed higher cardiac output (161.4 ± 12.8 ml per min) and lower total peripheral resistance (0.63 ± 0.05 mm Hg–min per ml) and mean arterial pressure (102.9 ± 3.9 mm Hg) than did control rats (cardiac output: 89.0 ± 7.6; total peripheral resistance: 1.31 ± 0.11; mean arterial pressure: 117.5 ± 5.11; p < 0.005). No differences in portalsystemic shunt rate or vasopermeability between both groups were observed. After saline infusion, fractional sodium excretion increased to 4.31 ± 0.16% in controls but only 2.11 ± 0.02% in cirrhotic animals. In this group, cardiac output decreased by 49.6 ± 5.1% whereas mean arterial pressure and total peripheral resistance increased by 7.1 ± 0.6 and 112 ± 10%, respectively. In control rats, no significant hemodynamic changes were observed. Blood gases did not change after expansion in any group. Saline infusion induced an increase in histamine–mediated vasopermeability in cirrhotic rats but not in control rats. Also albumin distribution space increased more in cirrhotic than in control animals. Heart weight was higher in cirrhotic rats.

These results suggest that the lack of adequate natriuretic response to saline infusion in cirrhotic animals is a multifactorial phenomenon. An ineffective replenishment of the vascular tree produced by increased vasopermeability and the probable existence of cardiomyopathy in cirrhotic rats could also explain the experimental findings.
Biological Significance of Enhanced Mitochondrial Membrane Potential in Regenerating Liver
Authors: Nishihira Tomohiko , Tanaka Junji , Nishikawa Kastuhide , Jikko Akira , Taki Yoshiro , Morimoto Taisuke , Koizumi Kenji , Kamiyama Yasuo , Ozawa Kazue , Tobe Takayoshi
Published: March 2007

Liver mitochondrial membrane potential was assessed during regeneration following partial hepatectomy in rabbits. Absorbance change of safranine O per milligram of mitochondrial protein was used to evaluate mitochondrial membrane potential. Absorbance change was calibrated to the membrane potential in millivolts produced by valinomycin–induced potassium diffusion potential. At 24 hr after hepatectomy, absorbance change of safranine O per milligram of mitochondrial protein increased from 15.0 ± 2.2 × 10-3 to 37.4 ± 3.3 × 10-3 per mg (p < 0.005). This represents a mitochondrial membrane potential increase from 77.0 ± 4.6 to 124.4 ± 6.7 mV. Phosphorylative activity increased from 59.9 ±5.0 to 106.1 ± 7.4 nmoles ATP synthesized per mg per min (p < 0.005). The enhancement of phosphorylative activity was closely linked to the elevation in liver mitochondrial membrane potential (r = 0.77, p < 0.005). We suggest that elevation of mitochondrial membrane potential, coupled with enhanced oxidative and phosphorylative activities, plays an important role in the regeneration process following hepatectomy.
Hepatorenal Syndrome Without Avid Sodium Retention
Authors: Dudley Francis J. , Kanel Gary C. , Wood Laurence J. , Reynolds Telfer B.
Published: March 2007

A urinary sodium concentration [U(Na)] of <10 mmoles per liter is considered important in differentiating hepatorenal syndrome from other causes of progressive renal impairment in patients with liver disease. However, occasionally, patients with hepatorenal syndrome have been recognized in whom the U(Na) is consistently >10 mmoles per liter. Eight such patients, in all of whom there was no clinical or laboratory evidence to implicate other causes of progressive renal impairment, were identified. The clinical features, hepatic and renal status and hospital course were compared with eight otherpatients who had hepatorenal syndrome and a U(Na) consistently <10 mmoles per liter. The mean U(Na) was 24 ± 4 mmoles per liter in the high U(Na) group and 3.7 ± 1.8 mmoles per liter in the low U(Na) group. All patients in both groups had acutely decompensated alcoholic hepatitis of similar severity and activity. The high U(Na) group had significantly less clinical ascites and peripheral edema and higher serum levels of sodium and chloride both at the onset of the hepatorenal syndrome and throughout the clinical course. Significant differences in the serum potassium and blood urea nitrogen levels became apparent between the two groups of patients as renal failure progressed, and the mean average blood urea nitrogen to serum creatinine ratio was significantly higher (p < 0.025) in the low U(Na) group (13.8 ± 0.9 vs. 10.1 ± 1.1). Mean urinary potassium concentration was significantly higher in the high U(Na) patients but urinary creatinine concentrations, specific gravity and sediment were similarin both groups of patients. Three of the patients from the high U(Na) group came to autopsy. In all, the only renal histological abnormality was reflux of proximal convolutedtubular epithelium into Bowman's capsule, a finding consistent with hepatorenal syndrome. It is concluded that, in patients with acute alcoholic hepatitis, a U(Na) >10 mmoles per liter does not exclude the diagnosis of hepatorenal syndrome. It is suggested that the clinical and biochemical differences between patients with the hepatorenalsyndrome and a high or low U(Na) can be explained by variations in the proximal tubularabsorption of sodium.
Covalent Binding of Acetaldehyde Selectively Inhibits the Catalytic Activity of Lysine–Dependent Enzymes
Authors: Mauch Teri J. , Donohue Terrence M. , Zetterman Rowen K. , Sorrell Michael F. , Tuma Dean J.
Published: March 2007

Hepatic ethanol metabolism generates the reactive intermediate, acetaldehyde, whichbinds to proteins. The binding of acetaldehyde to purified enzymes was determined in order to ascertain whether such binding altered their catalytic functions. [14C]Acetaldehyde was incubated with alcohol dehydrogenase, glucose–6–phosphate dehydrogenase, lactate dehydrogenase and RNase A, each at 37°C(pH 7.4). In some reactions, sodium cyanoborohydride was included for stabilization of Schiff bases, formed as a result of the reaction between acetaldehyde and the amino groups of the enzymes. Portions of each reaction mixture were removed for determination ofstable and total (stable plus borohydride–reducible) adducts. Alcohol dehydrogenase and lactate dehydrogenase were not inhibited by adduct formation. Glucose–6–phosphate dehydrogenase and RNase, the activities of which depend on a lysine residue at their catalytic sites, were inhibited in a dose– and time–dependent manner. The degree of inhibition directly correlated with total adduct formation. Phosphate, known to inhibit binding to the active site lysine of RNase, prevented the inhibition of catalytic activity caused by adduct formation. These findings indicate thatthe binding of acetaldehyde to lysine at the catalytic site can inhibit enzyme activity.
A Randomized Clinical Trial of Supplementary Parenteral Nutrition in Jaundiced Alcoholic Cirrhotic Patients
Authors: Naveau Sylvie , Pelletier Gilles , Poynard Thierry , Attali Pierre , Poitrine Alain , Buffet Catherine , Etienne Jean-Pierre , Chaput Jean-Claude
Published: March 2007

Between March 1982 and September 1983, 40 inpatients (25 men and 15 women, mean age 53 years) with alcoholic cirrhosis and total serum bilirubin ≥5 mg per dl were studied. Those with hepatocellular carcinoma, renal failure, hyponatremia, septicemia, spontaneous bacterial peritonitis, gastrointestinal bleeding, and hepatic coma were excluded. Patients were studied for 28 days. The two groups were offered an oral diet containing 40 kcal per kg per day. Patients in the supplementary parenteral nutrition group received 40 kcal per kg per day and 200 mg nitrogen per kg per day using a central catheter. The major endpoint was total serum bilirubin on Day 28.

On admission, serum bilirubin was not significantly different in the two groups: oral group, 12.5 ± 6.6 mg per dl; supplementary parenteral nutrition group, 12.3 ± 8.5 mg per dl. On Day 28, serum bilirubin was lower in the supplementary parenteral nutrition group (2.5 ± 1.4 mg per dl) than in the oral group (4.1 ± 2.2 mg per dl) (p < 0.02). Serum bilirubin was also lower in the supplementary parenteral nutrition group than in the oral group on Days 7, 14and 21 (p < 0.05). Analysis of covariance, considering serum bilirubin on admission and at randomization and time between admission and randomization, confirmed these results. On Day 28, anthropometric parameters, serum transferrin, prealbumin and retinol–binding protein were higherin the supplementary parenteral nutrition group, but the differences were not significant. Serum albumin was significantly lower in the supplementary parenteral nutrition group. The incidence of encephalopathy and sepsis was not significantly different between the two groups.
Hyperglucagonemia and Hyperammonemia: Which Is the Chicken and Which the Egg?
Authors: Conn Harold O. , Eriksson Siw L.
Published: March 2007

Elevated plasma ammonia level in hepatic cirrhosis has been attributed to a lack ofconversion of enteric ammonia into urea or to its entry into systemic circulation via portasystemic shunting, or to both. It is exaggerated by excessive protein intake. Because hyperglucagonemia is well documented in cirrhosis and a protein meal is an effective glucagon secretogogue, plasma glucose, insulin, glucagon, and ammonia levels were determined in 50 cirrhotic patients after an overnight fast. Effects of a protein meal were also assessed in 20 of these patients. Plasma glucose was normal and remained unaltered after a protein meal. Insulin, glucagon and ammonia levels were elevated, but only in patients with advanced liver dysfunction. Ammonia levels correlated significantly with glucagon (r = 0.61, p < 0.001), but not with insulin or glucose levels. Insulin and glucagon levels rose after a protein meal in all patients and controls, whereas a significant rise in the ammonia level occurred only in decompensated cirrhotics. Elevation of the ammonia level was significantly correlated with fasting glucagon (r = 0.54, p < 0.05), as well as with glucagon response (r = 0.65, p < 0.01), but not with basal insulin or insulin response. Furthermore, the rise in ammonia level occurred too early to be accounted for by enteric generation. Finally, direct effects of glucagon administration on plasma glucose and serum ammonia were examined in 15 cirrhotic patients. Glucose response was significantly blunted in cirrhotic patients as compared with normal subjects, whereas serum ammonia rose promptly but only in cirrhotics with maximum rise being noted in cirrhotic patients with advanced liver dysfunction. This study, therefore, suggests that hyperglucagonemia may contribute significantly to hyperammonemia in hepatic cirrhosis.
Hepatitis B virus pre-S gene-encoded antigenic specificity and anti-pre-S antibody: Relationship between anti-pre-S response and recovery
Authors: Budkowska Agata , Dubreuil Pascal , Capel Francis , Pillot Jacques
Published: March 2007

A solid-phase radioimmunoassay involving specific antibody was developed for determination of the pre-S gene-encoded epitopes of hepatitis B virus and anti-pre-S antibody in sera of hepatitis B patients. The reaction for pre-S determinants associated with HBsAg was quantitatively inhibited by soluble, polymerized human serum albumin, and the lower limit of the assay was about 1.6 ng of HBsAg per ml. Continuous expression of pre-S-coded antigenic sites on HBsAg particles in chronic hepatitis B patients seropositive for HBeAg or anti-HBe shows that these determinants may be considered as a marker of chronicity during hepatitis B virus infection. The anti-pre-S antibody was determined by inhibition of the reaction for pre-S determinants. This antibody, different from anti-HBs, was detected during HBsAg antigenemia in patients recovering from acute type B hepatitis, before anti-HBs response. Kinetics of synthesis of anti-pre-S antibody in the course of acute type B hepatitis, followed by elimination of HBsAg and recovery, suggest the possible role of this antibody in the immunological clearance of infective hepatitis B virus particles.
The mechanism of elevated alkaline phosphatase activity after bile duct ligation in the rat
Authors: Seetharam Shakuntla , Sussman Norman L. , Komoda Tsugikazu , Alpers David H.
Published: March 2007

Alkaline phosphatase activity in the liver and intestine increases after bile duct ligation, reportedly by increased enzyme synthesis. To ascertain the mechanism of this increased synthesis in the absence of a cDNA clone encoding the enzyme, we have estimated the concentration of liver and intestinal alkaline phosphatase mRNA by translational analysis. Monospecific antiserum to rat placental alkaline phosphatase was raised. The resulting antiserum precipitated two peptides of 53 and 56 kd after translation of liver poly(A)+ RNA. The precipitation of both peptides was blocked by the single 64 kd placental alkaline phosphatase. Processing of the cell-free products by microsomal membranes produced peptides of 62 and 64 kd. Antiserum to rat intestinal alkaline phosphatase also identified two peptides as products of intestinal RNA translation. After bile duct ligation, we confirmed a transient 2-fold increase in alkaline phosphatase activity in the intestine and a more constant 7-fold increase in the liver. However, the alkaline phosphatase mRNA concentration remained unchanged in both organs. We conclude that increased alkaline phosphastase synthesis after bile duct ligation results from an enhanced rate of translation of mRNA.
Ultrastructural immunocytochemical analysis of lymphocytes infiltrating bile duct epithelia in primary biliary cirrhosis
Authors: Yamada Gotaro , Hyodo Ichinosuke , Tobe Kazuo , Mizuno Motowo , Nishihara Takashi , Kobayashi Toshinari , Nagashima Hideo
Published: March 2007

Subpopulations of lymphocytes in portal areas, especially infiltrating bile duct epithelia were analyzed by light and electron microscopy using indirect peroxidaselabeled antibody method and monoclonal antibodies against pan-T (Leu 1), cytotoxic/suppressor T (Leu 2a), helper/inducer T (Leu 3a) and natural killer/K (Leu 7) and suppressor T (Leu 15) cells in liver biopsy specimens from four patients with primary biliary cirrhosis. Bile ducts with chronic nonsuppurative destructive cholangitis were observed in two patients. Leu 1+ and Leu 2+ cells were frequently seen in intimate contact with epithelial ductal cells. The majority of intraepithelial cells possessing Leu 2a antigen did not react with anti-Leu 15 antibody. Leu 3a+ or Leu 7+ cells seldom infiltrated ductal epithelia. These findings indicate that the majority of intraepithelial lymphocytes in bile ducts most likely represent Leu 2a+15- cytotoxic T cells. By immunoelectron microscopy, Leu 1+ or Leu 2a+ lymphocytes often breached the basement membrane of bile ducts and were present within dilated intercellular spaces between biliary epithelial cells. Furthermore, they often formed sharp or broad contacts with the epithelial cells, and occasionally pseudopods projecting from the surfaces of Leu 2a+ cells extended into the epithelial cells. Most of Leu 2a+ lymphocytes contained little cytoplasm with few granules and a small Golgi apparatus. Such findings suggest that cytotoxic T cells may contribute to the pathogenesis of chronic nonsuppurative destructive cholangitis in primary biliary cirrhosis.
A randomized trial of vasopressin and vasopressin plus nitroglycerin in the control of acute variceal hemorrhage
Authors: Gimson Alexander E. S. , Westaby David , Hegarty John , Watson Alastair , Williams Roger
Published: March 2007

A randomized trial was undertaken to determine efficacy of nitroglycerin when added to a vasopressin infusion in both reducing the complication rate and giving improved control of acute variceal hemorrhage. Seventy-two bleeding episodes in 57 patients were included, with vasopressin beng used on 34 occasions and vasopressin plus nitroglycerin on 38 occasions, for an infusion period of 12 hr. At the end of the 12-hr period, hemorrhage had been controlled significantly more frequently in those receiving combined therapy (26 of 38; 68%) than in those given vasopressin alone (15 of 34; 44%, p<0.05), although this difference was not statistically significant if those patients in whom therapy was discontinued due to drug complications were excluded from the analysis [hemorrhage controlled in the combined group (68%) and vasopressin alone (48%); x2=2.4, p>0.05]. Major complications requiring cessation of therapy were significantly less common in those given nitroglycerin—one occasion compared to seven in those given vasopressin alone (p<0.02). Thus, the addition of nitroglycerin to a vasopressin infusion results in a lower rate of complications and is more effective in controlling variceal hemorrhage.
Effect of experimental liver disease on the utilization for protein synthesis of orally administered α-ketoisocaproate
Authors: Muñoz Santiago , Walser Mackenzie
Published: March 2007

The incorporation of orally administered 1-14C-α-ketoisocaproate into the leucine of proteins in rats was compared with the incorporation of [3H]leucine itself administered simultaneously and expressed as a ratio, R. This ratio in whole body protein has been shown to be approximately equal to the nutritional efficiency of α-ketoisocaproate as a dietary substitute for leucine. In normal rats on a 14% protein diet, R in whole body protein (0.30 ± 0.01) and in the protein of various organs was the same whether the isotopes were given by single injection or 6-hr constant infusion. Thus, both techniques yield the same time-independent parameter, R, which measures the relative efficiency of α-ketoisocaproate as a substitute for leucine. R varied between organs as follows: liver (0.22 ± 0.01)<kidney<heart<salivary gland<brain<muscle (0.42 ± 0.01). In rats with galactosamine-induced acute liver failure (Group I), carbon tetrachloride-induced cirrhosis (Group II), or portal-systemic shunts (Group III), whole body protein R and R in the protein of organs other than the liver was generally increased compared with controls, as was R in circulating IgG in Group III; R in liver protein was unchanged (Groups II and III) or slightly lower than controls (Group I). Thus, severe liver disease and portal-systemic shunting both increase the utilization of α-ketoisocaproate for synthesis of protein in the body as a whole and in most organs. In the liver, however, α-ketoisocaproate utilization for protein synthesis is unaffected or slightly reduced.