bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver plasma membrane-associated fibroblast growth: Stimulatory and inhibitory activities during experimental cirrhosis
Authors: Belyaev Nickolay D. , Budker Vladimir G. , Deriy Ludmila V. , Smolenskaya Irina A. , Subbotin Vladimir M. 
Published: March 2007

During experimental CCl4 cirrhosis, an increase of membrane-associated factor stimulating 3T3 cell proliferation in vitro was observed. This stimulator is a 150-kD protein similar to one previously described. In situ perfusion released growth stimulatory activity, suggesting a peripheral plasma membrane protein localizing on basolateral surfaces. The activity increased with increasing number of CCl4 treatments, reaching a maximum at the 14th intoxication. It was faster than the proliferation of connective tissues determined histologically. Cessation of treatment caused a decrease in activity to that of the level of untreated liver, although the number of fibroblastlike cells remained large. This data, taken with the results of experiments with enriched hepatocyte fraction, may serve as an evidence in favor of hepatocyte origin of the factor.
A factor inhibiting fibroblast proliferation was measured in detergent extracts from membranes, suggesting an integral membrane protein. The activity of the inhibitory factor increased in acute liver lesions, but at the stage of maximal fibrogenesis this factor is reduced to levels comparable to those of the intact liver. Therefore it is unlikely that this factor is involved in CCl4-induced fibrogenesis at the final stages.
These factors may be common controls for various hepatic lesions causing fibrosis, both in clinical and experimental modeling. (Hepatology 1992;15:525-531).
Acetylcysteine and fulminant hepatic failure
Authors: Sheiner Patricia , de Majo Wilfred , Levy Gary A. 
Published: March 2007

Background.
When administered early after an overdose of acetaminophen, intravenous acetylcysteine prevents hepatic necrosis by replenishing reduced stores of glutathione. How acetylcysteine improves the survival of patients with established liver damage induced by acetaminophen, however, is unknown. This study was undertaken to determine whether the beneficial effect of acetylcysteine under such circumstances could be due to enhancement of oxygen delivery and consumption.

Methods.
We studied the effect of acetylcysteine on systemic hemodynamics and oxygen transport in 12 patients with acetaminophen-induced fulminant hepatic failure and 8 patients with acute liver failure from other causes. The acetylcysteine was given in a dose of 150 mg per kilogram of body weight in 250 ml of 5 percent dextrose over a period of 15 minutes and then in a dose of 50 mg per kilogram in 500 ml of 5 percent dextrose over a period of 4 hours; measurements were made before treatment began and after 30 minutes of the regimen.

Results.
In the patients with acetaminophen-induced liver failure, the infusion of acetylcysteine resulted in an increase in mean oxygen delivery from 856 to 975 ml per minute per square meter of body-surface area (P = 0.0036), due to an increase in the cardiac index from 5.6 to 6.7 liters per minute per square meter (P = 0.0021). Mean arterial pressure rose from 88 to 95 mm Hg (P = 0.0054) despite a decrease in systemic vascular resistance from 1296 to 1113 dyn · sec · cm−6 per square meter (P = 0.027). There was an increase in oxygen consumption from 127 to 184 ml per minute per square meter (P = 0.0007) associated with an increase in the oxygen-extraction ratio from 16 to 21 percent (P = 0.022). The effects in the patients with acute liver failure from other causes were similar.

Conclusions.
The increase in oxygen delivery and consumption in response to acetylcysteine may account for its beneficial effect on survival in patients with fulminant hepatic failure induced by acetaminophen.
Portosystemic shunt without surgery
Authors: Elta Grace H. , Eckhauser Frederic E. 
Published: March 2007

Objective.
- To determine the effectiveness of the Palmaz balloon expandable stent for the creation of a transjugular intrahepatic portosystemic shunt. The device is designed to achieve portal decompression in patients with variceal hemorrhage secondary to portal hypertension.

Design.
- Transjugular intrahepatic portosystemic shunting was performed in eight patients during a 9-month period. Mean follow-up was 5 months.

Patients.
- All patients had cirrhosis with portal hypertension and varices. Bleeding occurred in seven patients from esophageal varices and in one patient from hemorrhoids.

Main Outcome Measures.
- Shunt patency and recurrent variceal hemorrhage.

Results.
- Shunts created from a transjugular approach between a hepatic and a portal vein (diameters of 8 to 12 mm) lowered the average portosystemic pressure gradient from 36 to 11 mm Hg. Mean postoperative hospital stay was 7.7 days. Complete variceal decompression after transjugular intrahepatic portosystemic shunt placement was identified endoscopically in all eight patients. The patient treated for hemorrhoids rebled and was treated successfully by transfemoral balloon expansion of the shunt diameter from 8 to 12 mm. All shunts were patent at 1 to 9 months (mean, 5 months) of follow-up.

Conclusion.
- Initial results suggest that transjugular intrahepatic portosystemic shunt is a safe and effective method of portal decompression for the treatment of variceal hemorrhage.
Effects of Amiloride on Renal Lithium Handling in Nonazotemic Ascitic Cirrhotic Patients With Avid Sodium Retention
Authors: Angeli Paolo , De Bei Erica , Pria Manuela Dalla , Caregaro Lorenza , Ceolotto Giulio , Albino Grazia , Gatta Angelo 
Published: March 2007

The reliability of lithium clearance as an index of distal fluid delivery in cirrhosis with ascites and in other clinical conditions characterized by low fractional sodium excretion has not yet been proven. In particular, lithium reabsorption in the amiloridesensitive segment of the distal tubule, as evidenced in experimental studies, has not been excluded in such clinical conditions. Thus the acute effect of amiloride on renal lithium handling in 15 nonazotemic ascitic cirrhotic patients with avid sodium retention was evaluated after at least 5 days of controlled sodium intake. Renal plasma flow, glomerular filtration rate, fractional sodium excretion, fractional lithium excretion, fractional potassium excretion, fractional excretion of uric acid, plasma renin activity, plasma aldosterone and human atrial natriuretic peptide were evaluated before and for 6 hr after the administration of amiloride (20 mg/os).
After amiloride administration a volume replacement scheme was enacted with intravenous amounts of saline solution, determined by the diuretic and natriuretic effect of the drug, to avoid volume depletion. Amiloride induced a prompt and sustained increase in fractional sodium excretion (from 0.28% ± 0.09% to 1.0% ± 0.41%, p < 0.001) and a decrease in fractional potassium excretion (from 9.38% ± 5.98% to 3.28% ± 2.24%, p < 0.0025), whereas it did not affect fractional lithium excretion and fractional excretion of uric acid. No change was observed in renal plasma flow, glomerular filtration rate, plasma renin activity, plasma aldosterone and human atrial natriuretic peptide.
It was concluded that lithium is not reabsorbed in the amiloride–sensitive segment of the distal tubule in nonazotemic ascitic cirrhotic patients with avid sodium retention. (Hepatology 1992;15:651-654).
Effects of Ethanol on Intercellular Communications and Polarization of Hepatocytes in Short–Term Culture
Authors: Hashieh Imad Abou , Mathieu Sylvie , Gerolami André 
Published: March 2007

ABSTRPlCT

The formation of intracellular lumina with apical differentiation is observed in several cancerous epithelial cell lines including human hepatocarcinoma. This disorder of cell polarization can be induced by the inhibition of cell–cell communication, a known factor of carcinogenesis.
This work was designed to study the effects of ethanol on the differentiation of hepatocytes in short–term culture. Isolated hepatocytes were plated on plastic culture dishes that were 35 mm in diameter (106 cells/dish). Three hours after plating, the hepatocytes were incubated in the presence of 20 mmol/L ethanol for 1 hr. Treated cells were compared with controls using morphometric methods after conventional treatment for ultramicroscopy and by measuring cellular dye coupling by the fluorescent Lucifer Yellow CH transfer method.
Bile canaliculi formation decreased in alcoholtreated cells (6.5% vs. 9.9%, 2p < 0.05), whereas intracellular lumina incidence increased (3.1% vs. 0.5%, 2p < 0.01). In parallel, the dye–coupling capacity decreased significantly when hepatocytes were treated with alcohol (2p < 0.01).
This work shows that short–term ethanol treatment induces significant disturbances of cell polarization and inhibits the reestablishment of cell–cell communication in cultured hepatocytes. These disorders could, at least in part, explain the carcinogenic effects of ethanol. (Hepatology 1992;15:751-756).
Genetic Alterations in the Gene Encoding the Major Hbsag: Dna and Immunological Analysis of Recurrent Hbsag Derived From Monoclonal Antibody—Treated Liver Transplant Patients
Authors: McMahon Gerald , Ehrlich Paul H. , Moustafa Zeinab A. , McCarthy Linda A. , Dottavio Diane , Tolpin Mark D. , Nadler Paul I. , Östberg Lars 
Published: March 2007

ABSTRPlCTA gene region encoding a segment of the major surface protein, HBsAg, of hepatitis B virus was analyzed from serum samples after orthotopic liver transplantation of three hepatitis B virus chronic carrier patients treated with a human anti—hepatitis B virus monoclonal antibody (SDZ OST 577). Each of these three patients became HBsAg negative after transplantation and therapy with the human anti—hepatitis B virus monoclonal antibody but returned to HBsAg positivity (first detected 143,251 and 252 days after the transplantation). Polymerase chain reaction DNA amplification was performed on DNA from serum samples showing low levels of recurrent HBsAg and reduced antigen reactivity with SDZ OST 577 antibody. Polymerase chain reaction DNA included a 230–bp highly conserved, major S gene region that was cloned into M13 bacteriophage; analysis of this DNA segment provided a consensus of DNA sequences for the serum samples exhibiting altered reactivity with the therapeutic monoclonal. Analysis of independent DNA clones from serum samples of patients exhibiting low but detectable recurrent serum levels of posttherapy HBsAg revealed the presence of S protein variant sequences when compared with polymerase chain reaction DNA derived from the original infected liver or pretherapy serum HBsAg. Genetic variation was predominant in a highly conserved peptide domain that has previously been implicated in antibody binding and neutralizing antibody epitopes. In independent patients infected with eitheradworaywhepatitis B virus subtypes, single nucleotide changes resulted in one to two amino acid differences for each variant allele (residues 124, 129, 131, 137, 140 and/or 145) when compared with pretherapy viral DNA. Administration of serum containing one of these variant viruses to a single hepatitis B—naive chimpanzee resulted in subclinical hepatitis and detectable levels of circulating anti–HBs and anti–HBc antibodies 49 and 70 days after virus administration, respectively. Hepatitis B virus DNA was recovered on liver biopsy between 6 and 8 wk after inoculation, although the animal remained persistently seronegative for HBsAg. DNA sequence analysis of both primate and patient liver hepatitis B virus confirmed the presence of the DNA encoding the S protein variant and associates this DNA with the predominant hepatotropic virus in liver infection. (Hepatology 1992;15:757-766).
Non–A, Non–B Chronic Hepatitis Is Chronic Hepatitis C: A Sensitive Assay for Detection of Hepatitis C Virus Rna in the Liver
Authors: Hosoda Kazuhiko , Omata Masao , Yokosuka Osamu , Kato Naoya , Ohto Masao 
Published: March 2007

ABSTRPlCT

To study the role of hepatitis C virus in non–A, non–B chronic hepatitis, 49 liver biopsy samples from 40 patients with non–A, non–B chronic hepatitis and 9 control patients were analyzed by complementary DNA/polymerase chain reaction. Two segments of the HCV genome, one in the nonstructural region and the other in the noncoding region, were amplified by two sets of primer pairs. With use of the nonstructural region primers, hepatitis C virus RNA was detected in 24 (60%) of 40 patients with non–A, non–B chronic hepatitis. Of these 40 patients, RNA was detected in 19 (70%) of 27 patients positive for antibody to hepatitis C virus and in 5 (38%) of 13 patients negative for antibody to hepatitis C virus. However, with the noncoding region primers, hepatitis C virus RNA was detected in 38 (95%) of 40 patients with non–A, non–B chronic hepatitis. Of these patients, the RNA was detected in 26 (96%) of 27 patients positive for antibody to hepatitis C virus and also in 12 (92%) of 13 patients positive for antibody to hepatitis C virus. Hepatitis C virus RNA was not detected in any of the control patients. Sequence analysis showed homology between our samples and the prototype to be only 66% to 77% in the nonstructural region but 99% to 100% in the noncoding region.
We conclude that almost all patients with non–A, non–B chronic hepatitis in Japan are currently infected with hepatitis C virus, regardless of the presence or absence of antibody to hepatitis C virus. This assay appears useful for the diagnosis, treatment and prevention of hepatitis C virus infection. (Hepatology 1992;15:777-781).
Energy Expenditure and Substrate Oxidation in Patients With Cirrhosis: the Impact of Cause, Clinical Staging and Nutritional State
Authors: Müller Manfred J. , Lautz Hans U. , Plogmann Birgit , Bürger Mechthild , Körber Jürgen , Schmidt Friedrich W. 
Published: March 2007

ABSTRPlCT

Many clinicians subjectively feel that cirrhotic patients frequently have clinical signs of hypermetabolism. However, it is unknown whether hypermetabolism is a constant feature of chronic liver disease, corresponds to liver destruction and repair or is of prognostic value. This article is about resting energy expenditure and substrate oxidation rates in 123 patients with biopsy–proven cirrhosis differing with respect to cause, duration of the disease, biochemical parameters of parenchymal cell damage, cholestasis, liver function, number of complications, clinical staging and nutritional state.
Resting energy expenditure varied between 1,090 and 2,300 kcal/day and differed from the predicted values in 70% of the patients. Resting energy expenditure was closely related to fat–free mass, and 52% of the variability could be explained by fat–free mass, age and sex. Of all the patients, 18% were hypermetabolic and 31% were hypometabolic. Hypermetabolism showed no strict association with the cause of cirrhosis, the duration of the disease, liver function, cholestasis, cell damage, clinical staging, blood hemoglobin, plasma thyroid hormone levels or human leukocyte antigens. An increased resting energy expenditure was associated with significant losses of muscle, body cell mass and extracellular mass at unchanged body fat, whereas fat and fat–free mass were increased in hypometabolic patients when compared with normometabolic patients. Lipid oxidation was increased, but glucose oxidation was reduced in nearly all patients with cirrhosis. This was most pronounced at advanced stages of liver disease.
Although similar with respect to liver function and clinical staging, 76.2% of hypermetabolic patients had transplants within the observation period, compared with only 16.7% and 8.1% in the normometabolic group and hypometabolic group, respectively. Posttransplantation mortality was independent of pretransplantation resting energy expenditure, but it increased significantly in patients with losses in body cell mass.
In conclusion, hypermetabolism is not a constant feature of cirrhosis and results more from extrahepatic than from hepatic factors. It may cause malnutrition and contributes to the clinical outcome of patients with chronic liver disease. (Hepatology 1992;15:782-794).
Cholesterol Nucleation Time in Gallbladder Bile of Patients With Solitary or Multiple Cholesterol Gallstones
Authors: Jüngst Dieter , Lang Thomas , von Ritter Christoph , Pratschke Ekkehard , Paumgartner Gustav 
Published: March 2007

ABSTRPlCT

Patients with multiple cholesterol gallbladder stones have been found to be at a higher risk for the recurrence of gallstones after successful nonsurgical treatment than those with a solitary stone. Cholesterol gallstone recurrence, like primary gallstone formation, probably involves a triple defect with supersaturation, abnormally rapid nucleation of cholesterol in bile and altered gallbladder motor function. We investigated whether the increased recurrence rate of patients with multiple stones might be caused by more rapid nucleation. Therefore the time required for cholesterol monohydrate crystals to appear in ultracentrifuged bile of patients with solitary (n = 71) or multiple (n = 42) cholesterol gallstones was determined.
The cholesterol nucleation time was significantly (p < 0.01) longer in the bile from patients with solitary stones (< 1 to 16 days, median = 2.0 days) than in the bile from patients with multiple stones (< 1 to 8 days, median = 1.0 days). Moreover, 15 of 71 (21.1%) patients with solitary cholesterol stones but only 1 of 42 (2.4%) patients with multiple cholesterol stones showed a normal (> 4 days) nucleation time.
However, no difference in the cholesterol saturation index was found between the bile samples from patients with solitary stones and the bile samples from patients with multiple stones (1.55 ± 0.65 vs. 1.54 ± 0.59, mean ± S.D., respectively). The more rapid cholesterol nucleation in gallbladder bile may, therefore, be the major risk factor causing the higher percentage of stone recurrence in patients with multiple cholesterol stones as compared with patients with solitary cholesterol stones. (Hepatology 1992;15:804–808).
Adenomatous Hyperplasia in the Vicinity of Small Hepatocellular Carcinoma
Authors: Eguchi Akira , Nakashima Osamu , Okudaira Sadayuki , Sugihara Shigetaka , Kojiro Masamichi 
Published: March 2007

ABSTRPlCT

The nodular lesions seen in the noncancerous areas of the 80 consecutively resected small hepatocellular carcinoma associated with cirrhosis were pathomorphologically studied. A total of 51 nodular lesions were found, and they were classified into the following four groups: large regenerative nodule (30 nodules), adenomatous hyperplasia (12 nodules), atypical adenomatous hyperplasia (4 nodules) and adenomatous hyperplasia containing cancerous foci (5 nodules). Grossly, all large regenerative nodules were well demarcated, but some of the adenomatous hyperplasia group were vaguely nodular. Atypical adenomatous hyperplasia and adenomatous hyperplasia containing cancerous foci accounted for 43% of the adenomatous hyperplasia group found in the vicinity of the 16 resected hepatocellular carcinoma (20%) out of 80 cases. The mean size (±S.D.) of the adenomatous hyperplasias containing cancerous foci, 15.8 ± 2.2 mm, was significantly larger than 10.1 ± 2.6 mm of the adenomatous hyperplasias (p < 0.01). All adenomatous hyperplasias containing cancerous foci and 75% of the atypical adenomatous hyperplasias demonstrated a marked fatty change, but none of the large regenerative nodules were accompanied by any fatty changes.
This study demonstrated the morphological transition from adenomatous hyperplasia to hepatocellular carcinoma that was suggestive of multistep hepatocarcinogenesis. As a result, it is predicted that approximately 20% of all hepatocellular carcinomas may have the potential for being of multicentric origin and that approximately 40% of adenomatous hyperplasias may undergo malignant transformation, but it is difficult to estimate the exact number of incidences. The presence of varying degrees of fatty change may be one of the significant morphological markers for a malignant transformation from adenomatous hyperplasia to hepatocellular carcinoma. We should also be aware that adenomatous hyperplasias larger than 1.5 cm in size might already contain cancerous foci somewhere in the nodule. Accordingly, adenomatous hyperplasia should be treated as a premalignant lesion. (Hepatology 1992;15:843-848).
Liver Metabolic Zonation in Rat Biliary Cirrhosis: Distribution Is Reverse of That in Toxic Cirrhosis
Authors: Sokal Etienne M , Mostin Joelle , Buts Jean Paul 
Published: March 2007

ABSTRPlCT

Liver cell functional heterogeneity has been shown to persist in toxic CCl4 cirrhosis in growing rats, but the zonation observed in cirrhotic nodules may be different in other types of cirrhosis. To investigate this possibility, we looked at the zonal activities of two microsomal enzymes, glucose–6–phosphatase and NADPH dehydrogenase, in cirrhotic nodules from growing rats with chronic cholestasis. Zonal activities were measured by quantitative cytochemistry and microdensitometry. Liver cell heterogeneity was demonstrated, and we confirmed that the metabolic zonation is the mirror image of that observed in toxic cirrhosis, with periportal activity at the nodule periphery and perivenular activity at the nodule centers. Glucose–6–phosphatase activity was 2.06 times higher at the peripheries of the nodules than at the centers, whereas NADPH dehydrogenase activity at the nodule periphery was 72% of the nodule center activity.
We conclude that a liver cell functional heterogeneity persists in biliary rat cirrhosis, with zonation the reverse of that previously found in toxic CCl4 cirrhosis. (Hepatology 1992;15:904-908).
Hepatitis C: Evaluating the Seropositive Blood Donor
Authors: Martin Paul 
Published: March 2007

ABSTRPlCT

Objective:
To determine the epidemiologic, clinical, serologic, and histologic importance of antibodies to hepatitis C virus (anti–HCV) in blood donors.

Design:
Cross–sectional identification and prospective evaluation of seropositive donors; retrospective assessment of infectivity; and nested casecontrol study for risk factors.

Setting:
Liver unit of a referral–based university hospital.

Subjects:
Of 30 231 consecutive donors, 368 (1.2%) were found to be anti–HCV–reactive by enzyme–linked immunosorbent assay (ELISA). Two hundred and fifty–four of these 368 donors were evaluated for risk factors by comparison with 284 age– and sex–matched controls. Eighty–six spouses of seropositive donors were also evaluated.

Measurements and Main Results:
Twenty–four percent of the seropositive donors had a history of percutaneous exposure to blood. This rate increased to 45% when only those donors confirmed to be anti–HCV positive by a second–generation recombinant immunoblot assay (RIBA–2) were considered. A family history of liver disease (odds ratio, 2.8; 95% CI, 1.6 to 4.8), previous blood transfusion (odds ratio, 6.1; 95% CI, 3 to 12.5), and a history of tattooing or intravenous drug abuse (odds ratio, 8.4; 95% CI, 2.3 to 31) were associated with anti–HCV seropositivity. An elevated alanine aminotransferase (ALT) level was found in 58% of the seropositive donors. Of the 150 donors tested, 104 (69%; CI, 62% to 77%) were confirmed by RIBA–2 to be anti–HCV positive. Of the 105 donors who had a biopsy, 16% had normal histologic findings, 11% had minimal changes, 21% had chronic persistent hepatitis, 45% had chronic active hepatitis, and 7% had active cirrhosis. All 77 donors with RIBA–2–confirmed seropositivity had histologic abnormalities. Of 43 donors evaluated in an infectivity study, 82% were implicated in previous HCV transmission. Only 2.3% of the spouses were anti–HCV positive. The ELISA, RIBA–2, and ALT results correlated with infectivity and abnormal histologic findings.

Conclusions:
In our geographic area, almost 70% of donors who are anti–HCV positive by ELISA are confirmed to be positive by RIBA–2; most of these donors appear to be chronic carriers of HCV and have substantial liver disease.