bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pilot, double-blind, controlled 1-year trial of prednisolone treatment in primary biliary cirrhosis: Hepatic improvement but greater bone loss
Authors: Mitchison Harriet C. , Bassendine Margaret F. , Malcolm Archie J. , Watson Alex J. , Record Christopher O. , James Oliver F. W. 
Published: March 2007

A randomized, double-blind, 1-year pilot study of prednisolone treatment for primary biliary cirrhosis was undertaken. Nineteen patients received 30 mg prednisolone per day initially, with a maintenance dose of 10 mg per day. Seventeen patients received placebo. The groups were matched for age, menopausal status, hepatic histological stage and bilirubin.
Treatment was well tolerated without dropouts. Two patients receiving prednisolone developed diabetes, one a duodenal ulcer and one depression. One patient receiving placebo died of liver failure after 3 months.
Cholestatic symptoms (itch and fatigue) improved on prednisolone. There was significant (prednisolone vs. placebo) improvement in transaminase (p = 0.0214), alkaline phosphatase (p = 0.0032), procollagen III peptide (p = 0.0103), immunoglobulin G (p = 0.0012) and liver histology (p = 0.016); these changes were greatest among noncirrhotic patients.
No patient developed skeletal symptoms. Fifty-seven per cent had abnormal triolein breath tests prior to treatment, and 65% had abnormally low calcium absorption tests. Calcium absorption increased significantly in the treated group vs. placebo at 2 weeks (p < 0.02), but not at 1 year. Femoral photon absorptiometry fell in the prednisolone group after 1 year (-3.5% vs. placebo +0.5%, p < 0.05), as did trabecular bone volume (-6% vs. -2.8%, p < 0.005) and resorption surface (-11% vs. +2%, p < 0.02) on serial bone biopsy.
Prednisolone seems to exert a favorable hepatic effect in primary biliary cirrhosis but at the expense of increased bone loss to approximately twice the expected rate. Prednisolone treatment merits further assessment in primary biliary cirrhosis over a longer period, with attention to selection of patients most likely to benefit and continuing observation of bone mass to better establish the “cost/benefit” ratio.
Portal hypertension and ascites in acute hepatitis: Clinical, hemodynamic and histological correlations
Authors: Valla Dominique , Flejou Jean-François , Lebrec Didier , Bernuau Jacques , Rueff Bernard , Salzmann Jean-Louis , Benhamou Jean-Pierre 
Published: March 2007

We attempted to ascertain the mechanism of portal hypertension and ascites complicating acute hepatitis in 66 patients who underwent transvenous liver biopsy and measurement of hepatic venous pressure gradient. Increase in hepatic venous pressure gradient was related to the severity of acute hepatitis, as indicated by the significant correlation between the values for hepatic venous pressure gradient and serum bilirubin, serum albumin or coagulation factor V, and by its higher value in patients with, than in patients without, encephalopathy. Hepatic venous pressure gradient was higher in patients with, than in patients without, ascites (12.5 ± 3.4 vs. 8.4 ± 3.6 mmHg, respectively; p < 0.001). No ascites was clinically detectable in the patients in whom hepatic venous pressure gradient was below 6 mmHg.
We tested the hypothesis that sinusoidal collapse due to liver cell dropout was a major factor in portal hypertension. Semiautomatic determination of the fractional area of sinusoidal collapse on chromotrope-stained sections and automatic measurement of Sirius red-stained collagen fiber density were performed. Hepatic venous pressure gradient significantly correlated with fractional sinusoidal collapse area (r = 0.61, p < 0.001) and with Sirius red-stained collagen fiber density (r = 0.43, p < 0.01).
We conclude that portal hypertension in the course of acute hepatitis is related to the severity of liver damage and is a major factor in the development of ascites. Portal hypertension is mainly determined by intrahepatic vascular space being reduced by the collapse of sinusoids.
Aplastic anemia after liver transplantation for fulminant viral hepatitis: Black boX or bag of worms?
Authors: Zeldis Jerome B. 
Published: March 2007

Aplastic anemia developed in 9 of 32 patients (28 percent) undergoing orthotopic liver transplantation for acute non-A, non-B hepatitis, at one to seven weeks after the procedure. No patient previously had evidence of hematologic dysfunction or conditions known to be associated with aplastic anemia. No other cases of aplastic anemia were identified among 1463 patients undergoing liver transplantation for all other indications at the four centers participating in the study (chi-square = 415, P < 0.001; 95 percent confidence interval for the incidence of aplastic anemia after transplantation for non-A, non-B hepatitis, 13 to 44 percent, vs. 0.00 to 0.13 percent for all other indications).
The operative and postoperative treatment of these patients was not otherwise different, indicating that the aplastic anemia was a complication of the hepatitis, not of the transplantation proce- dure. Four of the nine patients died of complications due to infections. Three of the surviving patients have been followed for less than six months, one for one year, and one for two years. The two patients followed the longest have recovered marrow function to an appreciable degree, and two of the others have evidence of early recovery.
We concluded that patients undergoing ortho-topic liver transplantation for non-A, non-B hepatitis are at a high risk for the development of aplastic anemia.
Tissue–Specific Activity of Heterologous Viral Promoters in Primary Rat Hepatocytes and Hep G2 Cells
Authors: Xian-Jun Fang , Keating Armand , de Villiers Jean , Sherman Morris 
Published: March 2007

In preparation for studies using gene transfer, we have identified transcriptional control elements which are active in primary rat hepatocytes. We used plasmids which were constructed so that the promoter or enhancer of interest initiated transcription of the bacterial chloramphenicol acetyltransferase (CAT) gene. Plasmids were introduced into primary rat hepatocytes in culture, into Hep G2 cells and other human and animal cell lines and into bone marrow stromal cells, and CAT activity was assayed after 48 hr.
In primary rat hepatocytes, the highest CAT activity was obtained with plasmids carrying the Rous sarcoma virus long terminal repeat (pRSVCAT), or the SV40 early region promoter and enhancer (pSV2CAT). Hepatocytes carrying the murine cytomegalovirus immediate early promoter (pUCRNmCMVX/HCAT) also had appreciable CAT activity. No CAT activity was detected in rat hepatocytes carrying pSVOCAT (a promoterless construct), pUCRNtKCAT (herpes simplex thymidine kinase gene promoter), pLPVCAT (lymphocytotrophic papovavirus promoter) and pHBV1CAT (hepatitis B virus enhancer and core gene promoter). Therefore, for future studies of gene transfer in primary rat hepatocytes, the Rous sarcoma virus long terminal repeat or the SV40 early region promoter and enhancer can be effectively used to drive gene expression.
Hep G2 cells carrying pHBV1CAT had high CAT activity. Hep G2 cells carrying pHBV2CAT (similar to pHBV1CAT, but with the hepatitis B virus sequences in reverse orientation with respect to the CAT sequences) and pHBV3CAT (similar to pHBV2CAT, but hepatitis B virus sequences are separated from the CAT sequences by about 700 bases) also expressed CAT activity, but not as strongly as with pHBV1CAT. The hepatitis B virus enhancer and core gene promoter were also active in human nonliver cell lines but were virtually inactive in nonhuman cell lines.
Spontaneous Bacterial Empyema in Cirrhotic Patients: Analysis of Eleven Cases
Authors: Xiol Xavier , Castellote Jose , Baliellas Carme , Ariza Javier , Roca Ana Gimenez , Guardiola Jordi , Casais Luis 
Published: March 2007

Eleven episodes of spontaneous bacterial empyema were identified in eight cirrhotic patients with ascites. Criteria for spontaneous bacterial empyema included positive pleural fluid culture or polymorphonuclear cell concentration >500 cells/mm3, evidence of pleural effusion before an infectious episode and transudate characteristics during infection. In five cases, spontaneous bacterial empyema was culture–negative and was associated with spontaneous bacterial peritonitis. Ascitic fluid was culture–negative in two of these cases and culture–positive in three. Blood cultures were negative in all five of these cases. In six cases spontaneous bacterial empyema was culture–positive (Escherichia coli in four, Klebsiella pneumoniae in one and Clostridium perfringens in one). Four of these patients had the same organism in ascites; one had culture–negative spontaneous bacterial peritonitis and one had no infection of ascites. Blood cultures were positive in four of these patients; three died. Death was more frequent in patients with positive cultures than in those with negative ones (p < 0.05).
Patients with hydrothorax are prone to spontaneous bacterial empyema. This infection probably occurs through hematogenous seeding, but transfer of infected ascites from the abdominal cavity through the diaphragm cannot be excluded. Patients with spontaneous bacterial empyema may be asymptomatic or may be seen with fever, chills and dyspnea. Spontaneous bacterial empyema must be differentiated from parapneumonic empyemas. The presence of pleural effusion before the infectious episode, fluid characteristics and the organisms isolted are the clues for differential diagnosis. Treatment includes antibiotics; chest tube insertion probably is not necessary. (Hepatology 1990;11:365-370.)
Effect of Iron and Desferoxamine on Cell Growth And In Vitro Ferritin Synthesis in Human Hepatoma Cell Lines
Authors: Hann Hie-Won L. , Stahlhut Mark W. , Hann Christine L. 
Published: March 2007

To investigate the effects of iron supplementation on hepatoma cell growth, cells from a human hepatoma cell line, PLC/PRF/5, were grown in RPMI 1640 supplemented with 0, 10 and 20 μg/ml of FeSO4 and harvested weekly. At the end of 6 wk culture, cell mass measured 9.6, 14.7 and 13.2 gm, respectively. Amounts of ferritin from these cell masses were 0 (undetectable), 0.89 and 2.27 μg/gm of cells.
To study the effects of iron deprivation of hepatoma cells, three human hepatoma cell lines (PLC/PRF/5, Hep G2 and Hep 3B) were incubated in tissue culture medium mixed with graded amounts of an ironchelating agent, desferoxamine, for 48 to 96 hr at 37°C with 5% CO2. Over 50% cell death in PLC/PRF/5 cells and 30% to 50% cell death in Hep G2 and Hep 3B cells were observed 48 to 72 hr after exposure to desferoxamine. Addition of ferric citrate partially reversed the cytotoxic effect of desferoxamine. On the other hand, viability of control cells, human diploid cell line (WI 38), was not affected by desferoxamine. Even after 96 hr exposure to desferoxamine, cell death was only 2% to 4%.
These results suggest that (a) iron enhances tumor cell growth, (b) iron induces increased ferritin synthesis by tumor cells in vitro and (c) iron depletion causes tumor cell death but has little effect on normal human diploid cells.
These findings should be considered when designing treatment of patients with hepatoma. Iron oversupply in patients with cancer might enhance tumor growth and adversely affect cancer therapy. Iron chelation with desferoxamine might have a place in the treatment of patients with hepatoma in conjunction with other anticancer agents.(HEPATOLOGY 1990; 11:566:569.)
Immunolpathology of Acute Galactosamine Hepatitis in Rats
Authors: Jonker Meike A. , Dijkhuis Freke W.J. , Kroese Frans G.M. , Hardonk Machiel J. , Grond Joris 
Published: March 2007

Galactosamine hydrochloride induces liver disease in tats that morphologically resembles drug–induced hepatitis in man. In this study we analyzed the character of the inflammatory reaction following the toxic damage resulting from the administration of galactosamine hydrochloride using a broad panel of mono clonal antibodies to lymphocyte subsets and macrophages. Fat–storing cells were identified with a polyclonal anti–desmin antibody. Cellular proliferation was assessed by labeling S–phase cells with the thymidine analog bronmodeoxyuridine. Injection of galactosamine hydrochloride was associated with conspicuous hepatocyte necrosis and parenchymal granulocyte influx in the first 24 hr. thereafter, mononuclear inflammatory cells predominated, mainly T lymphocytes and macorphages, with maximal numbers at 48 hr. The majority of T lymphocytes were CD8–positive cells and were located in the portal tracts and parenchyma. CD4 positive T cells were scarce and confined to the portal tracts. Proliferation of fat–storing cells paralleled hepatocyte regeneration with maximal values after 48 to 72 hr.
The temporal relationship between infiltrating mononuclear cells, mainly T lymphocytes of CD8 phenotype and macrophages, fat–storing cell proliferation and hepatic gegeneration suggests pathophysiological interactions between these cell types in liver injury in the rat after galactosamine hydrochloride administration.(HEPATOLOGY 1990; 11:622:627.)
Micronodular Transpormation (Nodular Regenerative Hyperplasia) of the Liver: A Report of 64 Cases Among 2,500 Autopsies and A New Classification of Benign Hepatocellular Nodules
Authors: Wanless Ian R. 
Published: March 2007

Nodular regenerative hyperplasia is defined by he–patocellular nodules distributed throughout the liver in the absence of fibrous septa between the nodules. Most reports have been single cases so that the prevalencend clinical significance of nodular regenerative hyperplasia is uncertain. In this study, the hepatic histology of 2,500 consecutive autopsies was reviewed. A spectrum of nodular regenerative hyperplasia present in 2.6% of autopsy livers and qualitatively similar but lesser degrees of noduler transformation was found with nodular regenerative hyperplasia present in 2.6% of autopsy livers and qualitatively similar but lesser degrees of nodular transformation in a further 10.2%. Nodular transformation was also seen in 47% of livers with cirrhosis and 69% with portal veins was seen in all cases with nodlular regenerative byperplasal, but only 4.7% of these had evidence of portal hypertension.
The prevalence of various clinical states was compared in nodular regenerative hyperplasia and in controls. The reslults confirm, extend and quantify the spectrum of associated diseases. Nodular regenerative hyperplasia occurs in 5. 6% of individuals over age 80 and with increased frequency in patients with arteritis, polymyalgia rheumatica, massive tumor infiltration and mineral oil deposition. Nodular tumor infiltrtion and mineral oil deposition. Noduler regenerative hyperplasia appears to be the hepatic analogue of arterial and arteriolar nephrosclerosis.
A new classification of nodular transformation is proposed that encompasses the specturm of lessions described here and the previously defined entities of focal nodular hyperplasia, parial nodular transformation and “cirrhosis telangiectasia hepatis.” The major conclusion is that nodular regenerative yperplasia is a secendary and nonspecific tissue adaptation to tation to heterogeneous distribution of blood flow and does not represent a specific entity.(HEPATOLOGY 1990; 11:787–797.)
Splanchnic and Renal Extraction of Circulating Type Iii Procollagen Aminoterminal Propeptide in Patients With Normal Liver Function and in Patients With Alcoholic Cirrhosis
Authors: Bentsen Kirsten D. , Henriksen Jens H. , Bendtsen Flemming , Hørslev-Petersen Kim , Lorenzen Ib 
Published: March 2007

Splanchnic and renal extraction of circulating aminoterminal propeptide of type III procollagen and related antigens were studied in 12 patients with normal liver function and in 19 patients with alcoholic cirrhosis during catheterization.
Type III procollagen peptide in serum was measured in two assays: the Type III Procollagen Peptide Radioimmunoassay Kit, a new assay that selectively determines the intact propeptide (and larger type III propeptide–holding antigens) and the Type III procollagen Fab assay that measures both the intact propeptide and the smaller fragments that quantitatively dominate in serum.
A significant decrease in the concentration of the intact propeptide between the artery and the hepatic vein was found in the group with normal liver function (p < 0.01) and in patients with cirrhosis (p < 0.01). In patients with cirrhosis, however, the splanchnic extraction ratio of the intact propeptide (median = 0.04, range = –0.03 to 0.16) was significantly lower than in patients with normal liver function (median = 0.17, range = 0.05 to 0.36, p. < 0.01). The concentration of the intact propeptide in the hepatic vein was positively correlated to hepatic pressure (n = 18, r = 0.51, p < 0.05) and inversely correlated to indocyanine green clearance (n = 15, r = –0.61, p < 0.05). No splanchnic extraction could be demonstrated in the Type III propeptide Fab assay.
A significant renal extraction was found in the Fab assay, but not in Type III Procollagen Peptide Radioimmunoassay Kit. Similar extraction ratios were observed in both healthy patients (median = 0.11, range = 0.00 to 0.21) and cirrhotic patients (median = 0.14, range = 0.06 to 0.22).
Thus intact circulating type III procollagen peptide is extracted in the liver, and the extraction ratio is decreased in alcoholic cirrhosis. Smaller type III procollagen peptide–related antigens are extracted from the circulation by the kidneys.(HEPATOLOGY 1990;11:957–963.).
A Comparison of the Molecular Structure of Integrated Hepatitis B Virus Genomes in Hepatocellular Carcinoma Cells and Hepatocytes Derived From the Same Patient
Authors: Ogata Norio , Tokino Takashi , Kamimura Tomoteru , Asakura Hitoshi 
Published: March 2007

To elucidate critical genetic elements in the development of hepatocellular carcinoma associated with hepatitis B virus DNA integration, a single integrant in hepatocellular carcinoma cells and one species of multiple integrants in hepatocytes, both obtained from the same patient, were compared structurally using molecular cloning techniques. Both hepatitis B virus integrants showed similar inverted repeat sequences consisting of two defective virus genomes. The recombination of viral DNAs seemed to be mediated by short regions of base homology near the direct repeat 1 and at other regions of the virus genomes in both integrants. The virus component in the junction with host DNAs was the cohesive end region in each identical end of the viral integrant in hepatocellular carcinoma cells and in one end of the viral integrant in hepatocytes. The structure of the integrant in hepatocellular carcinoma cells was characterized by an inverted, duplicated conformation composed not only of integrated virus genomes but also of flanking cellular sequences. It was shown to be the so–called “alpha dimer” of satellite DNA. In contrast, the flanking, nonreiterated cellular DNA in the hepatocyte–derived clone did not show discernible rearrangement.
These findings suggest that a common mechanism underlies the integeration of hepatitis B virus DNA so that a similar organization of inverted repeat genomes is found in hepatocellular carcinoma cells and in hepatocytes. The unstable nature of cellular DNA where DNA integration occurs may be important in generating chromosome alterations found in hepatocellular carcinoma (HEPATOLOGY 1990;11:1017–1023.).
Immunohistochemical Study of Adhesion Molecules in Liver Inflammation
Authors: Volpes Riccardo , van den Oord Joost J. , Desmet Valeer J. 
Published: March 2007

Using monoclonal antibodies and in situ immunohistochemistry, we studied the distribution of “accessory” adhesion molecules (i.e., intercellular adhesion molecule–1 and leukocyte function-associated antigen–3) in 114 liver biopsy specimens with various inflammatory liver diseases and in 12 control liver biopsy samples without inflammation. The distribution of these adhesion molecules was compared with the presence on inflammatory cells of their natural ligands, lymphocyte function-associated antigen–1 and cluster of differentiation antigen–2, respectively.
In normal liver, intercellular adhesion molecule–1 and leukocyte function-associated antigen–3 reacted weakly with sinusoidal lining cells, portal vessel endothelium and scattered mononuclear inflammatory cells, whereas hepatocytes were constantly negative.
In contrast, all 114 biopsy samples of acute or chronic liver diseases revealed strong expression of intercellular adhesion molecule–1 and leukocyte function-associated antigen–3 on sinusoidal lining cells and on hepatocytes in areas of inflammation. Hepatocellular membrane positivity resulted in a “honeycomb pattern” of staining, which was panacinar in acute hepatitis and focal in chronic persistent or aggressive hepatitis. In various other chronic liver diseases, a multifocal periportal and intraacinar honeycomb pattern was detected. In all cases, a close topographical correlation was found between hepatocellular expression of intercellular adhesion molecule–1 and leukocyte function-associated antigen–3 on one hand and the presence of inflammatory cells expressing lymphocyte function-associated antigen–1 and cluster of differentiation antigen–2 on the other.
These data suggest that in inflammatory liver diseases adhesion between hepatocytes and inflammatory cells is mediated by two different pathways of cellular interaction, involving intercellular adhesion molecule–1/lymphocyte function-associated antigen–1 and leukocyte function-associated antigen–3/cluster of differentiation antigen–2. This may result in increased adherence and may facilitate antigen presentation to and activation of inflammatory cells. In this way, hepatocytes may play an active immunoregulatory role in the recruitment and retention of inflammatory cells during an immune response. (Hepatology 1990;12:59-65).