bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significance and specificity of antibodies to neutrophils detected by western blotting for the serological diagnosis of primary sclerosing cholangitis
Authors: Klein Reinhild , Eisenburg Joseph , Weber Paul , Seibold Frank , Berg Peter A. 
Published: March 2007

Antibodies against neutrophils have been detected in sera from patients with primary sclerosing cholangitis and inflammatory bowel diseases either by immunofluorescence or by enzyme-linked immunosorbent assay. To assess primary sclerosing cholangitis-specific antibodies, we examined sera from 30 patients with clinically and morphologically well-established primary sclerosing cholangitis by Western blotting against neutrophils and compared these results with those obtained by testing sera from patients with inflammatory bowel diseases.
By Western blot using sonified neutrophils, 24 (80%) of 30 primary sclerosing cholangitis sera were positive. Five antigenic determinants at 95, 60, 55, 40 and 30 kD were visualized. Twenty-eight of the primary sclerosing cholangitis sera also showed the characteristic perinuclear fluorescence pattern by immunofluorescence on neutrophils. Thus a serological diagnosis of primary sclerosing cholangitis could be made in 80% of patients based on these two methods. In contrast, only 9% of 23 patients with ulcerative colitis and 10% of 60 patients with Crohn’s disease were positive by Western blot, and these patients also showed positive perinuclear fluorescence pattern by immunofluorescence, suggesting an overlap between inflammatory bowel diseases and primary sclerosing cholangitis. Although some patients with classical primary biliary cirrhosis and autoimmune chronic active hepatitis had antibodies against primary sclerosing cholangitis epitopes, none of the patients with obstructive bile duct disorders, collagen diseases, Wegener’s granulomatosis or other hepatic and nonhepatic disorders were positive by Western blot, indicating the specificity of these five primary sclerosing cholangitis-related neutrophilic epitopes. (Hepatology 1991;14:114-1152.)
Iron and uroporphyrin in hepatocytes of inbred mice in experimental porphyria: A biochemical and morphological study
Authors: Siersema Peter D. , van Helvoirt René P. , Ketelaars Diane A. M. , Cleton Maud I. , de Bruijn Wim C. , Wilson Paul J.H. , van Eijk Henk G. 
Published: March 2007

Hexachlorobenzene-induced porphyria is iron dependent and characterized by the decreased activity of uroporphyrinogen decarboxylase and the accumulation of porphyrins in the liver. To examine the relationship between iron and porphyrins in liver tissue, we performed a biochemical and morphological (histological, ultrastructural and morphometrical) study in the livers of C57BL/10 mice. Mice were treated with hexachlorobenzene, iron dextran or the combination of hexachlorobenzene and iron dextran. An accumulation of porphyrins and an increased total iron content were found not only in the livers of mice treated with hexachlorobenzene and iron dextran but also in mice treated with iron dextran alone. In contrast, the amount of porphyrins was only slightly increased in the livers of mice treated with hexachlorobenzene alone. Needle-like structures, representing uroporphyrin crystals, were observed, histologically and ultrastructurally, in hepatocytes of mice treated with hexachlorobenzene and iron dextran and with iron dextran alone. Uroporphyrin crystals and ferritin iron were found in the same hepatocyte. A single uroporphyrin crystal, surrounded by ferritin iron, was observed in a hepatocyte of a mouse treated with hexachlorobenzene alone. Both in the livers of mice treated with hexachlorobenzene and iron dextran and in the livers of mice treated with iron dextran alone, morphometrical analysis showed that an increased area fraction of uroporphyrin crystals was associated with an increased area fraction of ferritin iron in hepatocytes.
Conclusions: In C57BL/10 mice, experimental porphyria can be induced by iron overload alone; uroporphyrin crystals and ferritin iron are located in the same hepatocyte; and the morphological co-occurrence of uroporphyrin crystals and ferritin iron in hepatocytes suggests a role for iron (as ferritin) in the pathogenesis of porphyria. (Hepatology 1991;14:1179-1188.)
Graft regeneration and host liver atrophy after auxiliary heterotopic liver transplantation for chronic liver failure
Authors: Willemse Pierre J. A. , Ausema Lambert , Terpstra Onno T. , Krenning Eric P. , Ten Kate Fibo W. J. , Schalm Solko W. 
Published: March 2007

We studied the size of the liver graft and the host liver in six consecutive patients undergoing auxiliary heterotopic liver transplantation for chronic endstage liver disease. In all cases, a liver reduced in size by left lateral hepatectomy was inserted. The sizes of the graft and host liver were estimated by planimetry of two-dimensional di-isopropyl iminodiacetic acid scintigrams taken 3, 7, 21, 90 and 180 days after surgery.
Graft size increased from a mean of 12.2 cm2 (95% confidence interval = 10.2 to 14.1) on day 3 to a maximum of 14.8 cm2 (95% confidence interval = 13.4 to 16.1) on day 21 and remained stable thereafter; in contrast, the host liver decreased in size from 9.6 cm2 (95% confidence interval = 6.8 to 12.3) on day 3 to 3.9 cm2 (95% confidence interval = 3.0 to 4.8) at mo 6.
We conclude that in patients with chronic liver failure, an auxiliary allograft reduced in size and placed adjacent to the host liver shows regenerative growth within 3 wk, whereas the host liver atrophies in 3 to 6 mo. (Hepatology 1992;15:54-57).
Sclerotherapy vs. esophageal transection vs. distal splenorenal shunt for the clinical management of esophageal varices in patients with child class A and B liver function: A prospective randomized trial
Authors: Kitano Seigo , Iso Yasunori , Hashizume Makoto , Yamaga Hirohiko , Koyanagi Nobuhiro , Wada Hiroya , Iwanaga Tetsuya , Ohta Masayuki , Sugimachi Keizo 
Published: March 2007

Ninety-six patients with good liver function (Child class A or B) and esophageal varices were randomly assigned to one of three groups given different treatments: endoscopic injection sclerotherapy (n = 32), esophageal transection (n = 32) or distal splenorenal shunt (n = 32). Five patients (5.2%) had to be excluded from this study because severe chronic pancreatitis made separation of the distal splenic vein from the pancreatic bed difficult. Esophageal transection was performed for these patients.
No deaths occurred during the 30 days of treatment. The 5-yr cumulative bleeding rates were 0%, 5.9% and 12.9% in the endoscopic injection sclerotherapy, esophageal transection and distal splenorenal shunt groups, respectively (no statistical significance). In no case in the three groups did death occur because of variceal bleeding. Sixteen patients died, mainly because of underlying liver disease; four were in the endoscopic injection sclerotherapy group, five were in the esophageal transection group and seven were in the distal splenorenal shunt group. No statistically significant difference in survival rate among the three groups was found.
These results show that endoscopic injection sclerotherapy is a satisfactory alternative to esophageal transection or distal splenorenal shunt for the clinical management of patients with esophageal varices. (Hepatology 1992;15:63-68).
Treatment of severe alcoholic hepatitis by infusion of insulin and glucagon: A multicenter sequential trial
Authors: Trinchet Jean-Claude , Balkau Beverley , Poupon Renée E. , Heintzmann François , Callard Patrice , Gotheil Cécile , Grange Jean-Didier , Vetter Denis , Pauwels Arnaud , Labadie Hélène , Chazouilleres Olivier , Mavier Philippe , Desmorat Hervé , Zarski Jean-Pierre , Barbare Jean-Claude , Chambre Jean-françois , Pariente Alexandre E. , Roulot Dominique , Beaugrand Michel 
Published: March 2007

Severe alcoholic hepatitis is still a therapeutic challenge. It has been recently advocated that a 3-wk infusion with insulin and glucagon reduces its short-term mortality rate. A multicenter, randomized, single-blind, sequential trial was designed to compare this treatment with placebo. The triangular boundary was defined with α = 0.05, β = 0.10 and estimated survival at 4 wk of 50% with placebo, 75% with treatment. Patients with biopsy-proven severe alcoholic hepatitis (presence of one or more of three criteria: encephalopathy, prothrombin activity ≤ 50%, bilirubinemia ≥ 100 μmol/L) were randomized into two groups; one treatment group received an infusion (12 hr/day) of an association of insulin (30 IU) and glucagon (3 mg), and a control group received an infusion of glucose. Treatments were administered during a 3-wk period, and the mortality rate was noted at 4 wk.
The decision to discontinue the trial was reached on the basis of results from the first 44 patients. Overall results were assessed in the 72 patients included at the time of this decision (treatment group: n = 37; control group: n = 35). Fifty-three patients had cirrhosis. No significant differences were noted between the two groups at inclusion on the basis of clinical, laboratory and histological criteria. The mortality rate was not significantly different in the two groups; 10 patients (27%) in the treatment group and 5 patients (14%) in the control group died. Causes of death were similar in the two groups and consisted primarily of gastrointestinal hemorrhage, hepatic failure and infectious events. Only one minor case of hypoglycemia was observed.
Treatment by the infusion of an association of insulin and glucagon is not beneficial in patients with severe biopsy-proven alcoholic hepatitis. (Hepatology 1992;15:76-81).
The clinical significance of molecular variation within the hepatitis B virus genome
Authors: Brown Jonathan L. , Carman William F. , Thomas Howard C. 
Published: March 2007

Although HBV has a circular DNA genome that is partially double stranded, it replicates by means of an RNA intermediate. The process is catalyzed by a translation product of the polymerase open reading frame that has reverse transcriptase activity. The enzyme is found in association with the virion and achieves a high rate of nucleotide misincorporation during transcription because such enzymes lack proofreading activity. The virus is remarkable for its efficient use of nucleic acid because the genome is only 3.2 kb long and yet it encodes four groups of proteins and their regulatory elements (1). This is achieved in some regions by reading the sequence through different frames to direct the synthesis of distinct proteins from the same genetic material. Only a few of the mutations that occur during the normal replication cycle therefore permit the entry of a new virus to the pool for natural selection. Nevertheless, patients with chronic hepatitis have been shown to have viruses with different sequences cocirculating, and some regions of the genome are poorly conserved between different isolates (2).
The existence of patients with evidence of HBV replication but no evidence of liver disease, both in the early phase of acute infection (3) and in some chronic infections (4), has led to the suggestion that the virus is not directly cytopathic but that it is the immune response to infected liver cells that causes the hepatitis (5). The development of polymerase chain reaction (PCR) sequencing techniques has allowed us to determine whether sequence variation occurs under host selection and offers an explanation for the variable outcome of HBV infection.
Fragmentation of bile duct stones by extracorporeal shock-wave lithotripsy: A five-year experience
Authors: Sauerbruch Tilman , Holl Joseph , Sackmann Michael , Paumgartner Gustav 
Published: March 2007

Over 5 yr, 103 elderly patients (mean age = 70 yr) with bile duct stones (mainly not amenable to endoscopic extraction) underwent adjuvant extracorporeal shock-wave lithotripsy using a first-generation kidney lithotripter. Disintegration of stones was achieved after a mean of 1.4 sessions in 92% of the patients. Spontaneous passage of fragments into the duodenum occurred in one fourth of the patients, and endoscopic extraction of fragments was necessary in 75% of the patients, resulting in complete clearance of the bile duct stones in 91 (88%) of 103 patients. The most important adverse effect was septic disease after extracorporeal shock-wave lithotripsy in 4% of the patients. The 30-day mortality rate was 1% (one patient), and another 15 patients died during a mean follow-up of 26 ± 14 mo (mainly of causes unrelated to biliary tract disease). Two of 91 patients who had been rendered stone free were readmitted because of recurrent stone disease during the follow-up period. Of the 43 patients who still had their gallbladders during extracorporeal shock-wave lithotripsy, 14% subsequently underwent cholecystectomy.
These data show that extracorporeal shock-wave lithotripsy of bile duct stones is a useful and safe adjunct to nonsurgical procedures for the removal of calculi in the biliary tree. (Hepatology 1992;15:208-214).
Vascular adhesion molecules in acute and chronic liver inflammation
Authors: Volpes Riccardo , van den Oord Joost J. , Desmet Valeer J. 
Published: March 2007

Adhesion to and penetration through the sinusoidal vascular endothelium is a mandatory step for leukocyte migration and accumulation at sites of liver inflammation. This leukocyte trafficking is controlled by interactions between adhesion molecules on leukocytes and corresponding ligands on endothelial cells.
We have analyzed the in situ distribution of two recently described vascular adhesion molecules (i.e., endothelial leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1) and of the lymphocyte “homing” receptor cluster of differentiation antigen-44 in normal and inflamed liver biopsy specimens. Endothelial leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1 were absent from normal liver tissue, but they were strongly expressed on sinusoidal lining cells in inflammatory liver diseases. Endothelial leukocyte adhesion molecule-1 expression predominated diffusely throughout the liver parenchyma in acute hepatitis; in contrast, vascular cell adhesion molecule-1 was mainly expressed in areas of periportal and intralobular inflammation in chronic active and persistent hepatitis. The “homing” receptor cluster of differentiation antigen-44 was weakly expressed on scattered mononuclear cells and on sinusoidal lining cells in normal liver tissue, but it was strongly up-regulated on mononuclear inflammatory cells and sinusoidal lining cells in acute and chronic hepatitis. In addition, reactivity for the cluster of differentiation antigen-44 was found on the membranes of variously sized clusters of hepatocytes in biopsy specimens with acute hepatitis.

De novo or up-regulated expression of these adhesion molecules on sinusoidal lining cells in inflamed liver biopsy specimens indicates that these cells actively modulate their phenotype in response to environmental factors, thus playing a key role in the recruitment of leukocytes in acute and chronic liver inflammation. (Hepatology 1992;15:269-275).
The effect of bile salts on carbonic anhydrase
Authors: Milov David E. , Jou Wou-Seok , Shireman Rachel B. , Chun Paul W. 
Published: March 2007

Bile salts are potent inhibitors of bovine carbonic anhydrase and human carbonic anhydrase I and human carbonic anhydrase II. To further characterize the binding of bile salts to carbonic anhydrase, rate constants for the CO2 hydration reaction in the presence of deoxycholate, cholate, glycocholate and taurocholate were determined using stop-flow experments. Values for the Michaelis-Menton dissociation constant for bovine carbonic anhydrase, human carbonic anhydrase I and human carbonic anhydrase II were found to be 5.2, 9.2 and 13.2 mmol/L, respectively. The inhibition constant values for the various bile salts tested ranged from 0.1 to 1 mmol/L for bovine carbonic anhydrase, 1.6 to 2.4 mmol/L for human carbonic anhydrase I and 0.09 to 0.7 mmol/L for human carbonic anhydrase II. Our results suggest a mechanism of noncompetitive carbonic anhydrase inhibition for bile salts.
Bile-salt binding to carbonic anhydrases as measured by scanning molecular sieve chromatography resulted in an increase in partition radius, molecular volume and surface area. The partition radius increased from 24 Å to 28 Å in the presence of 2.5 mmol/L sodium deoxycholate at critical micelle concentration. As determined by sedimentation equilibrium measurements, approximately 1 gm of carbonic anhydrase will bind 0.03 gm of deoxycholate, suggesting three to six binding sites for bile salt on the carbonic anhydrase molecule. The conformational changes and inhibition of carbonic anhydrases resulting from bile-salt binding may be important to the regulation of enzymatic activity in tissues along the enterohepatic circulation; by limiting bicarbonate availability this interaction may also contribute to the metabolic derangements seen in patients with cholestatic liver disease. (Hepatology 1992;15:288-296).
Temporal relationship of peripheral vasodilatation, plasma volume expansion and the hyperdynamic circulatory state in portal-hypertensive rats
Authors: Colombato Luis A. , Albillos Agustin , Groszmann Roberto J. 
Published: March 2007

Peripheral vasodilatation and plasma volume expansion are required to generate the hyperdynamic circulatory state observed in portal hypertension. To determine which of these factors is the initial event and to assess their temporal relationship with the development of hyperdynamic circulation, we sequentially measured plasma volume (by125I-albumin dilution), cardiac index (by thermodilution), mean arterial pressure (by catheterization), superior mesenteric and iliac arterial flows (by Doppler flowmetry) and calculated total and regional peripheral resistances in portal-hypertensive rats.Experimental groups were studied from day 1 through day 4 after portial portal-vein ligation (n = 110) or sham operation (n = 111). Decreased total peripheral resistance was detected within a day of portal-vein ligation (4.18 ± 0.21 mm Hg · min · ml−1.·100 gm vs. 5.19 ± 0.16 mm Hg · min · ml−1100 gm; p <0.01). Plasma volume increased significantly on day 2 (4.31 ± 0.07 ml · 100 gm−1vs. 3.86 ± 0.04 ml · 100 gm−1; p <0.05). Cardiac index and regional blood flows increased in parallel with plasma volume elevation. On day 4, maximum values of plasma volume (4.49 ± 0.08 ml · 100 gm−1vs. 3.73 ± 0.03 ml · 100 gm−1) coincided with fully developed hyperdynamic circulation, as shown by a significant elevation in cardiac index (32.3 ± 0.6 ml · min−1.100 gm−1vs. 25.5 ± 1.2 ml · min−1· 100 gm−1), iliac and mesenteric blood flow.On day 1, vasodilatation was present in the iliac arterial circulation. In contrast, the superior mesenteric artery vascular bed showed vasoconstriction in response to the portal outflow block. Vasodilatation of the superior mesenteric artery bed was delayed until day 4, the time point at which plasma volume is maximally expanded.In portal hypertension, peripheral vasodilatation is the first hemodynamic event in the development of hyperdynamic circulation. Vasodilatation is detectedfirst in the nonsplanchnic circulatory bed and precedes plasma volume expansion, which is then required for the development of the hyperdynamic circulatory state.
Lack of increase in heterozygous α1-antitrypsin deficiency phenotypes among patients with hepatocellular and bile duct carcinoma
Authors: Rabinovitz Mordechai , Gavaler Judith S. , Kelly Robert H. , Prieto Martin , Van Thiel David H. 
Published: March 2007

Homozygous α1-antitrypsin deficiency (PiZZ phenotype) is known to be associated with increased risk of cirrhosis and primary liver cancer. Although a relationship between heterozygous α1-antitrypsin deficiency and chronic liver disease was suggested recently, it is still a matter of controversy whether such patients are at increased risk of liver cancer. The goal of this study was to determine the prevalence of heterozygous α1-antitrypsin deficiency of different phenotypes among patients with primary hepatobiliary cancers.
We studied 82 patients with primary hepatobiliary cancer; 59 had hepatocellular carcinoma and 23 had bile duct carcinoma. α1-Antitrypsin quantitation and phenotyping were performed in each patient using standard methods. The distribution of the various Pi phenotypes was compared with that found in a normal population and reported elsewhere. Odds-ratio and X2 tests were used to measure the relative risk and the significance of association, respectively, between primary hepatobiliary cancers and heterozygous α1-antitrypsin deficiency.
Four patients in each of the cancer groups were heterozygous. Among the hepatocellular carcinoma patients, three had the PiMS phenotype and one had the PiMZ phenotype. Of these four heterozygous patients, only two had cirrhosis; one had cryptogenic cirrhosis and the other had hepatitis B virus-related cirrhosis. One noncirrhotic patient with a PiMZ phenotype had a fibrolamellar carcinoma. Of the four patients with bile duct carcinoma, three had the PiMS phenotype and one had the PiMZ phenotype. Of the four heterozygous patients, two had primary sclerosing cholangitis without associated inflammatory bowel disease and one patient had had previous biliary operations. Heterozygosity of α1-antitrypsin Pi types (non-PiMM) does not mark an increased estimated risk for hepatocellular carcinoma (odds ratio = 0.78; 95% confidence index = 0.28, 2.16; p = not significant), or bile duct carcinoma (odds ratio = 2.27; 95% confidence index = 0.77, 6.70; p = not significant). Based on these results, we conclude that heterozygous α1-antitrypsin deficiency is not associated with hepatocellular carcinoma or bile duct carcinoma. (Hepatology 1992;15:407-410).
Immunohistochemical study of extracellular matrix in acute galactosamine hepatitis in rats
Authors: Jonker Mieke A. , Dijkhuis Freke W. J. , Boes Adriana , Hardonk Machiel J. , Grond Joris 
Published: March 2007

A single injection of D-galactosamine hydrochloride induces acute self-limiting liver disease in rats that morphologically resembles drug-induced hepatitis in human beings. In this immunohistochemical study we examined the localization and expression of the hepatic extracellular matrix components fibronectin, laminin, collagen type I, collagen type III and collagen type IV and of the cell surface receptors (integrins) for fibronectin and laminin. Sections of liver tissue obtained at intervals of 6, 12, 18, 24, 30, 36, 48 and 72 hr and 7 and 21 days after galactosamine administration were immunostained with a panel of polyclonal monospecific antibodies and studied independently by two of us. Fibronectin was the first extracellular matrix component found to be increased, 12 hr after galactosamine injection, followed by collagen type III, and, in a later phase, collagen type IV, type I and laminin. Increased deposition of extracellular matrix was found in areas with liver cell necrosis and along sinusoids. Extracellular matrix immunoreactivity reached a maximum at 36 to 48 hr and decreased thereafter to preinjury levels 3 wk after galactosamine. Immunostaining for the fibronectin and laminin receptors revealed tissue localization identical to that of their ligands. However, the intensity of staining was opposite of that for the extracellular matrix, with a decrease of immunoreactivity after 24 to 48 hr.
The observed sequence of changes in hepatic extracellular matrix proteins after galactosamine injection resembles the repair reaction in other tissues and may reflect the particular function that each carries out during the process of liver healing after toxic injury. (Hepatology 1992;15:423-431).