bluuebunny/crossref_metadata_2025 huggingface dataset:
Inherited hyperammonemia: An algorithm for diagnosis
Authors: Batshaw Mark L.
Published: March 2007

Twenty-two patients with inherited hyperammonemic syndromes are presented. These patients represent 22 different families. The diagnosis was based mainly on family history, blood ammonium levels, acid base balance, urinary orotic acid, urinary and plasma amino acids and organic acids. The final diagnosis was confirmed by determination of liver enzyme activity. In 12 patients (54%), the first clinical manifestations were noticed after the neonatal period; 7 patients (31%) were diagnosed after infancy, and 8 (23%) after the age of 8 years. Two patients who represent the late-onset group of inherited hyperammonemic syndromes are presented in detail. The three most common diagnoses were ornithine transcarbamoylase deficiency, carbamoyl phosphate synthetase deficiency, and lysinuric protein intolerance, which comprised 59% of the diagnosed patients. Our data, based on one of the largest series reported, reveal a relatively large percentage of late-onset inherited hyperammonemic syndromes as compared with previous reports.
The pAS vector system and its application to heterologous gene expression in escherichia coli
Authors: Shatzman Allan R. , Rosenberg Martin
Published: March 2007

There are numerous proteins of biological interest which cannot be obtained from natural sources in quantities sufficient for detailed biochemical and physical analysis. The limited bioavailability of these molecules has made it impossible to consider their potential utilization as either pharmacological agents and/or targets. One solution to this problem has been the development of recombinant vector systems which are designed to achieve efficient expression of cloned genes in a variety of biological systems. This paper will describe the development and application of a particular set of vectors which have been designed to achieve efficient expression of essentially any gene coding sequence in Escherichia coli. The system utilizes efficient phage-derived transcriptional and translational regulatory signals and provides a strong regulatable promoter, an antitermination mechanism to ensure efficient transcription across any gene insert, high stability and, when appropriate, efficient translation initiation information. In addition, a wide variety of host strains have been developed in order to help control, stabilize and maximize expression of various cloned genes. The system has now been used to express efficiently more than 75 different prokaryotic and eukaryotic gene products. The application of this system to the expression and characterization of several oncogene products will be described.
Hepatofugal portal flow in cirrhosis: Observations on hepatic hemodynamics and the nature of the arterioportal communications
Authors: Rector William G. , Hoefs John C. , Hossack Kenneth F. , Everson Gregory T.
Published: March 2007

Six of 85 patients (7%) with alcoholic liver disease undergoing transhepatic portal pressure measurement had either stagnant (3 patients) or reversed (3 patients) portal blood flow documented by gentle hand injection of 1 to 2 ml of angiographic contrast. Portal blood flow was uniformly hepatopetal in 24 patients with nonalcoholic liver disease. Recurrent spontaneous hepatic encephalopathy and sodium retention occurred in 4 of 6 patients with stagnant or reversed portal flow; gastrointestinal bleeding was not seen. Standard laboratory tests of liver function were widely variable. Net portal pressure was lower in this group than in patients with alcoholic liver disease and forward portal flow (9.2 ± 2.6 vs. 15.6 ± 4.1 mm Hg, p < 0.001). Wedged hepatic vein pressure was 1 to 7 mm Hg higher than portal vein pressure in patients with reversed portal flow. The arterioportal extraction of bile acid was calculated from the difference in concentration between artery and portal vein, and total functional hepatic blood flow was calculated from the hepatic extraction and systemic clearance of indocyanine green. Extraction was 0%, and hepatic blood flow was 0.469 liter per min in a patient with hepatofugal portal flow and recurrent encephalopathy. Extraction was 20%, and hepatic blood flow was 4.014 liters per min in a patient who had never had encephalopathy. These data indicate that arterioportal communications may be sinusoidal or presinusoidal in patients who lose forward portal flow and that the amount of flow in the arterioportal circuit, together with its efficiency, largely determine the clinical outcome.
Renal response to atrial natriuretic peptide in patients with advanced liver cirrhosis
Authors: Salerno Francesco , Badalamenti Salvatore , Incerti Pierluigi , Capozza Loredana , Mainardi Laura
Published: March 2007

Sodium retention in liver cirrhosis is thought to be due to, among other things, lack of a natriuretic factor or failure to respond to one. α-Human-atrial natriuretic peptide is a peptide that accounts partly or entirely for the circulating natriuretic activity in man.

In the present study, we have evaluated the effects of the bolus administration of synthetic α-human-atrial natriuretic peptide (1 μg per kg) to patients with liver cirrhosis and variable degrees of sodium retention, α-Human-atrial natriuretic peptide induced rapid and marked increases of diuresis and natriuresis in patients without sodium retention or with moderate retention. The results were comparable to those obtained in six healthy control subjects. Conversely, the diuretic and natriuretic effects of α-human-atrial natriuretic peptide were attenuated or completely blunted in patients with avid sodium retention. The two groups of patients differed not only in basal sodium excretion, but also in plasma renin activity and in plasma aldosterone levels, suggesting that the reduced responsiveness to atrial natriuretic peptide might be due to excessive antagonism by antinatriuretic factors. The direct relationship between baseline sodium excretion rate and that stimulated by human-atrial natriuretic peptide administration was consistent with this interpretation. In none of the subjects did plasma renin activity peptide and cortisol levels change after human-atrial natriuretic peptide, while plasma aldosterone slightly declined in cirrhotics. Blood pressure fell after the administration of the peptide, with the drop greater in cirrhotic than in normal subjects. These data show that the hormonal and the vascular effects of human-atrial natriuretic peptide are not blunted in cirrhotics. Since angiotensin II plays a central role in sustaining blood pressure in patients with advanced liver cirrhosis, the marked drop in blood pressure has been tentatively ascribed to the specific ability of atrial natriuretic peptide to antagonize angiotensin, but other mechanisms cannot be excluded.

In conclusion, these data suggest that renal unrespon-siveness to atrial natriuretic peptide develops in patients with liver cirrhosis during the course of the disease and is strictly related to the severity of sodium retention.
Iron metabolism in the erythrophagocytosing Kupffer cell
Authors: Kondo Hitoshi , Saito Kainosuke , Grasso Joseph P. , Aisen Philip
Published: March 2007

Like the peritoneal macrophage, the isolated Kupffer cell is capable of processing and releasing iron acquired by phagocytosis of immunosensitized homologous red blood cells. When erythrophagocytosis is restrained to levels which do not affect cell viability, or less than 1.5 red cells/macrophage (phagocytic index of 150%), over 40% of iron acquired from red cells is released within 24 hr. More active erythrophagocytosis results in greater release of iron but progressive deterioration in cell viability. Iron release is temperature-dependent, the rate at 37° C being nearly 5-fold greater than at 4° C. Inclusion of either desferrioxaminine or apotransferrin in the culture medium augments iron release by 25 to 30%, with both agents together having an almost additive effect. Despite its effect on iron release, apotransferrin is not found in sonicates of Kupffer cells, while desferrioxamine appears to chelate iron within the cells. Ascorbate also enhances iron release, but at the expense of cell viability. Neither chloroquine nor colchicine at concentrations which do not affect cell viability influence iron release. The inflammatory state, characterized by hypoferremia due to impaired processing or release of iron by the reticuloendothelial system, may be modeled in vitro when serum from rats bearing turpentine-induced abscesses is included in the culture medium. Attempts to delineate the humoral agent responsible for this effect have not been successful, iron release being insensitive to the presence of interleukin-1, γ-interferon and tumor necrosis factor.
16,16-dimethyl prostaglandin E2 delays collagen formation in nutritional injury in rat liver†
Authors: Ruwart Mary J. , Rush Bob D. , Snyder Karen F. , Peters Ken M. , Appelman Henry D. , Henley Keith S.
Published: March 2007

Chronic nutritional injury was induced in rats by a high-fat, lipotrope-deficient diet. The hepatoprotective effect of 16,16-dimethyl prostaglandin E2 on the deposition of collagen and fat was assessed by histological evaluation and measurement of hydroxyproline. Dose-response studies established that optimal protection was achieved by the twice daily administration of 16,16-dimethyl prostaglandin E2 at 100 μg per kg (subcutaneous) or 250 μg per kg (oral). 16,16-Dimethyl prostaglandin E2 and a crystalline analog [(p-acetami-dobenzamido)phenyl ester of 16,16-dimethyl prostaglandin E2 significantly delayed both the deposition of collagen and the increase in hepatic hydroxyproline content. There was an excellent correlation between the histological assessment of collagen and the biochemical measurement of hydroxyproline. These data provide a rationale for the evaluation of prostaglandins in the treatment of human liver disease.
Localization of woodchuck hepatitis virus in the liver
Authors: Abe Kenji , Kurata Takeshi , Shikata Toshio
Published: March 2007

Localization of woodchuck hepatitis virus in liver tissue from 10 infected woodchucks was investigated immunohistochemically and ultrastructurally. Woodchuck hepatitis virus surface antigen was detected by immunoperoxidase methods in the cytoplasm of hepato-cytes with a fine granular and/or inclusion body appearance. Woodchuck hepatitis virus surface antigen positive hepatocytes were often found in the peripheral zone of hepatic lobules. In contrast to human hepatitis B core antigen, woodchuck hepatitis virus core antigen was observed only in the cytoplasm of hepatocytes, but not in the nuclei. In hyperplastic foci, woodchuck hepatitis virus antigen-positive hepatocytes were found in 3 of 8 animals. Furthermore, in 1 of 5 animals with hepatocel-lular carcinoma, woodchuck hepatitis virus surface antigen and woodchuck hepatitis virus core antigen were present in carcinoma cells. Electron microscopic examination revealed many filamentous structures (18 to 20 nm in diameter) in the cisternae of the endoplasmic reticulum. Noncoated core particles (18 to 20 nm in diameter) were found in the cytoplasm of the hepatocytes, but not in the nuclei. The coated particles (42 to 45 nm in diameter) were observed in the cisternae of the endoplasmic reticulum. These coated particles were shown to be morphologically identical to the virus particles in serum. These results indicate that woodchuck hepatitis virus core antigen is produced and assembled mainly in the cytoplasm of hepatocytes, and seems to be rapidly assembled into virion. The similarity of woodchuck hepatitis virus infection to human hepatitis B virus infection makes the woodchuck an excellent experimental model for the study of hepadna virus onco-genesis.
Microsomal specificity underlying the differing hepatic formation of bilirubin glucuronide and glucose conjugates by rat and dog
Authors: Sommerer Ursula , Gordon Ellen R. , Goresky Carl A.
Published: March 2007

Bilirubin monoglucuronide monoglucoside diester is one of the principal bilirubin conjugates in dog bile (and a lesser conjugate, in human bile), and bilirubin diglucoside is an occasional trace conjugate in dog bile whereas, in contrast, neither is detectable in rat bile. In order to investigate, in comparative fashion, the factors underlying the formation of glucuronide and glucose-containing conjugates, hepatic microsomes were isolated by differential centrifugation from the livers of both normal mongrel dogs and Sprague-Dawley rats, and their formation of bilirubin conjugates examined, in the presence of varying levels of UDP-glucuronate and UDP-glucose. Bilirubin and its conjugates were extracted and separated by high-performance liquid chromatography; a new methodology was devised, which clearly separates bilirubin diglucoside from bilirubin monoglucuronide, as well as bilirubin diglucuronide, the mixed monoglucuronide monoglucoside conjugate and bilirubin monoglucoside. At bilirubin levels of 12.5 μM, in the presence of equal amounts of both UDP-glucuronate and UDP-glucose, dog microsomes formed substantial amounts of both bilirubin diglucuronide and the mixed monoglucuronide-monoglucoside conjugate, and minor amounts of bilirubin monoglucuronide and bilirubin diglucoside. Microsomes from rat liver, under similar conditions, formed only bilirubin diglucuronide and bilirubin monoglucuronide. When only UDP-glucose was present, dog microsomes formed predominantly diglucoside and rat, predominantly monoglucoside. The findings imply that it is not the availability of the UDP-glycoside but rather the preference of the microsomal enzymic system for the different glycosidic nucleotides which dictates the varieties of bilirubin conjugates ordinarily formed in these two species.
Oral charcoal therapy of congenital erythropoietic porphyria
Authors: Tishler Peter V.
Published: March 2007

Günther’s disease, or congenital erythropoietic porphyria, is a rare autosomal recessive disorder of heme biosynthesis characteristically associated with diminished uroporphyrinogen III cosynthetase activity. Disfiguring photomutilation starts in childhood. Avoidance of sunlight has been the only sure way to prevent or retard photosensitivity. The treatments that have been tried have had limited success. A partial benefit after splenectomy has been reported, but there is little evidence of specific, long-term improvement. Haining and colleagues first reported suppression of bone marrow release of porphyrins by induced polycythemia, supporting the notion that disease activity can be modulated by diminishing porphyrin overproduction at the source (i.e., the bone marrow). Recently, Piomelli et al. reported complete suppression of symptoms in a 10-year-old child treated from birth with transfusion therapy and with splenectomy. Another approach is the use of orally administered sorbents such as charcoal and cholestyramine, which bind porphyrins in vitro, to retard enteral absorption of endogenous porphyrins excreted into the gut lumen. Cholestyramine has been reported to reduce photocutaneous sensitivity in porphyria cutanea tarda and to reverse the hepatic lesion in protoporphyria.

In this study, we compared different treatments for progressive photomutilation in a patient with congenital erythropoietic porphyria. The effects of short-term hypertransfusion were evaluated, as was the efficacy of long-term transfusion therapy over a two-year period. To test the potential usefulness of porphyrin-binding drugs, we estimated the enteral absorption of endogenous porphyrins in the proximal small bowel and monitored the effects on tissue and excreted porphyrins of short-term oral challenges with activated charcoal (ActaChar) and with cholestyramine. Charcoal therapy was more effective than cholestyramine and therefore was subsequently administered for a long period. The data collected allow comparison of long-term charcoal therapy and long-term blood-transfusion therapy. Treatment with charcoal for nine months lowered porphyrin levels in plasma and skin and resulted in a complete clinical remission during therapy. (A preliminary report on part of this work has appeared elsewhere).
Laparoscopy in the diagnosis of primary biliary cirrhosis: In the eye of the beholder
Authors: Lightdale Charles J.
Published: March 2007

Laparoscopic findings of the liver in 13 cases with primary biliary cirrhosis (PBC) diagnosed by wedge or needle biopsy were investigated. The characteristic features of laparoscopic appearance—gentle undulation—were observed in 11 out of 13 (85%) patients with PBC. These gentle undulations were irregularly shaped areas from 0.5 to 3 cm in diameter. Those observed in s-PBC were greater in number and more pronounced than those in a-PBC. In the concave areas of these undulations, the number of portal tracts was significantly greater than in the convex areas (p < 0.005). On the contrary, the number of interlobular bile ducts in the concave area was significantly less than in the convex area (p < 0.005). Therefore, gentle undulation was relatively specific to PBC, and was caused by scar formation and chronic non-suppurative destructive cholangitis in the portal area.
Understanding noncirrhotic portal hypertension: Ménage à FOIS
Authors: Wanless Ian R.
Published: March 2007

Twenty-six patients with the clinical and histologic diagnosis of primary biliary cirrhosis were reviewed. Nodular hyperplasia of the liver without fibrous rims, not reported hitherto in patients with primary biliary cirrhosis, was found in several patients with early histological stages. These changes resembled “nodular regenerative hyperplasia of the liver” and were usually present as multicellular thickness in zones 1 and 2 of the hepatic lobules. Such lesions were preferentially found in patients with esophageal varices, suggesting that the nodular hyperplasia may occur in relation to a disturbance of portal venous blood flow within the liver in primary biliary cirrhosis in early histological stages.
Intrahepatic pressure measurement: Not an accurate reflection of portal vein pressure
Authors: Fenyves Daphna , Pomier-Layrargues Gilles , Willems Bernard , Côté Jean
Published: March 2007

Previous studies have established the reliability of percutaneous portal venous pressure measurement using a Chiba needle, a procedure requiring fluoroscopic guidance. Intrahepatic pressure has been advocated by some as a simple and safe index of portal venous pressure. The aim of this study was to examine the reliability of intrahepatic pressure measurement and its relationship to portal venous pressure. Fifty patients requiring liver biopsy were included: 29 with cirrhosis (n = 20 micronodular, n = 9 macronodular) and 21 with various hepatic disorders but no cirrhosis. The procedure was performed under fluoroscopic guidance, using a Chiba needle connected to a manometer by a saline-filled catheter. Immediately prior to biopsy, each patient underwent measurement of: (i) 3 to 5 separate intrahepatic pressures, the intraparenchymal site being inferred by the lack of blood or bile return; and (ii) portal and hepatic venous pressures, the intravascular position of the needle being ascertained by the reflux of blood and the vessel identified with injection of contrast. Intrahepatic pressure measurements showed great intraindividual variability (variation coefficient up to 115%). Mean intrahepatic pressure (13.19 ± 8.32 mm Hg) was similar to portal venous pressure (14.43 ± 6.10 mm Hg) in the noncirrhotics but significantly lower in the cirrhotics (intrahepatic pressure = 18.34 ± 8.82 mm Hg, portal venous pressure = 22.52 ± 9.47 mm Hg; p < 0.01). The difference between these two parameters exceeded 3 mm Hg in 50% of patients (mean = 9 mm Hg, range = 4 to 19 mm Hg), both in cirrhotics and noncirrhotics. We conclude that intrahepatic pressure measurements are not reproducible and do not represent a reliable index of portal venous pressure.
Prognostic indicators in alcoholic cirrhotic men
Authors: Gluud Christian , Henriksen Jens H. , Nielsen Gert
Published: March 2007

The relationships between portal pressure, liver function and clinical variables on one hand and development of variceal hemorrhage and death on the other were investigated in 58 men with newly diagnosed alcoholic cirrhosis. Portal pressure was determined during hepatic vein catheterization as wedged minus free hepatic vein pressure, and median pressure was 14 mm Hg (range = 3 to 26 mm Hg). Fourteen of 31 patients (45%) had esophageal varices at upper gastrointestinal endoscopy (the size being considered large in nine patients).

During follow-up (median = 31 months; range = 2 to 51 months), 12 patients (21%) developed variceal hemorrhage. Applying Cox’s regression analysis, information about previous variceal bleeding (p = 0.0046), large varices at endoscopy (p = 0.012), hepatic vein pressure gradient (p = 0.0056) and indocyanine green clearance (p = 0.038) all contained significant prognostic information regarding development of variceal hemorrhage, even when easily obtained variables with known prognostic information were included [modified Child-Turcotte’s criteria and incapacitation index (a weighted sum of days without normal health)].

During follow-up, 17 patients (29%) died. Applying Cox’s regression analysis, large varices at endoscopy (p = 0.012) and hepatic vein pressure gradient (p = 0.019) contained significant prognostic information regarding death, in addition to the information contained in the modified Child-Turcotte’s criteria and incapacitation index. In conclusion, prediction of prognosis in alcoholic cirrhotic men may be significantly improved by information about size of esophageal varices and level of portal pressure.
The effect of chronic ethanol feeding on ornithine decarboxylase activity and liver regeneration
Authors: Diehl Anna Mae , Chacon Marco , Wagner Patrick
Published: March 2007

The effects of ethanol on liver regeneration are poorly understood. Acute and chronic exposure to ethanol have been found to exert opposite effects on the induction of ornithine decarboxylase, the rate-limiting enzyme for polyamine biosynthesis. Polyamines are necessary for DNA synthesis and liver regeneration after chemical or surgical liver injury. Short-term exposure to ethanol, which inhibits ornithine decarboxylase has been shown to inhibit DNA synthesis and liver regeneration, whereas more chronic exposure to ethanol increases ornithine decarboxylase activity and therefore could conceivably stimulate DNA synthesis and regeneration. To explore this later possibility, the effects of chronic ethanol consumption on ornithine decarboxylase activity, DNA synthesis and liver regeneration were studied in rats after sham laparotomy and partial hepatectomy. Chronic ethanol feeding failed to inhibit the induction of ornithine decarboxylase that occurred after partial hepatectomy and yet significantly inhibited posthepatectomy DNA synthesis and restitution of liver mass. These data suggest that the induction of hepatic polyamine biosynthesis is dissociated from DNA synthesis and liver regeneration after chronic consumption of ethanol.
Vitamin a hepatotoxicity in multiple family members
Authors: Minuk Gerald Y. , Kelly James K. , Hwang Wei-Sek
Published: March 2007

Three of five family members experienced symptoms and biochemical evidence of hepatitis that could not be explained on the basis of infectious, metabolic or immunologic disorders of the liver. A history of prolonged ingestion of moderate amounts of vitamin A (20,000 to 45,000 IU per day for 7 to 10 years) was obtained in each of the three family members and was absent in the remaining two unaffected individuals. A liver biopsy performed in one family member confirmed the diagnosis of vitamin A toxicity. This report emphasizes the finding that even moderate amounts of vitamin A, when ingested over a prolonged period of time, can cause significant hepatocellular injury.
A new variant of type IV glycogenosis: Deficiency of branching enzyme activity without apparent progressive liver disease
Authors: Greene Harry L. , Brown Barbara I. , McClenathan Daniel T. , Agostini Rocco M. , Taylor Suzanne R.
Published: March 2007

Type IV glycogenosis is due to branching enzyme deficiency and is usually manifested clinically by progressive liver disease with cirrhosis and hepatic failure between the second and fourth years of life. We describe a 5-year-old boy who, following an acute febrile illness at 2 years of age, was first noted to have hepatomegaly with mildly elevated serum transaminase levels. Liver biopsy revealed hepatic fibrosis with periodic-acid Schiff-positive, diastase-resistant inclusions in hepatocytes and fibrillar inclusions characteristic of amylopectin by electron microscopy. Enzymatic assay revealed deficient hepatic branching enzyme activity with normal activity of glucose-6-phosphatase, debranching enzyme and phosphorylase activities. During the succeeding 3 years, he grew and developed normally with apparent resolution of any clinical evidence of liver disease and only intermittent elevation in serum transaminase levels associated with fever and prolonged fasting. Repeat liver biopsy at 4 years of age showed persistence of scattered hepatocellular periodic-acid Schiff-positive, diastase-resistant inclusions, but no progression of hepatic fibrosis in spite of persistent deficiency of hepatic branching enzyme activity. Skeletal muscle and skin fibroblasts from the patient also showed deficient enzyme activity. Skin fibroblasts from both parents exhibited half the normal control activity, suggesting a heterozygote state.

This is the first documented patient with deficiency of branching enzyme but without evidence of progressive hepatic disease. This patient, coupled with reports of other patients with late onset hepatic or muscle disease with branching enzyme deficiency, suggests that the defect resulting in Type IV glycogen storage disease is more heterogenous and possibly more common than previously suspected.
Phenobarbital induction of cytochrome p-450 b,e genes is dependent on protein synthesis
Authors: Chianale Jose , Mulholland Leyna , Traber Peter G. , Gumucio Jorge J.
Published: March 2007

Phenobarbital induces liver cytochrome P-450 b,e proteins mainly by increasing the rate of transcription of these genes. The mechanism responsible for the phenobarbital increment in the rate of transcription of cytochrome P-450 b,e genes is unknown. The objective of this study was to assess whether active protein synthesis was needed for phenobarbital to induce the liver cytochrome P-450 b,e genes. Cycloheximide (2 mg per kg, i.p.) was administered 90 min prior to a single inductive dose of phenobarbital (80 mg per kg, i.p.) and mRNAS measured at 3, 6 and 12 hr by dot-blot hybridization. While phenobarbital increased cytochrome P-450 b,e mRNAs about 12-fold at 3 hr, this induction was abolished by cycloheximide. To define whether the absence of protein synthesis in hepatocytes inhibited the phenobarbital induction of cytochrome P-450 at the transcriptional level, in vitro transcription rates using isolated nuclei were measured. After phenobarbital administration, there was about a 20-fold increment in transcriptional rate of cytochrome P-450 b,e genes. This increment was abolished by prior injection of cycloheximide. It is proposed that either preexisting regulatory proteins or transacting factors dependent on active protein synthesis participate in the regulation of liver cytochrome P-450 b,e gene transcription after phenobarbital.
Cholesterol nucleation-influencing activity in t-tube bile
Authors: Groen Albert K. , Stout Jan P. J. , Drapers Jan A. G. , Hoek Frans J. , Grijm Rob , Tytgat Guido N. J.
Published: March 2007

Nucleation-influencing activity was determined in T-tube bile samples derived from patients with obstructive jaundice. Since native T-tube bile samples do not nucleate, nucleation-influencing activity was determined by measuring the influence of T-tube bile on the nucleation time of model bile. In the assay, T-tube bile was mixed with model bile, and the nucleation time of this mixture was compared with the nucleation time of a model bile supplemented with the same amount of lipid as present in the bile sample. The results were expressed as ratio of the nucleation time of the mixture and the nucleation time of the control (NTm/NTc). There was a significant difference (p < 0.01) between bile samples from patients with cholesterol gallstones and samples from patients with biliary obstruction due to other causes. More than 80% of the 33 samples from eight patients with stones were nucleation-promoting (NTm/NTc ≤ 0.6). Of the 40 bile samples from patients without stones, 7 were nucleation-promoting, 25 had no effect (NTm/NTc = 0.8 to 1.2) and 8 bile samples were nucleation-inhibiting (NTm/NTc ≥ 1.4). There was no correlation between the lipid or protein content of a T-tube bile sample and its nucleation-influencing activity.

The presence of both nucleation-promoting and nucleation-inhibiting activity in the same T-tube bile was demonstrated by chromatography on concanavalin A-Sepharose. More than 75% of the biliary protein did not bind to the column. This fraction showed nucleation-inhibiting activity. However, nucleation inhibitor present in this fraction was unstable, and after destruction of the inhibitor, the fraction showed promoting activity. This suggests that, in addition to inhibitor, this fraction also contained nucleation-promoting activity. About 10% of biliary protein did bind to concanavalin A-Sepharose and could be eluted with α-D-methylmannopyranoside. This fraction always contained nucleation-promoting activity. Both this factor and the nucleation-promoting factor that did not bind to concanavalin A were resistant to treatment with the proteolytic enzyme pronase. We conclude that T-tube bile contains at least three different classes of nucleation-influencing factors. The balance between promoting and inhibiting activity in a particular bile sample determines the overall nucleation-influencing effect of the sample. In bile from cholesterol gallstone patients, this balance is shifted towards promoting activity. One of the promoting factors probably is a glucose-/mannose-containing glycoprotein.
Serum 2′,5′-oligoadenylate synthetase activity during interferon treatment of chronic hepatitis B
Authors: Shindo Michiko , Okuno Tadao , Matsumoto Masayuki , Takeda Makoto , Takino Tatsuro , Sokawa Junko , Iwata Akira , Sokawa Yoshihiro
Published: March 2007

We measured 2′,5′-oligoadenylate synthetase activities in serum and peripheral blood mononuclear cells from 10 patients with chronic hepatitis B who were being treated with interferon so as to determine whether 2′,5′-oligoadenylate synthetase activity in serum reflected 2′,5′-oligoadenylate synthetase activity in peripheral blood mononuclear cells, and whether it could be used to monitor interferon treatment. Pretreatment values of 2′,5′-oligoadenylate synthetase activity in patients’ serum and peripheral blood mononuclear cells were not statistically different from values from control subjects. When interferon was administered, serum levels of 2′,5′-oligoadenylate synthetase began to rise within 3 hr, reached peak values at 12 hr and then declined. The levels of 2′,5′-oligoadenylate synthetase activity both in serum and peripheral blood mononuclear cells increased substantially during interferon treatment, ranging 2- to 50-fold greater than initial levels. The levels of 2′,5′-oligoadenylate synthetase in serum correlated closely with levels in peripheral blood mononuclear cells. In addition, when the levels of 2′,5′-oligoadenylate synthetase rose during interferon administration, serum hepatitis B virus DNA polymerase values fell, and, in some cases, DNA polymerase rose again when 2′,5′-oligoadenylate synthetase fell after discontinuation of interferon. These findings’ suggest that 2′,5′-oligoadenylate synthetase activity in serum accurately reflects the antiviral effect of interferon and could be used to monitor interferon treatment.
An experimental transmission of woodchuck hepatitis virus to young chinese marmots
Authors: Zhihong Jin , Guolong Zhao , Shisong Xiong , Pingyuan Kou , Lili Ma , Hongtao Chen , Jianying Qi , Qiuju Ba , Kai Mai
Published: March 2007

Fourteen young Chinese marmots (Marmota bobak sibirica Radde) were randomly allocated to two groups of seven each. They were injected intrahepatically with a standard woodchuck hepatitis virus challenge pool or a negative pool, prepared from sera of woodchucks with and without woodchuck hepatitis virus infection, respectively. Marmot No. 2 in the experimental group experienced an episode of seroconversion from woodchuck hepatitis surface antigen to anti-woodchuck hepatitis antibody. Woodchuck hepatitis virus DNA was detected, and woodchuck hepatitis surface antigen particles of both spherical and filamentous forms and intact woodchuck hepatitis virus virions were found in its serum. By contrast, none of the control group animals (receiving the negative pool) produced any marker of woodchuck hepatitis virus. This suggests that young Chinese marmots can get woodchuck hepatitis virus infection.
Pathology of chronic hepatitis b virus infection in children: With special reference to the intrahepatic expression of hepatitis B virus antigens
Authors: Hsu Hey-Chi , Lin Yon-Ho , Chang Mei-Hwei , Su Ih-Jen , Chen Ding-Shinn
Published: March 2007

The clinical, virologic and pathologic features of chronic hepatitis B virus infection were studied in 66 children, of whom 29 were symptomatic and 37 asymptomatic. The majority (79%) of symptomatic children had histologically aggressive diseases: 11 had chronic active hepatitis and 10 had cirrhosis. In contrast, most asymptomatic children had nonaggressive diseases (35 cases); only 2 had chronic active hepatitis. Nine of the 10 children with cirrhosis were under 6 years of age, and the cirrhosis was often advanced, indicating that hepatitis B virus infection can cause the rapid development of cirrhosis in early life. HBcAg was present in 71% of 62 cases examined and correlated well with the status of HBeAg in serum. Cytoplasmic HBcAg was more frequently associated with aggressive disease than was nuclear HBcAg expression alone or no detectable HBcAg in the liver. A male predominance (75%) was found, particularly in children with aggressive diseases (91%) compared to those with nonaggressive forms of disease (67%). Sera from mothers of 43 of these children were tested for HBsAg, and 51% were positive. HBsAg was particularly common among mothers of children with symptomatic disease (69%) or cirrhosis (100%). These findings suggest that male sex and perinatal infection are important factors in the development of overt chronic hepatitis B and cirrhosis in children.
Intraoperative ultrasound in detecting hepatic metastases
Authors: Taylor Kenneth J. W.
Published: March 2007

As a new screening procedure, intraoperative ultrasonography using high-resolution real-time instruments was used routinely in 84 colorectal cancer operations to scan the entire liver for liver metastases. In 10 operations (11.9%), intraoperative ultrasonography identified 14 previously unrecognized metastatic tumors, all of which were less than 2 cm in size and were nonpalpable. The sensitivity of this technique in detecting metastatic liver lesions (97.8%) was significantly superior (p < 0.01) to that of preoperative ultrasound (41.3%), computed tomography (47.8%), and surgical exploration (58.7%), while the specificity of each test was comparable (approximately 90%). High-resolution intraoperative ultrasonography is safe, simple to perform and more accurate than preoperative imaging and surgical exploratory methods. Therefore its use is encouraged during colorectal cancer surgery for screening of liver metastases.
A coded histologic study of hepatic graft-versus-host disease after human bone marrow transplantation
Authors: Shulman Howard M. , Sharma Pankaj , Amos Deborah , Fenster Frederick L. , McDonald George B.
Published: March 2007

We tested the hypothesis that liver histology from patients with graft-versus-host disease could be distinguished from other common liver diseases. Liver biopsies from 33 allogeneic marrow transplant recipients with acute and chronic graft-versus-host disease and 37 nontransplant liver disease patients without graft-versus-host disease were recut, restained and coded for blind review.

Analysis of individual histologic features showed significantly more cytologic aberration of bile duct epithelium and more cholestasis among biopsies with graft-versus-host disease when compared to biopsies without graft-versus-host disease (p ≤ 0.05). The duration of graft-versus-host preceding the biopsy influenced the histologic features. Biopsies before Day 35 showed frequent acidophilic bodies but infrequent bile duct changes. Biopsies from Days 35 to 90 posttransplant had more frequent bile duct exocytosis and disruption, and biopsies from patients with chronic graft-versus-host disease (beyond Day 90) showed more frequent portal fibrosis and bile duct dropout.

Pattern assessment of coded biopsies showed that a histologic diagnosis of graft-versus-host disease had a positive predictive value of 86%, a sensitivity of 66% and a specificity of 91%. False-negative diagnoses occurred most frequently in biopsies obtained less than 4 weeks posttransplant, usually because bile duct abnormalities were not present. False-positive diagnoses of graft-versus-host disease occurred in nongraft-versus-host disease biopsies with periportal inflammation and proliferated bile ducts. However, biopsies of chronic graft-versus-host disease had more frequent dropout and disruption of bile duct epithelium than did biopsies of acute or chronic hepatitis.

We conclude that a histologic diagnosis of hepatic graft-versus-host disease is likely to be correct if histology shows abnormal bile duct epithelium and cholestasis. While distinction between chronic graft-versus-host disease and non-A, non-B viral hepatitis is imprecise, cytologically atypical and destructive bile duct features favor chronic graft-versus-host disease.

The histologic appearance of graft-versus-host disease is similar to that of primary biliary cirrhosis.
Hepatic transplantation survival: Correlation with adenine nucleotide level in donor liver
Authors: Lanir Amos , Jenkins Roger L. , Caldwell Cary , Lee Robert G. L. , Khettry Urmila , Clouse Melvin E.
Published: March 2007

The hypothesis was tested that human donor livers with higher ATP content and energy charge achieve better results after hepatic transplantation. Biopsies were obtained from 25 donor livers immediately prior to implantation and analyzed for adenine nucleotides using high-performance liquid chromatography. The results were correlated with organ histology, transplant function and outcome. Significantly higher concentrations of ATP (4.22 ± 2.87 vs. 0.71 ± 0.69 nmoles per mg protein, p < 0.01), ADP (8.75 ± 2.96 vs. 4.49 ± 1.95 nmoles per mg protein, p < 0.01) and energy charge (0.43 ± 0.15 vs. 0.21 ± 0.04, p < 0.02) were found in successful (n = 20) relative to failed (n = 5) livers. No significant differences were found in AMP, xanthine or hypoxanthine for the two groups, although the average values were higher in failed livers. Fifteen recipients with liver ATP concentration above 2 nmoles per mg protein and energy charge above 0.3 recovered well. Five other successful patients with lower ATP concentration (0.70 ± 0.39 nmoles per mg protein) and energy charge (0.20 ± 0.03) had postoperative courses complicated by infection or prolonged hyperbilirubinemia. In five patients whose livers failed, all had low ATP content and energy charge. Of these, three received a replacement liver and two died shortly after the transplantation. The study demonstrates a direct correlation between high ATP content and good posttransplant outcome.
Pilot study of recombinant human interleukin 2 for chronic type B hepatitis
Authors: Kakumu Shinichi , Fuji Akihiko , Yoshioka Kentaro , Tahara Hirofumi , Ohtani Yoshiyuki , Hirofuji Hideo , Murase Kenichi , Aoi Tsuneto
Published: March 2007

Recombinant human interleukin 2 was administered to 10 patients with chronic type B hepatitis as a part of a pilot study to evaluate its antiviral activity. Patients received 1 to 3 x 105 units per day of interleukin 2 for 21 to 28 days, and all completed the treatment schedule. During therapy, serum values of DNA polymerase decreased in 6 and became negative in four patients. However, when therapy was discontinued, DNA polymerase levels increased to pretreatment levels in most cases. Serum HBeAg levels did not change during treatment. Serum aminotransferase levels transiently increased in 6 of the 10 patients during therapy; but once therapy was stopped, levels fell markedly. Side effects of interleukin 2 therapy included fever, chills, anorexia and fatigue. After 1 year of follow-up, three treated patients had lost HBeAg and had marked improvement in aminotransferase levels. These serologic and biochemical improvements occurred 1.5 to 11 months after therapy was stopped. Whether a 3- to 4- week course of interleukin 2 therapy leads to an increased rate of seroconver-sion from HBeAg to antibody in chronic type B hepatitis deserves further evaluation in prospectively randomized, controlled trials.
Is anti-hbc IgM a useful clinical test in patients with HBsAg-positive chronic hepatitis or primary hepatocellular carcinoma?
Authors: Lai Min Chan , Tong Myron J. , Nowicki Marek J. , Lee Shou-Dong
Published: March 2007

Seventy HBsAg-positive patients, including 24 with primary hepatocellular carcinoma, 34 with chronic active hepatitis, 12 with chronic persistent hepatitis and 30 asymptomatic healthy hepatitis B virus carriers were tested for anti-HBc IgM using the Corzyme-M test. Anti-HBc IgM was detected in 50% of the primary hepatocellular carcinoma patients, 26.5% of the chronic active hepatitis patients, 25% of the chronic persistent hepatitis patients, but in none of the healthy hepatitis B virus carriers. There was no correlation between the presence of anti-HBc IgM and HBeAg, hepatitis B virus DNA, ALT or α-fetoprotein levels in either the chronic active hepatitis or chronic persistent hepatitis patients. However, a significantly higher positive rate of anti-HBc IgM was noted in the HBeAg-positive or HBV DNA-positive primary hepatocellular carcinoma patients than in those with negative markers of viral replication, but no correlation was noted between the presence of anti-HBc IgM and serum ALT or α-fetoprotein levels in these primary hepatocellular carcinoma patients. Also, no differences in positivity for HBeAg, HBV DNA or levels of serum ALT were noted when patients with high titers of anti-HBc IgM were compared to those with low titers. Thus, anti-HBc IgM cannot distinguish between HBsAg-positive patients with chronic active hepatitis, chronic persistent hepatitis or primary hepatocellular carcinoma, does not correlate with serum ALT or α-fetoprotein levels and is only associated with markers for viral replication in primary hepatocellular carcinoma patients. Based on this, anti-HBc IgM appears to have a limited usefulness for diagnosis of either chronic hepatitis B or primary hepatocellular carcinoma. Since anti-HBc IgM was negative in all our asymptomatic healthy hepatitis B virus carriers, its detection in these individuals may indicate an underlying chronic liver disease which would merit further diagnostic investigation.
Hepatocellular carcinoma in type I glycogen storage disease
Authors: Limmer Joachim , Fleig Wolfgang E. , Leupold Dorothea , Bittner Reinhard , Ditschuneit Hans , Berger Hans-Günter
Published: March 2007

Patients suffering from Type I glycogen storage disease frequently develop hepatic tumors. Some of these were classified as carcinoma, with the majority of tumors representing benign adenomata. However, no evidence exists of malignant transformation of adenomata in these patients. Here, we describe the occurrence of a hepatocellular carcinoma in the adenomata-bearing liver of the elder of two sisters suffering from Type I glycogen storage disease at the age of 20 years, 6 years after the diagnosis had been made. Surprisingly, α-fetoprotein levels were normal throughout the entire course of this patient, whereas the younger sister had elevated levels despite the absence of malignant lesions. Thus, the clinical significance of α-fetoprotein remains unclear in both cases. Nocturnal feeding, although performed continuously over the 6 years after the diagnosis, had obviously failed to prevent the development of hepatic tumors in both patients.
De novo deposition of laminin-positive basement membrane in vitro by normal hepatocytes and during hepatocarcinogenesis
Authors: Albrechtsen Reidar , Wewer Ulla M. , Thorgeirsson Snorri S.
Published: March 2007

De novo formation of laminin-positive basement membranes was found to be a distinct morphologic feature of diethylnitrosamine/phenobarbital-induced hepatocellular carcinomas of the rat. The first appearance of extracellularly located laminin occurred in the pre-neoplastic liver lesions (corresponding to neoplastic nodules), and this feature became successively more prominent during the course of hepatocellular carcinoma development. Most groups of tumor cells were surrounded by laminin-positive basement membrane material. The laminin-positive material was also deposited along the sinusoids, a location where no laminin was seen in normal rat liver. The amount of extractable laminin from hepatocellular carcinomas was significantly higher (approximately 100 ng per mg tissue) than that of normal liver tissue (less than 20 ng per mg). In vitro experiments demonstrated that normal and pre-neoplastic rat hepatocytes had the capacity to lay down basement membrane-like material. This occurred, however, only when the hepatocytes were cocultured with certain feeder cells or when grown in the presence of their conditioned media. These results indicate that during experimental hepatocarcinogenesis in the rat some as yet undefined humoral factor(s) might influence the hepatocytes to turn on genes encoding the basement membrane components and further stimulate the assembly and deposition of basement membranes.
Hepatic injury associated with the use of nitrofurans: A clinicopathological study of 52 reported cases
Authors: Stricker Bruno H. Ch. , Blok Roeland A.P. , Claas Frans H. J. , Van Parys Geert E. , Desmet Valeer J.
Published: March 2007

Fifty cases of nitrofurantoin-associated hepatic injury and two cases of nifurtoinol (hydroxymethylnitro-furantoin)-associated hepatic injury reported to the Netherlands Centre for Monitoring of Adverse Reactions to Drugs were analyzed in detail. In 38 cases, a causal relationship was considered likely [i.e., “highly probable” (n = 4), “probable” (n = 23) or “possible” (n = 11)]. In 25 cases, hepatic injury was of the acute type whereas 13 cases presented a chronic type of reaction. Both types were more common in the elderly. Eighty per cent of the acute reactions appeared within the first 6 weeks of treatment and were sometimes accompanied by fever (28%), rash (12%) and eosinophilia (16%). Biochemically, the pattern was mainly hepatocellular (32%), whereas mixed cholestatic-hepatocellular (4%) and cholestatic (4%) patterns were uncommon. Although mild to moderate liver enzyme elevations (60%) were common, these were primarily symptomatic. The reaction was fatal in one “acute” and one “chronic” case. In the chronic cases, nuclear (82%) and smooth muscle (73%) antibodies and LE cells (50%) were frequently present. HLA typing showed no increase of the HLA B8 or HLA DRw3 haplotype. HLA DR2 (56%) and HLA DRw6 (56%) were more frequent than in controls (both 29%), but this was not statistically significant. Histology showed mainly necrosis, varying from spotty to massive, in the acute cases and a pattern consistent with chronic active hepatitis in the chronic cases. The incidence of symptomatic nitrofurantoin-induced hepatic injury in The Netherlands may be estimated at approximately 1:3,000 to 5,000 (0.020 to 0.035%). The mechanism of nitrofurantoin-induced hepatic injury seems to be immunoallergic.