bluuebunny/crossref_metadata_2025 huggingface dataset:
Stereoselective Dendrimer Catalysis
Authors: Kassube Jutta K. , Gade Lutz H.
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis by Substitution of Heteroatoms. Synthesis by Substitution of a Halogen
Authors: Lequeux T. P.
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Properties and Applications of Supports for Enzyme‐Mediated Transformations in Solid‐Phase Synthesis
Authors: Basso Alessandra , Braiuca Paolo , Ebert Cynthia , Gardossi Lucia , Linda Paolo
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Extraction Chromatography versus Solvent Extraction: How Similar Are They?
Authors: Horwitz E. Philip , McAlister Daniel R. , Dietz Mark L.
Published: March 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Preoperative interleukin‐6 production by mononuclear blood cells predicts survival after radical surgery for colorectal carcinoma
Authors: Clinchy Birgitta , Fransson Annelie , Druvefors Bengt , Hellsten Anna , Håkansson Annika , Gustafsson Bertil , Sjödahl Rune , Håkansson Leif
Published: March 2007

BACKGROUND.

Colorectal cancer is one of the most common forms of cancer in the Western world. Staging based on histopathology is currently the most accurate predictor of outcome after surgery. Colorectal cancer is curable if treated at an early stage (stage I‐III). However, for tumors in stages II and III there is a great need for tests giving more accurate prognostic information defining the patient population in need of closer follow‐up and/or adjuvant therapy. Furthermore, tests that provide prognostic information preoperatively could provide a guide both for preoperative oncologic treatment and the surgical procedure.

METHODS.

Peripheral blood mononuclear cells (PBMCs) were isolated preoperatively, within a week before primary surgery, from 39 patients undergoing surgery for colorectal cancer. The PBMCs were cultured in vitro for 24 hours in the presence of autologous serum and lipopolysaccharide (LPS). Interleukin‐6 (IL‐6) production was measured with enzyme‐linked immunosorbent assay (ELISA). Staging based on histopathology was performed in all patients. Patients were followed for at least 54 months.

RESULTS.

A production of >5000 pg/mL of IL‐6 identified colorectal cancer patients with a poor prognosis. Eight out of 13 patients with >5000 pg/mL IL‐6 died from cancer within the follow‐up period, whereas no cancer‐related deaths were recorded among 21 patients with 5000 pg/mL IL‐6 or less. A multivariate Cox regression analysis, stratified for T‐ and N‐stage, identified IL‐6 production as an independent prognostic factor.

CONCLUSIONS.

IL‐6 production in vitro by PBMC can predict survival after radical surgery for colorectal cancer. Cancer 2007. © 2007 American Cancer Society.
Induction of organ‐selective CD4+ regulatory T cell homing
Authors: Siewert Christiane , Menning Astrid , Dudda Jan , Siegmund Kerstin , Lauer Uta , Floess Stefan , Campbell Daniel J. , Hamann Alf , Huehn Jochen
Published: March 2007

Compelling evidence suggests that Foxp3+CD25+CD4+ Treg play a fundamental role in immunoregulation. We have previously demonstrated that Treg have to enter peripheral tissues to suppress ongoing inflammation. However, relatively little is known about how Treg acquire the expression of homing receptors required for tissue‐ or inflammation‐specific migration. Migratory properties of conventional naïve T cells are shaped by the tissue microenvironment and organ‐specific dendritic cells during priming. Here, we show that this basic concept also holds true for CD25+CD4+ Treg: Priming of Treg within peripheral LN led to the expression of selectin ligands, which facilitate migration into inflamed skin, whereas activation within mesenteric LN led to induction of the integrin α4β7, which is required for migration into mucosal tissues. Furthermore, we could establish in vitro culture systems containing either dendritic cells from mesenteric and peripheral LN, or retinoic acid and IL‐12 as polarizing compounds to induce mucosa‐ and skin‐seeking Treg, respectively. Together, our results demonstrate that Treg, similarly to conventional T cells, can be configured with organ‐selective homing properties allowing efficient targeting into distinct tissues.
Hepatic fibrosis and cirrhosis after chronic administration of alcohol and “low-dose” carbon tetrachloride vapor in the rat
Authors: de la M. Hall Pauline , Plummer John L. , Ilsley Anthony H. , Cousins Michael J.
Published: March 2007

Rats were exposed to carbon tetrachloride vapor, 5 days/wk, 6 hr/day, for periods of 5 or 10 wk at a concentration that by itself caused only fatty change with minimal liver cell necrosis and no fibrosis. The same carbon tetrachloride exposure when given in association with chronic alcohol feeding resulted in extensive hepatic fibrosis at 5 wk and established micronodular cirrhosis at 10 wk. The periodicity of the exposure profile was chosen to simulate that of human exposure to environmental toxins, albeit at a higher dose than would be permitted in the workplace. The development of significant liver injury in this animal model raises the possibility that some chronic liver injury in humans may be due to alcohol potentiation of other hepatotoxins present in the environment at subtoxic levels. (Hepatology 1991;13:815-819).
HLA class I antigen expression as a measure of response to antiviral therapy of chronic hepatitis B
Authors: Paul Robert G. , Roodman Stanford T. , Campbell Carolyn R. , Bodicky Carol J. , Perrillo Robert P.
Published: March 2007

HLA class I antigen expression on peripheral blood mononuclear cells was evaluated by flow cytometry in 21 HBeAg-positive patients with chronic hepatitis B. Measurements were made before, during or after treatment with recombinant interferon-α-2b, either given alone or after a 6 wk course of prednisone. Immunohistochemical staining for human leukocyte class I antigen was also evaluated in 28 percutaneous liver biopsy specimens either obtained before or after therapy (N = 27) and during therapy in one instance. The amount of HLA class I antigen on peripheral blood mononuclear cells varied markedly among individual patients, but the overall results indicated that the level of inducible antigen did not correlate with increments of ALT during therapy or with a virological response to therapy. Hepatocyte staining for HLA class I antigen was observed in a minority of biopsy specimens (29%) and also did not appear to predict a response or correlate with the severity of histological disease. These data do not support current theories concerning pathogenetic mechanisms in chronic hepatitis B nor do they suggest that spontaneous display of HLA class I antigen on hepatocytes or interferon-induced expression of these antigens on peripheral blood mononuclear cells is a critical determinant for a response to therapy. (Hepatology 1991;13:820-825.)
Memory T cells represent the predominant lymphocyte subset in acute and chronic liver inflammation
Authors: Volpes Riccardo , van den Oord Joost J. , Desmet Valeer J.
Published: March 2007

T cells can be divided into two main phenotypic subpopulations-i.e., the CD45RA-positive (2H4-positive) “naive” subset and the CD45RO-positive (UCHL1-positive) “memory” subset.

In light of this recent functional reinterpretation of T-lymphocyte subpopulations, we reinvestigated the composition of the inflammatory infiltrate in liver biopsy specimens from patients with acute and chronic hepatitis. In normal liver, the few scattered mononuclear cells present in portal tracts and in the intralobular parenchyma consisted of both CD45RA-positive (2H4-positive) naive and CD45RO-positive (UCHL1-positive) memory T cells. In inflammatory liver diseases, portal tract and periportal and intralobular areas of inflammation consisted virtually only of CD45RO-positive (UCHL1-positive) memory T cells, which strongly expressed the CDw29 (4B4) antigen, and the adhesion molecules LFA-1, CD2, LFA-3, CD44 and VLA-4 and the activation marker human leukocyte antigen-DR.

These results indicate that activated memory T cells represent the predominant subpopulation of lymphocytes in areas of liver inflammation. Memory T cells strongly express various homing receptors and adhesion molecules, which probably allow them to accumulate at inflammatory sites and to strengthen interaction with target cells. Furthermore, the increased number of memory T cells with enhanced interferon-γ production in areas of liver inflammation may contribute to the maintenance and up-regulation of immune responses occurring in inflammatory liver diseases. (Hepatology 1991;13:826-829.)
Morbidity and mortality from chronic hepatitis B virus infection in family members of patients with malignant and nonmalignant hepatitis B virus-related chronic liver diseases
Authors: Lok Anna S. F. , Lai Ching-Lung , Chung Hau-Tim , Lau Johnson Y. N. , Leung Elsie K. Y. , Wong Loretta S. K.
Published: March 2007

Three-hundred forty-one HBsAg-positive family members of 152 patients with chronic hepatitis B virus infection (47 asymptomatic carriers, 59 with chronic hepatitis, 17 with cirrhosis and 29 with hepatocellular carcinoma) were prospectively studied to determine the morbidity and mortality from chronic hepatitis B virus infection in the family members of patients with malignant and nonmalignant hepatitis B virus-related chronic liver diseases. Most of the family members had no history of acute hepatitis, were asymptomatic and were unaware of their carrier status. However, 5.3% had stigmata of chronic liver disease, 6% had serum ALT levels that exceeded two times the upper limit of normal and 78% of those who had biopsies had chronic hepatitis with or without cirrhosis.

During a follow-up period of 12 to 90 mo (median = 39 mo), 3% had symptoms of chronic liver disease; 24% had transient, recurrent or persistent elevation in serum ALT levels, 1.4% had cirrhosis and 1% had hepatocellular carcinoma. Neither hepatocellular carcinoma in the index patient nor a previous history of hepatocellular carcinoma in the family was associated with an increase in the morbidity and mortality from chronic hepatitis B virus infection in the HBsAg-positive family members. (Hepatology 1991;13:834-837.)
Estrogen receptors, progesterone receptors and heat-shock 27-kD protein in liver biopsy specimens from patients with hepatitis B virus infection
Authors: Ciocca Daniel R. , Jorge Arturo D. , Jorge Oliver , Milutín Carlos , Hosokawa Roberto , Lestren Marcelo Díaz , Muzzio Estela , Schulkin Sergio , Schirbu Ricardo
Published: March 2007

It has been proposed that in the human liver, the estrogen receptor gene may become inappropriately expressed as a consequence of HBV integration, contributing to cell transformation. This study was undertaken to examine estrogen receptor status in patients with hepatitis B virus infection and to analyze the expression of progesterone receptor and of a heatshock 27,000-D protein (hsp27), both of which are estrogen regulated in estrogen target tissues. Receptor proteins were detected in liver biopsy specimens by immunocytochemistry using antireceptor monoclonal antibodies; a monoclonal antibody was also used to detect hsp27. Estrogen receptor and progesterone receptor were mainly seen in the nuclei of hepatocytes. The presence of hepatitis B virus infection did not always result in elevated estrogen receptor expression, but in general the expression of this receptor protein was higher in hepatitis B virus-positive patients than in patients with the same pathological findings (hepatitis, cirrhosis, hepatocarcinoma) but without hepatitis B virus. This was more clearly seen in the patients with hepatitis. Although estrogen receptor expression was moderate to high in many samples, the expression of the two biochemical markers of estrogen action at postreceptor levels (progesterone receptor and hsp27) was low or absent in most of the liver tissues examined, suggesting that in the liver the interaction of estrogen-estrogen receptor-DNA has characteristics inherent to this tissue. (Hepatology 1991;13:838-844.)
Direct evidence for cytotoxicity associated with expression of hepatitis delta virus antigen
Authors: Cole Susan M. , Gowans Eric J. , Macnaughton Thomas B. , De La M. Hall Pauline , Burrell Christopher J.
Published: March 2007

It has been postulated that hepatocyte injury resulting from infection with hepatitis D virus may be caused by a direct virus cytotoxicity in contrast to immune-mediated injury associated with hepatitis B virus. We have transfected HeLa and HepG2 continuous cell lines with a recombinant plasmid containing the hepatitis D antigen gene under the inducible control of the human metallothionein promoter. The addition of zinc to the cell culture medium then led to the expression of hepatitis D antigen associated with, in the short term, a significant reduction in the rate of RNA but not DNA synthesis and, in the longer term, cell death. The necrotic cells had pyknotic nuclei and shrunken eosinophilic cytoplasm; these necrotic cells resembled the apoptotic bodies seen in hepatitis D virus-related hepatitis. The level of hepatitis D antigen in individual cells that produced these changes was similar to the level of hepatitis D antigen in hepatocytes from a chimpanzee with acute hepatitis D virus infection. We conclude that the expression of hepatitis D antigen resulted in significant cytotoxic changes in these cells, providing strong support for the view that hepatitis D antigen may be specifically cytotoxic to infected hepatocytes in vivo. (Hepatology 1991;13:845-851.)
Non-Hodgkin's lymphoma presenting as a primary tumor of the liver: Presentation, diagnosis and outcome in eight patients
Authors: Scoazec Jean-Yves , Degott Claude , Brousse Nicole , Barge Janine , Molas Georges , Potet François , Benhamou Jean-Pierre
Published: March 2007

We report the diagnostic, prognostic and therapeutic features of non-Hodgkin's lymphoma in eight patients in whom the disease was seen as a primary tumor of the liver. This series illustrates the variety of situations in which lymphoma might be diagnosed: (a) abdominal pain and hepatomegaly (three cases), (b) incidental finding at evaluation of a patient with cirrhosis (two cases), (c) secondary neoplasm after treatment for Hodgkin's disease (one case) and (d) complication of AIDS (two cases). In most cases, clinical and/or radiological features were nonspecific. However, the combination of the following features must be considered as suggestive: occurrence of an apparently primary hepatic tumor in an immunocompromised patient, absence of the usual serum tumor markers and increased serum lactic dehydrogenase activity. The final diagnosis was based on histological examination of specimens obtained by ultrasonically guided liver biopsies or at surgery. All cases belonged to unfavorable histological subtypes. Immunohistochemical findings on paraffin-embedded sections demonstrated the B-lymphocyte lineage of the seven tumors available for study. In the three patients without coexisting disease, complete remission was obtained by surgery alone or combined with chemotherapy. In the two patients with coexisting cirrhosis, outcome was rapidly unfavorable, with death occurring less than 3 mo after diagnosis. Among the three immunocompromised patients, two experienced a rapid unfavorable outcome, and the remaining one was in complete remission after surgery and chemotherapy. In conclusion, primary non-Hodgkin's lymphoma of the liver arising in patients without coexisting disease has a slow progression and might be successfully treated by surgery. In contrast, lymphomas occurring in patients with a coexisting disease, and especially, as a complication of AIDS, have a much poorer prognosis and a low response to therapy. (Hepatology 1991;13:870-875.)
Bioelectric impedance analysis: Experience with male patients with cirrhosis
Authors: Guglielmi Francesco William , Contento Francesco , Laddaga Lucia , Panella Carmine , Francavilla Antonio
Published: March 2007

Bioelectric impedance analysis is a new, convenient and portable method used to estimate total body water and to assess body composition in healthy people. We used the tetrapolar bioelectrical impedance analysis method in 58 cirrhotic patients to assess its clinical applicability. Whole-body resistance, reactance and impedance were measured and compared with those of 30 healthy volunteers matched for age and sex. The resistance and impedance values of ascitic cirrhotic patients (resistance = 461 ± 80Ω; impedance = 462 ± 80 Ω) and nonascitic cirrhotic patients (resistance = 487 ± 96 Ω; impedance = 489 ± 97 Ω) were comparable with the resistance (488 ± 44 Ω) and impedance (491 ± 44 Ω) of controls. However, a significant (p < 0.05) reduction in whole body reactance was found in patients with ascites and in those without ascites (34 ± 9 Ω vs. 47 ± 12 Ω) as compared with healthy subjects (56 ± 7 Ω). In 10 ascitic patients total body water was determined both before and after paracentesis; the volume of intraperitoneal fluid removed (7.9 ± 3.8 L) could not be fully accounted for but only detected as an average volume of 1.9 ± 1.0 L independently of the initial volume of the ascites. Our data clearly demonstrate that tetrapolar bioelectric impedance analysis is not adequate for measuring variations of “compartmentalized” fluid in the abdomen. (Hepatology 1991;13:892-895.)
Propranolol in the prevention of the first hemorrhage from esophagogastric varices: A multicenter, randomized clinical trial
Authors: Conn Harold O. , Grace Norman D. , Bosch Jaime , Groszmann Roberto J. , Rodés Joan , Wright Steven C. , Matloff Daniel S. , Garcia-Tsao Guadalupe , Fisher Rosemarie L. , Navasa Miguel , Drewniak Steven J. , Atterbury Colin E. , Bordas Jose M. , Lerner Emanuel , Bramante Christina
Published: March 2007

To assess the effectiveness of propranolol in the prevention of initial variceal hemorrhage, a doubleblind, randomized trial was carried out in three centers. Patients with cirrhosis (78% alcoholic), hepatic venous pressure gradients greater than 12 mm Hg and endoscopically proven esophageal varices were randomly assigned to propranolol (51 patients) or placebo (51 patients). Of the 102 patients, 58% were Child's class A, 34% were Child's class B and 8% were Child's class C. Daily dosage was determined by the administration of progressively increasing doses of propranolol with the hepatic vein catheter in place to achieve a 25% decrease in hepatic venous pressure gradient, a decrease in hepatic venous pressure gradient to less than 12 mm Hg or a decrease in resting heart rate to less than 55 beats/min. During a mean follow-up period of 16.3 mo, 11 patients in the placebo group (22%) bled from esophageal varices compared with 2 in the propranolol group (4%) during a mean period of 17.1 mo (p < 0.01). Three additional patients (6%) in the placebo group bled from portal hypertensive gastropathy compared with none in the propranolol group. Propranolol appeared effective in preventing bleeding from large varices. Eleven deaths (22%) occurred in the placebo group compared with eight deaths (16%) in the propranolol group (NS). The mean dose of propranolol was 132 mg/day, and the median dose was 80 mg/day. Using a compliance index (pill count, clinic attendance, alcohol and propranolol levels and alcohol history), 81% of the propranolol patients and 77% of the placebo patients were considered compliant. Complications severe enough to require cessation of therapy occurred in eight patients (16%) in the propranolol group and four in the placebo group (8%) (NS). We conclude that propranolol effectively prevents the first variceal hemorrhage in patients with alcoholic cirrhosis and large esophageal varices but does not improve survival. (Hepatology 1991;13:902-912.)
Clonality and clonal evolution of hepatocellular carcinoma with multiple nodules
Authors: Hsu Hey-Chi , Chiou Tzyy-Jen , Chen Jen-Yang , Lee Chu-Shue , Lee Po-Huang , Peng Shian-Yang
Published: March 2007

To determine the clonal evolution of hepatocellular carcinoma, the integrated hepatitis B virus DNA patterns of the main tumor, satellites and/or metastatic lesions were analyzed by Southern-blot hybridization in 28 hepatocellular carcinomas, including three HBsAg-seronegative cases. Unicentric or multicentric hepatocellular carcinoma was confirmed by histopathological criteria in 89% of the cases. Among 17 unicentric hepatocellular carcinomas, minor changes of the integration pattern-including partial loss or addition of the integration sites or both-were detected in the metastatic lesions in 29% of the cases. Furthermore, none of five cases with free-form hepatitis B virus DNA in the primary tumor had detectable free hepatitis B virus DNA in the metastatic lesions. These results suggest that the alteration of integrated hepatitis B virus DNA pattern during the course of tumor growth and metastasis may occur more often than previously perceived and that the switch-off of virus replication may be related to tumor metastatic potential. In eight cases with unilateral, multicentric hepatocellular carcinoma, two clones were detected in six cases, three were seen in another and four were seen in one. One case of note was a 9-yr-old boy with two histological types and two different integration patterns, one associated with vascular invasion and lung metastasis. Three patients with bilateral hepatocellular carcinoma were confirmed to have bicentric or tricentric hepatocellular carcinoma rather than intrahepatic dissemination and had survival rates similar to those in unicentric hepatocellular carcinoma. Three invasive HBsAg-seronegative hepatocellular carcinomas were found to have hepatitis B virus DNA integration and were of unicentric origin. These results suggest that Southern-blot analysis is not only a valuable tool for the study of tumor clonal origin and evolution of hepatitis B virus-related hepatocellular carcinoma, but it also provides valuable information to better understand its biological behavior. (Hepatology 1991;923-928.)
Ascitic fluid pH and lactate: Insensitive and nonspecific tests in detecting ascitic fluid infection
Authors: Runyon Bruce A. , Antillon Mainor R.
Published: March 2007

Ascitic fluid pH and lactate concentration have been proposed as useful tests for the detection of ascitic fluid infection. However, past studies involved small numbers of infected patients, and all did not use optimal culture techniques. This large study was performed using highly sensitive culture methods and sought (a) to compare the sensitivity, specificity and accuracy of pH and lactate to that of the ascitic fluid neutrophil count and (b) to determine whether evaluation of ascitic fluid pH or lactate (or arterial-ascitic fluid pH or lactate gradient) would result in improved decision-making regarding empirical treatment of suspected ascitic fluid infection.

Analysis of 206 ascitic fluid specimens obtained in 175 patients, including 101 infected specimens, revealed that ascitic fluid (or arterial-ascitic fluid) pH and lactate were less than 50% sensitive in detecting bacterial peritonitis and that these tests did not improve clinical decision-making about empirical treatment of suspected ascitic fluid infection. Although statistically significant differences in ascitic fluid pH were detected between infected samples and control samples, these differences did not appear to be clinically helpful. The ascitic fluid pH was 0% sensitive in detecting the presence of bacteria in the absence of neutrophils (i.e., no such specimens had a pH lower than 7.35). Ascitic fluid pH correlated well with neutrophil count and appears to be, at least in part, an indirect measure of the presence of neutrophils in ascitic fluid. Measurement of pH or lactate (or arterial-ascitic fluid gradients) is not helpful in the clinical management of infected ascitic fluid (Hepatology 1991;13:929-935.)
Diet and cimetidine induce comparable changes in theophylline metabolism in normal subjects
Authors: Anderson Karl E. , McCleery Reneé B. , Vesell Elliot S. , Vickers Florence F. , Kappas Attallah
Published: March 2007

This study compared the effects of diet and cimetidine on theophylline metabolism and examined interactions between these effects. Twelve men received a high-protein diet for 15 days and at another time a high-carbohydrate diet also for 15 days. Cimetidine, 800 mg daily at bedtime, was administered on days 10 through 15 of each dietary period. Theophylline metabolism was studied after the administration of a single intravenous 3 mg/kg dose on days 8 and 15 of each dietary period. Changing from a high-protein to a high-carbohydrate diet decreased theophylline clearance by about the same extent (30% ± 10%) as treatment with cimetidine (37% ± 5% during a high-protein diet and 30% ± 5% during a high-carbohydrate diet). Cimetidine did not significantly influence the effects of diet on theophylline clearance. Conversely, dietary composition did not influence the degree of inhibition of theophylline metabolism induced by cimetidine. Depending on the direction of the change in protein/carbohydrate ratio, the effects of diet and cimetidine treatment were either additive (theophylline clearance was most prolonged during the highcarbohydrate regimen with concurrent cimetidine administration) or counteractive (increasing the dietary protein/carbohydrate ratio at least partially counter-acted the inhibitory effect of cimetidine). In individual subjects, effects of cimetidine on theophylline metabolism were somewhat more consistent than diet-induced changes. The results are further evidence that diet and drugs can have similar effects on hepatic drug metabolism rates in humans. Variations in diet over time and individual differences in responses to diet may provide the potential for considerable instability of drug metabolism rates in free-living subjects. Therefore during treatment with a drug having a narrow therapeutic index, it may be important to consider the potential significance of drug-nutrient interactions and drug-drug interactions in producing subtherapeutic or excessive drug levels. (Hepatology 1991;13:941-946.)
FK 506 ameliorates the hepatic injury associated with ischemia and reperfusion in rats
Authors: Sakr Mahmoud F. , Zetti Giorgio M. , Hassanein Tarek I. , Farghali Hassan , Nalesnik Michael A. , Gavaler Judith S. , Starzl Thomas E. , Van Thiel David H.
Published: March 2007

The effect of FK 506 on regeneration of the liver was studied in rats after a two-thirds partial hepatectomy after 60 min of ischemia of the unresected liver. The animals were divided into three distinct groups of 10 rats each. Group 1 (controls) received 0.5 ml saline solution intravenously 30 min after the induction of ischemia. Groups 2 and 3 were injected with FK 506 (0.3 mg/kg) intravenously 30 min after and 24 min before the induction of hepatic ischemia, respectively. The hepatic content of ATP and serum levels of ALT and lactate dehydrogenase were determined on each animal. In addition, the histological appearance and mitotic activity of the remnant liver was determined at regular 24-hr intervals after hepatic ischemia. All 10 control animals died within 72 hr. Treatment with FK 506 resulted in improved survival in groups 2 and 3 (30% and 80%, respectively). The improved survival seen in the FK 506-treated animals was reflected by a restoration of hepatic ATP content, a reduction in the serum levels of ALT and lactate dehydrogenase, an amelioration of hepatic necrosis and neutrophilic infiltration and an increase in the mitotic activity of the liver. These results suggest that FK 506 ameliorates the hepatic injury associated with ischemia/reperfusion and has a potent stimulatory effect on liver cell regeneration that may make it valuable as a hepatoprotective agent when administered to organ donors before graft harvesting. (Hepatology 1991;13:947-951.)
Morphological changes of hepatic microcirculation in experimental rat cirrhosis: A scanning electron microscopic study
Authors: Haratake Joji , Hisaoka Masanori , Yamamoto Osamu , Horie Akio
Published: March 2007

Morphological changes of hepatic microcirculation, especially peribiliary plexus, in experimental rat cirrhosis that resulted from the repeated intraperitoneal injections of N-diethylnitrosamine, 100 mg/kg body weight/one shot/week, were examined by scanning electron microscope. Control rats were treated with saline. Whole blood vessels of the rats were perfused by saline and stuffed with methylmethacrylated resin. Multiple nodular changes were seen in the livers after the five injections (5 wk) of N-diethylnitrosamine, and diffuse nodular transformations mimicking human cirrhosis after six injections (6 wk) were also seen. Overall changes in experimental rats were numerous vascular channels mainly composed of venous branches around the parenchymal nodules, increased arterioportal anastomoses and flattening of veins, especially hepatic vein branches. Peribiliary plexuses of the experimental rats were much richer in the vessels than those of the controls, and many dilated veins, ramified from portal vein branches, were present in the former. Direct connections between peribiliary plexuses and sinusoids or between peribiliary plexuses and portal veins increased in the experimental rats. Studies concerning microcirculatory changes of peribiliary plexuses in experimental rat cirrhosis are rare. It was concluded that the abnormal peribiliary plexuses in this experimental series might participate in a collateral circulation under a state of portal hypertension. (Hepatology 1991;13:952-956).
Bile salts stimulate glycoprotein release by guinea pig gallbladder in vitro
Authors: O'Leary Daniel P. , Murray Francis E. , Turner Bradley S. , Lamont Thomas J.
Published: March 2007

Alterations in the composition of bile during cholesterol gallstone formation appear to be responsible for increased release of gallbladder mucin, a potent cholesterol nucleating agent. We investigated the effects of bile salts on release of radiolabeled glycoproteins by explants of guinea pig gallbladder in organ culture. Bile salts, in concentrations of 1 to 5 mmol/L, caused a dose-dependent release of [3H]-glycoproteins with a range of potencies in this order: chenodeoxycholate > deoxycholate > > cholate > ursodeoxycholate = control. Chenodeoxycholate and deoxycholate were significantly more potent than cholate (p < 0.0001). Unconjugated and taurine-conjugated bile salts were of similar potency. Bile salts also caused increased release of glycoproteins from explants of guinea pig gastric antrum and colon. The bile salts released after bile salt exposure included mucin and lower molecular weight glycoproteins from the gallbladder. Release of glycoproteins in response to bile salts was not inhibited by indomethacin, atropine or propranolol, nor was it dependent on extracellular calcium or microtubules. Glycoprotein release in response to bile salts was associated with membrane damage as indicated by a dose-dependent leakage of the cytoplasmic enzyme lactate dehydrogenase, although light microscopy did not reveal structural damage to epithelial cells. We conclude that hydrophobic bile salts stimulate gall-bladder glycoprotein release in vitro by a detergent effect on the plasma membrane rather than by a receptor-mediated secretory pathway. (Hepatology 1991;13:957-961.)
Spironolactone and canrenoate: Different antialdosteronic diuretic agents
Authors: Gumucio Jorge J. , Gentilini Paolo
Published: March 2007

Plasma levels of canrenone and androgen receptoractive materials (ARM) were determined during long-term oral K-canrenoate or spironolactone therapy in cirrhotics with chronic recurrent ascites. Mean plasma canrenone level was approximately 3 times higher under K-canrenoate than under spironolactone treatment; moreover, the levels were not dose related. Either type of treatment did not affect plasma aldosterone and testosterone concentrations. Plasma ARM during K-canrenoate treatment did not change, whereas in the spironolactone group a 3-fold increase of ARM occurred (p <0.05). No dose-related effect was evident with the latter treatment. The lower incidence of gynecomastia in the K-canrenoate group was not correlated with values of plasma canrenone or ARM (p > 0.05).

Our study questions the traditional view that the mode of action of spironolactone is via its metabolite canrenone. The two antialdosterone drugs, although equally effective in clearing ascites from cirrhotics, appear to act through partially different metabolites. The lower incidence of antiandrogenic or estrogen-like side effects during K-canrenoate seems to be related to metabolites other than canrenone itself.
Congestive gastropathy in cirrhosis-how bad is red?
Authors: Blackstone Michael O.
Published: March 2007

In a prospective study of the natural history of congestive gastropathy, 212 consecutive cirrhotic patients (75 treated with sclerotherapy) were included. Mean follow-up was 46 months. Mild gastropathy (mosaiclike pattern) was found in 110 patients and severe gastropathy (granular mucosa with cherry spots) was found in 20. Prevalence of Helicobacter pylori, formerly Campylobacter pylori, was 50% in patients without, 43% in those with mild, and 28% in those with severe gastropathy. Congestive gastropathy was significantly more frequent in patients treated with sclerotherapy (83% vs. 50%, P < 10−5). Sixty-month actuarial proportions of patients free of anemia (in the absence of hematemesis or melena), were 17% with severe, 02% with mild, and 93% without gastropathy (P < 10−8). Corresponding figures for overt bleeding were 25%, 73%, and 87% (P < 10−8), whereas those for survival were 46%. 72%. and 85%(P = 0.0005). respectively. A multivariate regression analysis supported the following conclusions: (a) sclerotherapyand the presence of large esophageal varices significantly increase the risk of congestive gastropathy, which (b) is a significant risk indicator of both chronic and overt bleeding but does not independently affect survival.
Activation of the hepatocarcinogen aflatoxin B1 by forms of human hepatic cytochromes P-450: Some do and some don't
Authors: Bonkovsky Herbert L.
Published: March 2007

Twelve forms of human hepatic cytochrome P-450 were expressed in hepatoma cells by means of recombinant vaccinia viruses. The expressed P-450's were analyzed for their abilities to activate the potent hepatocarcinogens aflatoxin B1 to metabolites having mutagenic or DNA-binding properties. Five forms, P-450's IA2, IIÁ3, IIB7, IIIA3, and IIIA4, activated aflatoxin B1 to mutagenic metabolites as assessed by the production of His revertants of Salmonella typhimurium in the Ames test. The same P-450's catalyzed conversion of aflatoxin B1 to DNA-bound derivatives as judged by an in situ assay in which the radiolabeled carcinogen was incubated with cells expressing the individual P-450 forms. Seven other human P-450's, IIC8, IIC9, IID6, IIE1, IIIA5, and IVB1, did not significantly activate aflatoxin B1 as measured by both the Ames test and the DNA-binding assay. Moreover, polyclonal anti-rat liver P-450 antibodies that crossreact with individual human P-450's IA2, IIA3, IIIA3, and IIIA4 each inhibited aflatoxin B1 activation catalyzed by human liver S-9 extracts. Inhibition ranged from as low as 10% with antibody against IIA3 to as high as 65% with antibody against IIIA3 and IIIA4. These results establish the metabolic activation of aflatoxin B1 in human liver involves the contribution of multiple forms of P-450.
Hepatic interferon-α gene transcripts and products in liver specimens from acute and chronic hepatitis B virus infection
Authors: Nouri-Aria Kayhan T. , Arnold Joachim , Davison Fergus , Portmann Bernard C. , Meager Anthony , Morris Alan G. , Alexander Graeme J. M. , Eddleston Adrian L. W. F. , Williams Roger
Published: March 2007

In this study we have examined the localization of interferon-α in liver tissue from acute and chronic hepatitis B virus carriers to establish whether the defect in interferon-α production reported in chronic hepatitis B virus infection is at a pretranscriptional or posttranscriptional level using in situ hybridization and immunohistochemical techniques. Interferon-α messenger RNA transcripts and the immunoreactive protein were abundant in liver tissue and in particular in hepatocytes from patients with acute hepatitis B virus infection who ubsequently recovered. In contrast interferon-α polypeptide was present in a significantly lower number of sinusoidal cells, mononuclear cells and hepatocytes in chronic hepatitis B virus carriers. Although a high proportion of patients with chronic hepatitis B virus infection had cells that expressed interferon-α messenger RNA transcripts, the number of such cells was significantly less than in acute hepatitis B virus infection, indicating that the defect in the hepatic interferon-α synthesis is at the level of gene activation. Furthermore, using double immunohistochemical staining, the number of hepatocytes containing HBcAg correlated inversely with the proportion of neighboring sinusoidal cells expressing interferon-α These data support previous observations that interferon-α production is reduced in chronic hepatitis B virus infection and are consistent with the view that this cytokine is important in the clearance of the virus. (Hepatology 1991;13:1029-1034.)
A randomized controlled trial of a 12-month course of recombinant human interferon-α in chronic delta (type D) hepatitis: A multicenter Italian study
Authors: Rosina Floriano , Pintus Cristina , Meschievitz Carlton , Rizzetto Mario
Published: March 2007

To determine whether long-term therapy with recombinant interferon-α can improve the course of chronic delta hepatitis, 61 Italian patients with this disease were randomly assigned to receive either interferon-α-2b three times a week (5 MU/m2 for 4 mo and then 3 MU/m2 for another 8 mo) or no treatment. At the end of the 12-mo study, all patients were followed-up for 12 additional months. Normalization or decrease of more than 50% from baseline of serum ALT levels occurred in 42% of treated patients the fourth month of therapy, 26% the twelfth month and 3% the twenty-fourth month vs. 7%, 7% and 0%, respectively, in the control group. However, relapses occurred in 7 of 8 (87.5%) responders 1 to 10 mo (mean = 3.5 mo) after cessation of therapy.

Liver biopsies were carried out at baseline and during the twelfth month of treatment. Histological improvement, mostly caused by decrease of portal inflammation, was observed in 57% of treated and 36% of untreated patients. Measures of antiviral activity (serum hepatitis delta virus RNA and intrahepatic hepatitis delta antigen) showed similar levels in treated and control patients. In treated patients the percentage of patients who were negative for HDV RNA never exceeded that of baseline.

Although interferon-α in the dosage given in this study had no antiviral effect on patients with chronic hepatitis D, it reduced hepatic inflammation as measured by ALT levels. Whether a longer duration or reinstitution of interferon-α therapy would achieve longterm control of ALT levels and prevent chronic liver damage is not known. (Hepatology 1991;13:1052-1056.)
Large molecular form of serum HBeAg in chronic hepatitis B virus infection: Relation to liver cell damage
Authors: Kurai Kiyohiko , Iino Shiro , Kurokawa Kiyoshi , Shimoda Kazumi , Hino Kunihiko
Published: March 2007

We have separated circulating HBeAg into small and large molecular forms by agarose gel electrophoresis and analyzed the relationship between the two forms and other clinical features of chronic hepatitis B, especially in regard to liver cell damage. The large HBeAg accounted for 7.3% ± 3.4% of serum HBeAg in 9 subjects with normal liver histological findings or nonspecific reactive hepatitis, 38.0% ± 27.8% in 32 patients with chronic persistent hepatitis and 65.6% ± 23.3% in 21 patients with chronic active hepatitis (p < 0.01). A positive correlation was seen between the height of aminotransferase elevations and the percentage of large HBeAg. Three patients who progressed from histologically normal liver or nonspecific reactive hepatitis to chronic active hepatitis had dramatic increases in the percentage of large HBeAg. The finding that the presence of large HBeAg in serum correlated with the severity of hepatitis suggests that HBeAg may play an important role in determining the degree of liver injury in chronic hepatitis B. (Hepatology 1991;13:1057-1060.)
Orthotopic liver transplantation for incurable alveolar echinococcosis of the liver: Report of 17 cases
Authors: Bresson-Hadni S. , Franza A. , Miguet J. P. , Vuitton D. A. , Lenys D. , Monnet E. , Landecy G. , Paintaud G. , Rohmer P. , Becker M. C. , Christophe J. L. , Mantion G. , Gillet M.
Published: March 2007

Between 1986 and 1989, orthotopic liver transplantations were performed in our unit for 17 patients with incurable alveolar echinococcosis. Ten patients had hilar involvement (group I), and seven patients had posterior localization (five of them had chronic Budd-Chiari syndrome) (group II). The delay between diagnosis and the orthotopic liver transplantation was more than 48 mo in group Ia (six patients), less than 24 mo in group Ib (four patients) and less than 48 mo in group II. Previous operations were more common in group Ia than in group Ib and II. Five patients have died-four in group I and one in group II. The actuarial survival rate at 15 mo was 75%. Early reoperations were frequent (69%), mainly caused by rebleeding. Bacterial and fungal infections occurred only in group Ia (four cases) and group II (three cases). In eight patients (palliative group), residual foci of infected nonhepatic tissue occurred after surgery. The titer of specific antibodies decreased during the first 3 mo in all the patients but one. In patients with radical liver transplantation, the complete disappearance of specific antibodies occurred within 2 yr in four cases. In the remaining five patients, specific antibodies remained detectable, but no evidence of recurrence has been obtained up to now. In the palliative group, a peak of specific IgM occurred at 3 mo; an increase of specific IgG was observed later. The growth of residual parasitic foci was relatively slow, and all these patients remained asymptomatic with a mean follow-up of 19 mo. We conclude that orthotopic liver transplantation is feasible in incurable alveolar echinococcosis and could be proposed without delay to patients with parasitic Budd-Chiari syndrome or complicated secondary biliary cirrhosis. In the other cases, the best time to perform an orthotopic liver transplantation is more difficult to determine. Nevertheless, in the perspective of an orthotopic liver transplantation, the management of these patients has to change, and repetitive laparotomies for palliative surgical procedures have to be replaced by interventional radiology. (Hepatology 1991;13:1061-1070.)
Eosinophil-induced chronic active hepatitis in the idiopathic hypereosinophilic syndrome
Authors: Foong Anthony , Scholes John V. , Gleich Gerald J. , Kephart G. M. , Holt Peter R.
Published: March 2007

A 19-yr-old man had features of chronic hepatitis with piecemeal necrosis as the sole clinical feature of the idiopathic hypereosinophilic syndrome. Liver biopsy specimens demonstrated the presence of activated eosinophils and, by immunohistochemical staining, major basic protein in areas of hepatic cell damage. The case demonstrates the clinical presentation of the idiopathic hypereosinophilic syndrome as chronic hepatitis and the association between eosinophil infiltration and degranulation with the presence of hepatocyte necrosis. (Hepatology 1991;13:1090-1094.)
Primary biliary cirrhosis: Relation between hepatic function and pulmonary function in patients who never smoked
Authors: Krowka Michael J. , Grambsch Patricia M. , Edell Eric S. , Cortese Denis A. , Dickson Rolland E.
Published: March 2007

We studied the relationship between selected variables of hepatic and pulmonary function in 47 patients with primary biliary cirrhosis, who were participating in a prospective study to assess sequential pulmonary function at yearly intervals. An additional 20 patients with primary biliary cirrhosis, who were liver transplant candidates awaiting transplantation, were studied. None of the 67 patients ever smoked cigarettes. Severity of primary biliary cirrhosis was characterized by histological stage and the Mayo risk score derived from a Cox regression model that used the following variables: serum bilirubin and serum albumin levels, age, prothrombin time and clinical severity of edema. Pulmonary function assessment included key variables describing expiratory airflow (forced expiratory volume in 1 sec divided by forced vital capacity) and efficiency of gas exchange (steadystate diffusing capacity for carbon monoxide). We found a significant relationship between histological stage of primary biliary cirrhosis and steady-state diffusing capacity (p = 0.02) and between the Mayo risk score for disease severity and steady-state diffusing capacity (p = 0.03). Progressive deterioration of steady-state diffusing capacity was associated with increasing severity of primary biliary cirrhosis. No relationship existed between pulmonary function and the presence of sicca complex or Sjögren's syndrome or the clinical manifestations of portal hypertension (e.g., esophageal varices, ascites and splenomegaly). No significant relationship existed between expiratory airflow and severity of primary biliary cirrhosis. We conclude that in patients with primary biliary cirrhosis who have never smoked, a statistically significant relationship exists between the severity of the liver disease and the efficiency of gas exchange measured by steady-state diffusing capacity. This association is not related to clinical manifestations of portal hypertension, sicca complex or Sjögren's syndrome. (Hepatology 1991;13:1095-1100.)