bluuebunny/crossref_metadata_2025 huggingface dataset:
Recognition of major histocompatibility complex antigens on cultured human biliary epithelial cells by alloreactive lymphocytes
Authors: Saidman Susan L. , Duquesnoy Rene J. , Zeevi Adriana , Fung John J. , Starzl Thomas E. , Demetris Jake A.
Published: March 2007

We have developed anin vitrosystem to study the interactions between biliary epithelium and lymphocytes using cultured human biliary epithelial cells. No class II antigens were detected by immunoperoxidase staining of the normal biliary epithelial cells, but alloactivated lymphocyte culture supernatants were able to induce class II expression. The activity of the supernatants was blocked with an anti-γ-interferon monoclonal antibody. In addition, recombinant human γ-interferon alone induced the expression of class II antigens and increased the intensity of class I staining of cultured biliary epithelial cells. Biliary epithelial cell-induced proliferation of alloreactive T lymphocytes demonstrated that the major histocompatibility complex molecules carry functional lymphocyteactivating determinants. The recognition of major histocompatibility complex determinants was confirmed by monoclonal antibody-blocking studies and by stimulation of an alloreactive T-cell clone. However, the biliary epithelial cells were much less potent stimulators than arterial endothelial cells tested in the same assay system. (Hepatology 1991;13:239-246).
Circulating tumor necrosis factor, interleukin-1 and interleukin-6 concentrations in chronic alcoholic patients
Authors: Khoruts Alexander , Stahnke Laura , McClain Craig J. , Logan George , Allen John I.
Published: March 2007

Although altered cytokine homeostasis has been implicated in the pathogenesis of alcoholic liver disease, the relationship between cytokines and metabolic consequences of alcoholic liver disease is unknown. We, therefore, sought to correlate circulating concentrations of tumor necrosis factor-α, interleukin-1 and interleukin-6 to clinical and biochemical parameters of liver disease in chronic alcoholic patients. We used an enzyme-linked immunosorbent assay to measure plasma tumor necrosis factor and interleukin-1 and a bioassay to measure serum interleukin-6 in three groups of alcoholic men as follows: (a) actively drinking alcoholic men without evidence of chronic liver disease, (b) nondrinking alcoholic men with stable cirrhosis and (c) patients with acute alcoholic hepatitis. Mean cytokine concentrations were elevated in cirrhotic patients and alcoholic hepatitis patients compared with controls and alcoholic patients without liver disease. Tumor necrosis factor-α and interleukin-1α concentrations remained elevated for up to 6 mo after diagnosis of alcoholic hepatitis, whereas interleukin-6 normalized in parallel with clinical recovery. Concentrations of all three cytokines were correlated with biochemical parameters of liver injury and hepatic protein synthesis plus serum immunoglobulin concentrations. We could not demonstrate a relationship between cytokine concentrations and peripheral endotoxemia. Percentages of peripheral blood monocytes that reacted with monoclonal antibodies to CD25 (interleukin-2 receptor) and human lymphocyte antigen-DR were similar for alcoholic patients and controls. These data suggest that tumor necrosis factor-α and interleukin-1α are related to some of the metabolic consequences of both acute and chronic alcohol-induced liver disease, whereas interleukin-6 is related to abnormalities seen in acute liver injury. (Hepatology 1991;13:267—276).
Cyclosporine enhances the growth of carcinogen-induced enzyme-altered foci in rat live
Authors: Yabu Koji , Warty Vijay S. , Shinozuka Hisashi
Published: March 2007

Cyclosporine, a powerful immunosuppressant, has been used successfully for organ transplantation. Its efficacy on liver transplants of patients with primary hepatic tumors remains controversial because of a high rate of recurrence of the original tumors in the transplanted livers. In this study, we experimentally tested whether cyclosporine exerts any effects on the growth of carcinogen-initiated liver cells using the short-term assays of rat liver carcinogenesis. Dietary cyclosporine, which maintained sufficient levels of blood cyclosporine and suppressed host immune functions, enhanced the development of the glutathione S-transferase, placental form-positive hepatocyte foci in the liver of male F-344 rats treated with a single weekly dose of diethylnitrosamine (75 mg/kg) for 3 wk. Dietary cyclosporine also accelerated the growth of preformed glutathione S-transferase, placental form-positive foci induced by a single dose of diethylnitrosamine (250 mg/kg) followed by the promoting regimen of a choline-deficient diet. It is possible that the enhancement of the size of hepatocyte foci by cyclosporine could be due to stimulation of growth or inhibition of regression. The mechanisms by which cyclosporine modifies the growth of preneoplastic lesions in the liver are not yet fully understood. Possible involvement of immunologically relevant cells in the liver, Kupffer cells and pit cells in the process is suggested. (Hepatology 1991;13:304-309.).
Regulation of insulin-like growth factor II Gene expression by hepatitis B virus in hepatocellular carcinoma
Authors: d'arville CAROLYN N. , Nouri-Aria Kayhan T. , Johnson Philip , Williams Roger
Published: March 2007

In this study we investigated the regulation of insulin-like growth factor II gene expression to explain a role for this growth factor in concert with hepatitis B virus involvement in the development of hepatocellular carcinoma from cirrhosis.

Sections of normal liver and tumor and non-tumorbearing liver disease tissue were hybridized in situ with [35S]-labeled insulin-like growth factor II oligonucleotide probe. Parallel sections were tested for presence of insulin-like growth factor II polypeptide using immunohistochemistry. To investigate a possible role for hepatitis B virus in insulin-like growth factor II gene expression in hepatocellular carcinoma, results were analyzed against patient seropositivity for hepatitis B virus.

Levels of insulin-like growth factor II transcripts in normal liver (n = 4) sections and in those from nontumor-bearing individuals (n = 10) were so low that specific signal was not detectable above homogeneous tissue background. In contrast, 4 of 8 (50%) of the sections of hepatocellular carcinoma arising from cirrhosis or noncirrhotic chronic liver disease with hepatitis B virus involvement showed increased expression of insulin-like growth factor II messenger RNA transcripts. Up-regulation was observed in cell foci in the hepatocellular regions of the surrounding cirrhotic lobular cells and the fibrous septa. Numerous cell foci were observed in patchy distribution in the tumor areas. The level of insulin-like growth factor II messenger RNA transcripts in sections of hepatocellular carcinoma arising from cirrhotic and noncirrhotic tissues obtained from patients seronegative for hepatitis B virus was similar to that of normal liver. Immunohistochemical study demonstrated that similar cells in the cirrhotic liver lobules containing insulin-like growth factor II messenger RNA transcripts also contained immunoreactive polypeptide. In contrast, we saw no positive staining for insulin-like growth factor II in tumor cells.

These results imply a role for insulin-like growth factor II in the pathogenesis of cirrhotic/noncirrhotic chronic liver disease to hepatocellular carcinoma where there is evidence of hepatitis B virus involvement. Alterations in posttranscriptional events for insulin-like growth factor II in tumor cells may contribute to the maintenance or progression of the malignant phenotype. (Hepatology 1991;13:310-315).
Hepatitis B virus integration in hepatitis B virus-related hepatocellular carcinoma in childhood
Authors: Chang Mei-Hwei , Chen Pei-Jer , Chen Jen-Yang , Lai Ming-Yang , Hsu Hey-Chi , Lian Der-Cheng , Liu Yueh-Giao , Chen Ding-Shinn
Published: March 2007

In Taiwan, hepatocellular carcinoma is one of the major malignancies in children between 5 and 14 yr of age. We studied the status of hepatitis B virus DNA in the hepatocellular carcinoma and nontumorous liver tissues of eight children with positive serum HBsAg and maternal HBsAg.

The hepatocellular carcinoma tissues from five of the eight children showed integration of hepatitis B virus DNA into host cellular DNA sequences. A pattern of single-site integration in four children and a multiple-site integration pattern in one child were demonstrated. In the remaining three children, hepatitis B virus DNA could not be demonstrated in the tumor tissues. Using subgenomic fragments of the hepatitis B virus genome as probes, we found that the X gene fragment and the surface antigen gene fragment were the most conserved sequences. The single-site integration of hepatitis B virus DNA in childhood hepatocellular carcinoma may have hit the critical region, resulting in insertional mutagenesis and early development of hepatocellular carcinoma. With a short incubation period and less exposure to environmental carcinogens during early life, childhood hepatocellular carcinoma may provide a good model to study the carcinogenic potential of hepatitis B virus. (Hepatology 1991;13:316-320).
Epidemiological studies with anti-hepatitis C virus
Authors: Bove Joseph R.
Published: March 2007

In a survey carried out from 1985 through 1986, volunteer blood donors to The Greater New York Blood Program were tested for two surrogate markers for non-A, non-B hepatitis-elevation of alanine aminotransferase level and presence of antibody to hepatitis B core antigen. Stored serum samples from selected donors were also recently tested for antibody to hepatitis C virus (anti-HCV). Anti-HCV was detected in 0.9% to 1.4% of donors and was higher in black and Hispanic donors than in white donors. Anti-HCV prevalence increased with increasing age through the fourth decade of life, but decreased thereafter, possibly reflecting the disappearance of detectable antibody with time. Anti-HCV correlated with both alanine aminotransferase level and the presence or absence of antibody to hepatitis B core antigen. These associations suggest that donor screening for elevation of alanine aminotransferase level and presence of antibody to hepatitis B core antigen was, as expected, at least partially effective in preventing transfusionassociated non-A, non-B hepatitis. The detection of anti-HCV in donors who have neither an elevation of alanine aminotransferase level nor presence of antibody to hepatitis B core antigen suggests that donor screening for anti-HCV will further reduce the risk of transfusion-associated hepatitis.
Temporal relationship between the decrease in arterial pressure and sodium retention in conscious spontaneously hypertensive rats with carbon tetrachloride-induced cirrhosis
Authors: López Clara , Jiménez Wladimiro , Arroyo Vicente , Clària Joan , La Villa Giorgio , Asbert Mónica , Gaya Joan , Rivera Francisca , Rodés Joan
Published: March 2007

It has been proposed that the initial event of sodium retention in cirrhosis is a peripheral arteriolar vasodilation causing underfilling of the arterial vascular compartment and stimulation of the renin-aldosterone and sympathetic nervous systems. To test this hypothesis, systolic blood pressure, sodium balance and urinary excretion of sodium and aldosterone were sequentially measured in 13 conscious spontaneously hypertensive rats submitted to a cirrhosis induction program with carbon tetrachloride and phenobarbital and in 14 control hypertensive animals. No significant differences were found between control and cirrhotic rats in any of the measured parameters during the first 7 wk of the study. The eighth week sodium retention developed in cirrhotic rats as indicated by a positive sodium balance and a marked decrease of sodium excretion. At the same time a significant reduction in systolic blood pressure and a great increase in urinary excretion of aldosterone were detected. These changes were more marked the ninth week of the study. In cirrhotic rats there was a highly significant direct correlation between systolic blood pressure and urinary sodium excretion. Postmortem examination showed a histological picture of cirrhosis in all animals given carbon tetrachloride and ascites in six of them. These results indicate that the onset of hyperaldosteronism and sodium retention in conscious spontaneously hypertensive rats with carbon tetrachloride-induced cirrhosis is chronologically related to a significant decrease in arterial pressure, thus supporting the “peripheral arterial vasodilation hypothesis” of ascites. (Hepatology 1991; 13:585-589.)
Lichen planus and the liver
Authors: Gumucio Jorge J. , Powell Frank C. , Rogers Roy S. , Dickson Rolland E.
Published: March 2007

Objective-

To assess the association of lichen planus with liver complaints and with known etiological factors of liver diseases.

Design-

A multicentre case-control study. Interviews were conducted by trained medical investigators on the basis of a structured questionnaire. At the interview patients and controls were asked for consent to blood samples being taken to determine transaminase activities and the presence of hepatitis B virus surface antigen.

Setting-

Outpatient departments of 27 Italian general and teaching hospitals that were collaborating in the Gruppo Italiano Studi Epidemiologici in Dermatologia (GISED).

Subjects-

Incident cases and controls were eligible. A total of 577 patients with lichen planus and 1031 controls with dermatological diseases other than lichen planus were interviewed. Less than 1% of the people contacted refused to participate. Patients and controls were matched for sex and age in 5 year intervals.

Results-

The risk of lichen planus was higher in patients with a history of liver diseases requiring hospital admission or specialist consultation (relative risk = 1.6; 95% confidence interval = 1.2 to 2.2), those who had had liver biopsy (5.5; 1.9 to 15.6) and those with a history of viral hepatitis (1.9; 1.1 to 3.1). High activities of liver enzymes and positive results of tests for hepatitis B virus surface antigen were also associated with lichen planus. The association with alcohol consumption was not clearly confirmed by a dose-risk relationship.

Conclusion-

This study adds quantitative epidemiological evidence to the clinical observation that liver disease is a risk factor for lichen planus although not a specific marker of it.
How does endoscopic sclerotherapy alter splanchnic hemodynamics?
Authors: Gumucio Jorge J. , Calés Paul
Published: March 2007

Endoscopic sclerotherapy is widely employed for esophageal variceal hemorrhage. However it has side effects and can aggravate portal hypertension by suppression of portosystemic shunt. The purpose of the present investigation was to study the effect of variceal thrombosis on hepatic venous pressure gradient and azygos blood flow. Eight alcoholic cirrhotic patients with a first variceal hemorrhage were included. According to Child Pugh's classification, 4 patients were group A, 2 group B and 2 group C. At each session 40 to 60 ml of 1 p. 100 polidocanol were injected into the varices. A hemodynamic study was performed in each patient before and about 1 week after variceal obliteration (mean 3.3 procedures). Mean value of hepatic venous pressure gradient was 16.6 ± 5.5 mm Hg and 17.0 ± 3.8, respectively, before sclerotherapy and after eradication of varices; azygos blood flow 663 ± 506 ml/min before and 682 ± 522 after; cardiac output was 6.5 ± 0.7 ml/min before and 6.5 ± 0.8 after. None of these differences were significant. These results suggest that endoscopic sclerotherapy using polidocanol does not change hepatic venous pressure gradient and azygos blood flow, and does not lower blood flow through the gastroesophageal collaterals draining into the azygos vein. This is consistent with the hypothesis that thrombosis remains localized.
IgA triggers tumor necrosis factor α secretion by monocytes: A study in normal subjects and patients with alcoholic cirrhosis
Authors: Devière Jacques , Vaerman Jean-Pierre , Content Jean , Denys Chantal , Schandene Liliane , Vandenbussche Paul , Sibille Yves , Dupont Etienne
Published: March 2007

Under endotoxin-free conditions, peripheral blood mononuclear cells and purified monocytes isolated from healthy control subjects and patients with alcoholic cirrhosis disclose elevated tumor necrosis factor α messenger RNA level and produce tumor necrosis factor α in response to stimulation by either soluble polymeric IgA or monomeric IgA bound to the surface of culture dishes but not by soluble monomeric IgA. Polymeric IgA induces tumor necrosis factor α secretion in a dose-dependent fashion. These results suggest that cross-linking of Fcα receptors on human monocytes induces the messenger RNA accumulation and the secretion of the cytotoxic and immunoregulatory cytokine tumor necrosis factor α. Furthermore, it is shown that lipopolysaccharide-induced tumor necrosis factor α secretion by peripheral blood mononuclear cells is synergistically enhanced in the presence of solid phase monomeric IgA but not in the presence of either soluble monomeric or polymeric IgA. Although increased lipopolysaccharide-induced tumor necrosis factor α secretion is observed at baseline in alcoholic cirrhotic patients, this synergism is also expressed in this group of patients. These observations could be of pathophysiological relevance in alcoholic cirrhosis because monomeric IgA deposits along the liver sinusoids and increased serum levels of polymeric IgA are common even in the early stages of this disease. (Hepatology 1991;13:670-675.)
Characterization of liver-associated natural killer cells in patients with liver tumors
Authors: Winnock Maria , Lafon Marie-Edith , Boulard Annick , Ferrer Anne-Marie , Saric Jean , Dubuisson Liliane , Bioulac-Sage Paulette , Balabaud Charles
Published: March 2007

The existence of a marginal lymphocyte population in rat liver sinusoids has already been demonstrated using the sinusoidal lavage method. We used the same technique to study the lymphocyte population in human liver obtained ex vivo after partial hepatectomy for benign or malignant tumors and compared it with peripheral and portal blood lymphocyte populations. Percentages of lymphocyte surface phenotypes were evaluated by flow cytometry.

The lymphocyte population obtained from human liver is mainly made up of CD56+ (35%) cells. This percentage is three times greater than that found in peripheral and portal blood. Two-color flow cytometry analysis showed that within the CD56+ liver cell population, at least three distinct subsets could be found: (a) CD3+/CD56+/CD16−; (b) CD3−/CD56+/CD16−; and (c) CD3−/CD56+/CD16+. Although these subsets were also present in peripheral and portal blood, the percentage distribution was completely different because most CD56+ cells in peripheral and portal blood belonged to the CD3−/CD56+/CD16+ subset.

These results show the existence of a heterogeneous natural killer cell population in human livers with tumors. The functional significance of this heterogeneity still needs to be explained. (Hepatology 1991;13:676-682.)
Impaired pressor reactivity in cirrhosis: Evidence for a peripheral vascular defect
Authors: Macgilchrist Alastair J. , Sumner David , Reid John L.
Published: March 2007

The blood pressure responses to intravenous infusions of norepinephrine and angiotensin II, sympathetic and nonsympathetic vasoconstricting agents, respectively, were measured in 20 patients with cirrhosis (10 Child-Pugh grade A and 10 Child-Pugh grades B or C) and in 20 healthy subjects. The log PD20 (dose of agonist required to raise blood pressure by 20 mm Hg) for norepinephrine was 4.78 ± 0.36 (mean ± S.D.) in patients with severe cirrhosis and 4.36 ± 0.37 in controls, p < 0.01. Log PD20 for angiotensin II was 3.16 ± 1.06 in patients with severe cirrhosis and 1.97 ± 0.74 in controls, p < 0.01. Cardiovascular responses to selective sympathetic agonists were measured in 10 other cirrhotic patients (all Child-Pugh grades B or C) and in 10 healthy controls. Log PD20s for phenylephrine, an α-1 adrenoceptor agonist, and for alphamethylnorepinephrine; an α-2 adrenoceptor agonist, were increased in cirrhosis (phenylephrine = 5.35 ± 0.49 vs. 4.95 ± 0.35, p < 0.05; alphamethylnorepinephrine = 4.05 ± 0.26 vs. 3.44 ± 0.55, p < 0.001). In contrast, log CD20 (dose of agonist required to raise the heart rate by 20 beats/min) for isoproterenol, a β-adrenoceptor agonist, was similar in cirrhotic patients and controls (2.81 ± 0.38 vs. 2.94 ± 0.45, p = 0.49). These studies demonstrate that pressor reactivity to both sympathetic and nonsympathetic agonists is impaired in severe cirrhosis, that the impaired sympathetic responses are not caused by generalized sympathetic desensitization and that the site common to the four agonists with impaired responses is the peripheral vascular smooth muscle. (Hepatology 1991;13:689-694.)
Recurrence of hepatitis C virus infection after orthotopic liver transplantation
Authors: Martin Paul , Muñoz Santiago J. , Di Bisceglie Adrian M. , Rubin Raphael , Waggoner Jeanne G. , Armenti Vincent T. , Moritiz Michael J. , Jarrell Bruce E. , Maddrey Willis C.
Published: March 2007

Identification of the hepatitis C virus-the main cause of posttransfusion and sporadic non-A, non-B hepatitis-and the development of a diagnostic serological test have allowed us to study possible recurrence of this type of hepatitis after liver transplantation. Six of 34 consecutive transplant recipients were found to have had antibodies to hepatitis C before transplantation. All six patients had possible exposure to hepatitis C, through blood transfusion or intravenous drug use. Five of the six patients were positive for antibodies to hepatitis C after 1 yr of follow-up. Two of these patients had clinical and histological evidence of acute viral hepatitis in their allografts. In one patient this led to hepatic injury and dysfunction of two successive grafts. In contrast, none of the twentyeight patients who were seronegative for hepatitis C virus antibodies before transplantation has converted to seropositivity after transplantation despite perioperative blood transfusions. These results suggest that hepatitis C diagnosed serologically recurs in a minority of transplant recipients and that de novo seroconversion must be uncommon. (Hepatology 1991;13:719-721.)
Kupffer cell activity and hepatic microvascular events after acute ethanol ingestion in mice
Authors: Eguchi Hiroshi , McCuskey Patricia A. , McCuskey Robert S.
Published: March 2007

After acute ethanol ingestion in C57B1/6 mice, phagocytic activity of Kupffer cells and hepatic microcirculation were examined by in vivo and electron microscopy. A ratio of Kupffer cells that phagocytosed 0.8 μm fluorescent latex particles to sinusoids containing blood flow (number of Kupffer cells/number of sinusoids containing blood flow) was used as a measure of Kupffer cell phagocytic activity. Three hours after ingestion of 1 gm/kg ethanol, number of Kupffer cells/number of sinusoids containing blood flow increased in both periportal and centrilobular regions by 62% and 66%, respectively, and blood ethanol was no longer detectable. Ultrastructurally, activation of KC was evidenced by the presence of many pseudopodia and filopodia. Numbers of swollen endothelial cells were increased in both regions by 249% and 174%. Interruption of sinusoidal blood flow by leukocytes was aggravated in both regions by 127% and 167%. Thirty minutes and 3 hr after ingestion of 4 gm/kg ethanol, no significant increase in number of Kupffer cells/number of sinusoids containing blood flow was seen, although number of Kupffer cells were also activated as seen with electron microscopy. An increased number of swollen endothelial cells was observed in both regions by 100% and 71% by 30 min and by 200% and 384% by 3 hr. The interruption of sinusoidal blood flow by leukocytes was also increased (periportal = 161%, centrilobular = 196%) as were sticking or plugging leukocytes in sinusoids (periportal = 320%, centrilobular = 120%) by 3 hr. The diameter of centrilobular sinusoids was decreased by 3 hr. Latex particles and platelets were attached to the sinusoidal wall after both low and high dosing. These findings suggest that acute ethanol ingestion activated Kupffer cells and affected the functions of leukocytes, platelets and endothelial cells. (Hepatology 1991;13:751-757.)
Adenine arabinoside monophosphate and acyclovir monophosphate coupled to lactosaminated albumin reduce woodchuck hepatitis virus viremia at doses lower than do the unconjugated drugs
Authors: Ponzetto Antonio , Fiume Luigi , Forzani Barbara , Song Shi Yun , Busi Corrado , Mattioli Alessandro , Spinelli Cosima , Marinelli Maria , Smedile Antonina , Chiaberge Elisabetta , Bonino Ferruccio , Gervasi Gian Battista , Rapicetta Mariella , Verme Giorgio
Published: March 2007

The woodchuck was selected to study the efficacy of liver-targeted antiviral drugs on hepadnavirus replication. Nineteen woodchucks chronically infected with woodchuck hepatitis virus were treated with adenine arabinoside monophosphate or acyclovir monophosphate, either free or conjugated with the liver-targeting molecule lactosaminated human serum albumin.

Circulating woodchuck hepatitis virus DNA levels remained unchanged in untreated animals and in those receiving the carrier lactosaminated human serum albumin alone; in contrast, they were consistently lower after 5 days of treatment with the antiviral drugs. Free and conjugated adenine arabinoside monophosphate were active at doses of 10 and 0.75 mg/kg, respectively, and free and coupled ACVMP were active at doses of 20 and 2.6 mg/kg, respectively.

These results indicate that the dosages of adenine arabinoside monophosphate and acyclovir monophosphate required to inhibit hepadnavirus growth can be sharply reduced by coupling the drugs to lactosaminated human serum albumin. (HEPATOLOGY 1991;14:16-24.)
Specificities of serum α-fetoprotein in HBsAg+ and HBsAg− patients in the diagnosis of hepatocellular carcinoma
Authors: Lee Hyosuk , Chung Young Hwa , Kim Chung Yong
Published: March 2007

Serum α-fetoprotein level is often elevated in patients with chronic liver disease and patients with hepatocellular carcinoma. One of the most difficult problems frequently encountered in practice is differentiating hepatocellular carcinoma from chronic liver disease. This study investigated the specificity and predictive value positive of serum α-fetoprotein at various levels in the diagnosis of hepatocellular carcinoma, using 54 patients with histologically proven hepatocellular carcinoma and 200 patients with chronic liver disease (40 patients with chronic active hepatitis and 160 patients with cirrhosis) as nontumor controls. Among 254 patients, 170 (66.9%) were HBsAg+. A wide range of overlap (from 0 to 6,400 ng/ml) in the distribution of serum α-fetoprotein levels between hepatocellular carcinoma and chronic liver disease patients was observed mainly among HBsAg+ patients. In contrast, the overlapping range of serum α-fetoprotein levels between HBsAg− patients with hepatocellular carcinoma and chronic liver disease was remarkably narrow (from 0 to 200 ng/ml). Therefore the specificity and predictive value positive of α-fetoprotein at a given level were significantly lower in HBsAg+ than in HBsAg− patients, especially when α-fetoprotein was between 25 and 200 ng/ml. The specificities of α-fetoprotein at 200 ng/ml and 400 ng/ml in HBsAg+ patients were 79.8% and 91.5%, respectively, whereas these specificities were both 100% in HBsAg+ patients. The predictive values positive at 200 ng/ml and 400 ng/ml in HBsAg+ patients were 53.6% and 72.5%, respectively, in contrast to 100% at both levels in HBsAg− patients. The serum α-fetoprotein level, which showed a predictive value positive of 95% in HBsAg+ hepatocellular carcinoma patients, was 3,200 ng/ml, whereas that in HBsAg− hepatocellular carcinoma patients, was 200 ng/ml.

We conclude that serum HBsAg status should be considered when serum α-fetoprotein is measured as an independent test to diagnose hepatocellular carcinoma, and suggest that regular serum α-fetoprotein determination may be more useful in HBsAg− patients with chronic liver disease for the early diagnosis of hepatocellular carcinoma than in HBsAg+ patients. (HEPATOLOGY 1991;14:68-72.)
Acidosis protects against lethal oxidative injury of liver sinusoidal endothelial cells
Authors: Bronk Steven F. , Gores Gregory J.
Published: March 2007

The purposes of this study were to determine the pH dependence of lethal endothelial cell injury during oxidative stress and the pH dependence of those cellular mechanisms proposed to result in endothelial cell killing. Oxidative stress was produced in rat liver sinusoidal endothelial cells with H2O2 (5 mmol/L). Cell survival was dependent on the extracellular pH. Indeed, after 180 min of incubation with H2O2, cell survival was only 27% at pH 7.4,45% at pH 6.8 (p <0.05) and 62% at pH 6.4 (p <0.05). Despite improved cell survival at pH 6.4 compared with pH 7.4, the magnitude of ATP hydrolysis and glutathione depletion was similar. In contrast to cell survival, lipid peroxidation as measured by malondialdehyde generation was increased twofold at pH 6.4 compared with pH 7.4. A rapid and profound loss of the the mitochondrial membrane potential occurred during oxidative stress at pH 7.4 that was delayed at pH 6.4 (0.3% vs. 20% of the initial value at 30 min, p <0.0001). After 60 min of incubation with H2O2, NAD(P)H oxidation was greater at pH 7.4 than at pH 6.4 (100% vs. 64%, p <0.05). The results indicate that the protective effect of acidosis against cell death during oxidative stress is associated with the inhibition of NAD(P)H oxidation and delayed loss of the mitochondrial membrane potential. Acidosis appears to maintain organelle and cell integrity during oxidative stress by influencing the redox status of NAD(P)H. (HEPATOLOGY 1991;14:150-157.)
The pattern of vasopressin-induced reduction in biliary output of cholephilic probes in the rat can be mimicked by dialysis
Authors: Yamaguchi Yashushi , Hardison William G. M.
Published: March 2007

During a recent study using isolated perfused rat liver, we concluded that the effects of vasopressin on biliary excretion of several anionic and cationic cholephilic probes could best be explained by passive diffusion of these probes through a paracellular pathway with permeability increased by vasopressin. Replication of the results of that study in an in vitro dialysis system would support the passive nature of the selective efflux of these cholephilic probes from the rat biliary tree and render metabolic events an unlikely explanation for the biliary excretory patterns of the probes. We studied biiary excretion of two bile acids—taurodehydrocholate and taurocholate—and two cholephilic cations—propidium and tributylmethylammonium—perfused single-pass through the isolated rat liver. We collected bile and measured probe output before and during infusion of 10−8 mol/L vasopressin. We also studied rates of diffusion of these probes in artificial solution and in whole rat bile through a 3,500 mol wt cut-off cellulose dialysis membrane. The relative order of probe efflux rates from the biliary tree with vasopressin administration paralleled their diffusion rates through the dialysis membrane. The only exception was that the biliary tree manifested charge selectivity. The data are compatible with the passive efflux of probe from the biliary tree, and metabolic events need not be invoked to explain their pattern of biliary excretion with vasopressin administration. (HEPATOLOGY 1991;14:175-179.)
ATP-dependent canalicular transport of cysteinyl leukotrienes
Authors: Ballatori Ned
Published: March 2007

The liver is the major organ which eliminates leukotriene C4 (LTC4) and other cysteinyl leukotrienes from the blood circulation into bile. Transport of LTC4 was studied using inside-out vesicles enriched in canalicular and sinusoidal membranes from rat liver. The incubation of canalicular membrane vesicles with [
3
H]LTC4 in the presence of ATP resulted in an uptake of LTC4 into vesicles. The initial rate of ATP-stimulated LTC4 uptake was about 40-fold higher in canalicular than in sinusoidal membrane vesicles.

When liver plasma membrane vesicles were incubated in the absence of ATP, an apparent transient uptake of LTC4 was observed which was temperaturedependent and not affected by the osmolarity. This indicates that LTC4 was bound to proteins on the surface of plasma membrane vesicles. Two proteins with relative molecular weights of 17,000 and 25,000 were detected by direct photoaffinity labeling as major LTC4-binding proteins. One protein (M

r
25,000) was ascribed to subunit 1 (Ya) of glutathione S-transferase which was associated with the membrane.

LTD4, LTE4, N-acetyl-LTE4, and ω-carboxy-N-acetyl-LTE4 were also transported into liver plasma membrane vesicles in an ATP-dependent manner with initial rates relative to LTC4 (1.0) of 0.46, 0.11, 0.35, and 0.22, respectively. Mutual competition between the cysteinyl leukotrienes and S-(2,4-dinitrophenyl)-glutathione for uptake indicated that they are transported by a common carrier. Apparent K

m
values of the transport system for LTC4, LTD4, and N-acetyl-LTE4 were 0.25, 1.5, and 5.2 μM, respectively. The ATP-dependent transport of LTC4 into vesicles was not inhibited by doxorubicin, daunorubicin, or verapamil, or by the monoclonal antibody C219, suggesting that the transport system differs from P-glycoprotein.

Liver plasma membrane vesicles prepared from mutant rats deficient in the hepatobiliary excretion of cysteinyl leukotrienes lacked the ATP-dependent transport of cysteinyl leukotrienes and S-(2,4-dinitrophenyl)-glutathione. These results demonstrate that the ATP-dependent carrier system is responsible for the transport of cysteinyl leukotrienes and glutathione S-conjugates from the hepatocytes into bile.
Cystic fibrosis—correct chloride conductance can cure cells
Authors: van Dyke Rebecca W.
Published: March 2007

We have used retrovirus-mediated gene transfer to demonstrate complementation of the cystic fibrosis (CF) defect in vitro. Amphotropic retroviruses were used to transduce a functional cystic fibrosis transmembrane conductance regulator (CFTR) cDNA into CFPAC-1, a pancreatic adenocarcinoma cell line derived from a patient with CF that stably expresses the chloride transport abnormalities characteristic of CF. CFPAC-1 cells were exposed to control virus (PLJ) and CFTR-expressing virus (PLJ-CFTR); viral-transduced clones were isolated and subjected to molecular and physiologic analysis. RNA analysis detected a viralderived CFTR transcript in all of the PLJ-CFTR clones that contained unrearranged proviral sequences. Agents that increase intracellular cAMP stimulated 125I efflux in PLJ-CFTR clones but not PLJ clones. Whole-cell patch-clamp performed on three responding clones showed that the anion efflux responses were due to cAMP stimulation of Cl conductance. Our findings indicate the expression of the normal CFTR gene confers cAMP-dependent Cl channel regulation on CF epithelial cells.

The cystic fibrosis transmembrane conductance regulator (CFTR) was expressed in cultured cystic fibrosis airway epithelial cells and Cl− channel activation assessed in single cells using a fluorescence microscopic assay and the patch-clamp technique. Expression of CFTR, but not of a mutant form of CFTR (ΔF508), corrected the Cl channel defect. Correction of the phenotypic defect demonstrates a causal relationship between mutations in the CFTR gene and defective Cl transport which is the hallmark of the disease.
Liver biopsy: Increased risks in patients with cancer
Authors: Conn Harold O.
Published: March 2007

Nine thousand two hundred twelve liver biopsies were performed according to a defined protocol, and data were prospectively recorded to identify risk factors for major bleeding. There were 10 fatal and 22 nonfatal hemorrhages (0.11% and 0.24%, respectively). By comparison with a control group that did not hemorrhage, malignancy, age, sex, and the number of passes were the only predictable risk factors. The risk of fatal hemorrhage in patients with malignancy is estimated to be 0.4%; for nonfatal hemorrhage, 0.57%. In patients undergoing liver biopsy for nonmalignant disease, the risks are 0.04% and 0.16%, respectively.
Surface modification and characterization of chitosan or PLGA membrane with laminin by chemical and oxygen plasma treatment for neural regeneration
Authors: Huang Yi‐Cheng , Huang Chun‐Chieh , Huang Yi‐You , Chen Keh‐Shaw
Published: March 2007

Attachment to and proliferation on the substrate are deemed important considerations when Schwann cells (SCs) are to be seeded in synthetic nerve grafts. Good attachment is a prerequisite for the SCs to survive. Fast proliferation will yield large numbers of SCs in a short time, which appears to be promising for stimulating peripheral nerve regeneration. However, surface properties are the dominating factor in influencing the interactions between cells and synthetic nerve grafts. The aim of this study was to investigate the surface effects of laminin modified PLGA and chitosan membranes after chemical method and plasma treatment. Laminin, the extracellular matrix protein, is a permissive protein for SCs adhesion used in neural regeneration. The surface properties of laminin modified membranes were assayed by BCA, FTIR and XPS analysis. Results showed that laminin was covalently bonded onto the surface of both PLGA and chitosan membranes either by chemical method or by oxygen plasma treatment. The cell affinity of the laminin modified membranes was verified by Schwann cells culturing. Our results also indicate that oxygen plasma is indeed a better method to incorporate laminin onto the surface of membrane. Laminin‐modified chitosan membrane significantly increases SCs attachment and affinity for directing peripheral nerve regeneration. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Antibacterial and osteogenic properties of silver‐containing hydroxyapatite coatings produced using a sol gel process
Authors: Chen W. , Oh S. , Ong A.P. , Oh N. , Liu Y. , Courtney H.S. , Appleford M. , Ong J.L.
Published: March 2007

Since bacterial infection is a rising complication following the wide use of implant, there is considerable attention on the effect of implant surface properties on bacterial adhesion. In this study, the effect of silver (Ag) doped hydroxyapatite (HA) coatings on initial antibacterial adhesion and osteoblast cell proliferation and differentiation was investigated. Using a sol‐gel process, HA coatings doped with 1 wt % AgNO3 (AgHA1.0) and 1.5 wt % Ag (AgHA1.5) were prepared. Coated surfaces were characterized using X‐ray diffraction (XRD) and contact angles measurements. The initial bacteria adhesion was evaluated using a RP12 strain of Staphylococcus epidermidis (ATCC 35984) and the Cowan I strain of Staphylococcus aureus, whereas osteoblast proliferation and differentiation were evaluated using human embryonic palatal mesenchyme cells (HEPM), an osteoblast precursor cell line. In this study, XRD analysis of all surfaces indicated peaks corresponding to HA. Contact angles for AgHA surfaces were observed to be significantly lower when compared to HA surfaces. In vitro initial bacterial adhesion study indicated a significantly reduced number of S. epidermidis and S. aureus on AgHA surfaces when compared to HA surface. The use of HEPM cells indicated no significant difference in double‐stranded DNA (dsDNA) production between all surfaces. Additionally, no differences in alkaline phosphatase specific activity were observed between HA and AgHA1.0 surfaces. Overall, it was concluded that AgHA1.0 has the similar biological activity as HA, with respect to bone cell proliferation and differentiation. In addition, the AgHA1.0 was also concluded to have the ability to minimize the initial bacteria adhesion. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Hemocompatibility evaluation of poly(diol citrate) in vitro for vascular tissue engineering
Authors: Motlagh Delara , Allen Josephine , Hoshi Ryan , Yang Jian , Lui Karen , Ameer Guillermo
Published: March 2007

One of the ongoing challenges in tissue engineering is the synthesis of a hemocompatible vascular graft. Specifically, the material used in the construct should have antithrombogenic properties and support the growth of vascular cells. Our laboratory has designed a novel biodegradable, elastomeric copolymer, poly(1,8‐octanediol citrate) (POC), with mechanical and degradation properties suitable for vascular tissue engineering. The hemocompatibility of POC in vitro and its ability to support the attachment and differentiation of human aortic endothelial cell (HAEC) was assessed. The thrombogenicity and inflammatory potential of POC were assessed relative to poly(l‐lactide‐co‐glycolide) and expanded poly(tetrafluoroethylene), as they have been used in FDA‐approved devices for blood contact. Specifically, platelet aggregation and activation, protein adsorption, plasma clotting, and hemolysis were investigated. To assess the inflammatory potential of POC, the release of IL‐1β and TNF‐α from THP‐1 cells was measured. The cell compatibility of POC was assessed by confirming HAEC differentiation and attachment under flow conditions. POC exhibited decreased platelet adhesion and clotting relative to control materials. Hemolysis was negligible and protein adsorption was comparable to reference materials. IL‐1β and TNF‐α release from THP‐1 cells was comparable among all materials tested, suggesting minimal inflammatory potential. POC supported HAEC differentiation and attachment without any premodification of the surface. The results described herein are encouraging and suggest that POC is hemocompatible and an adequate candidate biomaterial for in vivo vascular tissue engineering. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Encapsulation and osteoinduction of human periodontal ligament fibroblasts in chitosan–hydroxyapatite microspheres
Authors: Inanç Bülend , Eser Elçin A. , Koç Aysel , Baloş Köksal , Parlar Ateş , Murat Elçin Y.
Published: March 2007

Periodontal ligament cells play a crucial role in the regeneration of periodontal tissues and an undifferentiated mesenchymal cell subset is thought to exist within this population. The aim of this study was to assess the osteogenic differentiation potential of human periodontal ligament fibroblasts (hPDLFs) in three dimensional (3D)‐osteogenic culture environment following encapsulation in chitosan–hydroxyapatite (C/HA) microspheres with the size range of 350–450 μm. Human PDLF cultures were established and three experimental groups were formed: (i) two‐dimensional (2D)‐culture as single cell monolayer, (ii) 3D‐static culture of C/HA encapsulated hPDLFs, and (iii) 3D‐dynamic culture of C/HA encapsulated hPDLFs in a rotating wall vessel bioreactor. The cells were cultured in standard culture medium supplemented with β‐glycerophosphate, dexamethasone, and ascorbic acid. After 21 days, immunohistochemistry was performed using antibodies against osteonectin, osteopontin, bone‐sialoprotein, and osteocalcin as osteogenic differentiation markers. Phase‐contrast and scanning electron microscopy observations were used for histological and morphological evaluation. The combined effects of osteoinductive medium and HA‐containing composite microsphere material on encapsulated hPDLFs resulted in the transformation of a considerable portion of the cells into osteoblastic lineage at the end of the experiments. Results demonstrate the ability of hPDLFs to undergo osteogenic differentiation upon induction in vitro, both under 2D and 3D culture conditions. C/HA microspheres in microgravity bioreactor may serve as a suitable 3D environment to support the osteogenic differentiation of human PDLFs, in vitro. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Comparison between sol‐gel‐derived anatase‐ and rutile‐structured TiO2 coatings in soft‐tissue environment
Authors: Rossi S. , Moritz N. , Tirri T. , Peltola T. , Areva S. , Jokinen M. , Happonen R.‐P. , Närhi T.
Published: March 2007

The bioactivity of the surface reactive TiO2 coatings for medical implants can be locally modified by CO2 laser processing to match with the properties of surrounding tissues. The TiO2 coatings heat‐treated at 500°C exhibit in vitro bioactivity. With further CO2 laser treatment they exhibit enhanced in vitro bioactivity. The aim of this in vivo study was to compare the performance of heat‐treated anatase‐structured TiO2 coatings with preheat‐treated and CO2 laser‐treated rutile‐structured coatings in terms of their ability to attach soft connective tissues. The coatings were characterized with TF‐XRD and AFM. TiO2‐coated discs were implanted in rats. The samples were analyzed with routine histology, SEM‐EDS, and TEM. In both groups, already at 3 days, soft connective tissues were in immediate contact with the surface. No thick crystalline CaP layer was detected by SEM‐EDS, but a thin amorphous CaP layer was detected by XPS. No gap between the cell membrane and the coating could be observed in TEM pictures. No differences were observed between the anatase‐ and rutile‐structured coatings in terms of tissue responses. Further studies are needed to verify if the tissues are adherent to the surface of the implant. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Biochemical composition of the superficial layer of articular cartilage
Authors: Crockett R. , Grubelnik A. , Roos S. , Dora C. , Born W. , Troxler H.
Published: March 2007

To gain more information on the mechanism of lubrication in articular joints, the superficial layer of bovine articular cartilage was mechanically removed in a sheet of ice that formed on freezing the cartilage. Freeze‐dried samples contained low concentrations of chondroitin sulphate and protein. Analysis of the protein by SDS PAGE showed that the composition of the sample was comparable to that of synovial fluid (SF). Attenuated total reflection infrared (ATR‐IR) spectroscopy of the dried residue indicated that the sample contained mostly hyaluronan. Moreover, ATR‐IR spectroscopy of the upper layer of the superficial layer, adsorbed onto silicon, showed the presence of phospholipids. A gel could be formed by mixing hyaluronan and phosphatidylcholine in water with mechanical properties similar to those of the superficial layer on cartilage. Much like the superficial layer of natural cartilage, the surface of this gel became hydrophobic on drying out. Thus, it is proposed that the superficial layer forms from hyaluronan and phospholipids, which associate by hydrophobic interactions between the alkyl chains of the phospholipids and the hydrophobic faces of the disaccharide units in hyaluronan. This layer is permeable to material from the SF and the cartilage, as shown by the presence of SF proteins and chondroitin sulphate. As the cartilage dries out after removal from the joint, the phospholipids migrate towards the surface of the superficial layer to reduce the surface tension. It is also proposed that the highly efficient lubrication in articular joints can, at least in part, be attributed to the ability of the superficial layer to adsorb and hold water on the cartilage surface, thus creating a highly viscous boundary protection. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007