bluuebunny/crossref_metadata_2025 huggingface dataset:
High cholestanol and low campesterol-to-sitosterol ratio in serum of patients with primary biliary cirrhosis before liver transplantation
Authors: Nikkilä Katriina , Höckerstedt Krister , Miettinen Tatu A.
Published: March 2007

Serum levels of cholesterol precursors (squalene, Δ8-cholestenol, desmosterol and lathosterol), plant sterols (campesterol and sitosterol), cholestanol and cholestanol/noncholesterol sterol ratios were related to liver damage and liver transplantation indications in healthy controls (n = 26) and in 31 patients with primary biliary cirrhosis divided into group I (S-bilirubin < 21 μmol/L; n = 14), group II (S-bilirubin 21 to 108 μmol/L; n = 7) and group III (elected for liver transplantation; S-bilirubin 109 to 520 μmol/L; n = 10). The mean sérum respective lathosterol levels in controls and in group I were three and two times higher than those in groups II and III, respectively. The plant sterol contents were higher in group II than in groups I and III and the campesterol/sitosterol ratios were lowest in group III. The serum cholestanol levels were high even in group I (i.e., in patients without icterus) and increased progressively to group III, up to 6 and 13 times those in group I and the control group, respectively. The cholestanol/noncholesterol sterol ratios increased progressively from the controls to groups I, II and III. The serum cholestanol levels were positively related to serum bilirubin levels in all primary biliary cirrhosis patients (n = 31, r = 0.906) and to the plant sterol levels in the control group and group I, but significantly negatively in group III. The cholestanol vs. precursor sterol correlations were negative in most cases. In conclusion, our findings suggest that determination of serum cholestanol and lathosterol levels and cholestanol/plant sterol, campesterol/sitosterol and campesterol/lathosterol ratios might aid staging of liver damage in primary biliary cirrhosis. The high serum cholestanol level associated with the low campesterol/sitosterol ratio could be a significant indicator of end-stage primary biliary cirrhosis and, finally, of the need for liver transplantation. (Hepatology 1991;13:663-669.)
Fucosyltransferases: Differential plasma and tissue alterations in hepatocellular carcinoma and cirrhosis
Authors: Hutchinson Winston L. , Du Ming-Qing , Johnson Philip J. , Williams Roger
Published: March 2007

To determine whether abnormal metabolism of l-fucose in hepatocellular carcinoma is accompanied by alterations in the activities of fucosyltransferases, the latter were determined in plasma and liver tissue of patients with this disease and in cirrhotic and normal subjects. Activities of α-2/α-3 and α-6-l -fucosyltransferases were all significantly greater in plasma from patients with hepatocellular carcinoma than in plasma from cirrhotic patients or normal subjects (p < 0.025). The activity of each enzyme was dependent, to a similar extent, on Mn2+, Mg2+ and triton X-10, irrespective of the source, and all displayed pH optimums in the range of 7.5 to 8.0.

In contrast, activities of α-2/α-3 fucosyltransferases were significantly lower (p < 0.025) in homogenates prepared from tumorous liver tissue than in that prepared from nontumorous tissue from hepatocellular carcinoma and cirrhotic patients, whereas for the α-6 enzyme the situation was reversed (typically, tumor tissue levels were 5 pmol/hr/mg; in nontumor tissue they were 2 pmol/hr/mg). Activities of galactosyl and mannosyltransferase in tumor tissue were greater in all cases than in nontumor cirrhotic tissue. Plasma fucosyltransferases are specifically elevated in hepatocellular carcinoma but different mechanisms appear to underlie the changes seen for α-2/α-3 and α-6-l-fucosyltransferases. (Hepatology 1991;13:683-688.)
Susceptibility to autoimmune chronic active hepatitis: Human leukocyte antigens DR4 and A1-B8-DR3 are independent risk factors
Authors: Donaldson Peter T. , Doherty Derek G. , Hayllar Karen M. , McFarlane Ian G. , Johnson Philip J. , Williams Roger
Published: March 2007

After nearly 18 years of research, the association between human leukocyte antigens A1-B8-DR3 and autoimmune chronic active hepatitis still provokes debate. The principal reasons for this are disease heterogeneity and racial variation in the distribution of human leukocyte antigens between populations. The aim of the present study was to reexamine the relationship between these antigens and autoimmune chronic active hepatitis in a well-characterized series of patients. Ninety-six outpatients with autoimmune chronic active hepatitis and an additional 14 referred for liver transplantation with end-stage autoimmune chronic active hepatitis were studied. Human leukocyte antigen frequencies were compared with those of 100 racially and geographically matched controls. The A1-B8-DR3 haplotype was present in 38% of patients compared with 11% of controls (x
2 = 20.6, p < 0.0005). When all the DR3-positive patients were eliminated, there was a striking secondary association with DR4; 35 (80%) of 44 remaining patients were DR4 positive compared with 31 (39%) of 79 DR3-negative controls (Fisher's exact probability test p = 0.000031, pc = 0.0013). In addition patients with A1-B8-DR3 are seen at a significantly younger age than those without (39.75 yr vs. 48.21 yr, p < 0.025), relapse more frequently (52% of patients with A1-B8-DR3 relapsed on one or more occasions compared with 34% of patients without this haplotype) and are more frequently referred for liver transplantation. These data indicate for the first time that two genes within the major histocompatibility complex closely linked to the DR3 and DR4 genes independently confer susceptibility to autoimmune chronic active hepatitis. (Hepatology 1991;13:701-706.)
Randomized comparative study of hemaccel vs. albumin infusion after total paracentesis in cirrhotic patients with refractory ascites
Authors: Salerno Francesco , Badalamenti Salvatore , Lorenzano Elettra , Moser Pamela , Incerti Pierluigi
Published: March 2007

Fifty-four cirrhotic patients with refractory ascites were treated with one-session large-volume paracentesis and randomly assigned to two groups. The first group was infused with human albumin, and the second group was infused with hemaccel at doses with comparable oncotic power. The two groups were compared for incidence of complications, recurrence of massive ascites after hospital dismissal and survival rate.

The incidence of complications traditionally related to paracentesis, the probability of requiring readmission to the hospital for ascites (p = 0.48) and the probability of survival after entry into the study (p = 0.85) were the same for the two groups. A multivariate analysis of 16 parameters, including treatment modality, identified absolute unresponsiveness to diuretics as the only independent predictor of mortality. These results indicate that hemaccel infusion may safely replace albumin infusion after total paracentesis for cirrhotic patients with refractory ascites. (Hepatology 1991;13:707-713.)
Evaluation of postprandial hyperemia in superior mesenteric artery and portal vein in healthy and cirrhotic humans: An operator-blind echo-Doppler study
Authors: Sabbá Carlo , Ferraioli Giovanna , Genecin Paul , Colombato Luis , Buonamico Paolo , Lerner Emanuel , Taylor Kenneth J. W. , Groszmann Roberto J.
Published: March 2007

In an operator-blind design, we used an echo-Doppler duplex system to examine superior mesenteric artery and portal vein hemodynamics on two consecutive mornings in 12 fasting cirrhotic patients and 12 matched controls, randomized to a standardized 355 kcal mixed-liquid meal vs. water. Cross-sectional area and mean velocity were recorded from the portal vein and superior mesenteric artery at 30 min intervals, from 0 min to 150 min after ingestion. Flows were calculated. Pulsatility index, an index related to vascular resistance, was obtained for the mesenteric artery. Baseline flows did not differ between cirrhotic patients and control patients, but pulsatility index was reduced in the cirrhotic subjects. Maximal postprandial hyperemia was attained at 30 min. Cirrhotic patients showed a blunted hyperemic response to food. In normal controls, portal vein area increased significantly after the meal from 30 min to 150 min, whereas in cirrhotic patients a significant difference occurred only at 30 min. Pulsatility index in both groups was significantly reduced after eating, and this reduction persisted up to 150 min. No changes after ingestion of water were observed. Echo-Doppler was very sensitive in detecting postprandial splanchnic hemodynamic changes and differences between cirrhotic patients and normal subjects. Mesenteric artery pulsatility index was more sensitive than flow in detecting baseline hemodynamic differences. In cirrhotic patients, portal postprandial hyperemia was mainly related to the increase in mean velocity. (Hepatology 1991;13:714-718.)
Ethanol interferes with regeneration-associated changes in biotransforming enzymes: A potential mechanism underlying ethanol's carcinogenicity?
Authors: Diehl Anna Mae , Bisgaard Hanna Cathrine , Kren Betsy T. , Steer Clifford J.
Published: March 2007

The effects of chronic ethanol consumption on enzyme systems involved in carcinogen activation and detoxification were studied in a rat model of liver regeneration. In control rats, steady-state messenger RNAs of cytochrome P450j decreased 12 to 24 hr after partial hepatectomy but were fully recovered by 48 to 72 hr. In contrast, messenger RNA levels of cytochrome P450b and P450d did not vary significantly during that period. Steady-state messenger RNA levels for the placental form of glutathione S-transferase decreased within 30 min after partial hepatectomy but fluctuated until levels returned to normal by 48 hr. Preliminary nuclear run-on analyses suggest that the regulation of cytochrome P450j and the placental form of glutathione S-transferase messenger RNA levels involves posttranscriptional control in these animals. In ethanol-fed rats, as in controls, expression of cytochrome P450j and the placental form of glutathione S-transferase decreased transiently after partial hepatectomy. However, compared with control values, messenger RNA levels for cytochrome P450j were greater in ethanol-fed rats at each time point. Similar results were noted for placental glutathione S-transferase levels from 12 to 48 hr after partial hepatectomy. Ethanol feeding had no apparent effect on steady-state messenger RNA levels of cytochrome P450d, P450b or the multidrug-resistant gene. In both ethanol and control rats, only prehepatectomy levels of cytochrome P450 transcripts correlated with levels of the respective P450 isoenzymes. These data indicate that liver regeneration selectively decreases the steady-state messenger RNA expression of certain isoenzymes of cytochrome P450 and glutathione S-transferase. Chronic ethanol consumption induces basal messenger RNA expression of cytochrome P450j and blunts regeneration-associated decreases in cytochrome P450j and glutathione S-transferase expression. These alterations may be involved in ethanol's ability to function as a co-carcinogen in liver. (Hepatology 1991;13:722-727.)
Inhibition of rat hepatic mitochondrial aldehyde dehydrogenase-mediated acetaldehyde oxidation by trans -4-hydroxy-2-nonenal
Authors: Mitchell David Y. , Petersen Dennis R.
Published: March 2007

The hepatic oxidation of ethanol has been demonstrated to cause peroxidation of cellular membranes, resulting in the production of aldehydes that are substrates for hepatic aldehyde dehydrogenases. It was the purpose of this study to evaluate the cooxidation of the lipid peroxidation product, trans-4-hydroxy-2-nonenal, and acetaldehyde by high-affinity mitochondrial aldehyde dehydrogenase, which is of prominent importance in the oxidation of ethanol-derived acetaldehyde. Experiments were performed for determination of kinetic parameters for uninhibited acetaldehyde and 4-hydroxynonenal oxidation by semipurified mitochondrial aldehyde dehydrogenase prepared from male Sprague-Dawley rat liver. The affinity of the enzyme for the substrate at low substrate concentrations and the Michaelis-Menten constant of mitochondrial aldehyde dehydrogenase for acetaldehyde were 25 and 10 times greater, respectively, than those determined for 4-hydroxynonenal. Coincubation of acetaldehyde with physiologically relevant concentrations of 4-hydroxynonenal (0.25 to 5.0μmol/L) with mitochondrial aldehyde dehydrogenase demonstrated that 4-hydroxynonenal is a potent competitive or mixed-type inhibitor of acetaldehyde oxidation, with concentration of 4-hydroxynonenal required for a twofold increase in the slope of the Lineweaver-Burk plot for acetaldehyde oxidation by ALDH of 0.48 μmol/L. The results of this study suggest that the aldehydic lipid peroxidation product, trans-4-hydroxy-2-nonenal, is a potent inhibitor of hepatic acetaldehyde oxidation and may potentiate the hepatocellular toxicity of acetaldehyde proposed to be an etiological factor of alcoholic liver disease. (Hepatology 1991;13:728-734.)
Hepatocyte growth factor (hepatopoietin A) rapidly increases in plasma before DNA synthesis and liver regeneration stimulated by partial hepatectomy and carbon tetrachloride administration
Authors: Lindroos Pamela M. , Zarnegar Reza , Michalopoulos George K.
Published: March 2007

An enzyme-linked immunosorbent assay was used to measure the level of hepatocyte growth factor in rat plasma at various times after two-thirds partial hepatectomy or CCl4 administration. An initial 17-fold rise and 13-fold rise in the level of hepatocyte growth factor was observed 2 hr after partial hepatectomy and CCl4 treatment, respectively, well before the onset of DNA synthesis in the liver. The peaks of DNA synthesis in remnant livers and livers exposed to CCl4 occurred at 24 hr and 48 hr, respectively, as determined by 5-bromo-2′-deoxyuridine labeling and [3H]thymidine uptake by the liver. A later peak level (17-fold above control) of hepatocyte growth factor at 24 hr after CCl4 treatment coincided with strong immunostaining of damaged or necrotic hepatocytes around central veins with an antibody to hepatocyte growth factor. This suggests a later intrahepatic origin of the signals for liver regeneration after hepatotoxic injury subsequent to the early extrahepatic production of hepatocyte growth factor at 2 hr after CCl4 administration. The absence of staining in the liver remnants in partially hepatectomized rats implies that the increase in hepatocyte growth factor seen in the plasma is caused by production at extrahepatic site(s). Possible sources include the pancreas, brain, thyroid and salivary glands, and Brunner's glands of the duodenum. Norepinephrine also increases in plasma as early as 2 hr after hepatectomy. In vitro, [3H]thymidine incorporation into hepatocyte DNA in the presence of hepatocyte growth factor is greater if 10−5 mol/L norepinephrine is also present in the media. In contrast with other growth factors whose production by hepatocytes coincides with the peak of DNA synthesis (transforming growth factor α and acidic fibroblast growth factor), the hepatocyte growth factor increase in plasma occurs long before DNA synthesis and coincides with the observed increase in plasma norepinephrine at 2 to 4 hr after two-thirds partial hepatectomy. The concurrent elevation in plasma levels of the strongest hepatocyte mitogen (hepatocyte growth factor) and the strongest hepatocyte mitogenic amplifier (norepinephrine) probably serves to provide the mitogenic signal that initiates the first round of DNA synthesis during liver regeneration. (Hepatology 1991;13:743-749.)
Biliary tract disease in rats with experimental small bowel bacterial overgrowth
Authors: Lichtman Steven N. , Keku John , Clark Richard L. , Schwab John H. , Sartor Ryan B.
Published: March 2007

Small bowel bacterial overgrowth, which develops in surgically created jejunal self-filling blind loops, is associated with hepatic injury in susceptible rat strains. The histological findings are portal tract inflammation and bile duct proliferation and destruction. In this study, evidence of injury to the extrahepatic and intrahepatic bile ducts in susceptible and resistant inbred rats with self-filling blind loops was determined by bile flow rates, histological appearance of cross-sections of bile ducts and cholangiography. Lewis and Wistar rats with self-filling blind loops had thickening of the cross-sectional area of the extrahepatic bile ducts compared with controls and nonsusceptible Buffalo rats (p < 0.001). Daily metronidazole therapy significantly reduced thickening of bile ducts in Lewis and Wistar rats with self-filling blind loops. Bile flow was increased in Lewis and Wistar rats with blind loops compared with controls (p < 0.05).

Cholangiograms of Lewis and Wistar rats with self-filling blind loops demonstrated extrahepatic ductal dilatation and ectasia with irregular, beaded, rapidly tapering and tortuous intrahepatic ducts. Blinded cholangiographical scores of susceptible rat strains with self-filling blind loops were higher (score = 5.9 ± 2.3) than those of controls (1.2 ± 0.4), rats with blind loops treated with metronidazole (0.8 ± 1.3) and nonsusceptible Buffalo rats with blind loops (0.6 ± 0.9) (p < 0.01). Biliary histological and cholangiographical abnormalities found in this rat model resemble features of primary sclerosing cholangitis. This animal model will be useful in exploring mechanisms of the association of hepatobiliary inflammation with intestinal injury and investigating potential therapeutic agents. (Hepatology 1990;13:766-772.)
Treatment of hepatocellular carcinoma
Authors: Gumucio Jorge J. , Di Bisceglie Adrian M.
Published: March 2007

Fifty-one patients with unresectable hepatocellular carcinoma were treated by embolization of the hepatic artery with Gelfoam powder, contrast material and three chemotherapeutic agents (doxorubicin, mitomycin, cisplatin). Twelve patients (24%) had a partial response with a decrease in the tumor diameter by at least 50%, 13 patients (26%) had only minor responses, 12 (24%) had stabilization of disease and the remainder had progressive disease. Tumor liquefaction was noted on computed tomographic scanning in 70% of patients, and 23 of 34 patients with elevations in serum alphafetoprotein values had a greater than 50% reduction following treatment. The median patient survival time from treatment was 207 days. Most patients experienced transient pain, fever, nausea and elevations in serum aminotransferase activities as a result of therapy. Ascites developed in 14 patients. There were two treatment-related deaths: one from tumor hemorrhage and one from liver failure. Chemoembolization therefore appears to have significant activity in patients with hepatocellular carcinoma and is relatively well tolerated.

This study reports the results of resection in 72 cirrhotic patients with hepatocellular carcinoma from Europe. One and 3 year survival rates were 68% and 51% respectively. Survival was significantly higher in Child's class A than in class B or C patients. Patients with a thickly encapsulated tumor lived longer than those with an infiltrating tumor and also had a significantly lower recurrence rate. There was no relationship between the size of the tumor or the presence of symptoms and survival. These data suggest that good results can be achieved by resection of hepatocellular carcinoma in European cirrhotic patients. A thickly encapsulated tumor and good liver function are the main determinants of low cancer recurrence and high survival.
Potential importance of the sexual transmission of non-A, non-B hepatitis
Authors: Gumucio Jorge J. , Perillo Robert P.
Published: March 2007

To identify previously unrecognized sources for acquiring acute hepatitis B and non-A, non-B (NANB) hepatitis, we interviewed patients with these types of hepatitis who were reported to two county health departments in the United States and matched control subjects for known and potential risk factors for acquiring hepatitis. Of 218 patients with hepatitis B and 140 patients with NANB hepatitis, 46% and 53%, respectively, had no commonly recognized source for infection. When these patients were compared with control subjects, significantly more patients with hepatitis B had multiple heterosexual partners, accounting for 14% of all hepatitis B infections; more patients with NANB hepatitis either had sexual or household contact with a person who had hepatitis in the past or had multiple heterosexual partners, accounting for 11% of all NANB infections. This is the first study to suggest that heterosexual transmission may play an important role in the spread of NANB hepatitis.
HBxAg in the liver from carrier patients with chronic hepatitis and cirrhosis
Authors: Wang Wenliang , London Thomas W. , Lega Laura , Feitelson Mark A.
Published: March 2007

Formalin-fixed, paraffin-embedded specimens from 110 cases of chronic hepatitis and 108 cases of cirrhosis were stained for HBxAg by the avidin-biotin complex technique using specific antisera made against full-length HBxAg polypeptide or derived synthetic peptides. These tissues were also stained for the HBsAg and HBcAg by the peroxidase—anti-peroxidase method. Among patients with chronic hepatitis, 86% were HBsAg positive in liver cells, 60% were surface antigen positive and 32% were core antigen positive. Among patients with cirrhosis, 97% were HBsAg positive in liver cells, 72% were surface antigen positive and 17% were positive for core antigen. Staining specificity was demonstrated, in part, by using preimmune sera in the place of primary antibody, by blocking of the primary antibody with the appropriate antigen before assay and by testing uninfected liver controls. The persistence and high frequency of HBxAg in liver cells from patients with chronic liver disease suggest that it may play one or more important roles in the pathogenesis of chronic infection. It is possible that detection of HBxAg in the liver could be an additional new diagnostic marker for hepatitis B virus infection. However, the function(s) of HBxAg in the pathogenesis of the chronic liver disease, if any, remains to be explained. (HEPATOLOGY 1991;14:29-37.)
IgM antibody to hepatitis C virus in acute and chronic hepatitis C
Authors: Quiroga Juan Antonio , Campillo María Luz , Catillo Inmaculada , Bartolomé Javier , Porres Juan Carlos , Carreño Vicente
Published: March 2007

To assess possible role of testing for IgM-specific antibody in the diagnosis and monitoring of patients with hepatitis C, we tested sera from 14 patients with acute and 97 patients with chronic non-A, non-B hepatitis for IgG and IgM antibody to hepatitis C virus. IgG antibody to hepatitis C virus was detected in 93% of acute cases and 91% of chronic cases. Of the 101 patients with IgG antibody to hepatitis C virus, 57% had IgM antibody to hepatitis C virus. None of the 20 healthy subjects or 40 patients with acute or chronic hepatitis A or hepatitis B had IgM antibody to hepatitis C virus. At the onset of clinical symptoms in acute hepatitis C, IgG antibody to hepatitis C virus was detected in 8 (57%) and IgM antibody to hepatitis C virus in 9 of 14 patients (64%). Eventually, both IgG and IgM antibody to hepatitis C virus became detectable in 13 of 14 patients with acute hepatitis C. Seven patients with antibody to hepatitis C virus resolved the acute infection within 6 mo and all seven cleared IgM antibody to hepatitis C virus, whereas two cleared IgG antibody to hepatitis C virus. Six patients had a chronic outcome of the acute infection and IgM antibody to hepatitis C virus persisted in detectable amounts for more than 6 mo in all (mean = 15.5 mo). Among 88 patients with chronic non-A, non-B hepatitis with IgG antibody to hepatitis C virus, IgM antibody to hepatitis C virus was detected in 45(51%). Twenty-four chronic cases were followed for at least 1 yr: IgM antibody to hepatitis C virus was detected in 13 (54%) at baseline and 8 of these remained positive for at least 1 yr. Patients who lost IgM antibody to hepatitis C virus did not have remission of disease activity. In summary, IgM antibody to hepatitis C virus persists after acute infection in patients who contract chronic hepatitis C; therefore, testing for this antibody may be useful in early identification of patients for antiviral therapy. (HEPATOLOGY 1991;14:38-43.)
Hepatitis C viral RNA in serum of patients with chronic non-A, non-B hepatitis: Detection by the polymerase chain reaction using multiple primer sets
Authors: Cristiano Karen , Di Bisceglie Adrian M. , Hoofnagle Jay H. , Feinstone Stephen M.
Published: March 2007

The recently introduced antibody test for hepatitis C virus infection has already proved to be valuable in many situations such as screening blood donors and diagnosing chronically infected patients, but this antibody assay has certain limitations. Hepatitis C virus itself is usually present in clinical specimens at very low titers; therefore a useful assay for the virus must have very high sensitivity. We have developed a simple, highly sensitive assay for hepatitis C virus RNA based on the polymerase chain reaction. In this test RNA extracted from hepatitis C virus—infected serum or plasma is used as the template for double polymerase chain reaction with nested primers. Sensitivity studies demonstrate that this assay is able to detect hepatitis C virus at or beyond the sensitivity level of chimpanzee infectivity. Preliminary studies in chronic non-A, non-B hepatitis showed that 16 of 36 patients positive for antibody to hepatitis C virus and 2 of 4 patients negative for antibody to hepatitis C virus were positive in the polymerase chain reaction test. By retesting the polymerase chain reaction—negative patients with several sets of polymerase chain reaction primers, we found hepatitis C virus RNA in 35 of the 40 patients including all 4 seronegative patients. Normal human plasma and plasma from patients with hepatitis B infection did not react in this test. This assay has proved to be valuable for determining the presence of hepatitis C virus RNA in various samples. Furthermore, it offers the possibility of diagnosis of hepatitis C virus infection in patients who do not react in the presently available antibody tests. (HEPATOLOGY 1991;14:51-55.)
Relationship between insulin sensitivity, insulin secretion and glucose tolerance in cirrhosis
Authors: Kruszynska Yolanta T. , Home Philip D. , McIntyre Neil
Published: March 2007

Hepatic insulin extraction is difficult to measure in humans; as a result, the interrelationship between defective insulin secretion and insulin insensitivity in the pathogenesis of glucose intolerance in cirrhosis remains unclear. To reassess this we used recombinant human C-peptide to measure C-peptide clearance in cirrhotic patients and controls and thus derive C-peptide and insulin secretion rates after a 75-gm oral glucose load and during a 10 mmol/L hyperglycemic clamp. Cirrhotic patients were confirmed as insulin-insensitive during a euglycemic clamp (glucose requirement: 4.1 ± 0.1 mg/kg/min vs. 8.1 ± 0.5 mg/kg/min; p < 0.001), which also demonstrated a low insulin metabolic clearance rate (p < 0.001). Although intolerant after oral glucose, the cirrhotic patients had glucose requirements identical to those of controls during the hyperglycemic clamp (cirrhotic patients: 6.1 ± 1.0 mg/kg/min; controls: 6.3 ± 0.7 mg/kg/min), suggesting normal intravenous glucose tolerance.

C-peptide MCR was identical in cirrhotic patients (2.93 ± 0.16 ml/min/kg) and controls (2.96 ± 0.24 ml/min/kg). Insulin secretion was higher in cirrhotic patients, both fasting (2.13 ± 0.26 U/hr vs. 1.09 ± 0.10 U/hr; p < 0.001) and from min 30 to 90 of the hyperglycemic clamp (5.22 ± 0.70 U/hr vs. 2.85 ± 0.22 U/hr; p < 0.001). However, with oral glucose the rise in serum C-peptide concentration was relatively delayed, and the insulin secretion index (secretion/area under 3-hr glucose curve) was not elevated. Hepatic insulin extraction was reduced both in fasting and during the hyperglycemic clamp (p < 0.001).

Thus hypersecretion and decreased insulin clearance contribute to the four- to sixfold increased insulin levels in cirrhotic patients (fasting and after oral or intravenous glucose). In response to intravenous glucose, this hyperinsulinemia compensates for peripheral-tissue insulin insensitivity, accounting for normal rates of glucose disposal. In response to oral glucose, compensation is only partial, glucose intolerance being most marked in those cirrhotic patients with a lower insulin secretory response (r = −0.76, p < 0.02). (HEPATOLOGY 1991;14:103-111.)
Asymptomatic bacterascites: Is it spontaneous bacterial peritonitis?
Authors: Pelletier Gilles , Lesur Gilles , Ink Olivier , Hagege Hervé , Attali Pierre , Buffet Catherine , Etienne Jean-Pierre
Published: March 2007

Asymptomatic bacterascites is defined as the presence of bacteria in ascitic fluid without clinical features of peritonitis or increased ascitic fluid polymorphonuclear cells. Asymptomatic bacterascites is a controversial entity, and little information is available regarding its spontaneous evolution. Clinical features, bacteriological data and outcome in 22 cirrhotic patients with asymptomatic bacterascites are reported and are compared with those of a group of 36 cirrhotic patients with spontaneous bacterial peritonitis. Eleven patients had gram-negative bacteria and 11 had one gram-positive bacteria. Only in three patients (13.6%) did peritonitis develop. Twelve patients received no antibiotic therapy, and in none did peritonitis develop. At 1 month, 27% of patients with asymptomatic bacterascites had died. Patients with asymptomatic bacterascites had less-severe liver disease; they more frequently had gram-positive bacteria in ascitic fluid and had a lower 1-mo mortality rate than did patients with spontaneous bacterial peritonitis.

We conclude that asymptomatic bacterascites is usually the transient residence of bacteria in ascitic fluid. Peritonitis rarely develops in patients with asymptomatic bacterascites and, in most of them, antibiotic therapy is not required. (HEPATOLOGY 1991;14:112-115.)
Impaired binding properties of thyroxine-binding globulin in hepatocellular carcinoma and chronic liver disease
Authors: Hutchinson Winston L. , White Yvette S. , Fagan Elizabeth A. , Johnson Philip J. , Williams Roger
Published: March 2007

To determine the factors underlying the apparent reduction in binding ability of thyroxine-binding globulin in hepatocellular carcinoma, hormonebinding characteristics were further examined in patients with this disease and in control subjects. No differences in affinity constants with respect to triiodothyronine or serum thyroxine-binding globulin from hepatocellular carcinoma, cirrhotic and normal subjects were found. The affinity for thyroxine was significantly reduced in hepatocellular carcinoma (0.41 ± 0.13 × 1010 mol−1) and cirrhotic (0.65 ± 0.1 × 1010 mol−1) patients compared with normal subjects (0.94 ± 0.7 × 1010 mol−1).

Investigations carried out on liver tissue obtained from patients with hepatocellular carcinoma and chronic liver disease showed that thyroxine-binding globulin within tumor tissue was elevated and bound less exogenous tracer hormone compared with that obtained from nontumor tissue. Tumor-derived thyroxine-binding globulin with altered binding properties is, at least partly, responsible for the abnormal behavior of the serum protein in patients with hepatocellular carcinoma. (HEPATOLOGY 1991;14:116-120.)
Immunophenotyping of lymphocytes in liver tissue of patients with chronic liver diseases by flow cytometry
Authors: Li Xiuming , Jeffers Lennox J. , Reddy Rajender K. , de Medina Maria , Silva Marcelo , Villanueva Steven , Klimas Nancy G. , Esquenazi Violet , Schiff Eugene R.
Published: March 2007

Immunological factors are important in the pathogenesis of a spectrum of hepatobiliary diseases. To characterize the nature of specific immunological responses in liver disease, we determined lymphocyte changes in liver tissue and in blood using flow cytometry. A total of 113 liver biopsy specimens was collected from patients with the following diseases: 19 chronic hepatitis B; 39 chronic non-A, non-B hepatitis; 27 alcoholic liver disease; 10 hepatic malignancy; 8 autoimmune hepatitis; 6 fatty liver and 4 primary biliary cirrhosis. The lymphocytes were isolated from the liver biopsy specimens by mechanical and enzymatic methods. The lymphocyte yield was 7,901 ± 575 cells/mg of liver tissue. The viability of lymphocytes was 97.7% ± 0.3%. Lymphocytes were stained with four pairs of two-color mixed fluorescein—conjugated monoclonal antibodies, including T4-T8 (CD4/CD8), T11-B1 (CD2-CD20), NKH1-T8 (CD56-CD8), IL-2R1-T11 (CD25-CD2), and the ratios were determined by an Epics Profile flow cytometer. Immunophenotyping of lymphocytes in whole blood samples was simultaneously analyzed.

Variability in lymphocyte yield and different patterns of lymphocyte subsets were found in the liver biopsy specimens. The yields of lymphocytes from patients with chronic non-A, non-B and autoimmune hepatitis were highest, and the lowest yield was from patients with fatty liver. Patients with primary biliary cirrhosis, fatty liver and hepatic malignancy had relatively high ratios of CD4/CD8, CD56/CD8 and CD25/CD2; whereas patients with chronic hepatitis B, autoimmune hepatitis and non-A, non-B hepatitis had lower ratios of CD4/CD8, CD56/CD8 and CD25/CD2. No difference in lymphocyte ratios between the patients with cirrhotic and noncirrhotic alcoholic liver disease was found. The ratio of CD2/CD20 decreased, and the ratios of CD56/CD8 and CD25/CD2 increased in patients with chronic non-A, non-B hepatitis after 6 mo of interferon treatment, whereas no significant changes occurred in subsets in patients with chronic hepatitis B. The patterns of lymphocyte subsets in blood samples did not correlate with those found in the corresponding liver samples.

These results demonstrate the feasibility of immunophenotyping lymphocyte subpopulations in small liver biopsy specimens using a novel approach. Such methodology is needed to establish the immunological mechanisms in liver damage and the effects of therapy. (HEPATOLOGY 1991;14:121-127.)
A simple method for biliary-enteric anastomosis and chronic bile diversion in the rat
Authors: Rudnicki Marek , McFadden David W. , Fischer Josef E.
Published: March 2007

A simple method of biliary-enteric anastomosis, without the use of surgical microscopy, is described. There were no signs of cholestasis after 3 mo of follow-up. A modified procedure using a silicone elastomer catheter as a stent for the biliary-enteric anastomosis resulted in biliary obstruction within 3 wk after surgery. Our experimental bile duct implantation technique is a simple and useful experimental method for the investigation of chronic biliary diversion and biliary physiology. Additionally, it can be performed safely and easily in a rodent model without sophisticated microscopic techniques. (HEPATOLOGY 1991;14:128-130.)
Studies on mechanisms of augmentation of liver regeneration by cyclosporine and FK 506
Authors: Francavilla Antonio , Starzl Thomas E. , Barone Michele , Zeng Qi-Hua , Porter Kendrick A. , Zeevi Adrianni , Markus Peter M. , van den Brink Marcell R. M. , Todo Satoru
Published: March 2007

Evidence could not be found of immune modulation of liver regeneration. The powerful immunosuppressive drug FK 506, which augments the response after partial hepatectomy in normal rats, had the same effect in T cell—deficient nude rats. The cytotoxicity of natural killer cells in treated nude rats was not significantly changed by FK 506 therapy. However, the serum of FK 506—treated nude rats increased hepatocyte proliferation when added to third-party hepatocyte cultures, suggesting that FK 506 had induced a serum growth factor in the nude rats or had suppressed an inhibitory factor. A hypothesis was advanced that FK 506 (and cyclosporine) affects hepatic growth by nonimmunological pathways. (HEPATOLOGY 1991;14:140-143.)
Permanent engraftment and function of hepatocytes delivered to the liver: Implications for gene therapy and Liver Repopulation
Authors: Gupta Sanjeev , Aragona Emma , Vemuru Ravikumar P. , Bhargava Kuldeep K. , Burk Robert D. , Chowdhury Jayanta Roy
Published: March 2007

To examine the distribution of intrasplenically transplanted hepatocytes, we used HBsAg-producing G7 HBV transgenic hepatocytes or cells labeled with 111In. Most hepatocytes translocated to the liver (55% ± 7%; mean ± S.D.); the spleen retained a smaller fraction (15% ± 3%); and some transplanted cells localized in lungs (3%) or pancreas (1%). Transplanted hepatocytes were rapidly assimilated into the liver lobule. Morphometrical quantitation indicated that the numbers of transplanted hepatocytes in the liver at 48 hr and at 9 mo after transplantation were similar. Serum HBsAg was detected in recipients of the G7 HBV hepatocytes during the 1-yr experiment. These results indicate that a large number of hepatocytes can be reproducibly delivered to the liver by transplantation into the spleen. Transplanted hepatocytes engraft rapidly, assimilate into host liver, maintain normal function and survive permanently. Systems for safe delivery and localization of hepatocytes in the liver represent a critical step toward successfully accomplishing hepatocyte-directed gene therapy and repopulation of the acutely devastated liver. (HEPATOLOGY 1991;14:144-149.)
Replacement of cholesterol gallstones by murideoxycholyl taurine gallstones in prairie dogs fed murideoxycholic acid
Authors: Cohen Bertram I. , Ayyad Nariman , Mosbach Erwin H. , McSherry Charles K. , Matoba Naoyuki , Hofmann Alan F. , Ton-Nu Huong-Thu , Peng Ying , Schteingart Claudio D. , Stenger Richard J.
Published: March 2007

The effect of two hydrophilic bile acids, murideoxycholic acid (3α,6β-dihydroxy-5β-cholanoic acid) and ursodeoxycholic acid, on cholesterol and bile acid metabolism and hepatic pathology and gallstone composition was studied in the prairie dog. Cholesterol gallstones were induced by feeding a diet containing 1.2% cholesterol for 75 days. The animals were divided into six groups, and gallstone regression was studied as follows: groups 2 and 5, chow plus 0.2% cholesterol; groups 3 and 6, chow plus 0.2% cholesterol plus 0.15% ursodeoxycholic acid; groups 4 and 7, chow plus 0.2% cholesterol plus 0.15% murideoxycholic acid. Animals in groups 2 to 4 were killed after an additional 6 wk; animals in groups 5 to 7 were killed after an additional 12 wk. Gallstone dissolution did not occur in any group. The gallstones in groups 2, 3, 5 and 6 were typical cholesterol aggregates, as determined by polarized light microscopy and Fourier transform infrared spectrometry. The gallstones of the murideoxycholic acid group were large, solitary, dark stones that appeared radiopaque under 22 kVp x-ray examination. Scanning electron microscopy showed that in these stones the cholesterol crystals had been replaced by an amorphous material, both within the stone and on the stone surface. Chemical analysis indicated that at the end of 12 wk the calcium/sodium salt of the taurine conjugate of murideoxycholic acid (murideoxycholyl taurine) comprised 70% of the stones; protein, cholesterol and small amounts of other bile salts were also present. In vitro studies confirmed the insolubility of the sodium and calcium salts of murideoxycholyl taurine. These studies indicate that the hydrophilic bile acids, murideoxycholic acid and ursodeoxycholic acid, did not achieve gallstone dissolution under the conditions used. In the animals fed murideoxycholic acid, an insoluble calcium salt of murideoxycholyl taurine replaced cholesterol as the major constituent of gallbladder stones. This is the first example of an insoluble dihydroxy taurine-conjugated bile acid; administration of the unconjugated bile acid induced precipitation of a kind of gallstone not previously reported. The final result was transformation of cholesterol stones to bile salt stones. (HEPATOLOGY 1991;14:158-168.)
Anodized titanium and stainless steel in contact with CFRP: An electrochemical approach considering galvanic corrosion
Authors: Mueller Yves , Tognini Roger , Mayer Joerg , Virtanen Sannakaisa
Published: March 2007

The combination of different materials in an implant gives the opportunity to better fulfill the requirements that are needed to improve the healing process. However, using different materials increases the risk of galvanic coupling corrosion. In this study, coupling effects of gold‐anodized titanium, stainless steel for biomedical applications, carbon fiber reinforced polyetheretherketone (CFRP), and CFRP containing tantalum fibers are investigated electrochemically and by long‐term immersion experiments in simulated body fluid (SBF). Potentiodynamic polarization experiments (i/E curves) and electrochemical impedance spectroscopy (EIS) of the separated materials showed a passive behavior of the metallic samples. Anodized titanium showed no corrosion attacks, whereas stainless steel is highly susceptibility for localized corrosion. On the other side, an active dissolution behavior of both of the CFRPs in the given environment could be determined, leading to delaminating of the carbon fibers from the matrix. Long‐term immersion experiments were carried out using a set‐up especially developed to simulate coupling conditions of a point contact fixator system (PC‐Fix) in a biological environment. Electrochemical data were acquired in situ during the whole immersion time. The results of the immersion experiments correlate with the findings of the electrochemical investigation. Localized corrosion attacks were found on stainless steel, whereas anodized titanium showed no corrosion attacks. No significant differences between the two CFRP types could be found. Galvanic coupling corrosion in combination with crevice conditions and possible corrosion mechanisms are discussed. © 2007 Wiley Periodicals, Inc. JBiomed Mater Res, 2007
Surface engineering of titanium thin films with silk fibroin via layer‐by‐layer technique and its effects on osteoblast growth behavior
Authors: Cai Kaiyong , Hu Yan , Jandt Klaus D.
Published: March 2007

The objective of the present study was to surface modify the titanium thin films to improve its biocompatibility. A layer‐by‐layer (LBL) self‐assembly technique, based on the electrostatic interactions mediated adsorption of chitosan (Chi) and silk fibroin (SF), was used leading to the formation of multilayers on the titanium thin film surfaces. The surface chemistry and wettability of LBL films were investigated by X‐ray photoelectron spectroscopy (XPS), water contact angle measurement, and atomic force microscopy, respectively. XPS and contact angle measurement results indicated that a full SF/Chi pair film was formed after the deposition layers of PEI/(SF/Chi)2 on the titanium film surfaces. The topographies of multilayered films were directly related to the corresponding outmost layer components. The build‐up of such SF/Chi pair films on titanium films may in turn affect the biocompatibility of the modified titanium films. Therefore, an in vitro investigation was performed to confirm this hypothesis. Cell proliferation, cell viability, DNA synthesis as well as differentiation function (alkaline phosphatase) of osteoblasts on LBL‐modified titanium films and control samples were investigated, respectively. Osteoblasts cultured on modified titanium films was found to be higher proliferation tendency than that on control (p < 0.05). Cell viability, alkaline phosphatase as well as DNA synthesis measurement indicated that osteoblasts on LBL‐modified films were greater (p < 0.05 or p < 0.01) than the control, respectively. These results suggest that surface engineering of titanium was successfully achieved via LBL deposition of Chi/SF pairs, and enhanced its cell biocompatibility. The approach presented in the study may be exploited as an efficient alternative for surface engineering of titanium‐based implants. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
The interaction between hydrolytic and oxidative pathways in macrophage‐mediated polyurethane degradation
Authors: McBane Joanne E. , Santerre J. Paul , Labow Rosalind S.
Published: March 2007

Although relatively resistant to oxidation, polycarbonate‐based polyurethanes (PCNUs) are degraded by monocyte‐derived macrophages (MDM) by a co‐mediated mechanism involving both hydrolytic and oxidative pathways. Since a previous study showed that PCNU pretreatment with H2O2 modulated degradation by esterases, human MDM were used to further elucidate this dual pathway mechanism of degradation for 14C‐radiolabeled PCNUs (synthesized with 1,6‐hexane diisocyanate:polycarbonatediol: butanediol with different stoichiometry (HDI431 and HDI321) or another diisocyanate 4,4′‐methylene bisphenyl diisocyanate (MDI321)). Scanning electron microscopy of PCNU slips pretreated with 20% H2O2 showed that HDI431 had visible holes with more radiolabel release than from the other PCNUs. When MDM were seeded on H2O2‐treated PCNUs, degradation of HDI321 and MDI321, but not HDI431 was decreased. Esterase activity was inhibited in MDM on all surfaces except MDI321, whereas inhibition of acid phosphatase occurred on all surfaces. The material surface itself, induced H2O2 release from live MDM, with more H2O2 elicited by phorbol myristate acetate treated MDM when cultured on HDI431 but not the other materials. H2O2 pretreatment affected cell function by chemically altering the material surface and MDM‐mediated degradation, known to be dependent on surface chemistry. The findings highlight that both oxidative and hydrolytic mechanisms need to be understood in order to tailor material chemistry to produce desired cell responses for in vivo applications. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Novel low temperature setting nanocrystalline calcium phosphate cements for bone repair: Osteoblast cellular response and gene expression studies
Authors: Sethuraman Swaminathan , Nair Lakshmi S. , El‐Amin Saadiq , Nguyen My‐Tien N. , Greish Yaser E. , Bender Jared D. , Brown Paul W. , Allcock Harry R. , Laurencin Cato T.
Published: March 2007

Low temperature setting calcium phosphate cements (CPC) formed from reactive calcium phosphate precursors are receiving great attention in the fields of orthopaedics and tissue engineering. The purpose of this study was to evaluate the mechanical properties and osteocompatibility of a novel calcium deficient hydroxyapatite (CDSHA) with a Ca/P ratio of 1.6 developed in our laboratories and compare it to a previously developed calcium deficient hydroxyapatite (CDHA) with a Ca/P ratio of 1.5. The results demonstrated that the calcium‐deficient hydroxyapatites (HA) formed from the CPCs were similar to biological HA at physiological temperature and the elastic moduli of CDHA and CDSHA were found to be 174.42 ± 20.41 MPa (p < 0.05) and 115.86 ± 24.8 MPa (p < 0.05), respectively. The surface morphologies of the two calcium deficient HA's formed were identical with a micro/nano porous structure as evidenced from SEM. The cellular proliferation on CDHA, and CDSHA, was comparable to the control, tissue culture polystyrene (TCPS) (p < 0.05). Alkaline phosphatase activity was significantly elevated on CDHA and CDSHA matrices at early time points when compared with the control (TCPS) (p < 0.05). Osteoblast cells gene expression on CDHA, and CDSHA showed type I collagen, alkaline phosphatase, osteocalcin, and osteopontin activity at both 7 and 14 days of culture. Thus, novel calcium‐deficient HAs, CDHA, and CDSHA formed at low temperature are promising candidates for orthopaedic applications based on their ability to promote osteoblast cell adhesion and gene expression in vitro. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007