bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distal splenorenal vs. portal-systemic shunts after hemorrhage from varices: A randomized controlled trial
Authors: Grace Norman D. , Conn Harold O. , Resnick Robert H. , Groszmann Roberto J. , Atterbury Colin E. , Wright Stephen C. , Gusberg Richard J. , Vollman Rudolph , Garcia-Tsao Guadalupe , Fisher Rosemarie L. , O’Hara Edward T. , McDermott William V. , Maselli Peter J. , Widrich Warren , Matloff Daniel S. , Horst Douglas , Banks Naomi , Alberts Jeanne 
Published: March 2007

Between 1975 and 1983, 303 cirrhotic patients with endoscopically proven major variceal hemorrhage were admitted to the participating hospitals of the Boston-New Haven Collaborative Liver Group. Of these, 274 were evaluated for admission to a prospective, randomized controlled trial comparing portal-systemic shunts with distal splenorenal shunts. The criteria for inclusion were as follows: (i) a portohepatic pressure gradient ≥ 12 mmHg; (ii) angiographic evidence of antegrade portal venous flow; (iii) angiographic demonstration that the inferior vena cava and portal, splenic and left renal veins were anatomically suitable for either a portal-systemic or distal splenorenal shunt, and (iv) the patient was a reasonable operative risk. Eighty-one patients from the six participating hospitals fulfilled the criteria and consented to participate. Thirty-eight patients were randomly assigned to have portal-systemic shunt and 43 to have distal splenorenal shunt.
After a follow-up period of 11 years (mean = 3.5 years for all patients), survival was found to be similar in the two groups of patients. The 30-day operative mortality was 13% for the portal-systemic shunt group and 9% for the distal splenorenal shunt patients. Late mortality was 55% for the portal-systemic shunt and 37% for the distal splenorenal shunt group. Total mortality was 68% for the portal-systemic shunt and 46% for the distal splenorenal shunt group. None of these differences is statistically significant. In those patients who survived >30 days after surgery, recurrent variceal hemorrhage occurred in four (12%) in the portal-systemic shunt group compared to seven in the distal splenorenal shunt group (18%) (NS). Portal-systemic encephalopathy occurred in 15 (45%) of the operative survivors in the portal-systemic shunt group compared to 20 (51%) in the distal splenorenal shunt group. Severe portal-systemic encephalopathy was observed with equal frequency in the two groups. There was no difference in the time of onset nor the severity of encephalopathy in the two groups.
We conclude that the operative mortality and cumulative survival are similar for the two operations and that the frequency and severity of hepatic encephalopathy following distal splenorenal shunt are similar to that after portal-systemic shunt. Based on our observations and previously published data, recurrent hemorrhage from varices appears to be more frequently prevented by portacaval anastomosis than by distal splenorenal shunt.
Biliary β2-microglobulin in liver allograft rejection
Authors: Adams David H. , Burnett David , Stockley Robert A. , Hubscher Stefan G. , McMaster Paul , Elias Elwyn 
Published: March 2007

β2-Microglobulin, which is associated with HLA class 1 antigens, was assayed in bile and serum from 19 patients following 22 liver transplants. Serum levels were elevated in all posttransplant patients irrespective of the presence of rejection. In contrast, biliary levels were significantly higher during episodes of acute rejection compared with posttransplant cholangitis (p < 0.01), stable graft function (p < 0.0001) and nontrans-plant samples (p < 0.0001). When bile/serum ratios were studied, the difference between the rejection and the other groups was even more significant, and if a ratio of 0.2 was considered diagnostic of rejection, the test had a sensitivity of 96%, a specificity of 87% with an accuracy of 90%. Therefore, these results suggest that the measurement of bile/serum ratios of β2-microglobulin following liver transplantation may be useful in diagnosing acute rejection.
When bile/serum ratios of β2-microglobulin were compared with those for other proteins, there was strong evidence to suggest that local release accounted for most of the increased biliary β2-microglobulin during rejection. These results provide further evidence that HLA class 1 antigens on the biliary epithelium may be important in liver allograft rejection.
The development of the intrahepatic bile ducts in man: A keratin-immunohistochemical study
Authors: Van Eyken Peter , Sciot Raf , Callea Francesco , Steen Kris Van Der , Moerman Philip , Desmet Valeer J. 
Published: March 2007

The development of the intrahepatic bile ducts in man was studied using an immunohistochemical technique on 56 liver specimens ranging in age from 6 weeks of gestation to 8 months after birth. On paraffin sections, two monoclonal anticytokeratin antibodies (CAM 5.2 and KL-1) that normally stain both hepatocytes and bile duct cells and two polyclonal anticytokeratin antisera that in normal adult liver stain bile ducts only were applied. For immunohistochemical staining of cryostat sections (only available from 14 weeks of gestation on), four monoclonal antibodies specifically directed against individual cytokeratin polypeptides 7, 8, 18 and 19 were used. Adult human hepatocytes contain cytokeratin 8 and 18 whereas bile duct cells also express cytokeratin 7 and 19 in addition to cytokeratin 8 and 18. On paraffin sections, primitive hepatocytes were stained with monoclonal antibodies CAM 5.2 and KL-1 from 6 weeks of gestation on. On cryostat sections, they were positive with monoclonal antibodies anticytokeratin 8 and 18 from the earliest time point examined (14 weeks). From 9 weeks of gestation on, portal vein branches were surrounded by a layer of cells showing a stronger positive reaction with monoclonal antibodies CAM 5.2 and KL-1 on paraffin sections and with monoclonal antibodies anti-cytokeratin 8 and 18 on cryostat sections (only available from 14 weeks on).
This layer, referred to as the ductal plate, first appeared around large portal vein branches close to the hilum and subsequently around more peripheral branches. The duct plates became duplicated over variably long segments of their perimeter, lumina appeared and tubular structures were formed. The latter gradually became incorporated in the connective tissue surrounding the portal vein, resulting in the appearance of individualized bile ducts. Ductal plate cells were stained by both polyclonal anticytokeratin antisera on paraffin sections. On cryostat sections (available from 14 weeks of gestation on), they were immunoreactive for cytokeratin 19 but negative with the monoclonal antibody directed against cytokeratin 7 until 20 weeks of gestation.
From then on, weakly positive staining for cytokeratin 7 was detected, but staining intensity subsequently increased and reached the level observed in adult liver at 1 month after birth. At birth, the smallest branches of the portal vein were still surrounded by a discontinuous ductal plate. We conclude that intrahepatic bile duct cells develop from hepatocytes around branches of the portal vein. During the phenotypic shift toward bile duct type cells, hepatocytes first display increased reactivity for cytokeratin 8 and 18 and express cytokeratin 19, followed only later on by cytokeratin 7. The intrahepatic bile duct system is still immature at birth.
Different capacities for amino acid transport in periportal and perivenous hepatocytes isolated by digitonin/collagenase perfusion†
Authors: Burger Hans-Jörg , Gebhardt Rolf , Mayer Claus , Mecke Dieter 
Published: March 2007

Periportal and perivenous hepatocytes were isolated from rat liver by digitonin/collagenase perfusion for investigating the acinar heterogeneity of amino acid transport activities related to glutamine and ammonia metabolism. Immunocytochemical staining of the respective subpopulations for glutamine synthetase demonstrated that periportal subpopulations were essentially free of glutamine synthetase-positive cells, whereas perivenous subpopulations showed a 2- to 3- fold enrichment of glutamine synthetase-positive hepatocytes. The high perivenous/periportal ratio of 59 found for glutamine synthetase activity as well as the perivenous/periportal ratios of other marker enzymes further indicated the good separation of periportal and perivenous cells.
α-Aminoisobutyric acid, histidine and glutamate were used to determine the distribution pattern of amino acid transport systems A, N and G−, as well as of the sodium-independent uptake of these compounds 1 hr after isolation and after maximal hormonal stimulation during primary culture. The strong heterogeneity of the sodium-independent transport of histidine, characterized by higher perivenous transport rates [perivenous/periportal ratio: 1.5 (1 hr) to 3.5 (48 hr)], suggests a significant role of facilitated diffusion, presumably in glutamine export. Conversely, the strong heterogeneity of the sodium-dependent glutamate transport (System G−) characterized by higher uptake rates in nonstimulated [perivenous/periportal ratio: 6.6 (1 hr)] and in hormonally treated perivenous hepatocytes (perivenous/periportal ratio: 2.2) reflects its possible significance with respect to the substrate availability for glutamine synthesis. The observed heterogeneities provide a basis for understanding how substrate fluxes related to glutamine metabolism might be established and regulated. In addition, our findings indicate that periportal and perivenous cells retain their zonal characteristics with respect to amino acid transport in primary culture for at least 48 hr.
Defective response to interferons in cells transfected with the hepatitis B virus genome
Authors: Onji Morikazu , Lever Andrew M. L. , Saito Izumu , Thomas Howard C. 
Published: March 2007

The interferon responsiveness of two cell lines transfected with the hepatitis B virus genome was investigated. A cosmid vector containing multiple copies of the hepatitis B virus genome was transfected into FL5-1 cells; it reduced their sensitivity to interferons as measured by inhibition of the cytopathic effect of Sindbis virus challenge. Similar vectors transfected into HeLa cells reduced their sensitivity to interferon as measured by production of β2-microglobulin.
This resistance to interferon in hepatitis B virus-transfected cells may be a trans-acting phenomenon related to nucleotide homology between hepatitis B virus DNA and sequences regulating the interferon-induced antiviral system. Alternatively, other mechanisms involving transcription or translation products of hepatitis B virus may be responsible.
Hepatitis B virus-induced cellular resistance to the action of interferon may be important in maintaining the chronic carrier state.
Isolation, culture and main characteristics of mouse fat-storing cells: Interaction with viruses
Authors: Chen Wan , Gendrault Jean-Louis , Steffan Anne-Marie , Jeandidier Eric , Kirn André 
Published: March 2007

Fat-storing cells were isolated from 15-day-old mouse sinusoidal cell cultures (Kupffer or endothelial cells), where they had multiplied abundantly; they were then purified by a negative selection method based on the fact that they do not possess Fc receptors, as do both other types of cells.
The fat-storing cells, which could be subcultured for at least 10 passages, have the main morphological characteristics already described in vivo, in particular, the rough endoplasmic reticulum and the lipid droplets, which become less and less apparent as the number of passages increases. Subcultured fat-storing cells, almost devoid of lipid droplets and vitamin A, were able to take up retinol, as the appearance of a typical autofluorescence indicated; the number of lipid droplets increased concomitantly. Furthermore, the cultured fat-storing cells were able to internalize one-μm-sized latex beads by phagocytosis. Infection of fat-storing cells with mouse hepatitis virus 3, ectromelia or Sindbis virus led to multiplication of the virus particles. There was a direct relation between the multiplication of mouse hepatitis virus 3 in cultured fat-storing cells and the susceptibility of the animals to the virus. In the case of Sindbis virus, interferon is produced, its production being independent of the presence of vitamin A.
Hepatic encephalopathy in thioacetamide-induced acute liver failure in rats: Characterization of an improved model and study of amino acid-ergic neurotransmission†
Authors: Zimmermann Christof , Ferenci Peter , Pifl Christian , Yurdaydin Cihan , Ebner Josef , Lassmann Hans , Roth Erich , Hörtnagl Heide 
Published: March 2007

An imbalance of excitatory and inhibitory amino acid-ergic neurotransmission has been suggested to play a role in the pathogenesis of hepatic encephalopathy. For further evaluation of this hypothesis, several parameters of amino acid-ergic neurotransmission were studied in rats with acute liver failure induced by the administration of 300 mg per kg thioacetamide by gavage on two consecutive days. By appropriate supportive care, hypoglycemia, renal failure and hypothermia were avoided. Rats were monitored clinically and neurologically. Hepatic encephalopathy evolved in four distinct, easily recognizable stages. Light and electron microscopic examination of brains of rats with hepatic encephalopathy revealed only a slight swelling of nuclei of neurons and astrocytes without signs of neuronal degeneration or brain edema.
In rats with hepatic encephalopathy, the concentrations of GABA, glutamate and taurine were decreased in the cerebral cortex, the hippocampus and the stria-tum, whereas those of aspartate and glycine were unchanged or increased.
GABAA and benzodiazepine receptors were studied as parameters for the postsynaptic GABAA-benzodiazepine receptor complex, glutamic acid decarboxylase as parameter for presynaptic GABA-ergic neurons and stimulation of benzodiazepine binding by GABA as a parameter for a GABA-mediated postsynaptic event. None of these parameters was different in hepatic encephalopathy as compared to controls. Similarly, Ca++/Cl−-dependent and -independent glutamate receptors as parameters for glutamatergic neurons were unchanged in rats with hepatic encephalopathy.
Thus, in rats with thioacetamide-induced liver failure and hepatic encephalopathy, changes of the concentrations of neurotransmitter amino acids occur in the brain. Other neurochemical parameters, however, failed to identify alterations of GABA-ergic or glutamatergic neurotransmission in hepatic encephalopathy.
Colchicine treatment of cirrhosis: Questions
Authors: Grace Norman D. 
Published: March 2007

There is preliminary evidence that colchicine, an inhibitor of collagen synthesis, may be beneficial in the treatment of cirrhosis of the liver. To evaluate the use of colchicine (1 mg per day, five days per week) in the treatment of hepatic cirrhosis, we performed a randomized, double-blind, placebo-controlled trial in which 100 patients were followed for up to 14 years. Forty-five patients had alcoholic cirrhosis, 41 had posthepatitic cirrhosis, and the remaining 14 had cirrhosis with various other causes. Histologic studies were available for 92 percent of patients. Seventy-three patients were in Child-Turcotte class A, 26 were in class B, and one was in class C.
Fifty-four patients received colchicine, and 46 received placebo. The overall survival in the colchicine group was markedly better than in the placebo group (median survival, 11 and 3.5 years, respectively; P < 0.001). The cumulative 5-year survival rates were 75 percent in the colchicine group and 34 percent in the placebo group; the corresponding 10-year survival rates were 56 percent and 20 percent. Among the 30 patients treated with colchicine who underwent repeated liver biopsies, histologic improvement was seen in 9; the liver appeared normal in 2, and 7 had minimal portal fibrosis. No histologic improvement was observed in the 14 members of the placebo group who had two or more biopsies. Few side effects were observed in either group.
Poly(A+)RNA levels of growth-, differentiation- and transformation-associated genes in the progressive development of hepatocellular carcinoma in the rat
Authors: Huber Brian E. , Heilman Carole A. , Thorgeirsson Snorril S. 
Published: March 2007

The development of chemically induced hepatocellular carcinoma in the rat proceeds through a series of premalignant changes that may ultimately progress to a primary malignant tumor. Using the selection technique based on diminished binding of preneoplasic hepatocytes to tissue culture plates precoated with asialofetuin, we have isolated poly(A+)RNA from early preneoplastic foci as well as preneoplastic persistent nodules and primary hepatocellular carcinoma induced by the Solt-Farber protocol in the Fischer rat. The steady-state poly(A+)RNA levels of genes traditionally associated with growth, differentiation and/or transformation were then determined to address the question of their temporal expression in the multistep nature of cancer development.
Ornithine decarboxylase- and P53-specific transcripts did not significantly change in preneoplastic foci but were increased in later-stage preneoplastic nodules and hepatocellular carcinoma. Albumin-specific transcripts were decreased in all hepatocellular carcinoma but there was no consistent coordinated increase in α-fetoprotein-specific transcripts. c-myc and raf transcripts increased at the very early preneoplastic foci stage and continued to increase throughout the neoplastic process. No L-myc or N-myc transcripts could be detected in any RNA sample. c-Ha-ras-specific transcripts were essentially unaltered in all RNA samples whereas no c-Ki-ras or N-ras transcripts could be detected throughout the neoplastic process. In addition, no dominant-acting transforming mutations in the ras gene family were detected by DNA transfection experiments using NIH/3T3 cells.
Selective hepatobiliary transport of nordeoxycholate side chain conjugates in mutant rats with a canalicular transport defect
Authors: Elferink Ronald P. J. Oude , de Haan Jan , Lambert Karel J. , Hagey Lee R. , Hofmann Alan F. , Jansen Peter L. M. 
Published: March 2007

Canalicular transport of bilirubin diglucuronide, dibromosulfophthalein and several glutathione conjugates is deficient in mutant TR− rats. In contrast, transport of cholyltaurine (taurocholate), a conjugated bile acid, is normal. Previous studies using normal rats have shown that C23 nor-dihydroxy bile acids are conjugated with sulfate or glucuronide during hepatic transport in contrast to the natural C24 bile acids, which are amidated with glycine or taurine. Studies were performed to test the hypothesis that (a) in the TR− rat, nordeoxycholate would be conjugated with glucuronate or sulfate just as in the normal rat, and (b) that such conjugates would have defective biliary secretion. [C23-14C]Nordeoxycholate was administered intravenously to bile fistula rats (TR− and normal), and the biliary recovery of metabolites was assessed by chromatography and mass spectrometry.
In both groups of rats, the major biotransformation product of nordeoxycholate was the side chain (23-ester) glucuronide. Conjugation on the nucleus with sulfate and glucuronide at the 3-position (ethereal linkage) also occurred, as well as amidation at the C23 carboxylic acid group. In the mutant rats, biliary secretion of the 3-sulfate and 3-glucuronide conjugates was less than 10% and 1%, respectively, of that of normal rats, whereas biliary secretion of the 23-ester glucuronide and the 23-taurine amidate, as well as unchanged nordeoxycholate, was not decreased. Canalicular secretion of nor-bile acid 3-ether glucuronides and 3-sulfates appears to involve the “bilirubin transport system,” which is deficient in mutant rats. Canalicular secretion of unconjugated, amidated or esterified nordeoxycholate is mediated via another pathway, probably the “bile acid transport system.” It is speculated that the “bile acid transport system” transports large organic anions with one (or more) negative charges on one side chain (“unipolar anions”), whereas the “bilirubin transport system” transports large organic anions with at least two separate negative side chains tentatively termed “multipolar anions,” which include the 3-sulfates and 3-glucuronides of bile acids.
Protein kinase C agonists inhibit bile secretion independently of effects on the microcirculation in the isolated perfused rat liver
Authors: Corasanti James G. , Smith Neil D. , Gordon Ellen R. , Boyer James L. 
Published: March 2007

The role of hormones in the regulation of bile secretion is not known; however vasoactive agents, which act via the phosphoinositide signal transduction pathway, may mediate changes in bile flow by altering the hepatic microvasculature. We therefore examined the effects of phorbol esters and diacylglycerol, agonists of the protein kinase C branch of the phosphoinositide cascade, on perfusion pressure and bile flow in a single-pass, hemoglobin-free, isolated perfused rat liver system with constant perfusate flow.
The active phorbol ester, 12,13-phorbol dibutyrate, produced a dose-dependent (maximal effect at 10−6
M), sustained and reversible decrease in bile flow from 1.09 ± 0.18 to 0.61 ± 0.09 μl per min per gm liver (37.2 ± 5.9%) while simultaneously increasing perfusion pressure from 12.3 ± 0.7 to 21.5 ± 2.5 cm H2O (74.0 ± 4.3%). Both effects were inhibited by the synthetic protein kinase C antagonist H-7. 1,2-Dioctanoyl-sn-glycerol, a diacylglycerol, produced changes in bile flow and perfusion pressure that were similar to, but more marked than, those caused by 12,13-phorbol dibutyrate, whereas the inactive phorbol ester 4α-phorbol didecanoate and the vehicle dimethyl sulfoxide had no effects on either parameter. 12,13-Phorbol dibutyrate infusion resulted in reversible decreases in oxygen consumption (23.3%) and a reversible vascular redistribution of trypan blue dye but did not alter hepatic venous effluent concentrations of K+. Increases in perfusion pressure produced by mechanical constrictions of the hepatic venous cannulae did not reproduce phorbol-induced changes in bile flow, suggesting that the cholestasis is not mediated by postsinusoidal increases in hepatic outflow resistance. Furthermore, the nonspecific vasodilators sodium nitroprusside (10−3
M) and papaverine (40 μM) prevented the phorbol-induced increases in perfusion pressure (p < 0.01) but did not block 12,13-phorbol dibutyrate’s cholestatic effects.
We conclude from this study that protein kinase C agonists have both vascular and nonvascular effects in the isolated perfused rat liver and that the cholestasis caused by these agents is independent of effects on the hepatic microcirculation.