bluuebunny/crossref_metadata_2025_split huggingface dataset:
The isolation of functionally heterogeneous hepatocytes of the proximal and distal half of the liver acinus in the rat
Authors: Gumucio Jorge J. , May Maryann , Dvorak Caroline , Chianale Jose , Massey Veronica 
Published: March 2007

The objective of this study was to isolate hepatocytes of the proximal half (Zones 1 and 2) or distal half (Zones 2 and 3) of the liver acinus. The zonal origin of the isolated hepatocytes was recognized by: (a) the presence in hepatocytes of a fluorescent marker, acridine orange, selectively delivered to either the proximal or the distal half of the acinus by in situ perfusion prior to cell isolation and (b) the measurement of the induction of cytochrome P-450 by phenobarbital, an induction known to occur predominantly in the distal half of the acinus.
Following the selective labeling of the acinus with acridine orange, livers were perfused with collagenase in either the portal to hepatic vein direction (anterograde) or in the retrograde direction. Hepatocytes isolated by either an anterograde or a retrograde perfusion were separated by centrifugation in a Percoll density gradient. This procedure isolated populations of proximal or distal hepatocytes, respectively, which were intact and 90% fluorescent. In an effort of assessing the heterogeneity of the separated proximal and distal hepatocytes, each population was further fractionated by centrifugal elutriation. This resulted in the arbitrary separation of proximal or distal hepatocytes into five fractions. Total cytochrome P-450 was determined spectrophotometrically in each of the fractions isolated from controls and after 3 days of the in vivo administration of phenobarbital. On the basis of the pattern of fluorescence in isolated hepatocytes and on the cytochrome P-450 inductive response to phenobarbital administration, it is proposed that: (a) the anterograde or retrograde perfusion of the liver with collagenase separated hepatocytes predominantly of the proximal or distal half of the liver acinus, respectively and (b) that hepatocytes of the distal half of the liver acinus responded to phenobarbital administration with the highest level of cytochrome P-450 induction, indicating that the isolated hepatocytes conserved the functional heterogeneity observed in vivo.
Further studies by immunofluorescence of the monoclonal antibodies associated with experimental non-A, non-B hepatitis in chimpanzees and their relation to D hepatitis
Authors: Shimizu Yohko K. , Purcell Robert H. , Gerin John L. , Feinstone Stephen M. , Ono Yasushi , Shikata Toshio 
Published: March 2007

To further investigate the specificity of the monoclonal antibodies (48-1 and S-1) associated with non-A, non-B hepatitis, extensive immunofluorescence studies were performed on liver biopsy specimens from chimpanzees with experimental hepatitis A, B, non-A, non-B or δ, or from normal chimpanzees. Both 48-1 and S-1 antibodies reacted in the same manner with liver biopsy specimens from 47 of 50 (94%) chimpanzees with acute or chronic non-A, non-B hepatitis and 15 of 18 (83%) chimpanzees with type D hepatitis.
Examinations of serial liver biopsy specimens revealed that the duration of expression of the antigen reacting with the antibodies in hepatocytes of chimpanzees infected with non-A, non-B viruses appeared to be longer than that of chimpanzees infected with the hepatitis δ-virus.
By thin-section electron microscopy, the presence of the microtubular aggregates, identical to those previously described for chimpanzees with non-A, non-B hepatitis and shown by immunoelectron microscopy to react with the antibodies, was noted in hepatocytes during the acute phase of hepatitis δ-virus.
The antibodies did not react with liver biopsy specimens from chimpanzees acutely or chronically infected with hepatitis B virus or hepatitis A virus, or from normal chimpanzees. The present results confirm our previous observations with the 48-1 and S-1 antibodies. Furthermore, the finding that these two antibodies were also associated with hepatitis D would support the possibility that non-A, non-B agents and the hepatitis δ-virus may have a similar nature or may elicit a similar host response.
The effects of ethanol and hyperosmotic perfusates on albumin synthesis and release
Authors: Rothschild Marcus A. , Oratz Murray , Schreiber Sidney S. , Mongelli Joseph 
Published: March 2007

Sucrose and ethanol inhibit albumin synthesis; sucrose via an osmotic mechanism and ethanol during its metabolism. The present study was undertaken to compare the effects of both of these agents on albumin synthesis and secretion, and to see if ethanol inhibition could be related to an osmotic effect.
Male, fed rabbits served as liver donors in all studies. There were a total of 35 studies: 13 control; 10 ethanol (39 to 52 mM); 4 cycloheximide (0.5 mM), and 8 sucrose (1%). Plasma volume was measured with 125I-albumin (human) and extracellular volume measured with either 99mTc diethylenetriamine pentaacetic acid or [14C]sucrose. During perfusion, rabbit albumin content in the perfusate was measured immunologically every 15 to 30 min for 225 min. Interstitial albumin efflux was measured by the rate of appearance in the perfusate of 125I-albumin given to 10 other rabbits 3 days prior to hepatic removal and perfusion.
During the initial 75 min of perfusion, 74% of the in vivo equilibrated exchangeable 125I-albumin appeared in the perfusate, and during this period the rabbit albumin that entered the perfusate was taken to represent efflux from the interstitial volume plus synthesis. Rabbit albumin appearing in the perfusate during the later period of 150 min was taken to represent mainly synthesis and was used to calculate the amount of albumin that would be synthesized in 75 min. The difference between these two values would be hepatic interstitial albumin appearing in the perfusate. Acute ethanol exposure reduced hepatic extracellular volume from 18.4 ± 0.3 to 14.1 ± 0.2 ml per 100 gm wet liver weight, did not significantly alter hepatic plasma volume (8.4 ± 0.3 vs. 7.5 ± 0.2 ml in alcohol studies) and reduced hepatic interstitial volume from 10.0 ± 0.4 to 6.6 ± 0.3 ml. Sucrose infusions in eight rabbits did not alter hepatic extracellular volume, averaging 17.2 ± 0.8 ml, nor were plasma volume (mean = 8.7 ± 0.5 ml) and calculated hepatic interstitial volume (mean = 8.5 ± 0.4 ml) significantly altered. The amount of albumin (mg per 100 gm wet liver weight per hr) released from control livers during the first 75 min averaged 48 ± 3 mg, decreased to 36 and 38 mg with ethanol and cycloheximide, respectively, but was not effected by sucrose, even though all of these test substances reduced synthesis during the later time periods (T-75 to T-225). The synthetic rates for this time period were 27 mg per 100 gm wet liver weight per hr in controls, 9.5 mg in ethanol studies, 6.4 mg in the cycloheximide studies and 12.3 mg in the sucrose studies. Ethanol and cycloheximide, thus, must have lowered albumin synthesis nearly immediately, but sucrose required a longer exposure.
Serum type III procollagen peptide concentrations in severe chronic active hepatitis: Relationship to cirrhosis and disease activity
Authors: McCullough Arthur J. , Stassen William N. , Wiesner Russell H. , Czaja Albert J. 
Published: March 2007

To analyze the correlations between the presence of cirrhosis and hepatocellular inflammation and the serum concentrations of the amino-terminal peptide of procollagen type III in chronic liver disease, we measured procollagen type III concentrations in paired serum samples from 46 patients (17 had cirrhosis) with severe chronic active hepatitis during a therapeutic treatment trial. Coded sera were analyzed for procollagen type III concentrations using both a standard and a recently described Fab radioimmunoassay to compare their relative diagnostic accuracy.
Mean procollagen type III levels were elevated to the same extent in the cirrhotic and noncirrhotic groups at entry into the study. In response to immunosuppressive therapy, the initially elevated procollagen type III levels improved to normal values at remission in both groups. Qualitatively, the results were similar using either assay, but the standard assay was more sensitive for identifying the clinical stage of disease (i.e., active disease vs. disease in remission) than the Fab assay. Since both procollagen type III levels and standard liver function tests correlated well individually with the presence or absence of active disease, they also correlated with each other when both entry and remission values were considered. However, procollagen type III levels correlated poorly with indicators of inflammation (histologic grade and serum transaminase levels) during active disease.
It is concluded that procollagen type III levels change in concert with standard liver function tests but do not quantitatively reflect inflammation or static measurements of hepatic fibrosis in severe chronic active hepatitis. However, these preliminary results suggest that procollagen type III can distinguish active disease from chronic active hepatitis in remission. Consequently, this test may be useful for monitoring disease activity and therapeutic response in severe chronic active hepatitis. For this purpose, the standard procollagen type III radioimmunoassay has greater diagnostic accuracy than the Fab radioimmunoassay.
Ethanol-induced increase in portal hepatic blood flow: Interference by anesthetic agents
Authors: Carmichael Frederick J. , Saldivia Victor , Israel Yedy , McKaigney John P. , Orrego Hector 
Published: March 2007

While a number of studies show that acute oral administration of ethanol results in increases in liver blood flow, a large body of evidence has also been presented in which such an effect is not observed. To shed light on this discrepancy, we have studied in rats, a number of variables that might modulate or inhibit the effect of ethanol. These included the use of three anesthetic agents studied at two different times after anesthetic administration and the effect of animal age, gender, batches and seasonal variation.
Portal blood flows were determined by the radiolabeled microsphere method in 12 separate experiments in awake rats. Ethanol given at doses ranging from 0.5 to 4.0 gm per kg consistently increased portal vein blood flow by approximately 50% (42.2 ± 3.5 to 63.4 ± 6.5 ml per min per kg). The interexperiment variation was 2.4 to 3.0%, showing remarkable consistency, typical of an all-or-none effect at the doses employed. On the other hand, the ethanol-induced increase in portal blood flow was completely suppressed by ketamine (75 mg per kg), thiopental (50 mg per kg) and fentanyl (15 μg per kg) when given 15 min prior to blood flow determinations. This suppression was dependent on the dose and duration of anesthesia. These anesthetic agents had no effect on basal hepatic arterial or portal blood flows. Ethanol or the anesthetics were without effects on hepatic artery blood flow. Neither gender, weight (150 to 350 gm) nor animal batch had effect on the response to ethanol. Similarly, there was no effect of seasonal variation. The increase in portal vein blood flow following a dose of 2 gm per kg of ethanol disappeared only after 6 hr when blood levels of ethanol had decreased to concentrations below 3 mM.
The consistency, under nonpathological conditions, of an increase in portal blood flow by ethanol is of interest because, as ethanol also increases liver oxygen consumption, an increment in oxygen delivery induced by ethanol could play a compensatory role preventing the occurrence of hypoxic liver damage.
The effect of peritoneovenous shunting on catecholamine metabolism in patients with hepatic ascites
Authors: Blendis Laurence M. , Sole Michael J. , Campbell Peter , Lossing Alan G. , Greig Paul D. , Taylor Bryce R. , Langer Bernard 
Published: March 2007

The elevated catecholamine levels in cirrhotic patients with ascites have been proposed to be due to sympathetic overactivity secondary either to reduced intravascular volume or to an underlying cardiovascular abnormality such as reduced pressor responsiveness. Furthermore, these elevated catecholamine levels have been proposed to be involved in the pathogenesis of salt and water retention. Therefore, the effect of peritoneovenous shunting on the circulating levels and renal excretion of catecholamines were studied in six patients with massive refractive ascites preoperative within the first 8 hr postoperative and by 2 weeks postoperative under metabolic conditions. The recirculation of ascites into the intravascular compartment resulted perioperatively in significant rises in cardiac output (p = 0.001), para-amino-hippurate clearance (p = 0.08), creatinine clearance, diuresis (p = 0.05) and natriuresis (p = 0.06). Systemic blood pressure remained unchanged while systemic vascular resistance decreased (p < 0.05).
Preoperative circulating levels of free catecholamine were highly elevated, and renal vein concentrations were about 25% higher than renal arterial levels. Peri-operatively, there was little change in circulating catecholamine levels or distribution of renal blood flow although renal artery and vein concentrations tended to equalize.
In contrast by 2 weeks postoperatively, free catecholamine levels had fallen to within the normal ranges: mean norepinephrine from 1,477.6 ± 194.6 to 395 ± 62.9 pg per ml (p < 0.05); epinephrine from 276 ± 74.2 to 65.7 ± 15.0 pg per ml (p < 0.02), and dopamine from 325.6 ± 175.2 to 47.9 ± 5.3 pg per ml. There was little change in circulating conjugated catecholamine levels, either urinary excretion or clearance of catecholamines, except epinephrine clearance which rose significantly (p < 0.05). Despite the normalization of circulating free catecholamine levels, the patients tended to remain hypotensive with a low peripheral vascular resistance. The return of circulating free catecholamine levels to normal following reexpansion of the intravascular volume by peritoneovenous shunting are in favor of their being elevated in response to vascular underfilling.
Accumulation of 7α-hydroxy-4-cholesten-3-one and cholesta-4,6-dien-3-one in patients with cerebrotendinous xanthomatosis: Effect of treatment with chenodeoxycholic acid
Authors: Björkhem Ingemar , Skrede Sverre , Buchmann Marie S. , East Cara , Grundy Scott 
Published: March 2007

Evidence was recently presented that an essential part of the accumulation of cholestanol in patients with cerebrotendinous xanthomatosis is due to acceleration of a novel pathway, involving 7α-hydroxylated intermediates in bile acid biosynthesis as precursors (J. Clin. Invest. 1985; 75:448-456). Such intermediates accumulate in patients with cerebrotendinous xanthomatosis due to lack of the mitochondrial 26-hydroxylase involved in the major pathway for bile acid biosynthesis. The new pathway may involve the following steps: 7α-hydroxycholesterol→7α-hydroxy-4-cholesten-3-one→cholesta-4,6-dien-3-one→4-cholesten-3-one→choles-tanol.
Accurate methods have been developed for assay of 7α-hydroxy-4-cholesten-3-one and cholesta-4,6-dien-3-one in serum, based on isotope dilution-mass spectrom-etry. The serum levels of 7α-hydroxy-4-cholesten-3-one as well as those of cholesta-4,6-dien-3-one were found to be markedly elevated in the three patients with cerebrotendinous xanthomatosis. Treatment of two of the patients with chenodeoxycholic acid reduced the serum levels of the two steroids by more than 80%. The concentration of cholestanol was reduced by 72% in one patient and by 48% in the other.
The possibility is discussed that accumulation of cholestanol in patients with cerebrotendinous xanthomatosis is secondary to accumulation of 7α-hydroxy-4-cho-lesten-3-one and cholesta-4,6-dien-3-one.
Dating gallstones
Authors: Ransohoff David F. 
Published: March 2007

We investigated the natural history of cholelithiasis in 59 samples of stones from the gallbladder or common bile duct in 15 patients, using as a tracer for the timing of stone formation the 14C released into the environment during nuclear weapons testing. The ages of the stones were correlated with the dates of onset of symptoms and with other clinical data.
None of 11 symptomatic patients had symptoms or complications until at least two years (mean ± SD, 8.0 ± 5.1 years) after stone formation began. There was a lag time of 11.7 ± 4.6 years between initial stone formation and cholecystectomy. The growth rates of stones from 11 symptomatic patients and 4 asymptomatic patients were similar (2.6 ± 1.4 and 2.6 ± 1.1 mm per year). Studies of two stones retrieved from the common bile duct showed that one had the same age as a cholecystic stone; the other, removed two years after cholecystectomy, apparently grew in the common bile duct.
The long latency period between the formation of gallstones and the onset of symptoms indicates that interruption of the natural progression of gallstone disease is potentially possible with medical therapy.
Inflammatory pseudotumor of the liver: An enigmatic lesion with polyclonal plasma cell proliferation
Authors: Larson Eric B. 
Published: March 2007

Five cases of inflammatory pseudotumour of the liver are reported and compared with seven individual previously published case reports. Clinical presentation was variable but often comprised low grade intermittent fever, vague abdominal symptoms, and a history of weight loss. Leucocytosis, raised erythrocyte sedimentation rate, and polyclonal hyperglobulinaemia were also sometimes detected. All five cases in the present series were considered to be clinically malignant; and in two the histological diagnosis was also that of malignancy.
The lesion is clearly inflammatory and reactive, but the aetiology remains unknown.
Acute and chronic hemodynamic effects of propranolol in unselected cirrhotic patients
Authors: Vorobioff Julio , Picabea Eduardo , Villavicencio Roberto , Puccini Viviana , Rossi Oscar , Bordato Juan , Audano Marcelo 
Published: March 2007

Different and contradictory results concerning the use of propranolol in the treatment of portal hypertension have been reported. This study was designed to investigate the hemodynamic effects of short- and long-term administration of propranolol in portal hypertensive patients. Portal pressure, cardiac index, heart rate and blood pressure were obtained in 18 unselected alcoholic cirrhotic patients with esophageal varices before and 60 min after the oral administration of 40 mg propranolol and again after 106 ± 35 days of continuous oral administration (mean dose = 158 ± 63 mg per day). Baseline portal pressure was 21.7 ± 7.2 mm Hg. It decreased after 60 min to 17.2 ± 5.5 mm Hg (p < 0.01) and after long-term administration of propranolol to 16.1 ± 5.7 mm Hg (p < 0.01). No decrease in portal pressure was noted in 9 of 18 (50%) patients after acute administration and 5 of 17 (30%) patients after long-term administration. Baseline cardiac index was 5.1 ± 1.2 liters. min-1 m-2. It decreased after 60 min to 3.9 ± 1.4 liters. min-1 m-2 (p < 0.01) and to 3.6 ± 1.0 liters. min-1 m-2 after long-term administration (p < 0.001). Baseline heart rate was 85 ± 11 beats per min. It decreased after 60 min to 75 ± 9 (p < 0.001) and after long-term administration to 62 ± 6 (p < 0.001) beats per min. Baseline mean arterial pressure was 108 ± 11 mm Hg. It decreased after 60 min to 97 ± 14 mm Hg (p < 0.01) and after long-term administration to 103 ± 14 mm Hg (not statistically significant). No significant correlations were found between the decrease in portal pressure and cardiac index nor between portal pressure and heart rate reductions
This study shows that, in unselected cirrhotic patients, propranolol administration fails to decrease portal pressure in a significant proportion of them. This parameter should be measured in every patient under pharmacologic treatment of portal hypertension, and its reduction should not be inferred through other hemodynamic measurements.
Diminished responsiveness of male homosexual chronic hepatitis B virus carriers with HTLV-III antibodies to recombinant α-interferon
Authors: McDonald J. A. , Caruso L. , Karayiannis P. , Scully L. J. , Harris J. R. W. , Forster G. E. , Thomas H. C. 
Published: March 2007

In a randomized controlled trial, 41 chronic hepatitis B virus carriers were allocated, by opening numbered computerized randomization envelopes, to receive recombinant interferon-α2A at three different doses: 2.5; 5.0, and 10.0 mU per m2. Thirty-two patients received treatment (6 for 3 months, 26 for 6 months), and 9 patients were controls (received no treatment). Ninety-three per cent of our patients were homosexual, and 41% had anti-HTLV-III in their serum
None of the control patients lost HBeAg. In contrast, six of the anti-HTLV-III-negative patients (33%) responded to treatment (p < 0.02): five of these responders were homosexual (p < 0.05). The response rate was greatest (44%) in the anti-HTLV-III-negative patients who received 10 mU per m2 of recombinant interferon-α2A. None of the anti-HTLV-III-positive patients responded to treatment. The percentage reduction of hepatitis B virus DNA was significantly less in the anti-HTLV-III-positive group in comparison to the anti-HTLV-III-negative group at 1 and 4 months of treatment and at 3 months after the end of treatment (p < 0.05). These patients were younger (33 vs. 42 years, p < 0.02), had lower mean baseline AST values (42 vs. 80 IU per liter, p < 0.02) and tended to have milder histo-logical disease
Homosexual men with HBeAg-positive chronic liver disease who are anti-HTLV-III-positive appear to be less responsive to the direct antiviral and immunomodulatory effects of recombinant interferon-α2A. This may be due to the subclinical immunosuppressive effects of co-infection with HTLV-III.