摘要:

AbstractIsolated rat liver perfusates contain a substance which inhibits3H‐thymidine uptake by phyto‐hemagglutinin‐stimulated human peripheral blood lymphocytes in a dose‐dependent, noncytotoxic fashion. Suppression is not due to interference of lymphocyte‐phytohemagglutinin interaction or dilution of the thymidine pool. Complete inhibition of thymidine uptake is achieved with less than 1.0figof material per ml (which is a potentially achievable concentrationin vivo).The release of this material is directly and quantitatively associated with hepatocellular injury as measured by release of glutamic pyruvate transaminase. The material is a highly basic protein with a molecular weight of approximately 65,000 to 80,000 daltons. It is a product of the hepatocyte rather than of nonparenchymal liver cells. Liver‐derived materials, such as the presently described molecule, may play a role inin situregulation of lymphocyte function during immunologically mediated li

ISSN:0270-9139    

DOI:10.1002/hep.1840020302

出版商:W.B. Saunders    

年代:1982

数据来源: WILEY

摘要:

AbstractSystemic and renal neurovascular reactivity was investigated in eight patients with cirrhosis and in eight control subjects with fatty liver during postural changes. In the supine position, mean renal blood flow averaged 1.51 and 2.97 ml per gm per min in patients and controls, respectively (p<0.02). During tilting, renal blood flow changed significantly (p<0.05) and equally in patients and controls (15ohead‐down tilt: 12 and 13% increase, respectively; 60ohead‐up tilt: 27 and 32% decrease, respectively). Mean arterial blood pressure was significantly lower in patients than controls (82 vs. 95 mm Hg, p<0.05) but did not change during the tilt. Plasma norepinephrine (NE) concentration was significantly higher in another eight patients with cirrhosis than in eight healthy controls (mean: 0.45 vs. 0.21 ng per ml in recumbency, p<0.02). Following 60ohead‐up tilt, the increase in NE was similar in both groups. In another 10 patients with cirrhosis in recumbency, the splanchnic arterial‐hepatic venous extraction of NE averaged 0.43 (p<0.01), and the hepatic clearance of NE averaged 315 ml per min which is of the same order as previously reported in healthy controls. The right kidney released NE into the systemic circulation. Renal venous plasma NE exceeded arterial concentration by 34% (p<0.01). It is concluded that sympathetic nervous activity is enhanced in patients with cirrhosis, and that this hyperactivity may be responsible for renal vasoconstriction in these patients. However, systemic and renal neurovascular reactivity seems to be maintained even at an advanced stage of the

ISSN:0270-9139    

DOI:10.1002/hep.1840020303

出版商:W.B. Saunders    

年代:1982

数据来源: WILEY

摘要:

AbstractWhen S‐carbamido(14C)methyl glutathione, a model compound of glutathione S‐conjugate, was administered i.v. to mice, radioactivity accumulated in the kidney within 1 to 2 min and then decreased gradually during the following 10 to 15 min with concomitant increase in hepatic radioactivity. Most hepatic radioactivity was accounted for by S‐carbamidomethyl cysteine and its N‐acetyl derivative, a mercapturic acid. The i.v. administration of S‐carbamido(14C)methyl cysteine resulted in rapid and predominant accumulation of radioactivity in the liver. In both cases, the radioactive urinary metabolites were fully accounted for by N‐acetyl‐S‐carbamidomethyl cysteine. N‐Acetyl‐S‐carbamido(14C)methyl cysteine administered to mice was accumulated preferentially in the kidney and was excreted into urine very rapidly. These results suggest the following series of events: glutathione S‐conjugate accumulated mainly in the kidney and is hydrolyzed into its component amino acids, presumably by γ‐glutamyl transferase and some peptidase(s) on the renal brush border membranes. The cysteine S‐conjugate which is formed in the tubular lumen is reabsorbed and transferred to the liver, acetylated to form N‐acetylcysteine S‐conjugate, and excreted in the urine. Thus, renal hydrolysis of glutathione S‐conjugates seems to be coordinated with acetylation in liver and with me

ISSN:0270-9139    

DOI:10.1002/hep.1840020304

出版商:W.B. Saunders    

年代:1982

数据来源: WILEY

摘要:

AbstractTo determine whether the aminopyrine breath test (ABT) and serum bile acid concentrations reflect histologic severity of chronic hepatitis, 56 patients were prospectively evaluated with liver biopsies and ABTs, and the results were compared to results of standard liver chemistry tests; 44 of these patients also had fasting and 2‐hr postprandial serum bile acid measurements. Mean values for the ABT were significantly lower, and serum bile acids were significantly higher in patients with chronic active hepatitis with bridging or cirrhosis than in patients with mild chronic active hepatitis or chronic persistent hepatitis. Thirty of 35 patients with bridging or cirrhosis had ABTs5.7% (sensitivity 0.86, specificity 0.84). Fasting and 2–hr postprandial bile acids were also more sensitive than standard chemistries in identifying patients with bridging or cirrhosis. Thus, the ABT and serum bile acids reflect histologic severity in chronic hepatitis patients and may be helpful in selecting patients for liver b

ISSN:0270-9139    

DOI:10.1002/hep.1840020305

出版商:W.B. Saunders    

年代:1982

数据来源: WILEY

摘要:

AbstractIn the rat, dimeric immunoglobulin A (dIgA) is cleared rapidly from the systemic circulation into bile by vesicular transport through the hepatocyte. Whether such transfer of dIgA occurs in man is controversial. The fate of dIgA and monomeric IgA (mIgA) was studied in rats with biliary drainage, and in parallel in 4 patients, 3 of whom had biliary drainage. Human dIgA and mIgA were prepared from myeloma sera and labeled with radioisotopes of iodine. Ten microcuries each of125I‐dIgA and131I‐mIgA (2 to 4μg protein) were given i.v. simultaneously. In the four patients,125I‐dIgA disappeared more rapidly from the serum than did131I‐mIgA. Biliary recovery of125I‐dIgA (expressed as per cent total dose given) was only 0.2 to 0.9% in 8 hr while that of131I‐mIgA was 0.1 to 0.2%. In contrast, biliary recovery over the same period in rats was 21 to 32% forl25I‐dIgA and 3.0 to 4.6% for131I‐mIgA. The data show that in man after injection of a trace amount of human myeloma IgA, rapid transport of dIgA into bile, as observed in the rat, was not seen. Although selective transport of dIgA over mIgA into bile occurred in man, the total amount of dIgA transported was small, and it is suggested that under physiological conditions, the major part of human biliary IgA is derived from

ISSN:0270-9139    

DOI:10.1002/hep.1840020306

出版商:W.B. Saunders    

年代:1982

数据来源: WILEY

摘要:

AbstractThe formation and clearance of circulating IgA immune complexes from blood to bile was investigated in this study. The i.v. injection of either MOPC‐315, an IgA M‐component with anti‐dinitrophenyl (DNP) specificity, or TEPC‐15, an IgA M‐component of a different specificity, was followed by i.v. injection of125I‐DNP10‐bovine serum albumin (BSA) as the antigen. The formation and clearance of IgA immune complexes in the circulation of MOPC‐315‐treated, but not TEPC‐15‐treated animals was deømonstrated by immunoprecipitation with polyacrylamide beads coated with rabbit anti‐mouse IgA. IgA‐125I‐DNP10‐BSA complexes were identified in the bile from MOPC‐315‐treated, but not TEPC‐15‐treated animals utilizing this same immunoprecipitation technique. These observations suggest that the liver or bile ducts transport IgA immune complexes from blood into bile. The clearance of125I‐DNP10‐BSA from the circulation was documented by coprecipitation with rabbit anti‐BSA and BSA. The clearance of this circulating antigen was slower in the MOPC‐315‐treated than in the TEPC‐15‐treated animals suggesting that under the conditions of the present experiment, circulating antigen is cl

ISSN:0270-9139    

DOI:10.1002/hep.1840020307

出版商:W.B. Saunders    

年代:1982

数据来源: WILEY

摘要:

AbstractThe effects on biliary lipids of 10 mg per kg per day of chenodeoxycholic acid (CDCA), 10 mg per kg per day of ursodeoxycholic acid (UDCA), and their equimolar combination (5 mg per kg per day of each), all administered for 45 to 60 days, were investigated in 18 patients with gallstones in a double‐blind study with a balanced latin square design. The molar percentage of cholesterol in bile (initial value 9.7 ± 2.2) was significantly lower after UDCA (5.4 ± 1.3) and the combination (5.2 ± 1.2) than after CDCA (7.2 ± 1.7).Nevertheless, when the ability to solubilize cholesterol was calculated, taking into account the percentage of biliary UDCA, then the differences in cholesterol saturation induced by UDCA alone and the combination also became considerable (saturation index: 0.94 ± 0.12 as compared to 0.81 ± 0.12).The total bile acid pool increased significantly after treatment with CDCA and the combination, but not after UDCA. Lithocholic acid was increased significantly only by treatment with CDCA.Diarrhea was observed in five patients with hypertransaminasemia and in four patients after CDCA, whereas both UDCA and the combination were well‐tolerated.We conclude that the administration of a combination of equimolar doses of CDCA and UDCA can be recommended for medical treatment of gallstones since it has greater effects on bile cholesterol saturation than either alone, is better tolerated than CDCA, and is less expensive

ISSN:0270-9139    

DOI:10.1002/hep.1840020308

出版商:W.B. Saunders    

年代:1982

数据来源: WILEY

摘要:

AbstractFasting levels of cholic acid conjugates were determined by radioimmunoassay in the serum of 24 patients with extensively documented Gilbert's syndrome and in 98 healthy controls without unconjugated hyperbilirubinemia. The Gilbert's syndrome patients studied included all three subtypes, as determined from studies of the plasma disappearance kinetics of sulf obromophthalein and indocyanine green. Although patients with structural liver disease severe enough to produce hyperbilirubinemia almost invariably have elevated fasting serum levels of cholic acid conjugates, values were normal in each of the Gilbert's syndrome patients, including patients with metabolic abnormalities in sulfobromophthalein and indocyanine green transport. It is concluded that the measurement of fasting serum levels of cholic acid conjugates is a useful adjunct to the diagnosis of Gilbert's syndrome.

ISSN:0270-9139    

DOI:10.1002/hep.1840020309

出版商:W.B. Saunders    

年代:1982

数据来源: WILEY

摘要:

AbstractThe steady‐state disposition of the β‐adrenoreceptor blocking drug, propranolol, and its metabolite, 4‐hydroxypropranolol, was studied in the anesthetized pregnant sheep near term. Following infusion of propranolol to the mother, steady‐state plasma concentrations were obtained at three dosage levels in each of the eight animals studied. Blood samples were obtained from: (i) maternal facial artery and hepatic vein; (ii) umbilical vein, and (iii) fetal carotid artery, portal vein, and right hepatic vein. Although total propranolol concentrations in maternal plasma were different from those in umbilical venous plasma, the concentrations ofunbounddrug were similar, suggesting that unbound drug had equilibrated across the placenta. Approximately 10% of propranolol was unbound in maternal plasma, compared with 30% in fetal plasma. Hepatic extraction of propranolol by the maternal liver was high, so that only 3 to 4% of the drug presented to the liver escaped uptake. In contrast, fetal hepatic extraction was low. Negligible amounts were removed from portal vein blood (right lobe), although one third was extracted from umbilical vein blood (left lobe). Mean peripheral arterial concentrations of 4‐hydroxypropranolol were 2‐ to 3‐fold higher in the fetus than in the mother.We conclude that the fetus is exposed to significant concentrations of propranolol and that the fetal hepatic extraction of this drug is considerably less efficient than in the adult. In contrast to the adult liver, the fetal liver does not appear to act as a single homogeneous organ, but rather as two dis

ISSN:0270-9139    

DOI:10.1002/hep.1840020310

出版商:W.B. Saunders    

年代:1982

数据来源: WILEY

摘要:

AbstractArteriohepatic dysplasia (syndromatic ductular hypoplasia, Alagille syndrome) is a condition of chronic cholestasis dating from infancy accompanied by characteristic facies, pulmonic stenosis, and other somatic abnormalities. The pathologic hallmark of arteriohepatic dysplasia is a paucity or absence of intrahepatic bile ducts, wildely regarded as a congenital deficiency. We present a longitudinal study of six infants and children with arteriohepatic dysplasia, stressing evolution of the characteristic pathology on liver biopsy. All patients were biopsied twice. All five liver biopsies performed during infancy (<6 months old) showed intrahepatic cholestasis and portal inflammation, and two infants had, in addition, giant cell transformation. No infant showed congenital absence of interlobular bile ducts. Three of five infants had normal numbers of interlobular bile ducts (0.5 to 1.0 interlobular bile ducts per triad) and two infants had a paucity of interlobular bile ducts (<0.5 per triad). Three infants showed focal destructive inflammation of interlobular bile ducts. All biopsies performed later in childhood, between 3 and 20 years of age, showed a paucity or absence of interlobular bile ducts. At this time cholestasis and inflammation had largely resolved but some fibrosis persisted. The number of interlobular bile ducts decreased with age in each patient but there was no characteristic age at which interlobular bile ducts disappeared completely. The presence of interlobular bile ducts in infancy followed later in childhood by paucity or absence of interlobular bile ducts, suggests that intrahepatic bile duct deficiency in some patients with arteriohepatic dysplasia is acquired rather than congenital. The mechanism of bile duct disappearance in these patients may have been destructive inflammation of duct epithelium.Histopathologic diagnosis of arteriohepatic dysplasia may be difficult or impossible in infancy since interlobular bile ducts may be present at that time. However, arteriohepatic dysplasia should be considered in the differential diagnosis of all infants with cholestasis and such infants should have careful clinical evaluation for the syndromatic features of arteriohepatic dysplasia. Evaluation of their liver biopsies should include specific morphometric assessment of interlobular bile ducts.

ISSN:0270-9139    

DOI:10.1002/hep.1840020311

出版商:W.B. Saunders    

年代:1982

数据来源: WILEY