Using quasi-elastic light scattering ( QLS ), we have characterized the macromolecular components in hepatic bile obtained from the dog and compared these results with data from model bile solutions containing the bile salt (BS) sodium taurocholate (TC), egg lecithin (L), and cholesterol (Ch). Native bile samples were obtained by direct catheterization of the common bile duct in a previously cholecystectomized dog fitted with a Thomas duodenal cannula. Hepatic bile was sampled during three secretory states: (A) unstimulated "fasting" bile, (B) "stimulated" secretion during an intravenous TC infusion, and (C) "secretin-stimulated" secretion. All three samples had comparable molar ratios of L/BS (0.21 +/- 0.03) and Ch/L (0.027 +/- 0.006) but differed in the total lipid concentration (BS + L + Ch): (A) 13.1 +/- 0.8, (B) 6.7 +/- 0.8, and (C) 3.0 +/- 0.4 g/dL. From the QLS autocorrelation functions measured on samples B and C, three macromolecular components (denoted 1 alpha, 1 beta, and 2) were resolved. Component 1 alpha (hydrodynamic radius R1 alpha = 10 +/- 2 A) is comparable in size to the micellar aggregates of model systems. Component 1 beta (R1 beta = 67 +/- 7 A) appears to reflect an average of biliary proteins. Component 2 (R2 = 650 +/- 15 A) is a trace component whose size and sedimentation behavior are compatible with those of the canalicular membrane vesicles postulated to be present in bile [ Godfrey , P. P., Warner, M. J., & Coleman , R. (1981) Biochem. J. 196, 11]. Serial dilution of the B and C bile samples with Tris buffer (0.15 M NaCl, pH 8.0) showed a remarkable similarity in the behavior of the 1 alpha component as compared to the mean hydrodynamic radius Rh of similarly diluted model bile solutions. When a critical dilution factor, d gamma, is reached, Rh increases abruptly from approximately 30 to approximately 400 A. Above a second dilution factor, d alpha, it then decreases to a value of approximately 150 A. Similar results were obtained on sample A but were shifted to higher dilutions. Such behavior is consistent with the presence of "mixed disk" micelles [ Mazer , N. A., Benedek , G. B., & Carey, M. C. (1980) Biochemistry 19, 601] in native bile which undergo a micelle-to-vesicle transition upon dilution. From the d gamma and d alpha values, estimates of the intermicellar bile salt concentrations were made for all three samples (range 1.4-6.2 mM) which agree well with previous experimental results on model and native bile. These studies offer compelling evidence for the existence of micellar aggregates in native bile whose size, structure, and equilibria are similar to those found in model bile solutions.

To evaluate the diagnostic significance of the collagen Type III (Col 1-3) N-terminal propeptide of procollagen Type III, with respect to activity and degree of liver fibrosis, Col 1-3 serum concentrations were measured in 111 patients with chronic liver diseases and in 60 patients were correlated with liver histology and morphometry. Col 1-3 was measured by a specific radioimmunoassay. Biopsies were read without knowledge of diagnosis. Periportal and intralobular lesions were assessed semiquantitatively by allocating 1 of 4 severity grades to each parameter. All portal areas were measured morphometrically. Compared to 27 normal controls, Col 1-3 concentrations were significantly elevated in patients with untreated chronic active hepatitis, cirrhosis and primary biliary cirrhosis, but not in chronic persistent hepatitis or fatty liver. Morphometrically measured portal tract area significantly correlated with Col 1-3 plasma levels. Among the semiquantitatively measured periportal lesions, the number of fibroblasts exhibited the closest relationship with Col 1-3 levels; there was no relationship between Col 1-3 levels and intralobular lesions. These data suggest that Col 1-3 serum levels reliably reflect the activity and degree of liver fibrosis and are useful along with liver biopsy in follow-up of patients with chronic liver disease.

1. Labelled serum protein appeared in the blood of normal and Morris hepatoma 5123 TC bearing rats 14 to 15 min after intracaval injection of radioactive leucine. Within this time albumin synthesis can be studied separately in vivo in liver and hepatomas. .Tumor bearing rats were killed within I 0 to 14 min after injection of [3H] or [14C]leucine. Postmitochondrial supernatants were prepared from 1%-labelled liver and 3H-labelled tumor, treated with sodium deoxycholate and combined. Albumin was purified from the mixture. The ratio [3H]protein to [Wlprotein decreased during purification from 7 to 1.2, suggesting that the tumor synthesized less albumin compared to total protein than the liver.3. Radiochemically pure albumin was isolated from liver and tumor homogenates from rats killed within 12 to 14 min after injection of ~-[1-14C]leucine. The specific radioactivity in albumin isolated from liver was 13 times higher than in that from tumor.4. The proportion of the incorporation of ~-[ l -~~C ] l e u c i n e into albumin to that into total protein was found to be 3.3O/, for liver and 0.8O/, for hepatoma homogenates.I n hepatectomized rats we demonstrated that the Morris hepatomas 5123 TC and 9121 and the Reuber hepatoma H 35 TC secreted little or no protein into the blood [1]. Those experiments gave no explanation for the mechanism of the observed failure of secretion of serum proteins by the hepatomas. Possibly, serum proteins were synthesized, but not released by the tumor, as suggested for the hepatomas 5123 and H 35 by Essner and Novikoff [ 2 ] , who reported the accumulation of electron-dense material in cytoplasmic granules. Another explanation would be that no serum proteins a t all were made in the hepatomas.This paper gives information whether, and to what extent, the tumor 5123 TC synthesizes serum albumin. Part of the work has been published in the form of abstracts [3,4]. MATERIAL AND METHODS Animals and TumorsAnimals were inbred Buffalo rats. They were kept in air conditioned rooms of 20" with regulated lighting (light, 9 a.m.-9 p.m.; dark, 9 p.m. to 9 a.m.) [5] and fed ad libitum with Altromin R

Liver biopsy is safe in in- and outpatients. Biopsy is particularly helpful in patients suspected of having liver disease in spite of normal ALT levels or in patients exhibiting unexplained elevated AP levels.