Extrahepatic Sources Research Articles

Neutral lipid precursors for gangliosides are not formed by rat liver homogenates or by purified cell fractions

As part of an ongoing investigation into the ganglioside and neutral glycosphingolipid biosynthetic pathways in rodent liver, the synthesis of ceramide, glucosylceramide and lactosylceramide was examined in homogenates and purified membrane fractions of rat liver. Ceramide synthesis and its stimulation by exogenously added d-sphingosine was demonstrated in homogenates and isolated membrane fractions, with activity concentrated in the endoplasmic reticulum. In contrast, significant fd-sphingosine- or ceramide-dependent formation of glucosylceramide, or glucosylceramide-dependent formation of lactosylceramide (in the presence of labelled UDP-[ 14C]glucose and UDP-[ 14C]galactose, respectively,) could not be demonstrated. The possibility is raised that liver may be dependent on extra-hepatic sources of neutral glycosphingolipids to support ganglioside biosynthesis.

Comparative volumes of hepatic and extrahepatic sources of ascitic fluid (AF) and lymphatic AF outflows in alcoholic cirrhosis

Comparative volumes of hepatic and extrahepatic sources of ascitic fluid (AF) and lymphatic AF outflows in alcoholic cirrhosis

UDP-glucuronyltransferase in perfused rat liver and in microsomes. Glucuronidation of bilirubin.

In perfused rat liver and in fistula rats the formation of bilirubin conjugates was studied after labeling with [14C]bilirubin,5-amino [14C]levulinic acid and [14C]hemin. The latter two compounds were used to study heme degradation to bilirubin from intrahepatic and extrahepatic sources, respectively. Bilirubin glucuronides were the major conjugates in fistula bile. In liver perfusion bile the proportion of non-glucuronide conjugates was increased. After a high dose of hemin (2.5 mumol) bilirubin glucuronides were decreased compared with other bilirubin conjugates both in fistula bile and in liver perfusion bile. In addition green pigments were formed. These alterations were reversed in chronically hemin-treated rats in which heme oxygenase had been induced. The interference of UDP-glucose and UDP-glucuronic acid with bilirubin glucuronidation and glucosidation was studied in liver microsomes. UDP-glucose did not affect bilirubin glucuronidation in native microsomes in which UDP-glucuronyltransferase activity is constrained. When this constraint was released by various treatments altering membrane structure UDP-glucose markedly inhibited bilirubin glucuronidation. However, under these conditions bilirubin glucosidation was unaffected by UDP-glucuronic acid. The results suggest that the release of the constraint of UDP-glucuronyltransferase in vivo may lead to a decrease of the proportion of bilirubin glucuronides to other bilirubin conjugates in bile.

Selective Measurement of Two Lipase Activities in Postheparin Plasma from Normal Subjects and Patients with Hyperlipoproteinemia

An assay has been developed for specific measurement of two different lipase activities in postheparin plasma. Lipoprotein lipase, derived from extrahepatic sources, is measured as protamine-inactivated lipase activity; hepatic lipase activity is protamine-resistant under the conditions of this assay. In 100 normal subjects, both enzyme activities were noted to be related to age and sex. Protamine-resistant lipase, which comprised 46-95% of the total activity, was highest in men over 18. Protamine-inactivated lipase activity was greatest in younger males and was age-correlated in women, doubling between the second and sixth decades. In 12 patients with hyperchylomicronemia, including five previously shown to have familial type I hyperlipoproteinemia, protamine-inactivated lipase activity was markedly reduced, whereas protamine-resistant lipase was below normal in only 1. The results were not due to lack of plasma activator, presence of plasma inhibitor, or diet, and the deficiency was not overcome by increasing the provoking dose of heparin from 10 U to 75 U/kg. Mean values for both lipase activities were not reduced in 32 other patients with hyperchylomicronemia, nine with "floating beta" lipoproteins (type III hyperlipoproteinemia), and 23 with hyperprebetalipoproteinemia (type IV). Mean protamine-resistant lipase activity was below normal in a group of four women with hypothyroidism, in whom protamine-inactivated lipase was not reduced. Both of the lipase activities were capable of hydrolyzing lipid in very low-density lipoproteins, but the relative rate of hydrolysis of chylomicrons by protamine-resistant lipase was markedly limited. These results indicate the importance of distinguishing between lipases of hepatic and extra-hepatic origin in the measurement of postheparin lipolytic activity.

Extrahepatic factor VIII synthesis. Lung transplants in hemophilic dogs.

SUMMARY Although the liver is playing a major role in factor VIII synthesis, extrahepatic sources of factor VIII have been postulated because transplanted hemophilic livers failed to make normal dogs hemophilic. By grafting normal lungs into severely affected hemophilic dogs it was demonstrated that small but definite amounts of factor VIII activity are being produced by the lung. These findings are compatible with the in vitro observations that factor VIII-like antigen is being synthetized by endothelial cells in culture.

Separation of lymphocytes and polymorphonuclear leukocytes by countercurrent distribution in aqueous two-polymer phase systems

The littoral cell population, on the other hand, is part of the RES; there is evidence that extensive transformation and migration of RES cells occurred within the liver during regeneration, and up to 50 % of the RES cell population in the liver remnant, particularly during the early period of regeneration, migrated to the liver from extrahepatic RES reserves to augment the deficiency [l, 21. The size of the proliferating pool, therefore, would depend, in part, on the contribution of the hepatic RES, and, in part, on the extent of cellular mobilization and migration from extrahepatic sources. The relative proportions could be expected to change rapidly with time, particularly as the physiological stress placed on the liver progressively decreases during regeneration. In the present studies, the actively proliferating pool of parenchymal cells was 85 %. The actively proliferating littoral cell population was 3 %; the potentially proliferative pool was >50 %, but this value could not be measured with precision.

HEMOBILIA SECONDARY TO LIVER ABSCESS. REPORT OF A CASE TREATED BY PARTIAL HEPATECTOMY.

A SERIOUS DEGREE of hemobilia (hemorrhage into the biliary tract) is uncommon. It usually results from extrahepatic sources such as rupture of a hepatic artery aneurysm into the bile duct or erosion of a biliary calculus into an adjacent vessel. 1,2 Even less common is hemobilia of hepatic origin which may be caused by trauma to the liver, 3,4 malignant tumors, 5 and many other rather esoteric conditions. This present report concerns a case of hemobilia secondary to a liver abscess which required a major resection of the right lobe of the liver for ultimate control. Report of a Case A 75-year-old female was admitted to the Surgical Services of the Massachusetts General Hospital on April 29, 1962, because of persistent and severe hemobilia. Sixteen months prior to admission, cholecystectomy and choledochotomy had been performed in another hospital. Multiple stones were removed from the common bile duct. Postoperative cholangiography showed

Mechanism underlying hypercholesteremia induced by triton WR-1339.

Sequential changes in the plasma lipids of rats injected with Triton were studied. It was observed that following a dose of Triton, the accumulation of triglyceride (neutral fat), cholesterol and phospholipid proceeded in plasma for about 36 hours, after which time a rapid diminution began. Excess triglyceride began both to accumulate and to disappear, respectively, before the other two substances. During the phase of accumulation, the excess cholesterol in plasma was not found to be reflected by any increase in cholesterol either in the liver tissue or in hepatic lymph. This lack of diffusibility of plasma cholesterol disappeared during the period of recovery. Injection of Triton retarded the escape of both injected triglyceride and phosphatide from the plasma of the liverless rat. Hypercholesteremia could be induced in the liverless rat by Triton injection if triglyceride, phosphatide or both were given with the Triton. It is suggested that the hypercholesteremia occurring after injection of Triton is due to the latter's ability to retain excess triglyceride and phospholipid which then in turn mobilizes and sequesters cholesterol from both extrahepatic and hepatic sources.