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Biomedical subjects

M J Phillips

Publications and source records attributed to M J Phillips.

At least 235 records · Page 13Linked to original sources
PubMed1976

Protection by propylthiouracil against carbon tetrachloride-induced liver damage.

Rats given a single intragastric dose of carbon tetrachloride (CCl4), 0.25, 0.50, or 1.0 ml per kg) showed a dose-dependent increase in SGOT, serum ornithine carbamyltransferase, and liver necrosis (graded histologically as 0 to 4+) 24 hr after the treatment. Daily intubation with propylthiouracil (PTU) for 10 days in doses of 5 to 50 mg per kg significantly reduced the elevation of SGOT activity, completely suppressed the serum ornithine carbamyltransferase changes, and reduced the degree of necrosis found 24 hr after the intragastric administration of CCl4. Similar protection was found when CCl4 was given intraperitoneally. When PTU was given in liguid diets for 6 days, protection against CCl4 was increased. PTU did not affect the absorption or covalent binding of 14CCl4 to lipids or proteins. Also, control and PTU-treated rats did not differ with respect to glucose-6-phosphatase activity and conjugated diene production after CCl4. Thus, it has been observed that PTU affords partial protection against some end-stage consequences of CCl4 liver injury such as cell necrosis and release of intracellular enzymes. However, PTU afforded no protection against early chemical effects such as covalent binding of CCl4 carbon, lipid peroxidation, or loss of glucose-6-phosphatase. Therefore, it is concluded that the mechanism of the PTU effect comes into play after the initial effects of CCl4 are exerted and in some unknown manner modulates the expression of these early effects.

Animals↗
PubMed1975

Hepatic disease in erythropoietic protoporphyria.

Two sisters had erythropoietic protoporphyria and a spectrum of liver disease. One (F.B.) died in hepatic failure within 3 months after the development of jaundice. Only 10 months before she died, she had exhibited only bromsulfalein retention and a borderline increase in serum transaminase. Surgical exploration because of the jaundice revealed patency of the bile ducts which was confirmed at autopsy. Wedge biopsy and autopsy specimens of liver showed an active cirrhosis with massive amounts of protoporphyrin in Kupffer cells, portal histiocytes, bile canaliculi and parenchymal cytoplasm. The other sister (L.R.) had never had symptomatic liver disease and only a slight increase in serum transaminase and bromsulfalein retention. On needle biopsy, the liver specimen showed portal inflammation with erosion of limiting plates, occasional bridging between triads and central areas of cell dropout. Protoporphyrin pigment was present in portal histiocytes, areas of central collapse and, more rarely, in parenchymal cytoplasm. These studies demonstrate that significant, progressive hepatic disease may occur insidiously in erythropoietic protoporphyria, and that once jaundice appears it may be followed rapidly by fatal hepatic failure.

Adult↗
PubMed1975

Albumin, fibrinogen and transferrin synthesis in isolated rat hepatocyte suspensions. A model for the study of plasma protein synthesis.

A system using hepatocyte suspensions in vitro was developed for studying the synthesis of albumin, fibrinogen and transferrin. Conditions for optimum survival of the hepatocyte and for synthesis of these plasma proteins were defined for this system. These conditions included the use of horse serum (17.5 percent, v/v, heat-inactivated), an enriched medium (Waymouth's MB 752/1), an O2 tension of between 18.7 times 10(3) and 26.7 times 10(3) Pa and constant stirring. Albumin, fibrinogen and transferrin synthesis rates were obtained of 0.32 p 0.094(10), 0.12 p 0.030(11) and 0.097 p 0.017(10) [mean p S.D. (n)]mg/h per g of hepatocytes respectively. These rates were maintained for the first 12h of study and synthesis continued at a diminished rate up to 48h. The synthesis of albumin was decreased in a medium containing less amino acids and glucose, but that of fibrinogen was substantially unaffected. ATP concentrations up to 12h and RNA/DNA ratios up to 24h were comparable with values in vivo. The ability to study cells up to 48h permitted us to find that the addition of a mixture of hormones consisting of glucagon, cortisol, tri-iodothyronine and growth hormone enhanced fibrinogen synthesis. Addition of insulin to the above mixture resulted in increased synthesis for albumin and transferrin but not for fibrinogen.

Adenosine Triphosphate↗
PubMed1975

Liver cell plasma membrane lipids and the origin of biliary phospholipid.

The liver cell plasma membranes of fed male Wistar rats were separated into a fraction rich in bile canaliculi and the remainder of the plasma membrane. Electron-microscopically, the bile canalicular fraction consisted almost exclusively of intact bile canaliculi with thier contiguous membranes. The remaining plasma membrane fraction consisted primarily of vesicles and sheets of membranes essentially free from the bile canaliculi. The bile canalicular membrane fraction contained relatively more total lipid, cholesterol, and phospholipid, and relatively less protein. Although the phospholipid composition of the two fractions was the same, the specific activity of the bile canalicular membrane phosholipids, up to 12 h following in vivo administration of [2-3H]glycerol, was always significantly greater than that of the remaining plasma membranes, and showed a biphasic response not found in the latter. The specific activity of the phosphatidylcholine, phosphatidylethanolamine and lysophosphatidylcholine of the bile canalicular membranes rose to a peak within 40 min after administration of the label, fell sharply and then rose to a second peak after 120 min. The specific activity of the sphingomyelin and phosphatidylserine plus phosphatidylinositol of the bile canalicular membranes and of all the phospholipids of the remaining plasma membranes diphasic pattern but increased steadily to reach a maximum at 120 min. The specific activity of biliary phosphatidylcholine followed a pattern identical to that of the phosphatidylcholine, phosphatidylethanolamine and lysophosphatidylcholine of the bile canalicular membrane fraction. These results show that the average rate of turnover of phospholipid in the bile canalicular membranes is considerably greater than that in the remaining plasma membrane and other cell membrane fractions; they indicate that the phospholipid of the bile canalicular membranes exists in two or more pools, turning over a different rates; and they support the concept that biliary phospholipid is derived from the bile canalicular membrane. The results also suggest that bile canalicular phospholipid may be derived from two different sources, in contrast to the remainong plasma membrane.

Animals↗
PubMed1975

Angiographic findings in multiple bile-duct hamartomas of the liver.

The angiographic appearance in a patient with multiple bile-duct hamartomas of the liver is described. The lesions showed abnormal vascularity, consisting of grapelike clusters of small rings, which could be confused with other benign and malignant conditions demonstrable by angiography; however, it may ultimately prove to be characteristic of this uncommon lesion. The angiographic differential diagnosis is discussed.

Adult↗
PubMed1975

Characterization of rat liver cell plasma membranes.

A method is described by which bile canalicular membranes (BCM) can be prepared, together with canaliculus-free plasma membrane (PM), both essentially free of contamination. The recovery of both fractions together was estimated to be 46%. The concentrations of total lipid, total phospholipid and cholesterol were substantially greater in the BCM, and polyacrylamide gel electrophoresis revealed differences in protein composition. The differences in lipid and protein composition of these two plasma membrane fractions are presumably related to their very different physiological functions.

Animals↗
PubMed1975

Microfilament dysfunction as a possible cause of intrahepatic cholestasis.

The effects of cytochalasin B on bile canalicular structure and function were examined. Three experimental models were used, cultured hepatocytes, isolated perfused liver, and in vivo infused liver. The techniques used were light and electron microscopy and, in selected instances, scanning electron microscopy, electron "stains" for microfilaments, and measurements of bile flow. Microfilament disruption and dilation of bile canaliculi were consistently found and closely paralleled a reduction in bile flow in both in vitro and in vivo infused animals. It is proposed that under normal circumstances, the microfilaments maintain the canaliculi in a contracted or partly contracted state. Hence, the microfilamentous network would provide tone to the canalicular system which would tend to reduce stagnation and facilitate the flow of bile. Removal of normal microfilament contractile function would be expected to produce canalicular ectasia and reduction of bile flow, as was observed. Microfilament dysfunction may therefore be a possible cause of intrahepatic cholestasis. Crucial to this hypothesis are the presence of actin-containing microfilaments in the pericanalicular web, and an action of cytochalasin B on their contractility. Evidence pertaining to these requirements is presented and discused.

Animals↗
PubMed1975

Effects of prolonged administration of triton WR-1339 to the rat on morphology and phospholipids of liver.

Rats received 10 injections of Triton WR-1339 over a 4-week period. Light and electron microscopy and analysis of lipids and acid phosphatase were performed on livers of untreated controls, of animals taken during the period of treatment, and of animals allowed 2 weeks to recover. The only morphologic change resulting from the treatment was the appearance in both hepatocytes and Kupffer cells of after cessation of treatment, the change in hepatocytes had almost disappeared whereas it had become accentuated in the Kupffer cells. The treatments resulted in a 75 per cent increase in the concentration of lipids which includes Triton taken into the liver, a 17 per cent decrease in concentration of total phospholipid and a 26 per cent increase in acid phosphatase. Among phospholipid classes, there were small decreases in phosphatidylethanolamine, phosphatidylcholine, and diphosphatidylglycerol, a small increase in sphingomyelin and a striking increase of bis(monscylglyceryl)phosphate from 2.5 to 55 mug. of P per gm. of fresh weight. Cerebrosides were also increased. In rats allowed 2 weeks to recover, values for those classes which had been decreased by the treatment showed a trend of return toward controls. These observations suggest that lysosomal material is transferred from hepatocytes to Kupffer cells.

Animals↗
PubMed1975

Electron microscopic cytochemical characterization of bile canaliculi and bile ducts in vitro.

Electron microscopic cytochemical localization of Mg++-activated adenosine triphosphatase (Mg++-ATPase) and 5-nucleotidase (AMPase) was investigated in bile canaliculus-rich and bile duct-containing fractions isolated from rat liver. Comparative cyochemical studies between prefixed and non-prefixed fractions revealed that the activity of both enzymes could be detected in the fractions under appropriate experimental conditions. However, the cytochemical activity of AMPase was much more sensitive to glutaraldehyde than that of Mg++-ATPase. Mg++-ATPase and AMPase reaction products were localized primarily on bile canalicular microvilli, that is, along the outer (luminal) surface of canalicular plasma membranes, but they were never observed on bile ductal microvilli. AMPase was also detectable on lateral hepatic plasma membranes. Mg++-ATPase demonstrated by the cytochemical technique described is a reliable enzyme marker for isolated bile canalicular membranes. At high magnification, Mg++-ATPase reaction product was also observed on the microfilaments surrounding isolated bile canaliculi. The possibility that the reaction product on the pericanalicular microfilaments may result from the hydrolysis of ATP byan actomyosin ATPase-like enzyme associated with these filaments is briefly discussed.

Adenosine Triphosphatases↗