Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Magnetic resonance (MR) imaging, localized in vivo proton spectroscopy, and T1 relaxation measurements were obtained from the livers of rats treated chronically with carbon tetrachloride and phospholipase D. The MR data correlated well with lipid changes measured biochemically and histologically. MR images appeared generally hyperintense during fatty infiltration, changing to hypointense mottling during cirrhosis. Water T1 relaxation times showed no statistically significant change at any time during the experiments from the control value of 908 ms (SE = 42 ms). Minor changes in lipid T1 values with time were noted. The average lipid T1 curve demonstrated a linear relation with time (r = 0.81), increasing from the control value of 283 ms (+/- 16 ms) to 365 ms (+/- 53 ms) at the end of the third week and decreasing slightly through the end of the experiment. Water-suppressed in vivo spectra showed quantitative changes in liver lipids which correlated well with the biochemical and histologic analysis. From the MR images and spectroscopy results it was possible to distinguish early fatty liver from more advanced cirrhosis.
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PMID:Chronic carbon tetrachloride and phospholipase D hepatotoxicity in rat: in vivo 1H magnetic resonance, total lipid analysis, and histology. 239 47

A new and rapid method for the production of liver cirrhosis in the rat is described. Rats were treated with carbon tetrachloride for 4 weeks and then injected i.p. with phospholipase D daily for 6 days. Controls received either carbon tetrachloride or phospholipase D only. Following the combined treatment cirrhosis developed rapidly; the liver developed micronodules and severe cirrhosis was accompanied by ascites and splenomegaly.
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PMID:Rapid induction of cirrhosis by administration of carbon tetrachloride plus phospholipase D. 402 73

1. We report the first demonstration of the pathophysiological importance and clinical applications of the relatively recently discovered circulating enzyme, phosphoinositol-specific phospholipase D. This enzyme is known to cleave the large variety of important cell-surface molecules linked to the cell membrane by glycan-phosphatidylinositol linkages (glycan-phosphatidylinositol anchors). 2. When measured in the sera of healthy individuals, phosphoinositol-specific phospholipase D activity was found to show a strong negative correlation with age, the degree of depreciation being greater than that measured for most other analytes. 3. Serum phosphoinositol-specific phospholipase D activity was considerably depressed in patients presenting with conditions leading to reduced liver synthetic reserve, such as hepatocellular carcinoma or liver cirrhosis caused by chronic viral hepatitis, and correlated with reduced albumin levels in these conditions, indicating that the liver is the site of phosphoinositol-specific phospholipase D synthesis and that phosphoinositol-specific phospholipase D may be used as an additional marker of liver synthetic reserve. 4. When measured in patients with acute liver disease, such as acute viral hepatitis, or in patients with bronchopneumonia, phosphoinositol-specific phospholipase D activity was found to be significantly raised, demonstrating features characteristic of an acute-phase reactant. 5. These findings indicate that, besides its pathophysiological importance, phosphoinositol-specific phospholipase D and the measurement of its activity in serum may have a useful place in the investigation of a range of clinical conditions, including tissue injury and inflammation.
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PMID:Inositol-specific phospholipase D activity in health and disease. 816 40

The endocannabinoid arachidonoyl ethanolamine (anandamide) is a lipid transmitter synthesized and released "on demand" by neurons in the brain. Anandamide is also generated by macrophages where its endotoxin (LPS)-induced synthesis has been implicated in the hypotension of septic shock and advanced liver cirrhosis. Anandamide can be generated from its membrane precursor, N-arachidonoyl phosphatidylethanolamine (NAPE) through cleavage by a phospholipase D (NAPE-PLD). Here we document a biosynthetic pathway for anandamide in mouse brain and RAW264.7 macrophages that involves the phospholipase C (PLC)-catalyzed cleavage of NAPE to generate a lipid, phosphoanandamide, which is subsequently dephosphorylated by phosphatases, including PTPN22, previously described as a protein tyrosine phosphatase. Bacterial endotoxin (LPS)-induced synthesis of anandamide in macrophages is mediated exclusively by the PLC/phosphatase pathway, which is up-regulated by LPS, whereas NAPE-PLD is down-regulated by LPS and functions as a salvage pathway of anandamide synthesis when the PLC/phosphatase pathway is compromised. Both PTPN22 and endocannabinoids have been implicated in autoimmune diseases, suggesting that the PLC/phosphatase pathway of anandamide synthesis may be a pharmacotherapeutic target.
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PMID:A biosynthetic pathway for anandamide. 1693 87