Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An elderly woman with Hodgkin's disease and hepatic involvement but without cholestasis presented with markedly depressed levels of serum esterified cholesterol and high density lipoproteins (HDL). Within five days of her first cycle of chemotherapy her serum HDL-cholesterol rose from 8-10 mg/dl to 88 mg/dl, and levels of the major HDL-apoprotein, apoA-I, rose from 60 to 138 mg/dl. The proportion of unesterified serum cholesterol fell from 60-80% to 27-30%. These observations suggest a relatively specific effect of the hepatic lymphoma on synthesis or release of lecithin:cholesterol acyltransferase.
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PMID:Reversible deficiency of serum high density lipoproteins in Hodgkin's disease. 376 60

The enzyme, acyl-coenzyme A:cholesterol acyltransferase (ACAT), is responsible for the intracellular esterification of cholesterol. Although it has been detected in the liver from a variety of animals and in human skin fibroblasts and human intestine, it has been reported to be absent from human liver. Since this enzyme may play an important role in cholesterol homeostasis, evidence for its presence in human liver was again sought. Using labeled oleoyl CoA and the endogenous cholesterol as reactants, ACAT was detected in fresh samples of human liver obtained from patients undergoing staging laparotomy for Hodgkin's disease. The enzyme is present almost exclusively in membrane fractions with little activity detected in cytosol. Microsomal ACAT activity was linear with incubation time for up to 10 min. After this, the rate of cholesterol esterification remained constant despite the fact that adequate acyl CoA was present as judged by the continued incorporation of oleate into triglyceride. ACAT activity is destroyed by heating at 100 degrees C for 10 min. It was inhibited only up to 20%-30% by 1 mM 5,5'-dithiobis-(2-nitrobenzoic acid), which completely inactivates the serum cholesterol esterifying enzyme, lecithin:cholesterol acyltransferase (LCAT). Like ACAT in human skin fibroblasts, human liver ACAT was also inhibited by progesterone in vitro. ACAT activity averaged 10.3 +/- 5.1 pmole cholesteryl oleate/min/mg microsomal protein for 3 normal livers and 39.0 +/- 12.5 for 2 fatty livers. Thus, the level of ACAT activity estimated for the whole liver was 2.1-35.8 mumol/hr in the fasting state. This activity may account for some portion of the cholesterol esters present in plasma VLDL in fasting normolipidemic individuals. However, it is likely that the major role of hepatic ACAT is in the regulation and maintenance of hepatic cholesterol homeostasis.
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PMID:Acyl-coenzyme A:cholesterol acyltransferase in human liver. In vitro detection and some characteristics of the enzyme. 742 86

An antibody against the lecithin:cholesterol acyltransferase (LCAT) enzyme, which negates cholesterol esterification in plasma, causing severe high-density lipoprotein deficiency (HD), was identified in a woman with a large-cell non-Hodgkin lymphoma. Successful treatment of the lymphoma resulted in clearance of the antibody and complete correction of the defective cholesterol esterification and HD. To our knowledge, an acquired LCAT deficiency leading to severe HD has not been reported previously in association with a malignant disease, and this patient represents the first such documented case.
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PMID:Severe high-density lipoprotein deficiency associated with autoantibodies against lecithin:cholesterol acyltransferase in non-Hodgkin lymphoma. 2227 Nov 27