Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clofibrate and many of its structural analogues induce proliferation of peroxisomes in the hepatic parenchymal cells of rodents and certain nonrodent species including primates. This induction is tissue specific, occurring mainly in the liver parenchymal cells and to a lesser extent in the kidney cortical epithelium. The induction of peroxisomes is associated with a predictable pleiotropic response, characterized by hepatomegaly, and increased activities and mRNA levels of certain peroxisomal enzymes. Using affinity chromatography, we had previously isolated a protein that binds to clofibric acid. We now show that this protein is homologous with the heat shock protein HSP70 family by analysis of amino acid sequences of isolated peptides from trypsin-treated clofibric acid binding protein and by cross-reactivity with a monoclonal antibody raised against the conserved region of the 70-kDa heat shock proteins. The clofibric acid-Sepharose column could bind HSP70 proteins isolated from various species, which could then be eluted with either clofibric acid or ATP. Conversely, when a rat liver cytosol containing multiple members of the HSP70 family was passed through an ATP-agarose column, and eluted with clofibric acid, only P72 (HSC70) was eluted. These results suggest that clofibric acid, a peroxisome proliferator, preferentially interacts with P72 at or near the ATP binding site.
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PMID:Identification of cytosolic peroxisome proliferator binding protein as a member of the heat shock protein HSP70 family. 237 Dec 72

Sera from 88 patients with progressive systemic sclerosis were examined for precipitating mitochondrial antibodies using sonicated rat liver mitochondrial fraction as an antigen source in immunodiffusion. Precipitin lines indicating the presence of anti-mitochondrial antibodies (AMA) in 22 patients were detected. Only six of 22 sera had, additionally, precipitating antibodies to nuclear antigens. Standardized reference sera containing antibodies to mitochondrial antigens (M-A, M-B and M-C systems) were used to further characterize the type of mitochondrial antibodies. M-B antibody was most commonly detected (72.7%) either alone (eight patients) or in combination (eight patients) with M-A and M-C antibodies. M-A antibody was found in 12 patients (54.5%) and M-C antibody was present in three. The antigen related to M-B is DNAase and trypsin sensitive, in contrast to the resistant M-A antigen. AMA were detected in 21 of 22 patients by indirect immunofluorescence. When solid phase ELISA was used to detect AMA using mitochondrial fraction as antigen, a significant difference (P less than 0.005) was noted between sera with and without precipitating mitochondrial antibody. The antibody was frequently present in patients with progressive systemic sclerosis detected 2 or more years earlier (P less than 0.01). Three patients were found to have primary biliary cirrhosis and others had pruritus, hepatomegaly or abnormal liver function tests. The implication of the findings is discussed.
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PMID:Precipitating autoantibodies to mitochondrial proteins in progressive systemic sclerosis. 643 13

It has been reported that the administration of interferon alpha-2b is of potential benefit in the treatment of mastocytosis based on a single patient study (NEJM, Feb 27, 1992, 326(9):619-623). Following this report, we administered interferon alpha-2b at a dose of 4 to 5 million units per square meter of body surface area for at least 12 months to one patient with mastocytosis with an associated hematologic disorder (patient 1), one patient with aggressive systemic mastocytosis (patient 2), and one patient with indolent mastocytosis (patient 3). Patients were monitored with the following clinical and laboratory parameters: serial bone marrow biopsies and aspirates, patient log of histamine release attacks, medication dependency, plasma tryptase levels, serum lactate dehydrogenase (LDH) levels, white blood cell counts and differentials, extent of urticaria pigmentosa lesions, bony involvement, and extent of gastrointestinal involvement and hepatomegaly. We also examined the ability of interferon alpha-2b to inhibit recombinant human stem cell factor (rhSCF)-dependent mast cell proliferation from CD34+ bone marrow-derived cells. All patients demonstrated continued progression of disease in one or more clinical criteria at one year of therapy. Similarly, interferon alpha-2b did not inhibit the culture of mast cells from CD34+ bone marrow-derived cells in the presence of SCF. Thus, in our study of three patients with systemic mastocytosis, treatment with interferon alpha-2b was found to be ineffective in controlling progression of disease.
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PMID:Treatment of three patients with systemic mastocytosis with interferon alpha-2b. 888 64