Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, we generated mice lacking microsomal triglyceride transfer protein (MTP) in the liver (Mttp(Delta/Delta)) and demonstrated that very low density lipoprotein secretion from hepatocytes was almost completely blocked. The blockade in lipoprotein production was accompanied by mild to moderate hepatic steatosis, but the mice appeared healthy. Although hepatic MTP deficiency appeared to be innocuous, we hypothesized that a blockade in very low density lipoprotein secretion and the accompanying steatosis might increase the sensitivity of Mttp(Delta/Delta) livers to additional hepatic insults. To address this issue, we compared the susceptibility of Mttp(Delta/Delta) mice and Mttp(flox/flox) controls to hepatic injury from Escherichia coli lipopolysaccharides, concanavalin A, and Pseudomonas aeruginosa exotoxin A. At baseline, neither the Mttp(Delta/Delta) nor the Mttp(flox/flox) mice had elevated serum transaminases or histologic evidence of hepatic inflammation. After the administration of the toxins, however, the Mttp(Delta/Delta) mice manifested higher levels of transaminases and, unlike the Mttp(flox/flox) mice, developed histologic evidence of hepatic inflammation. The toxic challenge induced tumor necrosis factor-alpha to a similar extent in Mttp(Delta/Delta) and Mttp(flox/flox) mice, but other parameters of injury (e.g. chemokine transcript levels and lipid peroxides) were disproportionately increased in the Mttp(Delta/Delta) mice. Our results suggest that blocking lipoprotein secretion in the liver may increase the susceptibility of the liver to certain toxic challenges.
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PMID:Blocking the secretion of hepatic very low density lipoproteins renders the liver more susceptible to toxin-induced injury. 1173 87

We describe a suggestive case of cystic fibrosis (CF) with a CF transmembrane conductance regulator (CFTR) mutation compatible with survival in which the diagnosis was missed in childhood. A 46-year-old man presented to our pediatric hospital with infertility and chronic cough, which had been present since 7 years of age. History was notable for high transaminase levels, hepatic steatosis sinusitis, chronic bronchitis, and duodenal inflammation. A sweat test was performed in duplicate and revealed a near-abnormal chloride level for adult age (77 mEq/L; normal value < 72 mEq/L). Significant findings of chronic bronchitis and bronchiectasis were found on x-ray film. A culture of sputum was positive for Pseudomonas aeruginosa. Spirometry showed a severe airflow limitation (FEV, 40%, and FVC, 61% of the predicted). CFTR mutation analysis showed the presence of homozygous 3849+10kbct mutation. Among CFTR mutations, 3849+ 10kbC>T has been reported frequently in adult patients with normal sweat tests and may cause a late diagnosis of CF. We conclude that because the diagnosis of CF might be missed during childhood, the diagnosis of CF in adults should be considered by practitioners, in subjects with chronic respiratory, gastrointestinal, and hepatic complaints.
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PMID:A missed cystic fibrosis diagnosis in childhood. 1654 75

s-adenosylmethionine (SAM) is the sole methyl donor modifying histones, nucleic acids, and phospholipids. Its fluctuation affects hepatic phosphatidylcholine (PC) synthesis or may be linked to variations in DNA or histone methylation. Physiologically, low SAM is associated with lipid accumulation, tissue injury, and immune responses in fatty liver disease. However, molecular connections among SAM limitation, methyltransferases, and disease-associated phenotypes are unclear. We find that low SAM can activate or attenuate Caenorhabditis elegans immune responses. Immune pathways are stimulated downstream of PC production on a non-pathogenic diet. In contrast, distinct SAM-dependent mechanisms limit survival on pathogenic Pseudomonas aeruginosa. C. elegans undertakes a broad transcriptional response to pathogens and we find that low SAM restricts H3K4me3 at Pseudomonas-responsive promoters, limiting their expression. Furthermore, this response depends on the H3K4 methyltransferase set-16/MLL. Thus, our studies provide molecular links between SAM and innate immune functions and suggest that SAM depletion may limit stress-induced gene expression.
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PMID:s-Adenosylmethionine Levels Govern Innate Immunity through Distinct Methylation-Dependent Pathways. 2632 61