Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morbidity and mortality rates of ARDS (acute respiratory distress syndrome) are high in patients with a history of chronic alcohol abuse. In addition to susceptibility to lung infection, alteration of local cellular functions in the lung has recently been proposed as a new mechanism of exacerbation of ARDS in patients with a history of chronic alcohol abuse. Clinical studies and studies using animal experiments have shown that a decrease in lung glutathione levels is associated with exacerbation of ARDS in chronic alcohol abuse. In the alcoholic lung, depletion of glutathione increases oxidative stress derived from activated neutrophils, resulting in decreased surfactant production, apoptosis and increased permeability of alveolar epithelial type II cells, in which TGF-beta1 may be involved. Acetoaldehyde has been suggested to be involved in the mechanism of exacerbation of ARDS by inducing lung remodeling through stimulation of fibronectin expression following nicotinic acetylcholine receptor stimulation and CREB activation in chronic alcohol abuse. More recently, antagonists of angiotensin II type-1 receptor (AT1 receptor) have been shown to prevent glutathione depletion, increase in TGF-beta1 expression and lung edema in endotoxemic rats with chronic alcohol administration. On the other hand, macrophage-derived prostaglandin E2 plays a protective role at an initial phase of ARDS by inhibiting cytokine production by macrophages and extravascular invasion of activated neutrophils. Our recent studies have shown that LPS-induced COX-2 expression and subsequent prostaglandin E2 production in rat alveolar macrophages are inhibited by ethanol incubation in vitro and ethanol administration in vivo. Only a decade has passed since alcohol abuse was demonstrated to be associated with increased mortality of ARDS and future studies are needed to clarify the mechanism underlying alcohol-induced exacerbation of ARDS.
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PMID:[Alcohol abuse as a risk factor for ARDS]. 1717 45

Non-alcoholic steatohepatitis (NASH) is commonly associated with obesity, type 2 diabetes, and/or hypertriglyceridemia, while alcoholic steatohepatitis (ASH) is associated with alcohol abuse. Both NASH and ASH patients can develop cirrhosis and hepatocellular carcinoma (HCC) if left untreated. However, the rate of tumorigenesis in NASH and ASH appears to be different. Individuals with NASH progress to HCC at a rate of 0.5% annually (Lindenmeyer and McCullough, 2018), when individuals with ASH progress to HCC at a rate of 3-10% annually (Schwartz and Reinus, 2012). Thus, the objective of our study is to determine if there are differences in NASH versus ASH in the levels of different proteins expressed involved in cancer development. The method used was measuring the proteins expressed in liver biopsied sections from NASH and ASH patients using immunohistochemical staining with fluorescent antibodies and then quantitating the fluorescence intensity morphometrically. The 20 proteins tested are parts of the Ingenuity Canonical Pathway of Molecular Mechanisms of Cancer and include: RAP2B, NAIP, FYN, PAK6, SUV39H1, GNAI1, BAX, E2F3, CKDN2B, BAK1, BCL2, DIABLO, RASGRF2, GNA15, PIK3CB, BRCA1, MAP2K1, BIRC3, CDK2, and ATM. In ASH, the proteins that showed upregulated levels of expression were SUV39H1, E2F3, BCL2, BAK1, BIRC3, and GNAI1. In NASH, the proteins that showed upregulated levels of expression were BAK1 and GNAI1 and the protein that showed downregulated level of expression was BCL2. Additionally, levels of expression for SUV39H1, E2F3, BCL2, BAK1, BIRC3, and GNAI1 were significant upregulated in ASH compared to NASH. These results showed significant differences in ASH compared to normal liver, and significant differences in ASH compared to NASH. Thus, we conclude that there are more proteins involved in tumorigenesis in ASH compared to NASH and in ASH compared to normal liver, which is consistent with the known tumor development rate in ASH and NASH.
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PMID:Alcoholic hepatitis versus non-alcoholic steatohepatitis: Levels of expression of some proteins involved in tumorigenesis. 2930 97