Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that Helicobacter pylori (H. pylori) infection might be associated with not only gastric ulcers but also gastric malignancies. Recently, it was reported that the Streptococcus anginosus (S. anginosus) DNA sequence was found in DNA samples extracted from esophageal cancers. Because smoking and alcohol abuse are regarded as risk factors for both esophgeal cancer and head and neck cancer, infection of S. anginosus might be associated with carcinogenesis of head and neck cancer. To investgate the involvement of S. anginosus infection in head and neck cancer, we analyzed 217 DNA samples prepared from head and neck squamous cell carcinomas. We performed PCR analysis with S. anginosus-16S ribosomal DNA-specific primers, and Southern blot analysis. For detection of S. anginosus in the oral and pharyngeal cavities, we used oropharyngeal bacteriological culture and PCR analysis of gingival smears of the patients. By PCR analysis, the S. anginosus DNA sequence was found in 217 out of 217 (100%) DNA samples obtained from head and neck cancers. By Southern blot analysis, positive bands were detected in 41 out of 125 (33%) samples. We could find no S. anginosus colony in oropharyngeal bacteriological culture dishes of 53 patients with and without head and neck cancer. On the other hand, we found the S. anginosus DNA fragment in 8 out of 8 DNA samples obtained from gingival smears by PCR analysis. These data indicate that the upper aerodigestive environment of the patients permitting S. anginosus infection was implicated in the carcinogenesis of head and neck squamous cell carcinoma.
Int J Mol Med 2000 Dec
PMID:Streptococcus anginosus in head and neck squamous cell carcinoma: implication in carcinogenesis. 1107 31

The central nervous system is particularly susceptible to alcohol effects and toxicity. Glial cells constitute the most common cell type in the brain and play critical roles in normal brain function and during infection and injury. Astrocytes in particular seem to be important targets for alcohol neurotoxicity during both development and in adulthood. To gain more insight into alcohol-mediated effects on astrocytes at the molecular level, gene expression in rat C6 glial cells was studied in the presence or absence of ethanol. The differential display of mRNA technique was used to screen the expressed genes in ethanol-treated rat C6 cells before and after treatment with lipopolysaccharide (LPS) combined with phorbol-12-myristate-13-acetate (PMA), conditions that mimic an infectious inflammatory state and cause immunologic activation. The present data show that fibronectin appeared as a major gene whose expression is increased in C6 cells by LPS plus PMA stimulation and decreased by chronic ethanol exposure, both in mRNA and protein levels. Fibronectin is a dimeric glycoprotein found in the extracellular matrix of most tissues, in the blood, and on cell surfaces and is involved in many cellular processes. These results show that chronic exposure to ethanol is associated with changes in astrocyte properties during immunologic activation that reduce fibronectin expression. The discovery of astrocyte fibronectin expression as a potential regulated target for chronic alcohol abuse may be useful in understanding, preventing, and treating some brain disorders associated with alcohol abuse and alcoholism.
Mol Pharmacol 2000 Dec
PMID:Differential fibronectin expression in activated C6 glial cells treated with ethanol. 1109 67

In septic patients, chronic alcohol abuse increases the incidence of the acute respiratory distress syndrome (ARDS). Because alveolar type II cell viability is critical for epithelial repair, our objective was to determine if chronic ethanol ingestion increased the sensitivity of type II cells to the inflammatory mediators upregulated during sepsis. In rats chronically fed ethanol, type II cell mitochondrial GSH was depleted, and tumor necrosis factor-alpha (TNF-alpha)-induced generation of mitochondrial reactive oxygen species (ROS) and apoptosis were potentiated. When added to the ethanol diet, the GSH precursor (-)-2-oxo-4-thiazolidinecarboxylic acid (Procysteine; Pro) but not N-acetylcysteine (NAC) normalized type II cell mitochondrial GSH. Likewise, Pro but not NAC normalized TNF-alpha-induced mitochondrial ROS and apoptosis. This suggested that chronic ethanol ingestion potentiated TNF-alpha-induced apoptosis in type II cells via mitochondrial GSH depletion. This may be particularly relevant in ARDS when type II cell viability is critical to repair of the damaged alveolar epithelium and may have important ramifications for the treatment of ARDS patients with a history of alcohol abuse.
Am J Physiol Lung Cell Mol Physiol 2001 Aug
PMID:Chronic ethanol ingestion potentiates TNF-alpha-mediated oxidative stress and apoptosis in rat type II cells. 1143 12

Human liver contains estrogen receptors (ER) which render it sensitive to estrogen. Chronic ethanol ingestion in humans and rats results in alterations of circulating sex steroid levels and expression of sex hormone-dependent phenotype. The analysis and quantitation of hepatic estrogen receptor (ER) activity and sex hormone-responsive proteins have been performed over the past two decades. Alcohol abuse appears to induce an increase in ER content of human liver, especially in patients with alcoholic hepatitis actively drinking. This observation is reproduced in an experimental model of chronic alcohol feeding of rats. In male rat liver, the increased ER expression induced by alcohol is associated with an elevated proliferation rate of the hepatocytes. In female liver, the ER content is not affected by alcohol intake and apoptosis prevails over proliferation. The feminization of the liver in males may protect the liver from the severe alcohol-induced liver injury seen in females.
Mol Cell Endocrinol 2002 Jul 31
PMID:Hepatic estrogen receptors and alcohol intake. 1216 Oct 8

Recent preclinical and clinical studies have indicated a possible involvement of the genes encoding for the GABA(A) receptor subunits alpha6, beta2, alpha1 and gamma2 in the genetic susceptibility to alcohol abuse. We have recently found an (R) to (Q) mutation in codon 100 of the alpha6 GABA(A) subunit, that segregated in a rat line selectively bred for its voluntary ethanol aversion, Sardinian alcohol nonpreferring (sNP), but not in their Sardinian alcohol preferring (sP) counterpart, selected for its ethanol preference. In the present study the molecular composition of other GABA(A) subunits (beta2, alpha1 and gamma2) were analyzed in order to further investigate the involvement of the GABA(A) receptors in the genetic predisposition to voluntary alcohol intake. Automated sequencing analysis indicated the presence of six new silent substitutions (289 T-->C in the beta2 gene; 115 G-->A in the alpha1 gene; 157 G-->A, 174 C-->T, 347 A-->G and 385 A-->T in the gamma2 gene), in sNP but not in sP rats. These polymorphisms were linked to the alpha6 R100Q mutation previously described in sNP rats. The strict association between the alpha6 point mutation and the new polymorphisms found in the beta2, alpha1 and gamma2 genes, demonstrate that such genes belong to the same cluster and are inherited together in the rat. These results sustain the synteny for these clusters between the rodent and human genomes, and suggest that mutated GABA(A) beta2, alpha6, alpha1 and gamma2 subunit genes might contribute to the expression of an ethanol nonpreferring phenotype in a rat line that voluntarily avoids alcoholic solutions.
Brain Res Mol Brain Res 2003 Feb 20
PMID:Molecular characterization of new polymorphisms at the beta2, alpha1, gamma2 GABA(A) receptor subunit genes associated to a rat nonpreferring ethanol phenotype. 1259 Nov 65

Erythrocyte uroporphyrinogen decarboxylase (UROD) activity was measured to classify 118 Spanish patients with porphyria cutanea tarda (PCT) into three subtypes: sporadic-, familial- and type III-PCT. Seventy-four patients (63%) had eythrocyte UROD activity within the normal range (74% to 126% of the mean activity of 43 healthy controls) and were classified as sporadic-PCT (47%) or as type III-PCT (16%) whenever a family history of PCT was documented. Forty-four patients (37%) had decreased UROD activity and were classified as familial-PCT. The frequency of both familial-PCT and type III-PCT was higher than reported in other countries. The clinical expression of PCT was associated with the coexistence of two or more risk factors in 80% of the sporadic-PCT patients and in 89% of the familial-PCT patients. Hepatitis C virus and alcohol abuse were risk factors frequently found in these patients, being unrelated to age of onset of skin lesions. A heavy alcohol intake was the main risk factor for type III-PCT. Estrogens appeared as a precipitating factor for women with familial-PCT. The H63D mutation in the hemochromatosis type 1 gene was more frequently found than the C282Y mutation. Both mutations appeared to play a role as precipitating factors in sporadic-PCT when associated with hepatitis C virus infection and alcohol abuse.
Cell Mol Biol (Noisy-le-grand) 2002 Dec
PMID:Precipitating/aggravating factors of porphyria cutanea tarda in Spanish patients. 1269 42

A nurse-administered, protocol-driven model (NP) for preventive services delivery was compared with a traditional physician reminder (PR) model with nursing back-up among 473 patients attending Internal Medicine and Family Medicine clinics. A total of 240 patients were randomized to the NP group and 233 to the PR group. Demographic characteristics including gender [71% female (NP) and 71% female (PR)], race (78% and 75% African American, respectively) and age (numbers of persons aged 18-54, 55-64 and 65+ years) were similar in each group. In the NP group 244/244 screening tests for breast, cervical and colon cancers and alcohol abuse were initiated or completed by nurses, while in the PR group 110/215 (51%) were initiated or completed by physicians. The NP group received 552/552 counseling services from nurses for tobacco, alcohol, nutrition, exercise and prostate screening, while in the PR group, physicians delivered 10% of the needed services (56/560). Aside from counseling for prostate cancer screening, which was 100% in both the NP and PR groups, all other between-group differences for each service were significant at the level of p<0.001. Results show the feasibility of a nursing protocol for initiating equitable cancer prevention services in a primary care setting.
Cell Mol Biol (Noisy-le-grand) 2003 Dec
PMID:Using a nursing protocol to assure equitable delivery of cancer-related prevention services. 1498 91

Several evidences indicate altered regulation of brain serotonergic mechanisms in alcohol abuse; changes in 5-HT2A receptor density and functioning have been observed in several lines of alcohol-preferring rats. Using quantitative autoradiography, the present study investigated the influence of chronic intragastric ethanol treatment on forebrain 5-HT2A binding sites in rats. Administration for 7 days of high doses of ethanol, which induced physical dependence, lowered the levels of 5-HT2A binding sites in the cingulate cortex, the frontal cortex and in the agranular insular cortex. The effect was observed immediately after the last ethanol administration, was statistically significant 14 h later, when marked withdrawal signs were observed, and remained significant after 8 days of detoxification, when withdrawal signs were no longer evident. No significant differences were detected in the claustrum, parietal cortex, piriform cortex, caudate putamen, olfactory tubercle, nucleus accumbens, shell and core. Chronic treatment with 6 g/kg of ethanol, which did not induce dependence, did not modify 5-HT2A binding sites. These long-lasting changes in brain 5-HT2A binding sites observed in the present study might contribute to specific aspects of ethanol dependence, such as development of depression and alcohol craving.
Res Commun Mol Pathol Pharmacol 2002
PMID:Autoradiographic analysis of 5-hydroxytryptamine 5-HT2A binding sites in the rat brain after chronic intragastric ethanol treatments. 1508 May 2

Acetaldehyde, the first product of ethanol metabolism, has been speculated to be involved in many pharmacological and behavioral effects of ethanol. In particular, acetaldehyde has been suggested to contribute to alcohol abuse and alcoholism. In the present paper, we review current data on the role of acetaldehyde and ethanol metabolism in alcohol consumption and abuse. Ethanol metabolism involves several enzymes. Whereas alcohol dehydrogenase metabolizes the bulk of ethanol within the liver, other enzymes, such as cytochrome P4502E1 and catalase, also contributes to the production of acetaldehyde from ethanol oxidation. In turn, acetaldehyde is metabolized by the enzyme aldehyde dehydrogenase. In animal studies, acetaldehyde is mainly reinforcing particularly when injected directly into the brain. In humans, genetic polymorphisms of the enzymes alcohol dehydrogenase and aldehyde dehydrogenase are also associated with alcohol drinking habits and the incidence of alcohol abuse. From these human genetic studies, it has been concluded that blood acetaldehyde accumulation induces unpleasant effects that prevent further alcohol drinking. It is therefore speculated that acetaldehyde exerts opposite hedonic effects depending on the localization of its accumulation. In the periphery, acetaldehyde is primarily aversive, whereas brain acetaldehyde is mainly reinforcing. However, the peripheral effects of acetaldehyde might also be dependent upon its peak blood concentrations and its rate of accumulation, with a narrow range of blood acetaldehyde concentrations being reinforcing.
Mol Psychiatry 2004 Jun
PMID:Genetic polymorphism in ethanol metabolism: acetaldehyde contribution to alcohol abuse and alcoholism. 1516 86

We decided to test the hypothesis that possibly by combining a narcotic antagonist and amino-acid therapy consisting of an enkephalinase inhibitor (D-phenylalanine) and neurotransmitter precursors (L-amino- acids) to promote neuronal dopamine release might enhance compliance in methadone patients rapidly detoxified with the narcotic antagonist Trexan (Dupont, Delaware). In this regard, Thanos et al. [J. Neurochem. 78 (2001) 1094] and associates found increases in the dopamine D2 receptors (DRD2) via adenoviral vector delivery of the DRD2 gene into the nucleus accumbens, significantly reduced both ethanol preference (43%) and alcohol intake (64%) of ethanol preferring rats, which recovered as the DRD2, returned to baseline levels. This DRD2 overexpression similarly produced significant reductions in ethanol non-preferring rats, in both alcohol preference (16%) and alcohol intake (75%). This work further suggests that high levels of DRD2 may be protective against alcohol abuse [JAMA 263 (1990) 2055; Arch, Gen. Psychiatr. 48 (1991) 648]. The DRD2 A1 allele has also been shown to associate with heroin addicts in a number of studies. In addition, other dopaminergic receptor gene polymorphisms have also associated with opioid dependence. For example, Kotler et al. [Mol. Phychiatr. 3 (1997) 251] showed that the 7 repeat allele of the DRD4 receptor is significantly overpresented in the opioid-dependent cohort and confers a relative risk of 2.46. This has been confirmed by Li et al. [Mol. Psychiatry 2 (1997) 413] for both the 5 and 7 repeat alleles in Han Chinese case control sample of heroin addicts. Similarly Duaux et al. [Mol. Psychiatry 3 (1998) 333] in French Heroin addicts, found a significant association with homozygotes alleles of the DRD3-Bal 1. A study from NIAAA, provided evidence which strongly suggests that DRD2 is a susceptibility gene for substance abusers across multiple populations (2003). Moreover, there are a number of studies utilizing amino-acid and enkephalinase inhibition therapy showing reduction of alcohol, opiate, cocaine and sugar craving behavior in human trials (see Table 1). Over the last decade, a new rapid method to detoxify either methadone or heroin addicts utilizing Trexan sparked interest in many treatment centers throughout the United States, Canada, as well as many countries on a worldwide basis. In using the combination of Trexan and amino-acids, results were dramatic in terms of significantly enhancing compliance to continue taking Trexan. The average number of days of compliance calculated on 1000 patients, without amino-acid therapy, using this rapid detoxification method is only 37 days. In contrast, the 12 subjects tested, receiving both the Trexan and amino-acid therapy was relapse-free or reported taking the combination for an average of 262 days (p < 0.0001F). Thus coupling amino-acid therapy and enkephalinase inhibition while blocking the delta-receptors with a pure narcotic antagonist may be quite promising as a novel method to induce rapid detox in chronic methadone patients. This may also have important ramifications in the treatment of both opiate and alcohol-dependent individuals, especially as a relapse prevention tool. It may also be interesting too further test this hypothesis with the sublingual combination of the partial opiate mu receptor agonist buprenorphrine.
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PMID:Narcotic antagonists in drug dependence: pilot study showing enhancement of compliance with SYN-10, amino-acid precursors and enkephalinase inhibition therapy. 1528 84


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