Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report addresses the effects of coal-derived trace and radioactive elements. A summary of our current understanding of health and environmental effects of trace and radioactive elements released during coal mining, cleaning, combustion, and ash disposal is presented. Physical and biological transport phenomena which are important in determining organism exposure are also discussed. Biological concentration and transformation as well as synergistic and antagonistic actions among trace contaminants are discussed in terms of their importance in mobility, persistence, availability, and ultimate toxicity. The consequences of implementing the President's National Energy Plan are considered in terms of the impact of the NEP in 1985 and 2000 on the potential effects of trace and radioactive elements from the coal fuel cycle. Areas of needed research are identified in specific recommendations.
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PMID:Potential health and environmental effects of trace elements and radionuclides from increased coal utilization. 54 Jun 19

The protein ASH (for abundant Src homology), composed of one Src homology region (SH) 2 and two SH3 domains, was cloned by screening human and rat cDNA libraries with an oligonucleotide probe directed to a consensus sequence of the SH2 domains. The rat-derived ASH peptide was comprised of 217 amino acids with a molecular mass of 25-28 kDa and was found to be ubiquitous in rat tissues. A human cDNA clone was also found to code for part of the same protein, suggesting that ASH is common to human and rat. The amino acid sequence of ASH was strikingly similar to Sem-5, the product of a nematode cell-signaling gene, and ASH is most probably a mammalian homologue of Sem-5. ASH bound in vitro to phosphotyrosine-containing proteins, including activated epidermal growth factor receptor, the ASH SH2 domain being responsible for the binding. Induced expression of an antisense ASH cDNA led to a reduction in cell growth. Considering these observations and the structural homology to Sem-5, ASH is likely to function as a ubiquitous signal transducer, possibly resembling Sem-5, which communicates between a receptor protein tyrosine kinase and a Ras protein.
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PMID:Cloning of ASH, a ubiquitous protein composed of one Src homology region (SH) 2 and two SH3 domains, from human and rat cDNA libraries. 138 39

A digestibility trial involving 20 Hampshire ram lambs and a 2-yr grazing study using 103 mature crossbred cows were conducted to determine the effects of methionine addition to a urea-grain supplement on intake and digestibility of dormant range grasses and on cow performance. In each trial, four treatment groups were supplemented with either a urea-grain control (CON), urea-grain plus methionine (MET, 3.3% DL-methionine), urea-grain plus inorganic sulfur (SUL, 3.0% sodium sulfate), or soybean meal (SBM). Supplements were designed to provide 45 and 360 g of CP.animal-1.d-1 (lambs and cows, respectively) and were balanced for ME, Ca, P, and K. Lambs had ad libitum access to mature prairie hay, whereas cows grazed dormant winter range from mid-November until mid-February. For the grazing study, forage OM intake (OMI) was determined in late November and in late January by the fecal output/indigestibility ratio technique. Controlled-release chromic oxide boluses were used as an external marker to estimate fecal output, and acid insoluble ash was used as an internal marker to predict OM digestibility (OMD). Mean daily DMI of mature prairie hay was 1,057 g/lamb and was not affected by supplementation. Apparent DM, NDF, and ADF digestibilities and N biological value did not differ (P > .10) among treatments. Nitrogen digestibility was increased (P = .06) for lambs fed the MET or SUL compared with CON.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of methionine addition to a urea-grain supplement on intake and digestibility of mature, dormant grasses and performance of cows grazing winter range. 844 Jun 72

Adhesion of human monocytes (MOs) results in the rapid transcriptional activation of cytokine genes that are dependent on nuclear factor (NF)-kappaB. Several pathways leading to activation of NF-kappaB have been described, including those involving reactive oxygen intermediates (ROIs) and members of the mitogen-activated protein (MAP) kinase superfamily. To investigate the involvement of tyrosine phosphorylation (TP) and oxidant generation in interleukin (IL)-8 and GRO messenger RNA induction, MOs and human alveolar macrophages (AMs) were adhered to plastic or exposed to a particulate pollutant, residual oil fly ash (ROFA). Both stimuli caused rapid TP and ROI production in MOs and AMs. However, neither NF-kappaB translocation nor IL-8 gene induction occurred in adhered or ROFA-exposed AMs. Analysis of MAP kinase activation found phosphorylation of Jun amino-terminal kinase (JNK) and p38 in the AMs, but not of extracellular regulated kinase/MAP kinase (ERK/MAPK). AMs stimulated with lipopolysaccharide activated ERK/MAPK, in addition to JNK and p38, and showed translocation of NF-kappaB. In contrast to AMs, MO adhesion or exposure to ROFA particles in suspension rapidly activated p38, JNK, and ERK/MAPK, and activated NF-kappaB binding as well as IL-8 mRNA expression. Pretreatment with the tyrosine kinase inhibitors genistein or herbimycin A before adherence had no effect on transcriptional activation in MOs, whereas adherence and ROFA-induced oxidant generation was inhibited in both MOs and AMs. Taken together, these data indicate that NF-kappaB activation or generalized transcriptional activation of cytokine genes are independent of changes in oxidant stress imposed on phagocytes by adhesion. Furthermore, the data suggest that certain environmental responses in AMs may be uncoupled from activation of NF-kappaB.
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PMID:Adhesion and pollution particle-induced oxidant generation is neither necessary nor sufficient for cytokine induction in human alveolar macrophages. 1065 41

Insight into the mechanism(s) by which ambient air particulate matter (PM) mediates adverse health effects is needed to provide biological plausibility to epidemiological studies demonstrating associations between PM exposure and increased morbidity and mortality. Although in vitro PM studies provide an understanding of mechanisms by which PM affects pulmonary cells, it is difficult to extrapolate from in vitro to in vivo mechanisms of PM-induced lung injury. We examined in vivo mechanisms of lung injury generated by oil combustion particles. Rats were pretreated with dimethylthiourea (DMTU) before intratracheal instillation of residual oil fly ash (ROFA). Animals were examined by bronchoalveolar lavage for biomarkers of lung injury, and lung tissues were examined by immunohistochemical, biochemical, and molecular approaches to identify ROFA-induced alterations in intracellular signaling pathways and proinflammatory gene expression. Significant increases in pulmonary inflammation, cytotoxicity, activation of ERK mitogen-activated protein kinase (MAPK), and increases in mRNA levels encoding macrophage inflammatory protein (MIP)-2, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, MCP-1 and matrilysin were observed. DMTU pretreatment inhibited ROFA-induced pulmonary inflammation, cytotoxicity, ERK MAPK activation, and cytokine gene expression. Our findings provide coherence with in vitro PM mechanistic information, allow direct in vitro to in vivo extrapolation, and demonstrate a critical role for oxidative stress in ROFA-induced lung injury and associated molecular pathology.
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PMID:Oxidative stress mediates air pollution particle-induced acute lung injury and molecular pathology. 1456 96

Understanding the mechanisms by which various types of air pollution particles (particulate matter, PM) mediate adverse health effects would provide biological plausibility to epidemiological associations of increased rates of morbidity and mortality. The majority of information regarding the means by which PM generates lung injury has been derived from in vitro studies. However, it is unclear as to what extent these mechanisms can be extrapolated to the in vivo situation. Current methods to assess mechanisms of PM-induced lung injury make it difficult to obtain site-specific, sensitive, and comprehensive determinations of cellular and molecular pathology associated with PM-induced injury. In the present study, the ability of laser capture microdissection (LCM) and protein microarray technologies were assessed to examine the effect of residual oil fly ash (ROFA) exposure on airway intracellular signaling pathways and transcription factor activation. Sprague-Dawley rats were intratracheally instilled with 0.5 mg/rat of ROFA. LCM was used to recover airway cells and protein extracts derived from the microdissected airways were analyzed by protein microarray. ROFA exposure increased p-ERK:ERK and p-I kappa B:I kappa B, suggesting changes in cell growth, transformation, and inflammation within the airway. These results are consistent with previously reported in vitro findings, demonstrating for the first time the credibility of applying LCM and protein microarray technologies to assess acute lung injury induced by environmental air pollutants.
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PMID:Application of laser capture microdissection and protein microarray technologies in the molecular analysis of airway injury following pollution particle exposure. 1520 40

This study has investigated a panel of immunomarkers in non-small cell lung carcinoma (NSCLC). Unsupervised hierarchical clustering analysis was used to investigate the possibility of identifying different subgroups in NSCLC based on their molecular expression profile rather than morphological features. A tissue microarray consisting of 284 cases of NSCLC was constructed. Immunohistochemistry was used to detect the presence of 18 biomarkers including synaptophysin, chromogranin, bombesin, NSE, GFI1, ASH-1, p53, p63, p21, p27, E2F-1, cyclin D1, Bcl-2, TTF-1, CEA, HER2/neu, cytokeratin 5/6, and pancytokeratin. Univariate analysis of all 18 markers for prognostic significance was performed. Immunohistochemical scoring data for NSCLC were analysed by unsupervised hierarchical clustering analysis. Kaplan-Meier survival curves were plotted for the different cluster groups of lung tumours identified by this method. Analysis of the three different World Health Organization (WHO) subtypes (adenocarcinoma, squamous cell carcinoma, large cell carcinoma) of NSCLC individually showed that different markers were significant in different subtypes. For example, p53 and p63 were significant for squamous cell carcinoma (p = 0.007 and p = 0.03, respectively), whereas cyclin D1 and HER2/neu were significant prognostic markers for adenocarcinoma (p = 0.025 and p = 0.015, respectively). These markers were not significant prognostic predictors for NSCLC as a group. Hierarchical clustering analysis of NSCLC produced four separate cluster groups, although the vast majority of cases were found in two cluster groups, one dominated by squamous cell carcinoma and the other by adenocarcinoma. The clinical outcomes of cases from the four cluster groups were not significantly different. Prognostic indicators vary between different morphological subtypes of NSCLC. Unsupervised hierarchical clustering analysis, based on an extended immunoprofile, identifies two main cluster groups corresponding to adenocarcinoma and squamous cell carcinoma; cases of large cell carcinomas are assigned to one of these two groups based on their molecular phenotype.
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PMID:Evaluation of immunohistochemical markers in non-small cell lung cancer by unsupervised hierarchical clustering analysis: a tissue microarray study of 284 cases and 18 markers. 1530 43

Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease characterized by left ventricular hypertrophy (LVH) predominantly affecting the interventricular septum. Cardiac myosin-binding protein C (cMyBP-C) mutations are common causes of FHC. Gene expression profiling was performed in left ventricles of 9-week-old wild-type mice, heterozygous cMyBP-C KO mice displaying asymmetric septal hypertrophy, and homozygous mice developing eccentric LVH. Knocking out one or two cMyBP-C genes leads primarily to gene expression changes indicating an increased energy demand, activation of the JNK and p38 parts of the MAPK pathway and deactivation of the ERK part, and induction of apoptosis. Altered gene expression for processes related to cardiac structure, contractile proteins, and protein turnover was also identified. Many of the changes were more pronounced in the homozygous KO mice. These alterations point to physiological and pathological adaptations in the prehypertrophic heterozygous KO mice and the hypertrophic homozygous mice.
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PMID:Altered myocardial gene expression reveals possible maladaptive processes in heterozygous and homozygous cardiac myosin-binding protein C knockout mice. 1806 Jul 37

Prognostic markers, such as NPM1, Flt3-ITD, and cytogenetic abnormalities have made it possible to formulate aggressive treatment plans for unfavorable acute myeloid leukemia (AML). However, the long-term survival of AML with unfavorable factors remains unsatisfactory. The latest data indicate that the standard dose of daunorubicin (DNR) at 45 mg/m2 is inferior to high dose 90 mg/m2 for induction therapy. The rates of complete remission and overall survival are significantly better in the high dose induction regimen. New regimens exploring the new liposomal encapsulation of Ara-C and DNR as well as addition of gemtuzumab ozogamicin monoclonal antibody have been studied. New agents, including the nucleoside analogues (clofarabine, sapacitabine, elacytarabine), FLT3 inhibitor (sorafenib), farnesyl-transferase inhibitor (tipifarnib), histone deacetylase inhibitor (vorinostat), lenalidomide, as well as DNA methyltransferase inhibitors (decitabine, azacitidine), were recently reported for AML treatment in the 2009 ASH annual meeting. This review also summarizes the updates of the clinical trials on novel agents including voreloxin, AS1413, behenoylara-C, ARRY520, ribavirin, AZD1152, AZD6244, and terameprocol (EM-1421) from the 2009 ASH annual meeting.
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PMID:Novel agents and regimens for acute myeloid leukemia: 2009 ASH annual meeting highlights. 2041 83

Noeggerathiales are a little known group of Carboniferous and Permian plants of uncertain systematic position that have been variously considered to be ferns, sphenopsids, progymnosperms, or a separate group. These heterosporous plants carry adaxial sporangia on leaf-like or disk-shaped sporophylls that form cones. Leaves are pinnate with a rather stiff appearance, and pinnules can be attached in either two or four rows. In the present report, we present the top of a noeggerathialean plant with leaves and strobili attached, Paratingia wudensis Wang, Pfefferkorn et Bek sp. nov., from an earliest Permian volcanic ash fall tuff in Inner Mongolia. The excellent preservation allows the reconstruction of the whole plant, the complex three-dimensional leaves with anisophyllous pinnules, the heterosporous strobili, and the spores in situ. The homology of leaves and strobili can be elucidated and contributes to an understanding of the debated taxonomic position of Noeggerathiales. The "anisophyllous" leaves carry pinnules arranged in four rows. The strobili are bisporangiate and have disk-shaped sporophylls, each with one ring of 10-14 adaxial sporangia around the strobilus axis. Megaspores have an equatorial bulge. This new species expands the known diversity of Noeggerathiales. It grew in a peat-forming forest, thus changing earlier interpretations of the growth of noeggerathialean plants with anisophyllous pinnules.
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PMID:Paratingia wudensis sp. nov., a whole noeggerathialean plant preserved in an earliest Permian air fall tuff in Inner Mongolia, China. 2162 54


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