Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fourteen patients with cerebral gliomas were studied with positron emission tomography (PET) using L-[methyl-11C]methionine (11C-MET). Positive images of tumour were obtained in all cases regardless of histological grades. The analysis of differential absorption ratio (DAR) showed the higher accumulation of 11C-MET in high grade gliomas than in low grade gliomas. PET study with 11C-MET will be of great value not only in delineating the location of gliomas, but also in making a qualitative diagnosis from the view point of the biological properties of gliomas.
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PMID:The accumulation of 11C-methionine in cerebral glioma patients studied with PET. 238 94

The interferons (IFNs) have been shown to be antagonistic to the growth stimulatory effects of mitogens on cultured cells. A report of the interactions of IFN-beta and platelet-derived growth factor on BALB/c-3T3 mouse cells established that IFN itself induced the secretion of a limited number of proteins from this cell line. The present work was undertaken to determine if other murine cell lines treated with homologous IFN-beta also secreted new or additional protein(s) in response to this agent and if this response correlated with other phenotypic properties of the cells. The cell lines examined included L929 cells and two derivatives of this line (GM347 and WDIFN), CAK-TK-, Swiss-3T3, and BALB/c-3T3. Each line was exposed to [35S]methionine in the absence and in the presence of IFN-beta, the supernatant fluids collected, and the radioactive, secreted proteins examined by fluorography after electrophoresis through SDS-containing polyacrylamide gels. Two cell lines (GM347 and Swiss-3T3) did not appear to secrete new or additional proteins after IFN treatment. However, four lines (L929, WDIFN, CAK-TK-, and BALB/c-3T3) did secrete new or additional proteins in response to IFN. Thus IFN-induced secretion of protein appeared to be a common but not universal phenomenon. In addition, although the number and apparent size(s) of the IFN-induced, secreted proteins were different in these various lines, one protein (Mr = 89-90,000) appeared to be secreted by each of them. In this respect it was unique. Moreover the IFN-induced secretion of protein did not appear to correlate with the antiviral or antiproliferative effects of IFN.
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PMID:Effect of interferon on secretion of proteins by various murine cell lines. 245 71

To evaluate the hypothesis of alpha-antagonism as a contributing factor to the vascular action of calcium entry blockade (CEB) in man, we have compared the action of verapamil, a CEB, on nonselective (norepinephrine, NE) and selective alpha 1-(methoxamine, MET) and alpha 2-(B-HT 933, BHT) adrenergic agonists in human forearm vasculature. All drugs were infused into the brachial artery at systemically ineffective rates. Blood pressure and heart rate were continuously monitored; forearm blood flow was measured through strain gauge plethysmography. Sixteen mild, untreated hypertensive patients were studied. Cumulative forearm blood flow dose-response curves to three cumulative infusion rates (3 min each) of NE (0.015, 0.05, 0.15 micrograms/100 ml tissue/min), MET (0.06, 0.6, 6 micrograms/100 ml tissue), and BHT (3, 10, 30 micrograms/100 ml tissue/min) were obtained during saline and after verapamil (0.9 micrograms/100 ml tissue/min X 15 min) infusion. Verapamil did not modify to any significant extent NE-mediated vasoconstriction, but clearly blunted the vascular action of either MET or BHT. Because NE is the physiological neurotransmitter, the data cast doubts about the relevance of alpha-antagonism as a mechanism of action of calcium entry blockade through verapamil. Besides, the data caution against generalizing by using data obtained through several compounds, including CEBs, of alpha-adrenergic stimuli.
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PMID:Verapamil and alpha-mediated vasoconstriction in human forearm: a comparison between norepinephrine and selective alpha 1- and alpha 2-adrenergic agonists. 245 39

An investigation was undertaken to evaluate the effect of both photoinitiators (camphor-quinone-amine systems) and the adhesion promoting monomer (4-MET) on photopolymerization of bonding liners and their adhesion to dentin. Photopolymerization of bonding liners was measured with differential scanning calorimetry (DSC). The bonding liner containing 2-(dimethylamino)ethyl methacrylate (DMAEMA) as a reducing agent decreased the rate of polymerization in the presence of 4-MET. On the other hand, the bonding liners containing N-phenylglycine (NPG) and N,N-dimethylaniline derivatives as a reducing agent showed good polymerization in the presence of 4-MET. The results of the tensile bond test suggested that bonding liners containing NPG and 4-(dimethylamino)benzoic acid (DMABA), one of the N,N-dimethylaniline derivatives, with or without 4-MET bonded well to dentin treated with EDTA 3-2. NPG and DMABA are recommended not only as reducing agents but also as aids in the diffusion of monomers into the dentin substrate. The relationship between the strength of the bond to dentin and photoirradiation of the bonding liner and composite resin was studied. Elongation of photoirradiation of both the bonding liner and composite resin was effective in impacting the strength of the bond to dentin. Furthermore, sufficient photoirradiation of the bonding liner prior to any filling of composite resin was especially important to obtain high bond strengths. SEM and TEM observations supported good adhesion being achieved by hybrid formations between photocurable bonding liners and dentin.
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PMID:[Formulation of photocurable bonding liner and adhesion to dentin. Effect of photoinitiator, monomer and photoirradiation]. 248 1

The human INT1L1 gene, which exhibits homology to the protooncogene INT1 is very closely linked to the MET gene and cystic fibrosis locus on human chromosome 7. In the present study we have isolated overlapping genomic clones that correspond to the mouse homolog of the INT1L1 gene and have used the cloned DNA as probes to examine the distribution of the mouse INT1L1 gene within a series of 35 mouse-hamster somatic cell hybrids. These analyses have localized the INT1L1 gene to mouse chromosome 6. In addition, we demonstrate that the mouse INT1L1 and MET genes are coamplified in lines of spontaneously transformed mouse NIH3T3 cells, indicating that these genes may remain closely linked within the mouse genome.
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PMID:Molecular cloning and localization to chromosome 6 of mouse INT1L1 gene. 253 31

Anti-insulin receptor monoclonal antibody MA-10 inhibits insulin receptor autophosphorylation of purified rat liver insulin receptors without affecting insulin binding (Cordera, R., Andraghetti, G., Gherzi, R., Adezati, L., Montemurro, A., Lauro, R., Goldfine, I. D., and De Pirro, R. (1987) Endocrinology 121, 2007-2010). The effect of MA-10 on insulin receptor autophosphorylation and on two insulin actions (thymidine incorporation into DNA and receptor down-regulation) was investigated in rat hepatoma Fao cells. MA-10 inhibits insulin-stimulated receptor autophosphorylation, thymidine incorporation into DNA, and insulin-induced receptor down-regulation without affecting insulin receptor binding. We show that MA-10 binds to a site of rat insulin receptors different from the insulin binding site in intact Fao cells. Insulin does not inhibit MA-10 binding, and MA-10 does not inhibit insulin binding to rat Fao cells. Moreover, MA-10 binding to down-regulated cells is reduced to the same extent as insulin binding. In rat insulin receptors the MA-10 binding site has been tentatively localized in the extracellular part of the insulin receptor beta-subunit based on the following evidence: (i) MA-10 binds to insulin receptor in intact rat cells; (ii) MA-10 immunoprecipitates isolated insulin receptor beta-subunits labeled with both [35S]methionine and 32P; (iii) MA-10 reacts with rat insulin receptor beta-subunits by the method of immunoblotting, similar to an antipeptide antibody directed against the carboxyl terminus of the insulin receptor beta-subunit. Moreover, MA-10 inhibits autophosphorylation and protein-tyrosine kinase activity of reduced and purified insulin receptor beta-subunits. The finding that MA-10 inhibits insulin-stimulated receptor autophosphorylation and reduces insulin-stimulated thymidine incorporation into DNA and receptor down-regulation suggests that the extracellular part of the insulin receptor beta-subunit plays a role in the regulation of insulin receptor protein-tyrosine kinase activity.
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PMID:An extracellular domain of the insulin receptor beta-subunit with regulatory function on protein-tyrosine kinase. 254 82

The cloning and sequencing of the oncogene of the avian erythroblastosis virus S13 is described. The oncogene, termed v-sea, was found to be another member of the protein-tyrosine kinase gene family. The oncogene was fused in frame with the retrovirus S13 envelope gene, thus generating a fusion protein with a structure resembling that of a growth factor receptor. Sequence comparisons revealed that the v-sea gene was most closely related to the insulin receptor family of protein-tyrosine kinases, the greatest similarity being with the human MET oncogene.
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PMID:The v-sea oncogene of avian erythroblastosis retrovirus S13: another member of the protein-tyrosine kinase gene family. 254 51

A panel of seven murine monoclonal antibodies reactive with human hepatocellular carcinoma (HCC) cell line, SK- HEP-1, resulted in the definition of four distinct antigen systems, designated HB4, HB5, HB1 and HJ2. HB4 antigen was found to be expressed specifically on HCC cell lines and fresh HCC specimens but not on normal liver. Immunoprecipitation tests suggest that the HB4 epitope may be a heat-stable carbohydrate determinant on a high molecular mass molecule. HB5 antigen was found to have less-restricted expression on a panel of normal adult tissues and on melanoma, astrocytoma, sarcoma, neuroblastoma and epithelial cancer cell lines. In fetal and adult liver, HB5 antigen localized to bile canaliculi and ducts. Under reducing conditions, three mAbs detected a Mr 140,000 glycoprotein using lysates of [125-I], [3-H]-glucosamine and [35-S]-methionine labeled SK-HEP-1 cells. Under non-reducing conditions an additional component of greater than Mr 200,000 was also detected. HB1 antigen was found on almost all monolayer cell lines and not on most cultured suspension cells. This antigen was also detected on cultured HCC cells inoculated into nu/nu mice. Immunoprecipitation experiments revealed that the HB1 antigen is a bimolecular complex with an Mr 170,000 alpha chain and Mr 130,000 beta chain under non-reducing conditions, and three subunits of Mr 140,000, Mr 30,000 and Mr 130,000 under reducing conditions. Two antibodies reacted with epitopes on the alpha chain. HJ2 antigenic determinant is a heat-stable component which could not be immunoprecipitated. This most widely expressed antigen was found in secreted form in many of the cells and tissues examined. These antibodies introduce new antigens which may serve as useful markers for the diagnosis, classification and investigation of HCC and other liver diseases.
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PMID:Serological analysis and biochemical characterization of monoclonal antibodies defining antigens of human hepatocellular carcinoma. 255 3

Strong linkage disequilibrium (LD) was found between DNA marker XV2c and the cystic fibrosis (CF) locus (delta = 0.46) and between DNA marker KM19 and CF (delta = 0.67) in 157 CF and 138 normal chromosomes from U.S. Caucasians. DNA haplotypes with nine polymorphic sites were created in 54 Caucasian families. There is a strong LD between the haplotypes and the presence of the mutant CF genes. This implies that the DNA polymorphisms examined are close to the CF gene and that one mutation of the CF gene predominates in the Caucasian population. Haplotype analysis can also be used to refine estimates of CF carrier risk in Caucasians. Data for XV2c and MET markers in 16 American black patients and their families revealed a different haplotype distribution and LD pattern with the CF locus. These data suggest that racial admixture alone does not explain the occurrence of CF in American blacks and that multiple alleles of the CF gene may exist in this population.
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PMID:Analysis of DNA polymorphism haplotypes linked to the cystic fibrosis locus in North American black and Caucasian families supports the existence of multiple mutations of the cystic fibrosis gene. 256 31

In the 100-year period 1880-1980 the Hutterite population increased from about 442 to 23,000 individuals in North America. There are three endogamous subdivisions in this Caucasian genetic isolate. A total of 11 cystic fibrosis (CF) families from Canada and the United States were investigated, including at least two families from each of the three subdivisions, the Dariusleut, Lehrerleut, and Schmiedeleut. A study of RFLPs for the loci D7S8, D7S23, MET, and D7S18 (also called D7S16) in the region of the CF gene in 10 families shows considerable genetic variability. There were three different extended CF gene-region haplotypes on CF chromosomes (CF haplotypes), and there were 13 different extended CF gene-region haplotypes on normal chromosomes (normal haplotypes). The three CF haplotypes have different D7S23 and MET haplotypes. Parents who have the same CF haplotype are, on the average, more closely related than parents who have different haplotypes, but only within the same subdivision. A marriage node graph of 11 families illustrates the complexity of Hutterite genealogies. The frequency distribution of CF haplotypes in the Hutterite sample differs notably from those of larger agglomerates of family data from collaborative studies, with respect to D7S8, MET haplotypes, and D7S23 haplotypes. We propose that there were at least three CF carriers among the founders of the Hutterite population and that copies of a particular CF haplotype in current individuals are identical by descent. The alternative that one or more genetically distinguishable CF haplotypes resulted from recombination since the founding of the population is considered to be less likely.
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PMID:Genealogical analysis of cystic fibrosis families and chromosome 7q RFLP haplotypes in the Hutterite Brethren. 256 32


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