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)

Amplification of oncogenes in primary tumours may have prognostic and/or therapeutic significance for patients with breast cancer. We have studied HER2/neu and c-myc amplification together with steroid receptors in human primary breast tumours and related the outcome with (relapse-free) survival. A strong inverse correlation was found between HER2/neu amplification and the presence of oestrogen and progesterone receptors. Actuarial 5-years survival showed that breast cancer patients with c-myc amplification in their primary tumours experience a shorter relapse-free survival, especially in node-negative and in receptor-positive tumours, whereas HER2/neu amplification may be of prognostic value for overall survival in receptor-negative tumours. Overall, in our hands, c-myc amplification appeared to be a more potent prognosticator than HER2/neu amplification in human primary breast cancer.
J Steroid Biochem Mol Biol 1992 Sep
PMID:Prognostic factors in human primary breast cancer: comparison of c-myc and HER2/neu amplification. 135 12

The genes encoding the regulatory subunits RI beta (locus PRKAR1B) and RII beta (locus PRKAR2B) of human cAMP-dependent protein kinase have been mapped in the basic CEPH (Centre d'Etude du Polymorphisme Humain) family panel of 40 families to chromosome 7p and 7q, respectively, using the enzymes HindIII and BanII recognizing the corresponding restriction fragment length polymorphisms (RFLPs). Previous data from the CEPH database and our present RFLP data were used to construct a six-point local framework map including PRKAR1B and a seven-point framework map including PRKAR2B. The analysis placed PRKAR1B as the most distal of the hitherto mapped 7p marker loci and resulted in an unequivocal order of pter-PRKAR1B-D7S21-D7S108-D7S17-D7S149- D7S62-cen, with a significantly higher rate of male than female recombination between PRKAR1B and D7S21. The 7q regulatory gene locus, PRKAR2B, could also be placed in an unambigous order with regard to the existing CEPH database 7q marker loci, the resulting order being cen-D7S371-(COL1A2,D7S79)-PRKAR2B-MET-D7S87++ +-TCRB-qter. Furthermore, in situ hybridization to metaphase chromosomes physically mapped PRKAR2B to band q22 on chromosome 7.
Genomics 1992 Sep
PMID:Mapping of the regulatory subunits RI beta and RII beta of cAMP-dependent protein kinase genes on human chromosome 7. 135 99

Kinins and substance P have been implicated in the pathogenesis of inflammatory arthritis by virtue of their abilities to induce vasodilation, edema, and pain. The relative biological potencies of these peptides in vivo would depend at least in part upon their rates of catabolism in the joint. We hypothesized that human synovial lining cells may regulate intraarticular levels of kinins and neuropeptides via degradation by cell surface-associated peptidases. We exposed intact human synovial fibroblasts to kinins and substance P, in the presence or absence of specific peptidase inhibitors, and measured the amount of intact substrate remaining and degradation product(s) generated over time. Aminopeptidase M (AmM; EC 3.4.11.2), neutral endopeptidase-24.11 (NEP-24.11; EC 3.4.24.11), and dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5) were identified on the cell surface of synovial cells. Bradykinin degradation was due entirely to NEP-24.11 (1.39 +/- 0.29 nmol/min per well). Lysylbradykinin was also degraded by NEP-24.11 (0.80 +/- 0.19 nmol/min per well); however, in the presence of phosphoramidon, AmM-mediated conversion to bradykinin (3.74 +/- 0.46 nmol/min per well) could be demonstrated. The combined actions of NEP-24.11 (0.93 +/- 0.15 nmol/min per well) and DAP IV (0.84 +/- 0.18 nmol/min per well) were responsible for the degradation of substance P. AmM (2.44 +/- 0.33 nmol/min per well) and NEP-24.11 (1.30 +/- 0.45 nmol/min per well) were responsible for the degradation of the opioid peptide, [Leu5]enkephalin. The identity of each of the three peptidases was confirmed via synthetic substrate hydrolysis, inhibition profile, and immunological identification. The profiles of peptidase enzymes identified in cells derived from rheumatoid and osteoarthritic joints were identical. These data demonstrate the human synovial fibroblast to be a rich source of three specific peptidases and suggest that it may play a prominent role in regulating peptide levels in the joint.
J Clin Invest 1992 Sep
PMID:Cultured human synovial fibroblasts rapidly metabolize kinins and neuropeptides. 138 26

The majority of infants born to HIV-positive mothers are not infected in utero, suggesting that the pregnancy factors produced by fetal trophoblasts may provide protection against HIV-1 infection. Except for steroid female hormones, little is known of other pregnancy factors that may regulate either resistance or susceptibility to HIV-1. Human chorionic gonadotropin (hCG)--the major glycoprotein produced by the placental trophoblast throughout the pregnancy--was tested on reverse transcriptase activity in HIV-infected ACH-2 lymphocytes and U1 monocytes. The results suggest that low non-cytotoxic doses of hCG (0.01-1.0 IU range) may inhibit viral replication in maternal blood cells.
FEMS Microbiol Lett 1992 Sep 01
PMID:Effect of human chorionic gonadotropin (hCG) on reverse transcriptase activity in HIV-1 infected lymphocytes and monocytes. 138 34

In an effort to generate a more complete bovine syntenic map of Type I comparative anchor loci, seven homologs to genes found on HSA5 were mapped using a panel of bovine x rodent hybrid somatic cells. Five HSA5 genes, CSF2, RPS14, PDGFRB, FGFA, and CSF1R, were assigned to bovine syntenic group U22 (chromosome 7), while two others, C9 and HGMCR, mapped to U10 and U5, respectively. Previous studies had assigned the HSA5 marker SPARC to bovine syntenic group U22. The mapping of genes spanning the length of HSA5 in cattle and also in mouse permits syntenic comparisons between prototypic genomes of three mammalian orders, providing insight into the evolutionary history of this region of the ancestral mammalian genome.
Genomics 1992 Sep
PMID:Synteny mapping in the bovine: genes from human chromosome 5. 138 98

Psychopathy ratings that employed the PCL-R (Hare, 1985, 1991) were compared in one clinical and three research samples (total N = 285). Differences among the samples were not related to whether ratings were completed under the expressed promise of confidentiality of a research context vs. a pre-parole psychological assessment. The problem of decision errors in prediction is highlighted to address the difficulty in integrating the PCL-R into correctional policy. General issues related to the clinical application of the PCL-R also are discussed.
J Clin Psychol 1992 Sep
PMID:The clinical application of the Psychopathy Checklist-Revised (PCL-R) in a prison population. 140 Nov 49

The purposes of this study were to evaluate (a) the effects of step rate and upper body support on the VO2 and HR responses to fixed work rates on the StairMaster 4000 (SM), (b) the accuracy of the SM settings, and (c) how HR compared with that measured during grade-walking on a treadmill. Six subjects worked at a slow step rate for 6 min and then a faster step rate for the last 6 min of a 12-min test at SM settings of 4, 7, and 10 METs. Gas exchange and HR measurements were made at minutes 4-6 and 10-12. Variations in step rate had no effect on HR (P = 0.45) or VO2 (P = 0.84). The effect of using the arms and hands for support was studied using 6 subjects who worked for 12 min at 4, 7, and 10 METs; the first 6 min without support, and the second 6 min with support. Support resulted in lower HR (P = 0.017) and VO2 (P = 0.002) values at 10 METs. The measured MET values were about 20% lower than those specified by machine settings: True MET values = 0.556 + 0.745 (SM setting). Finally, at the same VO2, systematically higher (7-11 b.min-1) HR values were observed for the SM relative to the treadmill.
Med Sci Sports Exerc 1992 Sep
PMID:Factors affecting the oxygen cost of stepping on an electronic stepping ergometer. 140 90

Vascular endothelial cell growth factor (VEGF), also known as vascular permeability factor, is an endothelial cell mitogen which stimulates angiogenesis. Here we report that a previously identified receptor tyrosine kinase gene, KDR, encodes a receptor for VEGF. Expression of KDR in CMT-3 (cells which do not contain receptors for VEGF) allows for saturable 125I-VEGF binding with high affinity (KD = 75 pM). Affinity cross-linking of 125I-VEGF to KDR-transfected CMT-3 cells results in specific labeling of two proteins of M(r) = 195 and 235 kDa. The KDR receptor tyrosine kinase shares structural similarities with a recently reported receptor for VEGF, flt, in a manner reminiscent of the similarities between the alpha and beta forms of the PDGF receptors.
Biochem Biophys Res Commun 1992 Sep 30
PMID:Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. 141 31

Genes homologous to those located on human chromosome 4 (HSA4) were mapped in the bovine to determine regions of syntenic conservation among humans, mice, and cattle. Previous studies have shown that two homologs of genes on HSA4, PGM2 and PEPS, are located in bovine syntenic group U15 (chromosome 6). The homologous mouse genes, Pgm-1 and Pep-7, are on MMU5. Using a panel of bovine x hamster hybrid somatic cells, we have assigned homologs of 11 additional HSA4 loci to their respective bovine syntenic groups. D4S43, D4S10, QDPR, IGJ, ADH2, KIT, and IF were assigned to syntenic group U15. This syntenic arrangement is not conserved in the mouse, where D4s43, D4s10, Qdpr, and Igj are on MMU5 while Adh-2 is on MMU3. IL-2, FGB, FGG, and F11, which also reside on MMU3, were assigned to bovine syntenic group U23. These data suggest that breaks and/or fusions of ancestral chromosomes carrying these genes occurred at different places during the evolution of humans, cattle, and mice.
Genomics 1992 Sep
PMID:Synteny mapping in the bovine: genes from human chromosome 4. 142 20

Breast cancer is the most common malignant tumor among women, comprising an estimated 24% of all cancer cases and 18% of all cancer deaths. At least half of the patients with primary breast cancer will ultimately die by metastatic disease. The tumor characteristics, the natural course of the disease and the response to therapy vary strongly. A number of recently detected cell biological parameters such as oncogenes/suppressor genes, growth factors and secretory proteins are more or less important prognostic factors, because they influence the characteristics and behavior of a tumor with respect to metastatic pattern, extent of cellular differentiation, growth rate and response to treatment. However, there is no clear consensus how best to identify patients at high or low risk. In our experience c-myc amplification and pS2 protein are strong prognosticators for relapse rate, while in advanced disease (apart from a negative estrogen/progesterone receptor/pS2 status) amplification of HER2/neu is a good prognosticator for failure to endocrine therapy. In the diagnosis of breast cancer, in vivo imaging of tumors by labeled hormones or other factors also forms a new development which might have implications for treatment too. With respect to treatment both endocrine and chemotherapy can cure a minority of patients with micrometastases, but in patients with advanced disease only a prolongation of (progression-free) survival can be reached. Response rates decrease with increasing tumor load. In the past decade a number of interesting new endocrine agents has been developed such as new (pure) (anti)steroidal agents, vitamins, aromatase inhibitors, analogs of peptide hormones, prolactin inhibitors and growth factor antagonists. However, less is known on the (potential) interaction between hormones, chemotherapeutic agents, retinoids, cytokins, growth factor antagonists and irradiation. Rapid detection of new powerful combination therapies are needed to improve treatment results during the nineties.
J Steroid Biochem Mol Biol 1992 Sep
PMID:Clinical breast cancer, new developments in selection and endocrine treatment of patients. 144 97


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