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)

We have studied mRNA levels for a variety of growth factors in biopsy specimens from malignant, benign and normal breast tissue. We found TGFb mRNA in all breast cancers and neoplastic breast tissues but the level of the TGFb mRNA were found to be higher in breast cancer (P = 0.01). TGFa mRNA was detected in a similar proportion of cancers as in neoplastic breast tissues but the TGFa receptor EGFR mRNA was detected in only 55% of breast cancers but in all non-neoplastic breast tissue tested. The presence of EGFR mRNA was inverted related to oestrogen receptor status and coexpression of TGFa and EGFR was observed in 28% of carcinomas, and significantly more commonly in ER negative tumours (P = 0.01). PDGF a and b chain transcripts coexisted in all normal and malignant breast tissue. Insulin-like growth factor II mRNA was present in all 15 samples of non-malignant breast tissue but in only 11 of 21 (52%) of carcinomas.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Growth factor expression in breast tissue. 228 95

To study the roles of substance P and endogenous neutral endopeptidase in mediating cough, we measured cough responses in awake guinea pigs in response to exogenous substance P and capsaicin aerosols in the presence and absence of the neutral endopeptidase inhibitors leucine-thiorphan and phosphoramidon. Substance P stimulated cough in very low concentrations (10(-17)-10(-16) M). In a second study where the investigator did not know whether substance P or diluent alone was aerosolized, substance P (10(-16) M) caused cough. Leucine-thiorphan (10(-5) M) and phosphoramidon (10(-5) M) potentiated substance P-induced cough; NEP inhibitors also potentiated capsaicin-induced cough significantly. These findings suggest that substance P is a potent stimulator of cough responses, that capsaicin-induced cough is mediated by substance P or another similar neuropeptide, and that cough responses are modulated by endogenous neutral endopeptidase.
J Clin Invest 1988 Dec
PMID:Neutral endopeptidase inhibitors potentiate substance P- and capsaicin-induced cough in awake guinea pigs. 246 67

The electropermeabilization (EPN) of living cells allows the uptake of non-permeant molecules and can reveal their potential activity on cells without the constraints of the plasma membrane crossing. We decided to compare the cytotoxicity of some anticancer drugs on electropermeabilized (EP) and non-permeabilized (NEP) cultured DC-3F cells exposed to the drugs for a short time. After EPN, the increase in cytotoxicity varies between 1 and more than 700 times, depending on the usual cell uptake pathway of a given drug. The most relevant increase of toxicity was observed with molecules such as netropsin (200-fold) and bleomycin (700-fold) which in ordinary conditions weakly diffuse through the plasma membrane. Only a 3-5-fold increase of the cytotoxicity was observed with lipophilic drugs able to rapidly diffuse through the plasma membrane (actinomycin D, NMHE) both in the case of drug-sensitive and resistant cell strains. This increased toxicity is clearly related to a facilitated uptake because, after electropermeabilization, the effects of melphalan (a drug which enters intact cells via leucine transporters) are not modulated by the external leucine concentration. Thus, EPN enables us to reveal the intrinsic toxicity of hydrophilic molecules which have a limited access to their intracellular targets. We propose that EPN can be used as a novel screening procedure of new cytotoxic molecules which could be modified thereafter in order to facilitate their cellular uptake.
Biochem Pharmacol 1988 Dec 15
PMID:Transient electropermeabilization of cells in culture. Increase of the cytotoxicity of anticancer drugs. 246 23

N-terminal as well as internal amino acid sequence data were obtained from the GH dependent, insulin-like growth factor (IGF) binding protein, BP-53, purified from human plasma. Based on these sequence data, full-length cDNA clones of BP-53 have been isolated, and the complete deduced sequence of BP-53 determined. This sequence contains a 27 amino acid putative signal sequence followed by a mature protein of 264 amino acids containing 18 cysteine residues clustered near the N- and C-terminus. The deduced protein sequence of BP-53 has 33% amino acid identity including conservation of all 18 cysteine residues with the recently cloned BP-28, a smaller human IGF-binding protein identified in amniotic fluid and also secreted by the cell line HEP G2. Expression of the cloned BP-53 cDNA in mammalian tissue culture cells results in secretion of the protein into the culture medium. This expressed protein is identical to plasma-derived BP-53 in its immunoreactivity, high affinity binding of IGF-I and IGF-II, and mobility on sodium dodecyl sulfate gel electrophoresis.
Mol Endocrinol 1988 Dec
PMID:Cloning and expression of the growth hormone-dependent insulin-like growth factor-binding protein. 246 30

A new endothelial cell growth factor (f-ECGF) was partially purified from the cultured medium of human fibroblast cells of embryonic lungs. The partially purified f-ECGF induced neovascularization in rabbit cornea. It showed a selective growth stimulatory activity on the endothelial cells in vitro, whereas acidic- and basic-fibroblast growth factors (a- and b-FGFs) showed a broad spectrum of growth stimulation among tissues or cells. f-ECGF did not compete with the binding of a-FGF to the cell surface receptor in HEP-G2 hepatoblastoma cell lines. These results indicated that f-ECGF is a new endothelial cell growth factor distinct from a- and b-FGFs which are known to be potent endothelial cell growth factors.
Cell Struct Funct 1989 Dec
PMID:Characterization of a new endothelial cell growth factor (f-ECGF) partially purified from the supernatant of human fibroblast cells. 248 61

Effect of prostacyclin analogue, beraprost sodium (Sodium (+/-)-(1R*, 2R*, 3aS*, 8bS*)-2, 3,3a,8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen+ ++-6- ynyl]-1H-cyclopenta-[b]benzofuran-5-butyrate, TRK-100), on the cardiovascular system of the anesthetized dog was investigated. TRK-100 was injected intra-arterially and intravenously to study the vasodilating effect of the drug by a magnetic flow meter. Intra-arterial injection of TRK-100 augmented blood flow of vertebral, coronary, renal, supramesenteric, hepatic and femoral artery at a dose range of 0.0003 to 3,000 micrograms/bed. The threshold doses of TRK-100 and PGI2 in the mesenteric artery were 0.003 micrograms and 0.0003 micrograms, respectively, and the same values were obtained in the splenic artery. Those were slightly lower than those of other arteries. Intravenous injection of TRK-100 augmented mesenteric and renal arterial flow to 193 +/- 30% and 118 +/- 4%, respectively. In this system augmentation of mesenteric and renal arterial flow was 179 +/- 19% and 135 +/- 1%, respectively, while vertebral, carotid, and femoral arterial flow decreased, respectively, to 71.4 +/- 2.1%, 80.0 +/- 9.4% and 61.4 +/- 5.6% by TRK-100 and 70.6 +/- 5.6%, 79.5 +/- 6.9% and 67.1 +/- 4.7% by PGI2. Inhibitory effects on heart functions such as cardiac output, left ventricular pressure, LV dP/dt, oxygen consumption, and cardiac work were seen. The effect was similar to PGI2. Coronary vascular resistance, total peripheral resistance and systemic blood pressure were also decreased by TRK-100 and PGI2.
Nihon Yakurigaku Zasshi 1989 Dec
PMID:[Cardiovascular effects of beraprost sodium (TRK-100), a prostacyclin analogue in the dog]. 251 28

The effects of the cardioplegic solution HTK on membrane potential (EM) and intracellular K and Na activities (aiK, aiNa) were studied in sheep cardiac Purkinje fibres by means of conventional and ion-selective microelectrodes. HTK contains (mM): Na 15, K 10, Ca 0, Mg 4, histidine 180. (1) In control conditions EM was -74.3 +/- 3.3 mV (n = 25), aiK was 116.4 +/- 4.1 mM (n = 7) and aiNa was 8.2 +/- 1.4 mM (n = 15). (2) Exposure to HTK led to a depolarization to -59.7 +/- 3.6 mV (n = 25) which exceeded by about 5-7 mV that induced in a Tyrode solution of 10 mM K and in a modified HTK solution supplemented by 2 mM Ca (n = 6). (3) Addition of 0.5 mM barium eliminated the difference in the steady-state depolarization. (4) HTK superfusion increased aiK to 120.1 +/- 4.4 mM (n = 7) and decreased aiNa to 3.9 +/- 0.9 mM (n = 15). (5) The decrease in aiNa was insensitive to amiloride (1 mM) and to external alkalization but was slightly increased by addition of 2 mM calcium. (6) When the calcium in Tyrode solution was lowered from 2.0 mM to 0.05 mM, aiNa hardly decreased during subsequent exposure to unmodified HTK and it increased in the presence of 0.1 mM dihydroouabain. We propose the hypothesis (1) that the difference in membrane depolarization between HTK and a 10 mM K-Tyrode is caused by a decrease in K conductance by the HTK solution and (2) that the aiNa decline mainly results from a coupled Ca influx via Na-Ca exchange due to a delayed washout of external calcium.
Pflugers Arch 1989 Dec
PMID:The cardioplegic solution HTK: effects on membrane potential, intracellular K+ and Na+ activities in sheep cardiac Purkinje fibres. 251 7

The kil gene encoded in bacteriophage Mu DNA was previously shown to reside between the end of the B gene at 4.3 kb and the EcoRI site at 5.1 kb from the left end. To precisely map the kil gene within this region, two series of BAL-31 deletion derivatives were created: one removed Mu DNA rightward from the Hpal site (4.2 kb) and the other removed Mu DNA leftward from the EcoRI site. The deleted Mu DNA was subcloned into the expression vector pUC19 under lac promoter control and tested for the expression of the killing function following IPTG induction. Using DNA sequencing analysis, the Mu DNA in Kil+ and Kil- clones was precisely determined, and the kil gene was mapped to the first open reading frame beyond the B gene. The expression of the kil gene was sufficient to induce dramatic morphological changes: cells became enlarged and predominantly spherical, reminiscent of the phenotype of certain cell mutants.
Virology 1989 Dec
PMID:Identification of the bacteriophage Mu kil gene. 253 53

Neutral endopeptidase (NEP, EC 3.4.24.11), purified from renal brush border, cleaves the Cys7-Phe8 amide bond of rat atrial natriuretic peptide (ANP), to generate the inactive metabolite (ANP cleaved at the Cys7-Phe8 bond; x-ANP). To determine if NEP contributes to the inactivation of circulating ANP, we investigated the degradation of rat ANP (rANP, 1-28) in the vasculature. Formation of x-ANP from exogenous ANP was studied in a mesenteric arterial preparation by perfusion in a single pass system in the presence and absence of the NEP inhibitors, thiorphan or phosphoramidon. In addition, a purified membrane fraction was prepared from mesenteric arterial homogenate and compared with an equivalent renal membrane fraction. Formation of x-ANP was quantified by a specific immunoassay (ELISA). Renal and vascular membranes shared the same pH optima for x-ANP formation (pH 7.5), although x-ANP generation was considerably greater in renal vs. vascular membranes (31.6 and 0.4 nmol min-1 mg-1 of protein, respectively). Both preparations were inhibited in a similar, dose-dependent manner by phosphoramidon, thiorphan or a polyclonal antibody to NEP. In perfused mesenteric arteries, 1.6 +/- 0.8 pmol of x-ANP were generated from 1 microgram of ANP; this formation was inhibited 51% by 10 microM phosphoramidon or thiorphan. Plasma levels of x-ANP after bolus i.v. administration of rANP in rats, were inhibited (70-80%) by thiorphan at comparable doses to those used in perfused mesenteric arteries. These studies indicate that ANP is degraded in the vasculature by NEP or an "NEP-like" enzyme(s).
J Pharmacol Exp Ther 1989 Dec
PMID:Rat vascular tissue contains a neutral endopeptidase capable of degrading atrial natriuretic peptide. 253 52

The herpes simplex virus transactivator, alpha TIF, stimulates transcription of the alpha/immediate early genes via a cis-acting site containing an octamer element and a conserved flanking sequence. The alpha TIF protein, produced in a baculovirus expression system, nucleates the formation of at least two DNA--protein complexes on this regulatory element. Both of these complexes contain the ubiquitous Oct-1 protein, whose POU domain alone is sufficient to allow assembly of the alpha TIF-dependent complexes. A second member of the POU domain family, the lymphoid specific Oct-2 protein, can also be assembled into similar complexes at high concentrations of alpha TIF protein. These complexes contain at least two cellular proteins in addition to Oct-1. One of these proteins is present in both insect and HeLa cells and probably recognizes sequences in the cis element. The second cellular protein, only present in HeLa cells, probably binds by protein-protein interactions.
EMBO J 1989 Dec 20
PMID:The octamer-binding proteins form multi-protein--DNA complexes with the HSV alpha TIF regulatory protein. 255 66


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