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)

The simple determination of the Neutral Metalloendopeptidase (NEP, Enkephalinase A) with the known fluorogenic substrate Dansyl-D-Ala-Gly-(pNO2)Phe-Gly is disturbed by high concentrations of the Angiotensin-Converting-Enzyme (ACE). ACE hydrolyzes this substrate too but to a smaller degree. In some tissues and body fluids a further substrate hydrolysis takes place by any indefinite proteases. Finally the enzymatic hydrolysis of the NEP-substrate is inhibited by phosphate ions. A method is proposed for the elimination of this disturbances in the NEP-determination with a phosphate-free buffer using two comparison tests with Lisinopril and o-Phenanthroline. The resulting NEP-activity is calculated very simple thereafter.
Pharmazie 1988 Sep
PMID:[The determination of neutral metalloendopeptidase (enkephalinase A) in biological material]. 285 71

A comparative study of the metabolic effects of two combined oral contraceptive preparations was undertaken in seven WHO Collaborating Centres for Research in Human Reproduction. A total of 847 subjects were randomly allocated to one of two pill groups - norethisterone lmg/ethinyl estradiol 35 micrograms (NET/EE) or levonorgestrel 150 micrograms/ethinyl estradiol 30 micrograms (LNG/EE). An additional 195 women using an IUD served as a comparison group. Blood samples were taken on admission, and at 3 and 12 months thereafter. Both pills induced changes in fasting and 2-hour glucose, triglycerides, total cholesterol, HDL-cholesterol, bilirubin, alkaline phosphatase, albumin, and total protein, but not aspartate aminotransferase. The most dramatic and probably most clinically important changes were an increase in triglycerides and a decrease in HDL-cholesterol. The NET/EE preparation appeared to induce a greater increase in triglycerides, but no significant difference was found between the two pill preparations with respect to HDL-cholesterol changes.
Contraception 1985 Sep
PMID:A randomized double-blind study of the effects of two low-dose combined oral contraceptives on biochemical aspects. Report from a seven-centred study. WHO Special Programme of Research, Development and Research Training in Human Reproduction. Task force on Oral Contraceptives. 286 58

Peptide retro-inverso modification was applied to the complete hydroxamate inhibitors of the three zinc metallopeptidases (neutral endopeptidase 24-11 (NEP, EC 3.4.24.11), aminopeptidase N (APN, EC 3.4.11.2), and a dipeptidylaminopeptidase (DAP) involved in the in vitro enkephalin degradation by brain tissues. Compounds corresponding to the general formula RN(OH)CO(CH2)nCH(CH2Ph)NHCOCH(R')COOH (n = 0, 1) were synthesized. In the first series of inhibitors (n = 0), the "retro-inverso" modification induced a large decrease in inhibitory potency for NEP as compared to that of the parent compounds. In contrast, the presence of a methylene group between the hydroxamate and CH alpha in the second series (n = 1) led to derivatives with inhibitory potencies in the nanomolar range, similar to their analogues with a natural amide bond. On the other hand, the retro-inverso modification led to a slight improvement in the inhibition of DAP and APN, in the first series of inhibitors, while the inverse result occurred in the second series. Thus, compounds containing an alpha-amino acid moiety in P'1 position behave as weak inhibitors of the three enzymes, with IC50 values in the micromolar range, and compounds bearing a beta-amino acid moiety in the same position are more specific than the parent compounds for NEP inhibition.
J Med Chem 1988 Sep
PMID:Retro-inverso concept applied to the complete inhibitors of enkephalin-degrading enzymes. 290 Aug 98

The mouse aprt promoter contains four GC boxes, which bind transcription factor Spl in vitro, and lacks both TATA and CCAAT boxes. Removal of the two most distal GC boxes of this promoter had little effect on APRT enzyme levels produced in a transient expression assay. Deletion of the distal three GC boxes resulted in a 50% reduction, and deletion of all GC boxes resulted in essentially complete loss of APRT activity. There are two predominant transcription start sites which are located within the region containing the GC boxes. The promoter behaved as a relatively strong promoter when compared to the RSV LTR promoter in a transient CAT assay, and operated in one orientation only. No upstream anti-sense transcripts were detected in either mouse CAK or liver cells, confirming that the mouse aprt promoter, unlike some other GC-rich promoters appears not to support bidirectional transcription.
Nucleic Acids Res 1988 Sep 12
PMID:Identification of DNA sequences required for mouse APRT gene expression. 290 25

In the present study, a culture system of human placental cells was established to examine the role of estrogen and androgen in progesterone (P4) formation. Normal human placentae were obtained at term, and cells were dispersed in Hank's Balanced Salt Solution (5 ml/g tissue) containing 0.1% collagenase, 0.1% hyaluronidase, 0.01% deoxyribonuclease, and 1% fetal bovine serum for 2 h at 37 C. Dispersed placental cells (10(6) cells/ml) were placed in medium 199 with modified Earle's salts (pH 7.4) containing 10% fetal bovine serum, 12.5 mM HEPES buffer, 26 mM NaHCO3, and 40 micrograms/ml Gentamycin-SO4 and incubated for 72 h at 37 C and 5% CO2 in air to allow cell attachment. Medium was then changed (time zero), and P4 formation was studied thereafter. Culture of placental cells for 96 h resulted in linear increases in P4 and estradiol (E2) formation, indicating the maintenance of cell viability and steroidogenic function. Mean +/- SE P4 formation at 48 h was 246 +/- 16 pg/micrograms DNA. To assess the role of estrogen on P4 formation, placental cells were incubated for a period of 48 h with various amounts (10(-7)-10(-4)M) of the antiestrogen ethamoxytriphetol (MER-25), the aromatase inhibitor 4-hydroxyandrostenedione (4-OHA), and/or E2. Both MER-25 and 4-OHA resulted in a dose-dependent decline (P less than 0.01) in P4 formation (greater than 80% decline at 10(-4)M MER-25 or 4-OHA). The marked reduction in P4 formation caused by 4-OHA alone was reversed by concomitant addition of E2; however, E2 alone had no effect. To assess the role of androgens on P4 formation, cells were incubated for 48 h with increasing amounts (10(-7)-10(-4)M) of androstenedione, dehydroepiandrosterone (DHA), or dihydrotestosterone. Although the formation of E2 was enhanced by DHA, formation of P4 was not affected by the aromatizable androgens DHA or androstenedione or the nonaromatizable dihydrotestosterone. The decline in P4 formation by human placental cells in culture elicited by MER-25 or 4-OHA supports the hypothesis of a regulatory role for estrogen in placental P4 formation during human pregnancy. The lack of effect of exogenous estrogen suggests that the action of estrogen on P4 formation may be permissive.
Endocrinology 1986 Sep
PMID:Regulation of progesterone formation by human placental cells in culture. 294 94

A growth hormone-dependent binding protein for insulin-like growth factors (IGF-I and IGF-II) has been isolated from human plasma. Analyzed on SDS gels, the preparation contained a major protein band of 53 kDa, and a minor band of 47 kDa. After transfer to nitrocellulose, both species bound iodinated IGF-I, and could be detected using an antibody raised against the purified preparation. In contrast, an IGF binding protein purified from human amniotic fluid bound IGF-I but was not detectable immunologically. The amino acid comparison of the plasma binding protein preparation was different from that reported for amniotic fluid and HEP G2 hepatoma proteins, and the unique amino-terminal sequence, Gly-Ala-Ser-Ser-Ala-Gly-Leu-Gly-Pro-Val-, was different from that of the amniotic fluid and hepatoma proteins. This study indicates that the growth hormone-dependent IGF binding protein of human plasma is structurally and immunologically distinct from other IGF binding proteins.
Biochem Biophys Res Commun 1986 Sep 30
PMID:Growth hormone-dependent insulin-like growth factor (IGF) binding protein from human plasma differs from other human IGF binding proteins. 294 61

It was the aim of this study to conduct simultaneous qualitative analysis of blood flow spectra of uteroplacental and foetal vessels in normal pregnancy, in growth retardation and in EPH gestosis using the pulsed Doppler method. In 237 women who had delivered we performed 291 measurements in uteroplacental vessels, 318 in the umbilical artery, 339 in the foetal aorta and 130 in the foetal common carotid artery. The blood flow spectra were evaluated with the help of the resistance and pulsation index ratio (RI/PI) as a measure of the resistance of the subsequent vascular system. We observed in uteroplacental vessels in EPH gestosis and retardation a significant elevation of the index values in the wall of the uterus outside or inside the placental margin. In foetal vessels we noted a highly significant increase of RI and PI in the umbilical artery and the foetal aorta--simultaneously, however, a drop in the index values in the foetal common carotid artery. These changes point on the one hand to the increased resistance in the capillary net of the placenta and a possible vascular constriction in the region of the lower abdominal organs and extremities, whereas on the other hand they point towards a compensatory lowering of the vascular resistance in the cerebral circulation--possibly as an expression of the risk of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
Geburtshilfe Frauenheilkd 1987 Sep
PMID:[Pathophysiologic and clinical aspects of measuring blood flow in utero-placental vessels, the umbilical artery, the fetal aorta and the fetal common carotid artery]. 296 May 86

We isolated 142 Hir- (host inhibition of replication) mutants of an Escherichia coli K-12 Mu cts Kil- lysogen that survived heat induction and the killing effect of Mu replicative transposition. All the 86 mutations induced by insertion of Tn5 or a kanamycin-resistant derivative of Tn10 and approximately one-third of the spontaneous mutations were found by P1 transduction to be linked to either zdh-201::Tn10 or Tn10-1230, indicating their location in or near himA or hip, respectively. For a representative group of these mutations, complementation by a plasmid carrying the himA+ gene or by a lambda hip+ transducing phage confirmed their identification as himA or hip mutations, respectively. Some of the remaining spontaneously occurring mutations were located in gyrA or gyrB, the genes encoding DNA gyrase. Mutations in gyrA were identified by P1 linkage to zei::Tn10 and a Nalr gyrA allele; those in gyrB were defined by linkage to tna::Tn10 and to a gyrB(Ts) allele. In strains carrying these gyrA or gyrB mutations, pBR322 plasmid DNA exhibited altered levels of supercoiling. The extent of growth of Mu cts differed in the various gyrase mutants tested. Phage production in one gyrA mutant was severely reduced, but it was only delayed and slightly reduced in other gyrA and gyrB mutants. In contrast, growth of a Kil- Mu was greatly reduced in all gyrase mutant hosts tested.
J Bacteriol 1986 Sep
PMID:Mutants of Escherichia coli defective for replicative transposition of bacteriophage Mu. 301 19

A synthetic chimeric gene, coding for the human epidermal growth factor fused to the signal peptide of Escherichia coli alkaline phosphatase, was cloned into E. coli under the transcriptional control of the trp-lac (tac) promoter. Following induction with isopropylthiogalactoside, the secretion of the correctly processed protein product into the bacterial periplasm was detected and quantitated by its specific binding to the epidermal growth factor receptor. The purified protein was identical to authentic human epidermal growth factor in size, amino acid composition, primary sequence, receptor binding, and stimulation of receptor protein-tyrosine kinase activity. Based on interspecies homologies, structural considerations, and reported studies with peptide fragments, structure-function analysis was initiated with alterations of targeted amino acid residues by oligonucleotide-directed mutagenesis. The receptor binding affinity of each mutant, relative to the wild type, was measured by both radioreceptor competition and receptor tyrosine kinase stimulation assays. In general, the values obtained by the two methods were in agreement for each species of epidermal growth factor and followed the order: wild type greater than Glu24----Gly greater than Asp27----Gly much greater than Pro7----Thr greater than Tyr29----Gly greater than Leu47----His. The relatively low values obtained with the last two mutants suggest that Tyr29 and Leu47 may be important for the biological activity of human epidermal growth factor.
J Biol Chem 1988 Sep 05
PMID:Cloning of authentic human epidermal growth factor as a bacterial secretory protein and its initial structure-function analysis by site-directed mutagenesis. 304 17

Intratumor macrophage numbers are enhanced by the administration of chemotactic f-MET-LEU-PHE - antitumor antibody - conjugates. The four f-MET-peptides f-MET-LEU-PHE, f-MET-LEU-PHE-o-methylester, formyl-norleucyl-phenylalanine and formyl-methionyl-phenylalanine, all chemotactic for human monocytes, where evaluated alone and conjugated to the melanoma directed monoclonal antibody ZME 018. f-MET-LEU-PHE-o-methyl-ester is the most active peptide, whereas f-MET-LEU-PHE - ZME 018 is the most active conjugate, not only inducing a response at the lowest concentration, but also the highest migrating cell numbers.
Biochem Biophys Res Commun 1988 Sep 30
PMID:Chemotactic monoclonal antibody conjugates: a comparison of four different f-Met-peptide-conjugates. 326 21


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