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)

Because of premature labour, probability of fetal retardation, discrepance at term of delivery, Rh-incompatibility or EPH-gestosis 185 patients were hospitalized. 76 pregnant women received twice 1.5 ml Celestan Depot i.m. (4.5 betamethasone acetate and 6mg betamethasome dinatrium phosphate per injection) within an interval of 24 hours. It was necessary to maintain a tocolysis for at least 48 hours as a minimum after the first injection of Celestan Depot. The other 109 patients without treatment of glucocorticoids were considered as a controlgroup. We could show that antepartum application of betamethasone before the 38. week of gestation was associated with a reduction of RDS in our premature infants. Only one baby of the betamethasone-treated infants died of hyaline membrane disease during the first 7 days of life compared with 11 of the control group. In 11 patients patients amniocentesis was performed before the first injection of glucocorticoids and was repeated 2 to 7 days later. The amniotid fluid lecithin phosphorus concentration was determined. In the same period of pregnancy and the same iterval the lecithin phosphours level of amniotic fluid was analysed in 11 other patients who were not rreated with glucocorticoids. The difference between amniotic fluid lecithin phosphorus concentration in the first and second anslysis was found significant by a level of significance of alpha = 5%. There was no evidence of an influence of the therapy with Celestan Depot on this increase. The excretion of oestorgens in the urine of 24 hours was analysed in 22 gradidae before and 7 days after the treatment with betamethasone. The oestogen values of the day before application of betamethasone served as baseline figures. All patients showed a market fall in urinary oestrogens excretion, especially after the second day of therapy. After day 2 the values returned rapidly to baseline values. There were no differences between treated and control groups in Apgar scores at birth or in the incidence of icterus neonatroum (bilirubine level is greater that 10 mg% in the serum). The results of our study support the hypothesis that in humans glucocorticoid administration to the fetus accelerates lung maturation. Relatively brief intrauterine exposure of human infants to pharmacological doses of betamethasone was associated with a substantial reduction in the incidense of RDS.
 ...
PMID:[First experiences with prenatal affection of infantile lung maturation by betamethason (author's transl)]. 115 18

The effects of prolonged hypothermic ischemia and subsequent normothermic perfusion on the energetic metabolism and intracellular pH (pHin) of isolated rat livers were studied by phosphorus-31 nuclear magnetic resonance spectroscopy. Nucleoside triphosphate (NTP) depletion and intracellular pH were studied within an 18-h-storage phase, by using the following preservation media: Eurocollins (EC), UW Lactobionate (UW) and Bretschneider's solution (HTK). Values obtained after 8-h ischemia were chosen to estimate the performance of the various media: NTP levels were 37 +/- 7%, 10 +/- 5% and 0% of control levels, respectively, in livers stored in UW, HTK and EC solutions. pHin reached values of 7.15 +/- 0.10 in UW and HTK, and 6.96 +/- 0.10 in EC-stored livers. Ischemic damage was assessed by reperfusing the stored organ with Krebs medium: NTP recovery was around 70 +/- 20% for the three solutions used. Recovery of pHin was near the control value (7.23 +/- 0.08), except for EC solution (7.05 +/- 0.20). The main results are that (i) the rates of NTP and pHin decrease are strongly dependent on the nature of the preservation solution, whereas (ii) NTP recovery is not significantly different during post-ischemic reperfusion. With regard to animal survival, UW solution is at present considered largely superior to EC medium for liver preservation. Thus, our data suggest that the rates of NTP depletion and pHin fall during cold preservation could be both considered as better indicators assessing liver injury than the post-ischemic NTP recovery.
 ...
PMID:Phosphorus-31 nuclear magnetic resonance of isolated rat liver during hypothermic ischemia and subsequent normothermic perfusion. 150 39

Composition of ration and season of sampling markedly affected the composition of blood in six tamed bison (Bison bison) steers and eight Hereford cattle (Bos taurus) steers. Observed values extended reported ranges for albumin, phosphorus and blood urea nitrogen (BUN) in bison serum. There were several differences between species in blood composition. In particular, erythrocytic and BUN values were higher in bison than in cattle. Overall mean values for bison and cattle receiving experimental rations were, respectively: BUN, 17.1 mg/dl and 14.1 mg/dl; hemoglobin, 17.8 g/dl and 13.3 g/dl; packed cell volume (PCV), 47.6% and 35.6%; red blood cells, 9.3 x 10(6)/mm3 and 8.2 x 10(6)/mm3; mean corpuscular volume (MCV), 51.3 mean 3; mean corpuscular hemoglobin, 18.9 pg and 16.1 pg. The significant changes in blood composition associated with changes in ration composition support the use of blood composition as an index of nutritional status. There were no sex-specific differences in blood of 20 bison from Elk Island National Park and 34 bison from Wood Buffalo National Park, Alberta. Alkaline phosphatase (ALP) level was higher in juvenile than in adult bison. Impoundment of wild bison for 24 hr was accompanied by a decrease in BUN and an increase in PCV. Wild bison that were killed during handling had significantly higher blood levels of ALP, glutamate oxaloacetate transaminase, MCV and phosphorus.
 ...
PMID:Effects of ration, season and animal handling on composition of bison and cattle blood. 713 55

Inhibition of tyrosine kinases is a possible approach for the treatment of cancer. We have investigated the catalytic mechanism of the epidermal growth factor receptor tyrosine kinase (EGF-RTK) in order to obtain information for use in structure-based searching for inhibitors. Initial rate studies imply that EGF-RTK forms a ternary complex together with ATP and peptide substrate. Investigation of pH and temperature dependence suggests that the kinase reaction requires the ionised form of a carboxylate (pK = 6.3) and the protonated form of another group (pK = 9.1). These characteristics are consistent with a mechanism where the carboxylate of Asp813(pK = 6.3) facilitates deprotonation of the tyrosyl hydroxyl of the peptide substrate, activating it as a nucleophile to attack the gamma-phosphorus of ATP which interacts with a protonated enzyme side-chain (pK = 9.1), possibly the guanidinium group of Arg817. This proposed catalytic mechanism was used to define a query when searching for inhibitors in a database of predicted three-dimensional structures. The procedure involved searching for compounds that mimic the ATP gamma-phosphate, tyrosyl hydroxyl and the tyrosyl aromatic ring, all of which seem to interact strongly with the enzyme during catalysis. This search allowed identification of inhibitors of EGF-RTK which were used to define queries for two-dimensional searching of a larger database, leading to the discovery of 4-(3-chloroanilino)quinazoline (CAQ) which is a potent inhibitor (Ki = 16 nM) of the enzyme. The compound is believed to be the first representative from a new structural class of anilinoquinazoline tyrosine kinase inhibitors. It follows competitive kinetics with respect to ATP and noncompetitive kinetics when the peptide is varied, implying that it functions as an analogue of ATP. CAQ is a novel and potent lead in the search for tyrosine kinase inhibitors as potential agents for the treatment of cancer.
 ...
PMID:Epidermal growth factor receptor tyrosine kinase. Investigation of catalytic mechanism, structure-based searching and discovery of a potent inhibitor. 808 Apr 38

Four primary zinc-binding pharmacophores (thiols, carboxylates, phosphorus acids, and hydroxamates) have been utilized in generating inhibitors of zinc metalloproteases such as ACE, NEP, the MMPs, and ECE. Although compounds which inhibit the activity of both ACE and NEP (vasopeptidase inhibitors, VPIs) have been reported which incorporate a thiol, carboxylate, or phosphorus acid pharmacophore, the generation of hydroxamate based vasopeptidase inhibitors has remained elusive. Herein we report the first potent vasopeptidase inhibitors which were generated from the incorporation of conformationally restricted dipeptide mimetics to an N-formyl hydroxylamine zinc-binding group. Compounds such as 13c and 13d are among the most potent in this series, exhibiting in vitro activity comparable to other classes of inhibitors.
 ...
PMID:N-formyl hydroxylamine containing dipeptides: generation of a new class of vasopeptidase inhibitors. 1069 48

Elevated serum levels of parathyroid hormone (PTH) contribute to the increased morbidity and mortality in renal failure patients. Parathyroid gland hyperplasia is a major cause of high serum PTH. The present studies used the rat model of renal failure to address the mechanisms underlying uremia-induced parathyroid hyperplasia and the antiproliferative properties of vitamin D therapy (1,25-dihydroxyvitamin D (1,25(OH)(2)D(3)) or its less calcemic analogs). Enhanced TGFalpha/EGFR co-expression is the major mitogenic signal in uremic parathyroid glands. At early stages of renal failure, vitamin D therapy efficiently counteracts uremia- and high phosphorus-induced hyperplasia by inhibiting the increases in parathyroid-TGFalpha/EGFR co-expression. In established hyperparathyroidism, characterized by highly enhanced-TGFalpha/EGFR co-expression, vitamin D therapy arrests growth by suppressing EGFR-growth signals from the plasma membrane and nuclear EGFR actions as a transactivator of the cyclin D1 gene, an important contributor to parathyroid hyperplasia in humans. In advanced renal failure, reduced-parathyroid vitamin D receptor levels limits the antiproliferative efficacy of vitamin D therapy. However, non-antiproliferative doses of 1,25-dihydroxyvitamin D enhance the anti-EGFR actions of EGFR-tyrosine kinase inhibitors (TKI). In fact, combined 1,25-dihydroxyvitamin D/TKI therapy inhibits parathyroid hyperplasia more efficiently than phosphorus restriction, the most powerful promoter of parathyroid growth arrest available at present.
 ...
PMID:1,25-Dihydroxyvitamin D downregulation of TGFalpha/EGFR expression and growth signaling: a mechanism for the antiproliferative actions of the sterol in parathyroid hyperplasia of renal failure. 1522 29

Previous studies have identified flooded landscapes (e.g., wetlands, impoundments) as sites of elevated methylmercury (MeHg) production. Here we report MeHg and total Hg (THg) concentrations and mass loadings in rivers in Minnesota during major flooding episodes in the summer of 2002. Frequent intense precipitation events throughout the summer resulted in extraordinarily wet conditions in east-central and northwestern Minnesota. Streamflow remained at record-setting high levels in many rivers and streams in these regions for several weeks. We observed high concentrations of MeHg (>1.4 ng/L) accompanied by high MeHg/THg ratios (0.39 to 0.50) in the Roseau River in northwestern Minnesota and in the Elk and Rum Rivers in east-central Minnesota. Very high MeHg mass loadings were observed in the Mississippi River just upstream of Minneapolis on July 17 (51 g MeHg/day) and July 23 (42 g MeHg/day), when MeHg concentrations at this site were 0.89 and 0.99 ng/L, respectively. The elevated MeHg concentrations in the Roseau River were associated with low dissolved oxygen and high dissolved reactive phosphorus concentrations, both of which are characteristic of anoxic waters. These rivers drain landscapes containing varying amounts of wetlands, and some of the MeHg discharged is thought to have been flushed from anoxic wetland soils. In addition, the flooding of vast areas of normally dry land surfaces probably also resulted in increased MeHg production, adding to the quantities of MeHg exported from these watersheds. Changing climate patterns are expected to result in more frequent heavy precipitation and flooding events in Minnesota. Our results suggest that as flooding and wet conditions in this region increase, the production of MeHg and its export from terrestrial areas to surface waters will increase also.
 ...
PMID:Elevated methylmercury concentrations and loadings during flooding in Minnesota rivers. 1625 39

It was reported that the parathyroid gland hyperplasia correlated with enhanced co-expression of TGF-alpha and its receptor EGFR at early stages of renal failure. This time, we investigated the time course for EGFR and its ligands, TGF-alpha, and EFG expression, and the influence of high-phosphorus (P) diet to EGFR and EGF expression, and the effect of EGFR-tyrosine kinase inhibitor (Gefitinib, [IRESSA; AstraZeneca]; TKI) in rat PTGs with established stage of renal failure. The levels of EGFR, EGF, TGF-alpha mRNA in rat PTGs were increased for the time periods. The serum intact PTH levels, and EGFR, EGFmRNA in rat PTGs were suppressed in normal-P diet group. Nuclei positive cells for PCNA in TKI group were suppressed. The levels of p21mRNA were increased in TKI group. These results suggested that the enhanced expression of EGFR, TGF-alpha and EGF participate in the cell proliferation of hyperplastic PTGs in established stage of renal failure.
 ...
PMID:[Enhanced expression of EGFR, TGF-alpha, EGF in hyperplastic parathyroid glands in established stage of renal failure in rats]. 1641 40

Each dental adhesive contains a specific functional monomer that determines its actual adhesive performance to tooth tissue. 4-methacryloxyethyl trimellitic acid (4-MET) is well-known as one of the functional monomers mostly available and consequently widely used in commercial adhesives. We therefore characterized the chemical interaction of 4-MET with hydroxyapatite (HAp) using X-ray Photoelectron Spectroscopy (XPS). XPS revealed that the peak representing -COO- of 4-MET shifted to a lower binding energy, when 4-MET was adsorbed onto HAp. Deconvolution of this shifted peak disclosed two components with a peak representing unreacted carboxyl groups and ester groups, and a peak suggesting chemical bonding of other carboxyl groups to Ca of HAp. XPS spectra of HAp treated with 4-MET also disclosed the surface to be enriched in calcium and decreased in phosphorus, indicating that phosphorus was extracted at a relatively higher rate than calcium. It can thus be concluded that true chemical bonding of 4-MET with calcium present in HAp occurred, as it was proven using XPS.
 ...
PMID:Analysis of chemical interaction of 4-MET with hydroxyapatite using XPS. 1733 95

Calcitriol is a standard therapy for secondary hyperparathyroidism in chronic renal failure. We evaluated whether the effect of daily or intermittent calcitriol administration is more efficient in enhancing bone growth in renal failure with advanced secondary hyperparathyroidism in weanling 5/6 nephrectomized rats loaded with phosphorus to induce severe secondary hyperparathyroidism. The animals were treated daily or three times weekly with calcitriol for 4 weeks but the total weekly dose of calcitriol was the same. Although calcitriol increased the serum calcium, it did not lower parathyroid hormone (PTH) or improve tibia and body length. Animals with renal failure and advanced secondary hyperparathyroidism had decreased PTH/PTHrP, which was accompanied by an increase in the cyclin kinase inhibitor p57(Kip2). Calcitriol treatment upregulated the PTH/PTHrP receptor but also increased inhibitors of cell proliferation such as p21(Waf1/Cip1), IGFBP3, and FGFR3. Calcitriol also enhanced markers of chondrocyte differentiation, such as IGF1, Vitamin D receptor, FGF23, and bone morphogenetic protein-7. Receptor activator of nuclear factor-kappabeta ligand levels improved with calcitriol treatment but without changes in osteoprotegerin suggesting an enhancement of osteo/chondroclastogenesis and mineralization. Overall, both daily and intermittent calcitriol had similar effects on endochondral bone growth in phosphorus-loaded rats with renal failure.
 ...
PMID:Bone growth during daily or intermittent calcitriol treatment during renal failure with advanced secondary hyperparathyroidism. 1771 61


1 2 3 4 5 Next >>