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 purpose of these experiments was to examine the influence of various fluid replacement drinks on exercise-induced disturbances in homeostasis during heavy exercise. Nine trained cyclists performed constant load exercise on a cycle ergometer to fatigue on three occasions with 1-week separating experiments. The work rate was set initially at approximately 85% of VO2max (range 82-88%) with fatigue being defined as a 10% decline in power output below the initial value. During each experiment subjects consumed one of the following three beverages prior to and every 15 min during exercise: (1) non-electrolyte placebo (NEP; 31 mosmol.kg-1); (2) glucose polymer drink containing electrolytes (GP; 7% CHO, 231 mosmol.kg-1), and (3) electrolyte placebo drink without carbohydrate (EP; 48 mosmol.kg-1). Both the GP and EP beverage contained sodium citrate/citric acid (C) as a flavoring agent while C was not contained in the NEP drink. Although seven of nine subjects worked longer during the GP and EP treatment when compared with the NEP trial, the difference was not significant (P greater than 0.05). No differences (P greater than 0.05) existed between the GP and EP treatments in performance time. Exercise changes in rectal temperature, heart rate, delta % plasma volume and plasma concentrations of total protein, free fatty acids, glucose, lactate, potassium, chloride, calcium, and sodium did not differ (P greater than 0.05) between trials.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fluid replacement drinks during high intensity exercise: effects on minimizing exercise-induced disturbances in homeostasis. 231 95

Intestinal absorption of crystalline DL-methionine (DL-MET) and DL-methionine hydroxy analog calcium (DL-HMA) were determined in a true-digestibility-balance assay using cecectomized (CEC) and sham-operated conventional (CONV) cockerels. The treatments consisted of fasted birds and birds crop-intubated (CI) with 30 g of a corn-soybean meal basal diet (16% CP) supplemented with 0, .2, or .4% of DL-MET or equimolar levels of DL-HMA. There was no detectable free D-MET or L-MET or HMA in the excreta of fasted birds or of those fed the unsupplemented basal diet. The intestinal absorption of DL-HMA was 95.9 +/- .8% (means +/- SE) for CEC and 98.8 +/- .8% for the CONV cockerels. The absorption of DL-MET was approximately 99.7 +/- .2% for the CEC and the CONV cockerels. In a second experiment procedures were developed for a bioavailability assessment by comparing the growth responses to CI and intraperitoneal-injected (IP) DL-MET or DL-HMA in chicks fed a crystalline-amino-acid diet deficient in methionine. Graded increments of pH-adjusted DL-MET or DL-HMA (in water solutions) were administered twice daily in a 7-day growth assay. Slope-ratio analysis indicated that bioavailability (+/- SE) of CI DL-HMA was 91.3 +/- 11.8% relative to the CI DL-MET on an equimolar basis. The bioavailability of CI DL-HMA was similar to that of IP DL-HMA, indicating that the intestinal absorption of DL-HMA was highly efficient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Absorption and bioavailability of DL-methionine hydroxy analog compared to DL-methionine. 233 Mar 31

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

We exposed helical strips of dog middle cerebral arteries to oxyhemoglobin for 5 hours, rinsed them with bathing medium, and stored them overnight; we compared the responses of strips thus treated with the responses of strips without oxyhemoglobin treatment. Relaxation induced by nicotine was abolished by hexamethonium and was markedly inhibited after exposure to oxyhemoglobin. A low concentration of KCl (5 mM) elicited relaxation that was abolished by ouabain and significantly reduced by oxyhemoglobin. Endothelium-dependent relaxation caused by calcium ionophore A23187 was attenuated, and that caused by substance P was reversed to contraction after exposure to oxyhemoglobin. Contraction elicited by substance P also depended on endothelium and was abolished by indomethacin. Relaxation induced by TRK-100, a stable analogue of prostaglandin I2, was moderately attenuated by oxyhemoglobin. On the other hand, concentration-dependent relaxation induced by papaverine and contractile responses to KCl, serotonin, and prostaglandin F2 alpha were not affected by oxyhemoglobin. Our results indicate that vasodilations mediated by vasodilator nerves, the electrogenic sodium pump, endothelium-derived relaxing factor, and prostaglandin I2 were impaired in dog cerebral arteries exposed to oxyhemoglobin. After exposure to oxyhemoglobin, vascular endothelium appears to participate in cerebroarterial contraction via a release of vasoconstrictor prostaglandins. These actions of oxyhemoglobin may be involved in the genesis of cerebral vasospasm after subarachnoid hemorrhage.
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PMID:Prolonged exposure to oxyhemoglobin modifies the response of isolated dog middle cerebral arteries to vasoactive substances. 247 Jan 67

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.
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PMID:The cardioplegic solution HTK: effects on membrane potential, intracellular K+ and Na+ activities in sheep cardiac Purkinje fibres. 251 7

Calcium 2-keto-L-gulonate (Ca-2-KLG, a key intermediate in vitamin C synthesis) is produced from calcium 2,5-diketo D-gluconate (Ca-2,5-DKG) by a variety of bacteria. A few bacterial species which efficiently convert glucose to Ca-2,5-DKG have been isolated in our laboratory. Our bacterial collection included species that possess the genes for production of Ca-2-KLG from Ca-2,5-DKG; however, the yield of the former is poor. A procedure for the preparation of spheroplasts in Ca-2,5-DKG- and Ca-2-KLG-producing bacteria was developed for the construction of recombinants (fusants), combining the genes for conversion of glucose to Ca-2-KLG efficiently by protoplast fusion. The standard procedure for spheroplast formation in Gram negative bacteria by the Tris-sucrose-EDTA-lysozyme system did not work in the organisms under investigation. The need for an alternative method was necessary. Our results show that, while the Tris-NaCl-EDTA-lysozyme system (pH 8.3) worked very well with bacterial strains of Gluconobacter oxydans (ATCC9937) and Acetobacter melanogenus (NCIM2259), the Tris-sucrose-EDTA-lysozyme system worked well for Erwinia herbicola (ATCC21998), Pseudomonas chlororaphis (NCIM2041) and Corynebacterium species (ATCC31090). However, none of these systems produced spheroplasts in Brevibacterium ketosoreductum (ATCC21914), for which a separate system is under development.
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PMID:A fast spheroplast formation procedure in some 2,5-diketo-D-gluconate- and 2-keto-L-gulonate- producing bacteria. 251 94

Many cell types display two classes of epidermal growth factor receptor (EGFR) as judged from EGF binding studies; i.e., a major class of low affinity EGFR and a minor class of high affinity EGFR. We have studied their respective contribution to the cascade of events elicited by EGF in human A431 carcinoma cells, using anti-EGFR mAb 2E9. This antibody specifically blocks EGF binding to low affinity EGFR, without activating receptors in intact cells, and thus enables us to study the effects of exclusive EGF binding to high affinity EGFR. We show that blocking of low affinity EGFR by mAb 2E9 has almost no effect on the activation of the receptor protein-tyrosine kinase by EGF, suggesting that EGFR kinase activation occurs exclusively through the subclass of high affinity EGFR (5-10%). In addition, we provide evidence that high affinity EGFR exists both in monomeric and dimeric forms, and that cross-phosphorylation of low affinity EGFR by high affinity EGFR may take place in dimers of both receptor types. We demonstrate that the following early cellular response to EGF are also unimpaired in the presence of mAb 2E9: (a) inositol phosphate production, (b) release of Ca2+ from intracellular stores, (c) rise in intracellular pH, (d) phosphorylation of EGF on threonine residue 654, (e) induction of c-fos gene expression, and (f) alteration in cell morphology. As possible nonspecific side effects, we observed that the EGF induced Ca2+ influx and fluid-phase pinocytosis were inhibited in A431 cells in the presence of mAb 2E9. We conclude, therefore, that the activation of the EGFR signal transduction cascade can occur completely through exclusive binding of EGF to the subclass of high affinity EGFR.
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PMID:Signal transduction by epidermal growth factor occurs through the subclass of high affinity receptors. 255 48

We had previously detected a transforming oncogene, designated PTC, in 25% of 20 papillary thyroid carcinomas. In order to characterize further the transforming activity of this tumour histotype, a new panel of tumour specimens from 16 patients was analysed by using a modified calcium phosphate-DNA coprecipitation transfection protocol. Tumour DNA from 10 patients (62%) displayed a transforming activity due to activation of three different oncogenes identified in four cases as PTC, in four cases as TRK, and in two cases as N-RAS. The same structural alterations of PTC and TRK (gene rearrangements) as well as of N-RAS (point mutation) detected in the NIH3T3 transformants, were also found in the original tumour DNAs, thus indicating that their activation was not due to transfection procedures. Since both PTC, a novel rearranged form of RET, and TRK display a tyrosine protein kinase activity, it is proposed that the activation of this class of oncogenes is specifically involved in the pathogenesis of papillary thyroid cancer.
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PMID:High frequency of activation of tyrosine kinase oncogenes in human papillary thyroid carcinoma. 259 68

We describe here the properties of tert-butyloxycarbonyl-Trp-Leu-Asp-Phe-NHNH2 (A-57696), a C-terminal hydrazide analogue of tert-butyloxycarbonyl-CCK4 (Boc-Trp-Met-Asp-Phe-NH2), at four cholecystokinin (CCK) receptor-bearing tissues, the guinea pig pancreas and gall bladder (Type A), guinea pig cortex (Type B), and NCI-H345 cells, a human small cell lung cancer cell line that expresses CCK-B/gastrin receptors. Using 125I-Bolton-Hunter-cholecystokinin octapeptide (26-33) (125I-Bolton-Hunter-CCK8) as the radioligand, A-57696 was found to be selective for cortical CCK-B receptors (IC50 = 25 nM), compared with pancreatic CCK-A receptors (IC50 = 15 microM). A-57696 behaved as a competitive antagonist in reversing CCK8-stimulated pancreatic amylase secretion and phosphoinositide breakdown. By Schild analysis, its Kd was determined to be 4.7 and 6.8 microM in amylase and phosphoinositide assays, respectively. A-57696 (100 microM) did not elicit gall bladder contraction, and it inhibited contractions induced by CCK8. The Kd of A-57696 at gall bladder CCK-A receptors was 19 microM. In contrast, A-57696 behaved as a partial agonist (80% of maximal CCK8 response) in stimulating calcium mobilization at CCK-B/gastrin receptors on NCI-H345 cells. A-57696 and CCK8 inhibited each other in calcium mobilization experiments utilizing the fluorescent dye Indo-1. Stimulatory actions of CCK8 and A-57696 were reversed by the CCK-B-selective (R)-L-365,260 (100 nM), whereas at the same concentration, the CCK-A-selective (S)-L-365,260 was ineffective. Binding studies using 125I-Bolton-Hunter-CCK8 and 125I-gastrin indicated that binding sites labeled by these two ligands displayed similar affinities for CCK8, desulfated CCK8, gastrin, A-57696, and both enantiomers of L-365,260. A-57696 represents a new class of CCK-A peptide antagonist at guinea pig pancreas a new class of CCK-A peptide antagonist at guinea pig pancreas and gall bladder. Its contrasting functional activities at guinea pig CCK-A and CCK-B/gastrin receptors in a human tumor cell demonstrate that, in addition to the previously described differences in binding specificity for selective agonists and antagonists, CCK-A receptors and CCK-B/gastrin receptors have different requirements for activation.
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PMID:Distinct requirements for activation at CCK-A and CCK-B/gastrin receptors: studies with a C-terminal hydrazide analogue of cholecystokinin tetrapeptide (30-33). 260 85

Actually the maximum preservation time for donor hearts is limited to 4 hours. The aim of this experimental study in dogs was to develop techniques allowing an extension of this period up to 24 hours. In the first part of the study the influence of diastolic arrest on the preservation of high energy phosphates was studied: The following methods of cardioplegic arrest were used: 1. hyperkalemic arrest 2. hyperkalemic arrest plus high magnesium 3. low sodium and calcium-free cardioplegia. In all experiments cardioplegic arrest was followed by cold storage (0.5 degrees C). Single dose K+ plus Mg2+ cardioplegia offered the least protection. The other two types of cardioplegia were better but the ATP content was still below 50% after 24 hrs preservation. Reperfusion after cardiac transplantation induced irreversible injury and function did not recover after transplantation. In the second part of the study continuous hypothermic perfusion with low sodium and calcium-free cardioplegia was studied. With this technique HEP content, myocardial structure and functional recovery were 100% after transplantation.
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PMID:[Long-term preservation of the heart in view of its transplantation. An experimental study]. 263 87


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