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)

TRK-100, a stable analogue of prostaglandin I2 (PGI2), relaxed isolated arteries of the dog precontracted with PGF2 alpha or K+; the relaxation was in the order of mesenteric and renal greater than coronary and femoral greater than basilar and middle cerebral arteries. The relaxation by TRK-100 was not affected by treatment with atropine, propranolol, cimetidine, aminophylline, and indomethacin, but was suppressed by diphloretin phosphate, a prostaglandin antagonist. Treatment with TRK-100 attenuated the contraction induced by PGF2 alpha and Ca2+ in mesenteric and basilar arteries previously exposed to Ca2+-free medium, but did not significantly alter the contractile response to Ca2+ in the arteries exposed to Ca2+-free medium and depolarized by excess K+. TRK-100 and nitroglycerin relaxed isolated mesenteric arteries to a similar extent; however, when continuously infused into mesenteric arteries in anaesthetized dogs, TRK-100 produced greater vasodilatation than nitroglycerin. It is concluded that TRK-100 relaxes dog mesenteric and renal arteries more than cerebral arteries; the relaxation appears to derive from interference with the release of Ca2+ from intracellular stores and with the transmembrane Ca2+ influx through a receptor-operated channel. TRK-100 may vasodilate large and small mesenteric arteries and resistance vessels to a similar extent, whereas nitroglycerin preferentially dilates the large artery.
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PMID:Vasodilator actions of TRK-100, a new prostaglandin I2 analogue. 310 28

For 7 working days running the ethyleneoxide (EtO) concentration has been determined in a medium sized sterilization plant of a medical endoscopy department. Sampling was taken from passive collectors of 3 M. The concentrations were 4 times (= 57% of the whole measured values) under the detection limit of 0.25 ppm = 0.46 mg/m3 in accordance with an eight hour shift; the EtO-level of 1.5, 2.1 and 9.2 ppm stayed for the remaining cases. Consequently the present valid TRK-value of 3 ppm was exceeded only one time. The exposition duration was between 0.6 and 13 years (median 5.5 years) for these 7 participants with a mean age of 33.4 (median 5.5 years). On the occasion of routine laboratory checks which included the analysis of important hematological, hepatological, nephrological and immunological values, no EtO-exposure has been found which was in causal connection with pathological findings. The search for specific RAST-IgE-antibodies against EtO in serum passed negatively. The enzyme activities of the gamma-GT correlated approximately with the anamnestic mentioned alcohol quantity, consumed daily.
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PMID:[Occupational medicine studies of 7 ethylene oxide-exposed endoscopy nursing professionals]. 312 77

In helical strips of dog cerebral arteries exposed to Ca2+-free medium under hypoxic conditions (95% N2 and 5% CO2), prostaglandin (PG) F2 alpha produced a slight tonic contraction. The addition of Ca2+ evoked a phasic contraction followed by relaxation and a sustained contraction, and reoxygenation elicited an additional tonic contraction of moderate magnitude. When the PGF2 alpha-induced contraction was stabilized in Ca2+-free medium, reoxygenation contracted the arteries only slightly. Treatment with the stable PGI2 analogues PGI2 methylester and TRK-100 attenuated the contractions caused by PGF2 alpha and Ca2+ and abolished almost completely the reoxygenation-induced contraction. Treatment with nitroglycerin inhibited the contractions caused by PGF2 alpha and Ca2+, but did not significantly alter the contraction induced by reoxygenation. The Ca2+ entry blockers diltiazem, flunarizine, and felodipine did not alter the PGF2 alpha-induced contractions, but attenuated the contractions caused by Ca2+ and reoxygenation. The vasodilator agents used appear to interfere differently with the release of Ca2+ from intracellularly stored sites and the transmembrane Ca2+ influx through receptor-operated channels under hypoxia and normoxia. The cerebroarterial contraction caused by reoxygenation may be associated mainly with increased Ca2+ influx from receptor activation and tissue oxygenation, which is markedly suppressed by PGI2 analogues and moderately attenuated by Ca2+ entry blockers but not significantly influenced by nitroglycerin.
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PMID:Reoxygenation and calcium-induced cerebroarterial contractions as affected by vasodilator agents. 314 91

Actions of a variety of vasodilators were compared in helical strips of the dog coronary artery, previously soaked in Ca2+-free medium under severe hypoxia. Ca2+ entry blockers, such as nifedipine and flunarizine, did not affect the PGF2 alpha-induced contraction in Ca2+-free medium, but strongly reduced the Ca2+-induced contraction under severe hypoxia in the strips stimulated by PGF2 alpha. The contraction obtained following reoxygenation was also reduced by the Ca2+ blockers. Nitroglycerin and isoproterenol inhibited the PGF2 alpha- and Ca2+-induced contractions as well as the reoxygenation-induced contraction. PGI2 methylester and TRK-100, stable analogues of PGI2, attenuated the PGF2 alpha-induced contraction in Ca2+-free medium, but not the Ca2+-induced contraction under hypoxia. PGI2 analogues inhibited the contraction due to reoxygenation to a greater extent than Ca2+ entry blockers, nitroglycerin and isoproterenol. The present study differentiated the inhibitory actions of various vasodilator agents on coronary artery contractions, possibly associated with the release of Ca2+, influx of Ca2+ through receptor-operated channel, and reoxygenation-induced facilitation of Ca2+ influx. Suppression by the vasodilators of the reoxygenation-induced coronary vasoconstriction may participate in the prophylaxis of no-reflow phenomena elicited by severe hypoxia.
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PMID:Different inhibition by vasodilators of coronary artery contraction. 324 34

Transfection of NIH 3T3 cells with cDNA clones containing either the entire coding sequences or the tyrosine protein kinase domain of the human TRK protooncogene results in the frequent generation of transforming genes. Activation of most of these TRK oncogenes involves acquisition of DNA sequences. These sequences, unlike those present in the original human TRK oncogene, are not derived from tropomyosin genes. The products of these in vitro-generated TRK oncogenes retain the parental tyrosine protein kinase activity and contain an intact carboxyl terminus. However, they exhibit distinct biochemical properties. Whereas some of them are nonglycosylated cytoplasmic molecules, others were found to be transmembrane glycoproteins. These results suggest that TRK oncogenes may induce malignant transformation by allowing their tyrosine kinase to interact with various substrates depending on the nature of their activating sequences. If so, the TRK kinase may serve as a pleiotropic marker to identify various cellular proteins whose unscheduled phosphorylation on tyrosine residues contributes to neoplastic transformation.
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PMID:Frequent generation of oncogenes by in vitro recombination of TRK protooncogene sequences. 336 59

TRK is a human transforming gene generated in a colon carcinoma by a somatic rearrangement that fused a nonmuscle tropomyosin gene to sequences that shared extensive homology with members of the tyrosine-protein kinase supergene family. These sequences are likely to be derived from a transmembrane receptor gene whose putative ligand binding domain has been replaced by tropomyosin. In the present studies, we have expressed the entire coding sequences of the TRK oncogene as well as its protein kinase-related carboxyl-terminal domain in Escherichia coli. Antisera raised against these bacteria-synthesized TRK polypeptides has allowed us to identify the gene product of the TRK oncogene as a 70-kDa protein. Immunoprecipitates containing p70TRK have an associated protein kinase activity specific for tyrosine residues. Moreover, p70TRK is phosphorylated in vivo in serine (75%), threonine (20%), and tyrosine (5%) residues. Finally, immunofluorescence and cellular fractionation studies indicate that p70TRK is preferentially located in the cytoplasmic fraction.
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PMID:Identification and biochemical characterization of p70TRK, product of the human TRK oncogene. 347 1

TRK-100, a stable PGI2 analogue structurally different from carbacyclines, was compared with other antiplatelet drugs for its effect on platelet functions using animal models. TRK-100 (10-300 nM) inhibited rat platelet aggregation induced by ADP (3 microM), collagen (12.5 micrograms/ml) and A23187 (10 microM), and its potency was about 1/3-1/7 that of PGI2. TRK-100 (0.3-3 mg/kg, p.o.) dose-dependently inhibited rabbit platelet adhesion (ED50: 2.2 mg/kg), and its effect lasted over at least 5 hr. In contrast, aspirin and ticlopidine (both at 300 mg/kg, p.o.) showed only a slight inhibition (4-7%). In the thrombocytopenia induced by collagen injection in rats, TRK-100 (3-300 micrograms/kg, i.v.; 0.1-3 mg/kg, p.o.) dose-dependently inhibited a decrease in platelet number, and its ED50 was 0.48-0.62 mg/kg orally and 13.7-16.4 micrograms/kg intravenously, while the inhibition by aspirin and ticlopidine (both at 1000 mg/kg, p.o.) was 40 and 37%, respectively. In the experimental thread thrombosis in rats. TRK-100 (0.03-3 mg/kg, p.o.) dose-dependently inhibited thrombus formation, and its ED50 was 0.46 mg/kg, being 21 and 87 times as potent as aspirin and ticlopidine, respectively. These results reveal that TRK-100 has a potent antiplatelet activity and is orally and intravenously effective for a variety of thrombosis models, suggesting that it may have a therapeutic value as an antithrombotic drug.
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PMID:Antithrombotic effect of TRK-100, a novel, stable PGI2 analogue. 355 83

External and internal chromate exposure of 103 stainless steel welders who were using manual metal are welding (MMA), metal inert gas welding (MIG) and both methods, were measured by ambient and biological monitoring. At the working places the maximum chromium trioxide concentrations were 80 micrograms/m3. The median values were 4 micrograms/m3 (MMA) and 10 micrograms/m3 (MIG). The median chromium concentrations in erythrocytes, plasma and urine of all welders were less than 0.60, 9.00 and 32.50 micrograms/l. For biological monitoring purposes, chromium levels in erythrocytes and simultaneously in plasma seem to be suitable parameters. According to our results, chromium levels in plasma and urine in the order of 10 and 40 micrograms/l seem to correspond to an external exposure of 100 micrograms chromium trioxide per cubic metre, the technical guiding concentration (TRK-value). Chromium concentrations in erythrocytes greater than 0.60 micrograms/l indicate an external chromate exposure greater than the TRK-value.
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PMID:Occupational chronic exposure to metals. I. Chromium exposure of stainless steel welders--biological monitoring. 365 96

Sodium dl-4-[1R,2R,3aS,8bS)-1,2,3a,8b-tetrahydro- 2-hydroxy-1-[(3S,4RS)-3-hydroxy-4-methyl-oct-6- yne-(E)-1-enyl]-5-cyclopenta[b]benzofuranyl]butyrate (TRK-100) is a stable analogue of prostacyclin (epoprostenol, PGI2). The drug was shown to be a potent inhibitor of platelet aggregation in vitro, induced by adenosine diphosphate (ADP), using platelet-rich plasma (PRP) from human and several animal species. The inhibitory activity of TRK-100 using human platelets was half that of PGI2 and eight times that of PGE1. There was a marked tendency for platelet clumps to disaggregate following secondary aggregation in the presence of TRK-100 at final concentrations higher than 1 ng/ml. This activity was similar to PGI2 and more than 30 times that of PGE1. TRK-100 was shown to induce the disaggregation of a pre-existing thrombus in the microcirculation of the hamster cheek pouch. A dose-dependent response was obtained following oral administration of the drug at levels of 50-200 micrograms/kg. Optimal activity was observed 30-60 min after dosing and activity was sustained throughout the experimental period. TRK-100 was more active than PGE1 in the test system and appeared to be of a similar potency to PGI2. Since this drug is stable, orally active and without the hypotensive activity of PGI2, it is considered to be a potentially useful agent for antithrombotic therapy.
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PMID:Effect of a stable prostacyclin analogue on platelet function and experimentally-induced thrombosis in the microcirculation. 391 23

The paper presents hygienic standards, either currently valid in the GFR or planned to be introduced in 1982, for industrial dusts containing free crystalline silica and asbestos. In addition, methods and apparatus for measuring dust respirable fraction concentrations at workplaces are discussed, as well as principles of work conditions evaluation and hygienic interpretation of measurements results. The basis of this interpretation is an assumption that the MAK (Maximale Arbeits-platzkonzentrationen) values for the dusts containing crystalline forms of silica and TRK (technische Richtkonzentrationen) for the dusts containing asbestos are average values for 1 year. Dustiness at workplaces is also evaluated for 1 year.
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PMID:[Measurement and evaluation of air contamination by dust in the Federal Republic of Germany]. 625 83


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