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 expression pattern of tyrosine kinase in bladder cancer cells was evaluated by PCR amplification with degenerate primers derived from conserved catalytic domain in tyrosine kinase. The results indicated that TRK-E and Arg kinases were more abundantly expressed than several other kinases in bladder cancer. In addition, we identified a novel clone whose sequence could not be matched in GeneBank. This clone may represent a serine/threonine kinase based on sequence similarity.
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PMID:Tyrosine kinase expression profile in bladder cancer. 925 93

Exposures to volatile nitrosamines were measured at 24 rubber manufacturing plants from 1992 to 1995. A total of 709 exposure measurements were taken in general areas or personal breathing zones to estimate exposure according to production types (seals, joints, tyres, gloves, etc.) and production steps, from mixing to storage. Five different nitrosamines were identified. N-Nitrosodimethylamine is the most frequently encountered nitrosamine and represents the most important fraction of the total nitrosamine concentration measured in a given sample. This fact is consistent with the use of rubber additives containing corresponding amine precursors. One hundred and forty-one of the 709 values exceeded the German target value (TRK) of 2.5 micrograms/m3 for all nitrosamines present from rubber vulcanisation, the only available standard for occupational nitrosamine exposures. The salt bath curing process generates particularly high nitrosamine levels, 90% of the 96 measurements being over the TRK, with many values exceeding 20 micrograms/m3. The reasons why the TRK is exceeded are generally well identified. To reduce nitrosamine emission levels it would be advisable to eliminate nitrogen oxide sources, principally by using a process other than salt bath curing, and to develop different rubber stocks that do not contain secondary aliphatic amine functional groups ("safe amines").
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PMID:Assessment of exposure to carcinogenic N-nitrosamines in the rubber industry. 934 27

Morphologic (Shimada classification--SC, original and modified histologic grades--OHG and MHG) and nonmorphologic (serum LDH, 1 p del, DNA index, N-myc copy number, telomerase activity, and expression of MRP, MDR1, and TRK) prognostic markers for NB have been reviewed. The functional role of these nonmorphologic markers in the development and progression of this disease include abnormal cell proliferation, resistance to chemotherapeutic agents, and induction of apoptosis. A statistically significant association between high OHG/MHG (grade 3), DNA index of 1 (diploidy), > 1 copy of N-myc per haploid genome and serum LDH of > or = 1500 IU/1 (p < 0.001 for each) has been described. In SC, undifferentiated histology and high MKI are associated with N-myc amplification. However, a lack of correlation between morphology and N-myc amplification has been found in localized NB. Confirmation of these observations must now be obtained on larger numbers of prospectively studied cases. Data on correlation for various prognostic markers could provide guidelines for identification of subsets of NB having strongly significant, readily determinable, reproducible, and relatively inexpensive prognostic markers that could ultimately be used to design an algorithm for risk-specific therapy.
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PMID:Correlation between morphologic and nonmorphologic prognostic markers of neuroblastoma. 938 56

TRK-530 is a newly synthesized diphosphonate derivative. We investigated the effect of TRK-530 on type II collagen-induced arthritis (CIA) in mice in comparison to that of prednisolone and indomethacin. TRK-530 at a dose of 25 mg/kg showed a tendency to inhibit CIA. TRK-530 at a dose of 50 mg/kg inhibited the development of the CIA in terms of the progression of footpad swelling, bone damage and histopathological changes. TRK-530 at a dose of 50 mg/kg also significantly inhibited the delayed type hypersensitivity (DTH) response to type II collagen, but not the production of anti-type II collagen IgG antibody in arthritic mice. To investigate the inhibitory mechanism of TRK-530, the type of effect of TRK-530 on the production of IL-1 beta in vitro was studied. TRK-530 at a concentration of 10(-4) M inhibited LPS-induced IL-1 beta production from J774.1 cells. In conclusion, TRK-530 inhibited CIA in mice. The inhibition of the DTH reaction to type II collagen and the inhibition of IL-1 beta production may partly participate the anti-rheumatoid action of TRK-530.
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PMID:The effect of TRK-530 on experimental arthritis in mice. 940 21

The exposure of employees to airborne dust and microorganisms was assessed in a waste processing plant established to recover reusable materials from unsorted domestic and industrial waste. Exposure criteria considered relevant were the quantity of the individual size-selected particle fractions, the morphological properties of the particles, their heavy metal content, and the degree of their contamination with various microorganisms and mold. In addition, separate microbiological analyses to determine potential pathogen concentrations in the air were made. The highest concentrations of total and fine dust were measured in the waste delivery area. A close correlation between the frequency of deliveries and the level of dust exposure was observed. In this area, fine dust concentrations exceeded the threshold limit value of 6 mg/m3 repeatedly for shorter periods. The average fine dust concentration during an entire work-shift, however, was considerably lower than this value. Particles with an aerodynamic diameter of 2 to 7 microns predominated both in the waste delivery and the processing areas. Fibrous dust particles were present in smaller numbers than spherical particles and consisted mainly of organic materials. Natural and artificial inorganic fibers were found only occasionally. The concentrations of lead, cadmium, nickel and mercury were considerably lower than the corresponding MAK and TRK values, and were--with the exception of lead--in the range of the respective metal concentrations in the atmosphere of urban areas. Microscopical examinations of used protective masks (protection category P2) revealed that dust particles were deposited even on the inner side of the masks. Most of the particles on this side were very small and carried nickel or titanium. Microorganism concentrations measured in air from the highly dust-exposed areas of the plant showed values up to 6.9 x 10(5) cfu/m3, with a mold content of 6.6 x 10(4) cfu/m3. Approximately 90% of the microorganisms were deposited on particles of the fine dust fraction (particle size < 7 microns), and more than 50% contaminated particles with an aerodynamic diameter of 2 to 4.7 microns. In the compost facility, mold concentrations of up to 8.4 x 10(5) cfu/m3 were measured. In contrast, the level of microbial contamination in the filtered air from the compost facility did not exceed the concentration measured in air outside the plant. The data which were obtained during the winter months are probably at the lower end of the average exposure range over the entire year. In regard to exposure assessment, it should be mentioned that particles with a size of 4 to 7 microns are not really "inert" particles, since they are preferential carriers for heavy metals and microorganisms. More studies in the future should be performed to establish, whether the level of exposure to microorganisms can be estimated indirectly by the determination of dust exposure.
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PMID:[Dust and microorganism count at delivery, sorting and composting of home refuse and home refuse-like industrial waste]. 940 5

The thyroid TRK-T3 oncogene results from the fusion of the tyrosine kinase (TK) domain of NTRK1 (one of the receptors for the Nerve Growth Factor) on chromosome 1 to sequences of a novel gene, TFG, on chromosome 3. The 68 kDa TRK-T3 fusion oncoprotein displays a constitutive tyrosine kinase activity resulting in its capability to transform mouse NIH3T3 cells. The TFG portion of TRK-T3 contains a coiled-coil domain most likely responsible for the constitutive, ligand-independent activation of the receptor tyrosine kinase activity. We have previously shown that TRK-T3 oncoprotein forms, in vivo, complexes of three or four molecules. By mean of different experimental approaches, we show here that TRK-T3 activity depends on oligomers formation. In addition, the analysis of different TRK-T3 mutants indicates that the TFG coiled-coil domain and its N-terminal region are both required for the activation and the fully transforming activity of the TRK-T3 oncoprotein, although, most likely, they play a role in different steps of the transforming process. The deletion of the coiled-coil domain abrogates the oligomers formation leading to a constitutive activation; the deletion of the N-terminal region, although not affecting phosphorylation and complexes formation, abrogates transformation, thus suggesting a role in cellular localization and/or interaction with substrata.
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PMID:Role of the TFG N-terminus and coiled-coil domain in the transforming activity of the thyroid TRK-T3 oncogene. 948 46

A new type of kappa-agonist, 17-cyclopropylmethyl-3, 14 beta-dihydroxy-4,5 alpha-epoxy-6 beta-[N-methyl-trans-3-(3-furyl) acrylamido]morphinan hydrochloride (1, TRK-820), was discovered by a new working hypothesis. The "message-address concept" for opioid antagonists and the "accessory site" for general antagonists were applied to design TRK-820. A unique structural feature of TRK-820, which is different from other prototypical kappa-opioid receptor agonists, is the existence of the 4,5-epoxymorphinan structure with a tyrosine-glysine moiety for endogenous opioid peptides such as dynorphins. TRK-820 exhibited high potency and high kappa-selectivity in guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. In the mouse acetic-acid-induced writhing model and mouse tail flick model of antinociception, TRK-820 was 85-140 times more potent than morphine and 85-350 times more potent than U-50488H. This structurally novel kappa-agonist showed neither aversion nor preference in the Conditioned Place Preference test, in spite of the fact that prototypes of kappa-agonists (U-50488H derivatives) demonstrated aversion.
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PMID:Discovery of a structurally novel opioid kappa-agonist derived from 4,5-epoxymorphinan. 950 72

TRK-530, a newly synthesized bisphosphonate, was assessed for its effects on the accumulation of superoxide anions derived from human formyl-methionyl-leucyl-phenylalanine-stimulated polymorphonuclear leukocytes (PMN), and for its effects on bone resorption using a pit formation assay. TRK-530 concentration-dependently inhibited superoxide accumulation derived from PMN and osteoclast pit formation stimulated by 1,25-dihydroxyvitamin D3. Incadronate and risedronate had a strong inhibitory effect on pit formation, but no antioxidative activity. These data suggest that the anti-bone resorption activities of TRK-530 are possibly unrelated to its antioxidant properties. However, it is difficult to conclude at present which mechanisms play the most important role in the anti-bone resorption activities of TRK-530.
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PMID:TRK-530 inhibits accumulation of superoxide anions derived from human polymorphonuclear leukocytes and bone resorption induced by activated osteoclasts. 953 11

TRK-530 is a novel synthetic bisphosphonate compound which exhibits inhibitory activity in the rat adjuvant arthritis (AA) model. We found that, during AA development, the concentrations of cytokine-induced neutrophil chemoattractant-1 (CINC-1) and tumor necrosis factor alpha (TNF-alpha) in the bone marrow increased, and that administration of TRK-530 decreased the concentrations of these cytokines. The suppression of these concentration increases paralleled the inhibition of paw edema. Paw edema inhibition by TRK-530 in rat AA may be the result of decreasing CINC-1 and TNF-alpha concentrations.
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PMID:Inhibitory effect of TRK-530 on inflammatory cytokines in bone marrow of rats with adjuvant arthritis. 959 90

TRK-530 is a novel bisphosphonate derivative. We examined the anti-inflammatory effects of TRK-530 on adjuvant arthritis (AA) rats. When TRK-530 at a dose of 2.5 mg/kg was administered for 2 weeks to AA rats, it inhibited destructive changes in arthritic joints such as paw edema, bone loss and joint degeneration. TRK-530 also inhibited splenomegaly and suppressed the increase in serum sialic acid which is measured as a systemic parameter of inflammation. To clarify the inhibitory mechanism of TRK-530, interleukin-1 (IL-1)-like activities of resident peritoneal macrophages in AA rats given TRK-530 were compared with those of control rats. We found that TRK-530 inhibited IL-1-like activity induced by bacterial lipopolysaccharide 6 weeks after administration when the IL-1-like activities of control rats were still at high levels. These findings suggest that TRK-530 exerts anti-inflammatory activities in AA rats.
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PMID:Inhibitory effects of TRK-530 on rat adjuvant arthritis. 959 91


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