Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thermolabile (TL) phenol sulfotransferase (PST) catalyzes the sulfate conjugation of phenolic monoamines such as dopamine. The level of activity of TL PST in at least one human tissue, the blood platelet, is controlled by a genetic polymorphism. We previously cloned and expressed a cDNA for human liver TL PST and localized its gene, STM, to human chromosome 16p11.2, a region of the chromosome to which the Batten disease gene is also localized. A cDNA for human brain TL PST with an identical open reading frame (ORF) has also been cloned. We have now isolated the human TL PST gene, STM, and have characterized its structural organization as an additional step toward understanding molecular mechanisms involved in the regulation of levels of TL PST activity in human tissue. STM consists of ten exons and nine introns, with a total length of approximately 8.4 kb. Exons range from 88-499 bp in length, while introns vary from 89-1855 bp. Many of the exon-intron splice junctions in STM are located at positions identical to those of splice junctions in the human dehydroepiandrosterone (DHEA) ST gene, STD, and the rat phenol or aryl ST gene. The first two STM exons are represented in the 5'-UTR of a longer TL PST cDNA expressed in both brain and liver, while exon III is represented in a shorter cDNA 5'-UTR expressed in both tissues. These observations suggest alternative transcription initiation and/or alternative splicing as explanations for the existence of TL PST mRNA species with two different 5'-UTRs. 5'-Flanking region(s) of STM contained neither canonical TATA nor CCAAT elements, but they did contain pyrimidine-rich stretches. Northern blot analyses showed that an mRNA species approximately 1.4 kb in length was expressed in human liver, kidney, lung, small intestine, spleen and leukocyte. Molecular cloning and structural characterization of STM will make it possible to study molecular genetic mechanisms involved in the regulation of TL PST activity in human tissue.
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PMID:Human thermolabile phenol sulfotransferase gene (STM): molecular cloning and structural characterization. 769 37

Receiver operating characteristics (ROC) analyses to evaluate and compare the diagnostic accuracy of Food and Drug Administration (510K)-cleared natural rubber latex (NRL)-specific immunoglobulin E (IgE) antibody immunoassays have not been performed using well-characterized skin-testing reagents. Sera were collected from 311 subjects (131 latex puncture skin test [PST] positive and 180 PST negative). All masked, coded sera were analyzed for latex-specific IgE antibodies in the Diagnostic Products Corporation microplate AlaSTAT, HYCOR HY-TEC RAST, and Pharmacia-Upjohn CAP System RAST FEIA (CAP). Diagnostic accuracy was evaluated using GraphRoc for Windows software to construct and analyze ROC curves in relation to the subjects' PST status and the results of the immunoassays. The ROC areas under the curve (AUCs) +/- standard error based on PST for the three diagnostic tests were 0.858 +/- 0.024, 0.869 +/- 0.024, and 0.924 +/- 0.017, respectively, for AlaSTAT, CAP, and HY-TEC. The HY-TEC system had a significantly greater AUC based on PST than those observed for AlaSTAT (P < 0.05) and CAP (P < 0.05) analyses. When the diagnostic tests were probed as to the cutoffs giving maximal diagnostic efficiency compared to PST, CAP and AlaSTAT yielded values of <0.35 kU of allergen IgE (kU(A))/liter and <0.35 kU/liter while the HY-TEC assay yielded 0.11 kU/liter. The diagnostic efficiencies based on PST in our cohort at these cutoffs were 87.1, 88.1, and 88.7%, respectively. The HY-TEC assay had a significantly greater AUC than CAP and AlaSTAT using PST as a diagnostic discriminator in our cohort. When the HY-TEC system was probed at its maximally efficient cutoff (0.11 kU/liter) versus HYCOR's recommended cutoff of 0.05 kU/liter, a loss of sensitivity of 8.4% was observed with a gain in specificity of 19.5%.
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PMID:Receiver operating characteristics analyses of Food and Drug Administration-cleared serological assays for natural rubber latex-specific immunoglobulin E antibody. 1168 55

Imatinib mesylate, a BCR/ABL fusion protein inhibitor, is the first-line treatment against chronic myelogenous leukemia. In spite of its advantageous viewpoints, imatinib still has genuine impediments like undesirable side effects and tumor resistance during chemotherapy. Nanoparticles with sustainable release profile will help in targeted delivery of anticancer drugs while minimizing deleterious side effects and drug resistance. The use of biopolymers like galactoxyloglucan (PST001) for the fabrication of imatinib mesylate nanoparticles could impart its use in overcoming multidrug resistance in chronic myelogenous leukemia patients with minimal side effects. This study involved in the synthesis of PST-Imatinib nanoconjugates with appreciable drug payload and excellent cytotoxicity against drug-resistant chronic myelogenous leukemia cell line (K562) in comparison with free drug. The use of bioinformatics tool revealed better binding affinity for the drug-polysaccharide complex than the drug alone with three proteins: 3QX3 (Topoisomerase), 1M17 (EGFR tyrosine kinase domain), and 3QRJ (ABL1 kinase domain). Assessment of the biochemical, hematological, and histopathological parameters in mice upheld the security and adequacy of the nanoconjugate compared to free drug. Although perspective investigations are warranted, in a condition like drug resistance in leukemia, this nanoconjugate would display a productive approach in cancer therapeutics.
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PMID:Computational and mechanistic studies on the effect of galactoxyloglucan: Imatinib nanoconjugate in imatinib resistant K562 cells. 2834 63