Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.2.3.23 (GAS)
 957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This chapter has covered the preparation of pedigree and datafiles suitable for linkage analysis, the calculation of gene frequencies and recombination fractions, the ordering of markers into a genetic map, and the placing of an unknown locus, such as a disease locus or phenotype, onto a fixed map of markers. The chapter has concentrated on the use of the GAS package, but some other programs for linkage analysis have also been mentioned.
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PMID:Gene ordering and localization by linkage analysis. 905 48

The molecular basis for the enhanced growth inhibition of MCF-7 human breast cancer xenografts by a combination of human interferon-beta (IFN-beta) and tamoxifen was investigated. Treatment of MCF-7, MDA-MB-231, and BT-20 cells with the combination of IFN-beta and tamoxifen resulted in enhanced antiproliferative effects in vitro. Treatment with the combination of IFN-beta and tamoxifen enhanced the expression of several IFN-beta-inducible genes in human breast carcinoma cell lines relative to levels induced by IFN-beta alone. Tamoxifen alone did not induce transcription of IFN-stimulated genes (ISGs). Augmentation of ISG expression by the combination of IFN-beta and tamoxifen was noted in breast tumor cell lines irrespective of their functional estrogen receptor (ER) status or their dependence on estradiol for growth, suggesting that upregulation of ISGs was independent of ER status. Enhancement of IFN-stimulated gene expression by tamoxifen occurred at the transcriptional level. Expression of transfected reporter genes under the control of IFN-alpha/beta regulated promoters was also enhanced in IFN-beta and tamoxifen-treated cells. Similarly, transcriptional induction of chimeric reporter plasmids driven by an IFN-gamma inducible promoter (GAS; IFN-gamma activated site) was also enhanced by the combination of IFN-gamma and tamoxifen. In tamoxifen treated cells, IFN-beta and IFN-gamma readily activated transcription factors ISGF-3 and GAF, respectively. Therefore, augmentation of ISG expression by tamoxifen is an early event in the antitumoral activity of this drug combination.
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PMID:Tamoxifen enhances interferon-regulated gene expression in breast cancer cells. 905 94

To investigate the role of putative virulence factors of Streptococcus pyogenes (group A streptococcus; GAS) in causing disease, we introduced specific mutations in GAS strain B514, a natural mouse pathogen, and tested the mutant strains in two models of infection. To study late stages of disease, we used our previously described mouse model (C3HeB/FeJ mice) in which pneumonia and systemic spread of the streptococcus follow intratracheal inoculation. To study the early stages of disease, we report here a model of long-term (at least 21 days) throat colonization following intranasal inoculation of C57BL/10SnJ mice. When the three emm family genes of GAS strain B514-Sm were deleted, the mutant showed no significant difference from the wild type in induction of long-term throat colonization or pneumonia. We inactivated the scpA gene, which encodes a complement C5a peptidase, by insertion of a nonreplicative plasmid and found no significant difference from the wild type in the incidence of throat colonization. However, there was a small but statistically significant decrease in the incidence of pneumonia caused by the scpA mutant. Finally, we demonstrated a very important effect of the hyaluronic acid capsule in both models. Following intranasal inoculation of mice with a mutant in which a nonreplicative plasmid was inserted into the hasA gene, which encodes hyaluronate synthase, we found that all bacteria recovered from the throats of the mice were encapsulated revertants. Following intratracheal inoculation with the hasA mutant, the incidence of pneumonia within 72 h was significantly reduced from that of the control strain (P = 0.006). These results indicate that the hyaluronic acid capsule of S. pyogenes B514 confers an important selective advantage for survival of the bacteria in the upper respiratory tract and is also an important determinant in induction of pneumonia in our model system.
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PMID:Role of putative virulence factors of Streptococcus pyogenes in mouse models of long-term throat colonization and pneumonia. 911 83

The Gen-probe group A Streptococcus direct test (GASD), a nucleic acid probe assay for detecting GAS from throat swabs, has recently been developed. The test uses an acridium ester-labeled DNA probe which is complementary to the rRNA of Streptococcus pyogenes. In this study, 318 single culturette throat swabs were tested by this method using culture as a "gold standard." After plating onto trypticase soy agar plates with 5% sheep blood, swabs were stored at 4 degrees C for no more than 72 h before the probe assay was performed. Our patient population consisted of symptomatic outpatients seen in the Memorial Hospital Emergency Department and in the Family Care Center. After discrepancy testing, sensitivity, specificity, and positive and negative predictive values were 91.4%, 97%, 91.4%, and 97%. The GASD is a rapid, easy-to-perform method for batch screening for streptococcal pharyngitis.
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PMID:Rapid antigen testing for group A Streptococcus by DNA probe. 914 10

Cytokine receptors activate multiple signal transduction pathways, resulting in the induction of specific target genes. We have recently identified a hematopoietic cell-specific immediate-early gene, DUB-1, that encodes a growth-regulatory deubiquitinating enzyme. The DUB-1 gene contains a 112-bp enhancer element that is specifically induced by the beta c subunit of the interleukin-3 (IL-3) receptor. To investigate the mechanism of DUB-1 induction, we examined the effects of dominant-negative forms of JAK kinases, STAT transcription factors, and Raf-1 in transient transfection assays. In Ba/F3 cells, IL-3 induced a dose-dependent activation of DUB-1-luciferase (luc) and GAS-luc reporter constructs. A dominant-negative form of JAK2 (truncated at amino acid 829) inhibited the induction of DUB-1-luc and GAS-luc by IL-3. A dominant-negative form of STAT5 (truncated at amino acid 650) inhibited the induction of GAS-luc but not DUB-1-luc. A dominant-negative form of Raf-1 inhibited the induction of DUB-1-luc but had no effect on the induction of GAS-luc by IL-3. The requirement for JAK2 in the stimulation of the DUB-1 enhancer was further supported by the suppression of DUB-1 induction in Ba/F3 cells stably expressing the dominant-negative JAK2 polypeptide. We hypothesize that IL-3 activates a JAK2/Raf-1 signaling pathway that is required for DUB-1 induction and is independent of STAT5.
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PMID:JAK2 is required for induction of the murine DUB-1 gene. 915 35

The purpose of this study was to examine the reasons people with an episode of Major Depression do or do not seek treatment for the episode. We interviewed 101 persons who met criteria for an RDC Major Depressive episode that lasted at least 4 weeks within 3 years of the interview date, exploring in detail the reasons they gave for seeking or not seeking treatment. GAS ratings indicated that all subjects were moderately impaired at the time of the episode. We found that 55% of the subjects did not seek treatment for this episode, while 45% did. Significant predictors of treatment seeking included a history of prior treatment, higher education, and greater episode length. Non-seekers felt they could handle the episode themselves, did not consider it serious or did not recognize it as an illness. Seekers on the other hand felt the episode was too painful and lasted too long and caused significant disruption in their interpersonal relationships and role functioning. We discuss the implications of these findings in terms of the importance of continued educational efforts to encourage treatment seeking as well as the need for further research to explore the manner in which people decide that affective signs and symptoms have reached a threshold that leads to treatment seeking.
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PMID:Barriers to seeking treatment for major depression. 916 55

STAT proteins are important transcription factors that regulate cell growth and differentiation. To elucidate the molecular mechanisms of insulin actions, we have studied how insulin activates STAT proteins in Hep3B cells. Insulin rapidly phosphorylated Stat1alpha at tyrosine residues and increased its specific binding activities to a GAS/ISRE consensus oligonucleotide. IL-4 also phosphorylated Stat1alpha and increased DNA binding activities to the same Stat1alpha responsive element. There was no increase in tyrosine phosphorylation of JAK family of kinases following insulin stimulation. In contrast, IL-4 stimulated tyrosine phosphorylation of JAK1, JAK2 and tyk2 in this cell line. These data indicate that insulin receptor signaling can activate the transcriptional regulatory function of STAT protein, and that insulin actions on Stat1alpha are mediated through signaling pathways independent of JAK family of kinases.
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PMID:Novel pathway of insulin signaling involving Stat1alpha in Hep3B cells. 919 89

GH is known to activate JAK2 tyrosine kinase and members of the Stat family of transcription factors, including Stats 1, 3, and 5. The recent observation that at least two Stat5 proteins (Stat5A and Stat5B) exist in mouse and human, raises the question of whether GH activates both Stat5A and Stat5B and, if so, whether the requirements for activation are the same. An initial report investigating this issue demonstrated GH-dependent activation of Stat5A but not Stat5B. In this paper, we demonstrate (in COS cells expressing rat GH receptor (rGHR) and either Stat5A or Stat5B, 3T3-F442A fibroblasts, and CHO cells expressing rGHR) that GH induces tyrosyl phosphorylation of both Stat5A and Stat5B. Similar time courses of phosphorylation were observed for the two proteins. Interestingly, the pattern of observed bands differs for the two forms of Stat5. Two closely migrating Stat5A bands can be detected in cells treated with or without GH. Both of these bands become tyrosyl phosphorylated in response to GH. Three species of Stat5B are observed in untreated cells. An additional, more slowly migrating Stat5B band, appears upon treatment with GH. The three more slower migrating Stat5B bands observed in response to GH contain phosphorylated tyrosyl residues. We further demonstrate that GH induces binding of Stat5A and Stat5B, as well as Stat1, to the GAS-like element in the beta-casein promoter. We and others have demonstrated previously that specific regions of GHR are required for GH-dependent activation of what is here identified as Stat5B. To gain insight into the mechanism by which GH promotes tyrosyl phosphorylation of Stat5A, GH-dependent tyrosyl phosphorylation of Stat5A was examined in CHO cells expressing truncated and mutated rGHR. The results indicate that Stat5A and Stat5B require the same regions of rGHR for maximal activation by GH: the C-terminal half of the cytoplasmic domain; tyrosines 333 and/or 338 in the N-terminal half of the cytoplasmic domain; and the regions required for JAK2 activation. To dissect further the mechanism by which GH activates Stat5A and B, the requirement for JAK2 in GH-dependent Stat5 tyrosyl phosphorylation was assessed using JAK2-deficient cells expressing GHR (gamma2A-GHR) and the wild-type parental cell line expressing GHR (2C4-GHR). GH-induced tyrosyl phosphorylation of Stat5B in 2C4-GHR cells but not in the JAK2 deficient, gamma2A-GHR cells, indicating that JAK2 is required for GH-dependent tyrosyl phosphorylation of Stat5B. Western blotting revealed that Stat5A is not expressed in this cell type. Taken together, these findings suggest that: 1) GH activates both Stat5A and Stat5B in several cell types; 2) the pattern of bands observed differs for Stat5A and Stat5B; 3) GH-dependent tyrosyl phosphorylation of Stat5A requires specific regions of GHR, and these requirements are the same as for Stat5B; and 4) JAK2 kinase is required for GH-dependent tyrosyl phosphorylation of Stat5B and, most likely, Stat5A.
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PMID:Growth hormone-induced tyrosyl phosphorylation and deoxyribonucleic acid binding activity of Stat5A and Stat5B. 923 97

An outbreak of scarlet fever involving 12 children occurred at a hospital day care centre from February to March 1996. Twenty-five throat isolates of Streptococcus pyogenes (GAS, group A streptococcus) available from 24 children, including 10 children with scarlet fever and 14 asymptomatic carriers, and one asymptomatic staff member were studied for the presence of genes encoding streptococcal pyrogenic exotoxin types A (speA), B (speB), and C (speC) and for protease activity. Antimicrobial susceptibilities using the E-test, cluster analysis by cellular fatty acid composition and random amplified polymorphic DNA (RAPD) patterns by means of arbitrarily-primed polymerase chain reaction (APPCR) of the isolates were performed to investigate the outbreak. Only one isolate from an asymptomatic child possessed the speA gene. All isolates possessed the speB gene and 24 (96%) isolates were positive for the speC gene. There was no difference in protease activity between isolates from children with scarlet fever and from asymptomatic carriers. Thirteen isolates (10 recovered from children with scarlet fever, two from asymptomatic children, and one from the staff member) were considered to be the same strain according to the identical antimicrobial susceptibility profile and RAPD patterns and were also considered to be similar by cluster analysis of fatty acid composition. These findings suggest that the outbreak was caused by a unique clone of GAS. We conclude that RAPD typing and cluster analysis by cellular fatty acids composition both provide a powerful tool for epidemiological investigation of GAS infections.
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PMID:Outbreak of scarlet fever at a hospital day care centre: analysis of strain relatedness with phenotypic and genotypic characteristics. 925

The Nb2 PRL receptor (PRL-R) is known to mediate PRL signaling to the interferon (IFN) regulatory factor-1 (IRF-1) gene via the family of signal transducers and activators of transcription or Stats. To analyze the components of the PRL-R/Stat/IRF-1 signaling pathway, various PRL-R, Stat, and IRF-1-CAT reporter constructs were transiently cotransfected into COS cells. First, mutations in the IFNgamma-activated sequence (GAS), either multimerized or in the context of the 1.7-kb IRF-1 promoter, failed to mediate a PRL response, showing that the IRF-1 GAS is a target of PRL signaling. Next, pairwise alanine substitutions into conserved residues in the proline-rich motif or Box 1 region and two tyrosine mutations, Y308F and Y382F, in the PRL-R intracellular domain all impaired PRL signaling to multimerized GAS or to the 1.7-kb IRF-1 promoter. Furthermore, these PRL-R mutants mediated reduced Stat1 binding to the IRF-1 GAS. Transfection of Stat1 further enhanced PRL signaling to the IRF-1 promoter, suggesting that Stat1 is a positive mediator of PRL action. These studies show that both membrane proximal and distal residues of the PRL-R are involved in signaling to the IRF-1 gene. Further, Stat1 and the GAS element are important for PRL activation of the IRF-1 gene.
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PMID:Multiple prolactin (PRL) receptor cytoplasmic residues and Stat1 mediate PRL signaling to the interferon regulatory factor-1 promoter. 925 25


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