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

Streptococci of Lancefield Group B (GBS) are known to cause maternal sepsis and neonatal infection, whereas streptococci Lancefield Group A (GAS) cause vulvo-vaginitis in both children and adults. Prevalence of SGB colonization of the lower genital tract of normal women is between 4-18%, with higher rates found in hospital personnel and delivery rooms. Such high carriage rates may be a significant factor in nosocomial transmission of GBS to neonates. Symptomatic infection is uncommon and usually secondary to other pathological states. Amnionitis is a complication of vaginal carriage of GBS and there is now evidence that chorioamnionitis is associated with pre-term labour and its attendant problems. GBS infection of the male genitalia has also been described. Intrapartum chemoprophylaxis has been shown to prevent early onset GBS disease of the neonate. Prevalence of GAS in the genital tract is lower than that for GBS, but is more likely to be symptomatic. The response to penicillin is usually prompt. Optimal drug regimens need to be determined, particularly for use in pregnancy.
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PMID:Streptococci and the genital tract. 884 14

M protein is thought to contribute to the ability of non-opsonized group A and group G streptococci (GAS and GGS, respectively) to resist phagocytosis by polymorphonuclear leukocytes. In previous studies, correlation between M protein expression and phagocytosis was determined by incubating these pathogens in human blood and comparing colony-forming bacterial counts prior to and after exposure to blood (direct bactericidal assay; DBA). Here, we report the application of flow cytometry to measure GAS and GGS resistance to phagocytosis. The results of the assays were in complete agreement with those from DBAs. Nevertheless, flow cytometry was regarded as superior to DBA because of its speed and potential uses for quantitative studies. In addition, the use of anti-CD11b monoclonal antibody for granulocyte staining guaranteed a non-compromized granulocyte function. The optimized protocol for flow cytometry presented here could be utilized to directly measure the involvement of individual protein types in bacterial resistance to phagocytosis.
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PMID:Measuring resistance to phagocytosis of group A and G streptococci: comparison of direct bactericidal assay and flow cytometry. 853 74

Vascular smooth muscle cells (VSMC) are the predominant cell type in the media of a normal artery. Injury to the vessel wall leads to platelet deposition and the release of numerous factors, including PDGF, which exerts its biological effects by binding to specific surface receptors on the smooth muscle cell membrane. We demonstrate that PDGF-stimulated smooth muscle cells activate the STAT (signal transducers and activators of transcription) family of proteins in addition to other signaling pathways (e.g., RAS-RAF-MAP Kinase). We show that the transcription factor p91 (STAT1 alpha) is rapidly activated by PDGF in VSMC and specifically binds to the regulatory elements SIE or GAS. We hypothesize that signal transduction by p91 plays an important role in VSMC, especially after injury with the release of growth factors such as PDGF.
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PMID:PDGF receptor-to-nucleus signaling of p91 (STAT1 alpha) transcription factor in rat smooth muscle cells. 854 54

We analyzed the activation and changes in the protein level of STAT1 as a consequence of in vivo treatment with superantigens. Ninety minutes after i.p. injection of the staphylococcal enterotoxin B (SEB), a complex containing STAT1 that was able to specifically bind to DNA containing GAS-like sequences was activated in mouse splenocytes. This complex had the same characteristics as that induced by IFN-gamma in several in vitro systems. Activation of the complex was inhibited by cyclosporin A, and Abs against IFN-gamma severely decreased the amount of complex detected. When splenocytes were analyzed 24 h after SEB treatment, a high increase in the amount of the STAT1 isoforms, STAT91 and STAT84, was observed by Western analysis, but binding to GAS-like sequences was clearly decreased when compared with analysis at 90 min. Nevertheless, when SEB was injected a second time 24 h after the first injection, the binding of STAT1 to GAS-like sequences had risen again. This approach corroborates the implication of IFN-gamma in the response to superantigens in vivo and shows the relevance of analysis of transcription factors in defining the molecular events involved in the immune response.
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PMID:Stat1 implication in the immune response to superantigens in vivo. 856 37

The rat homolog of sheep mammary gland factor (MGF)/Stat5 has been isolated and used to study the regulation of Stat5 during mammary gland development and PRL regulation in COS cells transfected with Stat5a and the PRL receptor. Two alternatively spliced isoforms, designated Stat5a1 and Stat5a2, were identified, the latter encoding a carboxy-terminal truncated protein. A polyclonal antibody to a carboxy-terminal peptide of Stat5a1 was generated and used to measure the level of this isoform during mammary gland development and after PRL induction in COS cells transiently transfected with Stat5a and the long form of the PRL receptor. Surprisingly, Stat5a mRNA and protein were readily detected both in virgin rats and after mammary gland involution. The levels of Stat5a increased during pregnancy, were highest in late pregnancy, and then, unexpectedly, decreased during lactation, the time at which the highest levels of milk protein gene expression are observed. Electrophoretic mobility shift assays using the specific anti-Stat5a1 antisera demonstrated that Stat5a1 comprises part of the heterogeneous, PRL-inducible, protein-DNA complex associated with the beta-casein GAS site. Immunocytochemical analysis detected considerable cytoplasmic and some nuclear staining for Stat5a1 during late pregnancy and predominantly nuclear staining during early lactation. The lack of correspondence of Stat5a gene expression and beta-casein gene expression suggests that Stat5 activation may facilitate the interaction of other factors binding within composite response elements identified recently in the milk protein gene promoters that are then responsible for the stable expression of milk protein genes in terminally differentiated mammary epithelial cells.
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PMID:Regulation of mammary gland factor/Stat5a during mammary gland development. 858 36

Among 148 patients presenting Panic Disorder (DSM-III-R), 18.9% have an alcohol disorder, 8.8% present abuse and 10.1% dependence. Mean age of onset of alcoholism was much earlier than panic disorder. Patients with alcoholism: a) are males more frequently (0.001); b) present more alcoholism in first grade relatives (0.05); c) use more often other drugs like: tobacco (0.01), coffee (p < 0.01), cocaine (p < 0.01) and cannabis (p < 0.001), d) patients with alcoholism refer a greater severity of their panic attacks when drinking large amounts of alcohol (25%) than the group without these problems (2.5%) (x2:14.8) (p < 0.001) e) according to the GAS the overall level of performance is lower in alcoholics (p < 0.005); f) present more anxiety measured by the HARS (p < 0.01), and therefore have more comorbid anxiety disorders according to DSM-III-R (p < 0.01). The clinical significance of these findings is discussed.
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PMID:[Comorbidity in panic disorders and alcoholism (II). Alcoholism in a sample of 148 patients with panic disorders]. 858 34

Binding of many cytokines to their cognate receptors immediately activates Jak tyrosine kinases and their substrates, STAT (signal transducers and activators of transcription) DNA-binding proteins. The DNA binding targets of STATs are sequence elements related to the archetypal gamma interferon activation site, GAS. However, association of interleukin 1 (IL-1) with Jak-STAT signaling has remained unresolved. We now report an element termed LILRE (lipopolysaccharide [LPS] and IL-1-responsive element) in the human prointerleukin 1beta gene (IL1B) which can be immediately induced by either lipopolysaccharide (LPS) or IL-1 protein to bind a tyrosine-phosphorylated protein. This LPS- and IL-1-induced factor (LIL factor) is recognized by an antibody raised against the N terminus of Stat1, but not by those specific for either the C terminus of Stat1 or any other GAS-binding STAT. Phosphotyrosine (P-Tyr) specifically inhibits formation of the LIL factor-DNA complex, suggesting the importance of P-Tyr for the DNA-binding activity, as has been found for all STAT dimers. Analysis of DNA-binding specificity demonstrates that the LIL factor possesses a novel GAS-like binding activity that contrasts with those of other STATs in a requirement for a G residue at position 8 (TTCCTGAGA). Further investigation has revealed that IL-6, but neither IL-4 nor gamma interferon, activates the LIL factor. Thus, the existence of such a STAT-like factor (LIL-Stat) relates the LPS and IL-1 signaling pathway to other cytokine receptor signaling pathways via the activation of STATs. Moreover, the unique DNA-binding specificity and antigenicity of this factor suggest that LPS, IL-1, and IL-6 may use a common signaling pathway.
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PMID:A novel STAT-like factor mediates lipopolysaccharide, interleukin 1 (IL-1), and IL-6 signaling and recognizes a gamma interferon activation site-like element in the IL1B gene. 862 85

Transcriptional regulation of the human histidine decarboxylase (HDC) gene by gastrin and the phorbol ester phorbol 12-myristate 13-acetate (PMA) was studied using transient transfection of human HDC promoter-luciferase constructs in a human gastric carcinoma cell line (AGS-B) that expresses the human cholecystokinin-B/gastrin receptor. The transcriptional activity of the human HDC promoter was stimulated 3-4-fold by gastrin and 13-fold by PMA, effects that could be blocked by down-regulation or antagonism of protein kinase C. 5'- and 3'-deletion analysis demonstrated that the sequence responsible for gastrin- and PMA-stimulated transactivation (gastrin response element (GAS-RE)) was located in a region (+2 to +24) downstream of the transcriptional start site (+1) in the human HDC promoter and contained a palindrome (5'-CCCTTTAAATAAAGGG-3'). When ligated upstream of the herpes simplex virus 1 thymidine kinase promoter, a single copy of the GAS-RE was sufficient to confer responsiveness to gastrin and PMA. Electrophoretic mobility shift assays with specific competitors and factor-specific antibody supershifts showed that the labeled GAS-RE bound a novel nuclear factor(s). In addition, both gastrin and PMA increased binding of this factor to the GAS-RE. Hence, the palindromic GAS-RE site is sufficient to explain the gastrin/PMA responsiveness of the human HDC promoter and appears to bind a novel transcription factor.
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PMID:The human histidine decarboxylase promoter is regulated by gastrin and phorbol 12-myristate 13-acetate through a downstream cis-acting element. 866 34

Tumor necrosis factor receptor p75 (TNF-R p75) is a 75-kDa type I transmembrane protein expressed predominantly on cells of hematopoietic lineage. TNF-R p75 belongs to the TNF receptor superfamily characterized by cysteine-rich extracellular regions composed of three to six disulfide-linked domains. In the present report we have characterized, for the first time, the complete gene structure for human TNF-R p75, which spans approximately 43 kbp. The gene consists of 10 exons (ranging from 34 base pairs to 2.5 kilobase pairs) and nine introns (343 base pairs to 19 kilobase pairs). Consensus elements for transcription factors involved in T cell development and activation were noted in the 5'-flanking region including T cell factor-1, Ikaros, AP-1, CK-2, interleukin-6 receptor E (IL-6RE), ISRE, GAS, NF-kappaB, and Sp1. The unusual (GATA)n and (GAA)(GGA) repeats found within intron 1 may prove useful for further genome analysis within the 1p36 chromosomal locus. Characterization of the human TNF-R p75 gene structure will permit further assessment of its involvement in normal hematopoietic cell development and function, autoimmune disease, and nonrandom translocations in hematopoietic malignancies.
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PMID:Human tumor necrosis factor receptor p75/80 (CD120b) gene structure and promoter characterization. 870 85

The accuracy of the pulse oximeter was examined in hypoxic patients. We studied 11 cyanotic congenital heart disease patients during surgery, and compared the arterial oxygen saturation determined by both the simultaneous blood gas analysis (CIBA-CORNING 288 BLOOD GAS SYSTEM, SaO2) and by the pulse oximeter (DATEX SATELITE, with finger probe, SpO2). Ninty sets of data on SpO2 and SaO2 were obtained. The bias (SpO2-SaO2) was 1.7 +/- 6.9 (mean +/- SD) %. In cyanotic congenital heart disease patients, SpO2 values were significantly higher than SaO2. Although the reason is unknown, in constantly hypoxic patients, SpO2 values are possibly over-estimated. In particular, pulse oximetry at low levels of saturation (SaO2 below 80%) was not as accurate as at a higher saturation level (SaO2 over 80%). There was a positive correlation between SpO2 and SaO2 (linear regression analysis yields the equation y = 0.68x + 26.0, r = 0.93). In conclusion, the pulse oximeter is useful to monitor oxygen saturation in constantly hypoxic patients, but the values thus obtained should be compared with the values measured directly when hypoxemia is severe.
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PMID:[Accuracy of a pulse oximeter during hypoxia]. 872 6


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