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)

This study employed grade of membership (GoM) analysis in a clinical setting to determine if the DSM-III-R personality disorder (PD) diagnostic criteria cluster into recognizable disorders resembling the official axis II nosology. The GoM model, based on fuzzy-set theoretic concepts, explicitly examines medical diagnostic systems by quantitatively identifying and characterizing subpatterns of illness within a broad class. A semistructured assessment of 110 outpatients was performed for 12 PDs and their 112 diagnostic criteria. GoM analysis was performed using internal variables of the 112 PD criteria rated as present or absent. Demographic variables, axis I and II diagnosis (structured clinical Interview for DSM [SCID]), and treatment response (Global Adjustment Scale [GAS]) information were used as external validators. Four pure types (PT) provided the most satisfactory solution to the data. PT-I is characterized by marked maladaptive personality pathology, which is manipulative, egocentric, impulsive, and alloplastic. PT-II consists primarily of exaggerated socially anxious and detached traits. PT-III is sociably dependent and autoplastic. PT-IV is essentially asymptomatic. GoM provides a more parsimonious handling of the PD criteria than provided by classifying according to DSM categories. The analysis fails to confirm the natural occurrence of any single specific axis II PD or cluster.
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PMID:A mathematical typology analysis of DSM-III-R personality disorder classification: grade of membership technique. 992 80

The severity of infection with Streptococcus pyogenes is strongly influenced by the host's genetics. This observation extends to the murine model of streptococcal infection, where the background of the mouse strain determines the infection outcome (BALB/c are resistant, whereas C3H/HeN are susceptible). To determine the extent to which the MHC complex (H2) contributed to diseases susceptibility, the response to S. pyogenes of congenic BALB mice from a resistant background (BALB/c), but carrying the H2(k) region of susceptible C3H/HeN mice (BALB/k), was examined. BALB/k were as susceptible as the H2 donor strain (C3H/HeN). Linkage analysis performed in F(2) backcross ([BALB/c x C3H/HeN] x BALB/c) mice confirmed the presence of a susceptibility locus within the H2 region on proximal chromosome 17. The possibility that modulation of T cell responses to streptococcal superantigens (GAS-SAgs) by different H2 haplotypes may influence disease severity was examined. BALB/k exhibited a significantly stronger response at the level of cell proliferation and cytokine production to GAS-SAgs than did BALB/c mice. However, the fact that T cell-deficient SCID-C3H/HeN mice also exhibited a susceptible phenotype suggests a more important contribution of innate effector cells to disease susceptibility. Lower transcriptional levels of certain inflammation-related regulatory genes located on chromosome 17 were detected in macrophages from susceptible than in those from resistant mice in response to infection. These results suggest that susceptibility to S. pyogenes may be associated with an altered transcription of specific genes that may compromise the endogenous regulatory processes controlling the inflammatory cascade and favor the progression to sepsis.
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PMID:The role of the MHC on resistance to group a streptococci in mice. 1614 32

We analyzed the differential gene expression between variants of MDA-MB-435 human breast cancer cell line that share an identical genetic background but have different metastatic ability. The major histocompatibility complex class II was found down-regulated in highly metastatic cells and correlated with MHC transactivator (CIITA) expression. Constitutive CIITA expression observed in poorly metastatic is driven by promoters III and IV of CIITA gene. Conversely, both promoters were ineffective in highly metastatic cells. The MHC class II and CIITA expression was restored in these cells upon stimulation with IFNgamma or by the treatment with a hypomethylating agent. Both treatments induced USF-1 and IRF binding complexes to promoter IV but only IFNgamma induced the binding of 435-Lung2 nuclear proteins to an ARE-1 site at the promoter III. Neither Southern blot nor bisulfite sequencing of promoter IV demonstrated strong hypermethylation of this promoter at the IFNgamma-responsive elements such as GAS, E-box or IRF-1. We suggest that partial or hemimethylation of promoter IV is sufficient to silence the CIITA expression in highly metastatic cells and that this epigenetic mechanism is responsible for the lack of MHC-II expression. Forced CIITA expression restored the MHC-II antigen expression in 435-Lung2 cells and abrogates spontaneous lung metastasis in both SCID and nude mice but also affected the tumorigenicity in nude mice. The increase in NK cell infiltration in nude mice bearing CIITA-tumors correlated with sign of tumor cell apoptosis and the increase in the number of NK cells in the spleens, suggesting that NK cells might be responsible for the observed antitumor activity.
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PMID:Differential expression of MHC class II molecules in highly metastatic breast cancer cells is mediated by the regulation of the CIITA transcription Implication of CIITA in tumor and metastasis development. 1634 78

Vaccination with J8-DT, a leading GAS vaccine candidate, results in protective immunity in mice. Analysis of immunologic correlates of protection indicated a role of J8-specific antibodies that were induced post-immunization. In the present study, several independent experimental approaches were employed to investigate the protective immunological mechanisms involved in J8-DT-mediated immunity. These approaches included the passive transfer of mouse or rabbit immune serum/antibodies in addition to selective depletion of T-cell subsets prior to bacterial challenge. Passive transfer of J8-DT antiserum/antibodies from mice and rabbits conferred significant resistance against challenge to mice. To exclude the possibility of involvement of other host immune factors, the studies were repeated in SCID mice, which highlighted the need for an ongoing immune response for long-lived protection. Depletion of CD4(+) and CD8(+) T-cell subsets confirmed that an active de novo immune response, involving CD4(+) T-helper cells, is required for continued synthesis of antibodies resulting in protection against GAS infection. Taken together these results indicate an involvement of CD4(+) T-cells in J8-DT-mediated protection possibly via an ability to maintain antibody levels. These results have considerable relevance to the development of a broad spectrum passive immunotherapy for GAS disease.
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PMID:Mechanism of protection induced by group A Streptococcus vaccine candidate J8-DT: contribution of B and T-cells towards protection. 1934 Mar 9

Given the limited explanatory power of the available neurobiological findings, results of long-term follow-up studies should still be considered as one criterion among others in the development of psychiatric classification systems regarding schizophrenia and affective disorders. A total of 323 first hospitalized inpatients of the Psychiatric Department of the University Munich were recruited at index time and followed up after 15 years. The full follow-up evaluation including several standardized assessment procedures (AMDP, PANSS, SANS, DAS, GAS) could be performed in 197 patients. The patients originally diagnosed according to ICD-9 were re-diagnosed according to ICD-10 and DSM-IV, using SCID among others. Schizophrenic patients had a much poorer outcome than affective or schizoaffective patients in terms of negative syndrome, deficit syndrome, psychosocial impairments and GAS results, and a higher prevalence of a chronic course. The logistic regression analyses performed to find optimized predictor combinations for the prognosis of a chronic course found, for example, the total Strauss-Carpenter Scale score, male gender and several other psychopathological syndromes to be relevant predictors. The findings reflect some long-term related validity for the differentiation between schizophrenia and affective disorders. The Strauss-Carpenter Scale, male gender as well as several psychopathological syndromes are the most relevant predictors for chronicity.
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PMID:The Munich 15-year follow-up study (MUFUSSAD) on first-hospitalized patients with schizophrenic or affective disorders: comparison of psychopathological and psychosocial course and outcome and prediction of chronicity. 2049 79

Fibroblast growth factor (FGF) receptor 2 (FGFR-2) polymorphisms have been associated with an increase in estrogen receptor and progesterone receptor (PR)-positive breast cancer risk; however, a clear mechanistic association between FGFR-2 and steroid hormone receptors remains elusive. In previous works, we have shown a cross talk between FGF2 and progestins in mouse mammary carcinomas. To investigate the mechanisms underlying these interactions and to validate our findings in a human setting, we have used T47D human breast cancer cells and human cancer tissue samples. We showed that medroxyprogesterone acetate (MPA) and FGF2 induced cell proliferation and activation of ERK, AKT, and STAT5 in T47D and in murine C4-HI cells. Nuclear interaction between PR, FGFR-2, and STAT5 after MPA and FGF2 treatment was also showed by confocal microscopy and immunoprecipitation. This effect was associated with increased transcription of PRE and/or GAS reporter genes, and of PR/STAT5-regulated genes and proteins. Two antiprogestins and the FGFR inhibitor PD173074, specifically blocked the effects induced by FGF2 or MPA respectively. The presence of PR/FGFR-2/STAT5 complexes bound to the PRE probe was corroborated by using NoShift transcription and chromatin immunoprecipitation of the MYC promoter. Additionally, we showed that T47D cells stably transfected with constitutively active FGFR-2 gave rise to invasive carcinomas when transplanted into NOD/SCID mice. Nuclear colocalization between PR and FGFR-2/STAT5 was also observed in human breast cancer tissues. This study represents the first demonstration of a nuclear interaction between FGFR-2 and STAT5, as PR coactivators at the DNA progesterone responsive elements, suggesting that FGFRs are valid therapeutic targets for human breast cancer treatment.
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PMID:Interaction between FGFR-2, STAT5, and progesterone receptors in breast cancer. 2146 42