Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The purpose of the audit was to assess the implementation of the protocols developed by Lothian University National Health Service Trust for post-exposure prophylaxis (PEP) against blood-borne virus infections. Patients at risk of infection after an injury were referred to the Department of Genitourinary Medicine (GUM) Edinburgh Royal Infirmary for assessment. A brief description of the incident, the time of the incident, the time of referral and the decision made was documented. The notes of these patients were reviewed 12 months later for the results of prospective HIV test after each incident. There were 76 referrals to the GUM Department in year 2001. Occupational Health (OH) and the Accident and Emergency (A&E) Departments each made 35 referrals. The latter cases were exposures in community settings. Amongst A&E referrals the time interval between the incident and assessment was significantly longer than for OH referrals (P=0.001). Female health workers reported exposure incidents sooner than their male counterparts (P=0.01). Post-exposure prophylaxis for HIV was offered to 22 (29%) of 76 referred individuals, and was accepted by 13 (59%) persons. The course of PEP drugs was discontinued by five (38%) of the 13 individuals after consented post-incident HIV testing of the source patients showed that they were HIV-seronegative. Five of eight individuals completed the course of PEP medication. Only 11 (14%) persons attended for serological testing for blood-borne virus infection three or more months after exposure. None of these 11 persons, one of whom had been given PEP medication, had become infected. Further training and emphasis on the necessity of immediate reporting of occupational incidents and consented post-incident HIV testing of the source patient is needed. The current guidelines appear to work fairly well, but further counselling of those with significant injuries to undertake HIV serological testing after appropriate time interval is required.
Int J STD AIDS 2004 Feb
PMID:Post-exposure prophylaxis for human immunodeficiency virus infection in the Royal Infirmary of Edinburgh--an audit. 1500 77

Tissue inhibitor of metalloproteinase-1 (TIMP-1) is one representative of the natural matrix metalloproteinase (MMP) inhibitor family, encompassing four members. It inhibits all MMPs, except several MT-MMPs, and a disintegrin with a metalloproteinase domain (ADAM)-10 with Kis < nM. Unexpectedly, its upregulation was associated to poor clinical outcome for several cancer varieties. Such finding might be related to the growth-promoting and survival activities of TIMP-1 for normal and cancer cells. In most cases, such properties are MMP-independent and binding of TIMP-1 to an unknown receptor system can trigger JAK (or FAK)/PI3 kinase/Akt/bad-bclX2 (erythroid, myeloid, epithelial cell lines) or Ras/Raf1/FAK (osteosarcoma cell line) signaling pathways. The relationship between viral infection and TIMP-1 expression is here underlined. Thus, TIMP-1 might display a dual influence on tumor progression; either beneficial by inhibiting MMPs as MMP-9 and by impairing angiogenesis or detrimental by favoring cancer cells growth or survival. We consider that the proMMP-9/TIMP-1 balance is of critical importance in early events of tumor progression, and might show promise as diagnostic and prognostic marker of malignancy.
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PMID:Beneficial and detrimental influences of tissue inhibitor of metalloproteinase-1 (TIMP-1) in tumor progression. 1578 25

Genital warts are the commonest sexually transmitted viral infection seen in genitourinary medicine clinics. As common as warts are, with extensive previous studies, literature searches on genital warts in transsexuals were unfruitful. Due to the nature and rarity of such a case, it was felt that it would be interesting to detail its management.
Int J STD AIDS 2005 May
PMID:Genital warts in a transsexual. 1594 73

Attention to viral infection of the male genital tract has been renewed over the last 15 years as a result of the prolific ongoing research on AIDS. Epidemiological studies of the virus in sperm and male genital tract contributes to the understanding of STD physiopathology and helps assessing their impact on male fertility. Recent advances in this field have allowed to offer Assisted reproductive techniques to couples with chronic viral infection, under strict and specific protocols. This paper presents an overview of these recent developments.
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PMID:[Male genital tract infection: the point of view of the virologist]. 1612 33

The immune response to viral infection involves complex network of dynamic gene and protein interactions. We present here the dynamic gene network of the host immune response during human herpesvirus type 6 (HHV-6) infection in an adult T-cell leukemia cell line. Using a pathway-focused oligonucleotide DNA microarray, we found a possible association between chemokine genes regulating Th1/Th2 balance and genes regulating T-cell proliferation during HHV-6B infection. Gene network analysis using an integrated comprehensive workbench, VoyaGene, revealed that a gene encoding a TEC-family kinase, ITK, might be a putative modulator in the host immune response against HHV-6B infection. We conclude that Th2-dominated inflammatory reaction in host cells may play an important role in HHV-6B-infected T cells, thereby suggesting the possibility that ITK might be a therapeutic target in diseases related to dysregulation of Th1/Th2 balance. This study describes a novel approach to find genes related with the complex host-virus interaction using microarray data employing the Bayesian statistical framework.
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PMID:Estimating immunoregulatory gene networks in human herpesvirus type 6-infected T cells. 1614 Feb 73

Viral infection elicits the activation of numerous cellular signal transduction pathways, leading to the induction of both innate and adaptive immunity. Previously we showed that entry of virion particles from a diverse array of enveloped virus families was capable of eliciting an interferon regulatory factor 3 (IRF-3)-mediated antiviral state in human fibroblasts in the absence of interferon production. Here we show that extracellular regulated kinase 1/2, p38 mitogen-activated protein kinase, and Jun N-terminal kinase/stress-activated protein kinase activities are not required for antiviral state induction. In contrast, treatment of cells with LY294002, an inhibitor of the phosphoinositide 3-kinase (PI3 kinase) family, prevents the induction of interferon-stimulated gene 56 (ISG56) and an antiviral response upon entry of virus particles. However, the prototypic class I p85/p110 PI3 kinase and its downstream effector Akt/PKB are dispensable for ISG and antiviral state induction. Furthermore, DNA-PK and PAK1, LY294002-sensitive members of the PI3 kinase family shown previously to be involved in IRF-3 activation, are also dispensable for ISG and antiviral state induction. The LY294002 inhibitor fails to prevent IRF-3 homodimerization or nuclear translocation upon virus particle entry. Together, these data suggest that virus entry triggers an innate antiviral response that requires the activity of a novel PI3 kinase family member.
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PMID:Identification of a novel pathway essential for the immediate-early, interferon-independent antiviral response to enveloped virions. 1635 47

Itk and Rlk are members of the Tec kinase family of nonreceptor protein tyrosine kinases that are expressed in T cells, NK cells, and mast cells. These proteins are involved in the regulation of signaling processes downstream of the TCR in CD4(+) T cells, particularly in the phosphorylation of phospholipase C-gamma1 after TCR activation; furthermore, both Itk and Rlk are important in CD4(+) T cell development, differentiation, function, and homeostasis. However, few studies have addressed the roles of these kinases in CD8(+) T cell signaling and function. Using Itk(-/-) and Itk(-/-)Rlk(-/-) mice, we examined the roles of these Tec family kinases in CD8(+) T cells, both in vitro and in vivo. These studies demonstrate that the loss of Itk and Rlk impairs TCR-dependent signaling, causing defects in phospholipase C-gamma1, p38, and ERK activation as well as defects in calcium flux and cytokine production in vitro and expansion and effector cytokine production by CD8(+) T cells in response to viral infection. These defects cannot be rescued by providing virus-specific CD4(+) T cell help, thereby substantiating the important role of Tec kinases in CD8(+) T cell signaling.
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PMID:Tec kinases Itk and Rlk are required for CD8+ T cell responses to virus infection independent of their role in CD4+ T cell help. 1642 86

The aim of the study was to discover if the prevalence of serological markers of hepatitis B virus infection among men who have sex with men (MSM) who attended a sexually transmitted infections clinic in Edinburgh, Scotland had changed in a 15-year period. This was a retrospective study of 3334 MSM attending the clinic as new patients. Forty-four men (1%) had hepatitis B surface antigenaemia. Overall, sera from 398 (12%) men gave positive results for anti-HBc. The seroprevalence of HBV in men aged 25-34 years and older men declined significantly during the study period. There was no significant change in seropositivity for anti-HBc in men aged 16-24 years. The proportion of men who had been vaccinated previously rose significantly during the most recent three-year period. Although there has been a decline in the prevalence of infection in clinic attendees, there is continued transmission of HBV in the local community.
Int J STD AIDS 2006 Aug
PMID:The changing prevalence of hepatitis B virus infection among men who have sex with men who attended a sexually transmitted infections clinic in Edinburgh, Scotland between 1989 and 2003. 1692 1

The clinical value of aciclovir, oral or topical, in the episodic treatment of recurrent herpes virus infection is limited. Betadine (povidone-iodine) could provide a cheap, effective alternative for managing symptomatic recurrences. We describe a case where povidone-iodine was used successfully to treat a recurrence of genital herpes simplex and review the literature supporting povidone-iodine in the treatment of genital tract infections.
Int J STD AIDS 2006 Dec
PMID:Betadine for herpes simplex infection. 1721 66

Kaposi's sarcoma (KS) is strongly associated with KS herpes virus infection, and inflammation plays an important role in this disease. We have shown that human KS biopsy-derived SLK cells, which are of endothelial origin and form KS-like tumors in nude mice, express the viral RNA pattern recognition receptors Toll-like receptor 3 (TLR3), retinoic acid-inducible gene-I (RIG-I), and melanoma-differentiation-associated gene 5 (MDA5). Furthermore, SLK cells have enhanced release of IL-6, IL-8 (CXCL8), RANTES (CCL5), and IP-10 (CXCL10) proteins in response to the synthetic viral RNA analog poly(I:C). SiRNA knockdowns demonstrated that TLR3 mediates this inflammatory response to poly(I:C) in SLK cells. Furthermore, knockdown of the RNA receptor RIG-I resulted in enhanced chemokine release, in a TLR3 pathway-dependent manner. Thus, exposure of KS cells to viral RNA ligands can result in a TLR3-mediated increase in the secretion of inflammatory proteins associated with KS cell growth that may contribute to disease.
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PMID:Opposing roles of RNA receptors TLR3 and RIG-I in the inflammatory response to double-stranded RNA in a Kaposi's sarcoma cell line. 1815 85


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