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)

This article presents an overview of the use of mathematical models to study the demographic impact of STDs. Written for the nonmathematician, the article introduces the basic concepts of mathematical epidemiology for infectious diseases, such as the mass-action principle, the threshold density concept, and the basic reproductive rate. Described are the main features that characterize the epidemiology of STDs and those features that differentiate them from other directly transmitted diseases, such as measles, rubella, and others. Also presented are major findings concerning the importance of sexual behavior on the dynamics of STD transmission, and the numerical analysis of the demographic impact on gonococcal and HIV infections using a mathematical model. The epidemiology of these two STDs is explored, as well as how the growth rate of the population can influence the epidemiology of these STDs. Finally, the authors demonstrate how, under some circumstances, early treatment of gonorrhea can reduce the demographic impact of HIV in regions most affected by both diseases.
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PMID:The impact of HIV and other STDs on human populations. Are predictions possible? 810 29

In the study and incidence of measles complications in the respiratory tract was analyzed in patients hospitalized in the Department of Infectious Diseases CSK WAM in 1972-1992 because of measles. In this period the (equal?) epidemiology of disease was observed in 1989/1990. In 17% hospitalized patients pharyngitis and/or pneumonia were observed as a typical complications of measles. High percentage of complications without consequences was probably connected with virus mechanism of infection.
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PMID:[Complications in the respiratory tract from measles]. 814 62

Vaccine efficacy and mortality in successive cohorts of children who routinely received either Edmonston-Zagreb high-titre (EZ-HT) or Schwarz standard (SW-STD) measles vaccines have been examined in a rural area of Senegal. The 2 vaccines were equally protective against measles infection (vaccination efficacy: EZ-HT 94%; SW-STD 93%). Children who did not attend a scheduled session to receive measles vaccine had a higher mortality rate between 9 months and 2 years of age than did children receiving either EZ-HT (mortality ratio [MR] = 1.81, 95% confidence interval [CI] 1.06-3.08) or SW-STD measles vaccine (MR = 1.74, 95% CI 0.95-3.21). Children of either sex vaccinated with EZ-HT had lower mortality than their equivalents who had not received any measles vaccine. There was no difference in overall mortality between recipients of EZ-HT and SW-STD (MR = 0.96, 95% CI 0.70-1.30). Using a Cox regression analysis to adjust for sex, age and significant background factors (season and death of mother), mortality rates tended to be lower for male recipients of EZ-HT than for boys receiving SW-STD (MR = 0.73, 95% CI 0.50-1.11) and higher for girls receiving EZ-HT than for girls receiving SW-STD (MR = 1.30, 95% CI 0.81-2.09) (test of interaction between sex and vaccine, P = 0.067). The tendency to reduced survival benefit for girls following receipt of high-titre measles vaccines substantiated observations from randomized trials in Guinea-Bissau, Senegal and Haiti. Existing data provide little support for the notion that high-titre vaccine is deleterious but it may not have the same beneficial effects as standard-titre measles vaccine.
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PMID:A comparison of vaccine efficacy and mortality during routine use of high-titre Edmonston-Zagreb and Schwarz standard measles vaccines in rural Senegal. 875 96

At 3-5 years of age, female recipients of Edmonston-Zagreb high-titre (EZ-HT) and Schwarz high-titre (SW-HT) measles vaccine had lower survival rates than female recipients of Schwarz standard measles vaccine (SW-STD) in Guinea-Bissau, Senegal and Haiti. In Senegal, the children who received high-titre vaccines have now been followed to the age of 5-7 years to determine whether the difference in mortality persisted, and whether differences in vaccine efficacy were apparent. At this age there was no difference in mortality between female recipients of high-titre and standard titre measles vaccines. There was no indication that high-titre EZ-HT vaccine at 5 months (EZ-HT,5m) provided suboptimal protection, as vaccine efficacy after exposure was 97% and 95%, respectively, for EZ-HT,5m and SW-STD,10m vaccines, whereas SW-HT,5m vaccine had an efficacy of 81%. The difference in mortality between recipients of high-titre vaccines and SW-STD observed in several studies during the first few years after vaccination may be explained by non-specific beneficial effects of the standard measles vaccine rather than a harmful effect of the high-titre vaccines.
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PMID:Five year follow-up of morbidity and mortality among recipients of high-titre measles vaccines in Senegal. 892 Jul 4

The British HIV Association (BHIVA) has published guidelines for immunization of HIV-infected adults. A chart review of 200 HIV-infected patients diagnosed was conducted to determine shortcomings in previous practice and determine which vaccines should routinely be given in specialist HIV clinics and which might be able to be delegated to primary care clinics. Data were collected on administration of three categories of vaccinations: (1) vaccines used in all individuals with chronic disease (pneumococcal, influenza, swine flu H1N1); (2) targeted vaccinations used in non-immune individuals with HIV who are at risk of exposure (hepatitis A and hepatitis B); (3) routine vaccines traditionally delivered to the whole population (measles/mumps/rubella [MMR], diphtheria/tetanus/pertussis and meningitis C/ACWY). Pneumococcal vaccine was delivered to 54% of eligible patients, 52% of eligible individuals completed a full hepatitis B programme of vaccination and 21% (42/200) were naturally immune; hepatitis A vaccine was delivered to 36% of eligible individuals. With increasing demands on resources, it seems likely that HIV services will have to harness resources of primary care in vaccine programmes in relation to routine vaccines. By improving communication between primary and secondary care mistakes with live vaccination decisions could be avoided; HIV services should continue to perform targeted and chronic disease vaccines, i.e. for category 1 and category 2 vaccines.
Int J STD AIDS 2012 Feb
PMID:Managing vaccines: defining the remit of primary care and specialist HIV clinics in the delivery of immunization to individuals with HIV infection. 2242 90

The measles virus (MV) phosphoprotein (P) and V proteins block the interferon (IFN) response by impeding phosphorylation of the signal transducer and activator of transcription 1 (STAT1) by the Janus kinase 1 (JAK1). We characterized how STAT1 mutants interact with P and JAK1 phosphorylation. Certain mutants of the linker, the Src-homology 2 domain (SH2), or the transactivation domain had reduced or abolished phosphorylation through JAK1 after IFN treatment. Other mutants, mainly localized in the linker, failed to interact with P as documented by the lack of interference with nuclear translocation. Thus the functional footprint of P on STAT1 localizes mainly to the linker domain; there is also some overlap with the STAT1 phosphorylation functional footprint on the SH2 domain. Based on these observations, we discuss how the MV-P might operate to inhibit the JAK/STAT pathway.
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PMID:The measles virus phosphoprotein interacts with the linker domain of STAT1. 2385 40

Pathway analyses of genome-wide association studies aggregate information over sets of related genes, such as genes in common pathways, to identify gene sets that are enriched for variants associated with disease. We develop a model-based approach to pathway analysis, and apply this approach to data from the Wellcome Trust Case Control Consortium (WTCCC) studies. Our method offers several benefits over existing approaches. First, our method not only interrogates pathways for enrichment of disease associations, but also estimates the level of enrichment, which yields a coherent way to promote variants in enriched pathways, enhancing discovery of genes underlying disease. Second, our approach allows for multiple enriched pathways, a feature that leads to novel findings in two diseases where the major histocompatibility complex (MHC) is a major determinant of disease susceptibility. Third, by modeling disease as the combined effect of multiple markers, our method automatically accounts for linkage disequilibrium among variants. Interrogation of pathways from eight pathway databases yields strong support for enriched pathways, indicating links between Crohn's disease (CD) and cytokine-driven networks that modulate immune responses; between rheumatoid arthritis (RA) and "Measles" pathway genes involved in immune responses triggered by measles infection; and between type 1 diabetes (T1D) and IL2-mediated signaling genes. Prioritizing variants in these enriched pathways yields many additional putative disease associations compared to analyses without enrichment. For CD and RA, 7 of 8 additional non-MHC associations are corroborated by other studies, providing validation for our approach. For T1D, prioritization of IL-2 signaling genes yields strong evidence for 7 additional non-MHC candidate disease loci, as well as suggestive evidence for several more. Of the 7 strongest associations, 4 are validated by other studies, and 3 (near IL-2 signaling genes RAF1, MAPK14, and FYN) constitute novel putative T1D loci for further study.
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PMID:Integrated enrichment analysis of variants and pathways in genome-wide association studies indicates central role for IL-2 signaling genes in type 1 diabetes, and cytokine signaling genes in Crohn's disease. 2409 38

Genitourinary medicine work requires public health actions. Notifiable infections may be seen in genitourinary medicine, but concerns over confidentiality could delay public health actions and outbreak management. To assess genitourinary medicine clinicians' awareness of notification of infectious disease, reporting practices and liaison with Health Protection Units, we sent postal surveys to 140 genitourinary medicine clinicians (SE HPA region) that explored prior public health training, Health Protection Unit liaison and management of possible clinical scenarios. Fifty-seven respondents reported median genitourinary medicine experience of 12 years; 29% had prior public health training, nine on the British Association for Sexual Health and HIV course. A total of 90% had heard of Health Protection Units and understood their role. Approximately one-third would not report key diseases at all, most reporting only on laboratory confirmation. In all, 83% would only notify acute hepatitis on lab confirmation; 50% would report suspected measles immediately (44% awaiting lab confirmation) and 40% would not pass on any patient details without consent. Clinicians have good knowledge of notification of infectious disease conditions but responses suggest it is not always used in clinical context. Reporting delays occur waiting for lab confirmation and liaison with local Health Protection Units may be hindered by confidentiality concerns, potentially delaying public health action. Doctors with prior public health training are more likely to report appropriately.
Int J STD AIDS 2015 Mar
PMID:Do genitourinary physicians report notifiable diseases? A survey in South East England. 2481 Feb 16

Virus replication efficiency is influenced by two conflicting factors, kinetics of the cellular interferon (IFN) response and induction of an antiviral state versus speed of virus replication and virus-induced inhibition of the IFN response. Disablement of a virus's capacity to circumvent the IFN response enables both basic research and various practical applications. However, such IFN-sensitive viruses can be difficult to grow to high-titer in cells that produce and respond to IFN. The current default option for growing IFN-sensitive viruses is restricted to a limited selection of cell-lines (e.g. Vero cells) that have lost their ability to produce IFN. This study demonstrates that supplementing tissue-culture medium with an IFN inhibitor provides a simple, effective and flexible approach to increase the growth of IFN-sensitive viruses in a cell-line of choice. We report that IFN inhibitors targeting components of the IFN response (TBK1, IKK2, JAK1) significantly increased virus replication. More specifically, the JAK1/2 inhibitor Ruxolitinib enhances the growth of viruses that are sensitive to IFN due to (i) loss of function of the viral IFN antagonist (due to mutation or species-specific constraints) or (ii) mutations/host cell constraints that slow virus spread such that it can be controlled by the IFN response. This was demonstrated for a variety of viruses, including, viruses with disabled IFN antagonists that represent live-attenuated vaccine candidates (Respiratory Syncytial Virus (RSV), Influenza Virus), traditionally attenuated vaccine strains (Measles, Mumps) and a slow-growing wild-type virus (RSV). In conclusion, supplementing tissue culture-medium with an IFN inhibitor to increase the growth of IFN-sensitive viruses in a cell-line of choice represents an approach, which is broadly applicable to research investigating the importance of the IFN response in controlling virus infections and has utility in a number of practical applications including vaccine and oncolytic virus production, virus diagnostics and techniques to isolate newly emerging viruses.
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PMID:Inhibitors of the interferon response enhance virus replication in vitro. 2539 Aug 91

The seroprevalence (SP) of measles and rubella virus antibodies is presented by age groups obtained in the IV Serosurvey of the Region of Madrid (2008-2009). The target population is composed of residents with ages ranging between 2 and 60 years in the Region of Madrid. A two-stage cluster sample is used. The SP of measles virus antibodies is 97.8% (CI 95%: 97.3-98.2). The highest SP is observed in the 2-5 year and 41-60 year age groups. The point estimate does not reach 95% in the 16-20 and 21-30 year age groups. The SP of rubella virus antibodies is 97.2% (CI 95%: 96.5-97.7). The SP is over 95% in all of the age groups. In immigrant women between the ages of 16 and 49, the SP is 95.9% (CI 95%: 93.7-97.4). The identification of groups susceptible to the measles virus in young adults could lead to outbreaks as a result of importing the virus. The circulation of the rubella virus is possible among immigrant women aged between 16 and 49 years, which could lead to the appearance of SRC cases. Epidemiological surveillance will allow the impact on the measles and rubella elimination plan to be determined in the future.
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PMID:Seroprevalence of measles and rubella virus antibodies in the population of the Community of Madrid, 2008-2009. 2595 94


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