Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mouse adenovirus type 1 (MAV-1) infection of B-cell-deficient and Bruton's tyrosine kinase (Btk)-deficient mice resulted in fatal disseminated disease resembling human adenovirus infections in immunocompromised patients. Mice lacking B cells or Btk were highly susceptible to acute MAV-1 infection, in contrast to controls and mice lacking T cells. To our knowledge, this is the first demonstration that mice with an X-linked immunodeficiency phenotype (Btk deficient) are susceptible to virus-induced disease. Mice lacking B cells or Btk on a C57BL/6 background succumbed with encephalomyelitis, hepatitis, and lymphoid necrosis. Mice lacking B cells on a BALB/c background succumbed with enteritis and hepatitis. Survival of acute MAV-1 infection correlated with early T-cell-independent neutralizing antibody and T-cell-independent antiviral immunoglobulin M. Treatment of MAV-1-infected Btk(-/-) mice 4 to 9 days postinfection with antiserum harvested 6 to 9 days postinfection from MAV-1-infected Btk(+/+) mice was therapeutic. Our findings implicate a critical role for B-cell function in preventing disseminated MAV-1 infection, particularly production of early T-cell-independent antiviral immunoglobulin M.
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PMID:Fatal disseminated mouse adenovirus type 1 infection in mice lacking B cells or Bruton's tyrosine kinase. 1514 Sep 55

In the USA, as well as internationally, rates of HIV infection among women continue to grow. In addition, women who inject drugs are at further increased risk for hepatitis C co-infection. The purpose of this study was to conduct qualitative and quantitative needs assessments for HIV/STD/hepatitis prevention among women in methadone maintenance programmes. Qualitative interviews and a quantitative, self-administered questionnaire were used to develop an understanding of their needs, and perceptions of what they believed would constitute effective prevention intervention programmes. Results supported women's interest in these services and provided feedback on how to structure prevention programmes by placing them in the context of women's lives and addressing concrete barriers (e. g. transportation, child care, confidentiality concerns) to facilitate adherence to these programmes. Respondents indicated a desire for HIV prevention information, but also wanted information on hepatitis, relapse prevention, stress management and accessing services. The development of such programming would require partnering with the target population and their service providers to develop feasible and effective interventions.
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PMID:HIV, STD and hepatitis prevention among women in methadone maintenance: a qualitative and quantitative needs assessment. 1520 11

The article describes men's perceptions of and experience with substance use and sexual behavior during incarceration. Grounded theory content analyses were performed on qualitative interviews conducted with 80 men, aged 18 to 29, in four U.S. states. Participants believed that drugs were easily available in prison. Half reported using substances, primarily marijuana or alcohol, while incarcerated. Key themes included the role of correctional personnel in the flow of substances in prison and the economic significance of substance trafficking. With regard to sexual behavior, most men acknowledged that it occurred but were hesitant to talk in-depth about it. There was a strong belief in "don't look, don't tell," and sex in prison was often associated with homosexual behavior or identity. Sex during incarceration was reported by 12 men, mostly with female partners. Participants were pessimistic about HIV/STD/hepatitis prevention efforts inside correctional facilities. These findings highlight the need for risk reduction programs for incarcerated men.
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PMID:A qualitative study of substance use and sexual behavior among 18- to 29-year-old men while incarcerated in the United States. 1553 47

In order to evaluate the occurrence of hepatotoxicity in patients treated with antiretroviral therapy (ART) who switch protease inhibitor (PI), and the role of viral hepatitis in its development, we performed a retrospective study on 182 HIV patients treated with ART for 24 months. The presence of hepatitis viruses and alanine transaminase levels were evaluated. Hepatotoxicity developed in a low number of subjects without co-infection, but was significantly higher in co-infected patients (14/51 versus 62/131, P = 0.01). Ritonavir was associated with higher rates of severe hepatotoxicity in the co-infected group. Patients presenting any problems related to ART, including the development of hepatotoxicity, continued therapy by switching PI. The occurrence of hepatotoxicity with second/third choice PIs, including ritonavir, remained stable. Our results suggest that switching PI does not increase the occurrence of drug-related liver toxicity.
Int J STD AIDS 2005 Feb
PMID:Development of hepatotoxicity in HIV patients switching at least one protease inhibitor. 1582 50

An audit of outcomes from the first year of implementation of a super-accelerated hepatitis B vaccination schedule was performed. One hundred and sixteen patients commenced vaccination for hepatitis B in the study period. All notes were located and reviewed. In all, 72.4% of patients completed three vaccinations compared with 61.5% in an earlier period using the old schedule. Serological response for 39 patients was measured at approximately 12 weeks post commencement of vaccination. Of these 69.2% had mounted some serological response, 48.7% a good response. As expected, a faster vaccination schedule improves completion rates for the first three injections. Early serological responses are encouraging and comparable to published data for new schedule vaccination responses at 12 weeks. It is anticipated that serological response will continue to improve over the year before a booster dose of hepatitis vaccination is due.
Int J STD AIDS 2005 Sep
PMID:Audit of outcome of super-accelerated hepatitis B vaccination schedule in a genitourinary medicine clinic. 1617 34

We report on an HIV-positive individual who developed a biochemical hepatitis likely to be due to excessive intake of dietary supplements, highlighting the need for clinicians to be vigilant over their use.
Int J STD AIDS 2005 Sep
PMID:What is your patient taking? Dietary supplements in an HIV-positive patient. 1617 36

Incarcerated men in the US are at increased risk for HIV, STDs and hepatitis, and many men leaving prison have unprotected sex with a primary female partner immediately following release from prison. This paper addresses risk to the primary female partners of men being released from prison (N = 106) by examining the prevalence of men's concurrent unprotected sex with other partners or needle sharing prior to and following release from prison (concurrent risk). Rates of concurrent risk were 46% prior to incarceration, 18% one month post release, and 24% three months post release. Multivariate analysis showed concurrent risk was significantly associated with having a female partner who had one or more HIV/STD risk factors and having a history of injection drug use. Findings demonstrate need for prevention programs for incarcerated men and their female partners.
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PMID:HIV, STD, and hepatitis risk to primary female partners of men being released from prison. 1621 88

The hepatitis B virus (HBV) envelope proteins have the ability to assemble three types of viral particles, (i) the empty subviral particles (SVPs), (ii) the mature HBV virions, and (iii) the hepatitis delta virus (HDV) particles, in cells that are coinfected with HBV and HDV. To gain insight into the function of the HBV envelope proteins in morphogenesis of HBV or HDV virions, we have investigated subdomains of the envelope proteins that have been shown or predicted to lie at the cytosolic face of the endoplasmic reticulum membrane during synthesis, a position prone to interaction with the inner core structure. These domains, referred to here as cytosolic loops I and II (CYL-I and -II, respectively), were subjected to mutagenesis. The mutations were introduced in the three HBV envelope proteins, designated small, middle, and large (S-HBsAg, M-HBsAg, and L-HBsAg, respectively). The mutants were expressed in HuH-7 cells to evaluate their capacity for self-assembly and formation of HBV or HDV virions when HBV nucleocapsid or HDV ribonucleoprotein, respectively, was provided. We found that SVP-competent CYL-I mutations between positions 23 and 78 of the S domain were permissive to HBV or HDV virion assembly. One mutation (P29A) was permissive for synthesis of the S- and M-HBsAg but adversely affected the synthesis or stability of L-HBsAg, thereby preventing the assembly of HBV virions. Furthermore, using an in vitro infection assay based on the HepaRG cells and the HDV model, we have shown that particles coated with envelope proteins bearing CYL-I mutations were fully infectious, hence indicating the absence of an infectivity determinant in this region. Finally, we demonstrated that the tryptophan residues at positions 196, 199, and 201 in CYL-II, which were shown to exert a matrix function for assembly of HDV particles (I. Komla-Soukha and C. Sureau, J. Virol. 80:4648-4655, 2006), were dispensable for both assembly and infectivity of HBV virions.
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PMID:Analysis of the cytosolic domains of the hepatitis B virus envelope proteins for their function in viral particle assembly and infectivity. 1702 Sep 42

The lack of good molecular markers for diagnosis as well as treatment assessment has rendered the hepatocellular carcinoma (HCC) a major challenge in health care. In this study, woodchucks were used as an animal model for hepatitis virus-induced HCC, and gene expression studies were performed using a human oligonucleotide microarray. An analysis approach combing supervised significant analysis of microarray (SAM), prediction analysis of microarray (PAM), and unsupervised hierarchical cluster methodologies statistically determined 211 upregulated and 78 downregulated genes between liver cancer and non-cancer liver tissues, and demonstrated > or = 93% accuracy in classifying the tissue samples. RT-PCR results confirmed the differential expression of selected sequenced woodchuck genes (SAT, IDH3B, SCD) in the microarray. Our study showed that differentially expressed genes were involved in transcription, RNA splicing, translation, cell cycle, metabolism, protein folding and degradation, apoptosis, immune response, metal binding, etc. Interestingly, some genes were involved with signaling pathways such as Ras/MAPK (MAPKAP1), Src-dependent pathways (CSK), hedgehog signaling pathway (HHIP), while Wnt signaling pathway may not be dominant in woodchuck HCC as shown by the downregulation of beta-catenin (TNNB1) and the upregulation of CXXC4 and CSNK2B. Numerous genes found in this study were also differentially expressed in human HCC and many other human cancers including breast, prostate and lung cancers, etc., serving as tumor suppressors, promoters, prognostic markers or chemotherapy targets. In conclusion, this study has demonstrated the robustness of the data analysis and the potential of using human microarrays on woodchuck samples. In particular, some of the differentially expressed genes in the woodchuck HCC can be further explored for possible molecular imaging targets or biological markers in human HCC.
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PMID:Gene expression studies of hepatitis virus-induced woodchuck hepatocellular carcinoma in correlation with human results. 1714 10

The objective of this study is to evaluate the current management practices of patients with HIV and hepatitis B or C co-infection. A postal survey was made of 186 clinics in the UK between October 2003 and January 2004. In total, 100/186 (54%) clinics responded: 16% estimated their hepatitis B prevalence to be above 10%, 27% estimated their hepatitis C to be above 10%. Problems were identified in a minority of clinics including: not routinely screening HIV-positive patients for hepatitis C (6%), restrictions on diagnostic tests required for the management of hepatitis infection and offering inappropriate treatment for hepatitis B infection. The use of diagnostic liver biopsies varied and clinics reported restrictions on access to hepatitis C therapy, with a consequent impact on waiting times. In conclusion, we identified several areas of concern in the diagnosis and management of HIV/hepatitis co-infection in several UK HIV treatment centres.
Int J STD AIDS 2006 Dec
PMID:Survey of HIV and hepatitis B or C co-infection management in the UK 2004. 1721 53


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