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)

Current STD control efforts are largely confined to female sex workers (FSWs) registered with the local Social Hygiene Clinics. This study was conducted to compare the prevalence of gonococcal and chlamydial infections and its behavioral correlates among registered FSWs in two major urban centers. FSWs in Manila and Cebu City consented to undergo an STD physical examination and standardized interview to measure socioeconomic markers and STD-related practices. The questionnaire was pretested in a series of four focus groups in Manila and subsequently administered in Tagalog and Cebuano by trained interviewers. Infection with N. gonorrhea was determined by culture and infection with C. trachomatis was defined by antigen detection. From July through September 1994 similar numbers of women were recruited in Manila (n = 311) and Cebu City (n = 300). However, thanks to the abilities of an interviewer who was previously a FSW, Cebu City was more successful at recruiting unregistered FSWs (50%) than was Manila (18%). The gonorrhea prevalence was 5 times greater among unregistered FSWs (70/185 or 37.8%) than registered FSWs (29/403 or 7.2%) (p 0.05). Prevalence of chlamydial infection was 2 times greater among unregistered FSWs (30.5%) than among registered ones (14.6%) (p 0.05). Unregistered FSWs reported fewer years working as a FSW, more partners in the prior week, and less current use of contraceptives (p 0.05). Rates of antibiotic use in the last week and douching in the last 24 hours were similar between the two groups. This study shows that unregistered FSWs are at a higher risk for acquiring and transmitting STDs, including HIV infection, than registered FSWs. There is an urgent need to implement interventions to reach this vulnerable group of women.
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PMID:Comparison of STD prevalence and the behavioral correlates of STD among registered and unregistered female sex workers in Manila and Cebu City, Philippines. 1234 61

Auditing the sensitivity of microscopic diagnosis of gonorrhoea is recommended by the current guidelines. A retrospective study was performed of 596 cases of positive cultures for Neisseria gonorrhoeae in modified New York City culture (MNYC) media diagnosed from 1995 to 1999. The sensitivity of the cervical slides in women was 51% while in men who have sex with men (MSM) the sensitivity of urethral and rectal slides were 89% and 54% respectively. The sensitivity of urethral slides in heterosexual men was 84%. Neisseria serovar 1B02 among MSM and serovar 1B31 among women were mostly undiagnosed with microscopy. Serovars 1A05, 1A21, B08 among heterosexual men were exclusively associated with negative microscopy. Microscopy is important in the rapid detection and treatment of gonorrhoea. Infections with certain serovars are less likely to be detected by microscopy; making them more likely to spread within the community. Culture from different ano-genital sites is essential to maximize detection of gonorrhoea in all patients.
Int J STD AIDS 2003 Jun
PMID:Sensitivity of microscopy for the rapid diagnosis of gonorrhoea in men and women and the role of gonorrhoea serovars. 1281 66

The metabolic syndrome in association with obesity is a major clinical problem inducing hypertension, diabetes mellitus, and atherosclerosis. Leptin induces angiogenesis by its proliferative effects on endothelial cells (ECs) via OB receptor (OB-Rb) gene. We evaluated the growth of ECs and intracellular signalings in response to leptin in vitro and the angiogenic effects of leptin in the cornea in vivo with and without adenovirus-mediated transfer of the OB-Rb gene in Zucker fatty (ZF) rats as a model for the metabolic syndrome. Recombinant adenovirus vector encoding rat OB-Rb (Ad.OB-Rb) or Escherichia coli. LacZ (Ad.LacZ) was transfected into cultured ECs from Zucker lean (ZL) rats and ZF rats. Leptin increased DNA synthesis dose-dependently in ECs from ZL rats but not ZF rats. Infection with Ad.OB-Rb, but not with Ad.LacZ, improved the growth effects of leptin in ECs from ZF rats. Leptin induced phosphorylation of Janus kinase (JAK)2, signal transducer and activator of transcription (STAT)3, and extracellular signal-regulated kinase (ERK) in ECs from ZL rats but not ZF rats. Infection with Ad.OB-Rb restored phosphorylation of JAK2 and STAT3 in ECs from ZF rats. Leptin induced angiogenesis in cornea from ZL rats, but not from ZF rats. Coadministration of leptin and Ad.OB-Rb induced angiogenesis in cornea from ZF rats. Ad.LacZ did not influence the angiogenic effects of leptin. The impaired endothelial function with the leptin resistance may be one of causes of the atherosclerosis in the metabolic syndrome.
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PMID:Effects of leptin on endothelial function with OB-Rb gene transfer in Zucker fatty rats. 1292 73

Infection with human papillomavirus (HPV) is one of the major preventable causes of cancer world-wide. Rapid increase in cervical cancer incidence also in some western countries with cervical cancer screening programmes is probably due to increase in background exposure to HPV in the young. HPV vaccines are in clinical trials and the results have been promising, but due to assortative transmission of the infection and multiple HPV types the effect of large-scale immunization on their spread will vary between different populations and by HPV type. Thus, it is difficult to predict the effect of vaccination on cancer incidence on the basis of efficacy trials only. In the following evaluation of population level, effectiveness of vaccination on cervical cancer incidence (1) and HPV prevalence (2) by combined cluster/individually randomized trials (1) and cluster/community randomized trials (2) are described.
Int J STD AIDS 2003 Dec
PMID:Effectiveness of preventive human papillomavirus vaccination. 1467 83

As part of the 2000 Global Burden of Disease study, we quantified the death and disability from injection-associated infections with hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). We modelled the fraction of incident infections attributable to health care injections in the year 2000 on the basis of the annual number of injections, the proportion of injections administered with reused equipment, the probability of transmission following percutaneous exposure, the prevalence of active infection, the prevalence of immunity and the total incidence. Infections in 2000 were converted into disability-adjusted life years (DALYs) in 2000-2030 using natural history parameters, background mortality, duration of disease, disability weights, age weights and a 3% discount rate. Four Global Burden of Disease regions where reuse of injection equipment in the absence of sterilization was negligible were excluded from the analysis. In the remaining 10 regions, in 2000, persons received an average of 3.4 injections per year, 39.3% of which were given with reused equipment. In 2000, contaminated injections caused an estimated 21 million HBV infections, two million HCV infections and 260,000 HIV infections, accounting for 32%, 40% and 5%, respectively, of new infections for a burden of 9,177,679 DALYs between 2000 and 2030. Injection overuse and unsafe practices account for a substantial burden of death and disability worldwide. There is a need for policies and plans for the safe and appropriate use of injections in countries where practices are poor.
Int J STD AIDS 2004 Jan
PMID:The global burden of disease attributable to contaminated injections given in health care settings. 1476 64

Elevations in matrix metalloproteinase 1 (MMP-1) and MMP-3 have been found in patients with Lyme arthritis and in in vitro models of Lyme arthritis using cartilage explants and chondrocytes. The pathways by which B. burgdorferi, the causative agent of Lyme disease, induces the production of MMP-1 and MMP-3 have not been elucidated. We examined the role of the extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways in MMP induction by B. burgdorferi. Infection with B. burgdorferi results in rapid phosphorylation of p38 and JNK within 15 to 30 min. Inhibition of JNK and p38 MAPK significantly reduced B. burgdorferi-induced MMP-1 and MMP-3 expression. Inhibition of ERK1/2 completely inhibited the expression of MMP-3 in human chondrocytes following B. burgdorferi infection but had little effect on the expression of MMP-1. B. burgdorferi infection also induced phosphorylation and nuclear translocation of STAT-3 and STAT-6 in primary human chondrocytes. Expression of MMP-1 and MMP-3 was significantly inhibited by inhibition of JAK3 activity. Induction of MMP-1 and -3 following MAPK and JAK/STAT activation was cycloheximide sensitive, suggesting synthesis of intermediary proteins is required. Inhibition of tumor necrosis factor alpha (TNF-alpha) significantly reduced MMP-1 but not MMP-3 expression from B. burgdorferi-infected cells; inhibition of interleukin-1beta (IL-1beta) had no effect. Treatment of B. burgdorferi-infected cells with JAK and MAPK inhibitors significantly inhibited TNF-alpha induction, consistent with at least a partial role for TNF-alpha in B. burgdorferi-induced MMP-1 expression in chondrocytes.
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PMID:Borrelia burgdorferi-induced expression of matrix metalloproteinases from human chondrocytes requires mitogen-activated protein kinase and Janus kinase/signal transducer and activator of transcription signaling pathways. 1510 98

The functional receptor for the flavivirus West Nile (WNV) infection has been characterized in this study with a combination of biochemical and molecular approaches. A 105-kDa protease-sensitive glycoprotein that binds WNV was isolated from the plasma membrane of cells permissive to WNV infection. The protein was subjected to peptide sequencing, and this glycoprotein was identified as a member of the integrin superfamily. Infection of WNV was shown to be markedly inhibited in Vero cells pretreated with blocking antibodies against alpha(v)beta(3) integrin and its subunits by receptor competition assay. It was also noted that cells pretreated with antibodies against alpha(v)beta(3) integrin can effectively inhibit flavivirus Japanese encephalitis but to a lesser extent flavivirus dengue infections. West Nile virus entry is independent of divalent cations and is not highly blocked by arginine-glycine-aspartic acid (RGD) peptides, suggesting that the interaction between the virus and alpha(v)beta(3) integrin is not highly dependent on the classical RGD binding motif. In addition, gene silencing of the beta(3) integrin subunit in cells has resulted in cells largely resistant to WNV infection. In contrast, expression of recombinant human beta(3) integrin substantially increased the permissiveness of CS-1 melanoma cells for WNV infection. Soluble alpha(v)beta(3) integrin can also effectively block WNV infection in a dose-dependent manner. Furthermore, WNV infection also triggered the outside-in signaling pathway via the activation of integrin-associated focal adhesion kinase. The identification of alpha(v)beta(3) integrin as a receptor for WNV provides insight into virus-receptor interaction, hence creating opportunities in the development of anti-viral strategies against WNV infection.
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PMID:Interaction of West Nile virus with alpha v beta 3 integrin mediates virus entry into cells. 1547 43

Theileria parasites infect and transform bovine lymphocytes, but host cell immortalization is reversible, as upon parasite death the lymphocytes rapidly die of apoptosis. Infection leads to a marked augmentation in the levels of lymphocyte c-Myc, and the parasite achieves this by inducing increased c-myc transcription and by prolonging the half-life of the transcription factor. Reduction in c-Myc turnover can be ascribed to CK2-mediated phosphorylation of the transcription factor. A parasite-dependent GM-CSF autocrine loop activates a JAK2/STAT3 signalling pathway that contributes to heightened c-myc transcription, and inhibition of the pathway leads to caspase 9 activation and apoptosis that can be directly ascribed to a reduction in c-Myc. An antiapoptotic role for c-Myc was clearly demonstrated by specific inhibition of c-myc expression with antisense oligonucleotides, and this correlates with loss of the antiapoptotic protein Mcl-1, and, consistently, ectopic expression of c-Myc abrogates B-cell death induced upon JAK2 inhibition. Thus, Theileria parasites ensure the survival of their host lymphocytes via specific activation of c-Myc.
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PMID:c-Myc activation by Theileria parasites promotes survival of infected B-lymphocytes. 1558 Feb 87

Few studies have reported on sexually transmitted infections at the US-Mexico border, so the prevalence of Chlamydia trachomatis in this population remains uncertain. This binational project investigated the prevalence of, and risk factors for, C. trachomatis among women along the Arizona, US-Sonora, Mexico border. Women who self-referred for routine gynaecological care were invited to complete an interviewer-administered questionnaire and to undergo a Pap smear, C. trachomatis test, and HPV test. In 2270 women, C. trachomatis prevalence overall was 8.2% as measured by hybrid capture and 2.6% by enzyme immunoassay. Infection was associated with young age, a history of new sexual partner(s) in the previous three months, HPV infection, and proximity of clinic to the international border. Antibiotic use in the previous 30 days was associated with decreased odds of infection. Women in Arizona-Sonora border communities are at increased risk for C. trachomatis infection compared to women attending clinics in non-border locations.
Int J STD AIDS 2004 Dec
PMID:Chlamydial infection in women along the US-Mexico border. 1560 88

Chronic lymphocytic leukemia follows an extremely variable clinical course with survival range from months to decades. Some patients present minimal symptoms and others organomegaly requiring rapidly therapy. Therapeutic options take into account efficacy, toxicity and prognostic factors. One of the well known prognosis factor is the clinical staging developed either by Rai et al. or by Binet et al. However, there is an important heterogeneity concerning the course of the disease among patients within a single stage group. Recently, several important observations related to the biologic significance of VH gene mutational status, expression of CD38, over-expression of ZAP-70 and chromosomal aberrations have led to the ability to identify high risk patients with rapid disease progression and lower survival. It has been demonstrated that the VH mutation status is clinically highly relevant. CLL patients with unmutated VH gene show an unfavourable course with a very rapid progression. Specific genomic aberrations have been associated with disease characteristics such as lymphadenopathy related to 11q deletion and resistance to treatment related to 17p deletion. VH gene mutation status and genomic aberrations appear separate parameters when considering their prognostic relevance but nevertheless they are correlated: unfavourable aberrations (11q- and 17p-) occur more frequently in VH unmutated CLL patients. According to these prognostic factors, several treatments including purine analogues and/or monoclonal antibodies have been tested with different schedules and doses of monoclonal antibodies (rituximab and alemtuzumab) considering safety to determine the better efficacy. Infections and haemolytic anemia remain the most frequent complications during conventional chemotherapy. In autologous transplant setting, the transplant related mortality is less than 10%, but survival curve do not show a plateau with about 50% of patients relapsing at 4 years. Conventional allogeneic transplantation could achieve durable remission and probably cure the disease but at the price of a too high transplant related mortality related to depressive immune status and old age of CLL population. In order to minimize the toxicity and to improve graft-versus-leukemia effect, development of reduced intensity conditioning (RIC) regimens appear particularly important for CLL patients. Recent studies, although a still short follow-up show very promising results and use of monoclonal antibodies in the conditioning or just after transplant could improve the results of allogeneic stem cell transplantation and cure a larger number of CLL patients. Recent advances to categorize CLL patients according to risk stratification regarding new prognostic factors (FISH, CD38, ZAP70, Ig mutational status) should allow to define better the best therapeutic strategy. In parallel, age, co morbidities and the notion of the risk-adapted strategy have also an important impact adding.
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PMID:[News in therapeutic management of chronic lymphoid leukemia]. 1582 Sep 19


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