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)

Gynecologic conditions associated with HIV infection were examined in 481 regular female sex partners of HIV-positive male blood donors enrolled in a study of heterosexual HIV transmission conducted at Chiang Mai University Hospital and Lampang Provincial Hospital in Thailand in 1992-96. Of these women, 224 (46.6%) were HIV-infected. HIV-positive and HIV-negative women were similar in terms of age, education, and age at first intercourse; however, a history of sexually transmitted disease was more common among the HIV-infected women (31.7%) than their uninfected counterparts (18.7%). HIV-infected women also were significantly more likely to have abnormal gynecologic conditions, including abnormal vaginal discharge at physical examination (odds ratio (OR), 2.6; 95% confidence interval (CI), 1.6-4.2) and cervical dysplasia (OR, 5.3; 95% CI, 2.0-15.2). Among HIV-positive women, the prevalence of abnormal vaginal discharge and bacterial vaginosis increased significantly with decreasing CD4 count. Syphilis, gonorrhea, chlamydia, and trichomoniasis rates were generally low and did not differ by HIV status. These findings suggest a need for further research on variations in gynecologic conditions associated with HIV infection in different countries.
Int J STD AIDS 1998 Nov
PMID:Gynaecological conditions associated with HIV infection in women who are partners of HIV-positive Thai blood donors. 986 81

Staphylococcus aureus is a cause of considerable morbidity and mortality in HIV-seropositive persons. Although methicillin-resistant S. aureus (MRSA) is encountered worldwide and in many areas of medical care, little has been reported on clinical infection with MRSA in patients with HIV. We report on an outbreak of MRSA infection in HIV antibody positive patients, using case reports to describe an outbreak of MRSA infection in HIV-seropositive persons. Six cases of clinical MRSA infection were reported over a 4-week period on patients on an HIV dedicated ward. All cases had previous AIDS diagnoses and low CD4 cell counts (median 8 x 10(6)/l; range 0 to 238). Two cases had infected skin lesions and 2 cases had infected indwelling central venous catheters with septicaemia. Two cases had pneumonia, one with concurrent infection at the entry site of a percutaneous endoscopic gastrostomy (PEG) feeding tube. Isolates of MRSA from the 6 cases were compared by pulsed-field gel electrophoresis of Sma1 chromosomal digests. The resultant banding pattern showed the same strain was responsible for all the infections. A seventh inpatient, the index case, had positive carriage with the same strain of MRSA. To define ongoing MRSA carriage after the outbreak, 29 consecutive ward patients were swabbed for MRSA: all were negative. All patients identified with MRSA infection responded to treatment with intravenous teicoplanin, although carriage was unaltered. Four of the 6 cases died within 7 weeks of diagnosis of MRSA. MRSA can cause severe morbidity in patients with end-stage HIV disease. A small outbreak of MRSA was controlled by simple precautionary measures with no subsequent ongoing transmission of MRSA.
Int J STD AIDS 1998 Dec
PMID:An outbreak of methicillin-resistant Staphylococcus aureus (MRSA) infection in HIV-seropositive persons. 987 18

Our objective was to examine the accuracy of diagnosis of HIV-associated central nervous system (CNS) toxoplasmosis. Individuals diagnosed with HIV-associated CNS toxoplasmosis and controls were ascertained from a population-based database. Diagnosis was confirmed by response to therapy or by histology. Symptoms, results of anti-Toxoplasma serology and use of Pneumocystis carinii pneumonia (PCP) prophylaxis were recorded. Central nervous system toxoplasmosis was confirmed in 54 (76%) of 75 patients. Reactive anti-Toxoplasma serology was associated with CNS toxoplasmosis (OR=20.4, 95% CI 3.1-175.8). Adjusting for CD4 and use of dapsone or aerosolized pentamidine, trimethoprim-sulphamethoxazole (TMP-SMX) for PCP prophylaxis was associated with lower likelihood of CNS toxoplasmosis (OR 0.3, 95% CI 0.1-0.7). Diagnosis of CNS toxoplasmosis is often incorrect. Another diagnosis is most likely in patients who are anti-Toxoplasma seronegative or who are receiving prophylactic TMP-SMX.
Int J STD AIDS 1998 Dec
PMID:Diagnostic accuracy of HIV-associated central nervous system toxoplasmosis. 987 25

Human severe combined immunodeficiency (SCID) can be caused by defects in Janus kinase 3 (JAK3)-dependent cytokine signaling pathways. As a result, patients are at high risk of life-threatening infection. A JAK3 -/- SCID mouse model for the human disease has been used to test whether transplant with retrovirally transduced bone marrow (BM) cells (JAK3 BMT) could restore immunity to an influenza A virus. The immune responses also were compared directly with those for mice transplanted with wild-type BM (+/+ BMT). After infection, approximately 90% of the JAK3 BMT or +/+ BMT mice survived, whereas all of the JAK3 -/- mice died within 29 days. Normal levels of influenza-specific IgG were present in plasma from JAK3 BMT mice at 14 days after respiratory challenge, indicating restoration of B cell function. Influenza-specific CD4(+) and CD8(+) T cells were detected in the spleen and lymph nodes, and virus-specific CD8(+) effectors localized to the lungs of the JAK3 BMT mice. The kinetics of the specific host response correlated with complete clearance of the virus within 2 weeks of the initial exposure. By contrast, the JAK3 -/- mice did not show any evidence of viral immunity and were unable to control this viral pneumonia. Retroviral-mediated JAK3 gene transfer thus restores diverse aspects of cellular and humoral immunity and has obvious potential for human autologous BMT.
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PMID:Virus-specific immunity after gene therapy in a murine model of severe combined immunodeficiency. 987 1

Variation in the clinical stage at which AIDS is diagnosed has hindered the ability of investigators to generate survival estimates which are stable across study cohorts. As a result, little is known about how clinical and sociodemographic factors are associated with survival, independent of AIDS diagnosis stage. By estimating survival following seroconversion while adjusting for baseline CD4 lymphocyte count, the present study generated survival determinants which were unconfounded by time-related changes in AIDS diagnosis. This study's findings indicate that the following factors were associated with significant decreases in HIV-related survival: older age; self-report of no known HIV transmission risk factors; and presence of cytomegalovirus, Mycobacterium avium complex, and Pneumocystis carinii pneumonia. Furthermore, survival decreased in a monotonic fashion with decreases in baseline CD4 count and with increases in calendar period. While this study's findings are consistent with previous investigators' reports of AIDS survival determinants, it will be important for future investigators to refine and update estimates of HIV-related survival determinants as clinical care for HIV-infected patients continues to improve.
Int J STD AIDS 1999 Jan
PMID:Determinants of survival in HIV-positive patients. 1021 25

CD45 is a transmembrane protein tyrosine phosphatase playing an essential role during T-cell activation. This function relates to the ability of CD45 to regulate p56(lck), a cytoplasmic protein tyrosine kinase necessary for T-cell antigen receptor (TCR) signaling. Previous studies have demonstrated that CD45 is constitutively associated in T-lymphocytes with a transmembrane molecule termed CD45-AP (or lymphocyte phosphatase-associated phosphoprotein). Even though the exact role of this polypeptide is unclear, recent analyses of mice lacking CD45-AP have indicated that its expression is also required for optimal T-cell activation. Herein, we wished to understand better the function of CD45-AP. The results of our studies showed that in T-cells, CD45-AP is part of a multimolecular complex that includes not only CD45, but also TCR, the CD4 and CD8 coreceptors, and p56(lck). The association of CD45-AP with TCR, CD4, and CD8 seemed to occur via the shared ability of these molecules to bind CD45. However, binding of CD45-AP to p56(lck) could take place in the absence of other lymphoid-specific components, suggesting that it can be direct. Structure-function analyses demonstrated that such an interaction was mediated by an acidic segment in the cytoplasmic region of CD45-AP and by the kinase domain of p56(lck). Interestingly, the ability of CD45-AP to interact with Lck in the absence of other lymphoid-specific molecules was proportional to the degree of catalytic activation of p56(lck). Together, these findings suggest that CD45-AP is an adaptor molecule involved in orchestrating interactions among components of the antigen receptor signaling machinery. Moreover, they raise the possibility that one of the functions of CD45-AP is to recognize activated Lck molecules and bring them into the vicinity of CD45.
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PMID:Interactions of CD45-associated protein with the antigen receptor signaling machinery in T-lymphocytes. 1031 63

The role of the host immune system in contributing to tumor regression following benzophenothiazine photodynamic therapy (PDT) was examined. Photodynamic therapy with 2-iodo-5-ethylamino-9-diethylaminobenzo[a]-phenothiazinium chloride (2I-EtNBS) eradicated EMT-6 mammary fibrosarcomas in 75-100% of treated mice. In contrast, PDT failed to inhibit tumor growth in T-cell-deficient nude mice. Furthermore, T-cell depletion studies with anti-CD8 antibody revealed that the CD8+ T-cell population was critical for an effective PDT response (tumor volume 14 days post-PDT: 262 mm3 vs 59 mm3 in controls; P < 0.01). Because anti-CD4 antibody inhibited tumor growth in the absence of PDT, the role of CD4+ T cells remains unclear. Depletion of natural killer (NK) cells in vivo with anti-asialo-GM1 antibody significantly reduced a suboptimal PDT effect relative to vehicle controls (tumor volume 13 days post-PDT: 513 mm3 vs 85 mm3, respectively; P < 0.001). However, splenic NK cells obtained from PDT-treated tumor-bearing mice were not cytotoxic in vitro against EMT-6 cells, suggesting that NK cells contribute to the PDT effect in vivo by an indirect mechanism. In addition, when mice with complete tumor regression following PDT were rechallenged 28 days later with 5 x 10(5) EMT-6 cells, tumor growth was significantly inhibited as compared to controls (tumor volume 40 days postrechallenge: 137 mm3 vs 833 mm3 in controls; P < 0.03; percent animals without tumor in five experiments: 67% vs 8% in controls). Collectively, these results demonstrate that CD8+ T cells are required to prevent tumor regrowth after 2I-EtNBS-PDT, NK cells contribute to this response and such PDT can elicit protective antitumor immunity.
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PMID:Role of the immune system in mediating the antitumor effect of benzophenothiazine photodynamic therapy. 1033 64

Binding of HIV-1 envelope glycoproteins to the surface of a CD4+ cell transduces intracellular signals through the primary envelope receptor, CD4, and/or the envelope coreceptor, a seven-transmembrane chemokine receptor. Macrophage-tropic strains of HIV-1 preferentially use CCR5 as an entry coreceptor, whereas T cell-tropic strains use CXC chemokine receptor-4 for entry. Intracellular signals transduced by HIV-1 envelope may have immunopathogenic consequences, including anergy, syncytium formation, apoptosis, and inappropriate cell trafficking. We demonstrate here that a recombinant envelope protein derived from an M-tropic isolate of HIV-1 can transduce CD4-dependent as well as CCR5-dependent intracellular signals in primary human CD4+ T cells. Novel HIV-induced intracellular signals that were identified include tyrosine phosphorylation of focal adhesion kinase (FAK) and CCR5, which are involved in cell adhesion and chemotaxis, respectively. HIV envelope-induced cellular association of FAK and CCR5 was also demonstrated, suggesting that ligation of CD4 and CCR5 leads to the formation of an activation complex composed of FAK and CCR5. Activation of this signaling pathway by HIV-1 envelope may be an important pathogenic mechanism of dysregulated cellular activation and trafficking during HIV infection.
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PMID:Induction of phosphorylation and intracellular association of CC chemokine receptor 5 and focal adhesion kinase in primary human CD4+ T cells by macrophage-tropic HIV envelope. 1038 44

The efficacy and toxicity of interferon-alpha2a (9MU/d) and bleomycin (15 mg every 2 weeks), each combined with zidovudine (2x250 mg/d), was compared in a randomized study in 26 men with progressing AIDS-related Kaposi's sarcoma (KS). The median CD4 count was 113/microl. Complete or partial response was achieved in one (8%) of 12 evaluable patients on interferon and in 2 (20%) of 10 patients on bleomycin (P = 0.43) during 4.7 and 5.3 months of treatment, respectively. The tolerability was comparable. During extended follow up, survival time was 24 and 13 months in the interferon and bleomycin arm, respectively. In a multivariate Cox regression analysis, CD4 lymphocytes <200/microl (relative risk 3.74; 95% CI: 1.30-10.8) and randomization to interferon (relative risk 0.37; 95% CI: 0.15-0.90) were significantly predictive of mortality. New AIDS-related events occurred more frequently in patients who had received bleomycin. The antiviral activity of interferon-alpha or the chemotherapy-mediated increase in the risk for opportunistic infections may explain these differences.
Int J STD AIDS 1999 Jun
PMID:A randomized trial of interferon-alpha2a and zidovudine versus bleomycin and zidovudine for AIDS-related Kaposi's sarcoma. Swiss HIV Cohort Study. 1041 79

Peptides corresponding to the fusion site in 210 kD BCR-ABL protein b3a2 (p210b3a2) were previously shown to bind to several HLA class I and II alleles. We have found that b3a2 peptide-specific CD4-positive T-helper cells were able to recognize p210b3a2-positive chronic myelogenous leukemia (CML) blasts in a DR4 restricted manner. Until now, there were no reports of b2a2 breakpoint-specific human T-cell responses. Here we show that repetitive stimulation of T lymphocytes with a 17mer peptide covering the fusion region in p210b2a2 also leads to specific T-cell responses. CD4 and CD4/CD8 double-positive clones obtained from a b2a2 peptide-specific cell line were cytotoxic and proliferative in an HLA-DR2a (DRB5*0101) restricted fashion. Autologous Epstein-Barr virus (EBV) transformed cells, expressing BCR-ABL(b2a2) on transfection, and allogeneic HLA-DR matched p210b2a2-positive cells from CML patients were, however, not lysed. BCR-ABL peptide-specific T-cell clones did respond to autologous EBV cells transfected with invariant chain (li) cDNA in which the HLA class II-associated invariant chain peptide (CLIP) was replaced by a BCR-ABL b2a2 fusion oligonucleotide sequence, illustrating the potential of these T cells to recognize an endogenous BCR-ABL(b2a2) ligand.
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PMID:A BCR-ABL oncoprotein p210b2a2 fusion region sequence is recognized by HLA-DR2a restricted cytotoxic T lymphocytes and presented by HLA-DR matched cells transfected with an Ii(b2a2) construct. 1041 96


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