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)

Three hundred and fourteen homosexual/bisexual men at risk for human immunodeficiency virus (HIV) infection (170 seroprevalent HIV-positive, 144 seronegative) were prospectively studied over 8 years to assess rates of HIV infection and disease progression, in conjunction with cellular and HIV serological markers. In HIV-positive subjects, CD4+ lymphocyte counts rose strikingly during the period surrounding seroconversion, then fell progressively over the intervening period to a mean level of 300 cells/mm3 when AIDS developed. Changes in CD8+ lymphocyte counts were less consistent. The trend for HIV serological markers over the study period was of progressive decline in the proportion of subjects with anti-p24 antibody, associated with an increase in the proportion of subjects with detectable HIV antigenaemia. However, only 45% of subjects tested had lost anti-p24 antibody by the time of AIDS diagnosis, and HIV antigen was detectable up to 4 years before this. Different HIV serological patterns were also observed in subjects presenting either with Kaposi's sarcoma or opportunist infections. Our data support the continued use of cellular and virological markers in the evaluation of HIV disease; however, the variability observed in this study highlights their limited ability in predicting specific clinical events. Care should therefore be taken to encompass both clinical and laboratory information in the medical assessment of the HIV-infected individual.
Int J STD AIDS
PMID:Eight year prospective study of HIV infection in a cohort of homosexual men--clinical progression, immunological and virological markers. 150 57

Immune function in 97 homosexually active men (none of whom had HIV infection) was assessed. Data revealed that mitogenesis in those who used volatile nitrites compared to those who did not was higher at 72 h but that there was no difference between the groups at 96 h. In those who had high as compared to low nitrite use, mitogenesis was higher at 72 h but decreased significantly by 96 h. These data support previous suggestions that immunosuppressive effects of nitrites alone cannot account for the development of Kaposi's sarcoma in homosexual men with HIV infection.
Int J STD AIDS
PMID:Effects of nitrite use on lymphocyte mitogenesis in homosexual men. 204 6

Anorectal lesions are uncommon in patients infected by the HIV virus (13%, 1 female and 15 males in our personal series). Certain neoplastic lesions are specific and must suggest the possibility of AIDS: Kaposi sarcoma, non-Hodgkin's malignant lymphoma and, in young subjects, intra-epithelial dysplasias, carcinomas in situ or squamous cell of the anus. Other lesions encountered in proctology should also raise the suspicion of HIV infection: anorectal lesions of STD including florid papillomatosis, most frequently (25%) in its severe and recurrent form, extensive herpetic lesions refractory to the usual treatments, Cytomegalovirus ulcers. The clinical history, specifying sexual habits, a history of drug abuse and looking for the presence of chronic diarrhoea, and a complete clinical examination looking for lymphadenopathy are important elements to be considered in favour of the diagnosis. Apart from painful emergencies requiring an immediate surgical procedure, the therapeutic of the patient's general state, the stage of the disease and the expected benefit for the patient's comfort.
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PMID:[AIDS and anorectal pathology]. 766 94

Kaposi's sarcoma (KS) occurs more often in men than in women and HIV-1-associated KS has a high occurrence in homosexual men (over 30%). Most cultures of KS tumours yield cells with properties of hyperplastic (not malignant) endothelial cells under the control of several cytokines. The role of HIV-1 may be in promoting high levels of some cytokines and providing stimulation to angiogenesis by the HIV-1 Tat protein, which synergizes with basic fibroblast growth factor in promoting these effects. Here we describe an immortalized AIDS-KS cell line (KS Y-1) and show that these cells produce malignant metastatic tumours in nude mice and are killed in vitro and in vivo (apparently by apoptosis) by a pregnancy hormone, the beta-chain of human chorionic gonadotropin. Similarly, chorionic gonadotropin kills KS SLK, cells from another neoplastic cell line (established from a non-HIV-associated KS), as well as the hyperplastic KS cells from clinical specimens grown in short-term culture, but does not kill normal endothelial cells. These results provide evidence that KS can evolve into a malignancy and have implications for the hormonal treatment of this tumour.
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PMID:Tumorigenesis and metastasis of neoplastic Kaposi's sarcoma cell line in immunodeficient mice blocked by a human pregnancy hormone. 765 55

The two major risk groups for acquisition of HIV in the UK are gay men and IDUs. Individuals from these risk groups vary in a number of respects in their life-style, which have the potential to affect the course of their HIV disease. This study compares gay men and IDUs from the Lothian Region of Scotland with respect to their AIDS defining diagnosis and subsequent CDC (Centers for Disease Control) stage IV events. Comparisons were made between the two risk groups for their AIDS defining diagnosis by performing chi square tests, Mann-Whitney tests and logistic regression. Subsequent CDC stage IV events were analysed using ordinal logistic regression and Cox regression. 89 IDUs and 56 gay men were included in the analysis. Oesophageal candida was a commoner AIDS-defining diagnosis in IDUs than gay men and Kaposi's sarcoma was diagnosed more frequently in gay men than IDUs. Subsequently oesophageal candida was also commoner in IDUs and CMV retinitis was seen more frequently in gay men. The role of prophylaxis and differences in diet are discussed as possible causes of the observed differences in the incidence of oesophageal candida. The higher incidence of CMV retinitis in gay men probably reflects the high level of sexual acquisition of CMV.
Int J STD AIDS
PMID:A comparison of AIDS-defining events and subsequent CDC stage IV events in IDUs and gay men. 784 20

Anorectal lesions in patients carrying the HIV virus are uncommon (13%, in our personal life, 1 women/15 men). The following raise the possibility of AIDS: Kaposi sarcoma, non Hodgkin's lymphoma and also with the young patients, intraepithelial dysplasia, in situ carcinoma or squamous carcinoma of the anus. Other anorectal lesions encountered in proctology, should lead to suspicion of HIV infection: anal involvement in STD, florid papillomatosis, the most frequent lesion in his serious form which recur on a interminable bases, extensive and chronic herpes, lesions refractory to standard treatment, megalovirus and ulcers. Date by history indicating sexual habits, toxicomania as well as the existence of chronic diarrhea and full physical examination scoking enlarged lymph nodes are all factors to be taken into consideration in support of the diagnosis. Apart from painful emergencies justifying immediate surgery, indications for surgery should be weighed in terms of the patient's general condition, the stage of advancement of the disease and expected benefit in terms of patient comfort.
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PMID:[Update of anal-perineal and rectal lesions observed in AIDS]. 801 11

Kaposi's sarcoma (KS) has a higher incidence in some parts of Africa than anywhere else in the world. Recent studies in western homosexual men with AIDS-KS suggest that KS may be caused by a putative sexually transmissible agent. Our analytical review of studies on KS in Africa before and during the AIDS era reveals a disparate epidemiological picture. Its occurrence in sexually inexperienced children; overwhelming male preponderance in an almost exclusively heterosexual population; rarity of concordant couples in areas of very high incidence; sequestration of high incidence to Eastern and Central Africa; and regional variations in incidence even in high-incidence countries are all difficult to reconcile with a conventional sexually transmissible aetiology. There is a need for prospective studies specifically designed to test the hypothesis in Africa. Also, we recommend that studies pursuing the aetiology of KS in western countries be linked with studies in high incidence areas in Africa.
Int J STD AIDS
PMID:Sexually transmissible agent and African Kaposi's sarcoma. 865 10

In order to describe the clinical features of AIDS, particularly injection drug use (IDU) related AIDS in patients attending the Regional Infectious Diseases Unit in Edinburgh a prospective review of the 680 HIV-positive patients, 30% of whom were women and 68% were infected via IDU was undertaken. The commonest AIDS-related clinical problem in Edinburgh was Pneumocystis carinii pneumonia (PCP). Whilst gender differences were not apparent in terms of clinical problems, differences were observed in risk groups as previously reported; Kaposi's sarcoma (KS), cytomegalovirus (CMV) and toxoplasmosis were commoner in homo/ bisexuals whilst oesophageal candidiasis was commoner in drug users. Extrapulmonary tuberculosis was uncommon unlike cohorts from the USA or Italy. Each patient with AIDS can expect 1-2 AIDS-related clinical events per year of survival. Considerable differences in mortality rates by risk group but not by gender were observed and explanations for this difference need to be considered further. The mortality rates for drug users were however remarkably similar to published rates from Amsterdam and the Bronx, New York.
Int J STD AIDS
PMID:Clinical features of AIDS in the Edinburgh City Hospital cohort. 879 81

A number of cytokines, including basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), oncostatin M (OSM), IL-6, and tumor necrosis factor alpha (TNF-alpha), have been postulated to have a role in the pathogenesis of Kaposi's sarcoma (KS). The proliferative effects of bFGF and OSM may be via their reported activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway in KS cells. We now report that KS cells express a recently identified focal adhesion kinase termed RAFTK which appears in other cell systems to coordinate surface signals between cytokine and integrin receptors and the cytoskeleton as well as act downstream to modulate JNK activation. We also report that the tyrosine kinase receptor FLT-4, present on normal lymphatic endothelium, is robustly expressed in KS cells. Treatment of KS cells with VEGF-related protein (VRP), the ligand for the FLT-4 receptor, as well as with the cytokines bFGF, OSM, IL-6, VEGF, or TNF-alpha resulted in phosphorylation and activation of RAFTK. Following its activation, there was an enhanced association of RAFTK with the cytoskeletal protein paxillin. This association was mediated by the hydrophobic COOH-terminal domain of the kinase. Furthermore, JNK activity was increased in KS cells after VEGF or VRP stimulation. We postulate that in these tumor cells RAFTK may be activated by a diverse group of stimulatory cytokines and facilitate signal transduction to the cytoskeleton and downstream to the growth promoting JNK pathway.
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PMID:Cytokine signaling through the novel tyrosine kinase RAFTK in Kaposi's sarcoma cells. 912 25

The present studies analyzed the biologic activity of a gene product (vIL-6) encoded by the recently discovered Kaposi's sarcoma-associated herpesvirus (KSHV) bearing 24.8% amino acid identity with human interleukin-6 (huIL-6). Based on this similarity, we hypothesized that this viral homolog might trigger the JAK/STAT pathway, which typically is engaged by IL-6 and other cytokines. Activation of receptor-associated Janus tyrosine kinases (JAKs) results in the subsequent phosphorylation of signal transducers and activators of transcription (STATs) leading to nuclear entry and transcriptional regulation of target genes. Treatment of HepG2 cells with culture medium containing recombinant KSHV-encoded vIL-6 led to rapid induction of JAK1 phosphorylation and a nuclear DNA-binding activity found to contain STAT1 and STAT3. An antibody to the IL-6 receptor (IL-6R) alpha subunit effectively neutralized the response to huIL-6 but failed to block STAT activation by vIL-6. In contrast, an antibody reactive with the gp130 subunit of IL-6R abrogated signaling of both responses. Moreover, a transfected cell line expressing human gp130 without IL-6Ralpha exhibited a robust response to vIL-6 but not to huIL-6. These results demonstrate that KSHV encodes a cytokine that activates specific JAK/STAT signaling via interactions with the gp130 signal transducing subunit independently of the IL-6Ralpha chain. This activity may have an impact on gp130-mediated signaling in response to native cytokines and thereby influence disease pathogenesis upon KSHV infection.
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PMID:A Kaposi's sarcoma-associated herpesvirus-encoded cytokine homolog (vIL-6) activates signaling through the shared gp130 receptor subunit. 923 71


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