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)

Clarithromycin can ameliorate symptoms and improve survival in disseminated Mycobacterium avium complex (DMAC) infection. Optimal combinations of this drug with other agents remain unknown. Granulocyte colony stimulating factor (G-CSF) is a cytokine that can improve phagocytosis of M. avium complex in vitro. We aim to determine if G-CSF administration is associated with improved survival in patients with DMAC in a retrospective, cohort study. Case records from 1991 to 1995 of 91 patients with DMAC at Parkland Memorial Hospital were reviewed for date of initial DMAC diagnosis, baseline CD4 count, race, sex, antiretroviral use, G-CSF use, therapy for DMAC (clarithromycin, ethambutol, ciprofloxacin and rifabutin) and date of death. Of 91 cases identified, 25 were treated with G-CSF and 66 never received this drug. Baseline characteristics were similar in each group including CD4 count (40 cells/mm3 vs 33 cells/mm3, P=0.68), clarithromycin use (18 patients vs 52 patients, P=0.90), and antiretroviral use (20 patients vs 42 patients, P=0.21). Subjects treated with G-CSF lived longer than those who did not receive this drug (355 days vs 211 days, P<0.01). In the subgroup treated with clarithromycin, G-CSF was also associated with increased survival (377 days vs 252 days, P<0.01). Cox proportional hazards model showed a decreased risk of death in patients treated with G-CSF (RH=0.22, P<0.01), clarithromycin (RH=0.13, P<0.01) and ethambutol (RH=0.51, P=0.02). Ciprofloxacin and rifabutin use did not influence survival. These data support the use of clarithromycin and ethambutol in the treatment of DMAC. Addition of G-CSF to a regimen of clarithromycin and ethambutol may increase survival in DMAC and should be studied prospectively.
Int J STD AIDS 1998 Jul
PMID:G-CSF association with prolonged survival in HIV-infected patients with disseminated Mycobacterium avium complex infection. 969 94

Eosinophils, along with mast cells are key cells involved in the innate immune response against parasitic infection whereas the adaptive immune response is largely dependent on lymphocytes. In chronic parasitic disease and in chronic allergic disease, IL-5 is predominantly a T cell derived cytokine which is particularly important for the terminal differentiation, activation and survival of committed eosinophil precursors. The human IL-5 gene is located on chromosome 5 in a gene cluster that contains the evolutionary related IL-4 family of cytokine genes. The human IL-5 receptor complex is a heterodimer consisting of a unique alpha subunit (predominantly expressed on eosinophils) and a beta subunit which is shared between the receptors for IL-3 & GM-CSF (more widely expressed). The alpha subunit is required for ligand-specific binding whereas association with the beta subunit results in increased binding affinity. The alternative splicing of the alpha IL-5R gene which contains 14 exons can yield several alpha-IL-5R isoforms including a membrane-anchored isoform (alpha IL-5Rm) and a soluble isoform (alpha IL-5Rs). Cytokines such as IL-5 produce specific and non-specific cellular responses through specific cell membrane receptor mediated activation of intracellular signal transduction pathways which, to a large part, regulate gene expression. The major intracellular signal transduction mechanism is activation of non-receptor associated tyrosine kinases including JAK and MAP kinases which can then transduce signals via a novel family of transcriptional factors named signal transducers and activators of transcription (STATS). JAK2, STAT1, and STAT5 appear to be particularly important in IL-5 mediated eosinophil responses. Asthma is characterized by episodic airways obstruction, increased bronchial responsiveness, and airway inflammation. Several studies have shown an association between the number of activated T cells and eosinophils in the airways and abnormalities in FEV1, airway reactivity and clinical severity in asthma. It has now been well documented that IL-5 is highly expressed in the bronchial mucosa of atopic and intrinsic asthmatics and that the increased IL-5 mRNA present in airway tissues is predominantly T cell derived. Immunocytochemical staining of bronchial biopsy sections has confirmed that IL-5 mRNA transcripts are translated into protein in asthmatic subjects. Furthermore, the number of activated CD4 + T cells and IL-5 mRNA positive cells are increased in asthmatic airways following antigen challenge and studies that have examined IL-5 expression in asthmatic subjects before and after steroids have shown significantly decreased expression following oral corticosteroid treatment in steroid-sensitive asthma but not in steroid resistant and chronic severe steroid dependent asthma. The link between T cell derived IL-5 and eosinophil activation in asthmatic airways is further strengthened by the demonstration that there is an increased number of alpha IL-5R mRNA positive cells in the bronchial biopsies of atopic and non-atopic asthmatic subjects and that the eosinophil is the predominant site of this increased alpha IL-5R mRNA expression. We have also shown that the subset of activated eosinophils that expressed mRNA for membrane bound alpha IL-5r inversely correlated with FEV1, whereas the subset of activated eosinophils that expressed mRNA for soluble alpha IL-5r directly correlated with FEV1. Hence, not only does this data suggest that the presence of eosinophils expressing alpha IL-5R mRNA contribute towards the pathogenesis of bronchial asthma, but also that the eosinophil phenotype with respect to alpha IL-5R isoform expression is of central importance. Finally, there are several animal, and more recently in vitro lung explant, models of allergen induced eosinophilia, late airway responses (LARS), and bronchial hyperresponsiveness (BHR)--all of which support a link between IL-5 and airway eosinophilia and bronc
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PMID:IL-5 and IL-5 receptor in asthma. 969 19

Findings are presented from a cross-sectional study conducted in 1995 in Bobo-Dioulasso, Burkina Faso, in which the patterns of diseases and CD4 counts among 266 HIV-infected adults of mean age 33 years were analyzed. The bioclinical spectrum of subjects' HIV disease is described and a simple alternative proposed to CD4 enumeration for screening and monitoring HIV-infected Africans. Dermatological symptoms and diarrhea were the most frequent signs associated with B-stage disease, while cachexia and digestive candidosis were the most frequent AIDS-defining diseases (ADD). Peripheral facial paralysis and cutaneo-mucous diseases were associated with weak immune deficiency. Pulmonary tuberculosis (TB) was close to B-stage diseases, and chronic diarrhea was borderline between B and C stages. Cachexia was the most frequent C-stage symptom (47.8%). 90% of CDC C-stage subjects had CD4 counts of less than 350 per mcl, while only 75% had CD4 counts under 200/mcl. Regression analysis identified the lymphocyte count, clinical stage, and platelet count as predictors of CD4 count below 350/mcl. A lymphocyte count of less than or equal to 2500/mcl and clinical stage of B or higher is proposed to determine the CD4 threshold and to determine those patients in need of treatment to prevent wasting and opportunistic infections.
Int J STD AIDS 1998 Aug
PMID:A proposal for basic management of HIV disease in west Africa: use of clinical staging and haemogram data. 970 95

The objectives of this study were to describe the clinical and radiological features at presentation, and the natural history of HIV-related bronchopulmonary Kaposi's sarcoma. A retrospective review of medical records and chest radiographs was performed in 106 HIV-infected homosexual men with bronchopulmonary Kaposi's sarcoma diagnosed at bronchoscopy between September 1988 and November 1994. The majority of patients had evidence of advanced HIV disease at diagnosis (median CD4 cell count was 15 x 10(6)/l, range 0-288), and 93% had had a diagnosis of cutaneous Kaposi's sarcoma for a median duration of 11 months prior to diagnosis of their bronchopulmonary disease. The most frequent symptoms at presentation were cough (92%), dyspnoea (69%), pleuritic pain (20%), haemoptysis (13%) and wheezing (10%). The most common radiological finding in 73% of our series was of poorly defined and confluent opacities, with predominant middle and lower zone involvement. Median survival was 4 months (range 0-37 months) from diagnosis and 9 months (range 1-25) from the onset of symptoms. Treatment with either chemotherapy or radiotherapy was associated with a significantly reduced risk of death (hazards ratio (HR)=0.48, 95% CI=0.26-0.87). Factors associated with a poor survival, after adjustment for treatment effect were older age (HR=1.79, 95% CI=1.22-2.84) for each 10-year increase in age; a history of pleuritic pain (HR=2.97, 95% CI=1.39-6.32); presence of pleural effusion on X-ray (HR=2.01, 95% CI=1.13-3.59) and a prior diagnosis of cutaneous Kaposi's sarcoma (HR=1.8, 95% CI=1.00, 3.24). Bronchopulmonary Kaposi's sarcoma occurs mainly in patients with advanced HIV disease and a prior history of cutaneous disease. Survival is poor, and adverse prognostic factors include older age at diagnosis and the presence of pleural disease.
Int J STD AIDS 1998 Sep
PMID:Bronchopulmonary Kaposi's sarcoma in 106 HIV-1 infected patients. 976 35

Chancroid is caused by infection with Hemophilus ducreyi, and is associated with an increased risk for the sexual transmission of HIV-1. The authors assessed whether the clinical and histological features of chancroid are changed by HIV infection, using 320 male patients who presented during February-November 1994 to the City of Nairobi Special Treatment Clinic with a clinical diagnosis of chancroid. 109 subjects were HIV seropositive and 211 were HIV seronegative. A detailed history, physical examination, swabs for Hemophilus ducreyi culture and blood for HIV serology, syphilis serology, and CD4 counts were obtained from all patients. Punch biopsies from an ulcer were obtained from 10 patients and either fixed in 10% formalin or snap frozen in Optimum Cutting Temperature (OCT) medium compound at -70 degrees Celsius. Patients were treated with erythromycin and followed for 3 weeks. HIV patients had ulcers of longer duration than did HIV-seronegative patients. Although cure rates were similar at 3 weeks, HIV patients had lower cure rates at 1 week (23% vs. 54%). A dense interstitial and perivascular inflammatory infiltrate extending from the reticular to deep dermis was present in all biopsies. The infiltrate consisted of equal amounts of CD4 and CD8 T-lymphocytes as well as macrophages. The histological and immunohistochemical picture was identical for HIV-positive and HIV-negative patients. Study findings therefore indicate that HIV infection slows the healing rates of chancroid ulcers despite appropriate antibiotic therapy. The clinical difference cannot be attributed to an altered histopathological response to HIV infection.
Int J STD AIDS 1998 Sep
PMID:Clinical and in situ cellular responses to Haemophilus ducreyi in the presence or absence of HIV infection. 976 37

We aim to assess the usefulness of the cytomegalovirus (CMV) pp65 antigenaemia test, also called the CMV direct antigen test (DAT), in the management of patients with advanced human immunodeficiency virus (HIV) infection; we studied all patients who had pp65 assays between 8 September 1995 and 30 August 1996. Twenty-three patients had 31 tests. The mean CD4 cell count was 20/mm3. The tests were negative in 16 patients, of whom 12 have not developed CMV end-organ disease after a mean follow up of 114 days (range 14-269 days), whilst the remaining 4 patients had previously treated CMV disease. Eleven patients had positive tests: 4 had active CMV disease, 2 subsequently developed CMV retinitis, 2 died within a fortnight of multi-drug resistant tuberculosis (MDR-TB), one was lost to follow up and 2 have remained disease-free. This test has a positive predictive value of 43% and a negative predictive value of 94%, Fisher's exact test P=0.03. The pp65 antigenaemia assay can be performed in a standard virology laboratory avoiding the problems associated with polymerase chain reaction (PCR), a result is available within 5 h, and it is semi-quantifiable. However, a large prospective study is required to determine the comparative value and roles of the pp65 antigenaemia assay and DNA PCR in the management of CMV disease, especially with regard to the use of primary prophylaxis and pre-emptive therapy.
Int J STD AIDS 1998 Sep
PMID:Cytomegalovirus pp65 antigenaemia as an indicator of end-organ disease in AIDS. 976 40

Intrathymic T-cell differentiation is under the control of the thymic microenvironment, which acts on maturing thymocytes via membrane as well as soluble products. Increasing data show that this process can be modulated by classical hormones, as exemplified herein by prolactin (PRL) and growth hormone (GH), largely secreted by the pituitary gland. Both PRL and GH stimulate the secretion of thymulin, a thymic hormone produced by thymic epithelial cells. Conversely, low levels of circulating thymulin parallel hypopituitary states. Interestingly, the enhancing effects of GH on thymulin seem to be mediated by insulinlike growth factor 1 (IGF-1) since they can be abrogated with anti-IGF-1 or anti-IGF-1-receptor antibodies. The influence of PRL and GH on the thymic epithelium is pleiotropic: PRL enhances in vivo the expression of high-molecular-weight cytokeratins and stimulates in vitro TEC proliferation, an effect that is shared by GH and IGF-1. Differentiating T cells are also targets for the intrathymic action of PRL and GH. In vivo inoculation of a rat pituitary cell line into old rats results in restoration of the thymus, including differentiation of CD4- CD8- thymocytes into CD4+ CD8+ cells. Furthermore, PRL may regulate the maintenance of thymocyte viability during the double-positive stage of thymocyte differentiation. Injections of GH into aging mice increase total thymocyte numbers and the percentage of CD3-bearing cells, as well as the Concanavalin-A mitogenic response and IL-6 production by thymocytes. Interestingly, similar findings are observed in animals treated with IGF-1. Lastly, the thymic hypoplasia observed in dwarf mice can be reversed with GH treatment. In keeping with the data summarized earlier is the detection of receptors for PRL and GH on both thymocytes and thymic epithelial cells. Importantly, recent studies indicate that both cell types can produce PRL and GH intrathymically. Similarly, production of IGF-1 and expression of a corresponding receptor has also been demonstrated. In conclusion, these data strongly indicate that the thymus is physiologically under control of pituitary hormones PRL and GH. In addition to the classical endocrine pathway, paracrine and autocrine circuits are probably implicated in such control.
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PMID:Role of prolactin and growth hormone on thymus physiology. 981 5

Our aim was to investigate if the clinical benefits of combination antiretroviral therapy recently reported from clinical trials are reproduced in a population-based HIV surveillance scheme. This surveillance scheme is estimated to cover 90% of the HIV-positive population currently under immunological monitoring in Scotland. Our results showed a considerable reduction in new AIDS cases among this group from 107 in 1995 to 59 in 1996 and an estimated 58 in 1997 (allowing for reporting delay). There was a similar fall in deaths from 75 in 1995 to 59 in 1996 and an estimated 24 in 1997. These observations are temporally associated with increasing prescription of antiretroviral therapy in Scotland throughout 1996 and 1997. Examination of those individuals monitored in both 1996 and 1997 showed that from their first CD4 count in 1996 to their first count in 1997 there has been a median gain of 6 CD4 cells/mm3 (95%CI 0-12) compared with a median fall of 27 CD4 cells/mm3 (95%CI -35, -17) for those monitored in both 1995 and 1996. Highest median gains in CD4 cell counts from 1996 to 1997 were seen in those receiving triple or quadruple therapy (median gain 32CD4 cells/mm3). These results are further strengthened by the results of a separate longitudinal analysis showing a highly significant (P < 0.001) effect of treatment on CD4 cell loss with the highest mean CD4 gains being seen in those in triple or quadruple therapy. Our results indicate that the benefits of combination antiretroviral therapy previously seen in clinical trials are being reproduced at a population level. It remains to be seen if these benefits can be sustained in the long term.
Int J STD AIDS 1998 Oct
PMID:The recent impact of antiretroviral combination therapy on CD4 counts, AIDS and death in HIV-infected persons: routine HIV surveillance in Scotland. 981 3

The objective of this study was to describe the medical, attitudinal and cultural correlates of antiretroviral uptake amongst people living with HIV/AIDS (PLWHA) in Australia. Stratified purposive sampling produced a sample of 925 PLWHA, which represents 8.3% of the current population of PLWHA in Australia. Respondents completed a self-administered questionnaire which revealed that 78% of respondents were using antiretroviral drugs for HIV/AIDS. Logistic regression revealed that PLWHA were more likely to use antiretroviral drugs if they had more favourable attitudes toward antiretroviral drugs, if they had been diagnosed with an AIDS-defining illness, and if they had ever had a CD4/T-cell count below 400 copies/ml blood. Women were less likely than men to use antiretroviral drugs, and logistic regression revealed different predictors of antiretroviral drug use amongst men and women. Given the importance of attitudes toward antiretroviral drugs, it is likely that if the current confidence in antiretroviral drugs were to change, this would be reflected in an equally rapid cessation of treatment amongst many PLWHA.
Int J STD AIDS 1998 Oct
PMID:Antiretroviral uptake in Australia: medical, attitudinal and cultural correlates. 981 7

Alterations in body shape due to fat loss and/or redistribution have been described in HIV-infected individuals and associated with the use of antiretroviral (ARV) combination therapy. Certain of these changes have been referred to as peripheral lipodystrophy (LD) and we describe 12 patients who were recognized with this condition between September 1997 and February 1998. It occurred in 12.5% of patients on ARV combination therapy that included a protease inhibitor (PI). In early descriptions the emphasis was on the abdomen, which may be grossly enlarged. In our patients this feature was much less marked. Patients with LD were significantly older than those on PI therapy who did not develop this condition (P=0.016). Although all had raised triglyceride (TG) levels, the elevations were not severe (maximum=6.3 mmol/l). CD4 lymphocyte and viral load levels suggested an optimal response to ARV therapy at the time LD developed. Appearances may be disfiguring but no serious systemic consequences of LD have been observed. Most individuals have chosen to remain on their present ARV combinations. When LD occurs, it appears to be a marker of effective response to anti-HIV therapy.
Int J STD AIDS 1998 Oct
PMID:Disorders of fat distribution in HIV infection. 981 10


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