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)

The correlation between sexually transmitted infections and cervicovaginal dysplasia has been evaluated in a cohort of 135 women who tested positive for human immunodeficiency virus type I (HIV-1) and were admitted to Amedeo di Savoia Hospital of Turin during the years 1997 and 1998 (stages B2 and B3 or C2 and C3). Of these women. 31 presented with sexually transmitted diseases (STDs; mean age, 33.5 +/- 5.9 years). Among them, 14 were affected by cervicovaginal dysplasia of differing severity; human papillomavirus (HPV) infection was found in 13 subjects (10 with cervicovaginal dysplasia). Herpes simplex virus type 2 (HSV-2) infection was detected in six women. Finally, Trichomonas vaginalis and Candida albicans were found in 10 and in 6 patients, respectively. Immunologic and hematologic evaluations were performed in the patients affected by STDs; in 28 patients of our case report unaffected by STDs but of similar ages (34.1 +/- 5.6 years) and stage of infection; and in 20 HIV-negative women unaffected by STDs. A significant reduction among the patients affected by STDs, as compared to those unaffected, was found in the case of white cells, CD4+ T cells, and ratio values (CD4 +/ and CD8 + T cells). Moreover, red cell count and hemoglobin concentration were lower in those women in the STD group. A lack of correlation was found between HIV RNA loads and CD4 + T cell counts and between HIV RNA and hemoglobin concentration in the patients with cervicovaginal dysplasia and in those affected by HSV-2 infection, which differed from the findings in subjects affected only by trichomoniasis or candidiasis. This suggests that the two former pathologic conditions (cervico-vaginal dysplasia and HSV-2 infection), other than HIV- I infection, may contribute to the impairment of these values. Moreover in our case report, T vaginalis and HSV-2 infections, which are suspected to have an oncogenic potential, do not seem to be relevant in the induction or facilitation of genital neoplastic diseases. Noteworthy is that the patients affected by HSV-2 infection, such as those affected by genital neoplastic diseases, showed the most compromised values of total white cells, CD4+ T cells, ratio index, red cells, and hemoglobin concentration.
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PMID:Sexually transmitted infections and cervicovaginal dysplasia in a cohort of human immunodeficiency virus-positive women in Turin. 1127 Apr 19

Intermittent administration of recombinant interleukin-2 (rIL-2) to individuals infected with human immunodeficiency virus (HIV) has been shown to raise and maintain the absolute number of circulating CD4(+) T cells to normal or near normal levels. One of the signaling pathways triggered by IL-2 is the Janus kinase-signal transducer and activator of transcription (JAK-STAT). In particular, IL-2 activates the tyrosine kinases JAK1 and JAK3 and the transcription factors STAT3 and STAT5. We have previously observed that most HIV(+) individuals, unlike healthy seronegative controls, show a constitutive activation of STAT1 and a C-terminal truncated isoform of STAT5 (STAT5 Delta). In the present study, we have analyzed the protein level and activation state of STAT5 isoforms expressed in peripheral blood mononuclear cells of two HIV-infected individuals who showed a good or a poor response to intermittent IL-2 administration, respectively, and of a single individual before and after initiation of Zidovudine monotherapy. We provide evidence that both therapeutic interventions enhanced the expression and activation of the C-terminal truncated isoform of STAT5 (STAT5 Delta) in vivo.
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PMID:Expression and activation of a C-terminal truncated isoform of STAT5 (STAT5 Delta) following interleukin 2 administration or AZT monotherapy in HIV-infected individuals. 1128 43

The objective of this study was to examine prescription and acceptance of antiretroviral therapy (ART) and Pneumocystis carinii pneumonia (PCP) prophylaxis in jail and at release. A retrospective cross sectional design was used, by record review, of 77 inmates receiving HIV-related care in the San Francisco City and County Jail and released to the community in 1997. Average CD4 cell count was 335/microl. Fifteen had undectable HIV RNA, and average viral load was 19,826 copies/ml. Fifty-eight per cent were put on ART in jail. Lower CD4 cell count was associated with ART (P=0.017). All inmates with CD4 cell counts less than 200/microl received PCP prophylaxis. According to 1996 guidelines, 72% of those eligible for ART were on therapy. Of 24 inmates released on ART, 71% followed medical advice and picked up medication at release. HIV care in the San Francisco Jail met high standards and exceeded levels reported in other populations.
Int J STD AIDS 2001 Jun
PMID:Jail inmates and HIV care: provision of antiretroviral therapy and Pneumocystis carinii pneumonia prophylaxis. 1136 19

Skeletal infections with atypical mycobacteria are a manifestation of advanced HIV disease, most patients having CD4 counts of less than 100 cells/mm(3). We report a case of Mycobacterium xenopi vertebral osteomyelitis in a patient on HAART with a CD4 count of 490 cells/mm(3) and viral load below the level of detection at the time of diagnosis.
Int J STD AIDS 2001 Jun
PMID:Mycobacterium xenopi osteomyelitis in a patient on highly active antiretroviral therapy (HAART). 1136 25

Metabolic complications are being increasingly recognized among HIV-infected patients treated with potent combination antiretroviral therapies. We sought to assess the association of dyslipidaemia with adherence to protease inhibitor (PI) therapy and with the markers of clinical response to antiretroviral therapy (CD4 count, HIV RNA viral level) through a prospective, cross-sectional cohort study. Fifty-six HIV-infected patients who were already on, or who were started on PI-containing antiretroviral therapy were monitored for the development of dyslipidaemias. Therapy with PI-containing antiretroviral therapy was significantly associated with elevated serum triglyceride level (>250 mg/dl) (52% vs 8%, P=0.001). Patients with an adherence rate of at least 80% to a PI-containing regimen were significantly more likely to have elevated low density lipoprotein (LDL) cholesterol level as compared to patients with an adherence rate of <80% (79% vs 26%, P=0.03). Patients with an adherence rate of at least 80% to a PI-containing regimen were also significantly more likely to have severe hypertriglyceridaemia (>800 mg/dl) as compared to patients with an adherence rate of <80% (21% vs 4%, P=0.04). Viral load at the last study visit did not correlate with total cholesterol (r=-0.39, P=0.30), LDL cholesterol (r=0.57, P=0.30), or triglyceride level (r=0.55, P=0.20). However, there was a significant correlation between the last viral load and high density lipoprotein (HDL) cholesterol (r=0.79, P=0.035), i.e. lower viral load was associated with higher HDL cholesterol level. In conclusion, dyslipidaemia in patients with HIV infection was significantly associated with adherence to PI-containing antiretroviral therapy. Patients who are adherent to PI-containing regimens at least 80% of the time warrant close monitoring for the development of dyslipidaemia.
Int J STD AIDS 2001 Jul
PMID:Dyslipidaemia in HIV-infected patients: association with adherence to potent antiretroviral therapy. 1139 83

HIV-1 infection leads to T cell dysfunction and apoptosis in vivo and in vitro. The shared common gamma chain of IL-2R and its associated Janus kinase, JAK3, are indispensable for normal T cell function and survival. We have reported that CD4 ligation with HIV gp120 inhibits T cell receptor-induced activation and expression of JAK3. We have also shown that while some strains of HIV-1, such as NL4-3, induce apoptosis of infected CD4(+) T cells, other strains, such as HIV-1 IIIB, do not. Interestingly, we show here that infection of CD4(+) T cells with HIV-1 NL4-3, but not IIIB, inhibited activation and expression of JAK3. NL4-3-infected T cells were unable to upregulate JAK3 expression following stimulation through TCR/CD3. In addition, NL4-3, but not IIIB, inhibited tyrosine phosphorylation and expression of STAT5, a downstream target of JAK3. These data suggest a correlation between apoptosis of HIV-1-infected T cells and inhibition of the JAK3/STAT5 activation pathway.
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PMID:HIV-1 NL4-3, but not IIIB, inhibits JAK3/STAT5 activation in CD4(+) T cells. 1148 9

We examined the relationship between the haematogenous dissemination of Mycoplasma fermentans and non-Hodgkin's lymphoma (NHL) in 265 HIV-1 positive patients. A polymerase chain reaction (PCR) assay was used to detect M. fermentans in peripheral blood mononuclear cells (PBMCs) from 50 patients enrolled consecutively from an HIV outpatient clinic in 1991 (cohort 1), 56 patients with lower respiratory tract infection who underwent bronchoscopy in 1992 (cohort 2), and 159 patients who were enrolled into a natural history cohort study in 1994 (cohort 3). The incidence of NHL among the patients was determined in 1998. The PBMCs of 29 patients (10.9%) were positive for M. fermentans (8 in cohort 1, 13 in cohort 2 and 8 in cohort 3) and 11 patients (4.2%) developed NHL which was confirmed histologically (3 in cohort 1, 4 in cohort 2 and 4 in cohort 3). We found a statistically significant association between the presence of M. fermentans and the development of NHL in the combined cohort (risk ratio [RR]=6.78 [95% confidence interval (CI) 2.21--20.84], P=0.003 Fisher's exact test [FET]). This association remained significant even after adjustment in a multivariate analysis for CD4 cell count and HIV disease status at the time of M. fermentans testing (RR=7.97 [95% CI=2.16--29.47], P=0.002).
Int J STD AIDS 2001 Aug
PMID:An association of disseminated Mycoplasma fermentans in HIV-1 positive patients with non-Hodgkin's lymphoma. 1148 89

Our objective was to assess, in the clinical setting, the predictors of immune reconstitution (IR) and its relation with long-term clinical benefit, in HIV patients with advanced disease after highly active antiretroviral therapy (HAART) through an observational study. A retrospective cohort study in a clinical setting of 383 consecutive adult patients with advanced HIV infection (CD4+ cells <200/mm(3) at baseline), starting their first protease inhibitor (PI)-containing regimen was observed. Immune reconstitution was defined as CD4 count >200 cells/mm(3) and an increase > or =100 cells from baseline, anytime since starting HAART. Clinical benefit was defined as decreased mortality and reduction in AIDS-defining events, AIDS-related complex (ARC) events, major infections and hospitalization (days spent in hospital). During a mean follow-up of 808 days, 261 patients (68.1%) achieved IR. About 50% of these patients reached this result within one year after starting HAART. In multivariate analysis, predictors of immune recovery were sex (female) and baseline CD4 count higher than 50 cells/mm(3). The group of patients with IR had greater clinical benefit with lower mortality, fewer AIDS-defining events, shorter lengths of stay in hospital, fewer ARC events and fewer major infections during all the follow-up (P < 0.0001, tests for trends). However, although they did less remarkably than the first group of patients, even those patients who did not achieve IR experienced a significant decrease in the incidence of all the above events, as compared with the first and sometimes the second trimester after starting their HIV therapy. About 70% of HIV patients with advanced disease achieved IR after starting HAART. Such a benefit is a time-dependent effect and may even take more than 2 years to occur. Predictors of IR were sex (female) and higher baseline CD4 count (>50 cells/mm(3)). The patients who achieved immune recovery performed clinically better than patients who did not. Also the patients who failed to gain such a strong immunological recovery experienced a long-term clinical benefit. This suggests that PI-containing regimens, in advanced HIV disease, may produce a significant clinical benefit, at least temporary, even for patients who do not achieve a substantial immune response.
Int J STD AIDS 2001 Sep
PMID:Long-term clinical benefit after highly active antiretroviral therapy in advanced HIV-1 infection, even in patients without immune reconstitution. 1151 66

Although influenza vaccination is recommended for individuals with HIV infection, there are no data indicating an increased incidence or severity of influenza in this population. We sought to describe the clinical manifestations and morbidity of influenza in HIV-infected patients. All cases of influenza occurring in HIV-infected individuals over 3 years at a large county hospital were reviewed. Forty-three cases of influenza were diagnosed. Most patients presented with typical signs and symptoms of influenza, including cough (90%), myalgias (64%), and fever (52%). Sore throat and headache occurred in less than half of patients. The mean CD4 cell count and HIV viral load in patients with influenza was 340 cells/mm(3) and 3.34 log copies/ml, respectively. No significant differences in CD4 counts or viral loads were noted in patients with pneumonia (n=7) compared with patients without pneumonia (n=36), P>0.5. Six patients were hospitalized. One patient each had encephalitis and renal failure, although the relationship to influenza was not clear. No new or unusual clinical manifestations were observed. The rate of pulmonary complications was similar to other studies in HIV-negative patients; however, the hospitalization rate was higher than commonly seen in HIV-negative individuals.
Int J STD AIDS 2001 Oct
PMID:Clinical manifestations of influenza in HIV-infected individuals. 1156 31

Prior to the use of highly active antiretroviral therapy (HAART), cytomegalovirus retinitis (CMV-R) in AIDS patients was characterized by multiple relapses and decreased survival. Recent data suggest that CMV-R in patients treated with HAART may remain relapse-free for long periods. We performed a study of the effects of HIV protease inhibitors (PIs) on the incidence of relapse and time to death in AIDS patients with CMV-R treated with anti-CMV therapy. Medical records of all AIDS patients with CMV-R at Parkland Memorial Health and Hospital System treated with anti-CMV agents were reviewed for date of diagnosis of CMV-R, date of CMV-R relapse, type and duration of anti-CMV therapy, and duration of PI therapy. Relapse rates in subjects treated with PIs were compared with the relapse rates in those who were not treated with PIs. The primary endpoint was the time to relapse and death as determined by Kaplan-Meier analysis. Multivariate analysis was performed by Cox proportional hazard model. One hundred and nine cases of CMV-R were identified in 75 patients. Median follow-up time was 247 days (range 31-1818 days). There were 0.54 relapses per 1000 patient days in the group treated with PIs compared with 1.83 relapses per 1000 patient days in the non-PI treatment group (relative risk [RR]=0.29, P<0.01). Time to relapse was increased in the PI treatment group compared with the non-PI treatment group (endpoint not reached vs 182 days, P<0.001, log-rank). Similarly, the time to relapse or death was increased in the PI group compared with the non-PI group (543 days vs 103 days, P<0.001, log-rank). Multivariate analysis utilizing the Cox proportional hazards model demonstrated that only PI therapy but not anti-CMV therapy was associated with decreased risk of CMV-R relapse or death. Only 3 patients with an undetectable HIV viral load and one patient with a CD4 count >120 cells/microl had a relapse. We conclude that patients with CMV-R treated with HAART containing a PI have increased time to relapse and have prolonged survival.
Int J STD AIDS 2001 Oct
PMID:Protease inhibitor therapy is associated with markedly prolonged time to relapse and improved survival in AIDS patients with cytomegalovirus retinitis. 1156 33


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