HIV-Tat dependent chemotaxis and invasion, key aspects of Tat mediated pathogenesis

Extracellular Tat acts as a pleiotropic molecule inducing several biological effects on different target cells. Tat stimulates the chemotaxis of numerous cell types and it appears to have oncogenic activities, including acting as a co-factor for Kaposi's sarcoma. The Tat protein has been shown to bind integrins through an RGD amino acid motif. Tat is an angiogenic factor able to induce the migration and invasion of endothelial and KS cells through the interaction of its basic domain with the VEGF receptor VEGFR2 (Flk-1/KDR). We have also found that Tat is able to mimic chemokines, activating monocyte migration through the `chemokine like' cysteine-core domain. Tat is a chemoattractant for dendritic cells, and both the RGD and basic domains appear to be involved in this response. In a recent study we demonstrated that Tat is chemotactic for PMN and induces Ca<sup>2+</sup> mobilization in vitro. Experiments using synthetic peptides showed that Tat activities on PMN are mediated by the `chemokine like' region. Finally Tat is also able to induce B cell chemotaxis, while its activity on helper T cells has not yet been clarified. Here we review data on Tat-dependent chemotaxis and discuss the possible implications in Tat mediated pathogenesis. This revised version was published online in July 2006 with corrections to the Cover Date.     

Dermatophyte agents in the city of São Paulo, from 1992 to 2002

Dermatophytosis are superficial mycoses caused by fungi that can invade stratum corneum and keratinized tissues. In order to study the frequency of dermatophytes species and the clinical manifestations caused by these fungi, in S?o Paulo, SP, Brazil, the authors analyzed cultures isolated at the Mycology Laboratory from a selected population (15,300 out-patients of the Hospital das Clínicas, Department of Dermatology, Faculty of Medicine of University of S?o Paulo) from January 1992 to June 2002. The most prevalent dermatophyte was Trichophyton rubrum (48.7%), followed by Microsporum canis (20.9%), Trichophyton tonsurans (13.8%), Trichophyton mentagrophytes (9.7%), Epidermophyton floccosum (4.1%), and Microsporum gypseum (2.5%). These agents determined more than one clinical manifestation, i.e., tinea corporis (31.5%), tinea capitis (27.5%), tinea unguium (14.8%), tinea cruris (13.9%), tinea pedis (9.9%), and tinea manuum (1.9%). Clinical variants of dermatophytosis and their relationship to the etiologic agents were studied and the results were compared to those obtained in previous studies in other regions of Brazil and in other countries.     

Renal artery stenting in patients with chronic ischemic heart disease

Objectives : To investigate the role of renal stenting in selected patients with chronic ischemic heart disease and renal artery stenosis. Methods : Consecutive patients, with chronic ischemic heart disease and severe hypertension and/or impaired renal function undergoing renal stenting, were prospectively enrolled. Mid‐term (at least 2 years) follow‐up was performed to assess both changes in renal function [serum creatinine and estimated glomerular filtrate rate (eGFR)] and blood pressure (BP) control (number of required drugs) and to record the incidence of clinical major adverse events. Moreover, in the first consecutive 24 patients, out‐of‐range pressure values at 24‐hr BP monitoring and GFR at renal scintigraphy were measured at baseline and 1 month after stenting. Results : Seventy patients treated by stenting on 86 renal arteries entered the study. Procedural success rate was 99% and no major complication occurred. At 2‐year follow‐up, both mean serum creatinine (?0.1 ± 0.7 mg/dl at follow‐up compared to baseline, P = 0.6) and eGFR (+3.7 ± 23.5 ml/min/1.73m² at follow‐up compared to baseline, P = 0.2) did not significantly change while the number of drugs required to control BP significantly decreased (2.7 ± 0.8 to 2.2 ± 0.7, P < 0.0001). In the subset of 24 patients evaluated at 1 month, GFR significantly increased (62 ± 20 ml/min to 67 ± 21 ml/min; P = 0.008) and the rate of the out‐of‐range systolic pressure values at 24‐hr monitoring significantly decreased (51–33%, P = 0.005). Elevated baseline creatinine values and the presence of global renal ischemia were identified as predictors of poor outcome at the multivariate analysis. Conclusions : In selected patients with chronic ischemic heart disease and hypertension and/or renal insufficiency, renal stenting may be performed with very low periprocedural complications and results in unchanged renal function and improved BP control. © 2010 Wiley‐Liss, Inc.     

Angiogenic properties of human immunodeficiency virus type 1 Tat protein.

Extracellular human immunodeficiency virus type 1 (HIV-1) Tat protein promotes growth of spindle cells derived from AIDS-associated Kaposi sarcoma (AIDS-KS), an angioproliferative disease very frequent in HIV-1-infected individuals. Normal vascular cells, progenitors of AIDS-KS cells, proliferate in response to Tat after exposure to inflammatory cytokines, whose levels are augmented in HIV-1-infected individuals and in KS lesions. Here we show that Tat also promotes AIDS-KS and normal vascular cells to migrate and to degrade the basement membrane and stimulates endothelial cell morphogenesis on a matrix substrate. These effects are obtained at picomolar concentrations of exogenous Tat and are promoted by the treatment of the cells with the same inflammatory cytokines stimulating expression of the receptors for Tat, the integrins alpha 5 beta 1 and alpha v beta 3. Thus, under specific circumstances, Tat has angiogenic properties. As Tat and its receptors are present in AIDS-KS lesions, these data may explain some of the mechanisms by which Tat can induce angiogenesis and cooperate in the development of AIDS-KS.     

HIV-1 Tat protein mimicry of chemokines

The HIV-1 Tat protein is a potent chemoattractant for monocytes. We observed that Tat shows conserved amino acids corresponding to critical sequences of the chemokines, a family of molecules known for their potent ability to attract monocytes. Synthetic Tat and a peptide (CysL_24–51) encompassing the “chemokine-like” region of Tat induced a rapid and transient Ca²⁺ influx in monocytes and macrophages, analogous to β-chemokines. Both monocyte migration and Ca²⁺ mobilization were pertussis toxin sensitive and cholera toxin insensitive. Cross-desensitization studies indicated that Tat shares receptors with MCP-1, MCP-3, and eotaxin. Tat was able to displace binding of β-chemokines from the β-chemokine receptors CCR2 and CCR3, but not CCR1, CCR4, and CCR5. Direct receptor binding experiments with the CysL_24–51 peptide confirmed binding to cells transfected with CCR2 and CCR3. HIV-1 Tat appears to mimic β-chemokine features, which may serve to locally recruit chemokine receptor-expressing monocytes/macrophages toward HIV producing cells and facilitate activation and infection.     

Association of family history of epilepsy with earlier age at seizure onset in patients with focal cortical dysplasia

OBJECTIVE: To establish the contribution of family history of epilepsy to seizure onset in patients with focal cortical dysplasia (FCD). PATIENTS AND METHODS: From January 1998 to January 2001, we prospectively evaluated 19 consecutive patients (10 male, 9 female) with a diagnosis of FCD based on magnetic resonance imaging. All patients and at least 1 family member were directly interviewed by the same observer after completion of a semistructured questionnaire. Initially, we classified patients into 2 groups: presence or absence of family history of epilepsy. Patients with a family history of epilepsy were subdivided into 2 groups: patients with a family history of epilepsy in first-degree relatives or multiple relatives (n=5) and patients with a family history of epilepsy in relatives who were not first-degree (n=4). Statistical analysis was performed with use of the nonparametric tests Kruskal-Wallis and Kaplan-Meier (survival analysis). P=.05 was considered statistically significant. RESULTS: The ages of the patients ranged from 3 to 41 years (mean, 15.6 years). All patients had similar type and extent of cortical dysgenesis. Ages at seizure onset varied from 1 month to 22 years, with a mean of 5.8 years. Nine patients had a family history of epilepsy. The mean age at the first seizure in patients with a family history of epilepsy was 2.6 years compared with 8.5 years in those with no relatives having epilepsy (P=.02). When patients with a family history of epilepsy were classified further, the mean age at first seizure was 1.9 years for patients with a family history of epilepsy in first-degree or multiple relatives and 3.9 years for patients with a family history of epilepsy in relatives who were not first-degree compared with 8.5 years for patients with no family history of epilepsy (P=.04). CONCLUSION: Our results show that a family history of epilepsy is associated with an earlier age at seizure onset in patients with FCD. Although this is a preliminary finding and a larger sample is needed to confirm these results, we believe these observations provide evidence that genetic modifiers could become an important issue in the clinical presentation of patients with dysplastic lesions.     

Analysis of FIM instrument scores for patients admitted to an inpatient cardiac rehabilitation program

OBJECTIVE: To evaluate in an inpatient cardiac rehabilitation program (a phase IB) whether length of stay (LOS), discharge to home, and improvement in physical function differed between patients with lower and higher degrees of functional independence on admission. DESIGN: A retrospective study. SETTING: A public acute long-term care hospital. PATIENTS: All cardiac rehabilitation patients (N = 143) admitted to the hospital from January 1998 through June 1999. Patients were divided into a higher- and a lower-functioning group by using the admission FIM instrument scores above and below the midpoint of 72. Comparisons in LOS, discharge disposition, and functional gains between these 2 groups were then performed. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: FIM scores, FIM change, FIM gains per week, LOS, and discharge disposition. RESULTS: Total FIM scores at discharge were significantly higher than those on admission (25%, P <.0001). The median value of total FIM gains per week was 7.78 with a stay of 17 days and a home discharge rate of 76%. The higher-functioning group (n = 106) differed from the lower group (n = 37) with shorter stay (15 vs 23d, P <.0001), greater FIM gains per week (8.6 vs 4.8, P =.002), and greater likelihood of discharge to home or community (84% vs 54%, P <.001). The average incremental FIM change in each group was the same. In multivariate analysis, both admission (P =.001) and discharge (P <.001) FIM scores were the best predictors of patients' discharge disposition to home. CONCLUSIONS: Admission FIM scores are important predictors for the clinical course and discharge outcomes of cardiac rehabilitation patients, with those with higher admission FIM scores having a shorter LOS and greater likelihood of discharge to home. The admission FIM scores can help to establish realistic goals.     

Toward 90-90-90: identifying those who have never been tested for HIV and differences by sex in Lesotho

To reach HIV epidemic control it is important to ensure that those who have never been tested access HIV testing and counseling (HTC) particularly in the context of a generalized HIV epidemic. Using data from the 2014 Lesotho Demographic Health Survey bivariate and multivariate logistic regressions were conducted to determine the associations between never tested for HIV and key socio-cognitive characteristics by sex. Marginal probabilities at the means were calculated for the socio-cognitive variables for men and women to ascertain the magnitude of the differences in the likelihood of never being tested by sex. We stratified by gender and controlled for age, education, religion, marital status, place of residence, and years circumcised (for men only). Results indicate that more men than women have never been tested (χ^2?=?461.16, p?p?p?p?p?p?相似文献