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Find video protocols related to scientific articles indexed in Pubmed.
Anal human papillomavirus infection prevalence in men who have sex with men is age-independent: a role for recent sexual behavior?
Future Microbiol
PUBLISHED: 08-27-2014
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Considering that data available on age-specific prevalence of anal human papillomavirus (HPV) infection among men who have sex with men (MSM) are limited and conflicting, we aimed to assess the age-related trend of this infection in HIV-uninfected MSM.
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A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART.
PLoS ONE
PUBLISHED: 08-25-2014
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We previously found that a very low geno2pheno false positive rate (FPR ? 2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ? 2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART.
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Cytology and human papillomavirus testing on cytobrushing samples from patients with head and neck squamous cell carcinoma.
Cancer
PUBLISHED: 01-24-2014
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The increasing incidence of human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) highlights the need for simple and effective tools to evaluate head and neck lesions and their HPV status. The main objective of the current study was to investigate the association between abnormal cytology and HPV infection, assessed on cytobrushing samples, and histologically confirmed HNSCC. Second, the authors attempted to investigate whether HPV status on cytobrushing samples reflected that of the tumoral tissue.
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Prevalence of anal human papillomavirus infection and cytologic abnormalities among HIV-infected and HIV-uninfected men who have sex with men.
J Int AIDS Soc
PUBLISHED: 01-01-2014
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Human papillomavirus (HPV) is responsible for 85% of anal cancers. Recently, anal cancer incidence has been increasing, particularly in men who have sex with men (MSM). Cytology may be a useful tool for the detection of anal precancerous lesions. We assessed the prevalence and determinants of anal HPV infection and cytologic abnormalities among HIV-infected and -uninfected MSM.
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Risk factors for tuberculosis in foreign-born people (FBP) in Italy: a systematic review and meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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In Italy, TB notifications in foreign-born people (FBP) are steadily increasing. To investigate this issue we did a meta-analysis on risk factors for FBP people. A systematic search was performed in PubMed and EMBASE from Jan-1980 to Jan-2013. We analysed HIV status, previous TB-treatment, intravenous drug use and alcohol abuse, and multidrug resistant TB. Odd ratio was used as a measure of effect. One and two-stages approaches were used. In the main analysis we used a 2-stages approach to include studies with only aggregate estimates. Among 1996 references, 18 fulfilled inclusion criteria. In TB-affected FBP people positive HIV-status was about 3 times higher than among Italians, after 1996 when combined antiretroviral therapy for HIV was introduced (OR: 2.91; 95%CI: 1.37; 6.17). No association was found between FBP and intravenous drug users in adults; after 1-stage meta-analysis foreign born people from highly endemic countries had a 4 times higher risk to be multidrug resistant TB than Italian people. Finally, TB-affected FBP were less likely than Italians to be alcoholics (OR: 0.10 95%CI: 0.01; 0.84) or of having received previous TB-treatment (OR: 0.55; 95%CI: 0.43; 0.71). An association of multidrug resistant TB with immigrant status as well as an association of Tuberculosis with HIV-positive status in foreign-born people are major findings of this analysis. Drugs and alcohol abuse do not appear to be risk factors for TB in FBP, however they cannot be discharged since may depend on cultural traditions and their role may change in the future along with the migratory waves. An effective control of TB risk factors among migrants is crucial to obtain the goal of TB eradication.
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The potential impact of routine testing of individuals with HIV indicator diseases in order to prevent late HIV diagnosis.
BMC Infect. Dis.
PUBLISHED: 09-19-2013
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The aim of our work was to evaluate the potential impact of the European policy of testing for HIV all individuals presenting with an indicator disease, to prevent late diagnosis of HIV. We report on a retrospective analysis among individuals diagnosed with HIV to assess whether a history of certain diseases prior to HIV diagnosis was associated with the chance of presenting late for care, and to estimate the proportion of individuals presenting late who could have been diagnosed earlier if tested when the indicator disease was diagnosed.
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Circulation of HIV-1 CRF02_AG among MSM Population in Central Italy: A Molecular Epidemiology-Based Study.
Biomed Res Int
PUBLISHED: 08-10-2013
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Introduction. The evolutionary and demographic history of the circular recombinant form CRF02_AG in a selected retrospective group of HIV-1 infected men who have sex with men (MSM) resident in Central Italy was investigated. Methods. A total of 55 HIV-1 subtype CRF02_AG pol sequences were analyzed using Bayesian methods and a relaxed molecular clock to reconstruct their dated phylogeny and estimate population dynamics. Results. Dated phylogeny indicated that the HIV-1 CRF02_AG strains currently circulating in Central Italy originated in the early 90s. Bayesian phylogenetic analysis revealed the existence of a main HIV-1 CRF02_AG clade, introduced in the area of Rome before 2000 and subsequently differentiated in two different subclades with a different date of introduction (2000 versus 2005). All the sequences within clusters were interspersed, indicating that the MSM analyzed form a close and restricted network where the individuals, also moving within different clinical centers, attend the same places to meet and exchange sex. Conclusions. It was suggested that the HIV-1 CRF02_AG epidemic entered central Italy in the early 1990s, with a similar trend observed in western Europe.
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Radiation recall dermatitis in course of epidemic Kaposis sarcoma.
Dermatol Ther
PUBLISHED: 03-28-2013
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Radiation recall dermatitis is an acute, rare skin reaction confined to previously irradiated areas that can be triggered by chemotherapeutic drugs (generally doxorubicin and taxanes), which are administrated after radiotherapy. We describe this case report to discuss the timing of the different choice of treatments of progressive Kaposiss sarcoma (KS) disease. KS, the neoplastic disease associated with HHV-8 infection, is still the most commonly diagnosed malignancy in HIV-1 patients, even if its incidence dramatically declined in the highly active antiretroviral therapy (HAART) era. The cutaneous form of disease generally improves with HAART alone or in association with local treatment (cryotherapy, radiotherapy, intralesion chemotherapy), whereas disseminated and/or progressive disease needs to be treated with systemic chemotherapy. In selected patients with progressive disease, systemic and local therapeutic options should be associated. We report a case of a 30-year-old HIV-1-positive man, affected by epidemic cutaneous and mucosal KS, who received several cycles of chemotherapy in succession with radiotherapy and other chemotherapy treatments for disease progression. After 7?months, the end of the last rechallenge with chemotherapy, the patient presented cutaneous painful and ulcerated lesions on the same skin areas previously irradiated.
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Performance of the linear array HPV genotyping test on paired cytological and formalin-fixed, paraffin-embedded cervical samples.
J Mol Diagn
PUBLISHED: 01-23-2013
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Detection and genotyping of human papillomavirus (HPV) from formalin-fixed, paraffin-embedded (FFPE) samples may be difficult when using assays based on amplification of large fragments. The objective of the present study was to investigate the performance of the Linear Array HPV Genotyping Test (Linear Array) on FFPE cervical cone biopsy specimens using paired cytologic samples obtained immediately before the conization as a criterion standard. Thirty-nine samples of grade 2 or higher cervical intraepithelial neoplasia were selected; all of the corresponding cytological samples were positive by the Linear Array and had a report of atypical squamous cells of undetermined significance or worse. A valid Linear Array test result was obtained for 38 FFPE specimens (97.4%, 95% CI 88.0 to 99.9). Specifically, 34 were HPV-positive (89.5%, 95% CI 76.5 to 96.9) and 4 were HPV-negative (10.5%, 95% CI 3.4 to 23.5). The overall agreement of the results obtained for the cytologic and histologic paired samples was good (Cohens ? = 0.85, SE = 0.082, P = 0.000). Further analysis of samples with negative or invalid Linear Array test results, both modifying the nucleic acids extraction protocol and using the INNO-LiPA assay, suggested that failure of the Linear Array test in HPV detection from tissues was probably due to DNA fragmentation. Parallel analysis of paired FFPE and cytologic samples is extremely useful for evaluation of the efficiency of PCR-based assays in HPV detection and genotyping from tissue samples. In the present study, false-negative results were obtained in a limited percentage of cases, our data depicting the successful performance of the Linear Array test on FFPE samples.
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Identification of episomal human papillomavirus and other DNA viruses in cytological anal samples of HIV-uninfected men who have sex with men.
PLoS ONE
PUBLISHED: 01-01-2013
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To date, there have been only few studies that investigated integration of anal Human Papillomavirus (HPV). Most of them were conducted on HIV-infected individuals and mainly analyzed samples from high-grade lesions and invasive cancer. We aimed to investigate HPV physical status in HIV-negative men who have sex with men (MSM) with a detectable anal HPV infection, irrespective of the presence of lesions. We also sought to explore the presence of other circular DNA viruses in the anal region. Study participants were attendees of an STI screening program, which were also screened for anal HPV infection and cytological abnormalities. HPV physical status was assessed using multiply-primed RCA. HPV16-positive samples were also analyzed using E2/E6 multiplex PCR, qRT-PCR and APOT assay. RCA and virus-specific PCR were employed to investigate the presence of other DNA viruses. Anal HPV infection was detected in 76.9% of the 230 MSM enrolled. The anal cytological reports were: 129 NILM, 37 ASC-US and 28 L-SIL (36 samples were inadequate for interpretation). HPV physical status was evaluated in the 109 anal specimens that harbored one or two different HPV genotypes. Integration was observed only in one HPV16-positive sample (0.9%), in which integrate-derived viral transcripts of type B were detected. Integration occurred in chromosome 14 q. In 22 of the 53 (41.5%) mucosal HPV-negative samples, RCA restriction results would seem to indicate the presence of circular DNA viruses. Indeed, cutaneous HPV (4 samples), MCPyV (5 samples) and TTV (4 samples) were detected. In conclusion, anal HPV integration was rarely evidenced in HIV-uninfected MSM with no or mild anal cytological abnormalities, although the integration rate may have been underestimated because of the limitations of the employed assays. Other DNA viruses were detected in the anal samples of these individuals, although the significance of this occurrence needs to be assessed.
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Human mesenchymal stem cells derived from induced pluripotent stem cells down-regulate NK-cell cytolytic machinery.
Blood
PUBLISHED: 07-29-2011
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A major issue in immunosuppressive biotherapy is the use of mesenchymal stem cells (MSCs) that harbor regulatory capacity. However, currently used bone marrow-derived MSCs (BM-MSCs) are short-lived and cannot assure long lasting immunoregulatory function both in vitro and in vivo. Consequently, we have generated MSCs from human induced pluripotent stem (IPS-MSCs) cells that share similar properties with embryonic stem cells (ES-MSCs). Herein, we compared the immunoregulatory properties of ES/IPS-MSCs with those of BM-MSCs and showed, for the first time, that IPS-derived MSCs display remarkable inhibition of NK-cell proliferation and cytolytic function in a similar way to ES-MSCs. Both MSCs disrupt NK-cell cytolytic machinery in the same fashion that BM-MSCs, by down-regulating the expression of different activation markers and ERK1/2 signaling, leading to an impairment to form immunologic synapses with target cells and, therefore, secretion of cytotoxic granules. In addition, they are more resistant than adult BM-MSCs to preactivated NK cells. IPS-MSCs could represent an attractive alternative source of immunoregulatory cells, and their capacity to impair NK-cell cytotoxicity constitutes a complex mechanism to prevent allograft rejection.
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Long-lasting inhibitory effects of fetal liver mesenchymal stem cells on T-lymphocyte proliferation.
PLoS ONE
PUBLISHED: 04-22-2011
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Human bone marrow mesenchymal stem cells (BM-MSC) are multipotent progenitor cells that have transient immunomodulatory properties on Natural Killer (NK) cells, Dendritic Cells (DC), and T cells. This study compared the use of MSC isolated from bone marrow and fetal liver (FL-MSC) to determine which displayed the most efficient immunosuppressive effects on T cell activation. Although both types of MSC exhibit similar phenotype profile, FL-MSC displays a much more extended in vitro life-span and immunomodulatory properties. When co-cultured with CD3/CD28-stimulated T cells, both BM-MSC and FL-MSC affected T cell proliferation by inhibiting their entry into the cell cycle, by inducing the down-regulation of phospho-retinoblastoma (pRb), cyclins A and D1, as well as up-regulating p27(kip1) expression. The T cell inhibition by MSC was not due to the soluble HLA-G5 isoform, but to the surface expression of HLA-G1, as shown by the need of cell-cell contact and by the use of neutralizing anti-HLA-G antibodies. To note, in a HLA-G-mediated fashion, MSC facilitated the expansion of a CD4(low)/CD8(low) T subset that had decreased secretion of IFN-?, and an induced secretion of the immunomodulatory cytokine IL-10. Because of their longer lasting in vitro immunosuppressive properties, mainly mediated by HLA-G, and their more efficient induction of IL-10 production and T cell apoptosis, fetal liver MSC could be considered a new tool for MSC therapy to prevent allograft rejection.
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Comparative evaluation of different DNA extraction methods for HPV genotyping by linear array and INNO-LiPA.
J. Med. Virol.
PUBLISHED: 04-20-2011
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In order to investigate the influence of DNA extraction on two PCR-based HPV genotyping tests (Linear Array, Roche and INNO-LiPA Extra, Innogenetics), three different procedures were used to purify DNA from 28 cervico-vaginal samples tested previously by the Hybrid Capture 2: the AmpliLute Liquid Media Extraction kit (Roche), the QIAamp DNA Blood mini kit (QIAGEN), and the NucliSENS EasyMAG automated platform (bioMérieux). All HC2-positive samples were found positive by both assays, independently of the extract used. Type-specific concordance (i.e., identical HPV type-specific profile in all the extracts of the same sample) was observed in 55% and 75% of the cases testing samples by the Linear Array and the INNO-LiPA, respectively. Using the DNA extracted with the two manual methods the results were concordant in 75% of the cases both for the Linear Array and the INNO-LiPA. When comparing the Linear Array results obtained on either of the two manual extracts with those obtained following automated extraction, 65% of the samples showed type-specific concordance in both cases. The INNO-LiPA results were concordant in 80% of the cases comparing the AmpliLute versus the automated extract, while concordant results were observed in 90% of the cases when comparing the QIAGEN versus the automated extract. In conclusion, the Linear Array and INNO-LiPA results are affected by the method of DNA extraction. Consequently, different HPV type-specific profiles may be observed using different extracts of the same sample. The use of consistent protocols for DNA purification is a priority to guarantee intra-assay reproducibility over time.
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Interferon-alpha triggers B cell effector 1 (Be1) commitment.
PLoS ONE
PUBLISHED: 04-02-2011
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B-cells can contribute to the pathogenesis of autoimmune diseases not only through auto-antibody secretion but also via cytokine production. Therapeutic depletion of B-cells influences the functions and maintenance of various T-cell subsets. The mechanisms governing the functional heterogeneity of B-cell subsets as cytokine-producing cells are poorly understood. B-cells can differentiate into two functionally polarized effectors, one (B-effector-1-cells) producing a Th-1-like cytokine pattern and the other (Be2) producing a Th-2-like pattern. IL-12 and IFN-? play a key role in Be1 polarization, but the initial trigger of Be1 commitment is unclear. Type-I-interferons are produced early in the immune response and prime several processes involved in innate and adaptive responses. Here, we report that IFN-? triggers a signaling cascade in resting human naive B-cells, involving STAT4 and T-bet, two key IFN-? gene imprinting factors. IFN-? primed naive B-cells for IFN-? production and increased IFN-? gene responsiveness to IL-12. IFN-? continues this polarization by re-inducing T-bet and up-regulating IL-12R?2 expression. IFN-? and IFN-? therefore pave the way for the action of IL-12. These results point to a coordinated action of IFN-?, IFN-? and IL-12 in Be1 polarization of naive B-cells, and may provide new insights into the mechanisms by which type-I-interferons favor autoimmunity.
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Cord blood CD133 cells define an OV6-positive population that can be differentiated in vitro into engraftable bipotent hepatic progenitors.
Stem Cells Dev.
PUBLISHED: 03-23-2011
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Cell therapy represents the most promising alternative strategy for end-stage liver diseases and hepatic progenitors are the best candidates. We have identified a reservoir of immature hepatic precursors within human cord blood, which can derive engraftable bipotent progenitors. We isolated a stem cell subset CD133+/CD34+/OV6(low) expressing a surface-marker profile consistent with that of fetal liver cells. Upon induction of hepatic commitment by a medium containing cytokines and factors involved in vivo oval-cell activation, a heterogeneous cell population displaying characteristics of functional oval-cell-like bipotent hepatic progenitors was obtained. The cells expressed markers of hepatocytes and cholangiocytes and were highly enriched in OV6, c-Met, c-Kit, and Thy-1. They also displayed liver functional activity as glycogen storage, urea production, albumin secretion, and inducible CyP2B6 activity. When injected into liver-damaged severe-combined immunodeficient mice, induced bipotent hepatic progenitors appropriately engrafted livers of recipient animals, where they formed clusters of human-derived cells expressing human leucocyte antigen-class I, Hep-Par1, and OV6 antigens. Human-specific albumin, alpha-fetoprotein, and cytokeratin 19 were also expressed. In transplanted animals, AST serum levels showed a significative reduction with regard to controls. This human model for in vitro progenitor-cell activation may provide a powerful tool for elucidating the pathways and synergies that regulate this complex process and can represent a valuable source, exploitable for liver cell-based therapies and regenerative medicine.
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Lymphocyte cell-cycle inhibition by HLA-G is mediated by phosphatase SHP-2 and acts on the mTOR pathway.
PLoS ONE
PUBLISHED: 02-16-2011
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Human leukocyte antigen G (HLA-G) is involved in regulating T-cell responses through its interaction with inhibitory receptors belonging to the immunoglobulin-like transcript family (ILT). In this context, we investigated the pathways involved in the control of cell-cycle entry of T cells following HLA-G interaction with its inhibitory receptor. We show that HLA-G acts through its interaction with the LILRB1 receptor expressed on T lymphocytes. Both HLA-G and LILRB1 antibodies block the inhibitory effect of HLA-G and restore T-cell proliferation. The interaction of HLA-G with T lymphocytes is associated with phosphorylation of SHP-2 phosphatase, but not SHP-1. In addition, in activated T cells, their incubation with HLA-G is not associated with a decrease in the TCR or CD28 downstream pathways, but is associated with dephosphorylation of the mTOR molecule and p70S6K. In contrast, Akt, which acts upstream of mTOR, is not affected by HLA-G. The inhibition of SHP-2 by NSC-87877(5 µM), a chemical inhibitor of SHP-2, or the use of siRNA, abrogates dephosphorylation of mTOR and impairs the overexpression of p27(kip) in the presence of HLA-G. Together, these results indicate that HLA-G is associated with activation of phosphatase SHP-2, which inhibits the mTOR pathway and favors the inhibition of the cell-cycle entry of human-activated T cells.
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Membrane-bound IL-15 stimulation on peripheral blood natural kiler progenitors leads to the generation of an adherent subset co-expressing dendritic cells and natural kiler functional markers.
Haematologica
PUBLISHED: 01-17-2011
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Human peripheral blood natural killer progenitors represent a flexible, heterogeneous population whose phenotype and function are controlled by their membrane-bound IL-15. Indeed, reciprocal membrane-bond IL-15 trans-presentation commits these cells into NK differentiation, while membrane-bound IL-15 stimulation with its soluble ligand (sIL-15R?) triggers a reverse signal (pERK1/2 and pFAK) that modifies the developmental program of at least two subsets of PB-NKPs. This treatment generates: i) the expansion of an immature NK subset growing in suspension; ii) the appearance of an unprecedented adherent non-proliferative subset with a dendritic morphology co-expressing marker, cytokines and functions typical of myeloid dendritic cells (CD1a(+)/BDCA1(+)/IL-12(+)) and NK cells (CD3-/NKp46(+)/ CD56(+)/IFN?(+)). The generation of these putative NK/DCs is associated to the rapid inhibition of negative regulators of myelopoiesis (the transcription factors STAT6 and GATA-3) followed by the transient upregulation of inducers of myeloid development, such as the transcription factors (PU.1, GATA-1) and the anti-apoptotic molecule (MCL-1).
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HLA-G in organ transplantation: towards clinical applications.
Cell. Mol. Life Sci.
PUBLISHED: 10-21-2010
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HLA-G plays a particular role during pregnancy in which its expression at the feto-maternal barrier participates into the tolerance of the allogenic foetus. HLA-G has also been demonstrated to be expressed in some transplanted patients, suggesting that it regulates the allogenic response. In vitro data indicate that HLA-G modulates NK cells, T cells, and DC maturation through its interactions with various inhibitory receptors. In this paper, we will review the data reporting the HLA-G involvement of HLA-G in human organ transplantation, then factors that can modulate HLA-G, and finally the use of HLA-G as a therapeutic tool in organ transplantation.
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Population dynamics of HIV-1 subtype B in a cohort of men-having-sex-with-men in Rome, Italy.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 08-13-2010
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A recent increase in HIV diagnoses among men-having-sex-with-men (MSM) has been shown by surveillance data from Europe and Italy, and new approaches to inferring viral population dynamics from heterochronously sampled gene sequences have been developed. The aim of this study was to reconstruct the epidemiological history of HIV-1 subtype B in a homogeneous group of Italian MSM using a coalescent-based Bayesian framework. A total of 125 HIV-1 subtype B pol sequences were analyzed using Bayesian methods and a relaxed molecular clock to reconstruct their dated phylogeny and estimate population dynamics. At least 10 epidemiological clusters of 3-9 isolates were identified: half including the largest clades originated in the early 1990s and the other half radiated from 1999. Demographic analysis showed that the HIV epidemic grew in accordance with a logistic model characterized by a rapid exponential increase in the effective number of infections (r = 1.54 year) starting from the early 1980s and reaching a plateau 10 years later. Our data suggest that the HIV B epidemic entered our MSM population through multiple transmission chains about 20 years later than in other Western European country. Epidemiological clusters originating in the early 2000s suggest a recent re-emergence of HIV in Italian MSM.
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Characterization of the patterns of drug-resistance mutations in newly diagnosed HIV-1 infected patients naïve to the antiretroviral drugs.
BMC Infect. Dis.
PUBLISHED: 07-16-2009
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The transmission of HIV-1 drug-resistant strains in drug naive patients may seriously compromise the efficacy of a first-line antiretroviral treatment. To better define this problem, a study in a cohort of newly diagnosed HIV-1 infected individuals has been conducted. This study is aimed to assess the prevalence and the patterns of the mutations recently associated with transmitted drug resistance in the reverse transcriptase (RT) and in protease (PR) of HIV-1.
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The preventive phase I trial with the HIV-1 Tat-based vaccine.
Vaccine
PUBLISHED: 04-20-2009
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The native HIV-1 Tat protein was chosen as vaccine candidate for phase I clinical trials based on its role in the natural infection and AIDS pathogenesis, on the association of Tat-specific immune response with the asymptomatic stage as well as on its sequence conservation among HIV clades. A randomized, double blind, placebo-controlled phase I study (ISS P-001) was conducted in healthy adult volunteers without identifiable risk of HIV infection. Tat was administered 5 times monthly, subcute in alum or intradermic alone at 7.5 microg, 15 microg or 30 microg, respectively (ClinicalTrials.gov identifier: NCT00529698). Vaccination with Tat resulted to be safe and well tolerated (primary endpoint) both locally and systemically. In addition, Tat induced both Th1 and Th2 type specific immune responses in all subjects (secondary endpoint) with a wide spectrum of functional antibodies that are rarely seen in natural infection, providing key information for further clinical development of the Tat vaccine candidate.
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The cooperative induction of hypoxia-inducible factor-1 alpha and STAT3 during hypoxia induced an impairment of tumor susceptibility to CTL-mediated cell lysis.
J. Immunol.
PUBLISHED: 03-07-2009
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Hypoxia is an essential component of tumor microenvironment. In this study, we investigated the influence of hypoxia (1% PO(2)) on CTL-mediated tumor cell lysis. We demonstrate that exposure of target tumor cells to hypoxia has an inhibitory effect on the CTL clone (Heu171)-induced autologous target cell lysis. Such inhibition correlates with hypoxia-inducible factor-1alpha (HIF-1alpha) induction but is not associated with an alteration of CTL reactivity as revealed by granzyme B polarization or morphological change. Western blot analysis indicates that although hypoxia had no effect on p53 accumulation, it induced the phosphorylation of STAT3 in tumor cells by a mechanism at least in part involving vascular endothelial growth factor secretion. We additionally show that a simultaneous nuclear translocation of HIF-1alpha and phospho-STAT3 was observed. Interestingly, gene silencing of STAT3 by small interfering RNA resulted in HIF-1alpha inhibition and a significant restoration of target cell susceptibility to CTL-induced killing under hypoxic conditions by a mechanism involving at least in part down-regulation of AKT phosphorylation. Moreover, knockdown of HIF-1alpha resulted in the restoration of target cell lysis under hypoxic conditions. This was further supported by DNA microarray analysis where STAT3 inhibition resulted in a partly reversal of the hypoxia-induced gene expression profile. The present study demonstrates that the concomitant hypoxic induction of phospho-STAT3 and HIF-1alpha are functionally linked to the alteration of non-small cell lung carcinoma target susceptibility to CTL-mediated killing. Considering the eminent functions of STAT3 and HIF-1alpha in the tumor microenvironment, their targeting may represent novel strategies for immunotherapeutic intervention.
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Phase I therapeutic trial of the HIV-1 Tat protein and long term follow-up.
Vaccine
PUBLISHED: 02-07-2009
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A randomized, double blind, placebo-controlled phase I vaccine trial based on the native Tat protein was conducted in HIV-infected asymptomatic individuals. The vaccine was administered five times subcute with alum or intradermally without adjuvant at 7.5microg, 15microg or 30microg doses, respectively. The Tat vaccine was well tolerated both locally and systemically and induced and/or maintained Tat-specific T helper (Th)-1 T-cell responses and Th-2 responses in all subjects with a wide spectrum of functional anti-Tat antibodies, rarely seen in HIV-infected subjects. The data indicate the achievement of both the primary (safety) and secondary (immunogenicity) endpoints of the study.
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Human renal cancer cells express a novel membrane-bound interleukin-15 that induces, in response to the soluble interleukin-15 receptor alpha chain, epithelial-to-mesenchymal transition.
Cancer Res.
PUBLISHED: 02-03-2009
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Although interleukin-15 (IL-15) is a powerful immunomodulatory factor that has been proposed for cancer immunotherapy, its intratumoral expression may be correlated with tumor progression and/or poor clinical outcome. Therefore, neoplasias potentially sensitive to immunotherapy should be checked for their IL-15 expression and function before choosing immunotherapy protocols. Primary human renal cancer cells (RCC) express a novel form of membrane-bound IL-15 (mb-IL-15), which displays three major original properties: (a) It is expressed as a functional membrane homodimer of 27 kDa, (b) it is shed in the extracellular environment by the metalloproteases ADAM17 and ADAM10, and (c) its stimulation by soluble IL-15 receptor alpha (s-IL-15Ralpha) chain triggers a complex reverse signal (mitogen-activated protein kinases, FAK, pMLC) necessary and sufficient to ~induce epithelial-mesenchymal transdifferentiation (EMT), a crucial process in tumor progression whose induction is unprecedented for IL-15. In these cells, complete EMT is characterized by a dynamic reorganization of the cytoskeleton with the subsequent generation of a mesenchymal/contractile phenotype (alpha-SMA and vimentin networks) and the loss of the epithelial markers E-cadherin and ZO-1. The retrosignaling functions are, however, hindered through an unprecedented cytokine/receptor interaction of mb-IL-15 with membrane-associated IL-15Ralpha subunit that tunes its signaling potential competing with low concentrations of the s-IL-15Ralpha chain. Thus, human RCC express an IL-15/IL-15R system, which displays unique biochemical and functional properties that seem to be directly involved in renal tumoral progression.
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Anal cytological abnormalities and epidemiological correlates among men who have sex with men at risk for HIV-1 infection.
BMC Cancer
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The incidence of anal cancer, a Human Papillomavirus (HPV)-related neoplasia, has been increasing in recent decades, mainly in men who have sex with men (MSM). Cytological changes of the anal epithelium induced by HPV can be detected through an anal pap smear. This study aimed to evaluate the prevalence and epidemiological correlates of anal cytological abnormalities among relatively young MSM at risk for HIV-1 infection, to help clarify whether or not this population deserves further investigation to assess the presence of anal cancer precursor lesions.
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p16/Ki-67 dual staining in cervico-vaginal cytology: correlation with histology, Human Papillomavirus detection and genotyping in women undergoing colposcopy.
Gynecol. Oncol.
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To evaluate the CINtec PLUS assay (mtm laboratories), a new immunocytochemical method for the simultaneous detection of p16(INK4a) and Ki-67, in liquid-based cervico-vaginal cytology, investigating the association of the dual staining with HPV infection and genotyping as well as cytological and histological abnormalities.
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Prevalence, genotype diversity and determinants of anal HPV infection in HIV-uninfected men having sex with men.
J. Clin. Virol.
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Anal human papillomavirus (HPV) infection is very common in men having sex with men (MSM), but the available data on its burden and characteristics mainly concern HIV-infected individuals.
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TLR ligands stimulation protects MSC from NK killing.
Stem Cells
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Mesenchymal Stem Cells (MSC) play a fundamental role in allograft rejection and Graft-versus-Host Disease (GvDH) through their immunosuppressive abilities. Recently, Toll like Receptors (TLR) have been shown to modulate MSC functions. The aim of this study was to investigate the effects of several TLR ligands on the interaction between MSC and NK cells. Our results show that TLR-primed adult bone marrow and embryonic MSC are more resistant than unprimed MSC to IL2-activated NK-induced killing. Such protection can be explained by the modulation of NKG2D ligands MICA and ULBP3 and DNAM1 ligands by TLR-primed MSC. These results indicate that MSC are able to adapt their immuno-behaviour in an inflammatory context, decreasing their susceptibility to NK killing. In addition, TLR3 but not TLR4-primed MSC enhance their suppressive functions against NK cells. However, the efficiency of this response is heterogeneous, even if the phenotypes of different analyzed MSC are rather homogeneous. The consequences could be important in MSC-mediated cell therapy, since the heterogeneity of adult MSC responders may be explored in order to select the more efficient responders. Stem Cells 2013;
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.