67 research outputs found
Synergy between the pharmacological chaperone 1-deoxygalactonojirimycin and the human recombinant alpha-galactosidase A in cultured fibroblasts from patients with Fabry disease.
Generation and characterization of a defective HIV-1 Virus as an immunogen for a therapeutic vaccine
BACKGROUND: The generation of new immunogens able to elicit strong specific immune responses remains a major challenge in the attempts to obtain a prophylactic or therapeutic vaccine against HIV/AIDS. We designed and constructed a defective recombinant virus based on the HIV-1 genome generating infective but non-replicative virions able to elicit broad and strong cellular immune responses in HIV-1 seropositive individuals. RESULTS: Viral particles were generated through transient transfection in producer cells (293-T) of a full length HIV-1 DNA carrying a deletion of 892 base pairs (bp) in the pol gene encompassing the sequence that codes for the reverse transcriptase (NL4-3/ÎRT clone). The viral particles generated were able to enter target cells, but due to the absence of reverse transcriptase no replication was detected. The immunogenic capacity of these particles was assessed by ELISPOT to determine Îł-interferon production in a cohort of 69 chronic asymptomatic HIV-1 seropositive individuals. Surprisingly, defective particles produced from NL4-3/ÎRT triggered stronger cellular responses than wild-type HIV-1 viruses inactivated with Aldrithiol-2 (AT-2) and in a larger proportion of individuals (55% versus 23% seropositive individuals tested). Electron microscopy showed that NL4-3/ÎRT virions display immature morphology. Interestingly, wild-type viruses treated with Amprenavir (APV) to induce defective core maturation also induced stronger responses than the same viral particles generated in the absence of protease inhibitors. CONCLUSIONS: We propose that immature HIV-1 virions generated from NL4-3/ÎRT viral clones may represent new prototypes of immunogens with a safer profile and stronger capacity to induce cellular immune responses than wild-type inactivated viral particles.This study was supported by grants FIS PI050265, FIS PI040503, FIS PI070291, FIS Intrasalud 080752, FIS PS09/01297, FIS PI10/02984, SAF2006-26667-E, FIT 09-010-205-9, FIPSE 36780/08, FundaciĂłn MĂștua Madrileña, TRA-094, EC10-153, ISCIII-RETIC RD06/0006, HIVACATâHIV Development Program in Catalonia, FIPSE 36630/07, UE Program Health 2009 CHAARM. Spanish Health Institute Carlos III (ISCIII) and the Health Department of the Catalan Government (Generalitat de Catalunya). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S
Sensitivity to food additives, vaso-active amines and salicylates: a review of the evidence
Development and Validation of a Method for the Determination of Quinolones in Muscle and Eggs by Liquid Chromatography-Tandem Mass Spectrometry
Characterization of a discontinuous epitope of the HIV envelope protein gp120 recognized by a human monoclonal antibody using chemical modification and mass spectrometric analysis
Fabry's disease: a comparison of the effectiveness of two different enzyme replacement therapies
Hepatitis C and kidney disease
Hepatitis C virus (HCV) infection is often associated with kidney diseases such as membranoproliferative glomerulonephritis (MPGN),
with and without cryoglobulinemia, membranous glomerulonephritis (MGN) or glomerulosclerosis (FSGN). The aim of our study was to
determine the frequency of HCV with or without hypertransaminasemia in patients with chronic nephropathy in the predialytic phase. We
tested 340 subjects with chronic renal insufficiency (CRI) from our hospital's nephrology outpatient clinic for anti-HCV antibodies. In
positive subjects we tested for HCV RNA by PCR method, monitoring, for at least 4 months, common biohmnoral parameters including
transaminases (AST, ALT). Of the 340 subjects, 46 (13.5%) were positive for HCV RNA, and 8 of these (17%) showed constant alteration
of transaminases. HBsAg was found in 8 of the total study population (2.3%), and none of these showed altered transaminases. Type II
diabetes mellitus was found in 26% (12/46) of the HCV-RNA positive patients, and in only 12.5% (37/294) of the negative ones. The
kidney diseases we found in the 46 HCV-RNA positive patients were: diabetic nephropathy in 11 (23.9%), MPGN in 7 (15.2%), MPGN +
cryoglobulinemia in 2 (4.3%), interstitial nephropathy in 4 (8.7%), IgA mesangial GN in 3 (6.5%), hypertensive nephropathy in 2 (4.3%),
focal and segmental GN in 1 (2.2%), urologic disease in 4 (8.7%), other (hematological, genetic, iatrogenic) in 3 (6.6%), unknown in 9 (19.6%). Our data show that the most frequent kidney diseases associated with HCV infection were diabetic related nephropathy and MPGN with and without cryoglobulinemia. HCV infection had a positive association with diabetes. It is interesting to note that in this study population the hepatitis C concomitant to kidney disease was unusually mild: only 4 of the 46 subjects (9%) showed clinical,
biohumoral and ultrasound evidence of cirrhosis
Enzyme replacement therapy in patients with Fabry disease: state of the art and review of the literature
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