Institution
Federal University of São Paulo
Education•São Paulo, Brazil•
About: Federal University of São Paulo is a education organization based out in São Paulo, Brazil. It is known for research contribution in the topics: Population & Transplantation. The organization has 27971 authors who have published 49365 publications receiving 935536 citations. The organization is also known as: Universidade Federal de São Paulo & Universidade Federal de Sao Paulo.
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Harvard University1, National Institutes of Health2, Stanford University3, University of Colorado Denver4, Karolinska Institutet5, University of Debrecen6, Kuwait University7, University of California, San Francisco8, Cincinnati Children's Hospital Medical Center9, Newcastle upon Tyne Hospitals NHS Foundation Trust10, Mayo Clinic11, University of Pennsylvania12, Boston Children's Hospital13, Hamad Medical Corporation14, Ain Shams University15, American University of Beirut16, University of São Paulo17, Federal University of São Paulo18, University of Toronto19, University of California, Irvine20, University of Utah21, University of Antioquia22, University of Düsseldorf23, University of Ulm24, University of Amsterdam25, University of Basel26
TL;DR: It is demonstrated that patients with hypomorphic RAG mutations, especially those with delayed-onset combined immune deficiency and granulomatous/autoimmune manifestations (CID-G/AI), produce a broad spectrum of autoantibodies and indicates that environmental triggers may modulate the phenotypic expression of autoimmune manifestations.
Abstract: Patients with mutations of the recombination-activating genes (RAG) present with diverse clinical phenotypes, including severe combined immune deficiency (SCID), autoimmunity, and inflammation. However, the incidence and extent of immune dysregulation in RAG-dependent immunodeficiency have not been studied in detail. Here, we have demonstrated that patients with hypomorphic RAG mutations, especially those with delayed-onset combined immune deficiency and granulomatous/autoimmune manifestations (CID-G/AI), produce a broad spectrum of autoantibodies. Neutralizing anti-IFN-α or anti-IFN-ω antibodies were present at detectable levels in patients with CID-G/AI who had a history of severe viral infections. As this autoantibody profile is not observed in a wide range of other primary immunodeficiencies, we hypothesized that recurrent or chronic viral infections may precipitate or aggravate immune dysregulation in RAG-deficient hosts. We repeatedly challenged Rag1S723C/S723C mice, which serve as a model of leaky SCID, with agonists of the virus-recognizing receptors TLR3/MDA5, TLR7/-8, and TLR9 and found that this treatment elicits autoantibody production. Altogether, our data demonstrate that immune dysregulation is an integral aspect of RAG-associated immunodeficiency and indicate that environmental triggers may modulate the phenotypic expression of autoimmune manifestations.
147 citations
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TL;DR: A great diversity of different species causing trichosporonemia is found, including a high frequency of isolation of T. asteroides from blood cultures that is lower than that of T asahii only and the first T. asAHii isolate belonging to genotype 4 in South America is reported.
Abstract: The reevaluation of the genus Trichosporon has led to the replacement of the old taxon Trichosporon beigelii by six new species. Sequencing of the ribosomal DNA (rDNA) intergenic spacer 1 (IGS1) is currently mandatory for accurate Trichosporon identification, but it is not usually performed in routine laboratories. Here we describe Trichosporon species distribution and prevalence of Trichosporon asahii genotypes based on rDNA IGS1 sequencing as well as antifungal susceptibility profiles of 22 isolates recovered from blood cultures. The clinical isolates were identified as follows: 15 T. asahii isolates, five Trichosporon asteroides isolates, one Trichosporon coremiiforme isolate, and one Trichosporon dermatis isolate. We found a great diversity of different species causing trichosporonemia, including a high frequency of isolation of T. asteroides from blood cultures that is lower than that of T. asahii only. Regarding T. asahii genotyping, we found that the majority of our isolates belonged to genotype 1 (86.7%). We report the first T. asahii isolate belonging to genotype 4 in South America. Almost 50% of all T. asahii isolates exhibited amphotericin B MICs of ≥2 μg/ml. Caspofungin MICs obtained for all the Trichosporon sp. isolates tested were consistently high (MICs ≥ 2 μg/ml). Most isolates (87%) had high MICs for 5-flucytosine, but all of them were susceptible to triazoles, markedly to voriconazole (all MICs ≤ 0.06 μg/ml).
147 citations
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TL;DR: Structural analysis indicates that 3-O-sulfation at C-3 of 4-alpha-L-fucose 1-> units is responsible for the anticoagulant activity of the polymer, indicating that the brown algae Padina gymnospora contain different fucans.
Abstract: The brown algae Padina gymnospora contain different fucans. Powdered algae were submitted to proteolysis with the proteolytic enzyme maxataze. The first extract of the algae was constituted of polysaccharides contaminated with lipids, phenols, etc. Fractionation of the fucans with increasing concentrations of acetone produced fractions with different proportions of fucose, xylose, uronic acid, galactose, and sulfate. One of the fractions, precipitated with 50% acetone (v/v), contained an 18-kDa heterofucan (PF1), which was further purified by gel-permeation chromatography on Sephadex G-75 using 0.2 M acetic acid as eluent and characterized by agarose gel electrophoresis in 0.05 M 1,3 diaminopropane/acetate buffer at pH 9.0, methylation and nuclear magnetic resonance spectroscopy. Structural analysis indicates that this fucan has a central core consisting mainly of 3-beta-D-glucuronic acid 1-> or 4-beta-D-glucuronic acid 1 ->, substituted at C-2 with alpha-L-fucose or beta-D-xylose. Sulfate groups were only detected at C-3 of 4-alpha-L-fucose 1-> units. The anticoagulant activity of the PF1 (only 2.5-fold lesser than low molecular weight heparin) estimated by activated partial thromboplastin time was completely abolished upon desulfation by solvolysis in dimethyl sulfoxide, indicating that 3-O-sulfation at C-3 of 4-alpha-L-fucose 1-> units is responsible for the anticoagulant activity of the polymer.
147 citations
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TL;DR: The physical activity parameters of MHD patients were compatible with a sedentary lifestyle and this inactivity was worsened by aging, diabetes and higher BMI.
Abstract: Background. The assessment of physical activity and energy expenditure is relevant to the care of maintenance haemodialysis (MHD) patients. In the current study, we aimed to evaluate measurements of physical activity and energy expenditure in MHD patients from different centres and countries and explored the predictors of physical activity in these patients. Methods. In this cross-sectional multicentre study, 134 MHD patients from four countries (France, Switzerland, Sweden and Brazil) were included. The physical activity was evaluated for 5.0 6 1.4 days (mean 6 SD) by a multisensory device (SenseWear Armband) and comprised the assessment of number of steps per day, activity-related energy expenditure (activity-related EE) and physical activity level (PAL). Results. The number of steps per day, activity-related EE and PAL from the MHD patients were compatible with a sedentary lifestyle. In addition, all parameters were significantly lower in dialysis days when compared to non-dialysis days (P < 0.001). The multivariate regression analysis revealed that diabetes and higher body mass index (BMI) predicted a lower PAL and older age and diabetes predicted a reduced number of steps. Conclusions. The physical activity parameters of MHD patients were compatible with a sedentary lifestyle. This inactivity was worsened by aging, diabetes and higher BMI. Our results indicate that MHD patients should be encouraged by the health care team to increase their physical activity.
147 citations
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TL;DR: The main focus of the present review will be on the central command, the arterial baroreflex and chemoreflex, and the exercise pressure reflex.
Abstract: During dynamic exercise, mechanisms controlling the cardiovascular apparatus operate to provide adequate oxygen to fulfill metabolic demand of exercising muscles and to guarantee metabolic end-products washout. Moreover, arterial blood pressure is regulated to maintain adequate perfusion of the vital organs without excessive pressure variations. The autonomic nervous system adjustments are characterized by a parasympathetic withdrawal and a sympathetic activation. In this review, we briefly summarize neural reflexes operating during dynamic exercise. The main focus of the present review will be on the central command, the arterial baroreflex and chemoreflex, and the exercise pressure reflex. The regulation and integration of these reflexes operating during dynamic exercise and their possible role in the pathophysiology of some cardiovascular diseases are also discussed.
147 citations
Authors
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Name | H-index | Papers | Citations |
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Majid Ezzati | 133 | 443 | 137171 |
Christian Guilleminault | 133 | 897 | 68844 |
Jean Rivier | 133 | 769 | 73919 |
Myron M. Levine | 123 | 789 | 60865 |
Werner Seeger | 114 | 1113 | 57464 |
Katherine L. Tucker | 106 | 683 | 39404 |
Michael Bader | 103 | 735 | 37525 |
Paulo A. Lotufo | 89 | 622 | 100527 |
Fernando Q. Cunha | 88 | 682 | 31501 |
Paul R. Sanberg | 87 | 635 | 29745 |
Harold A. Chapman | 87 | 191 | 26617 |
Ricardo T. Gazzinelli | 86 | 340 | 28233 |
Carlito B. Lebrilla | 86 | 495 | 25415 |
Roger S. McIntyre | 85 | 807 | 32040 |
Sergio Tufik | 85 | 1424 | 35174 |