Bright futures.
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Biomedical subjects
Publications and source records attributed to M Maldonado.
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Abrogation of peripheral tolerance in transgenic mice that express a uniform B-cell receptor may create a powerful tool to examine the molecular mechanisms that underlie the autoimmune response in B cells. Here we report that processes that induce a systemic lupus erythematosus-like syndrome in normal mice, namely chronic graft vs host reaction, trigger systemic autoimmunity in a well-established transgenic mice model of B cell receptor peripheral tolerance. The induction of graft vs host reaction in mice that carry both a rearranged B cell Ag receptors specific for hen egg lysozyme and expressing chronically circulating hen egg lysozyme Ag resulted in induction of high and sustained levels of circulating anti-hen egg lysozyme autoantibodies and glomerulonephritis with proteinuria. This was associated with marked changes in expression of cell-surface proteins, such as CD23 and complement receptor 2. B cells from the graft vs host-induced mice could proliferate in vitro in response to self-Ag, and upon stimulation with anti-IgD demonstrated rapid phosphotyrosine phosphorylation of specific proteins, which could not be induced in the anergic double transgenic B cells. Conversely, loss of tolerance was not associated with a higher induction in the level of Syk kinase phosphorylation following stimulation with anti-IgD. Taken collectively, these data establish that 1) processes that induce a systemic lupus erythematosus-like syndrome in normal mice can abrogate peripheral tolerance in transgenic mice expressing self-tolerized B cells, and that 2) loss of tolerance in this model is associated with marked changes in surface expression of B cell coreceptors as well as with selective changes in IgD-induced signaling by discrete tyrosine-phosphoproteins, but not Syk kinase.
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The necessity of assuring the quality of polydrugs, especially those with low aqueous solubility and in vivo absorption, has led to the development and evaluation of new techniques that can reduce the time and cost of analysis. This study examines the efficiency and accuracy of an automated dissolution system, fitted with an integrated multicomponent detector, for analysis of generic polydrugs using multiple linear regression (MLR). Trimethoprim and sulphamethoxazole were chosen as model drugs for this study and comparison was made with a conventional analysis based on HPLC. Both analytical systems under study gave reproducible and accurate results. Analysis of variance showed that there was no significant statistical difference between the methods of analysis, nor any statistical difference between the measured amounts of drug in the three different formulations. We have demonstrated that low cost instrumentation coupled with MLR data processing provides entirely satisfactory drug analysis to standard at least as good as that achieved using HPLC and provides an opportunity to reduce the time and analysis cost of other generic formulations.
OBJECTIVE - To analyze immediate and late results of percutaneous mitral valvotomy (PMV) in patients < or = 18 year. METHODS - Between August '87 and July '97, 48 procedures were performed on 40 patients. The mean age was 15.6 years; 68.7% were females four of whom were pregnant. RESULTS - Success was obtained in 91.7% of the procedures. Immediate complications were severe mitral regurgitation (6.3%) and cardiac tamponade (2.0%). Late follow-up was obtained in 88.8% of the patients (mean value=43.2+/-33.9 months). NYHA functional class (FC) I or II was observed in 96.2% of the patients and restenosis developed in five patients, at a mean follow-up of 29.7+/-11.9 months. Three patients presented with severe mitral insufficiency and underwent surgery. Two patients died. CONCLUSION - PMV represents a valid therapeutic option in young patients. In these patients, maybe because of subclinical rheumatic activity, restenosis may have a higher incidence and occur at an earlier stage than in others persons.
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Küpffer cells (KCs) have been implicated in leukocyte recruitment and microvascular dysfunction associated with liver inflammation. The overall objective of this study was to assess the role of KCs and polymorphonuclear (PMN) leukocytes on the oxidative stress elicited in the liver as a consequence of hind limb reperfusion in rats subjected to tourniquet shock, a shock model that differs from other models in that hepatic injury is a consequence of remote organ damage. Colloidal carbon clearance from blood and its incorporation into KCs demonstrate that these cells are activated after the 2 h hind limb reperfusion period and that they are responsible for the observed oxidative stress and for PMN leukocyte recruitment and activation. Liver oxidative stress in this model is evidenced by increased liver tissue GSSG/GSH ratio, thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, myeloperoxidase (MPO) activity, an index of tissue-associated neutrophil accumulation, and a significant loss in total tissue superoxide dismutase (SOD) activity. Mean arterial blood pressure (MAP), as well as plasma levels of alanine aminotransferase (ALT), an index of hepatic tissue injury, total SOD activity, plasma levels of alpha-tocopherol and beta-carotene, and total plasma nitrite are also affected as a consequence of KC activation after the 2 h hind limb reperfusion period. Inhibition of KC activity by gadolinium chloride (GdCl3) reverted most of the above alterations to values that do no differ from those found in control animals. These results support the hypothesis that hepatic and systemic oxidative stress elicited by hind limb reperfusion in rats subjected to tourniquet shock is both KC and PMN leukocyte dependent.
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