155 resultados para foulant rejection
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Background. Despite advances in immunosuppressive therapy in the past decade, allograft rejection remains an important cause of kidney graft failure. Cytokines play a major role in the inflammatory and immune responses that mediate allograft outcomes. Several studies have shown that the production of cytokines varies among individuals. These variations are determined by genetic polymorphisms, most commonly within the regulatory region of cytokine genes. The aim of the present study was to assess the effect of allelic variation on acute rejection episodes (ARE) or chronic allograft nephropathy (CAN) after kidney transplantation.Methods. To determine a possible correlation between the interferon (INF)-gamma +874 polymorphism and kidney allograft outcome, we isolated genomic DNA from 74 patients who underwent isolated kidney allografts and were classified into 2 groups-a rejection and a nonrejection group-for comparison with a control group of 163 healthy subjects.Results. We genotyped INF-gamma +874 polymorphisms in all groups. The transplant group showed a significantly increased homozygous genotype T/T (P = .0118) compared with healthy controls. Similarly, considering only patients with CAN, the homozygous genotype T/T (P = .0067) was significantly increased compared with the healthy controls. The rejection group indicated a significant increased homozygous genotype Tic compared with the control group (P = .0061).Conclusion. Homozygous genotype T/T was associated with increased levels of INF-gamma and greater numbers among the rejection and CAN cohorts.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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The search for biological antitumor agents has been pursued for over half a century. Snake venom has been shown to possess a wide spectrum of biological activities. The objectives of the present review are to evaluate the existing controversies on this subject published in a number of papers and to propose probable explanations for the phenomena observed. We reported our results obtained in a study, in which we evaluated the action of the venoms of Crotalus durissus terrificus and Bothrops jararaca on Ehrlich ascites tumor cells. We noticed an important antitumor effect, mainly with Bothrops jararaca venom, as well as an increase in the functional activity of macrophages. We also observed an increase in the number of mononuclear and polymorphonuclear cells with Bothrops jararaca venom. Considering these findings, we postulate that both Borhrops jararaca and Crotalus durissus terrificus venoms can act directly on tumor cells. In addition, we propose an indirect mechanism, based on the stimulation of the inflammatory response, to inhibit tumor growth and to promote its rejection.
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In order to evaluate the role of underlying disease in the high mortality observed in acute renal failure (ARF) and risk factors related to the development of oliguric ARF in renal allograft recipients, two groups were selected: 34 patients with native kidneys, aged 16 and 57 years, and presenting ischemic ARF caused by cardiovascular collapse, with no signs of infection at the time of diagnosis; and 34 renal allograft recipients who developed ARF immediately after transplantation, without rejection. ARF was defined either as 30% increase of basal plasmatic creatinine in patients with native kidneys or non-normalization of plasmatic creatinine at day 5 after transplantation in renal allograft recipients; oliguria as diuresis ≤ 400 mL/24 h. There were no differences in age, male frequency, oliguria presence and duration, need for dialysis, and infection episodes for renal allograft recipients and patients with native kidneys. The development of sepsis (3% and 41%) and death rate (3% and 44%) were higher in patients with native kidneys (p < 0.01). The renal allograft recipients with both oliguric (n = 18) and nonoliguric (n = 16) ARF were evaluated and no difference was observed in the recipient's age, donor's age, cold ischemia time, time elapsed until plasmatic creatinine normalization, donor's plasmatic creatinine or urea, and mean arterial pressure. No differences were observed between the groups regarding frequency of infection episodes during ARF and frequency of death. In conclusion, renal allograft recipients presented a lower death rate and were less susceptible to sepsis. Cold ischemia time, age, and hemodynamic characteristics of the donor did not affect the development of oliguria.
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Cyclosporin A is a selective immunosuppressant, used in organ transplants to prevent graft rejection. Cyclosporin A can cause various side effects including gingival overgrowth. The aim of this work was to evaluate gingival overgrowth of rats treated daily with 10 mg/kg body weight of Cyclosporin A for 60 days, as well as the regression after the interruption of treatment. All rats treated with Cyclosporin A developed gingival overgrowth, with increased thickness of the epithelium, height and width of the connective tissue. The density of fibroblasts and collagen fibers also increased. Five to 90 days after the interruption of treatment with Cyclosporin A, there was a progressive reduction of the gingival volume and of collagen fibers and fibroblast densities. The reduction was more pronounced in the initial periods and after 90 days did not return to the normal values.
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The study of the association between two random variables that have a joint normal distribution is of interest in applied statistics; for example, in statistical genetics. This article, targeted to applied statisticians, addresses inferences about the coefficient of correlation (ρ) in the bivariate normal and standard bivariate normal distributions using likelihood, frequentist, and Baycsian perspectives. Some results are surprising. For instance, the maximum likelihood estimator and the posterior distribution of ρ in the standard bivariate normal distribution do not follow directly from results for a general bivariate normal distribution. An example employing bootstrap and rejection sampling procedures is used to illustrate some of the peculiarities.
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Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. A genetic deficiency due to mutations in the gene encoding for human PNP causes T-cell deficiency as the major physiological defect. Inappropriate activation of T-cells has been implicated in several clinically relevant human conditions such as transplant tissue rejection, psoriasis, rheumatoid arthritis, lupus, and T-cell lymphomas. Human PNP is therefore a target for inhibitor development aiming at T-cell immune response modulation. In addition, bacterial PNP has been used as reactant in a fast and sensitive spectrophotometric method that allows both quantitation of inorganic phosphate (Pi) and continuous assay of reactions that generate P i such as those catalyzed by ATPases and GTPases. Human PNP may therefore be an important biotechnological tool for P i detection. However, low expression of human PNP in bacterial hosts, protein purification protocols involving many steps, and low protein yields represent technical obstacles to be overcome if human PNP is to be used in either high-throughput drug screening or as a reagent in an affordable P i detection method. Here, we describe PCR amplification of human PNP from a liver cDNA library, cloning, expression in Escherichia coli host, purification, and activity measurement of homogeneous enzyme. Human PNP represented approximately 42% of total soluble cell proteins with no induction being necessary to express the target protein. Enzyme activity measurements demonstrated a 707-fold increase in specific activity of cloned human PNP as compared to control. Purification of cloned human PNP was achieved by a two-step purification protocol, yielding 48 mg homogeneous enzyme from 1 L cell culture, with a specific activity value of 80 U mg -1. © 2002 Elsevier Science (USA). All rights reserved.
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We report the singular filtration properties of an ultrafiltration membrane made with mesoporous silica that exhibits cylindrical pores aligned mostly normal to the support. This membrane supported on tubular commercial macroporous alumina supports was prepared by the interfacial growth mechanism between stable silica-surfactant hybrid micelles made of the association of silica oligomers with polyethyleneoxide-based (PEO) surfactants and sodium fluoride, a well-known silica condensation catalyst [Boissière et al., An ultrafiltration membrane made with mesoporous MSU-X silica, Chem. Mater. 15 (2003) 460-463]. It appears that the combined effect of the silica nature of the membrane, whose surface charge can be easily adjusted by changing the pH and the non-connected cylindrical shape of the pores provides a new behavior in the retention properties, as proved by the filtration of polyoxyethylene polymers (PEO) with different molecular weights. Depending on the filtration conditions, a rejection rate of 80% and a steep cut-off at 2000 Da can be obtained or, on the reverse, polymers three times bigger than the pore diameter can diffuse through the membrane. This new filtration mechanism, which opens up new modes of separation modes, is explained in the light of both topology of the porous network and pH-dependent interactions between PEO polymers and silica porous media. © 2004 Elsevier B.V. All rights reserved.
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We report preparation and the singular filtration properties of an ultrafiltration membrane made with MSU-type mesoporous silica that exhibits cylindrical pores aligned mostly normal to the support. This membrane supported on tubular commercial macroporous alumina supports was prepared by the interfacial growth mechanism between stable silica-surfactant hybrid micelles made of the association of silica oligomers with polyethyleneoxide-based (PEO) surfactants and sodium fluoride, a well-known silica condensation catalyst. It appears that the combined effect of the silica nature of the membrane, whose surface charge can be easily adjusted by changing the pH and the non-connected cylindrical shape of the pores provides a new behavior in the retention properties, as proved by the filtration of polyoxyethylene polymers (PEO) with different molecular weights. Depending on the filtration conditions, a rejection rate of 80 % and a steep cut-off at 2,000 Da can be obtained or, on the reverse, polymers three times bigger than the pore diameter can diffuse through the membrane. This new filtration mechanism, which opens up new modes of separation modes, is explained in the light of both topology of the porous network and pH-dependent interactions between PEO polymers and silica porous media. © 2005 Elsevier B.V. All rights reserved.
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Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of nucleosides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. The lack of such an activity in humans, owing to a genetic disorder, causes T-cell impairment, and drugs that inhibit this enzyme may have the potential of being utilized as modulators of the immunological system to treat leukemia, autoimmune diseases, and rejection in organ transplantation. Here, we describe kinetics and crystal structure of human PNP in complex with 7-methyl-6-thio-guanosine, a synthetic substrate, which is largely used in activity assays. Analysis of the structure identifies different protein conformational changes upon ligand binding, and comparison of kinetic and structural data permits an understanding of the effects of atomic substitution on key positions of the synthetic substrate and their consequences to enzyme binding and catalysis. Such knowledge may be helpful in designing new PNP inhibitors. © 2005 Elsevier Inc. All rights reserved.
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The patient with anophthalmia may present feelings of inferiority and rejection. Knowing his/her needs and expectations contribute to a better technical intervention. Purpose: To elaborate a questionnaire of the psychosocial profile of the patient with anophthalmia with indication of ocular prosthesis. Methods: An exploratory research was used to elaborate the questionnaire, by means of a guided interview followed by writing down what was said by the interviewees, who were adult patients of the Bucco-Maxillo-Facial Prosthesis Center of FOSJC - UNESP. The guided interview was made up of 14 items directly related to the future outline of the profile. Each item of the interview resulted in questions of the questionnaire, which was pretested twice before reaching its final version. Results: The patients reported, in the exploratory research, unpleasant feelings with the loss of the eye; relationship shyness; expectations regarding surgery and prosthesis use; a wish to receive explanations and to hold their opinion about the treatment. The questionnaire of the psychosocial profile of the patient with anophthalmia with indication of ocular prosthesis is, therefore, made of 43 questions divided into 5 blocks in order to aid the comprehension of the inquired aspects and to facilitate both the computation of data and discussion, and also to improve the selection of questions according to the objective of the researcher or professional. Conclusions: It was concluded that the questionnaire was viable, can be used in full or by selecting blocks and provide a panorama of the patient's history related to the problem he/she faces, from the loss of the ocular globe to the confection of the prosthesis.
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The digital image processing has been applied in several areas, especially where it is necessary use tools for feature extraction and to get patterns of the studied images. In an initial stage, the segmentation is used to separate the image in parts that represents a interest object, that may be used in a specific study. There are several methods that intends to perform such task, but is difficult to find a method that can easily adapt to different type of images, that often are very complex or specific. To resolve this problem, this project aims to presents a adaptable segmentation method, that can be applied to different type of images, providing an better segmentation. The proposed method is based in a model of automatic multilevel thresholding and considers techniques of group histogram quantization, analysis of the histogram slope percentage and calculation of maximum entropy to define the threshold. The technique was applied to segment the cell core and potential rejection of tissue in myocardial images of biopsies from cardiac transplant. The results are significant in comparison with those provided by one of the best known segmentation methods available in the literature. © 2010 IEEE.