1,721,374 research outputs found
On the road to clinical xenotransplantation
No full textIn recent years the development of novel immunosuppressive strategies and new lines of engineered pigs have enabled improved xenograft survival in the clinically-relevant pig-to-primate models (especially in islet xenotransplantation). Furthermore, researchers have now developed appropriate biomolecular tools to address rapidly the remaining barriers and render organs from source pigs more "compatible" with man. Efficacy has been the main focus of the research conducted in the last few years. However, other fundamental issues, such as those regarding the physiology, the safety, the ethics and regulatory aspects of xenotransplantation, will need to be addressed satisfactorily prior to proceeding with clinical xenotransplantation trials. © 2009
Suramin induces deoligomerization of human tumor necrosis factor alpha
No full text: Suramin inhibits the biological activity of human tumor necrosis factor alpha (TNF) through a direct action on the ligand rather than on its receptors (Grazioli, L., Alzani, R., Ciomei, M., Mariani, M., Restivo, A., Cozzi, E., and Marcucci, F. (1992) Int. J. Immunopharmacol. 14, 637-642). In order to clarify the mechanism whereby suramin leads to inhibition of TNF, we investigated the possibility that suramin might modify the quaternary structure of TNF which is biologically active as a trimer. For this purpose we used a new assay (double streptavidin sandwich assay) designed for the rapid detection of oligomer-monomer conversion of proteins. Taking advantage of this assay we observed, upon incubation with suramin, dissociation of TNF. Suramin-induced dissociation of TNF was confirmed by gel filtration chromatography. Under conditions of partial dissociation, two molecular species were separated. One of higher molecular weight, corresponding to trimeric TNF, was biologically active, whereas the other, corresponding to monomeric TNF, was inactive. These results are at variance with others recently reported, where suramin has been shown to induce microaggregation of several polypeptides (Middaugh, C. R., Mach, H., Burke, C. J., Volkin, D. B., Dabora, J. M., Tsai, P. K., Bruner, M. W., Ryan, J. A., and Marfia, K. E. (1992) Biochemistry 31, 9016-9024). This suggests that suramin inhibits the bioactivity of different protein molecules through opposite effects on their quaternary structure. The present results are, to our knowledge, the first demonstration of a drug inhibiting a target molecule through dissociation of its quaternary structure
C1q-binding donor-specific antibody assays help define risk and prognosis in antibody-mediated rejection
No full textAntibody-mediated rejection represents the first cause of graft loss in renal transplant recipients, and it is imperative to identify appropriate tools to enable risk stratification of such patients. Lately, the usefulness of measuring complement-binding anti–human leukocyte antigen (HLA) donor-specific antibodies (DSAs) in renal transplantation has been intensely debated. While the jury is still out, recent data suggest that monitoring complement-binding DSAs may help to recognize high-risk patients and possibly trigger more effective interventions in selected patients
Immunotherapeutic approaches with monoclonal antibodies to immunological diseases
No full textThe molecular events triggered by the interaction of the immune system with an antigen and leading to an immune response have been characterized in recent years. This information has provided the background to develop immunotherapeutic approaches to allograft rejection and to autoimmune diseases utilizing monoclonal antibodies to molecules which play a role in the immune response. The clinical trials performed thus far are described. The significance of the results obtained in these trials and the future potential developments are discussed
Islet xenotransplantation: Current status of preclinical studies in the pig-to-nonhuman primate model
No full textPURPOSE OF REVIEW: Porcine islets are a major focus of current research in nonhuman primate xenotransplantation models. Major advances have been obtained recently and these are briefly described. RECENT FINDINGS: Reports by three independent centres have described 6-month porcine islet xenograft survival in nonhuman primates. Two of these have obtained such results by interfering with the CD40/CD154 co-stimulatory pathway. While these results are groundbreaking, the immunosuppressive regimens used are not viewed as clinically applicable and will need to be modified before islet xenotransplantation can be considered for clinical trials. In contrast, preliminary results by Gianello and colleagues have demonstrated 6-month survival of diabetic nonhuman primates transplanted subcutaneously with encapsulated porcine islets, in the complete absence of immunosuppression. The confirmation and full assessment of these results are eagerly awaited. Importantly, to date, no evidence of xenozoonoses has been observed following porcine islet xenotransplantation to nonhuman primates. SUMMARY: Of the possible organ candidates for xenotransplantation, porcine islets are the closest to a possible clinical application. Prior to the initiation of ethical and safe clinical trials, however, further efforts to generate additional efficacy and safety data in the nonhuman primate model will be indispensable. © 2008 Lippincott Williams & Wilkins, Inc
Immunological challenges and therapies in xenotransplantation
No full textXenotransplantation, or the transplantation of cells, tissues, or organs between different species, was proposed a long time ago as a possible solution to the worldwide shortage of human organs and tissues for transplantation. In this setting, the pig is currently seen as the most likely candidate species. In the last decade, progress in this field has been remarkable and includes a better insight into the immunological mechanisms underlying the rejection process. Several immunological hurdles nonetheless remain, such as the strong antibodymediated and innate or adaptive cellular immune responses linked to coagulation derangements, precluding indefinite xenograft survival. This article reviews our current understanding of the immunological mechanisms involved in xenograft rejection and the potential strategies that may enable xenotransplantation to become a clinical reality in the not-toodistant future. © 2014 Cold Spring Harbor Laboratory Press; all rights reserved
INTRODUZIONE ALLA MECCANICA DELLE TERRE E DELLE ROCCE
No full textLa meccanica delle terre e delle rocce è la disciplina che studia il comportamento delle rocce lapidee e delle rocce sciolte o "terre", sotto l'applicazione di un carico. La conoscenza del comportamento meccanico del terreno è basilare per poter prevedere e valutare gli spostamenti indotti da carichi agenti naturali o da manufatti. Questo libro è stato scritto per dare una solida base ai concetti della meccanica dei sistemi continui a coloro che hanno intrapreso studi nel campo delle scienze della Terra. Lo scopo che ci siamo prefissati è quello di rendere chiari i principi fisici che sono alla base dei fenomeni oggetto di studio e di ribadire che la matematica è lo strumento che sintetizza tali fenomeni mediante equazioni costitutive, scritte sulla base delle condizioni imposte dall'analisi del fenomeno
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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