Mycophenolate mofetil and its mechanisms of action.
TL;DR: The efficacy of regimes including CellCept(R) in preventing allograft rejection, and in the treatment of rejection, is now firmly established and it is hoped that the drug will have the same effect in humans.
About: This article is published in Immunopharmacology.The article was published on 2000-05-01. It has received 1238 citations till now. The article focuses on the topics: Mycophenolate & Mycophenolic acid.
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TL;DR: This guideline aims to assess available diagnostic tests and therapies, and attempts to provide a rational approach to the diagnosis and treatment in adults, children and in pregnancy.
Abstract: Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by persistent thrombocytopenia (peripheral blood platelet count < 150 · 10 ⁄ l) due to autoantibody binding to platelet antigen(s) causing their premature destruction by the reticuloendothelial system, and in particular the spleen (Woods et al, 1984a,b). Although the basic underlying pathophysiology of ITP has been known for 50 years (Harrington et al, 1951), the literature shows that the investigation and management of patients with thrombocytopenia vary widely, and is not evidence-based, due to a lack of clinical trials and quality research. Despite major advances in our understanding of the molecular basis of many blood disorders, the diagnosis of ITP remains one of exclusion; there are currently no robust clinical or laboratory parameters that are able to establish the diagnosis of ITP with accuracy. This guideline aims to assess available diagnostic tests and therapies, and attempts to provide a rational approach to the diagnosis and treatment in adults, children and in pregnancy. Although natural history data are becoming available (Cohen et al, 2000; Djulbegovic & Cohen, 2001; Portielje et al, 2001), there are few randomized trials in ITP and many of the recommendations, like those of the American Society of Hematology (ASH) Panel (George et al, 1996), are based on expert opinion.
711 citations
Cites background from "Mycophenolate mofetil and its mecha..."
...However, the numbers of patients treated to date are small and larger studies are required (Zimmer-Molsberger et al, 1997; Allison & Eugui, 2000; Howard et al, 2002)....
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TL;DR: This work considers the nature of drug targets, and by classifying known drug substances on the basis of the discussed principles it provides an estimation of the total number of current drug targets.
Abstract: What is a drug target? And how many such targets are there? Here, we consider the nature of drug targets, and by classifying known drug substances on the basis of the discussed principles we provide an estimation of the total number of current drug targets.
693 citations
TL;DR: Evidence exists to support each of the five proposed mechanisms of action, and distinct virus/host combinations may preferentially favour one or more of these mechanisms during antiviral therapy.
Abstract: The nucleoside analogue ribavirin has antiviral activity against many distinct viruses both in vitro and in vivo. Five distinct mechanisms have been proposed to explain the antiviral properties of ribavirin. These include both indirect mechanisms (inosine monophosphate dehydrogenase inhibition, immunomodulatory effects) and direct mechanisms (interference with RNA capping, polymerase inhibition, lethal mutagenesis). Recent concerns about bioterrorism have renewed interest in exploring the antiviral activity of ribavirin against unique viruses. In this paper, we review the proposed mechanisms of action with emphasis on recent discoveries, as well as the implications of ribavirin resistance. Evidence exists to support each of the five proposed mechanisms of action, and distinct virus/host combinations may preferentially favour one or more of these mechanisms during antiviral therapy.
434 citations
Cites background from "Mycophenolate mofetil and its mecha..."
...MPA is a potent uncompetitive inhibitor of IMPDH and does not need to be metabolically activated (reviewed in [23])....
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Kunming Institute of Botany1, Chinese Academy of Sciences2, University of Montpellier3, University of Mauritius4, Chiang Mai University5, Mae Fah Luang University6, Iloilo Science and Technology University7, Thailand Ministry of Agriculture and Cooperatives8, World Agroforestry Centre9, Aix-Marseille University10, Ohio State University11, VIT University12, Shenzhen University13, University of Electronic Science and Technology of China14, University of Santo Tomas15, University of Science and Technology16, University of Agricultural Sciences, Dharwad17, University of the Philippines Visayas18, Ramakrishna Mission19
TL;DR: This manuscript reviews fifty ways in which fungi can potentially be utilized as biotechnology and provides a flow chart that can be used to convince funding bodies of the importance of fungi for biotechnological research and as potential products.
Abstract: Fungi are an understudied, biotechnologically valuable group of organisms. Due to
the immense range of habitats that fungi inhabit, and the consequent need to compete against a diverse array of other fungi, bacteria, and animals, fungi have developed numerous survival mechanisms. The unique attributes of fungi thus herald great promise for their application in biotechnology and industry. Moreover, fungi can be grown with relative ease, making production at scale viable. The search for fungal biodiversity, and the construction of a living fungi collection, both have incredible economic potential in locating organisms with novel industrial uses that will lead to novel products. This manuscript reviews fifty ways in which fungi can potentially be utilized as biotechnology. We provide notes and examples for each potential exploitation and give examples from our own work and the work of other notable researchers. We also provide a flow chart that can be used to convince funding bodies of the importance of fungi for biotechnological research and as potential products. Fungi have provided the world with penicillin, lovastatin, and other globally significant medicines, and they remain an untapped resource with enormous industrial potential.
404 citations
Cites background from "Mycophenolate mofetil and its mecha..."
...As this enzyme is more essential in the T- and B-lymphocytes than in other cell types, and its isoform in the lymphocytes is more sensitive to mycophenolic acid, the drug has a more potent cytostatic effect on lymphocytes than on other cell types, and thereby suppresses the immune system (Allison and Eugui 2000)....
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TL;DR: Understanding how thiopurines contribute to the development of cancer will facilitate clinical decisions about the potential risks to patients of long-term treatment for chronic inflammatory disorders.
Abstract: Thiopurines have diverse clinical applications and their long-term use as anti-rejection drugs in transplant patients has been associated with a significantly increased risk of various types of cancer. Although they are slowly being replaced by a new generation of non-thiopurine immunosuppressants, it is anticipated that their use in the management of inflammatory and autoimmune diseases will continue to increase. Therapy-related cancer will remain a potential consequence of prolonged treatment for these generally non-life-threatening conditions. Understanding how thiopurines contribute to the development of cancer will facilitate clinical decisions about the potential risks to patients of long-term treatment for chronic inflammatory disorders.
402 citations
References
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15,827 citations
TL;DR: Two young unrelated girls with similar but not identical manifestations of immunological deficiency were found to have no measurable adenosine-deaminase (A.D.A.) enzyme activity in their red blood-cells, suggesting they may be heterozygous, and their affected children homozyguous, for a mutant A.A.A.'s gene.
1,549 citations
TL;DR: Experimental evidence suggests that cyclosporin A affects an early stage of mitogenic triggering of the immunocompetent lymphoid cell, which contrasts with other immunosuppressives and cytostatic drugs in its weak myelotoxicity.
Abstract: The fungus metabolite cyclosporin A is a small peptide acting as a novel antilymphocytic agent. It strongly depressed appearance of both direct and indirect plaque-forming cells and produced a clear dose-dependent inhibition of haemagglutinin formation in mice upon oral administration. Skin graft rejection in mice and graft-versus-host disease in mice and rats were considerably delayed by cyclosporin A which also prevented the occurrence of paralysis in rats with experimental allergic encephalomyelitis. This compound was not only highly effective in preventing development of Freund's adjuvant arthritis, but in addition improved the symptoms in rats with established arthritis, although it is inactive in acute inflammation. This new agent contrasts with other immunosuppressives and cytostatic drugs in its weak myelotoxicity. Experimental evidence suggests that cyclosporin A, rather than being cytostatic or lympholytic, affects an early stage of mitogenic triggering of the immunocompetent lymphoid cell.
1,341 citations
Journal Article•
TL;DR: The in vitro cytotoxic effect of spleen cells of mice immunized by tumour allografts was studied by measuring target cell inactivation as a function of release of radioactive label (51Cr) or loss of cloning efficiency.
Abstract: The in vitro cytotoxic effect of spleen cells of mice immunized by tumour allografts was studied by measuring target cell inactivation as a function of release of radioactive label (51Cr) or loss of cloning efficiency. When sensitized lymphoid cells were incubated with target cells at a ratio of 100:1, up to 90 per cent of the incorporated label was released within 6–9 hours, while the number of clone-forming cells was reduced by up to 99 per cent in the same time period. Isoantiserum from the graft recipients, as well as its 19S and 7S fractions, protected target cells against the toxic effect of the spleen cells, but a lipoprotein antigen isolated from the tumour cells failed to inhibit the cytotoxic reaction. Target cell lysis as measured by specific release of 51Cr was partially inhibited by actinomycin-D and by cycloheximide at concentrations which effectively blocked DNA-dependent RNA and protein synthesis.
1,329 citations
TL;DR: The biology of these carbohydrate-binding adhesive proteins are reviewed and the potential for developing anti-inflammatory antagonists that could inhibit binding events that are selectin-mediated is discussed.
Abstract: Although a bewildering array of cell surface carbohydrate structures have been described, the physiological relevance of any of these complex molecules has often eluded biologists. A family of cell surface glycoproteins, the "selectins," has a characteristic ability to use some of these carbohydrate structures in adhesive mechanisms that help localize leukocytes to regions of inflammation. This article will review the biology of these carbohydrate-binding adhesive proteins and discuss the potential for developing anti-inflammatory antagonists that could inhibit binding events that are selectin-mediated.
1,229 citations