PubMed Central (PMC3 - NLM DTD)
(2,081,148 recursos)
Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).
Mostrando recursos 121 - 140 de 420
121.
Genetic markers of osteoarticular disorders: facts and hopes - Brandi, Maria Luisa; Gennari, Luigi; Cerinic, Marco Matucci; Becherini, Lucia; Falchetti, Alberto; Masi, Laura; Gennari, Carlo; Reginster, Jean-Yves
Osteoarthritis and osteoporosis are the two most common age-related chronic disorders of articular joints and skeleton, representing a major public health problem in most developed countries. Apart from being influenced by environmental factors, both disorders have a strong genetic component, and there is now considerable evidence from large population studies that these two disorders are inversely related. Thus, an accurate analysis of the genetic component of one of these two multifactorial diseases may provide data of interest for the other. However, the existence of confounding factors must always be borne in mind in interpreting the genetic analysis. In addition, each...
122.
Gene therapy moves forward - The Second International Meeting on Gene and Cell Therapies of Arthritis and Related Disorders, 17-18 May 2001, Montpellier, France - Robbins, Paul D; Jorgensen, Christian; Evans, Christopher H
The field of gene therapy for bone and joint disorders has grown considerably over the last two and a half years. Investigators have shown that ex vivo or in vivo gene transfer is highly effective in blocking arthritis or facilitating repair of damaged cartilage or bone. The feasibility of applying gene therapy for the treatment of arthritis in humans has also been demonstrated. Thus, gene therapy appears poised to make significant contributions to the clinical treatment of joint and bone diseases in the near future.
123.
Advances in Targeted Therapies III, Nassau, Bahamas, 27 April-1 May 2001 - Wollheim, Frank A
This conference was the third in a series focusing on developments in the therapy of rheumatoid arthritis (RA) and other rheumatic conditions with biologicals; in many ways, it was perhaps the best one so far. One strength of the meeting was the mix of scientists from academia and from industry, and of workers in basic science as well as clinical investigators. The risks of inhibition of tumor necrosis factor (TNF) were covered in depth for the first time. A number of putative and actual new targets were presented. An updated consensus document on the use of TNF inhibitors will appear...
124.
Genetic epidemiology: Systemic lupus erythematosus - Ahmad, Yasmeen A; Bruce, Ian N
Systemic lupus erythematosus is the prototype multisystem autoimmune disease. A strong genetic component of susceptibility to the disease is well established. Studies of murine models of systemic lupus erythematosus have shown complex genetic interactions that influence both susceptibility and phenotypic expression. These models strongly suggest that several defects in similar pathways, e.g. clearance of immune complexes and/or apoptotic cell debris, can all result in disease expression. Studies in humans have found linkage to several overlapping regions on chromosome 1q, although the precise susceptibility gene or genes in these regions have yet to be identified. Recent studies of candidate genes, including...
125.
Articular cartilage and changes in arthritis: Matrix degradation - Mort, John S; Billington, Caron J
While many proteases in articular cartilage have been described, current studies indicate that members of two families of metalloproteases â?? MMPs and the ADAMTSs â?? are responsible for the degradation of the major components of this tissue. Collagenases (MMPs) make the first cleavage in triple-helical collagen, allowing its further degradation by other proteases. Aggrecanases (ADAMTSs), in conjunction with other MMPs, degrade aggrecan, a component of the proteoglycan aggregate. Anti-neoepitope antibodies that recognize the cleavage products of collagen and aggrecan generated by these enzymes are now available and are being used to detect the sites of action and to quantitate degradation...
126.
Articular cartilage and changes in arthritis: Noncollagenous proteins and proteoglycans in the extracellular matrix of cartilage - Roughley, Peter J
Cartilage contains numerous noncollagenous proteins in its extracellular matrix, including proteoglycans. At least 40 such molecules have been identified, differing greatly in structure, distribution, and function. Some are present in only selected cartilages or cartilage zones, some vary in their presence with a person's development and age, and others are more universal in their expression. Some may not even be made by the chondrocytes, but may arise by absorption from the synovial fluid. In many cases, the molecules' function is unclear, but the importance of others is illustrated by their involvement in genetic disorders. This review provides a selective survey...
127.
Morgenröthe or business as usual: a personal account of the 2nd Annual EULAR Congress, Prague - Wollheim, Frank A
The 2nd Annual European League Against Rheumatism (EULAR) Congress, held in Prague, 13â??16 June 2001, was an impressive event with a record turnout of 8300 delegates. It offered a large variety of first-class state of the art lectures by some 180 invited worldwide speakers. Several new and ongoing therapeutic developments were discussed. The aim to attract the young scientific community was only partly achieved, and the dependence on industry posed some problems. The organization, however, was a big improvement compared with the previous congress in this series. The number of submitted abstracts was relatively low (1200) compared with the number...
128.
From immunoglobulin gene fingerprinting to motif-specific hybridization: advances in the analysis of B lymphoid clonality in rheumatic diseases - Voswinkel, Jan; Gause, Angela
In rheumatic diseases, autoantibody-producing cells of interest are often hidden in a polyclonal B-lymphocyte population. Immunoglobulin gene fingerprinting is a useful approach to screen for expanding clones and to detect recirculation between different locations. The gene fingerprinting approach and the Southern blot technique have been amalgamated, using electrophoretic transfer of a PCR product from an acrylamide gel onto a nylon membrane followed by hybridization with specific oligonucleotide probes. In contrast to conventional fingerprinting, the authenticity of immunoglobulin genes can be confirmed, individual genes can be detected and handling radionucleotides can be avoided. Also, the membrane may be reused for further...
129.
Ex vivo gene transfer in the years to come - Pap, Thomas; Gay, Renate E; Müller-Ladner, Ulf; Gay, Steffen
Synovial fibroblasts (SFs) have become a major target for ex vivo gene transfer in rheumatoid arthritis (RA), but efficient transduction of RA-SFs still is a major problem. The low proliferation rate and heterogeneity of RA-SFs, together with their lack of highly specific surface receptors, have hampered a more extensive application of this technique. Improving transduction protocols with conventional viral vectors, therefore, as well as developing novel strategies, such as alternative target cells, and novel delivery systems constitute a major challenge. Recent progress in this field will lead to the achievement of high transgene expression, and will facilitate the use of...
130.
The Novartis-ILAR Rheumatology Prize 2001 Osteoarthritis: from molecule to man - Pelletier, Jean-Pierre; Martel-Pelletier, Johanne
During our careers, we have developed new and innovative concepts pertaining to the pathophysiology of osteoarthritis which have assisted in the development of new therapeutic approaches. Moreover, our laboratory has long sought to develop protective agents for osteoarthritic structural joint tissues. The most significant concepts that have originated from our lab are briefly outlined in this commentary.
131.
Lyme disease and current aspects of immunization - Kamradt, Thomas
Lyme disease is a tick-borne multisystem disease that affects primarily the skin, nervous system, heart and joints. At least three species of Borrelia burgdorferi sensu lato, namely Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii, can cause the disease. This review will focus mainly on the pathophysiology of Lyme arthritis, the long-term outcome of Lyme disease, and the recently licensed vaccine against Lyme disease.
132.
Articular cartilage and changes in Arthritis: Collagen of articular cartilage - Eyre, David
The extracellular framework and two-thirds of the dry mass of adult articular cartilage are polymeric collagen. Type II collagen is the principal molecular component in mammals, but collagens III, VI, IX, X, XI, XII and XIV all contribute to the mature matrix. In developing cartilage, the core fibrillar network is a cross-linked copolymer of collagens II, IX and XI. The functions of collagens IX and XI in this heteropolymer are not yet fully defined but, evidently, they are critically important since mutations in COLIX and COLXI genes result in chondrodysplasia phenotypes that feature precocious osteoarthritis. Collagens XII and XIV are...
133.
A critical appraisal of clinical practice guidelines for the treatment of lower-limb osteoarthritis - Pencharz, James N; Grigoriadis, Elizabeth; Jansz, Gwenderlyn F; Bombardier, Claire
Clinical practice guidelines are important tools to assist clinical decision-making. Recently, several guidelines addressing the management of osteoarthritis (OA) have been published. Clinicians treating patients with OA must ensure that these guidelines are developed with consistency and methodological rigour. We undertook a qualitative summary and critical appraisal of six medical treatment guidelines for the management of lower-limb OA published in the medical literature within the past 5 years. A review of these six guidelines revealed that each possesses strengths and weakness. While most described the scope and intended patient populations, the guidelines varied considerably in the rigour of their development,...
134.
Staphylococcus aureus and Wegener's granulomatosis - Popa, Eliane R; Stegeman, Coen A; Kallenberg, Cees GM; Willem Cohen Tervaert, Jan
Wegener's granulomatosis (WG) is a form of systemic vasculitis. It is characterized by granulomatous inflammation in the upper and lower airways, vasculitis and necrotizing glomerulonephritis, and is strongly associated with antineutrophil cytoplasmic antibodies against proteinase 3. Since the etiology of the disease is not clear, treatment, consisting of corticosteroids and immunosuppressives, is nonspecific and associated with severe side effects. Pinpointing the trigger(s) of the disease would highly improve treatment. Clinical evidence shows that an infectious agent, the bacterium Staphylococcus aureus, is a risk factor for disease relapse, suggesting its involvement in the pathogenesis of WG. Here we review both clinical...
135.
Clues to the etiology of autoimmune diseases through analysis of immunoglobulin genes - Link, Jason M; Schroeder, Harry W
The role of autoantibodies in the etiology of autoimmune diseases remains unclear. However, an examination of the sequences of these autoantibodies can be informative. Antibody sequences that violate constraints normally imposed during ontogeny and during development point to a failure of regulation. The existence of clonally related sequences indicates that production of these antibodies may frequently be driven by self-antigen. A better understanding of the mechanisms that normally constrain the composition of the antibody repertoire and of the nature of the inciting and/or driving antigens may yield new insights into both the pathogenesis and potential treatment of these crippling diseases.
136.
Commentary on "Genetic linkage and transmission disequilibrium of marker haplotypes at chromosome 1q41 in human systemic lupus erythematosus", by RR Graham et al. - Barton, Anne C; Worthington, Jane
Genome-wide linkage analysis studies in families with systemic lupus erythematosus (SLE) have revealed consistent evidence of linkage to several regions of the genome. In a previous issue of this journal, Graham and colleagues described their approach to following up the linkage data for one of these regions, 1q41â??42. Using methods based on the transmission disequilibrium test, the region likely to harbour a SLE disease gene was refined to 2.3 Mb. This commentary discusses their approach and identifies lessons that may be applicable to the investigation of other complex diseases.
137.
Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value - van Boekel, Martinus AM; Vossenaar, Erik R; van den Hoogen, Frank HJ; van Venrooij, Walther J
The diagnosis of rheumatoid arthritis (RA) is primarily based on clinical symptoms, so it is often difficult to diagnose RA in very early stages of the disease. A disease-specific autoantibody that could be used as a serological marker would therefore be very useful. Most autoimmune diseases are characterized by a polyclonal B-cell response targeting multiple autoantigens. These immune responses are often not specific for a single disease. In this review, the most important autoantibody/autoantigen systems associated with RA are described and their utility as a diagnostic and prognostic tool, including their specificity, sensitivity and practical application, is discussed. We conclude...
138.
The life cycle of chondrocytes in the developing skeleton - Shum, Lillian; Nuckolls, Glen
Cartilage serves multiple functions in the developing embryo and in postnatal life. Genetic mutations affecting cartilage development are relatively common and lead to skeletal malformations, dysfunction or increased susceptibility to disease or injury. Characterization of these mutations and investigation of the molecular pathways in which these genes function have contributed to an understanding of the mechanisms regulating skeletal patterning, chondrogenesis, endochondral ossification and joint formation. Extracellular growth and differentiation factors including bone morphogenetic proteins, fibroblast growth factors, parathyroid hormone-related peptide, extracellular matrix components, and members of the hedgehog and Wnt families provide important signals for the regulation of cell proliferation,...
140.
Glucocorticoids: do we know how they work? - Saklatvala, Jeremy
It is not known to what extent glucocorticoid hormones cause their anti-inflammatory actions and their undesirable side effects by the same or different molecular mechanisms. Glucocorticoids combine with a cytoplasmic receptor that alters gene expression in two ways. One way is dependent on the receptor's binding directly to DNA and acting (positively or negatively) as a transcription factor. The other is dependent on its binding to and interfering with other transcription factors. Both mechanisms could underlie suppression of inflammation. The liganded receptor binds and inhibits the inflammatory transcription factors activator protein-1 and NF-κB. It also directly induces anti-inflammatory genes such...
121.
