Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
9385581 An association between salivary gland disease and serological abnormalities in Sjögren's 1997 Oct In the labial salivary glands (LSGs) of 16 primary and 18 secondary Sjögren's syndrome (SS) patients, infiltrating lymphocytes were histologically and immunohistochemically examined; also, the serum levels of rheumatoid factor, antinuclear antibodies, anti-DNA antibodies, anti-SS-A and anti-SS-B antibodies, and immunoglobulins (including IgG, IgM and IgA) were all assayed. An immunohistochemical analysis of the lymphocyte subsets in LSGs revealed that severe lymphocytic infiltration was frequently accompanied by marked B cell accumulation both in primary and secondary SS patients. Furthermore, local B cell accumulation was also closely associated with elevated levels of anti-SS-A and anti-SS-B antibodies and IgG, and this association was statistically significant in the group with primary SS but not in the group with secondary SS. Thus, local lymphocytic infiltration, especially B cell accumulation, in the salivary glands is suggested to be involved in serological abnormalities in primary SS, while complicated autoimmune diseases other than SS may also be involved in serological abnormalities in secondary SS.
11225138 Prevalence of rheumatic diseases in a rural population in western India: a WHO-ILAR COPCOR 2001 Feb BACKGROUND: COPCORD (Community oriented program from control of rheumatic diseases) is a global initiative of the WHO/International League of Associations from Rheumatology (ILAR). The prevalence data from the first Indian COPCORD survey (Stage 1), carried out in village Bhigwan (Dist. Pune), in 1996, is presented. AIM: To study the rural prevalence of rheumatic-musculoskeletal symptoms/diseases (RMSD). METHODS: A cross-sectional survey of the village (non-randomised selection) was completed in five weeks, using validated questionnaires, served by 21 trained volunteers. 746 patients (18.2%, 95% CI: 17-1-19-4) were identified (Phase 1) from 4092 adults (response 89%), and systematically evaluated (Phase 2 and 3) by a medical team, including a rheumatologist; limited investigations were carried out and diagnosis confirmed during a planned 12 week initial follow-up. Standard clinical criteria were used for the diagnosis; point prevalence estimates (prev)/confidence interval (CI) are shown in parenthesis. RESULTS: There was a dominant distribution of 'pain at all sites' (articular/soft tissues) in the females; painful neck (9.5%), back (17.3%), and calf (8.5%) appeared significant when compared to the Bhigwan males and the Indonesian and the Chinese rural COPCORD results. 55% RMSD were due to soft tissue rheumatism (5.5%) and an ill-defined/unclassifiable symptom-related-diagnosis (7.1%). Osteoarthritis (5.8%) and inflammatory arthritis (IA) were seen in 29% and 10% patients respectively. 240 patients (5.9%) with chronic knee pains did not show any clinical evidence of OA. The prev of rheumatoid arthritis (0.5%, 95% CI: 0.3-0.7), as classified by the American College of Rheumatology, was the highest ever reported from an Asian rural COPCORD study. Though unclassifiable IA (0.9%, 95% CI: 0.6-1.1) was seen, well defined reactive arthritis, TB, leprosy and connective tissue disorders were not observed. Gout was diagnosed in five patients (0.12%). CONCLUSIONS AND DISCUSSION: The Bhigwan COPCORD survey demonstrates a significant rural spectrum of RMSD. It provides a reasonable speculation about the Indian rheumatological burden. Further, an eight year prospective study is in progress to identify new cases and risk factors, and educate people (Stages 2 and 3).
11825305 The pharmacological management of drug-induced rheumatic disorders. 2001 Oct Many drugs can induce adverse effects such as rheumatoid disorders, which we need to be aware of in order to best detect and manage them. New drugs are constantly entering the marketplace and can cause an increasing number of disorders. Through this article, we review the prevention and pharmacological management of drug-induced rheumatic disorders. These include articular and peri-articular manifestations induced by fluoroquinolones, retinoids, cyclosporin, drug-induced disorders of bone metabolism such as corticosteroid-induced osteoporosis and drug-induced osteomalacia, and multisystemic manifestations including drug-induced lupus and arthritis induced by vaccinations and cytokines.
11520171 Reliability, validity, and sensitivity to change of the Cochin hand functional disability 2001 Aug OBJECTIVE: To assess the reliability, validity and sensitivity to change of the Cochin hand functional scale in hand osteoarthritis (OA). BACKGROUND: The Cochin hand functional disability scale has been validated in rheumatoid arthritis. DESIGN: Patients with hand OA according to Altman's criteria were included. Impairment outcome measures (VAS of pain, hand score of tenderness, clinical hand score of impairment, Kallman's radiographic scale), functional disability measures [Cochin scale, Revel's functional index (RFI), Dreiser's functional index (DFI)] and patients' perceived handicap (VAS) were recorded twice, at baseline and at a 6-month follow-up visit. Interobserver reliability was assessed using the intraclass correlation coefficient (ICC) and the Bland and Altman method. Construct (convergent and divergent) validity was investigated using the Spearman rank correlation coefficient and a factor analysis was performed. Sensitivity to change was assessed using the effect size (ES) and the standardized response mean (SRM), and the non-parametric Spearman rank correlation coefficient (r) was used to assess the correlation between quantitative variable changes and patient's overall opinion. RESULTS: 89 patients (8 males, mean age 63 years) were included. Interobserver reliability was excellent (ICC=0.96). The Bland and Altman method showed no systematic trend. Correlations of the Cochin scale score with RFI (r=0.86), DFI (r=0.87), VAS of handicap (r=0.67), VAS of pain (r=0.54), tenderness (r=0.51), clinical impairment (r=0.32), and Kallman's radiographic scale (r=0.13) indicated a good construct validity. Factor analysis extracted four main factors, accounting for 65% of the total variance. 51 patients were evaluated at the 6-month visit. The Cochin scale score had worsened with SRM and ES values of -0.26 and -0.17 respectively. Changes in the score had one of the highest correlation (r=0.47) with the patient's overall opinion. CONCLUSION: The Cochin hand functional disability scale which was first developed to assess the rheumatoid hand can be used to evaluate functional disability in hand OA.
15991932 AntiTNF-alpha agents in the treatment of inflammation. 1998 Nov Tumour necrosis factor/cachecin (TNF-alpha) and lymphotoxin (LTalpha / TNF-alpha), 2 members of the TNF family of cytokines, have numerous biological functions, such as induction of apoptosis, cytotoxicity, inflammation, immunoregulation, proliferation and antiviral responses. Although TNF-alpha is produced by many cell types, the majority comes from activated macrophages. The related molecule, LT-alpha is produced mainly by activated lymphocytes and shares many of TNF's properties. TNF-alpha is active in both of its molecular forms, a secreted 17 kDa mature form and a transmembrane 26 kDa precursor. It induces activity by stimulating 2 distinct receptor subtypes, TNFR1 (55 kDa) and TNFR2 (75 kDa). The activation of TNFR1 is generally thought to trigger the majority of inflammatory and apoptotic effects, although TNFR2 has recently been shown to play more of a role in signal transduction than was initially thought. TNF-alpha is responsible for the induction of apoptosis in certain cell types, where it plays a pivotal role in the induction of cytotoxicity, killing of neoplastic cells and deletion of autoreactive T-cell clones. This cytokine, and in particular, its overproduction, has been implicated in the pathogenesis of a variety of immunologically mediated inflammatory diseases, including endotoxic shock, inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA). Currently, there is an intense effort underway to regulate TNF-alpha production and activity, in order to treat diseases where TNF-alpha is thought to be pathologically indicated. To achieve this goal, the pharmaceutical industry is currently pursuing a 2 pronged strategy: a) testing biological agents such as antibodies against TNF-alpha or soluble TNF-alpha receptor constructs, and b) identifying small molecular inhibitors directed against targets such as phosphodiesterase-IV (PDE-IV) and TNF-alpha converting enzyme (TACE), a subgroup of the matrix metalloproteinases (MMP). The main difficulties in the clinical implementation of the biological agents are: development of immunogenicity, lack of oral availability and the high cost of production. The currently available small molecular compounds exhibit poor bio-availability and low selectivity, resulting in unacceptable side effects and a low therapeutic index. Despite these hurdles, numerous companies are actively pursuing agents that inhibit TNF-alpha.
11878772 T-cell tolerance and autoimmune diabetes. 2001 Herein we describe the major signaling events that occur in T-cells upon T-cell receptor (TCR) engagement, and the mechanisms responsible for the induction of T-cell anergy that may ultimately lead to the development of immunospecific therapies in T-cell mediated autoimmune diseases. A new type of antigen presenting molecule (dimeric MHC class-II/peptide, DEF) endowed with antigen-specific immunomodulatory effects such as induction of Th2 polarization and T-cell anergy is also described as a potential antidiabetogenic agent. According to our preliminary results, the MHC II/peptide-based approach may provide rational grounds for further development of antigen-specific immunotherapeutic agents such as human-like MHC lI/peptide chimeras endowed with efficient down-regulatory effects in CD4 T-cell-mediated autoimmune diseases such as Type 1 diabetes, multiple sclerosis, primary biliary cirrhosis, and rheumatoid arthritis.
11866925 [Study on the modulation of the inflammatory response in mouse hepatic vasculitis with sod 2000 Aug OBJECTIVE: To identify the regulatory effect of sodium selenite and vitamin E on complement-neutrophil-reactive oxygen species (ROS)-activation feedback mechanism-mediated inflammatory response. METHODS: The modulation of inflammatory response through the complement-neutrophil-ROS-activation feedback cycle with sodium selenite and alpha-tocopherol was verified both in vitro tests by chemiluminescense technique and complement fixation to detect ROS production and complement activation as well as in vivo mouse hepatic vasculitis models to test for the regulation of the inflammatory response. RESULTS: Convincing results were observed as the incidence of hepatic vasculitis dropped from 100% in the control group down to 20% in the seleno-antioxidant vitamin E treated group, indicating down regulation of the inflammatory response. CONCLUSIONS: Elucidation of the mechanism of complement mediated inflammatory response is a promising area for new therapeutic developments in the modulation of inflammatory response. This study suggests that selenium, vitamin E and other antioxidants may be the useful therapeutic agents in those disorders in which upregulation of inflammatory response has been implicated, e.g. ischemia, reperfusion injury, severe sepsis, rheumatoid arthritis and hepatitis.
11711546 Interstitial collagens I, III, and VI sequester and modulate the multifunctional cytokine 2002 Feb 1 The binding of certain growth factors and cytokines to components of the extracellular matrix can regulate their local availability and modulate their biological activities. We show that oncostatin M (OSM), a profibrogenic cytokine and modulator of cancer cell proliferation, specifically binds to collagen types I, III, IV, and VI, immobilized on polystyrene or nitrocellulose. Single collagen chains inhibit these interactions in a dose-dependent manner. Cross-inhibition experiments of collagen-derived peptides point to a limited set of OSM-binding collagenous consensus sequences. Furthermore, this interaction is found for OSM but not for other interleukin-6 type cytokines. OSM binding to collagens is saturable, with dissociation constants around 10(-8) m and estimated molar ratios of 1-3 molecules of OSM bound to one molecule of triple helical collagen. Furthermore, collagen-bound OSM is biologically active and able to inhibit proliferation of A375 melanoma cells. We conclude that abundant interstitial collagens dictate the spatial pattern of bioavailable OSM. This interaction could be exploited for devising collagenous peptide-antagonists that modulate OSM bioactivity in tumor growth and fibrotic disorders like rheumatoid arthritis and hepatic fibrosis.
11669173 A reduced functionality of Gi proteins as a possible cause of fibromyalgia. 2001 Oct OBJECTIVE: The etiopathogenesis of fibromyalgia (FM), a syndrome characterized by widespread pain and hyperalgesia, is still unknown. Since the involvement of Gi proteins in the modulation of pain perception has been widely established, the aim of the present study was to determine whether an altered functionality of the Gi proteins occurred in patients with FM. METHODS: Patients with FM and other painful diseases such as neuropathic pain, rheumatoid arthritis (RA), and osteoarthritis, used as reference painful pathologies, were included in the study. The functionality, evaluated as capability to inhibit forskolin-stimulated adenylyl cyclase activity, and the level of expression of Gi proteins were investigated in peripheral blood lymphocytes. RESULTS: Patients with FM showed a hypofunctionality of the Gi protein system. In contrast, unaltered Gi protein functionality was observed in patients with neuropathic pain, RA, and osteoarthritis. Patients with FM also showed basal cAMP levels higher than controls. The reduced activity of Gi proteins seems to be unrelated to a reduction of protein levels since only a slight reduction (about 20-30%) of the Gi3alpha subunit was observed. CONCLUSIONS: Gi protein hypofunctionality is the first biochemical alteration observed in FM that could be involved in the pathogenesis of this syndrome. In the complete absence of laboratory diagnostic tests, the determination of an increase in cAMP basal levels in lymphocytes, together with the assessment of a Gi protein hypofunctionality after adenylyl cyclase stimulation, may lead to the biochemical identification of patients with FM.
11479761 Minimum ten-year follow-up clinical and radiographic results of Mark I and Mark II Lord ty 2001 The purpose of this study was to evaluate the clinical and radiographic results in 103 hips in 88 patients who had cementless primary Lord type femoral component (stem), with a mean follow-up of 11.8 years (range, 10 to 16 years). The original diagnoses were: osteoarthritis in 77 hips, rheumatoid arthritis in 15, and osteonecrosis of the femoral head in 11. Clinical results were assessed using the Harris hip score. Biological fixation, stem full-fit ratio in the intramedullary canal, and bone remodeling were evaluated by X-ray findings. The average clinical hip scores were: 47.1 points preoperatively, 81.7 points at 1 year, 86.6 points at 5 years, 79.0 points at 10 years, and 76.8 points at 15 years. By setting the endpoint at the time when loosening was radiologically confirmed, the 10-year survivorship of the femoral component was 96.9%, and the 16-year survivorship was 95.9%. The full-fit ratio between the bone implant interface just after surgery showed a significant relationship to stability of the femoral component. The decrease in the hip score at 10 years was caused by aseptic loosening of the acetabular threaded cup. However, the femoral component was stable for more than 10 years after the operation. In conclusion, long-term acceptable durability can be expected with the Lord type femoral component.
11436705 [Isoforms modulation of CD44 adhesion molecule in a murine model of ischemia and intestina 2000 Gut ischemia-reperfusion (G-IR) induces a systemic inflammatory response, in which leukocyte contribution to this injury in distant organs is important. ICAM-1 as well as CD11/CD18 have been involved in leukocyte infiltration in liver and lungs. CD44 adhesion molecule plays an essential role in other inflammatory processes such as rheumatoid arthritis and allergic contact dermatitis, however its implication in G-IR has not been described. In order to establish a possible role of CD44 in the development of systemic inflammation by G-IR, we have studied CD44 mRNA expression by RT-PCR in a murine model of gut ischemia reperfusion. Animals subjected to G-IR showed an increased number of CD44 variable isoforms expressed in liver and spleen compared to non-treated animals or animals subjected to laparotomy. This finding indicates that G-IR specifically induces the expression of different CD44 variable isoforms. Liver CD44 upregulation in animals subjected to G-IR suggests a contribution of this molecule to lymphocyte activation and migration to this injured organ. Moreover, increased isoform expression in spleen may be induced by the proinflammatory environment resulting from a systemic depuration activity.
11342354 Bone marrow cell graft engineering: from bench to bedside. 2001 Mar Bone marrow transplantation (BMT) has the potential to treat hemoglobinopathies (sickle cell and thalassemia) autoimmunity (diabetes, lupus, multiple sclerosis, rheumatoid arthritis, Crohn's colitis) and enzyme deficiency states. Graft versus host disease (GVHD) is a major complication and limitation to the therapeutic application of BMT. There have been many clinical trials and experimental animal models that have attempted to control GVHD through the engineering of the donor bone marrow cells (BMC). Historically, several methods have demonstrated effectiveness in controlling GVHD; however they were also associated with a marked increase in the rate of graft failure. Highly purified hematopoietic stem cells (HSC) engraft quite readily in genetically-matched recipients while they do not engraft as easily in MHC-disparate recipients. The numbers of HSC must be increased 100-200 fold in order to overcome the allogeneic barrier. We were the first to phenotypically and to functionally characterize a novel cell in the bone marrow that enables engraftment of highly purified HSC in allogeneic recipients. The discovery of graft facilitating cell populations has resulted in the restoration of the engraftment-potential of purified HSC between genetically-disparate individuals. The addition of facilitating cells (FC) to T cell-depleted BMC grafts results in allogeneic engraftment without GVHD or graft failure. New strategies of BMC engineering that retain FC and HSC but avoid GVHD have allowed successful engraftment in mismatched and older recipients. These techniques have expanded the therapeutic potential of BMT to virtually every candidate as well as to non-malignant diseases in which the morbidity associated with conventional BMT could not be accepted. This article reviews the transition of the FC technology from bench to bedside and discuss the potentially broad-reaching applications of BMT and mixed chimerism.
11310833 CXCR3 chemokine receptor distribution in normal and inflamed tissues: expression on activa 2001 Mar Using new human CXCR3 chemokine receptor-specific monoclonal antibodies, we studied human CXCR3 tissue distribution in lymphoid and nonlymphoid organs, as well as in inflammatory conditions, including rheumatoid arthritis, Hashimoto's thyroiditis, and dermal vasculitis. CXCR3 was expressed by certain dendritic cell subsets, specifically myeloid-derived CD11c positive cells, not only in those present in normal lymphoid organs, but also in germinal centers generated in inflammatory conditions. CXCR3 expression was also detected in some lymphocyte subsets such as intraepithelial lymphocytes of secondary lymphoid organs and infiltrating lymphocytes in inflammatory conditions. In addition, CXCR3 was constitutively expressed by endothelial cells (EC) of vessels of medium and large caliber but not in small vessels from different organs. Finally, enhanced CXCR3 expression was found in EC and in infiltrating lymphocytes with an activated phenotype in inflammatory diseases. The CXCR3 chemokine receptor may play a role in the regulation of leukocyte migration to inflammatory sites.
11269318 Glycosylation and the immune system. 2001 Mar 23 Almost all of the key molecules involved in the innate and adaptive immune response are glycoproteins. In the cellular immune system, specific glycoforms are involved in the folding, quality control, and assembly of peptide-loaded major histocompatibility complex (MHC) antigens and the T cell receptor complex. Although some glycopeptide antigens are presented by the MHC, the generation of peptide antigens from glycoproteins may require enzymatic removal of sugars before the protein can be cleaved. Oligosaccharides attached to glycoproteins in the junction between T cells and antigen-presenting cells help to orient binding faces, provide protease protection, and restrict nonspecific lateral protein-protein interactions. In the humoral immune system, all of the immunoglobulins and most of the complement components are glycosylated. Although a major function for sugars is to contribute to the stability of the proteins to which they are attached, specific glycoforms are involved in recognition events. For example, in rheumatoid arthritis, an autoimmune disease, agalactosylated glycoforms of aggregated immunoglobulin G may induce association with the mannose-binding lectin and contribute to the pathology.
11260023 Common variable immunodeficiency treated with a recombinant human IgG, tumour necrosis fac 2001 Mar Common variable immunodeficiency (CVI) is characterized by a failure in B-cell differentiation and impaired immunoglobulin secretion, but with a variable clinical presentation, including the development of sarcoidal granulomas and autoimmune diseases, as well as an increased incidence of malignancies. We present a 21-year-old white man who carried a diagnosis of juvenile rheumatoid arthritis and presented 6 years later with scarring alopecia showing sarcoidal granulomas. Further work confirmed the diagnosis of CVI, and with increasing systemic symptoms, it was elected to treat the patient with a tumour necrosis factor (TNF)-alpha antagonist, a TNF-alpha receptor IgG1 fusion protein. The patient showed improvement in his systemic symptoms and some hair regrowth after 3 months of therapy, and continued improvement in his systemic disease with only mild scalp hair thinning in the areas of prior involvement after almost 1 year of therapy. CVI and sarcoid may have overlapping clinical and immunological findings. Previous therapies for CVI, including intravenous immunoglobulin, have not altered the mortality of the disease. TNF-alpha is a primary cytokine and is elevated in CVI, and specific inhibition of TNF-alpha in this patient was effective in moderating his disease, including his skin disease.
11224479 Current understanding of methotrexate pharmacology and efficacy in acute leukemias. Use of 2001 Feb BACKGROUND AND OBJECTIVES: Methotrexate (MTX) is a key drug in the curative regimen of children with acute lymphocytic leukemia. This drug is widely used not only in the treatment of neoplastic diseases such as leukemia, lymphoma, choriocarcinoma, head and neck cancer and osteogenic sarcoma, but also for various autoimmune diseases, e.g., rheumatoid arthritis and psoriasis, and for the prevention of graft-versus-host disease after transplantation. The development of drug resistance is the limiting factor in the use of MTX. This review will outline the mechanisms of acquired and natural resistance to MTX that have been studied in patients affected by acute lymphocytic leukemia and acute myelocytic leukemia and the cell cycle genes involved in MTX resistance. This information may improve the use of MTX or could lead to the development of better drugs. Moreover a short description of newer antifolates with their mechanisms of action is presented. EVIDENCE AND INFORMATION SOURCES: The authors of this review have a long-standing interest in the mechanism of action of and resistance to MTX and other antifolates. Information from journal articles covered by the Science Citation Index and Medline has been reviewed together with work performed by the authors. PERSPECTIVES: Antifolates continue to be an extremely important class of drugs for the treatment of non-neoplastic as well as neoplastic diseases. New inhibitors that target dihydrofolate reductase as well as other folate-dependent enzymes are being evaluated in the clinic, and show promise.
10994530 Cholera toxin and related enterotoxins: a cell biological and immunological perspective. 2000 Aug Cholera toxin (Ctx) from Vibrio cholerae and the closely related Escherichia coli heat-labile enterotoxin (Etx) are the primary virulence factors responsible for causing cholera and traveller's diarrhea, respectively. Studies on the mode of action of these toxins on gut epithelial cells have revealed important insights into the mechanisms of toxin uptake and trafficking in eukaryotic cells. However, of perhaps even greater fascination have been the discoveries that Ctx and Etx exhibit remarkable immunological properties. When either of these toxins is administered via mucosal routes, it triggers a potent mucosal and systemic anti-toxin immune response. By contrast, local or systemic immunization with other soluble protein antigens usually stimulates only a meagre immune response, or results in a state of immunological tolerance. Even more striking are the findings that when Ctx or Etx are mixed with heterologous antigens, they function as adjuvants, leading to stimulation of mucosal responses to the admixed antigen, and the abrogation of oral tolerance. In addition, recent observations have shown that the receptor-binding component of these toxins can down-regulate inflammatory diseases associated with the induction of autoimmune disorders such as rheumatoid arthritis, diabetes, and multiple sclerosis. While the underlying mechanisms responsible for these remarkable properties have yet to be resolved, it is clear that the toxins' ability to bind to cell surface receptors plays an important role in their potent immunogenicity, adjuvanticity, and immunotherapeutic properties. This review provides an overview of the latest developments within the Ctx/Etx field, with a special emphasis on the cell entry mechanisms and immunomodulatory action of Ctx/Etx and their component subunits.
10919413 Factor VIII inhibitors. Laboratory diagnosis of inhibitors. 2000 The diagnosis of inhibitors of blood coagulation is often the most challenging problem in the clinical laboratory. Immediate attention must be given to the following patient groups whose principal laboratory abnormality is the prolonged activated partial thromboplastin time (aPTT): the patient with (1) hemophilia who previously responded to an adequate dose of clotting factor product and now fails to show effective clinical response to the same replacement concentrate; (2) previously benign clinical history who now presents with soft tissue bleeding or emergent internal hemorrhaging; (3) sudden onset of generalized ecchymoses who was previously well; (4) postpartum state; (5) malignancy, lymphoma, rheumatoid arthritis, or other autoimmune disorders; and (6) drug reactions. Immediate attention must be given to the prolonged prothrombin time (PT), aPTT, and thrombin time (TT) in order to respond to urgent queries from a perplexed internist, hematologist, intensivist, or surgeon caring for a patient with unexpected bleeding. Sometimes the problem of a prolonged "clotting time" arises preoperatively, causing unanticipated delay in operative procedures. For this reason, the laboratory support, usually in the coagulation section of a clinical laboratory or reference laboratory, must be quick, unequivocal and precise. The most common finding is an isolated mild, moderate, or severe prolongation of the aPTT with a normal PT, TT, and platelet count. The aPTT mixing study (The Mix), usually modified for time and temperature, along with appropriate controls, is the seminal test. This is the basis for all further testing. It may be supported by direct factor assays, and, therefore, the laboratory must know the reagent responsiveness and sensitivity for each clotting factor. By definition, complete correction of the aPTT in a 1:1 mix of patient and reference plasma is a factor deficiency. In this article, incomplete or minimal correction of The Mix will be characterized with particular attention to the various inhibitor assays, in other words, Oxford, Bethesda, and Nijmegen assays and the enzyme-linked immunosorbent assay (ELISA). An investigative approach to final characterization of the intensity (quantification) of the inhibitor and the exclusion of a lupus anticoagulant (LA) will be discussed.
10801257 Lessons from genetically engineered animal models XI. Novel mouse models to study pathogen 2000 May Crohn's Disease (CD) affects more than 500,000 individuals in the United States and represents the second most common chronic inflammatory disorder after rheumatoid arthritis. Although major advances have been made in defining the basic mechanisms underlying chronic intestinal inflammation, the precise etiopathogenesis of CD remains unknown. We have recently characterized two novel mouse models of enteritis that express a CD-like phenotype, namely the TNF DeltaARE model of tumor necrosis factor (TNF) overexpression and the SAMP1/Yit model of spontaneous ileitis. The unique feature of these models is that they closely resemble CD for location and histopathology. These genetically manipulated new models of intestinal inflammation offer a powerful tool to investigate potential causes of human disease and may allow the development of novel disease-modifying therapeutic modalities for the treatment of CD.
10744338 Inhibition of transcription factors by anti-inflammatory and anti-rheumatic drugs: can var 2000 Mar 1. The drugs used in the treatment of rheumatoid arthritis (RA) form a diverse group with unpredictable adverse effects, mostly weak efficacy and variable responses. Despite their differences, a common feature of many anti-inflammatory and disease-modifying anti-rheumatic drugs (DMARD) is inhibition of pro-inflammatory transcription factors, particularly nuclear factor (NF)-kappaB and activator protein (AP)-1. 2. The present brief review identifies those drugs capable of inhibiting transcription factors, particularly steroids, gold salts, D-penicillamine, cyclosporine A and possibly salicylates. 3. The newer biological inhibitors of tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta are capable of indirect inhibition of NF-kappaB activation, although even with these potent agents the problem of variability in response has not disappeared. 4. The development of selective inhibitors of the transcription factor NF-kappaB should have the benefit of the anti-inflammatory drugs and DMARD, both new and old. 5. It is hypothesized that this strategy will overcome much of the variability in the therapeutic response and adverse effects that limit the usefulness of the existing drugs in the treatment of RA.