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ID PMID Title PublicationDate abstract
12847547 Analysis of MHC region genetics in Finnish patients with juvenile idiopathic arthritis: ev 2003 Jul This study used Finnish juvenile idiopathic arthritis (JIA) probands with pauciarticular and rheumatoid factor (RF) negative polyarticular subtypes of JIA to further define the genetic susceptibility to JIA. We examined 16 markers spanning an 18 cM region of chromosome 6 encompassing the MHC and surrounding genomic region in a set of 235 Finnish JIA nuclear families and 639 Finnish control individuals. Analysis by case/control association and transmission disequilibrium test (TDT) methods each demonstrated strong evidence for a susceptibility locus near the D6S2447 microsatellite (P<10(-6) for both methods) that is flanked by DQB1 and DRB1. Analysis of the DRB1 locus suggested that DRB1*0801 and DRB1*1101 rather than DQA1 or other HLA alleles may be responsible for conferring susceptibility to disease. These findings are consistent with the most compelling results of previous reports on HLA associations and suggest a JIA DRB1 shared epitope encompassing critical amino-acid residues in the third hypervariable region of this molecule. Most importantly, in pauciarticular patients, the strong association does not extend to proximal markers as it does in polyarticular patients (P<0.00001). Analysis strongly suggests that the difference is because of additional JIA susceptibility loci within the MHC being present in polyarticular RF negative patients.
16819079 [The role of omega-3 polyunsaturated fatty acids in clinical medicine.]. 2003 Mar In recent years there has been a growing interest in the use of omega-3 polyunsaturated fatty acids as medical therapeutic agents, and a multitude of epidemiological and clinical studies have evaluated their role in health and disease. A drug containing high concentration of omega-3 polyunsaturated fatty acids has been approved for the treatment of hypertriglyceridemia and following myocardial infarction in some European countries. Furthermore, there is a growing body of evidence suggesting that these fatty acids may be of benefit in several other diseases. To date, the majority of research has focused on cardiovascular diseases including hypertension, atherosclerosis and the prevention of sudden cardiac death, where these fatty acids may be useful. In addition, several studies have suggested a beneficial effect in severe acute and chronic inflammatory diseases, particularly rheumatoid arthritis and immunoglobulin A nephropathy, although the results have not been consistent. Finally, the role of omega-3 polyunsaturated fatty acids in the structure and function of nervous tissue has prompted investigations on their effect on neurological development of premature and young infants and their use as therapeutic agents in psychiatric disorders. In this article we review the scientific evidence for the role of omega-3 polyunsaturated fatty acids in clinical medicine.
15169980 T-cell large granular lymphocyte leukemia and related disorders. 2004 T-cell large granular lymphocyte (LGL) leukemia is a clonal proliferation of cytotoxic T cells, which causes neutropenia, anemia, and/or thrombocytopenia. This condition is often associated with autoimmune disorders, especially rheumatoid arthritis, and other lymphoproliferative disorders. The diagnosis is suggested by flow cytometry demonstrating an expansion of CD8(+)CD57(+) T cells and is confirmed by T-cell receptor gene rearrangement studies. Mounting evidence suggests that LGL leukemia is a disorder of dysregulation of apoptosis through abnormalities in the Fas/Fas ligand pathway. In most patients, this is an indolent disorder, and significant improvement of cytopenias can be achieved with immunosuppressive agents such as steroids, methotrexate, cyclophosphamide, and cyclosporin A. This review provides a concise, up-to-date summary of LGL leukemia and the related, more aggressive, malignancies of cytotoxic T cells and natural killer cells.
15102433 IkappaB kinases: key regulators of the NF-kappaB pathway. 2004 Feb The nuclear factor (NF)-kappaB pathway is important for the expression of a wide variety of genes that are involved in the control of the host immune and inflammatory response, and in the regulation of cellular proliferation and survival. The constitutive activation of this pathway is associated with inflammatory and autoimmune diseases, such as asthma, rheumatoid arthritis and inflammatory bowel disease, in addition to atherosclerosis, Alzheimer's disease, cancer and diabetes. One of the key steps in activating the NF-kappaB pathway is the stimulation of the IkappaB (inhibitor of kappaB) kinases. Recent data indicate that these kinases activate the NF-kappaB pathway through distinct steps that are operative in both the cytoplasm and the nucleus. A better understanding of the mechanisms that activate this pathway provides the potential for defining new therapeutic targets that might prevent the aberrant activation of NF-kappaB in a variety of human diseases.
12948911 Potential future dermatological indications for tacrolimus ointment. 2003 Jul Tacrolimus ointment is a steroid-free topical immunomodulator developed for the treatment of atopic dermatitis, a common, chronic inflammatory skin disease. By inhibiting T-cell activation and cytokine production, topically applied tacrolimus modulates inflammatory responses in the skin. Numerous clinical trials have shown that it is effective and well tolerated for the treatment of atopic dermatitis, its licensed indication. In addition, numerous publications suggest that tacrolimus ointment may provide effective treatment for a variety of other inflammatory skin disorders, many of which are very difficult to manage with standard therapy. This paper reviews currently available evidence regarding the use of tacrolimus ointment in a range of dermatological disorders, including psoriasis, lichen planus, pyoderma gangrenosum, lichen sclerosus, contact dermatitis, leg ulcers in rheumatoid arthritis, steroid-induced rosacea and alopecia areata. It also provides recommendations for future clinical studies with tacrolimus ointment.
12887954 Abdominal amyloidosis: spectrum of radiological findings. 2003 Aug Amyloidosis is a disease characterized by the deposition of fibrillar protein amyloid of beta-structure in organs or tissues. It is usually classified as either a primary disease or secondary to a co-existent condition, such as rheumatoid arthritis, tuberculosis, or neoplasm (particularly multiple myeloma or renal cell carcinoma). Amyloid protein deposition can be seen in a variety of organs though it occurs with higher frequency in the gastrointestinal tract, kidney, and heart. Amyloidosis can have a wide spectrum of manifestations in nearly every abdominal organ. Some of these, for example, multiple cystic submucosal masses of the stomach, amyloidosis of the gallbladder, and dirty soft tissue infiltration of the subcutaneous fat, have not yet been covered in the radiological literature. The combination of various imaging techniques and the identification of characteristic computed tomography (CT) hepatic features may help in the differentiation of amyloidosis from other infiltrative diseases; however, confirmative diagnosis can usually only be achieved by tissue biopsy.
12745948 The possession of technical aids among persons with a somatic chronic disease. 2003 Apr 22 PURPOSE: Previous research has highlighted disability as a determinant of the need for technical aids; surprisingly, disease as a potential determinant has been ignored. The goal of the present study was to determine whether the possession of technical aids is dependent on the type of chronic disease, illness duration, co-morbidity, disability, age, and several other factors. METHODS: The study was performed in a representative sample of persons with a somatic chronic disease (n=2262). Type of chronic disease, time post-diagnosis and co-morbidity were assessed by the patient's general practitioner. Disability was assessed with the Sickness Impact Profile. The possession of technical aids and other characteristics were assessed by questionnaire. RESULTS: Type of chronic disease (osteoarthritis, rheumatoid arthritis, diabetes and COPD), disability, age and gender were significantly and independently associated with the possession of technical aids. CONCLUSIONS: Apart from disability, disease-, age-, and gender-related characteristics determine the possession of technical aids. A detailed assessment of these characteristics is required in order to ensure that technical aids meet personal needs.
12592305 14. Immunologic rheumatic disorders. 2003 Feb We provide the basics for the clinician who might be called on to consider the diagnosis of diseases such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) in their practice. We will emphasize clinical recognition and first-line laboratory testing. Only characteristics of the classic rheumatic inflammatory diseases, RA, SLE, Sjögren syndrome, scleroderma, and dermatomyositis/polymyositis, will be covered. In the past decade, RA is the only disease for which treatment has substantially improved. The treatment of RA has been revolutionized by the use of methotrexate and, more recently, tumor necrosis factor inhibitors. The goal of RA treatment today is to induce a complete remission as early as possible in the disease process, with the mantra being "elimination of synovitis equals elimination of joint destruction." The hope is that if the major mediators of Sjögren syndrome or SLE or scleroderma can be identified and then blocked, as in the example of tumor necrosis factor inhibitors in RA, more specific treatments will become available. Thus, RA has become an excellent model of this evolving paradigm. Through the identification of major mediators in its pathogenesis, novel and highly efficacious therapeutic agents have been developed.
12395742 [Pyoderma gangrenosum]. 2002 Sep 28 GENERAL CHARACTERISTICS: Rare cause of cutaneous ulceration, pyoderma gangrenosum is among the group of neutrophilic dermatites characterized by the richness of the mature neutrophilic polynuclear dermal infiltrate. The primary lesion is a pustule sitting on an inflammatory base; extremely painful, it rapidly ulcerates. The lesion rapidly extends to more than 10 cm in diameter, has a regular, sharp border and a peripheral roll of flesh exhibiting purulent channels on the inside and a red granulous surface often covered with a pustular coating. Little is known of this disease. CONCOMITANT AFFECTIONS: In more than 50% of cases, pyoderma gangrenosum is associated with other diseases, which must be systematically searched for. These may be digestive, essentially inflammatory enterocolitis with frequent development of peristomal ulceration, rheumatismal affections notably rheumatoid arthritis, hematological affections (benign monoclonal gammapathy, chronic myeloid hemopathy). FROM A PARACLINICAL POINT OF VIEW: There are no specific examinations. A cutaneous biopsy should be performed in all cases, notably to eliminate other causes of ulceration. Since concomitant disease can be subsequently revealed, it is essential to renew the paraclinical investigations, even after the disease has healed. NO CODIFIED TREATMENT: Treatment of the cause, if it can be cured, may be sufficient to permit regression of the lesions. Local treatments to provoke budding and hence avoid surinfection are mandatory. In the progressive and extensive forms, systemic treatment, notably high dose corticosteroids, is indicated. Surgery, a priori, is excluded.
12041520 Lipoma arborescens of the hip. 2002 May Lipoma arborescens is a rare intra-articular lesion characterized by extensive villous proliferation of the synovial membrane and hyperplasia of subsynovial fat. Although it has been described as arising from traumatic, inflammatory, rheumatologic, developmental, and neoplastic causes, its etiology remains unknown. This article describes in detail--for the first time in the orthopedic literature-a case of lipoma arborescens of the hip. Clinical presentation, histologic and radiographic findings, and treatment of this rare lesion are discussed. Based on clinical, radiologic, and surgical evaluation, differential diagnosis for this lesion should include other conditions that cause synovial thickening, proliferation, and joint effusion--for example, synovial chondromatosis, pigmented villonodular synovitis, synovial hemangiomatosis, and rheumatoid arthritis. Description of this case covers the full radiologic evaluation, including magnetic resonance imaging (MRI), diagnostic pathologic description, and minimum 24-month follow-up. Although lipoma arborescens of the hip is a rare condition, it should be considered in the differential diagnosis of patients with its characteristic clinical prodrome and MRI findings confirming a periarticular fatty mass.
17491665 Novel insights in the regulation of the immune system: a report on the FASEB summer resear 2004 Spring The bi-annual FASEB autoimmunity conference organized last year by Betty Diamond and Stephen Miller brought together some 150 delegates studying various aspects of autoimmune diseases such as lupus, rheumatoid arthritis and autoimmune diabetes. The conference provided numerous insights into the latest research on autoimmunity and answered many basic research type questions that are important for understanding the complex nature of these diseases. Because some time has elapsed since the conference, data from a number of talks has already been published. Thus, I will present an overview of some of the most interesting and at the same time, still unpublished data on T cells presented at the conference. The balance between tolerance and immunity is controlled through a variety of mechanisms such as the presence or absence of co-stimulation or negative regulation of a T cell response. CD4+ CD25+ regulatory T cells were also a focus of interest. Talks that I will discuss focused on the role of molecules such as GITR, Foxp3 and B7 for the development and function of regulatory T cells and the importance of these molecules in the prevention of autoimmunity. As well, a novel form of CTLA-4 and the use of 4-1BB co-stimulation blockade for the control of autoimmunity will be discussed.
15861323 Anti-inflammatory properties of statins. 2004 Nov Increasing clinical and experimental evidence indicates that some beneficial effects of statins, known as efficient therapeutic agents in cardiovascular disease treatment, may result from their ability to modulate vascular and endothelial cell gene expression by mechanisms independent of cholesterol reduction. It has been shown that statins exhibit direct anti-inflammatory properties via inhibition of proinflammatory cytokine and chemokine secretion, as well as through adhesion molecule expression on leukocytes. Another important mechanism by which statins may modulate the immune response is inhibition of interferon gamma-induced expression of class II major histocompatibility complexes. Class II major histocompatibility complex expression is central to immune regulation in T cell-mediated autoimmune diseases, indicating a potential beneficial role of statins in these pathologies. Indeed, promising new preclinical data indicate that statins might be useful in the treatment of multiple sclerosis and rheumatoid arthritis.
15654511 Neutrophil recruitment in mast cell-dependent inflammation: inhibitory mechanisms of gluco 2004 Dec Mast cells are strategically localized along the microvasculature in tissues in close contact with the external environment, such as the skin, lung and intestines. By releasing a multi-faceted spectrum of proinflammatory mediators, such as cytokines and chemokines, mast cells have the capacity to coordinate trafficking of leukocytes. Mast cells play a pathophysiological role in numerous inflammatory diseases as diverse as hypersensitivity reactions, ischemia/reperfusion injury and rheumatoid arthritis. On the other hand, mast cells act also as tissue sentinels and are critically involved in the host defensive response against microbial infection by stimulating neutrophil recruitment. Glucocorticoids are powerful agents frequently used in mast cell-dependent diseases, although the anti-inflammatory mechanisms of these compounds are not completely understood at present. In order to circumvent steroid-associated side-effects and develop more specific therapeutics, numerous studies have examined the mechanisms underlying glucocorticoid inhibition of mast cell-dependent neutrophil recruitment. Based on recent findings, it may be suggested that glucocorticoids selectively inhibit the expression and function of certain adhesion molecules and chemokines. This review summarizes current insights into the underlying mechanisms of mast cell-regulated tissue accumulation of neutrophils and the inhibitory effects of glucocorticoids.
15621572 The role of CD40-CD154 interactions in autoimmunity and the benefit of disrupting this pat 2004 Sep Many tissue injuries and immune mediated pathologies such as graft allo-rejections were found to involve CD40-CD40 ligand (CD40L, CD154) signaling pathway. The disruption of this pathway in many animal models led to the improvement of graft survival in these models. CD40-CD154 interactions were also shown to play a significant role in the maintenance of autoimmunity, and the production of auto-antibodies in systemic lupus erythematosus (SLE). High-level expression of CD154 has been detected on T cells from patients with active SLE, rheumatoid arthritis (RA) and other autoimmune diseases, indicating that such cells could account for the high-level expression of immune accessory molecules on B cells of patients with active disease. An increased serum level of soluble CD154 was also reported in SLE, RA, and Sjogren's disease in correlation with the relevant auto-antibodies and with the clinical disease activity. Anti-CD154 antibody therapy prevents auto-antibody production and renal immune complex deposition in lupus nephritis, indicating that disruption of this pathway could be a beneficial treatment in SLE. However, the etiology of the higher than expected number of thromboembolic events in anti-CD154 treated SLE patients should be investigated and preventive measures should be considered.
15474860 Role of tumor necrosis factor alpha in asthma. 2004 Nov Asthma is a heterogeneous disease in which various cytokines orchestrate airway inflammation. Tumor necrosis alpha (TNF-alpha) is a proinflammatory cytokine that has been implicated in the modulation of inflammation in various diseases, including asthma. Although TNF-alpha blocking strategies have been an effective therapeutic modality in diseases such as rheumatoid arthritis, their role in asthma and the effects of the blockade in asthma is poorly understood. This article examines the role of TNF-alpha in asthma and the effects of blocking TNF-alpha as a possible therapeutic option in patients with severe corticosteroid-dependent asthma.
15464021 Interleukin-18 bioactivity: a novel target for immunopharmacological anti-inflammatory int 2004 Oct 1 Interleukin-18 is a member of the interleukin-1 family of cytokines with pro-inflammatory and tumor-suppressive properties. Its ability to potently enhance the production of interferon-gamma indicates in particular the crucial function of interleukin-18 as an immunomodulatory molecule. In fact, high levels of interleukin-18 are detected in human diseases associated with immunoactivation including viral or bacterial infections and chronic inflammation. Animal models suggest suppression of interleukin-18 bioactivity as a novel therapeutic concept specifically for the treatment of chronic inflammatory diseases such as rheumatoid arthritis, Crohn's disease, and psoriasis. Here we introduce into the biology of interleukin-18 and review immunopharmacological strategies that aim at reducing interleukin-18 bioactivity in human disease.
15174967 Therapeutic potential of targeting IL-1 and IL-18 in inflammation. 2004 Jun Interleukin (IL)-1 and IL-18 are cytokines that play a major role in autoimmune and inflammatory human disease. Both cytokines drive a wide range of pro-inflammatory effector networks in many cell types and use common signal transduction cascades. IL-1, IL-18 and other members of the IL-1 superfamily are expressed at elevated levels in tissue and fluid samples isolated from patients with many chronic inflammatory diseases. These cytokines are primary drivers in acute and chronic animal models of inflammation and their blockade has been shown to ameliorate disease in preclinical studies. Biological agents that target IL-1 have demonstrated efficacy in patients with rheumatoid arthritis, and further agents targeting IL-1 or IL-18 neutralisation are in clinical development. The potential for such agents spans human disease where tissue destruction is a primary end point of cytokine action.
15115315 The beneficial and detrimental effects of linoleic acid on autoimmune disorders. 2004 Feb Type 1, or cellular, immune response is characterized by overproduction of IL-1, IL-2, IFN-gamma and TNF-alpha and is the underlying immune mechanism of some autoimmune disorders such as psoriasis, alopecia areata, rheumatoid arthritis, Crohn's disease, multiple sclerosis, insulin-dependent diabetes mellitus and experimental autoimmune uveitis. Type 2 immune response is seen in allergic and antibody-mediated autoimmune diseases and is characterized by IL-4, IL-6 and IL-10 overproduction. Linoleic acid is a precursor of prostaglandin E2 (PGE2) and its intake results in tissue production of PGE2, especially in the absence of other polyunsaturated fatty acids (PUFAS) which inhibit this conversion. PGE2 decreases the production of IL-1, IL-2, IFN-gamma and TNF-alpha and proliferation of TH1 cells and increases the production of IL-4, leading to suppression of the type 1 immune response. Taken together, linoleic acid, the major PUFA of maize oil, could have therapeutic efficacy against cellular autoimmune disorders. On the other hand, excessive intake of linoleic acid may aggravate type 2 autoimmune disorders.
14754394 Endothelial chemokines in autoimmune disease. 2004 Compelling evidence now exists supporting the involvement of chemokines in the pathogenesis of autoimmune diseases. Examples of chemokines and chemokine receptors being involved in mediating autoimmune disease exist for rheumatoid arthritis, multiple sclerosis, allograft rejection, systemic lupus erythematosus, psoriasis, atopic dermatitis, lichen planus, and graft-versus-host-disease. Expression of chemokines by endothelial cells appears to be an important step in the development of these diseases. Since chemokines are small molecular weight molecules that act through G-protein coupled receptors, they make attractive drug targets. Several antagonists of chemokine - chemokine receptor interactions have been used to successfully alleviate some or all of the symptoms associated with many of these diseases in animal models. Further investigation of the involvement of chemokines in the pathogenesis or progression of autoimmune diseases may lead to practical clinical advances in diagnosis, prognosis, and therapy of such diseases.
12802737 Variation of podophyllotoxin in leaves of Eastern Red Cedar (Juniperus virginiana). 2003 May Leaves of Eastern red cedar (Juniperus virginiana L. Cupressaceae) have been reported to contain podophyllotoxin, a pharmaceutical compound used to manufacture drugs for treatment of cancer, rheumatoid arthritis, genital warts, psoriasis, and multiple sclerosis. Podophyllotoxin content of leaves of immature, mature male, and mature female plants (approximately 1.45 mg x g -1) was significantly higher than that of leaves of juvenile plants (0.60 mg x g -1). Sampling date also affected podophyllotoxin content. Leaves harvested in January and April exhibited higher podophyllotoxin contents (1.56 and 1.45 mg x g -1, respectively) than leaves harvested in February and June (1.06 and 1.08 mg x g -1, respectively). There was no obvious pattern or trend in the data due to sampling date. There was no significant interaction between plant type and sampling date. These results indicate that foliage of mature Eastern red cedar, a waste product of the lumber industry, could be a low-yielding, but relatively stable, source of podophyllotoxin.