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ID PMID Title PublicationDate abstract
12802339 Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B. 2003 Jun 12 Protein tyrosine phosphatases regulate signal transduction pathways involving tyrosine phosphorylation and have been implicated in the development of cancer, diabetes, rheumatoid arthritis and hypertension. Increasing evidence suggests that the cellular redox state is involved in regulating tyrosine phosphatase activity through the reversible oxidization of the catalytic cysteine to sulphenic acid (Cys-SOH). But how further oxidation to the irreversible sulphinic (Cys-SO2H) and sulphonic (Cys-SO3H) forms is prevented remains unclear. Here we report the crystal structures of the regulatory sulphenic and irreversible sulphinic and sulphonic acids of protein tyrosine phosphatase 1B (PTP1B), an important enzyme in the negative regulation of the insulin receptor and a therapeutic target in type II diabetes and obesity. We also identify a sulphenyl-amide species that is formed through oxidation of its catalytic cysteine. Formation of the sulphenyl-amide causes large changes in the PTP1B active site, which are reversible by reduction with the cellular reducing agent glutathione. The sulphenyl-amide is a protective intermediate in the oxidative inhibition of PTP1B. In addition, it may facilitate reactivation of PTP1B by biological thiols and signal a unique state of the protein.
12761894 Nitric oxide synthase I mediates osteoclast activity in vitro and in vivo. 2003 Jun 1 Bone resorption is responsible for the morbidity associated with a number of inflammatory diseases such as rheumatoid arthritis, orthopedic implant osteolysis, periodontitis and aural cholesteatoma. Previous studies have established nitric oxide (NO) as a potentially important mediator of bone resorption. NO is a unique intercellular and intracellular signaling molecule involved in many physiologic and pathologic pathways. NO is generated from L-arginine by the enzyme nitric oxide synthase (NOS). There are three known isoforms of NOS with distinct cellular distributions. In this study, we have used mice with targeted deletions in each of these isoforms to establish a role for these enzymes in the regulation of bone resorption in vivo and in vitro. In a murine model of particle induced osteolysis, NOS I-/- mice demonstrated a significantly reduced osteoclast response. In vitro, osteoclasts derived from NOS I-/- mice were larger than wild type controls but demonstrated decreased resorption. Although NOS I has been demonstrated in osteoblasts and osteocytes as a mediator of adaptive bone remodeling, it has not previously been identified in osteoclasts. These results demonstrate a critical role for NOS I in inflammatory bone resorption and osteoclast function in vitro.
12678866 The neuropeptides VIP/PACAP and T cells: inhibitors or activators? 2003 The structurally related neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) are released within the lymphoid organs following antigenic stimulation, and modulate the function of inflammatory cells through specific receptors. In activated macrophages, VIP and PACAP inhibit the expression at both mRNA and protein level of pro-inflammatory cytokines and chemokines, through effects on de novo expression or nuclear translocation of a number of transcription factors, i.e. NFkB, CREB, c-Jun, JunB, and IRF-1. In addition, VIP and PACAP promote Th2-type, and inhibit Th1-type responses in vivo and in vitro, through several mechanisms, including preferential survival of Th2 effectors and subsequent generation of Th2 memory cells. The function of VIP/PACAP as "macrophage deactivating factors" appears to be responsible for their protective effect in vivo in models of septic shock. Both deactivation of macrophages and inhibition of Th1-type responses appear to be responsible for the beneficial effect of VIP/PACAP in models of Th1-type autoimmune diseases such as rheumatoid arthritis.
12673950 [Mechanism of production and release of tumor necrosis factor implicated in inflammatory d 2003 Mar Tumor necrosis factor (TNF) is a potent inflammatory cytokine involved in many pathophysiological conditions including rheumatoid arthritis and Crohn's disease. Despite recent evidence regarding signal transduction via TNF receptor and its biological actions, the mechanism of TNF release remains poorly understood. To clarify how production and release of TNF are regulated, we focused on mast cells and microglia which are involved in allergic inflammation and brain damage or recovery, respectively. In RBL-2H3 mast cells, anti-allergic drugs including azelastine inhibited the release of TNF more potently than degranulation in response to antigen or ionomycin. It was also demonstrated that TNF releasing steps are regulated via the PKC alpha-dependent pathway. Furthermore, Rho GTPases, possibly Rac, were shown to be involved in antigen-induced TNF transcription through activating PKC beta I. In cultured rat brain microglia, we found that extracellular ATP triggers the release of TNF via the P2X7 receptor. ERK and JNK are also involved in ATP-induced TNF transcription, while p38 regulates the transport of TNF mRNA from the nucleus to the cytosol. Additionally, JNK and p38, but not ERK, are activated via the P2X7 receptor. A better understanding of the specific pathways that regulate TNF release for each effector cell may offer further possible therapeutic targets for inflammatory diseases.
12670535 Identification of a selectivity determinant for inhibition of tumor necrosis factor-alpha 2003 Mar Inhibition of tumor necrosis factor-alpha converting enzyme (TACE) is a widespread objective in the search for disease modifying agents to combat rheumatoid arthritis and other autoimmune diseases. Until recently, most of the inhibitors in the literature have shown concomitant activity against the related matrix metalloproteinases (MMPs), producing undesired side effects. Here we describe the successful search for a TACE selectivity mechanism. We built a homology model based on the crystal structure of the related snake venom protein atrolysin. Comparison of the model with crystal structures of MMPs suggested a uniquely shaped S1' pocket that might be exploited for selectivity. A novel gamma-lactam scaffold was used to explore the activity profile of P1' sidechains, resulting in highly selective compounds consistent with this hypothesis. Transferability of the hypothesis was then demonstrated with five other distinct scaffolds.
12643515 Abnormalities of serum antielastin antibodies in connective tissue diseases. 2003 Mar BACKGROUND: Antibodies (Abs) to alpha-elastin (elastin breakdown product) and tropoelastin (elastin precursor) are found in the serum of all human subjects and correlate with their respective serum peptide levels; however, peptide levels vary with age and some disease states. This study was undertaken to determine if serum elastin Abs, peptides, and elastin metabolism were altered in autoimmune diseases by detecting a changing ratio of serum anti-alpha:tropoelastin Ab levels. METHODS: Serum from patients with a variety of connective tissue diseases, including 28 with systemic lupus erythematosus (SLE), 24 with scleroderma, 18 with rheumatoid arthritis (RA), 10 with polymyositis, and 39 with vasculitis, was compared with serum from 19 age-matched healthy subjects for levels of antitropoelastin and anti-alpha-elastin Abs. RESULTS: We found an increase in IgG anti-alpha-elastin and a decrease in antitropoelastin Abs in the sera of patients with scleroderma (p < .02 and .00005) and SLE (p < .006 and .011). There was also a marked increase in anti-alpha-elastin Abs in patients with polyarteritis nodosa (p < .0005) and decreases in antitropoelastin Abs in patients with RA (p < .05), polymyositis (p < .01), and a variety of other vasculidities (p < .0003). CONCLUSIONS: Abnormal variations in elastin metabolism may be detected in several connective tissue diseases by measuring ratios of alpha- and tropoelastin IgG Abs as markers of elastin degradation and synthesis.
12625521 Validity and reliability of the EQ-5D self-report questionnaire in English-speaking Asian 2003 Feb Validity and reliability of a Singaporean English EQ-5D self-report questionnaire (EQ-5D) were evaluated among consecutive outpatients with rheumatic diseases attending a tertiary referral hospital in Singapore (a multi-ethnic, urban Asian country). Subjects were interviewed twice within a 2-week period using a standardized questionnaire containing the EQ-5D, Short Form 36 Health Survey (SF-36) and assessing demographic and psychosocial characteristics. To assess validity of the EQ-5D, 13 hypotheses relating responses to EQ-5D dimension/Visual Analogue Scale (EQ-VAS) to SF-36 scores or other variables were examined using the Mann-Whitney test, Kruskal-Wallis test, or Spearman's correlation coefficient. Test-retest reliability was assessed using Cohen's kappa. Sixty-six subjects were studied (osteoarthritis: 9, rheumatoid arthritis: 26, systemic lupus erythematosus: 23, spondyloarthropathy: 8; female: 72.7%; mean age: 44.3 years). Ten of 13 a-priori hypotheses relating EQ-5D responses to external variables were fulfilled, supporting the validity of the EQ-SD. Cohen's kappa for test-retest reliability (n = 52) ranged from 0.29 to 0.61. The Singaporean English EQ-5D appears to be valid in measuring quality of life in Singaporeans with rheumatic diseases; however, its reliability requires further investigation. These data provide a basis for further studies assessing the validity of the EQ-5D in Singapore.
12607404 [Radial segmentation of lymphocytes in peripheral blood of patients with non-small cell lu 2002 The term radial segmentation (RS) is applied to a characteristic nuclear deformation observed in peripheral blood in vitro in some neoplastic and normal cells. It concerns al mononuclear cells. RS positive lymphocytes were found as CD 4 cells. Different conditions and substances, i.e. anticoagulant or cyclosporin can induce the formation of RS nuclei in vitro. Elevated ratio of RS nuclei in peripheral blood has been observed in patients with some autoimmunological diseases i.e. rheumatoid arthritis, diabetes mellitus insulin-dependent, sarcoidosis. Reduced ratio of RS nuclei was observed in neoplastic diseases. The aim of the study was to analyze the incidence of RS nuclei of lymphocytes in vitro in peripheral blood (induced by cyclosporin) in patients with non-small cell lung cancer (NSCLC). Heparinized peripheral blood was obtained from controls and patients with primary NSCLC. The blood was incubated with cyclosporin, and then lymphocytes were isolated by Lymphoprep. RS positive lymphocytes were counted in smears stained with MGG stain. In peripheral blood from healthy donors the average incidence of lymphocytes RS was 3.314% and in patients with NSCLC 4.481% respectively. The difference between controls and patients with NSCLC was not significant. No correlation was found between incidence of RS and stadium of lung cancer.
12571424 Functional involvement of CD44 variant 7 in gut immune response. 2002 A major problem in inflammatory bowel disease (IBD) is the accumulation of highly activated T-helper cells that are refractory to apoptosis induction. Hence, persistent inflammatory lesions are prevalent and are the basis of chronic disease. In IBD upregulation of costimulatory molecules on lamina propria lymphocytes has been described leading to apoptosis resistance. CD44 is a cell adhesion molecule and a signalling receptor that functions as a costimulatory molecule in T-cell activation. Several variant isoforms of CD44 (CD44v) are expressed by alternative splicing of variant exons encoding extracellular regions. Particularly isoforms containing CD44v7 are expressed on T cells and macrophages in T-helper-1 (Th1)-mediated chronic inflammation and autoimmune diseases. In this review recent data on the functional involvement of CD44v7 isoforms in IBD are discussed. In a mouse model of experimental colitis blockade or deletion of CD44v7 protects mice from severe intestinal inflammation by inducing apoptosis in lamina propria mononuclear cells. Recently, we observed that in lamina propria mononuclear cells from the inflamed but not uninflamed mucosa of patients with Crohn's disease, blockade of CD44v7 isoforms also induces apoptosis. The finding that obstruction of CD44v7 isoforms can antagonize Th1-cytokine-dependent immune pathology identifies CD44v7 as a target in the treatment of inflammatory diseases such as IBD, rheumatoid arthritis, multiple sclerosis and other autoimmune diseases in which CD44v7 isoforms are upregulated.
21656986 Ultrasmall near-infrared gold nanoclusters. 2004 Optical fluorescence imaging is increasingly used to monitor biological functions of specific targets (1-3). However, the intrinsic fluorescence of biomolecules poses a problem when fluorophores that absorb visible light (350–700 nm) are used. Near-infrared (NIR) fluorescence (700–1,000 nm) detection avoids the background fluorescence interference of natural biomolecules, providing a high contrast between target and background tissues. NIR fluorophores have a wider dynamic range and minimal background as a result of reduced scattering compared with visible fluorescence detection. They also have high sensitivity, resulting from low infrared background, and high extinction coefficients, which provide high quantum yields. The NIR region is also compatible with solid-state optical components, such as diode lasers and silicon detectors. NIR fluorescence imaging is becoming a noninvasive alternative to radionuclide imaging in small animals (4, 5). Gold nanoparticles have been studied as molecular imaging agents because of their bright NIR fluorescence emission around 800 nm and low toxicity (6, 7). They can be tuned to emit in a range of wavelengths by changing their sizes, shapes, and composition, thus providing broad excitation profiles and high absorption coefficients. They can be coated and capped with hydrophilic materials for additional conjugation with biomolecules, such as peptides, antibodies, nucleic acids, and small organic compounds for in vitro and in vivo studies. Gold nanoparticles are approved by the United States Food and Drug Administration for treatment of patients with rheumatoid arthritis. Gold nanoclusters (AuNCs) possess an ultrasmall size of ~2 nm compared with quantum dots (QDs, ~20 nm) (8). AuNCs are less likely to have high reticuloendothelial system accumulation. AuNCs have been studied as agents for NIR fluorescence imaging of cancerous tissues through the enhanced permeability and retention effect (9).
12465164 Stochastic processes in the causation of rheumatic disease. 2002 Dec OBJECTIVE: Rheumatic disorders arise in certain individuals depending on the interaction of genetic and environmental factors, the contribution for each varying with the specific rheumatic disorder. However, a third variable, i.e., random or stochastic processes, may be important, but this has been poorly studied. We examined 3 rheumatic disorders to determine whether a simple stochastic process might be consistent with the incidence data. METHODS: A questionnaire and clinical survey of patients with ankylosing spondylitis, rheumatoid arthritis, and systemic sclerosis was performed to determine age at onset of first symptom. Population data were obtained from the Australian Bureau of Statistics. Computer modeling of the equation dN/dt = kP0 tr-1exp(-ktr/r) was performed, where dN/dt is the age-specific incidence rate, P0 is the proportion of population at risk, t is the age at onset, k is a constant, and r is the number of random events that must occur before the disease manifests. RESULTS: Analysis of the age-specific incidence for each of these 3 rheumatic disorders was consistent with the stochastic model, where r varied from 4 to 9. CONCLUSION: An examination of the age-specific incidence suggests that only a small number of random events need to occur in a predisposed population to allow the emergence of the rheumatic disorder. These random events might be environmental (e.g., infections or exposure to toxins) or due to acquired genetic changes (e.g., somatic mutations involving pivotal immune or growth/repair genes).
12407308 [Neurological manifestations of Whipple disease]. 2002 Oct Whipple disease is an uncommon chronic bacterial infection due to Tropheryma whipplei. Clinical manifestations are protean (joint pain, fever, weight loss, abdominal pain, lymphadenopathies), and the diagnosis is often delayed. Although previously considered a late manifestation of Whipple disease, neurological involvement is now frequently the initial clinical manifestation and represents the greatest risk for long-term disability. All patients should be treated and monitored as if they had central nervous system disease even if they are asymptomatic. Neurological manifestations include dementia (56 percent), abnormalities of eye movements (33p. cent), involuntary movements (28 percent), seizures, hypothalamic dysfunction, myelopathy, ataxia and psychiatric manifestations. Uveitis, retinitis, optic neuritis and papilloedema may be found. 80 percent of the reported cases of neuro-Whipple had associated systemic symptoms or signs but many patients are presenting without concurrent intestinal manifestation. Thus, the disease may remain undiagnosed or misdiagnosed, as rheumatoid arthritis or sarcoidosis. Traditionally, the diagnostic procedure of choice is biopsy of the duodenal mucosa by demonstrating PAS-positive foamy macrophages. However, not all cases have small bowel infiltration and tissue obtained from sites clinically affected may be helpful. CT and MR images of the central nervous system are normal or not specific: atrophic changes, mass lesions, focal abnormalities and hydrocephalus. The application of a PCR assay against Tropheryma whipplei has transformed the diagnosis. Positive results have been obtained from several tissues and from CSF and PCR is more sensitive than other techniques. All patients must be treated with antibiotics which cross the blood-brain barrier. Most agree that initial treatment with a combination of parenteral penicillin and streptomycin for at least 14 days is appropriate, thereafter cotrimoxazole orally 3 times a day for at least one and probably for two years. Third generation cephalosporins, rifampicin and chloramphenicol have been used successfully. PCR is recognized to be a useful tool for monitoring progress but it is sometimes difficult to reverse established neurological defects.
12369779 Localization of the mutation responsible for osteopetrosis in the op rat to a 1.5-cM genet 2002 Oct Osteopetrosis is caused by a heterogenous group of bone diseases that result in an increase in skeletal mass because of inadequate osteoclastic bone resorption. In the op osteopetrotic rat, the disease has been linked to a single genetic locus located at the proximal end of rat chromosome 10. In this study, we identified a 1.5-cM genetic interval that contains the mutation. We then generated an improved radiation hybrid (RH) map of this region to identify potential functional and positional candidates for the op gene. Using the rat genome radiation hybrid panel, we mapped 57 markers including 24 genes (14 that have not yet been mapped in the rat) and 10 expressed sequence tag markers. Included in the mapped genes are several candidate genes that might significantly influence the biochemical pathways involved in osteopetrosis. These include genes involved in osteoclast differentiation, apoptosis, and the functional capabilities of mature osteoclasts to resorb bone. Further analysis of the genes and expressed transcripts mapped to this region may yield important insights into the multifactorial control of osteoclast function and the mechanisms of failed bone homeostasis in diseases such as osteopetrosis, osteoporosis, and rheumatoid arthritis in which failed bone homeostasis is an instigating or exacerbating circumstance of the disease process.
12361838 Chloroquine cardiotoxicity: clinicopathologic features in three patients and comparison wi 2002 Sep BACKGROUND: Microscopic features of chloroquine cardiotoxicity are similar to those of Fabry disease. The purpose of the study was to compare clinicopathologic findings in both disorders. METHODS: Patients with a diagnosis of chloroquine cardiotoxicity or Fabry disease were identified who had undergone endomyocardial biopsy or autopsy at Mayo Clinic Rochester (1976-2000). Clinical information was collected from medical records and letters from referring physicians. Light and electron microscopy were performed in all cases. RESULTS: Three patients (two women, one man) with chloroquine cardiotoxicity ranged in age from 53 to 73 years. Chloroquine was given for rheumatoid arthritis in two and systemic lupus erythematosus in one. Three patients (two men, one woman) with Fabry disease ranged in age from 58 to 76 years. Two had angiokeratomas, but only one had a previous diagnosis of Fabry disease. All six patients presented with dyspnea. Light microscopy from all six revealed myocyte enlargement due to perinuclear vacuolization. By transmission electron microscopy, all six showed abundant myelinoid figures within involved myocytes. Curvilinear bodies were observed in two patients with chloroquine cardiotoxicity and in none with Fabry disease. CONCLUSIONS: Patients with cardiac dysfunction due to chloroquine cardiotoxicity or Fabry disease have similar ages, presenting clinical symptoms, cardiac light microscopy and sarcoplasmic myelinoid bodies ultrastructurally. Patients with Fabry disease may not have a personal or family history of the disease. Similarly, a history of chloroquine usage may not be known to the pathologist. In these settings, the presence of curvilinear bodies ultrastructurally is useful for the diagnosis of chloroquine cardiotoxicity.
12243507 The characteristics of cyclical and non-cyclical mastalgia: a prospective study using a mo 2002 Sep Breast pain (mastalgia) is a common condition (usually classified as cyclical or non-cyclical) the characteristics of which have never been studied using a standardized pain instrument. We have modified the short form of the McGill Pain Questionnaire (SF-MPQ) for the measurement of mastalgia, and have administered it to 271 women with breast pain and without breast cancer. The mean pain-rating index (sum of 15 descriptors of SF-MPQ) was similar between cyclical and non-cyclical pain, and was 12.0 (of 45) for the entire group. When compared to similar studies of pain at other sites, this falls in the same range as chronic cancer pain, and just below the pain of rheumatoid arthritis. Mean %VAS (visual analog scale) was 45.12 and mean %PPI (present pain index) was 39.9. Most women described their pain as 'heavy, aching and tender,' and these descriptors were given significantly higher ratings by women with cyclical pain. In women with non-cyclical mastalgia, the overall pain severity was related to the size of the painful area, and the steadiness of the pain, and the affective components were more prominent than in women with cyclical mastalgia. Thus, cyclical and non-cyclical mastalgia show some differences in their characteristics with substantial overlap. The total breast pain score was most efficiently estimated by a combination of the VAS, the PPI, and the quality of life questions (R2 = 0.96). Studies of breast pain should include both groups to better understand and characterize these differences, particularly with regard to a possible connection with breast cancer risk.
12207559 The role of neuroendocrine system in the pathogenesis of rheumatic diseases (minireview). 2002 Jun Interactions between the neuroendocrine and immune system play an important role in maintaining and restoring homeostasis. In susceptible individuals a dysfunction of the neuroendocrine system may be one of the risk factors involved in the pathogenesis of rheumatic diseases. Specific causes of altered neuroendocrine function are still not fully elucidated. Accumulation of genetical, environmental, behavioral and other risk factors during long preclinical period may result in chronic imbalances in homeostatic mechanisms maintained by neuroendocrine, microvascular and immune systems. Chronic inflammatory stress mediated by humoral and neural signals during active stages of the disease and autoantibodies against the structures of the neuroendocrine system may further participate in the neuroendocrine dysfunction. In a subset of patients with rheumatoid arthritis (RA), an assumed defect of the hypothalamic-pituitary-adrenocortical axis may be implicated in the pathogenesis. Results of some studies support the concept of adrenal dysfunction in women with premenopausal onset of the RA. Significantly lower levels of dehydroepiandrosterone sulfate (DHEAS) plasma levels of women who subsequently developed RA indicate that neuroendocrine dysfunction may be present already in preclinical period and thus are not only secondary due to ongoing inflammatory process. These findings are sketching the new prospects of possible primary prevention of RA in the future. The role of some other hormones including prolactin, growth hormone, sex hormones and involvement of autonomic nervous system in relation with the rheumatic diseases is also reviewed in the paper. Further research concerning their role in the pathogenesis of other rheumatic diseases will possibly provide new prospects in optimizing their therapy.
12097786 Daily hassles reported by chronic fatigue syndrome and fibromyalgia patients in tertiary c 2002 Jul BACKGROUND: This study aimed at providing insight in the frequency, emotional impact and nature of daily hassles, experienced by patients suffering from chronic fatigue syndrome (CFS) and/or fibromyalgia (FM), compared with patients with a chronic organic disease. METHODS: One hundred and seventy-seven CFS/FM patients, 26 multiple sclerosis (MS) and 26 rheumatoid arthritis (RA) patients were investigated within 2-6 months after diagnosis. All patients completed a self-report questionnaire assessing daily hassles and associated distress, a visual analogue scale assessing fatigue and pain and a depression and anxiety questionnaire. RESULTS: CFS/FM patients show a higher frequency of hassles, higher emotional impact and higher fatigue, pain, depression and anxiety levels compared with MS/RA patients. Three hassle themes dominate in the CFS/FM group: dissatisfaction with oneself, insecurity and a lack of social recognition. In contrast, hassles reported by MS/RA patients show a much larger diversity and are not focused on person-dependent problems. CONCLUSIONS: Patients recently diagnosed as suffering from CFS and/or FM are highly preoccupied and distressed by daily hassles that have a severe impact on their self-image, as well as their personal, social and professional functioning. An optimal therapeutic approach of CFS and FM should take account of this heavy psychosocial burden, which might refer to core themes of these patients' illness experience.
12064830 Treatment of chronic knee synovitis with arthroscopic synovectomy: longterm results. 2002 Jun OBJECTIVE: We examined the longterm results of arthroscopic synovectomy in chronic knee synovitis of rheumatoid arthritis (RA). METHODS: Forty-one knees of 38 patients (30 women, 8 men), mean age of 42.7 +/- 15.3 years, were evaluated clinically and radiographically at a mean 8.9 years (range 5.0-12.3) after arthroscopic synovectomy. Arthroscopic synovectomies were always performed with a shaver by the same physician after failure of at least one radioactive or chemical synovectomy. Radiographs were blindly read by 2 examiners. RESULTS: At the final evaluation, the clinical results (pain, range of motion, recurrent effusion) were good in 29 cases (70.7%) and poor in 12 cases (knee arthroplasty was required in 11 cases). Radiographs highlighted significant progression of joint damage (more than one Larsen score grade) in 16 knees (39.0%). No radiographically detectable change was observed in 12 cases (29.3%), and 11 knees (26.8%) had a change of only one Larsen score grade. There was a close correlation between the Larsen score at final examination and both Larsen score and arthroscopic score for cartilage damage at baseline. Only 4 knees (22%) with grade 0 or I on preoperative radiographs had significant progression of joint damage, compared to 12 knees (57%) with Larsen scores of 2 or 3 at baseline. CONCLUSION: These data suggest that arthroscopic synovectomy is a useful alternative treatment for chronic knee synovitis in RA after failure of radiation or chemosynovectomy, and that less severely damaged joints deteriorate less rapidly after synovectomy.
12063123 Specific interactions between cryogel components: role of extra domain A containing fibron 2002 Jun 18 Cryogel is a physical gel formed by heterophilic aggregation of extra domain A containing fibronectin [EDA(+)FN], plasma fibronectin (pFN), fibrinogen (Fbg) and heparin (Hep), which are found in high concentrations in the blood of patients suffering from rheumatoid arthritis. In this study, we clarify the specific interactions between cryogel components in terms of the affinity constant (K(A)), obtained by surface plasmon resonance (SPR). It is found that Fbg self-interactions occur at lower temperatures, and that K(A) of Fbg-Hep changes with temperature. Specifically, K(A) (2.0 x 10(8) [M(-1)]) of Fbg-Hep at 5 degrees C increases significantly from that (1.0x10(7) [M(-1)]) at 40 degrees C. K(A) of EDA(+)FN-Hep increases with temperature, by approximately 100-fold between 40 degrees C (K(A)=10(12) [M(-1)]) and 20 degrees C (K(A)=10(10) [M(-1)]). Although K(A) of the FN fragments of Hep-binding domain containing an EDA region [EDA(+)HBD(+)] and Hep increases with temperatures above 30 degrees C, K(A)s of HBD(+)-Hep and EDA(+)-Hep are not temperature-dependent. Therefore, EDA(+)HBD(+), formed as a special structure for high Hep affinity, exhibits temperature-dependent interaction with Hep. These results suggest that the main role of EDA(+)FN in cryogelation is to support the interaction with Hep.
15685387 A review of the use of infliximab to manage cutaneous dermatoses. 2004 Mar BACKGROUND: Infliximab is a chimeric monoclonal antibody that binds specifically to human tumor necrosis factor-alpha (TNF-alpha), decreasing the effect of the cytokine in inflammatory diseases. OBJECTIVE: The aim of this study was to review the efficacy and safety of infliximab in the treatment of dermatological diseases. METHODS: A MEDLINE search (1966-January 2003), using the keyword "infliximab" was performed to find relevant articles pertaining to the use of infliximab in dermatology. RESULTS: Infliximab has been used in the following dermatological diseases: psoriasis, Behcet's disease, graft versus host disease, hidradenitis suppurativa, panniculitis, pyoderma gangrenosum, SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome, sarcoidosis, subcorneal pustular dermatosis, Sweet's syndrome, toxic epidermal necrolysis, and Wegener's granulomatosis. There is a generally good safety profile for infliximab, which is similar to that when it is used to treat Crohn's disease and rheumatoid arthritis. CONCLUSION: Although not approved for use in dermatological diseases, there have been numerous reports of the efficacy of infliximab in cutaneous inflammatory diseases. The most promise lies in those diseases that have increased amounts of TNF-alpha in the cutaneous lesions, such as psoriasis.