Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2460416 | The influence of synovial fluids from patients with rheumatic diseases on chick embryo fib | 1988 | Primary chick-embryo fibroblasts (PCEF) were used as target cells to measure the influence of synovial fluids of patients suffering from osteoarthritis (OA; n = 5), rheumatoid arthritis (RA; n = 12) and psoriatic arthritis (PA; n = 2). The following metabolic cell products were measured: DNA, RNA, glycosaminoglycans (GAG), sulfated glycosaminoglycans, protein and collagen, with the same joint effusions being used in each test. Since it is not a single substance that provokes a stimulating or inhibiting effect in the joint, the crude synovial fluids were applied in these preliminary experiments. It was found that each type of synovial fluid showed an influence on the biological processes in the PCEF. The DNA, RNA and GAG syntheses were strongly influenced by the joint effusions, in contrast to the protein, collagen and sulfated glycosaminoglycan syntheses which were less affected. Generally, the nucleic acid synthesis differed significantly between the OA, RA and PA synovial fluids. The addition of heparin to the synovial fluids caused an additive inhibiting effect on the DNA synthesis but did not influence the other biochemical parameters. The synovial fluids of RA patients, and to a much greater extent those of PA patients, inhibited the thymidine incorporation whereas OA synovial fluids had a less pronounced effect. This result indicates a disease-dependent composition of the synovial fluids. RNA synthesis was diminished in all three groups, but again this effect was strongest in the case of the PA synovial fluids. GAG synthesis was markedly stimulated by the PA synovial fluids and somewhat, though to a lesser extent, by the OA and RA synovial fluids. The sulfated glycosaminoglycan synthesis in the PCEF, as revealed by 35S incorporation into the GAG, was less influenced and on the whole stimulated by the OA and RA synovial fluids. The same trend could be observed with regard to the collagen synthesis. The intracellular protein synthesis was less influenced by the OA (91.9%) and more strongly suppressed by the RA (78.7%) and the PA (76.7%) synovial fluids. PCEF therefore appear to be a convenient and sensitive target cell system to study alterations of biochemical processes caused by crude synovial fluids and also of different origin by individual factors isolated from synovial fluids. | |
| 2590802 | Effects of aerobic conditioning in lupus fatigue: a pilot study. | 1989 Dec | Fatigue, a complex symptom, significantly affects the quality of life in many patients with systemic lupus erythematosus (SLE). To understand this phenomenon, 23 patients with SLE and fatigue were studied. Standardized tests of depression (NIMH), fatigue, exercise tolerance (ETT) on a bicycle ergometer, and SLE activity were obtained. At baseline, SLE patients had significantly lower maximum oxygen consumption (VO2 max) than normals (p less than 0.005). Adjusted for age and sex, SLE patients perform at 54% of their expected maximum VO2, which is similar to published data from patients with rheumatoid arthritis. Depression by NIMH was not correlated with VO2 max or length of time on ETT. Fatigue measured by Profile of Mood States (POMS) was correlated with ETT time (r = 0.476, p less than 0.025) and with VO2 max (r = -0.402, p less than 0.07). After an 8-week aerobic conditioning programme the experimental group increased their aerobic capacity by 19% in contrast to 8% in controls. This change correlated with decreased fatigue as measured by visual analogue scales. Exercise did not exacerbate disease, and only two of 16 experimental subjects experienced transient joint symptoms during exercise. | |
| 2344264 | The importance of functional magnetic resonance imaging (MRI) in the planning of stabilizi | 1990 | Chronic inflammatory diseases, such as chronic polyarthritis or spondylarthritis ankylopoietica, can occasionally lead to vertebral instabilities of the occipitoatlantal or atlantoaxial level, requiring some form of stabilizing operation. By means of functional magnetic resonance imaging, i.e., with the cervical spine at its maximal range of flexion and extension, performed on 11 patients suffering from an instability at the above level, it was possible to demonstrate not only the extent of synovial tissue, but also how this sometimes excessive soft-tissue growth hinders an adequate reduction of the subluxated vertebrae. The importance of this investigation lies in the fact that the necessary operation can be planned appropriately. As such, three patients required a decompressing operation entailing resection of the posterior arch of the atlas, widening of the foremen magnum, or both. | |
| 1698273 | Conjunctival cytologic features of primary Sjögren's syndrome. | 1990 Aug | To determine whether there are specific cytologic features associated with primary Sjögren's syndrome (SS), the authors evaluated impression cytology specimens from three conjunctival sites (temporal bulbar [TB], inferior bulbar [IB], and inferior tarsal [IT]) from 38 SS eyes, 34 eyes of aqueous tear-deficient patients without SS, 35 eyes of seborrheic blepharitis patients, and 17 eyes of normal controls in a masked fashion. The following features were observed more frequently in SS eyes than in the eyes of the other groups: squamous metaplasia of the TB and IB (P less than 0.05), extensive (greater than 75%) goblet cell loss of the TB (P less than 0.05), mucous aggregates of the bulbar conjunctiva (P less than 0.05), and inflammatory cells intercalated with epithelial cells on the IT conjunctiva (P less than 0.06). The conjunctival inflammatory cell infiltrate correlated with the presence of extensive squamous metaplasia (P less than 0.01) in SS specimens. The inflammatory cells on the IT conjunctival epithelium were found to consist predominantly of T-lymphocytes by immunofluorescent staining of cytologic specimens from six eyes. Based on these findings, the authors speculated that conjunctival squamous metaplasia, in addition to aqueous tear deficiency, may be due to primary involvement of the dysfunctional immune system of SS. | |
| 2031665 | Subacute cutaneous lupus erythematosus-immunogenetic associations. | 1991 Feb | Thirty-two patients who fulfilled criteria for subacute cutaneous lupus erythematosus (SCLE) were examined for their immunogenetic associations. Our results confirm the previously reported association of HLA-DR3 (15/31 48% P less than 0.01) and also demonstrate an increase in HLA-DR2 (14/31, 45%, P = less than 0.05). These findings indicate there are two distinct immunogenetic (HLA) populations of Ro(SS-A) antibody-positive SCLE patients. The increased frequency of HLA-DR2 and DR3 appears to be associated with expression of the Ro(SS-A) antibody, since no HLA associations were seen in Ro(SS-A)-negative SCLE patients when compared with normal population controls. Furthermore, these data indicate that the distinctive cutaneous lesions of SCLE are not associated with one specific HLA allele, as previously suspected. These findings contrast with the relatively homogeneous immunogenetic background seen in other lupus erythematosus subsets with a high frequency of Ro(SS-A) antibody, i.e., neonatal lupus erythematosus and Sjögren's syndrome/lupus erythematosus overlap (increased frequency of HLA-DR3, DQw2 and DRW52). | |
| 2844672 | Antiarthritic synergism of combined oral and parenteral chrysotherapy. II. Increased inhib | 1988 Aug | We have observed an antiarthritic effect of combined chrysotherapy in adjuvant arthritis. Since superoxide radicals (O2-) are potent mediators of rheumatoid inflammation, we studied the combined effect of auranofin (AF) and injectable golds on luminol-dependent chemiluminescence (LDCL) and O2- generation by cytochrome-c reduction of activated leukocytes by different receptor-mediated stimuli: phorbol myristic acetate, 10(-6) M; f-Met-Leu-Phe, 10(-6) M; and poly-L-histidine, 10(-5) M. AF, 0.6 and 0.9 micrograms Au/ml, inhibited 34 and 58% of O2- generation, respectively; the addition to AF of 0.3 micrograms Au/ml of gold thiosulfate (GTS) increased this inhibition to 84 and 97% of the oxygen burst. Similar synergistic potentiation inhibition was obtained by LDCL. When the inhibition of O2- generation by the combined action of AF and GTS was compared with AF + gold sodium thiomalate (GTM), only GTS showed an activation on AF's inhibition of the oxygen burst of human leukocytes. The ligand thiosulfate in equimolar concentrations to GTS had a statistically significant (P less than 0.01) inhibitory effect on AF's blockade of O2- generation during the first 5 min of the interaction with the PMNs; thiomalate had no effect. Sequential pretreatment of PMNs with AF and GTS on O2- generation revealed that for synergism of combined gold action to take place, the cell membrane had to be subjected first to the action of oral gold or to the simultaneous combined action of oral and parenteral gold.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 1976627 | A novel transglutaminase-mediated post-translational modification of phospholipase A2 dram | 1990 Oct 5 | Transglutaminases (TG), which include coagulation Factor XIIIa, are calcium-dependent ubiquitous enzymes. TGs catalyze the formation of an isopeptide bond by cross-linking a specific glutamine and a lysine residue between two proteins or within the same protein molecule. Phospholipase A2 (PLA2) is a key enzyme in the regulation of prostaglandin and leukotriene biosynthetic pathways, which catalyzes the release of free fatty acids from the sn-2 position of membrane glycerophospholipids. This enzyme has been suggested to be pathophysiologically related to the initiation and propagation of several inflammatory diseases including juvenile rheumatoid and rheumatoid arthritis. Here, we describe a novel TG-catalyzed post-translational modification of PLA2 which dramatically increases the activity of this enzyme. This increase was dependent upon the time of preincubation, the concentration of TG and the presence of Ca2+. Size exclusion chromatography of TG-treated PLA2 yielded two peaks of PLA2 activity, with apparent molecular masses of 26 and 13 kDa, respectively. The 26-kDa species, a putative PLA2 dimer, contained epsilon-(gamma-glutamyl)-lysine isopeptide in about 1:1 molar ratio to PLA2, suggesting an intramolecular rather than intermolecular cross-linking. This hypothesis was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the 26- and 13-kDa species under denaturing conditions. The specific activity of the dimeric peak was 10-fold higher with respect to that of the monomeric enzyme. These data suggest that TG-catalyzed covalent cross-linking of PLA2 is intramolecular and that this may promote a noncovalent dimerization and subsequent activation of this enzyme via a conformational change. To our knowledge, this is the first demonstration that TG-mediated post-translational modification of an enzyme (e.g. PLA2) causes a striking increase in the catalytic activity of the enzyme. | |
| 2703725 | Perturbation of experimental ultraviolet light-induced erythema by passive transfer of ser | 1989 Apr | Several lines of investigation have implicated anti-Ro/SS-A antibody in the pathogenesis of photosensitive forms of cutaneous lupus erythematosus such as neonatal lupus erythematosus and subacute cutaneous lupus erythematosus. To further explore this possibility, we have developed a quantitative, experimental system for examining the effect of passively transferring anti-Ro/SS-A antibody-containing and antibody-deficient subacute cutaneous lupus erythematosus patient sera on one aspect of cutaneous photoreactivity, UV-induced erythema. Laser-Doppler velocimetry was used to quantitate the microvascular flow rates in normal control, disease control (rheumatoid arthritis, discoid lupus erythematosus), and subacute cutaneous lupus erythematosus serum-injected guinea pig skin test sites before and after combined ultraviolet B and A radiation from a solar simulator. Results, expressed as change in milli-electron voltage (perturbed milli-electron volts after irradiation minus baseline milli-electron volts before irradiation), revealed that subacute cutaneous lupus erythematosus serum injections consistently resulted in greater UV-induced microvascular flow rates than those elicited by normal or disease control serum injections. Anti-Ro/SS-A containing subacute cutaneous lupus erythematosus sera produced the greatest flow rates observed in this study. Earlier studies have suggested that the pathogenesis of lupus photosensitivity is very likely multifactorial. Our current data suggest that anti-Ro/SS-A autoantibody or other closely related humoral elements should also be considered among the factors which might contribute to this clinical phenomenon. | |
| 1998235 | [Leukotrienes. A review of the significance for disease in man and the possibilities for t | 1991 Jan 14 | The leukotrienes constitute a group of 5-lipoxygenase catalyzed metabolites of arachidonic acid, the cellular effects of which may be divided into two broad categories. Leukotriene B4 is predominantly a leukocyte stimulant, and has recently been observed to represent the inflammatory cell component of a mutual activation mechanism between inflammatory cells and the immune system. It is thus anticipated that LTB4 acts as an inflammatory mediator and immune regulator in a variety of immune-mediated disorders. The presence of LTB4 in inflamed tissues from patients with psoriasis, rheumatoid arthritis and chronic inflammatory bowel disease renders it probable that the novel class of 5-lipoxygenase inhibitors and LTB4 antagonists will be capable of influencing the clinical course of these diseases. The other main group is comprised of leukotrienes C4, D4 and E4, collectively known as slow reacting substance of anaphylaxis leukotrienes, and has been identified primarily in immediate hypersensitivity conditions, e.g. bronchial asthma in which the smooth muscle contractile and permeability increasing properties of SRS-A appears to contribute to the early bronchoconstrictor phase. Leukotriene D4, however, may also be involved in the late reaction mediated by inflammatory cells, since it has the ability to immobilize neutrophils attracted by LTB4 to the inflammatory focus. The ultimate elucidation of the importance of leukotrienes in different diseases awaits the outcome of clinical trials with the newly developed highly potent and specific 5-lipoxygenase inhibitors and leukotriene antagonists. | |
| 2290159 | Hypophospholipasemia A2 in systemic sclerosis. | 1990 Sep | Phospholipase A2 (PLA2), total and pancreatic, were quantitated in 91 sera of patients with systemic sclerosis (SSc). The mean total PLA2 of 216 +/- 161 U/ml (SD) was significantly lower (p less than 0.001) than in controls (317 +/- 128 U/ml). In 55 of 91 patients (60%) PLA2 was more than 1 SD and in 6 (7%) more than 2 SD below the normal mean. Serum pancreatic PLA2 was also significantly lower in SSc. The prevalence of low serum total PLA2 was significantly greater (p less than 0.001) than in healthy adults, or in patients with rheumatoid arthritis, systemic lupus erythematosus or vasculitis. Repeat assays of PLA2 activity in 10 patients with SSc documented persistence of low PLA2. Among 76 patients with SSc with complete clinical and laboratory assessment, there were 48 with low and 28 with normal (or slightly elevated) PLA2. These 2 groups showed no differences in disease manifestation or therapy. The group with low serum PLA2 had lower erythrocyte sedimentation rates (p less than 0.0005) and lower neutrophil (p less than 0.05) and monocyte counts (p less than 0.025) in the peripheral blood. The finding of low serum PLA2 activity adds to the spectrum of arachidonic acid pathway abnormalities associated with SSc, and may in part be related to the paucity of inflammatory changes observed in this disease. | |
| 2189154 | Polymyalgia rheumatica. | 1990 May | Polymyalgia rheumatica is a syndrome that occurs in the elderly and is characterized by pain and stiffness involving the neck, the shoulder girdle, and the hip girdle. The aching should be present for greater than one month. Polymyalgia rheumatica may be more common than reported. The etiology remains unknown. There is generally little found pathologically in this disease. The physical examination is often not impressive. Synovitis may be a main contributing factor to many of the symptoms seen in patients with polymyalgia rheumatica. Symptoms often do not correlate with physical findings. Polymyalgia rheumatica must be differentiated from many conditions since the diagnosis remains entirely clinical. Osteoarthritis, flu syndromes, inflammatory myopathies, fibromyalgia, and depression all have features that may mimic polymyalgia rheumatica. Malignancies and infections may also be difficult to separate from polymyalgia rheumatica. Polymyalgia rheumatica may also be extremely difficult to differentiate from seronegative rheumatoid arthritis in patients older than 50 years. Although some patients with polymyalgia rheumatica have underlying giant cell arteritis, the majority apparently do not. The distinction between polymyalgia rheumatica and giant cell arteritis cannot be made on the basis of laboratory studies and relies solely on clinical symptoms and physical findings. Although nonsteroidal antiinflammatory medications may control symptoms in patients with mild disease, most patients with polymyalgia rheumatica require low-dose corticosteroids. The tapering schedule for the corticosteroids is contingent upon the response of symptoms and laboratory parameters. Polymyalgia rheumatica usually follows a benign course with almost complete response to an adequate treatment program. Recently, there have been several studies suggesting that the course of polymyalgia rheumatica may not be as short and simple as once proposed. Nevertheless, many patients may be completely weaned from corticosteroids. Other agents have been used in this disease, but for the most part their use remains somewhat controversial. Patients must be monitored carefully. Most patients do well, and treatment is effective. | |
| 2785704 | Stimulation of interleukin 6-like B-cell differentiation factor production in human adhere | 1989 Mar | Abnormal production of immunoglobulin in the joint space is frequently observed in patients with rheumatoid arthritis (RA). We have previously demonstrated that adherent synovial cells (ASC) from patients with RA are involved in B-cell differentiation by their spontaneous production of B-cell differentiation factor (BCDF). The regulation of the production of this factor, however, has not yet been described. We investigated the effects of recombinant interleukin 1 alpha and beta (rIL-1 alpha and rIL-1 beta) on the production of BCDF in ASC. Increased production of BCDF was observed with increased rIL-1 concentration. Production of BCDF was detected 3 h after exposure of ASC to rIL-1 and increased throughout a 48-h culture. This BCDF, assayed on SKW6-CL4 cells, was found to share a common active site with interleukin 6. The effect of rIL-1 was almost neutralized by anti-IL-1 antibody and the addition of polymyxin B did not diminish the effect of rIL-1, indicating that rIL-1 itself stimulates ASC in vitro. These results suggest that IL-1 may play a regulatory role in the production of BCDF in synovial tissue. | |
| 2465489 | Common epitopes in Clq and collagen type II. | 1989 Feb | An epitope common for collagen type II and Clq was demonstrated by specific binding of a monoclonal anti-collagen type II antibody, MAb B1, to purified Clq. This was further substantiated by the affinity shown between F(ab')2 fragments of anti-Clq antibodies and rat chondrosarcoma collagen type II. The interaction between MAb B1 and Clq was demonstrated in hemolytic assays, in an enzyme-linked biotin-avidin assay and by the binding of Clq to MAb B1 immobilized on Sepharose 4B beads. MAb B1 recognized only purified Clq and not the macromolecular Cl complex, indicating that the epitope for MAb B1 was situated in the collagen-like region in Clq, where Clq and Cls are anchored. The binding of the purified collagen-like fragment of Clq to radiolabelled MAb B1 confirmed these findings. The affinity between MAb B1 and Clq was significantly increased if Clq was first reacted with heat aggregated IgG, indicating a demasking of the reactive epitope on binding to the aggregated IgG. The present findings raise the question of the pathogenetic significance of the presence of anti-collagen type II antibodies and free Clq, both of which are frequently seen in high amounts in rheumatoid arthritis. | |
| 2888867 | Photolytic degradation of benorylate: effects of the photoproducts on cultured hepatocytes | 1987 May | The photodegradation of benorylate [4'-(acetamido)phenyl-2-acetoxybenzoate], a drug frequently used in rheumatoid arthritis therapy, has been examined under different sets of experimental conditions. Several photoproducts have been isolated and identified on the basis of their IR, NMR, and MS spectra. The most significant photochemical process is the photo-Fries rearrangement of benorylate, leading to 5-acetamido-2'-acetoxy-2-hydroxybenzophenone (1). This compound undergoes a rapid transacylation to the isomeric 5'-acetamido-2'-acetoxy-2-hydroxybenzophenone (2). A primary culture of rat hepatocytes has been used to evaluate the possible toxicity of these two benzophenones, keeping in mind the following criteria: leakage of cytosolic enzymes, attachment index to culture plates, gluconeogenesis from lactate and fructose, glycogen balance, and albumin synthesis. At the concentrations assayed, neither of the two major photoproducts of benorylate (benzophenones 1 and 2) had significant toxic effects on liver cells in culture. | |
| 3776436 | Enzyme-linked immunosorbent assay of autoantibodies reacting with thyroid plasma membrane | 1986 Oct | A sensitive and specific enzyme-linked immunosorbent assay (ELISA) for the detection of autoantibodies reacting with thyroid plasma membrane antigens has been established. Autoantibodies reacting with thyroid plasma membrane antigens were detected by the ELISA in 95% of untreated hyperthyroid Graves', 68% of antithyroid drug-treated Graves' up to four months of the therapy, in 62% of Hashimoto's thyroiditis and in 8.9% of toxic nodular goitre. The ELISA was negative in 100% healthy blood donors, 100% non-toxic nodular goitre, in 12 patients with rheumatoid arthritis, 18 patients with scleroderma and 94% of patients with systemic lupus erythematosus. The mean value of autoantibodies titre was higher in untreated hyperthyroid Graves' (1:84,000) and lowest in positive patients with autoimmune disease of non-thyroid origin (1:4000). The cross-reactivity of antimicrosomal antigen antibodies was below 10%; there was no influence of antithyroglobulin antibodies on the ELISA; and most of the autoantibodies react with plasma membrane antigens different from the TSH binding sites. | |
| 2425596 | Auranofin modulates mast cell histamine and polymorphonuclear leukocyte collagenase releas | 1986 Apr | Auranofin, an orally gold preparation, effective in the treatment of rheumatoid arthritis, was found to be a potent noncytotoxic inhibitor of histamine and collagenase release from mast cells and polymorphonuclear (PMN) leukocytes respectively. Histamine release has been inhibited by auranofin in dose-dependent fashion. Auranofin at concentration of 10(-5) M inhibited 100% of the release, lower concentration 10(-6) M and 10(-7) M produced 80 and 40% decrease. The exposure of PMN-leukocytes to auranofin caused also dose-dependent inhibition of collagenase release. Auranofin at a concentration of 10(-4) M produced a marked reduction (75-100%) of enzyme release from human and rat blood PMN-leukocytes. The modest inhibition 40 and 15-20% at a concentration of 10(-5) M and 10(-6) M respectively was obtained. Auranofin more significantly suppressed collagenase release from leukocytes isolated from inflammatory exudate. Decrease of 100, 80 and 60% were observed upon addition of 10(-4) M, 10(-5) M and 10(-6) M of auranofin. These results suggest that therapeutic action of auranofin may be caused, at least in part, by the inhibition of cellular release of histamine and collagenase in the course of inflammation. | |
| 2090485 | Subclinical alveolitis in immunological systemic disorders. Transition between health and | 1990 Nov | A subclinical inflammatory alveolitis as assessed by BAL cell analysis may be present in a high proportion of symptomless patients with immunological systemic disorders and with normal chest roentgenogram. Subclinical alveolitis can be characterized by the relative proportions of the different cell populations comprising the alveolitis and by the activated state of the cells. Thus, subclinical alveolitis can be classified into two major groups: lymphocyte and neutrophil alveolitis. Lymphocyte alveolitis is frequently found in patients with extrathoracic granulomatosis (Crohn's disease, primary biliary cirrhosis, extrathoracic sarcoidosis) or with some collagen vascular diseases (Sjögren's syndrome, rheumatoid arthritis, systemic lupus erythematosus). Neutrophil alveolitis is a main finding in collagen vascular diseases, especially progressive systemic sclerosis, dermatopolymyositis and mixed connective tissue disease. In addition, alveolar macrophages may be spontaneously activated and release various mediators that could be relevant to the pathogenesis of interstitial lung disease. On the other hand, some other alveolar macrophage functions (antibacterial activity may be severely impaired in some diseases, for example systemic lupus erythematosus). Alveolar inflammation is associated with an increase in the permeability of the alveolar membrane responsible for an increased influx of blood proteins in the alveolar spaces. Although subclinical inflammation may also be detected by high resolution computed tomography (HRCT) scan and/or lung permeability scintigraphic studies, the significance and prognostic value remains unclear and clearly differs according to both the disease and the pattern of alveolitis. | |
| 2208285 | A nonsecretable cell surface mutant of tumor necrosis factor (TNF) kills by cell-to-cell c | 1990 Oct 19 | In addition to the induction of tumor regression, tumor necrosis factor (TNF) has been implicated as the causative agent in a number of pathologies, including cachexia, septic shock, rheumatoid arthritis, autoimmunity, and induction of HIV expression. We propose that this complex physiology might be manifest by different forms of TNF: the 17 kd secretory component, the 26 kd transmembrane form, or both. To determine whether the 26 kd form of TNF was biologically active and whether its biology differed from that of the secretory component, we generated uncleavable and solely secretable mutants of TNF and studied their biological activities. We found that an uncleavable mutant of the 26 kd cell surface transmembrane form of TNF kills tumor cells and virus-infected cells by cell-to-cell contact, and that TNF need not be internalized by its target to kill. Thus, the 26 kd integral transmembrane form of TNF may function in vivo to kill tumor cells and other targets locally in contrast to the systemic bioactivity of the secretory component. | |
| 2251435 | [Pneumopathy caused by methotrexate]. | 1990 | Methotrexate, an antifolate cytotoxic drug, is used in anticancer chemotherapy as well as an immuno suppressive in rheumatoid arthritis. It is responsible for numerous secondary effects, amongst which is a characteristic acute pneumonia known since 1969. This pneumonitis has been described in detail, up to the present time in 78 cases gathered in this review. The prevalence of this complication is estimated at around 7%. This pneumonia may occur whatever the age, indication for which methotrexate is prescribed, the route of administration of the product (including the intra-thecal route) and the dose. It includes dyspnoea, fever, (sometimes quite marked) and frequently an acute reversible respiratory failure. Radiologically the opacities are usually diffuse interstitial and symmetrical with a basal predominance with sometimes some confluence and occasionally a pleural reaction. In a small number of cases a transient mediastinal adenopathy has been described. Respiratory function tests show a rapidly developing restrictive syndrome accompanied by hypoxia and hypocapnia. Broncho-alveolar lavage is characterised by hypercellularity with a frank and apparently transitory lymphocytosis. Histologically the most frequent lesion sighted is an extensive acute granulomatous reaction with or without oedema. Most often the outcome is favourable (75% of cases). However 6 deaths due to respiratory failure have been reported. Even though there has not been any formal test, steroid therapy in high dosage seems to accelerate recovery. Progress to an irreversible pulmonary fibrosis is possible but rare. The mechanism of this drug related acute pneumonia is not known but would seem to resemble that of other granulomatosis. Besides this rapidly progressive pneumonitis, methotrexate is responsible for a very small number of cases of severe pulmonary oedema and of acute painful pleurisies. | |
| 1696081 | Immunomodulation by tachykinin neuropeptides. | 1990 | Substance P (SP) is an 11-amino-acid neuropeptide found in sensory neurons in the peripheral nervous system. In addition to having well-characterized functions as a peptide neurotransmitter, it also plays a major role in modulating inflammatory and immune responses. SP can alter the proliferative and physiological responses of both lymphocytes and macrophages. These effects are mediated by specific high-affinity SP receptors which have been characterized both kinetically and biochemically. The principle SP binding protein present on human lymphocyte cell membranes is a 58,000-MW hydrophobic glycoprotein. Cellular responses subsequent to the binding of substance P to its receptor that have been identified in various cell populations include phosphatidyl inositol turnover, arachidonic acid metabolism, immunoglobulin synthesis, and enzyme production and secretion. Evidence also suggests that SP modulation of inflammation is a factor in the pathophysiology of certain diseases such as rheumatoid arthritis. |