Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2267443 | [Membranous glomerulonephritis. Experience at the Instituto Nacional de la Nutrición Salv | 1990 Apr | The purpose of this retrospective study was to study the incidence of idiopathic and secondary forms of membranous nephropathy in our institution, its clinical course and progression to chronic renal failure, and the risk factors associated with it. Two hundred fourteen (16%) of the 1,287 renal biopsies obtained between 1962 and 1988 were primary glomerular diseases and 28 of this 214 (13%) were idiopathic membranous nephropathy. On the other hand 59 of 1,287 biopsies were membranous nephropathy of whom 28 were idiopathic, 27 secondary to systemic lupus erythematosus, 2 due to drugs, one associated with rheumatoid arthritis, and one more with breast cancer. The clinical picture was: nephrotic syndrome in 84%, hypertension in 15%, non-nephrotic proteinuria in 14%, chronic renal failure in 8.4%, and renal vein thrombosis in 6.3%. In the idiopathic group 75% of the patients were male while in the lupus group 85% were female. For the analysis of progression to chronic renal failure we excluded 5 patients with renal failure when the biopsy was taken, 2 because the nephropathy was due to drugs, one associated with breast cancer, and nine were within the first year of follow-up. Thus, for this analysis the group consisted of 22 patients with idiopathic form and 20 with systemic lupus erythematosus. The idiopathic and lupus groups were similar except for a lower serum albumin in the former. The progression to renal failure was seen in 9 patients: six in the idiopathic group and the other 3 in the lupus group; this difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2076188 | Reactivity of human tissues with monoclonal antibodies to myeloid activation and different | 1990 | We have characterized antimyeloid monoclonal antibodies (mAbs) produced to human rheumatoid arthritis (RA) synovial tissue macrophages (MPs) (8D7) and to lipopolysaccharide (LPS)-treated U937 cells (3D8). The 3D8 antigen is upregulated with LPS stimulation of monocytes/MPs and during monocyte maturation. The 8D7 antigen is upregulated on functionally distinct subpopulations of RA synovial tissue MPs. We used immunohistochemistry to determine the spectrum of reactivity of these unique mAbs on myeloid cell suspensions, monocytes, and mature tissue inflammatory and noninflammatory MPs. The antigens identified by the mAbs were characterized biochemically, by immunoprecipitation of solubilized 125I-labelled antigens from cell surfaces, and immunohistochemically by enzymatic digestion of myeloid cells followed by a cellular ELISA. MAb 3D8, characterized as an anti-CD13 antibody, recognizes a 150-170 kd antigen, has almost exclusive myeloid reactivity, but reacts with Langerhans' cells of the skin and thymus, pointing to shared antigens between these cells and MPs. Unlike 3D8 antigen, 8D7 antigen is strongly expressed in inflammatory states, being present on MPs in granulomata as well as in sarcoid lymph nodes. Both mAbs react with frozen and methanol-Carnoy's fixed, paraffin-embedded tissues and detect antigenic differences among human mononuclear phagocytes present in different anatomical sites and in varying stages of differentiation and activation. These mAbs should prove to be a valuable tool for studying heterogenous populations of myeloid cells. | |
| 1968905 | Activated peripheral blood mononuclear cells detected by murine monoclonal antibodies to p | 1990 Jan | Hybridoma producing monoclonal antibody to proliferating cell nuclear antigen (PCNA/cyclin) (TOB7, IgG1 kappa) was newly established. Using TOB7, PCNA was detected in the peripheral blood mononuclear cells (PBMC) in patients with systemic lupus erythematosus (SLE). Forty-four of 58 patients with SLE had PBMC expressing PCNA. The percentage of PCNA-positive PBMC in patients with SLE was 0-20% (mean: 2.63%) which was significantly higher (P less than 0.01) compared with normal controls (mean: 0.18%), patients with rheumatoid arthritis (mean: 0.83%), and patients with mixed connective tissue disease (mean: 0.38%). Patients with high numbers of PCNA positive PBMC tended to complicate pulmonary disorders (P less than 0.005), especially pulmonary fibrosis (P less than 0.005). In addition, the percentage of PCNA-positive cells in SLE patients correlated with the disease activity (r = 0.45, P less than 0.01). The lymphocyte subsets of PCNA-positive PBMC were examined, and most of those cells belonged to CD4- or CD8-positive T-cell populations in three lupus patients. Our findings indicate that PCNA-positive activated PBMC are present in SLE patients and the percentage of PCNA-positive PBMC may be used as an indicator of disease activity. | |
| 2680241 | Epoetin: human recombinant erythropoietin. | 1989 Nov | The chemistry, pharmacology, pharmacokinetics, clinical uses and efficacy, adverse effects, drug interactions, dosage and administration, and formulary considerations of epoetin are described. Erythropoietin, a glycoprotein hormone primarily synthesized in the kidney, is the chief regulator of red blood cell production. Erythropoietin concentrations increase in response to a hypoxic state, resulting in increased red blood cell formation, accelerated hemoglobin production, and premature movement of reticulocytes into the circulation. The human gene responsible for the production of erythropoietin recently was cloned, and the recombinant product--epoetin--has been made available through mass production. The apparent volume of distribution of i.v. epoetin approximates the assumed plasma volume both in healthy volunteers and in patients with chronic renal failure. Little is known about the metabolism and route of elimination of epoetin and erythropoietin. Epoetin recently was approved by the FDA for treatment of anemia associated with chronic renal failure. Clinical trials in patients receiving hemodialysis or peritoneal dialysis and in predialysis patients with renal dysfunction demonstrate epoetin's efficacy. Other potential indications include augmentation of blood production in patients enrolled in autologous blood donation programs and treatment of anemias associated with rheumatoid arthritis, sickle cell disease, acquired immunodeficiency syndrome, cancer, and premature birth. The most frequent adverse effect associated with epoetin therapy is the worsening or development of hypertension. Other adverse effects include thrombocytosis, hyperkalemia, rise in serum urea concentration, iron deficiency, and flu-like symptoms. No drug interactions with epoetin have been reported in humans. The recommended starting epoetin dosage in patients with chronic renal failure is 50-100 IU/kg three times weekly. Epoetin is available only as an injection for i.v. or s.c. administration. Epoetin provides a new therapeutic approach to the treatment of anemia associated with chronic renal failure in hemodialysis, peritoneal dialysis, and predialysis patients. Benefits of epoetin therapy include reduced need for blood transfusions, the amelioration of anemic symptoms, and an improved quality of life. | |
| 2547540 | The influence of intra-articular hyaluronic acid on PGE2 and cAMP of synovial fluid. | 1989 May | Prostaglandin (PG)E2, cyclic adenosine monophosphate (cAMP), white blood cells (WBC), total protein (TP), total complement activity (CH50) and beta-2-microglobulin (beta-2-m) were measured at baseline and after eight days in the synovial fluid (SF) of 16 patients affected with knee-joint effusion due to various arthropathies. The volume of SF was also calculated. Eight patients--4 with rheumatoid arthritis (RA), 2 with recurrent monoarthritis (RM) and 2 with osteoarthritis (OA) were randomly allocated to the treatment with intra-articular injection of Hyalgan (HA, Na-hyaluronate, 20 mg/2 ml), while eight patients having similar arthropathies--4 RA, 2 RM and 2 OA--were not treated (control group). In the patients treated with HA a significant reduction of SF volume (from 28.5 +/- 5.1 ml to 20.5 +/- 4.0 ml; p less than 0.02) and PGE2 (from 96.1 +/- 22.7 pg/ml to 66.2 +/- 14.5 pg/ml; p less than 0.05) was found, whereas cAMP concentration was significantly increased (from 4.5 +/- 0.7 pmol/ml to 7.2 +/- 1.2 pmol/ml; p less than 0.05). No significant variations were observed in the control group. Moreover, no differences in WBC count, TP and beta-2-m and CH50 were found in either group. These data could suggest an anti-inflammatory effect of HA that appears to be mediated by PG-inhibition as well as cAMP stimulation. | |
| 2561361 | Non-proteolytic activation of latent human neutrophil collagenase and its role in matrix d | 1989 | Collagenases are known to be associated with tissue destruction in chronic inflammatory diseases such as periodontal diseases and rheumatoid arthritis. Collagenases are secreted by circulating inflammatory cells (polymorphonuclear leukocytes and monocytes), resident mesenchymal cells and epithelial cells in latent forms, which can be activated by proteases and compounds reacting with protein thiol groups. We have studied here the effects of oxygen-derived free radicals (ODFR) on latent human neutrophil collagenase. Also, in order to elucidate the cellular sources of collagenases, the ability of human gingival crevicular fluid (GCF) collagenases both from adult periodontitis (AP) and localized juvenile periodontitis (LJP) patients to degrade soluble interstitial collagen types I and II was studied. ODFR generated by the xanthine oxidase/hypoxanthine system in the presence of trace amounts of iron and EDTA activated latent neutrophil collagenase to an equal extent as the known activators phenylmercuric chloride and gold thioglucose. ODFR activation was inhibited by desferoxamine and mannitol as well as by superoxide dismutase and catalase. Clear differences in the susceptibility of collagen types I and II to AP and LJP GCF collagenases were observed. AP GCF collagenase degraded type I and II collagens at equal rates, resembling the substrate-specificity of human neutrophil collagenase. LJP GCF collagenase degraded type I collagen considerably faster than type II collagen, which was only negligibly degraded. This corresponds to the substrate specificity of fibroblast collagenase. Zymographic evaluation of gelatinolytic proteases showed the presence of 90 and 68 kD gelatinases in both AP and LJP GCF. Non-proteolytic means apparently provide a potent activation pathway of neutrophil collagenase in vivo and the hydroxyl radical was identified to be one of the potent activating oxidants.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3571977 | Identification and specificity of a cDNA encoding the 70 kd mitochondrial antigen recogniz | 1987 May 15 | Mitochondrial autoantibodies are characteristic of the disease primary biliary cirrhosis (PBC), but the immunoreactive mitochondrial antigens have not been defined. We used a rat liver cDNA library in lambda gt 11-Amp3 to clone a 1370-base pair insert that coded for a polypeptide reactive with PBC sera. This insert was subcloned for expression into pBTA224, a plasmid vector in the same reading frame as lambda-Amp3. A positive clone, designated pRMIT, that expressed a fused polypeptide of 160 kd, was recognized by 25 of 25 sera from patients with PBC and none of 96 sera from normal persons or patients with systemic lupus erythematosus, rheumatoid arthritis, or chronic active hepatitis. This fused polypeptide was shown to correspond with the 70 kd mitochondrial autoantigen by several experiments. First, lysates of pRMIT in J101 absorbed out the 70 kd reactivity of PBC sera when probed against fractionated placental mitochondria. Second, affinity-purified antisera reactive with the fused polypeptide also reacted with the 70 kd mitochondrial antigen. Third, such affinity-purified antisera produced the characteristic anti-mitochondrial pattern of immunofluorescence on tissue sections. Finally, immunization of BALB/c mice with the fused polypeptide elicited antibodies to mitochondria. These murine antibodies reacted with the 70 kd mitochondrial protein and also produced typical mitochondrial immunofluorescence on tissue sections. The nucleotide and amino acid sequence of the recombinant protein, which encodes for approximately a 48 kd protein, showed no significant homologies with known proteins, and there were no homologies with mitochondrial genomic DNA. The availability of a recombinant form of the 70 kd mitochondrial autoantigen will allow several definitive questions to be addressed in PBC, including identification of B cell epitopes, T cell recognition, and a model of PBC in mice. | |
| 3106619 | Regulation of heme metabolism and monooxygeneses in liver and kidney: influence of therape | 1987 May | Two gold compounds, gold sodium thiomalate (AuTM) and auranofin (AF) are presently in clinical use in therapy of rheumatoid arthritis. The effects of varying doses of AF administered to rats by either the p.o. or the i.p. route on heme metabolism were determined. Twenty four hours after a single dose of AF, decreases in the sulfhydryl-containing enzymes, delta-aminolevulinic acid dehydratase and ferrochelatase activities were observed in the liver and kidneys. These decreases in heme biosynthetic enzymes were accompanied by decreases in cytochrome P-450-dependent enzymic activities and increases in microsomal heme oxygenase activity. These changes were observed with AF dosages as low as 5 mg/kg, with maximal changes occurring at a p.o. dose of about 15 mg of AF per kg and an i.p. dose of 5 to 10 mg of AF per kg. Dose-response studies with AuTM showed that maximal changes in heme metabolism occur at a lower dose of AF than of AuTM, even though AF was administered p.o. and AuTM was administered parenterally. In addition, the kidneys appeared to be more susceptible to the inhibitory effects of the two chrysotherapeutic agents than did the liver. The present studies demonstrate the p.o. drug AF affects heme metabolism in a manner similar to that reported previously with the parenterally administered AuTM. | |
| 1706969 | CD5+ B cells in autoimmune disease and lymphoid malignancy. | 1991 May | Evidence is accumulating that CD5+ B cells belong to a developmental lineage distinct from that of conventional B cells and mainly participate in natural immunity. They have attracted attention because of their involvement in autoimmunity and lymphoid malignancy in both mice and humans. Patients with rheumatoid arthritis and Sjögren's syndrome were found to show a striking increase in the number of CD5+ B cells. B cell-chronic lymphocytic leukemia cells frequently express CD5. However, there are arguments against the role for CD5+ B cells in autoimmune disease, particularly in murine and human systemic lupus erythematosus (SLE). Whereas most IgM anti-DNA antibodies are produced by CD5+ B cells, high-affinity, pathogenic IgG antibodies are produced mainly by CD5- B cells. Either of two possibilities can explain the failure of CD5 expression of B cells responsible for producing IgG anti-DNA antibodies: either the cells are conventional B cells or the cells are CD5+ B cells that lack CD5 expression. In studies using SLE-prone NZB x NZW F1 mice and their H-2-congenic progeny, we discussed herein the possibility that CD5+ B lineage cells are also responsible for the pathogenic IgG autoantibody production by phenotypic switching from CD5+ to CD5-, probably under a particular genetic background. A line of H-2-congenic NZB x NZW F1 progeny failed to produce IgG anti-DNA antibodies, but in turn, showed a marked clonal proliferation of CD5+ B cells. Thus, it appears that genetically determined signals for either proliferation or differentiation would lead CD5+ B cells to cause distinct disease, i.e., autoimmune disease or lymphoid malignancy. Further studies using H-2-congenic New Zealand mice may provide insights into the correlation between autoimmunity and related lymphoid malignancy. | |
| 1846631 | Induction of phospholipase A2 gene expression in human hepatoma cells by mediators of the | 1991 Feb 5 | Serum levels of phospholipase A2 (PLA2) activity have been shown to be elevated in cases of septic shock and rheumatoid arthritis. The cellular origin of serum PLA2, however, is not known. In this report, we demonstrate that human group II PLA2 expression and secretion are induced in hepatoma cells (HepG2) following treatment with interleukin-6 (IL-6), tumor necrosis factor (TNF), and interleukin-1 (IL-1). Of the three cytokines, IL-6 is the most potent. Significant synergy is observed between IL-6 and IL-1 and between IL-6 and TNF, but not between IL-1 and TNF. PLA2 induction does not occur in human YT cells, which are known to have receptors for both IL-1 and IL-6, indicating that the regulatory mechanism involved is cell type-specific. The results of RNA blot analysis indicate that the PLA2 gene is regulated in HepG2 cells at the pretranslational level. Induction of PLA2 synthesis in HepG2 cells in response to these cytokines resembles the induction of the acute phase plasma proteins which are synthesized in cultured hepatocytes and hepatoma cells following exposure to the same cytokines and in liver in response to inflammation and infection. In addition, a putative IL-6-responsive element, which is homologous to a similar element found in several acute phase genes, is present in the 5'-promoter-proximal region of the PLA2 gene. These results suggest that serum PLA2 is synthesized in and secreted from liver cells in response to inflammatory stimuli, mediated primarily by IL-6, and therefore should be classified as an acute phase protein. | |
| 1901643 | Interleukin-1 or phorbol induction of the stromelysin promoter requires an element that co | 1991 Jan 25 | Interleukin-1, a mediator of inflammation, or tumor promoting phorbol esters induce transcription of stromelysin, a metalloproteinase that degrades extracellular matrix molecules and that is overexpressed in diseases such as rheumatoid arthritis. Sequences required for induction of transcription of the human stromelysin promoter are contained on a 46 base pair fragment. This fragment contains a sequence with a high degree of similarity to the binding site for the transcription factor activator protein-1 (AP-1) and indeed, the AP-1 sequence of this fragment is necessary but not sufficient for the maximal response to phorbol 12-myristate 13-acetate (phorbol) or interleukin-1. Maximal induction requires functional cooperation between the AP-1 sequence and a neighboring upstream regulatory sequence (URS) of the stromelysin promoter which is also necessary but not sufficient. We demonstrate that both the AP-1 sequence and the URS bind phorbol or interleukin-1 induced nuclear proteins. Cooperation of the AP-1 sequence with another sequence present in the stromelysin promoter may be a general mechanism whereby the AP-1 element, which is found in many promoters, achieves a maximal and specific response to various stimuli. | |
| 2018703 | Pathogenic Escherichia coli found in food. | 1991 Jan | The bacteria constituting the species Escherichia coli are commonly found in the intestinal flora of man and animals, and were until late 1950s recognized as non-pathogenic normal cohabitants. However, certain strains might induce disease, and E. coli should therefore be regarded as a potential pathogenic organism. The pathogenic strains can cause distinct disease syndrome as different diarrheal diseases, wound infections, meningitis, septicemia, artherosclerosis, hemolytic uremic syndrome and immunological diseases such as reactive and rheumatoid arthritis. Several different groups of diarrhea-inducing strains are known. The enterotoxigenic E. coli (ETEC) strains produce one or more of toxins from the heat-labile and the heat-stable enterotoxin families. These strains possess specific adhesion fimbria for intestinal attachment and colonization. Some enteropathogenic E. coli strains (EPEC) produce one or more of the cytotoxins, but adhere also to intestinal cells interfering with the electrolyte transport system. The group of strains possessing invasive properties are designated enteroinvasive E. coli (EIEC). Recently, the enterohemorrhagic E. coli (EHEC) strains have been identified and shown to produce one or more of the cytotoxins (vero-cytotoxins, shiga-like toxins). Food originating from warm-blooded animals may be contaminated with E. coli, but contamination from human sources are more common for food involved in outbreak of disease. In general, strains causing disease in animals do possess other colonization factors than those found on human pathogenic strains. EIEC strains are, like Shigella, only known to induce disease in man. However, both healthy and sick cattle are suspected to be a major reservoir for EHEC strains, and several outbreaks have been associated with consumption of meat or meat products. Cheeses have been the source of outbreaks of both ETEC and EIEC in Europe and the USA, while water seems to be a major source for the different diarrheic E. coli strains affecting children and tourists in the 3rd world. Strains causing non-enteric disease are less known as being transmitted to humans with food as a vector, but the importance of some of these diseases, should implicate further research on what role food plays in spreading these organisms. The recipient of the potential pathogenic E. coli through food, the humans, are also of different risk of contracting diseases.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 1654139 | Tetracyclines inhibit connective tissue breakdown: new therapeutic implications for an old | 1991 | Tetracyclines have long been considered useful adjuncts in peridontal therapy based on their antimicrobial efficacy against putative periodontopathogens. However, recently these drugs were found to inhibit mammalian collagenases and several other matrix metalloproteinases (MMPs) by a mechanism independent of their antimicrobial activity. Evidence is presented that this property may be therapeutically useful in retarding pathologic connective tissue breakdown, including bone resorption. The experiments leading to this discovery are described and possible mechanisms are addressed, including the specificity of tetracyclines' anti-collagenase activity, the role of the drugs' metal ion (Zn2+, Ca2+)-binding capacity, and the site on the tetracycline molecule responsible for this nonantimicrobial property. Of extreme interest, the tetracycline molecule has been chemically modified in multiple ways, generating a new family of compounds called CMTs (chemically modified tetracyclines) that lack antimicrobial but still retain anti-collagenase activity. The first of these CMTs, 4-de-di-methylaminotetracycline, was found not to produce a major side-effect of antimicrobial tetracycline therapy--its administration to experimental animals did not result in the emergence of tetracycline-resistant microorganisms in the oral flora and gut. Numerous examples of the clinical potential of this non-antimicrobial property of tetracyclines in the treatment of periodontal and several medical diseases (e.g., sterile corneal ulcers, rheumatoid arthritis, skin bullous lesions, tumor-induced angiogenesis and metastasis) are discussed. | |
| 2347157 | Results of revision total knee arthroplasty performed for aseptic loosening. | 1990 Jun | One hundred thirty-seven revision total knee arthroplasties (TKA) performed in 117 patients with failed aseptic metal-to-plastic knees over ten years (1974-1984) were studied to determine the long-term clinical and roentgenographic results and were compared to primary TKA. The mean age was 65 years (range, 32-90 years). Fifty-three percent had rheumatoid arthritis, and 47% had osteoarthritis. The mean interval from initial to revision TKA (129 knees) was four years (range, three months to 11 years) and from the first to second revision (seven knees) was 2.4 years (range, seven months to 5.5 years). The most common reasons for failure were loosening (73%), patellar complications (13%), and instability (10%). The mean follow-up time was 5.2 years (range, two to 12 years). Function, instability, motion, and pain all improved after revision TKA, but these improvements were significantly less than those seen after primary TKA. One-third of the patients still ambulated with crutches, a walker, or not at all. While mean postoperative flexion was 100 degrees, 24% could not flex to 90 degrees. Most patients (90%) were malaligned at the time of failure and remained so after revision (78%). The increased incidence of radiolucent lines (tibial, 61%; femoral, 24%) was not related to increased failure. Complications were not increased over primary TKA. The failure rate was 5.8% at 5.2 years, or approximately 1% per year. A successful clinical result was defined as a knee with mild or no pain, mild or no instability, and flexion to at least 90 degrees.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3065059 | Nimesulide. A preliminary review of its pharmacological properties and therapeutic efficac | 1988 Dec | Nimesulide is a new non-steroidal anti-inflammatory analgesic agent given orally or rectally on a twice daily basis in a number of inflammatory and pain states. Although still at an early stage of clinical assessment, preliminary evidence suggests that nimesulide 200 to 400mg daily is significantly more effective than placebo in reducing the pain, fever and inflammatory symptoms of chronic rheumatoid arthritis or osteoarthritis, respiratory tract infections, otorhinolaryngological diseases, soft tissue and oral cavity inflammation, dysmenorrhoea, phlebitis/thrombosis, urogenital disease and postoperative pain states. In a number of comparative studies, nimesulide has also been shown to be more effective than piroxicam (in osteoarthritis), paracetamol (acetaminophen) [in respiratory tract inflammation], benzydamine or naproxen (in otorhinolaryngological disease), phenylprenazone (in laryngotracheitis/bronchitis, respiratory inflammation and otorhinolaryngological disease), Serratia peptidases (in postoperative or dental pain, trauma and phlebitis), ketoprofen (in postoperative dental pain) and mefenamic acid (in dysmenorrhoea). In addition, the efficacy of nimesulide has been observed to be comparable with that of aspirin, with or without vitamin C, and mefenamic acid (in respiratory tract infection), ibuprofen (in soft tissue disease), naproxen (in respiratory tract inflammation, dysmenorrhoea and postoperative pain states), suprofen and paracetamol (in postoperative pain states), benzydamine (in genitourinary tract inflammation) and dipyrone, paracetamol or diclofenac (in fever). The safety profile of nimesulide has yet to be fully established, although initial evidence suggests the usual adverse effects associated with non-steroidal anti-inflammatory drugs occur, possibly with a lower incidence of gastrointestinal problems than with other members in its therapeutic class. Nimesulide, therefore, appears to offer a useful alternative to other non-steroidal anti-inflammatory drugs in the treatment of patients with inflammatory conditions and/or pain and fever states. However, further definition of its efficacy and tolerability is clearly required, particularly in comparison with established or other new drugs in its therapeutic class. | |
| 2544031 | Effects of tiaprofenic acid on interleukin 1, phospholipase A2 activity, prostaglandins, n | 1989 Feb | IL-1 and prostaglandin (PGE2, PGF2 alpha, TXB2) concentrations, PLA2 activity, neutral protease activity, and collagenase activity specific for types I and II collagen were determined in the SF of patients suffering from RA, before and after treatment with TA. Active and latent forms of protease and collagenases were regularly detected but were unrelated to IL-1, PLA2, and PGE2. TA induced a significant decrease in tested eicosanoids but IL-1, PLA2, and proteases were unchanged. | |
| 2310781 | Stimulation of human chondrocyte prostaglandin E2 production by recombinant human interleu | 1990 Mar 9 | In this study we have examined the effects of recombinant cytokine preparations on the production of prostaglandin E2 (PGE2) by human articular chondrocytes in both chondrocyte monolayer and cartilage organ cultures. The cytokines chosen for this study included only those reported to be present in rheumatoid synovial fluids and which therefore could conceivably play a role in chondrocyte activation in inflammatory arthritis. Of the cytokines tested, interleukin-1 (IL-1; alpha and beta forms) consistently induced the highest levels of PGE2 production followed, to a lesser extent, by tumour necrosis factor (TNF; alpha and beta forms). The IL-1s were effective at concentrations 2-3 orders of magnitude less than the TNFs, with each cytokine demonstrating a dose-dependent increase in PGE2 synthesis for the two culture procedures. The increased PGE2 production by the chondrocytes exhibited a lag phase of 4-8 h following the addition of the IL-1 or TNF and was inhibited by actinomycin D and cycloheximide, indicating a requirement for de novo RNA and protein synthesis, respectively. Our results suggest that IL-1 may be the key cytokine involved in modulating chondrocyte PGE2 production in inflammatory arthritis; they further extend the list of human chondrocyte responses which are affected by both IL-1 and TNF. | |
| 2999173 | Detection and measurement of fat cell-binding immunoglobulins: a new method applicable to | 1986 Jan | This report describes a new method for detecting and quantitating those immunoglobulins G (IgG) in serum that are related to Graves' disease. The method is based on previous observations which indicate that the guinea pig fat cell membrane (FCM) is capable of binding Graves'-specific IgG, but does not bind the IgG common to Graves' disease and Hashimoto's disease, such as antimicrosomal antibodies. Crude FCM preparations were iodinated by a lactoperoxidase technique and were then treated with Triton X-100 to yield a solubilized radioiodinated FCM (SFCM) preparation. SFCM, which retained bovine (b) TSH binding and Graves'-IgG binding properties, provided a radioactively labeled receptor with which to test for the presence of fat cell-binding IgG (FBI) in immunoprecipitates prepared by reacting these IgG with antibody against the Fc fragment of human IgG. FBI values (percentage of added SFCM bound to immunoprecipitate; mean + SD) in IgG from 16 patients with thyrotoxicosis caused by Graves' disease (6.0 +/- 1.7) were completely separated from those in IgG from 16 normal subjects (0.4 +/- 0.3). IgG from 2 hypothyroid patients with Hashimoto's disease, which were strongly positive in the TSH binding inhibition (TBI) assay, yielded FBI values within the range in Graves' disease, but values in TBI-negative IgG from 15 other patients with Hashimoto's disease were normal (0.0 +/- 0.9). Moderately false positive FBI values were found in the IgG of 15 patients with rheumatoid arthritis or systemic lupus erythematosis, all rheumatoid factor positive, 3 of which were also TBI positive. In IgG from Graves' disease and those from patients with TBI-positive collagen-vascular disease, binding of SFCM was inhibited by bTSH in a dose-dependent manner. As with binding of TSH to thyroid plasma membranes, similar but less potent inhibition of binding of IgG to SFCM was produced by LH, FSH, and hCG, but not by insulin, glucagon, PRL, or ACTH. FBI values in TBI-negative IgG from patients with collagen-vascular disease were also decreased by TSH, but higher concentrations of bTSH were required. In 40 IgG from among the various clinical groups tested, a significant correlation was found between FBI values and TBI activity (r = 0.48; P less than 0.01). In addition, among 10 IgG from Graves' disease and 6 from collagen-vascular disease patients, a very close correlation (r = 0.89; P less than 0.001) was noted between their TBI activity and the extent to which their FBI values were decreased by a standard concentration of bTSH.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 1915519 | Chronic bilateral dacryo-adenitis in identical twins: a possible incomplete form of Sjögr | 1991 Jul | We report an unusual case of chronic bilateral dacryo-adenitis in 10-year-old identical twin sisters. Both girls presented with bilateral lacrimal gland enlargement and developed moderate xerophthalmia and keratitis. Both the lacrimal and minor salivary gland biopsies showed a non-granulomatous inflammatory infiltration of mono-nuclear cells. All granulomatous diseases and neoplasms could therefore be ruled out and only Sjögren syndrome and very few other forms of chronic dacryo-adenitis remained as possible diagnoses. Both patients and their parents were evaluated for auto-antibodies. Very low titres of smooth muscle antibodies were found in one, antinuclear antibodies in two and anti-dsDNA antibodies in all four members of the family. Even though the titres of antinuclear and anti-dsDNA antibodies increased in one of the sisters, both patients did not develop any sign or symptom of a systemic connective tissue disease. During the 6 years' follow up, both patients showed persistent tarsal gland enlargement but no other symptoms apart from a moderate xerophthalmia and occasional mild keratitis. | |
| 2452715 | Autoimmune manifestations of human immunodeficiency virus (HIV) infection. | 1988 Jun | The human immune deficiency virus (HIV) is not only capable of inducing a state of immunodeficiency, but it is also associated with a state of profound immune dysregulation. This immune dysregulation may manifest itself as autoimmune reactivity that may participate in the overall pathogenic process of HIV infection as well as in the development of a variety of autoimmune laboratory phenomena and clinical syndromes. If autoimmune mechanisms are operative in the immunopathogenesis of the virus itself in the form of autocytotoxicity, the knowledge of this is critically important for the development of effective forms of antiviral therapy. The recognition that individuals infected with HIV can develop a wide variety of autoimmune laboratory phenomena including hypergammaglobulinemia circulating immune complexes and autoantibodies is important to assist in the proper interpretation of tests. The development of clinical autoimmune syndromes in HIV-infected individuals, such as connective tissue disorders, immune cytopenias, and other conditions, is important to the clinician, who must recognize these alternative forms of disease presentation for accurate diagnosis and treatment. |