Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1940996 | Impairment of physical and psychosocial function in recurrent syncope. | 1991 | Physical and psychosocial function have rarely been assessed in syncope. We used two valid and reliable measures of health status, the Sickness Impact Profile (SIP) and the Symptom Checklist 90 (SCL-90-R), to assess functional impairment in 62 patients with recurrent syncope seen in a syncope specialty clinic. Mean total SIP scores were markedly elevated at 17 (SD = 14), indicating a level of impairment similar to severe rheumatoid arthritis and chronic low back pain. SIP psychosocial scores were significantly greater than SIP physical scores (20 vs 11, p less than 0.0001). SCL-90-R scores were also high, comparable to those of psychiatric inpatients. Somatization, anxiety and depression dimensions of the SCL-90-R were particularly elevated. SCL-90-R subscale scores were highly correlated with SIP psychosocial scores (all r greater than 0.4, and p less than 0.001). Neither age nor number of comorbid diseases correlated with measures of psychosocial function, suggesting that syncope itself causes psychosocial impairment. Although this was a referral population, these data suggest that function can be seriously impaired by syncope, that the degree of impairment is similar to that reported in other chronic diseases, and that syncope leads to significantly greater psychosocial than physical impairment. | |
| 1963552 | Influence of eicosanoids on fibroblast chemotaxis and protein synthesis in vitro. | 1990 Sep | Metabolism of fibroblasts plays a key role in wound healing, fibrosis, rheumatoid arthritis, and similar physiological and pathological processes. The regulatory influence of eicosanoids, an important class of inflammatory mediators, on fibroblast metabolism, in these processes is, to date, unclear. The aim of this study was to investigate the effect of some eicosanoids on chemotaxis and protein synthesis of fibroblasts in vitro. Of twelve eicosanoids tested, only 5(S)-HETE, LTB4, and 12(S)-HETE were active as chemo-attractants for fibroblasts. 5(S)-HETE was the most potent attractant. It exerted its maximal activity at 10(-10) mol/l. 12(S)-HETE and LTB4 caused similar dose dependent fibroblast chemotaxis with a maximum of activity at 10(-7) M and 5 x 10(-8) M, respectively. Hydroxylation of LTB4 on C20 or methylation of the carboxy group of 12(S)-HETE decreased reactivity of the parent compounds only slightly. Eicosanoid induced chemotaxis could be antagonized by 12(S)-HETE but not by the proteinaceous chemoattractants fibronectin, PDGF, or EGF. Receptors for peptide and eicosanoid mediated chemotaxis are thus different. Inhibition of collagen synthesis was observed in the presence of 5(S)-HETE and 12(S)-HETE while total protein synthesis was unaffected by 12(S)-HETE and augmented by 5(S)-HETE. These data suggest that certain eicosanoids specifically regulate fibroblast activities in wound healing and similar events of connective tissue reorganization. | |
| 2210913 | Immunomodulatory effect of a newly synthesized compound, TOK-8801 (N-(2-phenylethyl)-3,6,6 | 1990 | The immunopharmacological effects of a newly synthesized compound in vivo, TOK-8801 (N-(2-phenylethyl)-3,6,6-trimethyl-5,6-dihydroimidazo[2,1-b]thi azo le-2- carboxamide), on the anti-SRBC plaque-forming cell (PFC) response and delayed-type hypersensitivity (DTH) reaction were investigated. Oral administration of TOK-8801 (0.1-10 mg/kg) resulted in the suppression of the PFC responses to varying doses of antigen (5 x 10(6), 2 x 10(7), 1 x 10(8)) in C3H/He strain mice (7 W) which are high responders to SRBC antigen. On the other hand, the compound augmented the PFC response in aged mice (8-9 months) in which the PFC response was markedly depressed compared with that in young mice. In the experiment of the methylated human serum albumin-induced DTH reaction, TOK-8801 augmented the reaction in low responder (C57BL/6) mice by oral administrations of 0.1-1 mg/kg for 5 days from the sensitization, whereas suppressed the reaction in high responder (ICR) mice. These immunopharmacological actions of TOK-8801 were compared in dose and activity with those of lobenzarit and bucillamine. Thus, these results suggest that TOK-8801 may act as an immunomodulating agent and would be expected to be a useful agent for autoimmune diseases such as rheumatoid arthritis. | |
| 2117000 | Effects of associated cytokines (IL-1, TNF-alpha, IFN-gamma and TGF-beta) on collagen and | 1990 | The production of collagen and glycosaminoglycans (GAG) was studied in cultured human synovial cells exposed to four cytokines, alone or in dual combination, namely interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta). Among these cytokines, only TGF-beta (0.1-10 ng/ml) induced a significant and dose-dependent increase of collagen synthesis in a 24-h incubation. This effect was reversed when the factor was associated with either IL-1 beta (100-500 pg/ml), TNF-alpha (1-100 ng/ml) or IFN-gamma (100 U/ml). Except IFN-gamma which clearly inhibits the collagen production, the other cytokines IL-1 and TNF-alpha were not very effective when tested separately, although they generally induced a small reduction in collagen amount. IL-1 beta and TNF-alpha were found to be more efficient than TGF-beta in stimulating the production of GAG by the synovial cells. IFN-gamma exerted an antagonistic effect on the TGF-beta-induced stimulation of GAG synthesis. TNF-alpha and IL-1 beta were shown to have an additive effect on that production. The results indicate that interactions between cytokines present in the inflamed synovial tissue may modulate their respective actions and thus introduce differentials in their effect on collagen and GAG metabolism which are responsible for the alterations of synovial extracellular matrix in rheumatoid arthritis. | |
| 2818937 | Inhibition of CFU-GM by prostaglandins in a case of chronic T-cell lymphocytosis and neutr | 1989 Oct | A 45-year-old Caucasian female with seropositive rheumatoid arthritis was found coincidentally to have a circulating lymphocytosis (6.4 x 10(9)/l) and neutropenia (0.1 x 10(9)/l). Initial presentation was with mouth ulceration and recurrent infections. A spleen scan showed no evidence of splenomegaly and serum titres against EBV, CMV and toxoplasmosis were negative. No anti-neutrophil antibodies were found. Marrow aspiration demonstrated a lymphocytosis of 60% with reduced numbers of granular precursors. Lymphocytes in both blood and bone marrow were CD3, CD8, CD16 and HLA-DR positive. Lymphocyte conditioned medium (LCM) generated from the patient's blood lymphocytes (without phytohaemagglutinin) was found to inhibit allogeneic colony-forming unit, granulocyte-macrophage (CFU-GM) stem cells in semi-solid culture compared with control LCM. This inhibitory activity was abrogated by the cytolytic removal of CD8 cells prior to LCM production and was significantly reduced by co-culture with indomethacin. Culture of the patient's marrow at autostimulatory light density marrow cell concentrations showed poor spontaneous CFU-GM colony formation until marrow CD8 lymphocytes were removed cytolytically. Prednisolone was used therapeutically (40 mg/d) and resulted in the patient's neutrophil count rising from 0.06 x 10(9)/l to 1.1 x 10(9)/l and a fall in the total lymphocyte count to 1.9 x 10(9)/l. Reevaluation of the patient's LCM post steroid therapy showed loss of the previous inhibitory effect. The patient's neutrophil count is maintained on oral azathioprine and indomethacin. | |
| 2784139 | Immunomodulation by low-dose methotrexate. I. Methotrexate selectively inhibits Lyt-2+ cel | 1989 Mar 15 | We have studied the effect of methotrexate in murine acute graft vs host (GvH) disease at concentrations analogous to those used in human rheumatoid arthritis. The GvH reaction was induced by i.v. injection of parental spleen cells into a normal F1 recipient. The acute suppression of T cell function in GvH mice was prevented by methotrexate given orally for 10 days at 1.0 or 0.5 mg/kg but not at 0.25 mg/kg. T cell mitogen response and IL-2 secretion that were inhibited in GvH mice were restored by methotrexate. Protection from immunosuppression in drug-treated GvH mice lasted at least 3 wk after drug dosing was stopped. The mechanism of the protective effect appears to be a preferential inhibition of donor and host Lyt-2+ Ts cell proliferation. In mixing experiments we found that methotrexate inhibited Ts function in GvH mice. By dual fluorescence labeling we showed that the engraftment of donor Lyt-2+ cells was prevented by drug treatment. This was not true of donor L3T4+ cells which were clearly present in the spleens of GvH mice after methotrexate treatment. These donor L3T4 cells were functional in that they induced the production of anti-DNA autoantibodies in the methotrexate-treated GvH mice. | |
| 2536348 | Detection of anti-liver cell membrane antibody using a human hepatocellular carcinoma cell | 1989 Feb | A radioimmunometric technique for the detection of autoantibodies to liver membrane antigens has been developed using Alexander cells, a human hepatocellular carcinoma cell line. After incubation of Alexander cells with serum, antimembrane antibodies were detected by addition of 125I-labeled Protein A. Binding ratios in 15 children with uncontrolled autoimmune chronic active hepatitis and in seven children with primary sclerosing cholangitis were significantly higher than in 18 age-matched normal controls. Nine patients with inactive autoimmune chronic active hepatitis, 13 with alpha 1-antitrypsin deficiency and five with fulminant hepatic failure had ratios similar to controls. In nine patients with Wilson's disease, there was a modest but significant increase in binding ratio. In four children with autoimmune chronic active hepatitis, binding ratios fell during effective immunosuppressive therapy. Sera from patients with systemic lupus erythematosus or rheumatoid arthritis gave normal results, excluding that binding derives from Fc-mediated immune complex capture. A positive correlation was found between Alexander cell binding values and anti-liver-specific protein antibody titers, suggesting that the two assays detect antibodies against shared antigenic determinants. The Alexander cell assay is a simple, rapid and sensitive technique to detect antibody to liver cell membrane antigens. | |
| 2576260 | Noncontraceptive clinical benefits of oral contraceptives. | 1989 | The contraceptive benefits of oral contraceptives have become well known since the introduction of this birth control method in the 1960s. Since that time, a more sophisticated understanding of the hormonal components of the medication has developed, along with reduction in the dosages of these hormones. During the past decade in particular, the medical literature has documented a number of noncontraceptive benefits delineated by studies conducted in Europe and the United States. Users of oral contraceptives have reduced rates of both endometrial and ovarian cancer, and this protection persists even when oral contraceptive use is discontinued. The risk of ectopic pregnancy is reduced up to tenfold among oral contraceptive users and the risk of pelvic inflammatory disease (salpingitis), two- to fourfold. The necessity for performing surgical excision of benign breast cysts or functional ovarian cysts is substantially reduced in women who take oral contraceptives. There also is evidence that the risk of rheumatoid arthritis is reduced in oral contraceptive users. Finally, women who take oral contraceptives have less menstrual dysfunction, such as menorrhagia and dysmenorrhea, than do nonusers. In the United States, it has been estimated that as many as 50,000 hospital admissions are prevented annually because of the noncontraceptive benefits of these drugs. Accordingly, these benefits should be taken into account when discussing contraceptive methods with patients. | |
| 2508125 | The role of arachidonate metabolites in ocular inflammation. | 1989 | PGs and leukotrienes are said to be mediators of various aspects of inflammation. In the rabbit eye, PGs are primarily involved in vasodilation and at least in rabbits, disruption of the blood-aqueous barrier. These effects vary qualitatively in different species. In the responses of the eye to chemical, mechanical, or neurogenic injury, PG involvement is limited, as indicated by the fact that cyclooxygenase inhibitors do not totally abrogate the responses. Inflammation, whether in the eye or in other tissues, is more complex than the injury responses. Complement pathway, arachidonate metabolites, cytokines, and monokines are major components in inflammation, but not necessarily in the response of tissues to injury. Topical or intracameral administration of leukotriene B4 causes PMN chemotaxis without affecting the blood-aqueous barrier. Peptidoleukotrienes such as leukotriene C4 and D4, on the other hand, are not chemotactic, but they do increase the permeability of the conjunctival microvasculature. Cyclooxygenase and 5-lipoxygenase products have been detected in the anterior chamber during the course of experimentally induced ocular inflammation and in humans with uveitis, but whether their presence is incidental or causal is yet to be established. In spite of numerous investigations, the precise role and the extent of involvement of arachidonic acid metabolites in ocular and non-ocular inflammatory diseases remain controversial. Pharmacologic studies on the effects of CO inhibitors like indomethacin in experimental models of inflammation have provided evidence that PGs participate in vascular reactions but not in leukocyte infiltration. PGs are also capable of interacting with other vasoactive agents to enhance the responses. In humans, such roles for PGs in inflammatory diseases are probably incidental. In patients with rheumatoid arthritis, treatment with CO inhibitors provides symptomatic relief without attacking the underlying cause of the disease. Post-operative vascular leakage is reportedly inhibited by some cyclooxygenase inhibitors (Mishima et al., 1989), but it remains to be seen whether they effectively arrest the processes that in some cases lead to the progression of the disease. Most of the 5-lipoxygenase inhibitors examined to date in experimental animals have been found to be non-selective. Only recently have highly selective 5-LO inhibitors become available, and these are currently being examined. Thus, evidence from animal studies with 5-LO inhibitors suggests the involvement of LTB4 in leukocyte infiltration and of peptidoleukotrienes in bronchospasm as well as in increased microvascular permeability of the conjunctiva and other | |
| 3118510 | Acute nephropathy induced by gold sodium thiomalate: alterations in renal heme metabolism | 1987 Nov | Gold compounds are used clinically in rheumatoid arthritis therapy. Acute renal toxicity is observed in some patients receiving chrysotherapy. The present study addresses morphofunctional and biochemical changes in rat kidneys during the first 8 days following a single ip injection of gold sodium thiomalate (AuTM), one of the gold compounds presently in clinical use. Compared to controls, AuTM pretreatment resulted in increased urine output and elevated serum creatinine and urea nitrogen concentrations. Also, by Day 8, treated rats had decreased body weights and increased kidney weights. Postmortem examination on Day 1 showed pale and mottled kidneys and diffusely pale inner cortex. Microscopically, there was severe coagulative necrosis of the proximal tubular epithelium. Epithelial regeneration was prominent by Day 4 and was nearly complete by Day 8. The regenerating epithelium was hyperplastic with basophilic cytoplasm and pleomorphic nuclei. Alterations in renal heme biosynthesis and drug metabolism paralleled the morphologic changes. The activity of delta-aminolevulinic acid dehydratase and benzo[a]pyrene hydroxylase were inhibited on Days 1, 2, and 4 following AuTM administration. Decreases in monooxygenase activity were accompanied by decreases in renal cytochrome P-450 levels. In contrast, renal microsomal heme oxygenase activity was elevated 9.5-fold on Day 1 and 2.5-fold on Day 2. By Day 8, all renal enzymatic activities assayed for were similar to those obtained with untreated rats. | |
| 1793205 | Photopheresis: a clinically relevant immunobiologic response modifier. | 1991 Dec 30 | Photopheresis, the process by which peripheral blood is exposed in an extracorporeal flow system to photoactivated 8-methoxypsoralen (8-MOP), is an effective new treatment for certain disorders caused by aberrant T lymphocytes. It has become a standard therapy for advanced cutaneous T cell lymphoma and shows promise in the treatment of four autoimmune disorders (pemphigus vulgaris, the progressive systemic sclerosis form of scleroderma, rheumatoid arthritis, systemic lupus erythematosus) and in reversal of immunologic rejection of transplanted organs. Positive immunologic alterations observed in patients with AIDS-related complex merit further investigation, and preliminary trials in the management of patients with multiple sclerosis, myasthenia gravis and autoimmune insulin-dependent diabetes mellitus have recently been initiated. The inability of the treatment to meaningfully alter the course of the B cell malignancy, chronic lymphocytic leukemia, suggests that B cell proliferations, at least those involving malignant cells, may be more resistant to this treatment. The mechanism of action of photopheresis is likely to be multifaceted, but at least in experimental systems appears to involve an immunization against the pathogenic T cells, in a highly specific manner. Photoactivated 8-MOP initiates a cascade of cellular events by forming covalent photoadducts with nuclear DNA, with cell surface molecules and possibly with other cytoplasmic components of the ultraviolet exposed leukocytes. For reasons not yet clear, exposure of populations of T cells containing expanding a clone(s) of pathogenic T cells to photoactivated 8-MOP alters these cells so that their reinfusion induces a therapeutically significant immunologic reaction that targets unirradiated T cells of the same pathogenic clone(s). It is suggested that the specificity of the induced immunologic reaction may result, in sequence, from the exquisitely titratable damage that 8-MOP inflicts upon cells of the pathogenic clone(s), the return of these cells to an immunocompetent individual, the removal of the photo-damaged cells from the blood by the reticuloendothelial system and the preferential induction of an immune response against cells of the pathologically expanded clone(s). | |
| 1832174 | Augmentation of reverse arthus reaction by mast cells in mice. | 1991 Sep | Immune complex-induced injury is an important pathogenic factor in antibody-mediated nephritis, systemic lupus erythematosus, rheumatoid arthritis, and other diseases. In this study we investigated the role mast cells in immune complex-mediated injury in mouse skin. Reverse Arthus reaction was induced in mast cell-deficient WBB6F1-W/Wv mice and their congenic controls (WBB6F1(-)+/+). Serial skin sections were evaluated for neutrophil infiltration, edema, and hemorrhage. In WBB6F1-W/Wv mice the neutrophil influx was only 40% and edema 60% of that in congenic controls. Hemorrhage was also significantly reduced in the mast cell-deficient mice. After mast cell reconstitution, the magnitude of the reaction in WBB6F1-W/Wv was equivalent to that in WBB6F1(-)+/+ mice. Mast cell release in reverse Arthus reaction was evaluated by measuring fluorescence intensity after avidin-FITC staining of mast cell granules. There was a 70% decrease in fluorescence intensity. The 5-lipoxygenase inhibitor A-63162 significantly decreased neutrophil accumulation (40%), edema (60%), and hemorrhage in WBB6F1(-)+/+, but not in mast cell-deficient mice. Mast cell reconstitution of WBB6F1-W/Wv mice restored the effect of A-63162. The results indicate that mast cells and their mediators, including leukotrienes, make an important contribution to reverse Arthus reaction. | |
| 1864063 | Blood loss in total knee arthroplasty. | 1991 Aug | Over a two-year period, 112 consecutive primary total knee arthroplasties (TKA) were performed according to a standard protocol and were evaluated to determine the effects of intraoperative tourniquet deflation, suction drainage, and immediate continuous passive motion (CPM) on blood loss and the need for blood transfusions. It has been reported that these measures lead to increased morbidity following TKA. The tourniquet was deflated before closure, hemostasis was obtained, and two suction drains were placed for 24 to 48 hours. CPM was started immediately, and continued for a mean of seven days. Serial hematocrits (Hct) were obtained. Mean age of the 64 males and 48 females was 65 years. The diagnosis was osteoarthritis in 86% and rheumatoid arthritis in 14%. Seventy-three percent of the prostheses were cemented and 27% were uncemented. The mean tourniquet time was 104 minutes and the mean length of surgery was 140 minutes. Blood loss measured at surgery averaged 222 ml. Total calculated blood loss averaged 794 ml, but was higher for patients with a cemented versus uncemented prosthesis (p less than .05), and males versus females (p less than .005). It was not related to diagnosis, tourniquet time, or length of surgery. Of the 38% of patients requiring a transfusion (mean, 2.2 units), there was not a significantly greater drop in Hct (from 36.6 to 26.5; change, 10.1) when compared to patients not receiving a transfusion (from 43.1 to 32.5; change, 10.6). Therefore, the need for transfusion was related to preoperative Hct and not the intraoperative or postoperative blood loss.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 2283087 | Metal ion-catalyzed oxidation of proteins: biochemical mechanism and biological consequenc | 1990 | In the presence of O2, Fe(III) or Cu(II), and an appropriate electron donor, a number of enzymic and nonenzymic oxygen free radical-generating systems are able to catalyze the oxidative modification of proteins. Whereas random, global modification of many different amino acid residues and extensive fragmentation occurs when proteins are exposed to oxygen radicals produced by high energy radiation, only one or a few amino acid residues are modified and relatively little peptide bond cleavage occurs when proteins are exposed to metal-catalyzed oxidation (MCO) systems. The available evidence indicates that the MCO systems catalyze the reduction of Fe(III) to Fe(II) and of O2 to H2O2 and that these products react at metal-binding sites on the protein to produce active oxygen (free radical?) species (viz; OH, ferryl ion) which attack the side chains of amino acid residues at the metal-binding site. Among other modifications, carbonyl derivatives of some amino acid residues are formed; prolyl and arginyl residues are converted to glutamylsemialdehyde residues, lysyl residues are likely converted to 2-amino-adipylsemialdehyde residues; histidyl residues are converted to asparagine and/or aspartyl residues; prolyl residues are converted to glutamyl or pyroglutamyl residues; methionyl residues are converted to methionylsulfoxide residues; and cysteinyl residues to mixed-disulfide derivatives. The biological significance of these metal ion-catalyzed reactions is highlighted by the demonstration: (i) that oxidative modification of proteins "marks" them for degradation by most common proteases and especially by the cytosolic multicatalytic proteinase from mammalian cells; (ii) protein oxidation contributes substantially to the intracellular pool of catalytically inactive and less active, thermolabile forms of enzymes which accumulate in cells during aging, oxidative stress, and in various pathological states, including premature aging diseases (progeria, Werner's syndrome), muscular dystrophy, rheumatoid arthritis, cataractogenesis, chronic alcohol toxicity, pulmonary emphysema, and during tissue injury provoked by ischemia-reperfusion. Furthermore, the metal ion-catalyzed protein oxidation is the basis of biological mechanisms for regulating changes in enzyme levels in response to shifts from anaerobic to aerobic metabolism, and probably from one nutritional state to another. It is also involved in the killing of bacteria by neutrophils and in the loss of neutrophil function following repeated cycles of respiratory burst activity. | |
| 2483543 | Activity of human placental gamma globulin in blocking immune functions in vitro and in ab | 1989 Jul | In order to understand the mechanism of immunosuppression caused by infusion of placental gamma globulin (PGG) in patients with renal allografts, rheumatoid arthritis, and graft-versus-host disease (GVHD) following bone marrow transplantation (BMT), we have examined the effect of PGG in vitro and in a model of the xenogeneic, local graft-versus-host reaction (LGVHR). PGG inhibited lymphocyte proliferation in mixed lymphocyte cultures (MLC) (P less than 0.005) and depressed interleukin-2 (IL-2) levels in such cultures at 72 hours (P less than 0.01). In contrast phytohemagglutinin (PHA)- and pokeweed mitogen (PWM)-induced T and B lymphocyte blastogenesis was not affected by such PGG treatment. PGG neither decreased the [3H] TdR pulse incorporation in unstimulated lymphocytes nor affected cell viability. Cell cycle analysis by flow cytometry showed that PGG reduced the percentage of cells in S and G2, M phases during the MLC, but did not alter cell cycling during PWM-stimulated proliferation. An immunosuppressive effect of PGG on the LGVHR was tested in a model of intracutaneous transplantation of PGG-treated human lymphocytes into cyclophosphamide-immunosuppressed rats. Lymphoprep-separated human tonsillar lymphocytes were incubated with RPMI-1640 buffer containing: (1)PGG, 4 mg/ml, (2) human plasma albumin, 4 mg/ml, (3) mitomycin-C, 25 micrograms/ml, or (4) no additive. Cells of each preparation (3 X 10(7) cells in 0.1 ml) were injected intracutaneously into cyclophosphamide-treated male rats at separate abdominal locations. A fifth site received only the buffer solution. Five days after injection of cells, each rat received [125I]UdR (10 muCi) intraperitoneally and was killed after 5 hours.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3180576 | Two-stage reimplantation in infected total knee arthroplasty. | 1988 Nov | Twenty-one infected total knee arthroplasties (TKA) in 21 patients were treated from September 1980 through October 1987. Of these, 15 were followed for more than one year. Treatment of these patients consisted of thorough debridement of all infected tissue and components; a cement spacer was used in ten patients. The cement was impregnated with antibiotics. This procedure was followed for an average of 4.2 weeks with intravenous antibiotics and TKA utilizing antibiotic-impregnated cement. Five patients had rheumatoid arthritis and ten had osteoarthritis. The organisms included Staphylococcus coagulase negative (seven patients), Streptococcus group B (two patients), Streptococcus bovis (one patient), Enterococcus (one patient), Staphylococcus coagulase positive and Bacillus circulans (one patient), Staphylococcus coagulase negative and Enterococcus (one patient), Staphylococcus coagulase negative and Pseudomonas aeuriginosa (one patient), and Clostridium perfringens (one patient). Of the 15 patients, 12 appeared to be free of infection, two were obvious failures and required knee fusion, and one was suspected of having continued infection at five years and was treated elsewhere. Eleven patients with revision TKA were available for follow-up examinations at an average of 2.9 years (range, one to six years). One patient died five years after reimplantation but had been functioning well. One patient functioning at three years postreimplantation did not return for a later follow-up examination. The average knee score (modification of the Hospital for Special Surgery Knee Score) was 75.5 points (range, 48-94); average flexion was 81 degrees (range, 52 degrees-120 degrees), and average extension was +6 degrees (range, 0 degrees-30 degrees).(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3442967 | The production of pregnancy associated alpha glycoprotein (PAG) from human peripheral bloo | 1987 Sep | A sensitive enzyme-linked immuno-assay has been developed which can measure the amounts of pregnancy-associated alpha 2 glycoprotein (PAG) produced by human peripheral blood mononuclear cells (MNC) in culture. Ethinyl oestradiol, indomethacin and pokeweed mitogen (PWM) stimulated PAG production directly while indomethacin produced an additional increase in PAG production by PWM-stimulated MNC probably by inhibiting the production of prostaglandins with down-regulatory effects on the MNC. Oestrogen stimulation of MNC produced significant increases in PAG levels only by the MNC of women on oral contraceptives but not from the cells of males or of females of reproductive age not on oral contraceptives. Since PAG has immunosuppressive properties these observations may be of relevance in understanding the mechanisms involved in the significant decrease in the incidence of rheumatoid arthritis in women taking oral contraceptives. | |
| 1671423 | Correlation between antibodies to type II collagen and treatment outcome in bilateral prog | 1991 Feb 16 | Our aim was to assess whether "idiopathic" bilateral progressive sensorineural hearing loss (BPSHL) has an immunological cause in some patients; antibodies to native type II collagen were sought by an ELISA in eighteen patients with BPSHL, before and after corticosteroid treatment, and in twelve patients with Menière's disease, fifteen with otosclerosis, eighteen with rheumatoid arthritis, nine with fibrositis, and nine healthy controls. A positive result was defined as a mean dilution titre of 2 or more. Eight of eighteen BPSHL patients had positive titres--significantly (p less than 0.005) more than in any other group (one Menière's disease, two otosclerosis, and no others). The mean antibody titre was higher in the BPSHL group than in any other group (2.02 [SEM 0.62] vs 0.17 [0.17]) Menière's disease, 0.44 [0.32] otosclerosis, 0 all others; p less than 0.005). The nine BPSHL patients who showed a clinical response to corticosteroids (improvement in at least one tone by audiogram or 25 db in speech discrimination score) had the highest mean antibody titre (3.46 [0.88] vs 0.59 [0.59] for the nine non-responsive patients; p less than 0.04). We suggest that in some patients with BPSHL, immunity to type II collagen, a major constituent of the inner ear, may be important in the pathogenesis of the disorder. | |
| 2146995 | Purification and characterization of IgG immunoconglutinins from patients with systemic lu | 1990 Nov | The levels of IgG immunoconglutinins in plasma from patients with rheumatoid arthritis, systemic lupus erythematosus and primary biliary cirrhosis were monitored by ELISA. High levels of IgG immunoconglutinins were found mainly in plasma from patients with systemic lupus erythematosus. These immunoconglutinins bound to microtitre plate-fixed C3, C3b and C3c but poorly to C3d. This binding was inhibited by particle-bound C3b and iC3b but not by the corresponding soluble fragments. Furthermore, Western blot analysis revealed no immunoconglutinin-binding to reduced C3 peptides and no binding was shown to soluble C3 alpha and beta chain by ELISA. IgG immunoconglutinins were purified from three plasma specimens by affinity chromatography on activated thiol sepharose ATS/C3 fragments. Two immunoconglutinin preparations that preferentially recognize ATS-C3b, inhibited C5-convertase function by 50-100% while one immunoconglutinin that recognized ATS-C3d,g had no effect. The two former immunoconglutinins also inhibited all three factor I cleavages in C3 alpha chain but the latter inhibited only the third cleavage. None of the immunoconglutinins affected the binding of complement-coated anti-BSA/BSA complexes to CR1 (CD35) on human erythrocytes, but the two immunoconglutinins that inhibited all factor I cleavages also inhibited the factor I-induced release of anti-BSA/BSA complexes from CR1. The results show that immunoconglutinins recognize specific epitopes on bound C3 fragments and that they are able to modulate C3-mediated functions. | |
| 2281828 | Estrogen inhibits release of tumor necrosis factor from peripheral blood mononuclear cells | 1990 Sep | Cytokines, such as interleukin-1 (IL-1) and tumor necrosis factors (TNF), produced by cells of the monocyte-macrophage lineage in the local bone microenvironment, are potentially important local regulators of bone turnover. To investigate whether the protective effects of estrogen against postmenopausal bone loss may be mediated by inhibition of cytokine release, we studied the effects of 17 beta-estradiol, dihydrotestosterone, and hydrocortisone on TNF release from human peripheral blood mononuclear cells (PBMC) in vitro. In unstimulated cells derived from eight postmenopausal women, seven of whom had osteoporotic vertebral fractures, 17 beta-estradiol inhibited TNF release in a dose-dependent manner between 10(-6) and 10(-12) M but had no consistent effect on cells derived from men or premenopausal women. Dihydrotestosterone in concentrations of up to 10(-6) M had no effect on TNF release in any patient group, whereas hydrocortisone at 10(-6) M was a potent inhibitor of TNF release in all groups. Since TNF is a potent stimulator of bone resorption, the inhibitory effect of estrogen on TNF release may be part of the mechanism by which it exerts a protective effect on the skeleton in postmenopausal women. These observations may also be relevant in other inflammatory diseases of connective tissue, such as rheumatoid arthritis, in which disease activity may fluctuate as estrogen levels change--during the menstrual cycle, in pregnancy, and after the menopause. |