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ID PMID Title PublicationDate abstract
1616329 Interleukin 1 alpha and beta production by cells isolated from membranes around asepticall 1992 May Aseptic loosening of joint prostheses is accompanied by local osteolysis. To determine whether local production of interleukin 1 might contribute to such lysis, the number of interleukin 1 secreting cells in the pseudosynovial membrane surrounding prostheses was measured. Interleukin 1 alpha and beta secreting cells were identified by ELISPOT, a sensitive cytokine secreting assay. The proportion of interleukin 1 beta secreting cells in pseudosynovial membrane was comparable with the proportion occurring in the synovium of patients with rheumatoid arthritis and higher than that in normal subjects and patients with osteoarthritis. The proportion of interleukin 1 alpha producing cells was higher in pseudosynovial membrane than in diseased synovium. Overall, higher numbers of interleukin 1 beta than interleukin 1 alpha secreting cells were detected. A correlation was observed between the number of cells in pseudosynovial membrane producing interleukin 1 beta and those producing interleukin 1 alpha. When divided into area of origin, tissue samples from the femoral area contained a higher proportion of interleukin 1 beta producing cells than tissue in the acetabular or capsular regions, though due to variance within each group this difference did not reach significance.
1616632 Dynamic light scattering studies on hydrodynamic properties of fibrinogen-fibronectin comp 1992 Feb A high molecular weight 'cryogel' was obtained as insoluble complexes by cold incubation at near-freezing temperatures from heparinized plasma of patients with rheumatoid arthritis. After the cryogel was solubilized at 37 degrees C, 1:1 complex of fibrinogen and fibronectin was purified at room temperature by affinity chromatography on a gelatin-Sepharose 4B. Hydrodynamic properties of the complex were investigated as a function of temperature and NaCl concentration using a dynamic light scattering. The diffusion coefficients of the complex at 20 degrees C decreased with increasing of NaCl concentration as free fibronectin. The complex appears to be a more compact form at low ionic concentration, which is associated with conformational changes of fibronectin. The diffusion coefficient of the complex at 20 degrees C in 0.05 M TrisHCl(pII7.4) containing 0.5 M NaCl was estimated as 8.5 x 10(-8) cm2s-1. The complex did not dissociate over the temperature range from 20 to 37 degrees C. The diffusion coefficients of the complex decreased significantly at 12 degrees C and 40 degrees C. The thermal denaturation of fibrinogen molecule in the complex was observed at 40 degrees C. The CONTIN analysis of the light scattering data showed that the complex associated to form higher aggregates at 15 degrees C, but not at near-freezing temperature. The equilibrium between the complex and higher aggregates appeared reversible.
1490652 A French version of the Sickness Impact Profile (SIP): stages in the cross cultural valida 1992 The Sickness Impact Profile is a quality of life scale developed in the United States which is now widely used in clinical trials in chronic conditions such as chronic obstructive lung disease, angina, rheumatoid arthritis, chronic pain, psoriasis, inflammatory bowel disease and cancer. Validated generic scales permit cross cultural comparisons within disease processes in clinical trials. As a simple, direct translation of a scale is inadequate, we have created a French version of the original US version of the Sickness Impact Profile. The first phase was qualitative. A first French translation of the original US version was back translated into English by three independent translators. A second French version resulted from a consensus reached by a panel of lay subjects and health professionals after comparing the original US version, the first French version and the three back translations. This second version was tested with a group of 40 healthy volunteers. This qualitative phase resulted in a French Test Version with content and face validity. The quantitative phase assessed the equivalence of the rank order of each item, by sub scale, in the US version with that of the French Test Version, ie the rank of the French item was comparable (+/- 2) to the rank of the corresponding US item. The French Test Version was tested with 47 healthy subjects. Of the 136 items of the Sickness Impact Profile, 13 were retranslated to create a final French version. This was similarly tested on ten healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
8643722 Soft-tissue fungal infections: surgical management of 12 immunocompromised patients. 1996 Jun Isolated fungal soft-tissue infections are uncommon but may cause severe morbidity or mortality among transplant recipients and other immunosuppressed patients. Twelve immunocompromised patients illustrating three patterns of infection were treated recently at the Duke University Medical Center. These groups comprised (I) locally aggressive infections, (II) indolent infections, and (III) cutaneous manifestations of systemic infection. Patient diagnoses included organ transplant, leukemia, prematurity, chronic obstructive pulmonary disease, and rheumatoid arthritis. Time from immunosuppression to biopsy ranged from 5.5 to 31 weeks. Organisms included Aspergillus, Rhizopus, Fusarium, Paecilomyces, Exophiala, and Curvularia. Patients presented with necrotic ulcerations or nodules. Surgical treatment ranged from radical debridement to excisional biopsy to none. Antifungal chemotherapy also was employed in some cases. The mortality rate was 33 percent, two patients dying without evidence of fungal infection. Six of the eight survivors cleared their infections. Necrotic skin lesions with surrounding erythema in this population call for prompt examination, biopsy, and culture. Group I lesions mandate radical excision with rapid intraoperative microscopic control and systemic antifungal medication. Group II requires surgical control with or without antifungal therapy. Group III requires systemic antifungal therapy for metastatic infection. In our opinion, treatment of fungal soft-tissue infection should be tailored to infection type and requires a team approach of surgeon and expert infectious disease consultation.
8647251 Inhibition of neutrophil elastase by the alpha1-proteinase inhibitor-immunoglobulin A comp 1996 May 6 Neutrophil elastase is thought to be involved in cartilage destruction occurring in rheumatoid arthritis despite the local presence of alpha1-proteinase inhibitor. Part of synovial fluid alpha1-proteinase inhibitor forms a mixed disulfide with immunoglobulin A, which has been postulated to lack inhibitory activity. We show here that the immunoglobulin-inhibitor complex tightly inhibits neutrophil elastase and cathepsin G, bovine pancreatic trypsin and chymotrypsin, and porcine pancreatic elastase. Although the rate constant of inhibition of neutrophil elastase by immunoglobulin A-bound alpha1-proteinase inhibitor (k(ass) = 9.2 X 10(5) M(-1) x s(-1)) is about 10-fold lower than that measured with the free inhibitor, it is high enough to enable efficient inhibition of elastase in vivo.
8734360 Long-term follow-up of health in blood donors with primary selective IgA deficiency. 1996 May A 20-year health follow-up study of 159 initially healthy blood donors with a severe deficiency of serum IgA ( < 0.05 x 10(-3) g/L) and of 45 donors with decreased serum IgA (0.05 x 10(-3)-0.8 g/L) was carried out. The findings indicate that persons with a severe deficiency of and decreased serum IgA who are healthy as young adults have an increased susceptibility to pneumonia and recurrent episodes of other respiratory infections and a higher risk of developing autoimmune diseases in middle age. Vitiligo, autoimmune hypothyreosis, milk intolerance, and possible rheumatoid arthritis were associated with severe IgA deficiency, but otherwise different degrees of IgA deficiency seem to be similar with respect to the appearance of diseases. Regardless of the fact that a total of 163 (80%) of the 204 IgA-deficient subjects had-episodes of infections, drug allergy, or autoimmune or atopic disease, the finding of primary, selective IgA deficiency in a healthy adult per se does not seem to predict severe life-threatening illnesses at least during 20 years of life.
8648990 [Autoimmune diseases of the peripheral cornea. Immunopathology, clinical aspects and thera 1996 Feb Noninfectious ulceration of the peripheral cornea remains a major diagnostic and therapeutic challenge. The pathogenesis in most of these disorders is unclear, however, on the basis of systemic connective tissue diseases, autoimmune mechanisms are most likely involved. The peripheral cornea has distinct morphological and immunological characteristics that predispose for inflammatory reactions. Major differences exist regarding humoral and cellular components of the immune system. In the peripheral cornea there is more high-molecular IgM and initial complement component C1 than in the central cornea and may predispose for immune complex formation. The close contact to the conjunctival vasculature provides the basis necessary to generate an immune response. Langerhans cells and macrophages as important antigen presenting and processing cells are present in higher number in the peripheral cornea. Autoimmune diseases that affect the peripheral cornea include collagen vascular diseases and Mooren's ulcer. Although this association is obvious in advanced rheumatoid arthritis more subtle forms of polyarteritis nodosa or systemic lupus erythematosus require careful medical evaluation and workup. Ocular manifestations may present as the initial clinical signs and require careful workup in these potentially lethal disorders.
8561823 [Tissue engineering: artificial tissue replacement containing vital components]. 1995 Nov Tissue engineering as a new field of research has gained increasing importance in recent years. The interdisciplinary field combines, biomaterials cell biology, and cell culture bio-engineering technology. The main focus of tissue engineering is the synthesis of artificial constructs or tissues based on vital cells or cell matrix. Biomaterials provide a three-dimensional structure to shape or guide tissue development. Isolated cartilage cells from a patient can form new tissues when suspended in non-woven resorbable polymers for reconstructive surgery. To achieve sufficient amounts of autologous cells for transplant formation, cells from biopsies have to be multiplied in monolayer culture. Dedifferentiated and undifferentiated mesenchymal cells may be used for bone and cartilage engineering. High cell densities in three-dimensional cultures require perfusion techniques to stabilize culture conditions. Morphogenetic factors such as BMP (bone morphogenetic protein) are thought to play a key role in inducing and controlling phenotypic tissue formation. In conclusion, modern in vitro approaches open new avenues for the development of vital tissue replacements for the clinic. Tissues can be repaired with the patient's own cells eventually leaving no residual artificial materials. Tissue engineering further provides new approaches for in vitro models of the extracellular matrix or diseases which mainly affect this matrix such as rheumatoid arthritis or osteoarthritis. This article describes recent developments in connective tissue engineering and discusses the potential for human tissue repair and reconstructive surgery.
7672879 Leflunomide prevents the development of experimentally induced myasthenia gravis. 1995 Apr Myasthenia gravis is an autoimmune disease in which autoantibodies specific to the acetylcholine receptor (AChR) are formed, leading to a gradual destruction of the receptors in muscles that are responsible for picking up nerve impulses, and results in weakness and eventual loss of muscle function. The novel immunomodulating drug leflunomide (HWA 486) has been shown to be very effective in preventing and halting ongoing disease in an array of experimental autoimmune disorders and reactions leading to organ graft rejection. Further, recent data from phase II clinical trials indicate that this drug is efficacious and is safe in humans with rheumatoid arthritis. In the studies reported here, we found that rats immunized with AChR-protein and not receiving leflunomide developed experimental myasthenia gravis (EMG) between day 7 and 11 post-immunization, and about 79% of these animals expressed clinical signs of disease. Treatment of AChR-protein immunized rats with leflunomide, from the day of disease induction, totally suppressed the development of EMG. Thus, the results we have obtained using leflunomide in EMG indicate that this drug could be beneficial in combating myasthenia gravis in humans.
9371986 Iron chelation therapy. 1995 Mar Iron chelation therapy is essential to prevent death from cardiac toxicity in patients with thalassemia major or other severe refractory anemias who need regular blood transfusions. Iron chelating drugs also have potential for clinical use as antiproliferative agents in neoplastic diseases and to reduce free radical-induced tissue damage in rheumatoid arthritis, anthracycline-induced cardiotoxicity, and reperfusion injury. Experimental data and clinical trials also suggest they may have therapeutic value as adjuncts to antimalarial and anti-Pneumocystis carinii therapy and to reduce aluminum toxicity. There is therefore an urgent need for an orally active, inexpensive iron chelating drug, because desferrioxamine, the only currently widely available iron chelator, must be given parenterally and is expensive, making it unavailable for long-term use in many parts of the world. L1 (also known as deferiprone, 1-2 dimethyl-3-hydroxpyrid-4-one, DMHP, and CP20) has emerged as an orally active iron chelator with comparable efficiency to desferrioxamine in both short- and long-term clinical studies. Adverse side-effects, principally agranulocytosis and arthropathy, have raised doubts about its safety, and further trials are now planned to evaluate the incidence of these and other toxicities. Despite numerous studies, no other orally active agent has been shown in clinical trials to be as effective or as safe as L1.
7750987 Characterization of eukaryotic protein L7 as a novel autoantigen which frequently elicits 1994 Dec Autoantibodies targeted against cellular proteins and nucleic acids are a common feature of autoimmune diseases. In this study, we show that ribosomal protein L7 is a novel autoantigen in patients suffering from systemic lupus erythematosus (SLE) and other connective tissue diseases. From 24 patients diagnosed as having SLE, 18 produce antibodies which precipitate in vitro translated L7 protein. The anti-L7 titer appears to correlate with the active state of the disease. Anti-L7 autoantibodies were also detected in 7 of 13 patients with mixed connective tissue disease (MCTD), 2 of 7 patients with rheumatoid arthritis (RA), 1 of 4 patients with Sjögren's syndrome (SS) and in 1 patient with progressive systemic sclerosis (PSS). Anti-L7 autoantibodies belong to the IgG-class and detect specifically at least two epitopes on the L7 molecule, as shown by immunoprecipitation and immunoblotting. The epitope(s) of the highly conserved C-terminal region are preferentially recognized. Utilizing rabbit anti-L7 serum, autoimmune sera and affinity-purified anti-L7 autoantibodies in immunoblotting, and rabbit and chicken anti-L7 antibodies in indirect immunofluorescence, we detect L7 protein in the nuclei and in the cytoplasm of various cell-lines. Yet unlike most integral structural components of ribosomes, L7 is absent from nucleoli.
8088316 The gold anti-rheumatic drug auranofin governs T cell activation by enhancing oxygen free 1994 Sep Gold-containing drugs continue to be used in the treatment of rheumatoid arthritis, but their mode of action remains unknown. One model to explain gold action is that gold-containing compounds can alter free radical production in cells of the immune system, but direct evidence for this hypothesis has been lacking. In this study we show that auranofin can enhance the rapid flux of reactive oxygen species (ROS), which accompanies phytohemagglutinin activation of peripheral blood T cells. Blocking this enhancement by the addition of antioxidants can reverse the functional effects of the drug on T cell responses, which we have previously demonstrated. These results provide strong experimental support for a model in which gold anti-rheumatics act by modulating ROS production. Furthermore, our experiments suggest that auranofin may be a useful tool to investigate the postulated role of ROS in the intra cellular T cell signaling pathway.
8350308 Influence of interferon-gamma on isolated chondrocytes from human articular cartilage. Dos 1993 Jun The effect of human recombinant interferon-gamma (IFN-gamma) on cultured human cartilage cells was studied by 2 variables: cell proliferation and proteoglycan synthesis. Cell proliferation was determined from 3H-thymidine incorporation rates in monolayer cultured chondrocytes. Proteoglycan synthesis was determined from 35S incorporation rates in monolayers and in chondrocytes cultured in agarose gel. IFN-gamma concentrations used in these experiments ranged from 10(-6) micrograms/ml (0.025 U/ml) to 10(-2) micrograms/ml (250 U/ml). The lowest concentrations are comparable with the synovial fluid levels in inflamed joints of patients with rheumatoid arthritis. At these concentrations, IFN-gamma was found to induce a dose dependent decrease of cell proliferation and of proteoglycan synthesis in monolayer cultured human chondrocytes. The decrease of proteoglycan synthesis was ascribed both to an inhibition of the proteoglycan protein core production and to a downregulation of the glycosaminoglycan chain elongation.
8323397 Microfibrillar elements in the synovial joint: presence of type VI collagen and fibrillin- 1993 Jun OBJECTIVES: The aims were to isolate and positively identify the microfibrillar elements which have been observed in the synovial lining. In addition, synovial fluid was examined for these elements to improve the understanding of the role of these structures in health and disease. METHODS: Bacterial collagenase digestion of bovine synovial linings and human and bovine synovial fluids was used to release intact, non-denatured microfibrillar elements. The microfibrils were isolated by Sepharose CL-2B chromatography and viewed by rotary shadowing. They were characterised by immunogold labelling with specific antibodies. RESULTS: Intact type VI collagen microfibrils and fibrillin-containing microfibrils were isolated and positively identified in the synovial lining from bovine ankle joints by immunogold labelling. Type VI collagen microfibrils were also present in the synovial fluid. CONCLUSIONS: The role of the microfibrillar elements in vivo is not fully understood, but their distribution in the synovial lining suggests they have an important role in the mechanical and physical properties of this tissue. The presence of type VI collagen microfibrils in synovial fluid poses the intriguing possibility that it may represent a product of microfibril turnover and a potential early marker for rheumatoid arthritis. Alternatively, type VI collagen may be specifically secreted into the synovial fluid to interact with hyaluronan and form part of the structure of synovial fluid.
8351876 [The locomotor system in irreversible renal failure treated with regular dialysis]. 1993 May Changes of the locomotor apparatus in prolonged uraemia with regular dialyzation treatment determine the quality of life with all its consequences for the patient. The greatest impact on osteodystrophic disease (the most typical finding on the skeleton) is exerted by the length of dialyzation treatment. Of 216 patients having regular dialyzation treatment in 1979 to 1992 the authors observed osteodystrophic disease in 25, i.e. 11.6%. As to other most frequently observed changes they recorded osteoporosis in 12.9%, only very rarely osteomalacia and even osteopetrosis (1.8%). Carpal tunnel syndrome was recorded in 17.4% as a symptom of so-called dialyzation amyloidosis and in one man they observed the development of typical rheumatoid arthritis shortly after the onset of haemodialyzation. This is a rare observation not described in the literature so far. Crystalline arthropathy, incl. typical attacks of gout, were recorded only in 11 patients (5%). Changes on the locomotor apparatus in conjunction with irreversible renal failure with regular dialyzation treatment were recorded in 45%. It is important to differentiate findings which are not associated with uraemia and haemodialysis. This applies in particular to osteoarthritis deformans of the joints and spine. In major uraemic changes participates in particular secondary hyperparathyroidism. These changes comprise in particular osteolysis or even spontaneous absorption, erosive changes and destructive spondylopathy. Contemporary findings on the locomotor apparatus are so varied that they must be classified.(ABSTRACT TRUNCATED AT 250 WORDS)
1487164 Endomysial antibody: is it the best screening test for coeliac disease? 1992 Dec The sensitivities and specificities of the IgA and IgG antigliadin antibody and the IgA antireticulin antibody have been compared with the recently described endomysial antibody directed against the basement membrane of smooth muscle in monkey oesophagus. One hundred and seventeen patients with adult coeliac disease (21 untreated), 84 patients with inflammatory bowel disease, systemic lupus erythematosus and rheumatoid arthritis (comprising the disease control group), 47 normal controls and a miscellaneous group of 29 patients, who were selected because of a positive reticulin staining pattern, were investigated. These results were correlated with the degree of abnormality of the intestinal mucosa in patients with adult coeliac disease. Endomysial antibodies were found in all patients with untreated coeliac disease and subtotal villous atrophy and in 47% of patients on a non-strict gluten free diet. One patient on a strict gluten free diet was positive and had partial villous atrophy while all patients in disease control groups were negative. Results were variable with the antireticulin and antigliadin antibodies. Sensitivity and correlation with subtotal villous atrophy in the untreated patients was 100%. It is concluded that the endomysial antibody is superior to other current antibody tests and should be used in preference for the diagnosis of coeliac disease.
1481226 Steroids and "the pill": early steroid research at Searle. 1992 Dec The announcement from the Mayo Clinic in 1949 of the dramatic effectiveness of cortisone in the treatment of rheumatoid arthritis stimulated tremendous interest in steroid chemistry, endocrinology, and related areas of medicine. Shortly thereafter, G. D. Searle & Co. initiated a major effort in steroid research, the objective of which was to discover better steroid drugs than those available at that time or steroids that could be used for conditions for which no compounds were previously available. This effort was remarkably successful and resulted in the introduction of several important pioneering drugs. These included norethandrolone, marketed in 1956 as Nilevar, the first anabolic agent with a favorable separation between protein building and virilization, and spironolactone, introduced in 1959 as Aldactone, the first steroid antialdosterone antihypertensive agent. Of special importance was the research that culminated in the discovery of Enovid. This substance, a combination of the progestin norethynodrel and the estrogen mestranol was first approved in 1957 for the treatment of a variety of disorders associated with the menstrual cycle. The era of oral contraception began in May 1960, when Enovid was approved by the Food and Drug Administration for ovulation inhibition, and was immediately thereafter introduced for such use.
1477300 High-level expression and characterization of a mouse-human chimeric CD4 antibody with the 1992 Oct The use of murine anti-CD4 monoclonal antibodies (MAbs) has shown considerable promise for the treatment of allograft rejection and rheumatoid arthritis. We have constructed mouse-human anti-CD4 antibodies with the goal of increasing their clinical potential by decreasing immunogenicity and improving effector functions. The chimeric antibodies were constructed by cloning the heavy and light chain variable regions of M-T412, a murine antibody raised against the human CD4 antigen, and joining them to the human G1, G4, or kappa constant regions in mammalian expression vectors. After transfection into mouse myeloma cells, stable cell lines were isolated that secrete up to 140 micrograms/ml chimeric antibody in static culture. The chimeric antibodies were equivalent to the murine antibody in their binding characteristics and relative affinities. However, the chimeric M-T412 MAbs have enhanced activity when compared to the murine G2a MAb in mediating antibody-dependent cell-mediated cytotoxicity using human CD4+ target and effector cells.
1514889 Lower extremity amputation in scleroderma. 1992 Sep Scleroderma or Systemic Sclerosis (SSC) is a disorder characterized by fibrosis of the skin and multiple internal organs. The pathological lesion is a triad of small artery intimal proliferation, medial thinning and adventitial scarring. Autoamputation of fingers and toes is often seen, but only a few cases of limb amputation in scleroderma patients have been reported. The Pittsburgh Scleroderma databank includes 1,030 patients with SSC. Among these were seven patients who sustained lower limb amputation. There were four patients with the CREST variant of SSC, two with diffuse scleroderma, and one who had SSC/rheumatoid arthritis/polymyositis overlap who sustained limb amputation. Of the seven, three were male and five had a significant smoking history. Ages ranged from 46 to 71 years. All patients underwent amputation for nonhealing ulcerations. No problems with postoperative wound healing were seen. Pathologic changes typical of SSC in addition to atherosclerotic peripheral vascular disease were described in one case. Three patients were successfully fitted with prostheses and became independent ambulators. Four patients could not be fitted with prostheses. No skin problems were reported related to prosthetic use. Our review demonstrates that SSC patients who undergo amputation can become successful prosthetic users and should be considered for prosthetic prescription.
1407687 Potentiation by cyclooxygenase inhibitors of the release of catecholamines from the rabbit 1992 Jun 8 Salicylates, at the high therapeutic doses used in the treatment of rheumatoid arthritis, produce an increase in ventilation and augment the carotid body reactivity to hypoxic stimulus, leading to an exaggerated hyperventilation during hypoxia. These effects had been related to the action of salicylates as uncouplers of oxidative phosphorylation. In the present study, carried out in an in vitro preparation of the rabbit carotid body, we show that acetylsalicylic acid and indomethacin, two anti-inflammatory drugs that are also powerful inhibitors of cyclooxygenase, the prostaglandin-synthetizing enzyme, produce an increase in the [3H]catecholamine release evoked by low oxygen stimulation. The drugs did not affect basal normoxic release, a finding that suggests that at the concentration used these anti-inflammatory agents do not have uncoupling actions, and that their effects on hypoxic-induced release of [3H]catecholamines is mediated by their specific action as cyclooxygenase inhibitors. In agreement with this suggestion we found that prostaglandin E2 completely prevented the effects of both anti-inflammatory agents. In addition, our data indicate that endogenously synthetized prostaglandins are powerful modulators of chemoreceptor cell function.