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ID PMID Title PublicationDate abstract
9093772 Naturally occurring inflammatory arthritis of the spondyloarthropathy variety in Cayo Sant 1997 Jan OBJECTIVE: The establishment of an animal model is a major priority in the battle to control inflammatory arthritis. Exploration to date has not yet identified a viable model for rheumatoid arthritis (RA), while artificial (e.g., collagen-induced) models do not seem to accurately represent RA. They, at least superficially, resemble human spondyloarthropathy. This study assesses the evidence for a common naturally-occurring spondyloarthropathy in a colony of free-ranging rhesus macaques. METHODS: Skeletal elements of 275 Macaca mulatta of known age and troop affiliation from the Cayo Santiago colony [Caribbean Primate Research Center (CPRC)] were surveyed for the presence of spondyloarthropathy and osteoarthritis. Fisher exact tests established the independence of each pathological condition, age, sex, troop and specific joint. RESULTS: Spondyloarthropathy was evident in 10% of females and 7% of males. In surviving troops, its frequency in 82 animals over 8 years of age was 20%. The skeletal distribution of spondyloarthropathy was independent of troop membership. Osteoarthritis affected 20% of females and 4% of males and was independent of their troop. Significant differences in the frequencies of specific joint involvement were found when the natural model, particularly in the polyarticular subgroup, was compared to the collagen-induced model. CONCLUSIONS: Naturally-occurring spondyloarthropathy afflicts 20% of susceptible-aged individuals in surviving macaque troops at the CPRC. This phenomenon appears to present a unique natural model for the characterization of the genetic, immunological and environmental contributions to this disease, which afflicts 0.5-5% of the human population. This natural model would appear to supplant the need for the collagen-induced large animal model.
10996030 Prevention of collagen-induced arthritis in DBA/1 mice by oral administration of AZ-9, a b 2000 Sep Collagen-induced arthritis (CIA) is an excellent model of rheumatoid arthritis (RA) in humans that is induced in DBA/1 mice immunized with bovine type II collagen (CII). Here, we report that the induction of CIA was effectively suppressed by oral administration of AZ-9, a purified polysaccharide with the average molecular weight of approximately 200 kDa that was produced by a soil bacterium, Klebsiella oxytoca. When AZ-9 was administered at 125-250 mg/kg/day orally for 9 consecutive days after immunization with CII followed by its administration every 3 days, resulted in a marked reduction of the incidence and the severity of CIA. The serum level of anti-CII IgG2a and the production of IFN-gamma and IL-12 in the draining lymph node (LN) cells were significantly lower in AZ-9-administered mice than the untreated control. These findings suggest that orally administered AZ-9 suppressed CIA through attenuating a Th1-type response to CII. AZ-9 could be fragmented into smaller molecules (3-4 kDa) without losing its suppressive activity.
10949721 Probing antinuclear antibody specificities by peptide phage display libraries. 2000 Jul OBJECTIVE: To uncover the specificities of autoantibodies to nuclear proteins (ANA) in patients with juvenile rheumatoid arthritis (JRA). METHODS: Peptide ligands for ANA were selected by panning random peptide phage display libraries on antibodies binding to HEp-2 cells. Positive phage clones were identified by the immunoscreening technique. RESULTS: Groups of peptides were identified, some of which share the core motifs of KTTTnPY, RVADnL/I or RnNSPL. Perinuclear and nuclear staining of HEp-2 cells were obtained with patient serum antibodies binding to the phage displaying the core peptide motifs. In contrast, no significant reactivity was seen with the antibodies binding to the wild type phage. Antibodies to the phage displaying peptides containing some of the core motifs were detected more frequently in ANA-positive as compared to ANA-negative JRA patients. Homology search with the selected core motifs revealed a significant homology with a number of human nuclear proteins and proteins from potential infectious agents that could serve as trigger in the breakdown of tolerance. CONCLUSION: Panning of phage display libraries on antibodies reacting with cellular structures can lead to the identification of their specificities. Thus, the peptide epitopes reported here constitute additional information that may lead to the development of diagnostic tests and the identification of the parental antigens that initiated the B cell responses in patients with JRA.
10738690 In vitro and in vivo evaluation of diclofenac sodium loaded albumin microspheres. 2000 Mar The use of polymeric carriers in formulations of therapeutic drug delivery systems has gained widespread application, due to their advantage of being biodegradable and biocompatible. Among the microparticulate systems, microspheres have a special importance since it is possible to target drugs and provide controlled release. Diclofenac sodium (DS), is a potent drug in the NSAID group having non-steroidal, anti-inflammatory properties, and is widely used in the treatment of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis. In this present study, it was aimed to prepare microsphere formulations of DS using a natural biodegradable polymer as a carrier for intraarticular administration to extend the duration period of the dosage form in the knee joint. Microsphere formulations of DS which were prepared were evaluated in vitro for particle size, yield value, encapsulation efficiency, surface morphology, and in vitro drug release. Two appropriate formulations were selected for in vivo trials. For the in vivo studies, Technetium-99m labelled polyclonal human immunogammaglobulin (99mTc-HIG) was used as the radiopharmaceutical to demonstrate arthritic lesions by gamma scintigraphy. After the induction of arthritis in knee joints of rabbits, the radio-labelled microspheres loaded with DS were injected directly into the articular cavity and at specific time points gamma scintigrams were obtained to find the residence time of the microspheres in knee joints in order to determine the most suitable formulation.
11263786 Cysteine protease activity is up-regulated in inflamed ankle joints of rats with adjuvant- 2001 Mar OBJECTIVE: Cysteine proteases are postulated to play a role in tissue destruction in the joints of animals with arthritis. The purpose of the present study was to confirm the concept that cysteine proteases are enzymes involved in the pathology of rheumatoid arthritis (RA). METHODS: Arthritis was induced in Lewis rats by adjuvant injection (adjuvant-induced arthritis [AIA] model) and scored for inflammation. At necropsy, the rear paws were either fixed in formalin and assigned a histologic score (based on synovial cell proliferation, cartilage erosion, bone erosion, and fibroproliferative pannus) or frozen, cryosectioned, and assayed for enzyme activity either by in situ cytochemical staining with a post-azo-coupling method using a chromogenic substrate (Z-arg-arg-MNA) or by a novel assay placing the tissue section directly in a cuvette using the fluorogenic substrate Z-arg-arg-AMC. RESULTS: Enzymatic activity, measured either in frozen sections in situ or in the cuvette assay, was positively correlated with joint destruction (r = 0.7) and inflammation (r = 0.8). Activity was not inhibited significantly by Pefabloc (a serine protease inhibitor), EDTA (a metalloprotease inhibitor), or pepstatin A (an aspartyl protease inhibitor) but was inhibited by E-64 and vinyl sulfone irreversible inhibitors of cysteine proteases. The effect of one of the vinyl sulfone cysteine protease inhibitors, Mu-Leu-HomoPhe-vinylsulfone, was tested in vivo by dietary administration at 2.2 mg/kg/day in the AIA model; this resulted in a significant decrease in inflammation and in the amount of cysteine protease activity measured in the joint tissue. CONCLUSION: Cysteine protease activity levels increase in the diseased state and may be an important target for designing small molecule inhibitors to reduce the inflammation and tissue destruction associated with RA.
12092181 Antioxidant enzymes levels in children with juvenile rheumatoid arthritis. 2001 Jul Pathogenic mechanism of chronic inflammation is associated with increased production of superoxide anion and hydrogen peroxide. In the neutralization process of that anions, superoxid dismutase (SOD), catalase (CAT), and glutation peroxidase (GPx) are key enzymes. Aim of study consists of establishing of some clinic-biological correlations in JRA chronic inflammation in childhood between clinical status and determination of lipoperoxidation products and antioxidative enzymes in the blood. MATERIAL AND METHODS: Blood samples were obtained from 20 patients admitted in 2nd Clinic of Pediatrics, 4-6 months after onset of disease, diagnosed with JRA, oligoarticular form (6 cases), poliarticular form (9 cases) and systemic form (5 cases), as compared to 10 control subjects. SOD, CAT, GPx were measured comparing with malonildialdehyde (MDA), seric glutation (GSH) and usual inflammatory tests (ESR, fibrinogen, CRP). Determinations were repeated after 6 weeks of treatment. RESULTS: In all our cases, level of antioxidant enzymes (CAT, GPx) was decreased at time of diagnosis, concomitant with increased MDA, SOD and inflammatory tests. In most of cases, after 6 weeks of correct anti-inflammatory treatment, levels of enzymatic antioxidant markers were still decreased, as compared to usual inflammatory tests that came back to normal. Persistent decreased antioxidant enzymatic activity was found in cases that need immunomodulatory activity (Methotrexat). CONCLUSIONS: Determination of antioxidant enzymes level can be considered an evolution marker in JRA. More studies are necessary to find if antioxidant potential of blood can be used as following marker for immunosuppressive therapy.
11437490 Evaluation of the percentage of peripheral T cells with two different T cell receptor alph 2001 Jun Approximately 25% of mature T cells possess two distinct cytoplasmic T cell receptor (TCR) alpha-chains, due to productive gene rearrangements of both alleles. Expression of two different alpha-chains at the cell surface is a potential risk factor for development of autoimmunity. However, it has been difficult to determine the frequency of peripheral T cells with two different alpha-chains at the surface. Our new approach is based on comparing by flow cytometry the percentage of cells that express a given Valpha-chain between wild-type mice and mice that are hemizygous for a disrupted Tcra locus (Tcra+/-) and consequently unable to express two rearranged Tcra genes. We consistently found that approximately 8% of total peripheral T cells express two surface alpha-chains. The importance of dual alpha-T cells in autoimmunity was examined in a mouse model for rheumatoid arthritis, namely collagen-induced arthritis (CIA). No significant difference was observed between Tcra+/- mice and wild-type littermates, considering arthritis incidence, day of disease onset, and maximum arthritic score. We therefore conclude that there is incomplete phenotypic allelic exclusion in TCRalpha, and that the presence of a significant number of potentially multireactive T cells does not increase the susceptibility to develop autoimmune arthritis.
10980337 Genome analysis of collagen disease in MRL/lpr mice: polygenic inheritance resulting in th 2000 Aug 31 MRL/MpJ-lpr/lpr (MRL/lpr) mice develop collagen disease involving vasculitis, glomerulonephritis, arthritis and sialoadenitis, each of which has been studied as a model for polyarteritis, lupus nephritis, rheumatoid arthritis and Sjögren's syndrome, respectively. In the previous studies, we observed genetic segregation of these complex pathological manifestations throughout the genome recombination with a C57Bl/6-lpr/lpr or a C3H/HeJ-lpr/lpr (C3H/lpr) strain of mice which rarely develops such lesions, indicating that development of collagen disease is dependent on an MRL host genetic background. To clarify the mode of inheritance and the gene loci affecting four types of the lesions in MRL/lpr mice; vasculitis, glomerulonephritis, arthritis and sialoadenitis, a genetic dissection of the lesions was carried out by using MRL/lpr, C3H/lpr, (MRL/lprxC3H/lpr) F1 intercross, and MRL/lprx(MRL/lprxC3H/lpr) F1 backcross mice. Definition of each lesion was performed by histopathology under light microscopy, and genomic DNA of the backcross mice were subjected to association studies by chi-square analysis for determining which polymorphic microsatellite locus occurs at higher frequency among affected compared to unaffected individuals for each lesion. We observed that gene loci recessively associated with each lesion were mapped on different chromosomal positions. We conclude that each of four types of the lesions in MRL/lpr mice is under the control of different set of genes, suggesting the complex pathological manifestations of collagen disease result from polygenic inheritance.
10451604 [T lymphocyte immunological response to different antigenic fractions of Mycobacterium bov 1999 Apr BACKGROUND: The possible relationship of stress or heat-shock proteins (hsp) with the pathogenesis of autoimmune disease has been intensely studied recently. In adult rheumatoid arthritis, a bacterial hsp (65 kDa hsp from Mycobacterium tuberculosis or bovis) would have a cross reactivity with a hsp of ARTICULAR cartilage. AIM: To assess the cellular immune response to the 65 kA hsp from M Bovis in children. PATIENTS AND METHODS: The proliferative response of peripheral mononuclear cells of 20 children with juvenile chronic polyarthritis and 20 healthy controls, against the 65 kDa hsp and other antigenic fractions from M bovis, was studied. RESULTS: Patients with juvenile chronic polyarthritis had a intense reaction against 65 kDa fraction and a second fraction located between 32.5 and 27.5 kDa. Patients with a prolonged evolution of the disease (more than five years), reacted preferentially to an antigenic segment located between 32.5 and 27.5 kDa and those with a shorter evolution did so with an antigen of 27.5-18.5 kDa. CONCLUSIONS: These results support the hypothesis that 65 kDa hsp from M bovis is involved in the pathogenesis of chronic juvenile polyarthritis and suggest that patients with short or prolonged evolutions of the disease would react to different antigenic fractions.
10493688 Current treatment by United States and Canadian pediatric rheumatologists. 1999 Sep OBJECTIVE: To determine current treatment practices for 11 selected pediatric rheumatic diseases. METHODS: A questionnaire was mailed to 224 US and Canadian physicians who were listed in membership directories that included pediatric rheumatologists. RESULTS: One hundred seventy-four questionnaires (78%) were returned. Board certified pediatricians accounted for 86% of respondents. Nonsteroidal antiinflammatory drugs were the most commonly used medicines for all forms of juvenile rheumatoid arthritis (JRA), seronegative enthesopathy and arthropathy syndrome (SEA), and Henoch-Schönlein purpura, whereas oral corticosteroids were most frequently used for systemic lupus erythematosus (SLE), juvenile dermatomyositis, polyarteritis nodosa, and sarcoidosis. Intraarticular corticosteroid injection was the second most common therapy for pauciarticular JRA, but methotrexate (MTX) was second for polyarticular and systemic onset forms of JRA, and sulfasalazine was second for SEA. For all diseases, MTX was administered orally roughly twice as often as subcutaneously. In treating SLE, cyclophosphamide was used more frequently than azathioprine, cyclosporin A, or intravenous immunoglobulin. CONCLUSION: The results from this survey should allow individual practitioners to compare their treatment patterns to pediatric rheumatologists in the US and Canada as a whole.
10343524 A quantitative method for detecting deposits of amyloid A protein in aspirated fat tissue 1999 Feb OBJECTIVE: To describe a new, quantitative, and reproducible method for detecting deposits of amyloid A protein in aspirated fat tissue and to compare it with smears stained with Congo red. METHODS: After extraction of at least 30 mg of abdominal fat tissue in guanidine, the amyloid A protein concentration was measured by a monoclonal antibody-based sandwich ELISA. RESULTS: The concentrations in 24 patients with arthritis and AA amyloidosis (median 236, range 1.1-8530 ng/mg tissue) were higher (p < 0.001) than in non-arthritic controls, uncomplicated rheumatoid arthritis, and other types of systemic amyloidosis (median 1.1, range 1.1-11.6 ng/mg tissue). Patients with extensive deposits, according to Congo red staining, had higher concentrations than patients with minute deposits. CONCLUSION: This is a new, quantitative, and reproducible method for detecting deposits of amyloid A protein in aspirated fat tissue of patients with arthritis, even when minute deposits are present as detected in smears stained with Congo red.
9557893 Retinal changes and tumorigenesis in Ramon syndrome: follow-up of a Brazilian family. 1998 Apr 28 We report on the clinical evolution of the Brazilian family with Ramon syndrome described by de Pina-Neto et al. [1986, Am J Med Genet 25:441-443]. Three members (patients IV-2, IV-18, and IV-19) have developed pigmentary changes in the retina and paleness of the optic disk. Patient IV-18 also has developed giant hypertrophy of the labia minora that, when examined histopathologically, was found to be due to neoplastic fibroblast and epithelial proliferation caused by a fibromatous process similar to that reported in the gingivae of the patients with this syndrome. Audiologic function of patient IV-2 was normal, and no skin lesions were detected. The articular signs and symptoms show that the affected relatives developed rheumatoid arthritis, which is currently inactive in patient IV-18, whereas patient IV-2 did not develop these alterations.
9353633 Immunohistochemical study on type II collagen-induced arthritis in DBA/1J mice. 1997 Oct We performed immunohistochemical examinations on type II collagen-induced arthritis (CIA) mice, focusing attention on the changes in distribution of plasma proteins and extracellular matrix materials (ECM) and in expression of adhesion molecules. The limb joints of male DBA/1J mice immunized with bovine type II collagen were obtained at 6 to 20 weeks after the first immunization. In the early stage of CIA, deposition of fibrin, IgG, von Willebrand factor (vWF) and fibronectin was detected on the surface of the synovial lining layer and articular cartilage and in the articular cavity. In the stage of pannus formation, prominent proliferation of ICAM-1-positive capillaries and marked infiltration of LFA-1-positive neutrophils were observed in the pannus. The superficial portion of the pannus and basement membranes of proliferated capillaries were strongly positive for type IV collagen and laminin. In the late stage, the pannus invaded and destroyed articular cartilage and subchondral bone, and strongly positive immunostainabilities for both lysozyme and fibronectin were observed on the surface of the pannus and at the junctional portion between the pannus and the cartilage. The present immunohistochemical findings on the distribution of plasma proteins and ECM materials and the expression of adhesion molecules in CIA mice were similar to those in rheumatoid arthritis (RA) in many aspects. This suggests that CIA is a useful model for the investigation of RA.
11828732 [A case of lymphocytic interstitial pneumonia with Sjögren's syndrome and systemic lupus 2001 Oct A 47-year-old-woman was admitted to our hospital complaining of thirst and dry cough after catching cold. Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE) were diagnosed. Chest X-P and CT findings suggested strongly that she had interstitial pneumonia. Thoracoscopic lung biopsy was therefore performed, and the biopsy specimens showed marked infiltration of small lymphocytes and of plasma cells into the alveolar walls and interlobular septa. Since the infiltrating cells were not atypical and gene analysis did not show mono-clonality, we made a diagnosis of lymphocytic interstitial pneumonia (LIP). Because the patient's symptoms appeared only after she caught cold, we suspected that virus infections were somewhat involved in the etiology of these diseases. The level of human herpesvirus-6 (HHV-6) antibody was high, and furthermore, HHV-6 was detected using the polymerase chain reaction from lung biopsy specimens. We suspected in this case that LIP, SjS, and SLE had appeared concomitantly after an active HHV-6 infection.
10684105 [Sjögren's syndrome and malignant lymphoma]. 1998 Sep To diagnose and study the early stage of Sjögren's syndrome associated with malignant lymphoma, the authors used the PCR technique of B malignant lymphoma gene for lacrimal gland tissues in four patients with Sjögren's syndrome and in five patients suffering from B malignant lymphoma. The results showed that all cases of Sjögren's syndrome were negative and all cases of B malignant lymphoma were positive. These suggest that in general the patients with primary or secondary Sjögren's syndrome have no malignant lymphoma genes, but those who have chronic fever and enlarged superficial lymph nodes should under go this technique for early diagnosis and treatment of Sjögren's syndrome associated with malignant lymphoma.
10374420 Clinical manifestations and immunological features of primary Sjögren's syndrome with liv 1998 Mar OBJECTIVE: To evaluate the incidence, severity, clinical manifestations and immunological features relevant to liver involvement in 135 cases of primary Sjögren's syndrome. METHODS: One hundred and thirty-five patients with definite primary Sjögren's syndrome were analyzed retrospectively for liver involvement by the abnormalities of the liver enzymes, bilirubin level and liver biopsied section. RESULTS: The liver involvement in 30 patients (22.2%) could be etiologically ascribed to Sjögren's syndrome itself. The clinical spectrum and severity of this entity differed widely, 36.6% showed no relevant clinical symptoms, however jaundice was found in 46.7% of patients. Six patients showed pathological changes of chronic active hepatitis. 73.3% of all patients with liver involvement responded to steroid and immunosuppressive drugs, yet with a tendency to relapse (two cases). Liver cirrhosis was developed in five cases. The spectrum of serum autoantibodies in the patients with liver involvement showed no difference from those without liver involvement. Most of them were compatible with the serum profile of autoimmune hepatitis type-1. CONCLUSIONS: Liver involvement was complicated in 22.2% patients of primary Sjögren's syndrome. Clinical manifestations were non-specific and the main pathological change was chronic active hepatitis. The differential diagnosis between Sjögren's syndrome with liver involvement and type-1 autoimmune hepatitis could be only ascribed to other systemic clinical manifestations of Sjögren's syndrome.
9767249 Detection of anti-type VII collagen antibody in Sjögren's syndrome/lupus erythematosus ov 1998 Aug Bullous systemic lupus erythematosus (SLE) is a chronic, widespread, non-scarring, subepidermal blistering eruption associated with autoimmunity to type VII collagen. We describe a patient with Sj ogren's syndrome/lupus erythematosus overlap syndrome who showed transient blistering eruptions over limited skin surface and in oral mucosa. At the time of aggravation, the patient's serum contained IgG autoantibodies that bound to the dermal side of 1 mol/L NaCl-split normal skin, as determined by an indirect immunofluorescence test, and that reacted to type VII collagen, as determined by immunoblotting on dermal extract. Our observations suggest that a chronic, widespread, blistering eruption is not a prerequisite for the diagnosis of bullous SLE, and a mild, transient, blistering eruption could be a manifestation of type I bullous SLE.
9636956 Optic neuropathy in a child with primary Sjögren's syndrome. 1998 May An eight-year-old girl developed optic neuritis followed by primary Sjögren's syndrome confirmed by a lip biopsy. Glucocorticoid therapy combined during six months with monthly intravenous pulse cyclophosphamide ensured resolution of the sicca syndrome but failed to improve the visual impairment. This is the second pediatric case of optic neuritis associated with primary Sjögren's syndrome, and the first pediatric case in which optic neuritis was the only neurologic manifestation.
9424142 [Rheumatic manifestations associated with infection by the hepatitis C virus]. 1997 Oct The development in the past few years of laboratory test for hepatitis C virus allow us to associate it with a broad range of autoimmune manifestations such as cryoglobulinemia and Sjögren syndrome. As in other virus' infections, rheumatic manifestations have been described during VHC infection, but there are no large studies enough to know their true frequency and characteristic. The three reported patients in this issue presented and HCV related arthropathy once clinical picture, laboratory test and following, allowed us to exclude other diagnostics. Clinical manifestations ranged from arthralgias and intermittent arthritis to symmetric polyarthritis without any kind of join damage.
9236786 Slowly conducting, low-threshold components of sensory nerve potentials in peripheral neur 1997 Aug By recording the averaged potential from a microelectrode inserted into the nerve, small late components of the sensory nerve action potential can be analyzed. We studied the thresholds of the late components in median nerves of 15 normal subjects and 37 patients with peripheral neuropathies. Under normal conditions, the late components reflected the activities of small myelinated fibers which had high thresholds. In the patients with peripheral neuropathies, a part of the late components often had abnormally low thresholds, occasionally the lowest. The presence of low-threshold, late components was related to the pathologies of the different types of neuropathy and correlated with the numbers of regenerating clusters in sural nerve biopsies. These slowly conducting, low-threshold components may originate from regenerating or remyelinating fibers, and therefore should have prognostic value.