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ID PMID Title PublicationDate abstract
8821518 [Anti-inflammatory effect of Urtica dioica folia extract in comparison to caffeic malic ac 1996 Jan Urtica dioica extract is a traditionary used adjuvant therapeutic in rheumatoid arthritis. The antiphlogistic effects of the urtica dioica folia extract IDS 23 (Extractum Urticae dioicae foliorum) and the main phenolic ingredient caffeic malic acid were tested concerning the inhibitory potential on biosynthesis of arachidonic acid metabolites in vitro. The caffeic malic acid was isolated from Urtica folia extract using gel exclusion- and high performance liquid chromatography and identified by mass spectroscopy and nuclear magnetic resonance. Concerning the 5-lipoxygenase products IDS 23 showed a partial inhibitory effect. The isolated phenolic acid inhibited the synthesis of the leukotriene B4 in a concentration dependent manner. The concentration for halfmaximal inhibition (IC50) was 83 microns/ml in the used assay. IDS 23 showed a strong concentration dependent inhibition of the synthesis of cyclooxygenase derived reactions. The IC50 were 92 micrograms/ml for IDS 23 and 38 micrograms/ml for the caffeic malic acid. Calculating the content in IDS 23 the caffeic malic acid is a possible but not the only active ingredient of the plant extract in the tested assay systems. It is demonstrated that the phenolic component showed a different enzymatic target compared with IDS 23. The antiphlogistic effects observed in vitro may give an explanation for the pharmacological and clinical effects of IDS 23 in therapie of rheumatoid diseases.
8580800 Clonal CD3+CD8+ large granular lymphocyte (LGL)/NK-associated (NKa) expansions: primary ma 1995 Apr This study reports the clinical, haematological and immunophenotypic features of a series of 25 patients with clonal expansions of large granular lymphocytes (LGL)/NK-associated (NKa) cells. These showed a male predominance (16:9) with a median age of 67 (range 38-91) years; four had a documented history of rheumatoid arthritis, a further 18 had diverse clinical disorders, and the remaining three were clinically well. Mild anaemia was found in approximately half the patients and a lymphocytosis (seen in approximately 70% of the cases) was usually modest (< 10.0 x 10(9)/l). Neutropenia was the most frequently observed feature, and this was typically persistent in nature. Serum studies revealed few consistent features although positive rheumatoid factor and increased soluble CD8 levels were noted in 67% and 87% of those cases tested. Phenotypically, all cases were CD2+CD3+CD8+ and expressed membrane TCR alpha beta chains; most (17/22) were additionally CD5+ and (19/22) CD7+. The staining intensities of CD5 and CD7 antigens were however lower than that of normal CD4+ and CD8+ blood lymphocytes. Expression of NKa antigens was variable although 16/22 cases were CD16+CD56- and 19/22 were CD57+. Clonal CD3+CD8+ LGL/NKa expansions with a CD16+CD56+ composite phenotype were not seen in this patient series. Analyses of 'activation' antigens showed a consistent lack of CD25 expression by CD3+ cells, but increased CD3/Ia co-expression was found in a high proportion (19/25) of cases. Studies of CD45R isoform expression by CD8+ LGL/NKa cell fractions revealed a consistent CD45RA+RO- profile for all cases tested.(ABSTRACT TRUNCATED AT 250 WORDS)
8481059 IgG3 cryoglobulins in autoimmune MRL-lpr/lpr mice: immunopathogenesis, therapeutic approac 1993 Mar MRL-lpr/lpr mice spontaneously develop an autoimmune disease resembling systemic lupus erythematosus and rheumatoid arthritis. One of the unique serological abnormalities in this strain is remarkably high concentrations of cryoglobulins. Analysis of immunoglobulin components in their cryoglobulins has shown selective enrichment of a particular IgG subclass, IgG3. As IgG3 enrichment is also found in two other cryoglobulins, which are induced after injection with bacterial lipopolysaccharides or infection with malaria, IgG3 apparently represents a major source of murine cryoglobulins. Studies on murine IgG3 monoclonal antibodies (mAbs) have clearly shown that murine IgG3 have the unique physiochemical property to self associate through non-specific IgG3 Fc-Fc interaction, and that most of them can generate monoclonal cryoglobulins. Most strikingly, IgG3 monoclonal cryoglobulins with rheumatoid factor (RF) activity induce extensive pathological manifestations: skin vascular purpura and glomerulonephritis with 'wire loop' lesions. Although the cryoglobulin activity of IgG3 RF mAb is solely responsible for the generation of glomerular lesions (both RF and cryoglobulin activities are necessary for skin vascular lesions), the absence of nephritogenic activity by some IgG3 cryoglobulins supports the idea that qualitative features of cryoglobulins are critical to determine their pathogenic activity. The demonstration of a positive correlation between the production of IgG3 cryoglobulins and the development of lupus nephritis in MRL-lpr/lpr mice further substantiates the pathological importance of cryogenic autoantibodies. On the other hand, it should be emphasised that non-cryogenerating IgG3 autoantibodies may not be harmful, but even protective, as a result of their interaction with pathogenic IgG3 cryoglobulins. Finally, the development of an experimental model of cryoglobulinaemia associated with vascular and glomerular disease certainly represents an invaluable opportunity to study the molecular mechanisms responsible for the generation of cryoglobulins and their associated tissue lesions, and also to assess various therapeutic approaches. Our demonstration that anti-idiotypic mAb can prevent the pathogenic effects of the cryoprecipitable IgG3 RF mAb suggests strongly that such a therapeutic approach might be successful in similar diseases in man.
1355612 Activation of HLA-DR and interleukin-6 gene transcription in resting T cells via the CD2 m 1992 Sep Only a minority of T cells at cell-mediated immune lesions are antigen specific. In the lesions of human autoimmune disease, such as the synovial membrane in rheumatoid arthritis, the T cells are activated as shown by a variety of phenotypic and functional changes including the expression of HLA-DR and the production of interleukin-6 (IL-6). The stimulatory pathway involved is unknown but does not seem to involve the T-cell receptor. Alternative pathways of activation which may be involved include the CD2 molecule. It is shown that the formation of sheep red blood cell (SRBC) rosettes with resting T cells from human peripheral blood, which is equivalent to CD2/LFA-3 binding, leads to the de novo transcription of the HLA-DR and IL-6 genes and the expression of HLA-DR on the surface of the T cells. There was no transcription of the interleukin-2 (IL-2) or the interleukin-2 receptor (IL-2R) genes and Tac expression was not seen. The rosetted T cells did not proliferate. These are all characteristics of T cells at chronic inflammatory sites. It is concluded that receptor-ligand interactions between CD2/LFA-3, which are expressed in increased amounts in the rheumatoid joint, may be one pathway by which antigen non-specific T cells are recruited as effector cells in lesions of human autoimmune disease.
8759766 Inhibition of superantigen-induced proinflammatory cytokine production and inflammatory ar 1996 Aug 15 We have used fas-defective MRL-lpr/lpr mice to study the effects of the staphylococcal enterotoxin superantigens on the development of autoimmune, inflammatory joint disease in animals that are susceptible to the development of rheumatoid arthritis-like disease. We show that systematic administration by a single i.p. injection of staphylococcal enterotoxin B (SEB; 10 micrograms/mouse) caused a mild, inflammatory arthritis +30 days postchallenge in the knee joints of young (< 2-mo-old) MRL-lpr/lpr mice, but not aged-matched MRL +/+ mice. In aged (> 8-mo-old) MRL-lpr/lpr mice, but not in aged MRL +/+ mice, SEB caused a severe, inflammatory arthritis, as assessed histologically, and systemic autoimmune disease, including glomerulonephritis and autoantibody production. Furthermore, in aged MRL-lpr/lpr mice, SEB but not heat-denatured SEB caused acute weight loss and elevated levels of serum proinflammatory cytokines. Compared with highly purified peritoneal macrophages obtained from either aged MRL +/+, young MRL-lpr/lpr, or young MRL +/+, peritoneal macrophages obtained from aged MRL-lpr/lpr mice constitutively expressed 2- to 10-fold greater levels of TNF-alpha, IL-1 beta, IL-6, and IL-10, and produced elevated amounts of these cytokines when treated in vitro with SEB. SEB-challenged aged MRL-lpr/lpr mice treated with anti-TNF mAb (100 micrograms/mouse; every other day), anti-V beta 8 TCR mAb (250 micrograms/mouse; every other day), or orally with the novel TNF-alpha inhibitor MDL 201,449A (9-[(1R, 3R)-trans-cyclopentan-3-ol] adenine; 25 mg/kg/day) exhibited reduced inflammatory arthritis, autoantibody formation, and serum TNF-alpha levels, but not IL-10 levels, after +30 days of treatment. These data suggest that SEB is an extremely potent macrophage-activating factor in vitro and in vivo, enhancing several aspects of autoimmune disease in MRL-lpr/lpr mice, and that anti-TNF therapies may have potential use in inflammatory arthritis.
1322670 A rheumatoid factor from a normal individual encoded by VH2 and V kappa II gene segments. 1992 Aug OBJECTIVE: To gain insight into the immunoglobulin variable-region repertoire of anti-IgG antibodies (rheumatoid factors [RF]), we characterized the VH and V kappa gene segments utilized in an IgM-RF-secreting lymphoblastoid cell line (SSH23) isolated from a normal individual. METHODS: The cell line SSH23 was established by Epstein-Barr virus transformation of peripheral blood non-T mononuclear cells. First-strand complementary DNA (cDNA) was generated and used for polymerase chain reaction amplification of the heavy and light chain variable domains. The amplified variable domains were sequenced and compared with an extensive database of germline and cDNA V gene segments. RESULTS: The VH sequence was found to be identical to a previously described fetal VH2 incomplete cDNA and to differ by only 3 nucleotides from a JH proximal germline VH2 gene segment. To our knowledge, this is the first example of a VH2 rheumatoid factor. The V kappa 2-J kappa 4 light chain contains an uncommon 10-amino acid third complementarity-determining region (CDR 3). CONCLUSION: Utilization of preimmune fetal VH gene segments and unusual light chain junctional diversity appear to be features shared by many physiologic and pathologic rheumatoid factors.
8308773 Rheumatic manifestations in human immunodeficiency virus positive and negative individuals 1993 Nov OBJECTIVE: Assess the impact of human immunodeficiency virus (HIV) infection on the onset of rheumatic manifestations in HIV+ patients, and to compare them with a control HIV- group with similar risk factors. METHODS: We prospectively studied 74 consecutive HIV+ patients, looking for clinical and laboratory findings of rheumatic manifestations and compared them with 72 control subjects with similar risk factors for HIV who tested negative for HIV. RESULTS: Rheumatic manifestations were more frequently observed in the HIV+ group than the HIV-group (p < 0.001): Arthralgias were found in 34 (45%), arthritis in 8 (10%), and Reiter's syndrome in 6 (8%). Laboratory findings revealed rheumatoid factor in 16 (21%) HIV+ vs 2 (2%) in HIV-, antinuclear antibodies in 13 (17%) HIV+ vs 0 in HIV-, IgG anticardiolipin antibodies in 70 (94%) HIV+ vs 7 (9%) in HIV- (p < 0.001). Hyperuricemia was found in 31 HIV+ patients (41%), and hypouricemia in 4 (5%), compared with none in the HIV- group (p < 0.0001). Neoplasia were identified in 13 HIV+ patients, in 7 associated with hyperuricemia and 3 with hypouricemia. Of interest, 2 patients had urate abnormalities before the diagnosis of neoplasia. CONCLUSIONS: Our study suggests that rheumatic manifestations are more prevalent in HIV+ patients. In advanced HIV infection, hypo and hyperuricemia may be considered markers of neoplasia.
1451706 Investigation of joint disease. 1992 The role of nuclear medicine in the diagnosis and management of the major arthropathies is critically reviewed, with particular reference to osteoarthritis, rheumatoid and similar forms of arthritis, ankylosing spondylitis, non-specific back pain, gout, the neuropathic joint, avascular necrosis, infection and the consequences of prosthetic joint insertion. Attention is drawn both to practical applications and deficiencies in current techniques and knowledge.
8608686 Silicone breast implant--associated musculoskeletal manifestations. 1995 Nov Three hundred consecutive women with silicone breast implants (SBI), referred to the arthritis clinic with a variety of musculoskeletal complaints, were evaluated for the presence of underlying connective tissue disease. A complete history and physical examination were performed, as well as laboratory testing for C-reactive protein, rheumatoid factor; and autoantibody determination by indirect immunofluorescence and immunodiffusion. The group mean age was 44.4 years (range 25-69), the mean time from initial implant surgery to appearance of symptoms was 6.8 years (range: 6m-19y) and 83.3% of women studied had clinical manifestations highly suggestive of an underlying connective tissue disorder. Fifty-four percent met criteria for fibromyalgia and/or chronic fatigue syndrome, distinct connective tissue diseases was detected in 11%, undifferentiated connective tissue disease or human adjuvant disease was found in 10.6%, and a variety of disorders such as angioneurotic oedema, frozen shoulder, multiple sclerosis-like syndrome were present. Several other miscellaneous conditions including recurrent unexplained low grade fever, hair loss, skin rash, sicca symptoms, Raynaud's phenomenon, carpal tunnel syndrome, memory loss, headaches, chest pain, and shortness of breath were also seen accompanying specific and non-specific conditions. Seventy percent of patients who underwent explanation of the implants reported improvement of their systemic symptomatology. A significant proportion of SBI patients referred for rheumatic evaluation have clinical manifestations highly suggestive of an underlying connective tissue disease. Furthermore, improvement of their symptomatology follows explanation of the implants in over half of the patients.
8023820 Chronic renal disease and papillary necrosis associated with the long-term use of nonstero 1994 Jul The risk of renal papillary necrosis and renal dysfunction due to the chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) is unknown. In a prospective study of 259 heavy analgesic users seen in a general medical hospital over an 11-year-period beginning in January 1982, 69 new cases of analgesic nephropathy with renal papillary necrosis were confirmed by intravenous urogram (26.6%), ultrasonography (30.4%), and/or computed tomography (43%). Twenty-nine of these patients (42%) had consumed excessive quantities of NSAIDs alone; an additional nine patients (13%) had consumed NSAIDs predominantly in combinations with paracetamol, aspirin, phenacetin, caffeine, and/or traditional herbal medications. Of those patients who consumed NSAIDs alone, 17 had consumed only a single type of NSAID and the remaining 12 had consumed multiple types of NSAIDs. The amount of NSAIDs administered ranged from 1,000 to 26,600 capsules or tablets over a 2- to 25-year period. Renal impairment (serum creatinine, 126 to 778 mumol/L) was noted in 26 of these 38 patients (64.8%). The reasons given for consuming NSAIDs include gouty arthritis (18 patients), osteoarthritis (seven patients), rheumatoid arthritis (six patients), chronic headache (three patients), gouty arthritis plus chronic headache (three patients), and chronic backache (one patient). All patients were prescribed these drugs and were followed medically. The occurrence of analgesic nephropathy was predominantly in males (male to female ratio, 1.9:1). Most of the patients did not have the characteristic psychological profile attributed previously to analgesic abuse nephropathy. Associated addictive habits, such as the use of psychotropic drugs and sleeping tablets, purgative abuse, and alcoholism, were absent.(ABSTRACT TRUNCATED AT 250 WORDS)
7516184 TSG-6, an arthritis-associated hyaluronan binding protein, forms a stable complex with the 1994 Jun 14 TSG-6 is a secreted 35-kDa glycoprotein, inducible by TNF and IL-1. The N-terminal portion of TSG-6 shows sequence homology to members of the cartilage link protein family of hyaluronan binding proteins. The C-terminal half of TSG-6 contains a so-called CUB domain, characteristic for developmentally regulated proteins. High levels of TSG-6 protein are found in the synovial fluid of patients with rheumatoid arthritis and some other arthritic diseases. Here we show that TSG-6 readily formed a complex with a protein present in human, bovine, rabbit, and mouse serum. This complex was stable during SDS-PAGE under reducing conditions, and in the presence of 8 M urea. The protein that binds TSG-6 was purified from human serum and identified as inter-alpha-inhibitor (I alpha I) by N-terminal microsequencing. Microsequencing of the complex itself revealed the presence of TSG-6 and two of the three polypeptide chains of I alpha I (bikunin and HC2). Experiments with recombinant TSG-6 and I alpha I purified from human serum showed that the TSG-6/I alpha I complex is rapidly formed even in the apparent absence of other proteins at 37 degrees C, but not at 4 degrees C. The TSG-6/I alpha I complex was cleaved by chondroitin sulfate ABC lyase, suggesting that cross-linking by chondroitin sulfate is required for the stability of the complex.(ABSTRACT TRUNCATED AT 250 WORDS)
8913659 Methotrexate in primary Sjögren's syndrome. 1996 Sep OBJECTIVE: To determine the safety and efficacy of methotrexate (MTX) in the treatment of primary Sjögren's syndrome (SS). METHODS: An open, one-year pilot study of MTX (0.2 mg/kg body weight taken weekly) for the treatment of SS was performed. Seventeen patients with primary SS according to EEC criteria were enrolled in the study. Outcome was determined on the basis of clinical and laboratory parameters. RESULTS: Weekly administration of MTX resulted in improvement of the main subjective symptoms (dry mouth and eyes) as well as in the frequency of parotid gland enlargement, dry cough and purpura. However, no improvement in the objective parameters of dry eyes and dry mouth were observed. Persistent asymptomatic elevation of the hepatic transaminase levels led to a dosage reduction in 7 patients (41%). CONCLUSIONS: Weekly MTX may be an acceptable form of therapy for SS patients. Double-blind trials are needed to substantiate the efficacy of this therapeutic modality.
9084322 Aging and saliva: a review of the literature. 1996 May It is often assumed that salivary secretion reduces with age. About 25% of the elderly suffer from oral dryness and related complaints. Nevertheless, data on stimulated salivary flow rate in healthy elderly revealed no significant age-related decrease other than a slight decrease of the secretion from the (sero)mucous glands under conditions of minimal or extended stimulation. With regard to salivary gland morphology and composition of saliva, age-related changes have been reported in healthy individuals, too. With increasing age, the number of acini reduces and the amount of fatty and fibrous tissue increases. Moreover, animal studies revealed that the synthesis of proteins is reduced by 60% in advanced years. These data indicate that changes might occur in concentration and/or activity of the organic components of saliva. In human studies, the concentration of sIgA in labial saliva and the concentrations of high-molecular and low-molecular mucins in mucous saliva appeared to be reduced with age. Since sIgA and mucins are important in the immunologic and non-immunologic defense of the oral cavity, both defense systems are reduced in healthy elderly. Analysis of these data suggests that the oral soft tissues may become somewhat more susceptible to environmental factors due to a reduction of the immunological and non-immunological defense systems.
9019372 Observation of precorneal tear film in patients with Sjögren's syndrome. 1995 Dec The present study was designed to examine whether the lipid layer of the precorneal tear film has a role in the pathogenesis of dry eye. The study involved 104 eyes of 52 patients with primary Sjögren's syndrome. The lipid layer of the precorneal tear film was observed by non-contact specular microscopy, and relationships between grade of interference color and the tear function parameters were examined. The lipid layer was classified from Grade 1, with no interference color, to Grade 4, of most intense interference color. In addition to these four grades, an oil droplet type not previously described was characterized. The grade of interference color was closely related to the intensity of vital staining. The oil droplet type was associated with more severe ocular surface damage than were Grades 1 through 4. The findings of this study suggest that the state of the lipid layer of the tear film may have some involvement in the pathogenesis of dry eye.
7572159 Selective IgA deficiency with unusual features: development of common variable immunodefic 1995 Aug We report on a girl with selective IgA deficiency and persistently low complement component 4 (C4) levels compatible with heterozygous C4 deficiency. Deterioration of her serum immunoglobulin levels and transition to common variable immunodeficiency were observed within a 5 year follow-up. She also developed Sjögren's syndrome, autoimmune hemolytic anemia and immune thrombocytopenic purpura. While these abnormalities have been described before in various combinations, to our knowledge, they have not been reported in a single individual.
7570214 [Multiple colonic ulcers in a patient with Sjögren's syndrome]. 1995 Jun A 25-year-old female with Sjögren's syndrome was admitted to our hospital because of fever and abdominal pain. Multiple colonic ulcers were demonstrated by gastrographin enema and colonoscopy. Histological examination revealed the presence of necrotizing vasculitis in the submucosal region. Large dose of prednisolone (60 mg/day) brought a prompt relief of her symptoms and an improvement of positive inflammatory signs. Pseudoaneurysm in the arteria colica media, which had been demonstrated by abdominal selective angiography at the time of diagnosis, became extinct after the steroid treatment. Healing of ulcers were also noted by colonoscopy. A variety of extraglandular symptoms has been reported in Sjögren's syndrome. Multiple colonic ulcers due to vasculitis are rarely complicated but may have a great impact on the prognosis of the disease.
8591805 Acute transverse myelopathy and cutaneous vasculopathy in primary Sjögren's syndrome. 1995 Neurologic complications of primary Sjögren's syndrome (SS) may be under-estimated. Here, we report a patient with primary SS, who developed acute transverse myelopathy (ATM) and skin purpuric lesions simultaneously. In the first episode of myelopathy, the patient's neurologic deficits improved after steroid therapy. However, she died of recurrent myelopathy with systemic complications 4 months later. Review of the English-language literature revealed only 3 cases of primary SS associated with ATM, none of the 3 patients had skin lesions. Anti-Ro(SS-A) antibodies, and ATM in our patient suggests that immune-mediated vasculopathy may play a role in the pathogenesis of acute myelopathy in primary SS.
7522224 Serum viscosity is a sensitive test for monitoring primary Sjögren syndrome. 1993 Primary Sjögren's syndrome (pSS) is characterized by chronic inflammation, resulting in secondary changes in serum protein content. In an attempt to evaluate disease activity we have measured serum viscosity (SV) in 41 patients with pSS and compared SV with laboratory findings such as: total proteins, gamma-globulin concentrations, titre of rheumatoid factor (RF) and level of circulating immune complexes. SV was found to correlate with these laboratory parameters. The pSS patients with low serum viscosity had worse clinical abnormalities than those with the high SV. Thus SV affords a useful monitoring test for pSS patients.
1395220 Salivary gland echography in primary and secondary Sjögren's syndrome. 1992 Jul A series of different ultrasonographic abnormalities detected by salivary gland echography (SGE) were investigated for their discriminant power for Sjögren's syndrome (SS) in 53 patients with either primary SS (n = 27) or secondary SS (n = 26), as well as in 90 controls. Among the controls, 26 suffered from dry mouth and/or recurrent or persistent swelling of at least one parotid or submandibular gland due to other selected disorders, while 64 were healthy, asymptomatic subjects. Mild, evident or gross inhomogeneous parenchymal patterns were the only variables selected by stepwise discriminant analysis, when comparing patients to controls. However, a mild submandibular inhomogeneity did not prove useful for such a discrimination. Based on these data, a simplified evaluation and standardised quantification of salivary involvement, as detected by SGE, is proposed using an echographic score (range 0 to 6) which assigns points to the different degrees of glandular inhomogeneity. Score values above 0 showed a sensitivity of 88.8% in primary SS and of 53.8% in secondary SS, as well as a specificity of 84.6% and of 92.2% with respect to either symptomatic or healthy controls. The lower sensitivity of SGE for patients with secondary SS presumably was a result of their milder salivary involvement.
1578527 Pulmonary involvement in collagen vascular disease: a review of the pulmonary manifestatio 1992 Mar The pulmonary manifestations of collagen vascular diseases span an enormous range of clinical and radiographic findings. The breadth of these abnormalities is as diverse as the underlying diseases themselves. A comprehensive discussion of pulmonary involvement in four of these diseases, the Marfan syndrome, ankylosing spondylitis, Sjögren's syndrome, and relapsing polychondritis, is presented.