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ID PMID Title PublicationDate abstract
12879135 Pharmacology down under in 2000. 2000 Dec In December the pharmacologists and toxicologists of Australia and New Zealand get together for their annual scientific meeting, which is made up of pre-meeting workshops followed by invited lectures, symposia and free communications. This year, one of the pre-meeting workshops was on "Animal Models for the Development of Molecular Pharmaceuticals." Symposia included "Models and New Therapies for Traumatic Brain Injury" and "New Targets for Rheumatoid Arthritis." Novel medicines being developed in Australia revealed at the meeting included potassium channel blockers, C5a receptor agonists and antagonists, brain-derived neurotrophic factor mimetics and AM-36.
11142930 [Insufficiency fractures of the ileum and sacrum]. 2000 Oct Insufficiency fractures are fractures in bones with nontumorous disease (e.g., osteoporosis, rheumatoid arthritis or following radiation) at normal load. Two cases of insufficiency fracture of the ilium and sacrum are presented. Predisposing factors, clinical picture, imaging procedure and therapy are outlined.
17638090 Ibuprofen, the propionics and NSAIDs: personal reflections over four decades. 1999 In 1952 I re-joined the Pharmacological Division of the Research Department of the Boots Co. in Nottingham UK to work on rheumatoid arthritis (RA) but with the distinct disadvantage that the Division was housed in a group of rambling buildings attached to a Victorian house. The Division had moved there at the beginning of World War II from the centre of Nottingham as a precaution against bombing - a wise move since part of the Research Department was destroyed in an air raid in 1941. Hence the first six years of my research was carried out under rather unfavourable conditions, for my laboratory was one of the two 'front' rooms of the house.
11625707 ["Praying hands" of Albrecht Durer regarded by physicians]. 1999 Albrecht Durer is a great artist between Middle Ages and Renaissance. He is an author of Four Books on Human Proportions and Perspective. He is also the author of the study of the hands on blue paper - "Praying Hands". This person could have had various diseases: diabetes, rheumatoid arthritis, or a circulatory failure. The importance of Durer's works is illustrated by its historical, medical, and artistic interpretation.
11237555 Humanized antibody to human interleukin-6 receptor inhibits the development of collagen ar 2001 Mar In the present study, we demonstrated the anti-arthritic effect of humanized anti-human IL-6 receptor (IL-6R) antibody, MRA, in cynomolgus monkey. MRA can react with monkey IL-6R and block signal transduction of IL-6. Collagen-induced arthritis (CIA) was induced by twice immunizing with bovine type II collagen (CII) emulsified with complete adjuvant. MRA was intravenously injected once a week, from the day of the first collagen immunization, for 13 weeks. The symptoms of arthritis were evaluated using a visual scoring system and radiography. Inflammatory parameters (C-reactive protein (CRP), fibrinogen, and erythrocyte sedimentation rate (ESR) and concentrations of anti-CII antibody, anti-MRA antibody, and MRA were monitored regularly. At the end of the study, histological evaluation was carried out. MRA, at a dose of 10 mg/kg, gave rise to statistically significant suppression. The elevation of serum CRP and fibrinogen levels and ESR were also inhibited. Furthermore, radiographic and histological examination showed that MRA treatment suppressed joint destruction. Our results demonstrate that IL-6 plays an important role in monkey CIA and that MRA may be an attractive agent for the treatment of rheumatoid arthritis.
9663479 Distal musculoskeletal manifestations in polymyalgia rheumatica: a prospective followup st 1998 Jul OBJECTIVE: To determine the frequency and the characteristics of distal musculoskeletal manifestations in polymyalgia rheumatica (PMR). METHODS: Prospective followup study of 177 consecutive patients meeting clinical criteria for PMR, diagnosed over a 5-year period in 2 rheumatology secondary referral centers in Italy. RESULTS: Seventy-nine of the 177 patients (45%) had distal musculoskeletal manifestations. Peripheral arthritis occurred in 45 patients (25%), carpal tunnel syndrome in 24 (14%), distal extremity swelling with pitting edema in 21 (12%), and distal tenosynovitis in 5 (3%). These manifestations were usually associated with PMR proximal symptoms (69%); however, 31% of the episodes represented isolated relapse/recurrence at distal sites. Distal symptoms responded promptly to corticosteroids. No evidence of joint deformities, erosions, or development of rheumatoid arthritis was observed during the followup. The group of patients with peripheral arthritis included a higher proportion of females, had a longer duration of therapy, and had more relapses/ recurrences. Patients who had distal extremity swelling with pitting edema had a higher age at disease onset, a shorter duration of therapy, and lower initial and cumulative prednisone doses. CONCLUSION: Inflammatory involvement of distal articular and/or tenosynovial structures occurs in approximately half of the cases of PMR. Peripheral arthritis is associated with more severe disease, while distal extremity swelling with pitting edema appears to identify a more benign disease subset.
9817671 [Materials for joint replacement and friction and wear]. 1997 Mar Debilitating diseases such as osteo- and rheumatoid arthritis, trauma and bone cancer can be treated by using prostheses. The wear resistance of materials for joint replacement can affect the service-quality and service-life of prostheses. Materials for joint replacement and friction and wear were briefly reviewed in this paper.
21318793 Matrix metalloproteinases and their inhibitors. 2001 Matrix metalloproteinases (MMPs) are a group of 16 enzymes that are capable of degrading extracellular matrix components. Their catalytic function is dependent on a zinc ion in the active center. MMPs are separated in three groups: gelatinases (type IV-collagenases), stromelysins, and interstitial collagenases. Their physiological and pathological significance is to modulate the extracellular matrix-e. g., in embryogenesis, in the ovarian cycles, or in inflammatory diseases such as rheumatoid arthritis or fibrosis of the liver or kidney (1,2).
9709378 A monoarthritis model in rabbits induced by repeated intra-articular injections of lipopol 1998 Apr We attempted to develop a monoarthritis model using repeated intra-articular injections of high-dose Lipopolysaccharide (LPS). Furthermore, the effect of dexamethasone on this arthritis model by intra-articular administration was studied to examine whether the model can be used to screen anti-rheumatic drugs in a short time. Arthritis was induced by one, two or three intra-articular injections of LPS (5-50 micrograms/joint) at 4-day intervals into the knee joint. The rabbits were sacrificed at 7 days following the last injection of LPS. Three intra-articular injections of LPS at 50 micrograms/joint resulted in persistent joint swelling. Hyperplasia of synovium with some discolouration was macroscopically observed. Infiltration of mononuclear cells and lymphoid follicles were histologically observed as the synovial lesions. Concerning the articular bone/cartilage, trabecular destruction of gastrocnemius sesamoid bone and severe loss of safranin-O staining of articular cartilage were observed. Immunohistochemical analysis revealed that inflammatory cells and lymphoid follicles in the synovial lesions consisted predominantly of CD4+ T cells, with few CD8+ T cells. Treatment with dexamethasone markedly reduced the joint swelling and the articular destruction. The results suggest that this arthritis model in rabbits can be utilized to screen anti-rheumatic drugs as a model of rheumatoid arthritis.
9228139 Reliability, validity, and sensitivity of a Swedish version of the revised and expanded Ar 1997 Jul OBJECTIVE: To evaluate the reliability, validity, and sensitivity of a Swedish version of the Arthritis Impact Measurement Scales (AIMS2) in patients with rheumatoid arthritis (RA). METHODS: Reliability was assessed by a test-retest procedure with a 3-week interval and Cronbach's coefficient of internal consistency. Convergent validity was evaluated by correlation coefficients with the Health Assessment Questionnaire (HAQ), Mood Adjective Checklist (MACL), and disease activity variables. The sensitivity to change was assessed in 40 patients treated with disease modifying antirheumatic drugs, 24 mo after the start of the study. RESULTS: Significant differences were found for the Walking and Bending, Arthritis Pain, and Work scales (p < 0.05) in the test-retest reliability study. Internal consistency coefficients for the AIMS2 scales were 0.68-0.91. Convergent validity was established by significant correlations between the different scales in AIMS2 and the HAQ, MACL, and disease activity variables. Sensitivity to change was observed in 5 of 11 scales in AIMS2. CONCLUSION: After modifying some reliability problems due to a more differentiated scale and cultural differences between the Swedish and American patients with RA, the reliability, validity, and sensitivity to change of AIMS2 were found satisfactory.
10023856 Identification of arthritogenic adjuvants of self and foreign origin. 1999 Jan The lack of defined triggers for human inflammatory joint diseases warrants efforts to identify candidate molecules. For this task, it may be an important lead that nonspecific activation of the immune system can precipitate arthritis in rats. Consequently, arthritis-prone rat strains were used to search for disease-triggering factors among molecules which initially induce innate defence reactions rather than specific immune responses. A variety of immunological adjuvants were investigated by intradermal injection into DA and LEW.1AV1 rats and monitoring of clinical signs for 30 days. Several arthritogenic cell-wall structures from yeast and bacteria were identified, such as beta-glucan, lipopolysaccharide and trehalosedimycolate. The test procedures also revealed arthritogens of chemical origin, such as dioctadecyldiammoniumbromide (DDA = C38H80NBr) and heptadecane (C17H36). Furthermore, it allowed the precise definition of arthritogenic determinants of lipids, since C16H34 induced arthritis, whereas the closely related linear hydrocarbons C16H32, C16H33Br and C15H32 did not. The observed pathogenicity of organic lipids raised the question of whether endogenous lipids can also precipitate arthritis. Indeed, this was true for the cholesterol precursor squalene (C30H50). In conclusion, this article describes the rational use of arthritis-prone rat strains to identify arthritogenic factors of both foreign and self origin. Although structurally unrelated, the pathogenic molecules defined here share the feature of being nonspecific triggers of the immune system. This consolidates a general principle for the induction of adjuvant arthritis which may provide clues to the aetiology of human arthritides, including rheumatoid arthritis.
11798133 Sjögren's syndrome: immunological response underlying the disease. 2001 Sjögren's syndrome is a chronic autoimmnune disorder characterized primarily by the discomforts od dry eyes and dry mouth due to the progressive loss of exocrine gland function. Development of a number of animal models to study Sjögren's syndrome, especially the NOD mouse and its congenic partner strains, has permitted a systematic analysis of immunological and non-immunological factors that influence predisposition for development of the autoimmune response. These data are reviewed here.
11171687 Lack of evidence for an increased microchimerism in the circulation of patients with Sjög 2001 Mar OBJECTIVE: To examine the hypothesis that fetal microchimerism plays a part in the pathogenic process of Sjögren's syndrome (SS). METHODS: Genomic DNA samples were extracted from peripheral blood whole nucleated cells and the CD34+ cell enriched fraction of patients with SS and healthy women who had male offspring as well as nulliparous women. A Y chromosome-specific sequence was detected as a marker for fetal cells by a nested polymerase chain reaction (PCR) and by DNA hybridisation combined with PCR using specific primers and probes. All procedures were performed with great care to avoid the contamination of male DNA. RESULTS: A nested PCR and DNA hybridisation combined with PCR was established that can detect a single male cell out of 1.67x10(5) female cells. It was not possible to increase the sensitivity further because the amount of template DNA held in the PCR was limited. When these methods were used, no fetal cells were detected in any samples from patients with SS, though they were detected in whole nucleated cells from two healthy women who had delivered sons previously. CONCLUSIONS: The findings indicate that circulating fetal cells in patients with SS are uncommon (<1 in 1.67x10(5)), if they exist. With the conventional PCR based methods that were used, it is difficult to evaluate the quantitative difference in circulating fetal cells between patients with SS and healthy women.
10695658 Relationship between Sjögren's syndrome and human T-lymphotropic virus type I infection: 2000 Feb We have previously demonstrated a high prevalence of Sjögren's syndrome (SS) in patients with human T-lymphotropic virus type I-associated myelopathy (HAM) in Nagasaki prefecture. The present follow-up study compared the clinical and laboratory findings of SS with or without human T-lymphotropic virus type I (HTLV-I) antibody in this endemic area for HTLV-I infection. We investigated the clinical and laboratory manifestations in 83 patients with SS and HAM, including histologic examination of labial salivary glands and the prevalence of SS in patients with HAM. Definite SS was diagnosed in 13 out of 20 patients with HAM when the European Community criteria were used. The density of mononuclear cell infiltration in labial salivary glands was higher in HTLV-I-seropositive patients with SS (including patients with HAM) than in HTLV-I-seronegative patients. The volume of saliva and lacrima determined by the Schirmer or Saxon test was lower than normal but was not different among SS-HTLV-I-seronegative patients, HTLV-I-seropositive patients without HAM, and HTLV-I-seropositive patients with HAM. The proportions of patients positive for antinuclear antibody (ANA) and anti-SS-A (Ro) antibody or anti-SS-B (La) antibody were similar in the three groups. However, the low volume of saliva and the frequency of ANA in SS correlated with the degree of mononuclear cell infiltration in labial salivary glands. Our results suggested that HTLV-I infection is related to SS and that laboratory and clinical findings in SS closely correlate with the degree of mononuclear cell infiltration in the salivary glands.
10230585 Sjögren's syndrome: pathogenesis. 1999 Jan Sjögren's syndrome is a chronic inflammatory disease of the lacrimal and salivary gland with subsequent keratoconjunctivitis sicca and xerostomia. Histopathologic findings include damaged acini of the lacrimal and salivary glands with mononuclear cell infiltrates of lymphocytic and plasma cell type. The cause of the damage is cell-mediated cytotoxicity. The pathogenesis of Sjögren's syndrome is still unknown. The role of viral infections failed to show a causative effect. On the other hand, tissue destruction was shown to be mediated by activated T cells of CD4+ type that home into the lacrimal gland. This process is signal-mediated through the T-cell receptor that interacts with class II antigen on the epithelial cells of exocrine glands. This, in turn, induces the expression of Fas/APO-1 and Fas-mediated apoptosis of acinar cells. Granzyme A and perforin are cytolytic enzymes secreted by activated T lymphocytes that seem to participate in acinar cell destruction.
9855218 Adult onset Still's disease associated with Epstein-Barr virus infection in a 66-year-old 1998 Adult onset Still's disease (AOSD) is a distinct clinical entity which affects predominantly young adults aged 16-35 years. Onset in elderly individuals is exceptional. Several reports have suggested a viral trigger in the pathogenesis of this disease. We describe a 66-year-old woman who fulfilled the proposed diagnostic criteria of AOSD and suffered concurrently from acute Epstein-Barr virus (EBV) infection.
9607645 Young onset of primary Sjögren's syndrome: clinical and immunological characteristics. 1998 The objective of our study was to determine the clinical and immunological characteristics of primary Sjögren's syndrome (SS) in patients with a young onset of the disease. We included 144 consecutive patients (134 female and 10 male; mean age at onset 53 y; range 20-87 y) visited in our Units. All patients were white and fulfilled four or more of the diagnostic criteria for SS, proposed by the European Community Study Group in 1993. Disease onset was determined on the basis of the appearance of symptoms strongly suggestive of SS. In 13 (9%) patients, disease onset occurred before the age of 35. All were female and the disease onset occurred between 20-34 y (mean, 28 y). When compared with patients with older onset, patients with a young onset of the primary SS presented a higher prevalence of lymphadenopathy (54% vs 6%, P < 0.001), rheumatoid factor (70% vs 39%, P=0.034), anti-Ro/SS-A antibodies (70% vs 28%, P=0.004) and monoclonal immunoglobulins (23% vs 4%, P=0.02) in their sera. From the initial diagnosis of SS, three patients with a young-onset of the primary SS have developed lymphoproliferative disease at the time of the study, compared with one patient of the older-onset group (23% vs 1%, P=0.002). Our study shows several differences between younger and older onset patients, including a higher incidence of lymphomas in the younger, thus conferring to the age at onset of the disease a prognostic value.
9225875 Quantitative assessment of clinical disease status in primary Sjögren's syndrome. A cross 1997 Quantitative and qualitative assessment of the clinical disease manifestations in 41 primary Sjögren's syndrome (pSS) patients was performed according to a new classification model. Frequencies of subgrouped disease manifestations were as follows: 1) surface exocrine disease: 100%, 2) internal organ exocrine disease: 63%, 3) monoclonal B lymphocyte disease: 5%, 4) inflammatory vascular disease: 71%, 5) non-inflammatory vascular disease: 59%, 6) mediator induced disease: 98%. Summary scores for severity of surface exocrine disease correlated to the summary scores of all other disease manifestations (p = 0.02), to the summary scores of internal organ exocrine disease (p = 0.003), and to the summary scores of mediator induced disease (p = 0.03). Blood leucocyte counts showed significant negative correlations to levels of plasma IgG, serum IgA-RF, IgM-RF, anti-SSA/SSB antibodies, IL-6, and IL-1Ra. We conclude that the model made detailed analysis of the clinical presentation of pSS possible, and thus may assist in elucidating important pathobiological aspect of the disease.
11412725 [Sjögren's syndrome and multiple sclerosis]. 2001 May INTRODUCTION: Multiple sclerosis (MS) usually follows a relapsing-remitting course and attacks multiple areas of the central nervous system (CNS). Certain rheumatic diseases, including Sjögren's syndrome (SS), can present with a similar clinical picture. RESULTS: Two patients out 67 of 100 with MS exhibited xerophthalmia and xerostomia and positive Ro antibodies, thus fulfilling 55 diagnostic criteria. Case 1. A 62-year-old woman developed several episodes of numbress and weakness in her left extremity and ataxia. MRI demonstrated a high-intensity areas in periventricular white matter. Initial laboratory studies failure to demonstrate antinuclear antibodies. Xerostomia and xerophthalmia were apparent. Follow-up laboratory examinations showed elevated ANA, Anti-SSA and anti-SSB. Case 2. A 58-year-old woman was diagnosed as having MS at the age of 53 years. Several high-signal foci on MRI were demonstrated in the white matter. Initial serum findings including autoantibodies were unremarkable. Sicca syndrome was present. Laboratory investigations included elevated anti-SSA, anti-SSARo52 and ANA while anti-SSB was within normal limits. DISCUSSION: Primary SS is a chronic autoimmune inflammatory disease of unknown etiology. The CNS symptoms are present in 20-25% of the patients with SS. Some patients have a relapsing-remitting course mimicking MS. Focal brain lesions in SS can occur in the cerebral white matter. The features of our patients sufficiently mimicked those of MS and this disorder was the diagnosis in each patient at the time of initial evaluation. SS should be considered in th
10955332 Labeled neoglycoproteins and human lectins as diagnostic and potential functional markers 2000 Aug OBJECTIVE: The profile of glycans and their recognition by endogenous receptors (lectins) are increasingly attributed to disease process. Monitoring this can provide information on the pathogenesis of Sjögren's syndrome (SS). Commonly, plant lectins are employed for phenomenological glycan mapping. To go beyond this approach restricted to binding of exogenous probes, new markers measure ligand properties of glycans to human (not plant) lectins and the presence of sugar receptors completing a protein-carbohydrate recognition system. Carrier-immobilized sugar epitopes (neoglycoproteins) and purified human lectins establish this innovative panel. METHODS: The host defence molecules mannan binding lectin, serum amyloid P component, and the macrophage migration inhibitory factor-binding sarcolectin, selected for their involvement in cell destructive mechanisms, were purified and labeled. The plant lectins SNA and MAA were employed to monitor regulation of potential ligand sites for I-type lectins and galectins. Asialofetuin was tested as a "pan-galectin selective" probe. The specific binding characteristics were determined by quantitative morphometry and statistical analysis. RESULTS: Diagnostic information emerged from this analysis. The percentage of stained tissue area was significantly different between SS and control specimens after processing with GlcNAc and Man-bearing neoglycoproteins and the 2 tested serum lectins. For separation of cases of primary and secondary SS, the staining intensity with the asialoglycoprotein, sarcolectin, and the exogenous alpha2,6-sialylated glycan-binding lectin SNA was statistically significant. CONCLUSION: Saccharide-presenting probes to measure the cellular capacity to bind glycan epitopes and human lectins as sensors for endogenous binding sites have proven to be useful as diagnostic tools. We suggest the differences we observed reflect aberrations from the normal cellular homeostasis with relevance for the pathogenesis of SS and its manifestation as a primary or secondary syndrome.