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PMID	Title	PublicationDate	abstract
2524009	Isolation of CD4- CD8- mycobacteria-reactive T lymphocyte clones from rheumatoid arthritis	1989 May 18	The majority of peripheral T cells express a heterodimeric, alpha/beta T-cell receptor, which recognizes specific antigenic peptides bound to self major histocompatibility complex (MHC) molecules, and either the CD4 or CD8 surface markers. An additional subset of T cells, whose physiological function is unknown, express a distinct CD3-associated receptor composed of gamma and delta chains. This subset includes cells lacking both CD4 and CD8 surface markers, which may be involved in autoimmunity. The recognition specificity of the gamma/delta receptors is not well characterized and has been defined in only one case to date, a murine cell line which shows MHC-linked specificity. In this report, we describe the isolation of CD4- CD8-, gamma/delta TCR bearing T cell clones from the synovial fluid of a rheumatoid arthritis patient. These T cell clones respond specifically to mycobacterial antigens without MHC restriction.
2506344	Studies on type II collagen induced arthritis in rats: an experimental model of peripheral	1989 Jun	It was suggested that type II collagen induced arthritis in rats may be considered an experimental model for rheumatoid arthritis (RA) because of clinical, histological, and immunological similarities. However, some features separate it from RA. We studied 40 inbred female Wistar Furth rats. Two weeks after immunization with native human type II collagen, they had polyarthritis which progressed to ankylosis associated with ossifying enthesopathy and periosteal new bone formation. Inflammatory nodules of the tail appeared after 2 months, with radiological and histopathological aspects of multistage spondylodiscitis. Our findings suggest that collagen induced arthritis may be a relevant model of peripheral and axial ossifying enthesopathy.
3389901	Subcutaneous rheumatoid nodules.	1988 Jun	We describe seven children with subcutaneous rheumatoid nodules who had no clinical evidence of rheumatoid arthritis. Only one girl was seropositive for antinuclear factors and had a slightly raised erythrocyte sedimentation rate. Clinical aspects, risks for developing rheumatoid arthritis, and treatment of this entity are discussed.
2965555	Failure of oral thiomalate to act as an alternative to intramuscular gold in rheumatoid ar	1988 Mar	Ten patients with active rheumatoid arthritis (RA) were entered into a pilot study to evaluate the effectiveness of thiomalic acid as a disease modifying agent and to assess its toxicity. Oral thiomalic acid (100 mg) was given daily for up to six months. Changes in disease activity were recorded monthly and all side effects noted. No patient recorded any improvement in subjective well being, pain score, or duration of early morning stiffness. No significant change occurred in articular index or haemoglobin (Hb); the erythrocyte sedimentation rate (ESR) showed a tendency to increase. Only three patients completed six months' treatment; six withdrew because of toxic reactions (three with rashes and three with severe gastrointestinal upset) and one because of lack of effect. Thiomalic acid alone appears to have no significant antirheumatic activity and is associated with an unacceptably high incidence of adverse reactions.
2674295	Pneumococcal cellulitis: a rare manifestation of pneumococcaemia in adults.	1989 Jul	An elderly woman with rheumatoid arthritis of 8 years duration and for which she was receiving indomethacin, developed multifocal cellulitis with subsequent necrosis. Streptococcus pneumoniae type 1 was isolated from her blood and from blister fluid. Previous reported cases are summarised.
1811196	Radiolabelled white blood cell imaging in arthritis. Is it a blood pool effect?	1991 Dec	The aim of this study is to determine whether white blood cell imaging in inflammatory conditions is due to a blood pool effect as a result of an increased vascularity and vascular permeability, or whether cellular migration is the major contributing factor. It will be shown that white cell uptake is a specific phenomenon in the rheumatoid knee joint and not just a blood pool effect.
1763639	Swallowing problems in rheumatoid arthritis.	1991	Twenty-nine female patients with definite or classical rheumatoid arthritis (RA) and 30 controls were investigated in order to evaluate oral symptoms, particularly xerostomia, and swallowing difficulties in RA by means of a questionnaire, physical examination, stimulated saliva secretion, labial salivary gland biopsy, esophageal manometry and laboratory blood tests. Xerostomia was reported by 6 patients (21%), compared with no-one in the control group. Four of these 6 patients had decreased stimulated saliva secretion, compared with 2 of the remaining 23 patients. Dysphagia was experienced by 8 patients (28%), compared with one control subject. Dysphagia was associated with disease severity. Esophageal manometry revealed a decrease of the amplitude of the peristaltic pressure complex in the proximal part of esophagus in the RA group, indicating dysfunction of the striated muscles. No correlation was found between dysphagia and esophageal manometry results.
2649023	A tissue kallikrein in the synovial fluid of patients with rheumatoid arthritis.	1989 Feb	Tissue kallikrein is an enzyme that forms the vasoactive peptide kallidin from an endogenous substrate L-kininogen. Tissue kallikrein has been identified in joint fluids and in inflammatory infiltrates within synovial membranes. It is suggested that tissue kallikrein and kinins have an important role in synovitis and joint damage. Immunoreactive tissue kallikrein and amidase activity were both measured in the synovial fluid of 24 patients with rheumatoid arthritis (RA) and 12 with osteoarthritis (OA). Active enzyme concentrations were higher in RA than in OA and correlated well with the lysosomal enzymes beta-glucuronidase and lactate dehydrogenase. Both total immunoreactive tissue kallikrein and the proenzyme values were similar in RA and OA. Tissue kallikrein was localised by immunocytochemistry to the polymorphonuclear leucocytes present in the synovial fluid and membranes of patients with RA.
3518432	Efficacy and safety of diclofenac sodium in rheumatoid arthritis. Experience in the United	1986 Apr 28	Diclofenac sodium is a nonsteroidal, anti-inflammatory drug that has been studied in the United States for the treatment of rheumatoid arthritis in 681 patients, 468 of whom were enrolled in five multicenter, double-blind parallel controlled investigations. Results of these trials indicate that 150 mg daily of diclofenac is more effective than placebo and as effective as 2.4 g daily of ibuprofen or 3.6 g daily of aspirin. Moreover, the safety profile of diclofenac proved to be better than that of aspirin and similar to that of ibuprofen.
1765969	Morphological localization of hyaluronan in normal and diseased synovium.	1991 Oct	The morphological distribution of hyaluronan in normal and diseased synovium has been determined using a probe derived from the hyaluronan binding region of cartilage proteoglycan core protein. Normal synovium showed hyaluronan surrounding the lining layer cells with little in deeper layers. Rheumatoid synovium showed intense staining for hyaluronan throughout the tissue, notably associated with blood vessels and areas of dense cellular infiltration. Osteoarthritic tissues varied according to the degree of infiltration present, with inflamed specimens closely resembling rheumatoid tissue. The distribution of hyaluronan in diseased synovium suggests a role in aspects of the inflammatory process such as angiogenesis and cell traffic.
2062381	Structure of recombinant human rheumatoid arthritic synovial fluid phospholipase A2 at 2.2	1991 Jul 4	Phospholipases A2 (PLA2s) may be grouped into distinct families of proteins that catalyse the hydrolysis of the 2-acyl bond of phospholipids and perform a variety of biological functions. The best characterized are the small (relative molecular mass approximately 14,000) calcium-dependent, secretory enzymes of diverse origin, such as pancreatic and venom PLA2s. The structures and functions of several PLA2s are known. Recently, high-resolution crystal structures of complexes of secretory PLA2s with phosphonate phospholipid analogues have provided information about the detailed stereochemistry of transition-state binding, confirming the proposed catalytic mechanism of esterolysis. By contrast, studies on mammalian nonpancreatic secretory PLA2s (s-PLA2s) have only recently begun; s-PLA2s are scarce in normal cells and tissues but large amounts are found in association with local and systemic inflammatory processes and tissue injury in animals and man. Such s-PLAs have been purified from rabbit and rat inflammatory exudate, from synovial fluid from patients with rheumatoid arthritis and from human platelets. Cloning and sequencing shows that the primary structure of the human s-PLA2 has about 37% homology with that of bovine pancreatic PLA2 and 44% homology with that of Crotalus atrox PLA2. The human s-PLA2 is an unusually basic protein, yet contains most of the highly conserved amino-acid residues and sequences characteristic of the PLA2s sequenced so far. Here we report the refined, three-dimensional crystal structure at 2.2 A resolution of recombinant human rheumatoid arthritic synovial fluid PLA2. This may aid the development of potent and specific inhibitors of this enzyme using structure-based design.
2675908	Immune complex assays: diagnostic and clinical application.	1989	The presence of circulating immune complexes have been described in many different human disease states but the significance of their presence has always been a subject for debate. Improvements in the methods of detecting immune complexes have demonstrated a wide degree of heterogeneity, which accounts for the difficulty in obtaining accurate and reproducible measurements, even in the same individual. Techniques for isolating individual complexes, characterizing their pathophysiological properties, and biochemically analyzing the nature of the complexed antigen are now being used to provide data that is helping to clarify the role of immune complexes in the pathogenesis of disease. In addition, such studies are also providing data which is proving that immune complexes have a potential role in immune regulation.
3589769	Bypass arthritis and the blind intestinal loop.	1987 Jun	Arthritis and other inflammatory processes are well established complications of intestinal bypass operations, and recently have been reported after other gastrointestinal procedures. Bacterial overgrowth in blind intestinal loops, actual or functional, appears to be the underlying pathophysiologic mechanism responsible for these systemic inflammatory disorders. In the case we have reported, arthritis was the primary manifestation of blind loop remaining after incomplete reversal of a jejunoileal bypass. Surgical elimination of the blind loop was curative.
2871585	The effect of antirheumatic drugs on circulating immune complexes in rheumatoid arthritis.	1986 Jan	The relationship between antirheumatic drug treatment and levels of circulating immune complexes (125I-C1q binding activity) has been investigated in a prospective two-year study of patients with rheumatoid arthritis using the erythrocyte sedimentation rate (ESR) and serum C-reactive protein concentration as indices of disease activity. Twenty-eight patients were treated with non-steroid anti-inflammatory drugs, 14 patients had 'second line' drugs and 13 patients were treated with adrenal corticosteroids. Serum 125I-C1q binding activity did not change during non-steroid anti-inflammatory drug treatment; however, immune complex levels did fall during treatment with new (ICI 55,897, sulphasalazine) and established (gold, penicillamine) second line drugs. Serum 125I-C1q binding activity reflected the response to treatment shown by serum C-reactive protein and ESR. Serum C-reactive protein concentration and ESR fell with all doses of adrenal corticosteroids. In contrast, immune complex levels did not fall when doses of adrenal corticosteroids were below 20 mg/day prednisolone. 125I-C1q binding activity fell during high dose adrenal corticosteroid therapy (greater than 40 mg/day prednisolone; 1 g methylprednisolone infusions). Serial measurements of 125I-C1q binding activity correspond to ESR and the serum C-reactive protein concentration in distinguishing between anti-inflammatory drugs, which provide symptomatic relief only, and second line drugs which may retard disease progression. The fall in circulating immune complex levels during 'high' dose corticosteroid treatment, but not during 'low' dose treatment, suggests that corticosteroids have a dose-dependent effect on the immune system in addition to their anti-inflammatory properties.
2025311	Increased interleukin-2 production in response to human type I collagen stimulation in pat	1991 May	Peripheral blood mononuclear cells (PBMC) from patients with systemic sclerosis (SSc) produced increased amounts of interleukin-2 (IL-2), in a dose-dependent manner, in response to stimulation with human type I collagen, whereas PBMC from normal subjects did not. At a dose of 50 micrograms human type I collagen/10(6) PBMC, PBMC from SSc patients (n = 17) produced 8 times as much IL-2 as did PBMC from 16 normal subjects (P less than 0.005) and 3 times as much as did PBMC from a group of 13 rheumatoid arthritis patients (P less than 0.05). In contrast, IL-2 production by PBMC after nonspecific stimulation with the mitogen, phytohemagglutinin, did not differ among the SSc, rheumatoid arthritis, and normal control groups. Cell depletion experiments indicated that the IL-2-producing cells in SSc patients are CD4+. Thus, SSc patients have CD4 cells that are specifically sensitized to human type I collagen and can produce increased levels of IL-2. Measurement of IL-2 production stimulated by human type I collagen may be useful in evaluating disease activity, and further investigation of this process may contribute to the delineation of the pathogenesis of SSc.
2883939	Long-term treatment of rheumatoid arthritis with sulphasalazine, gold, or penicillamine: a	1987 Mar	Life-table analysis was applied to the records of 317 patients with rheumatoid arthritis (RA) treated with sulphasalazine (SAS), 201 treated with sodium aurothiomalate (gold), and 163 with penicillamine. They comprised all those treated in our department with these drugs between January 1973 and July 1984. Risks of treatment termination for all reasons were similar for each drug at five years (gold 92%, penicillamine 83%, SAS 81%). The risk of treatment termination due to inefficacy was less for gold (29.5%) than for penicillamine (38.1%) or sulphasalazine (41.2%). Adverse effects, however, led to withdrawal of gold in 57%, penicillamine in 41.2%, and SAS in 37%; the most effective drugs appeared most toxic. Serious adverse effects were much more common in association with gold (17.4%) and penicillamine (12.3%) than with SAS (1.6%). Sulphasalazine appears as well tolerated over long periods in RA as gold or penicillamine and is associated with fewer serious adverse effects; of these drugs, it might therefore be considered the agent of first choice.
3432608	[Radiological picture of the hand and foot in systemic lupus erythematosus].	1987 Dec	A detailed examination of the hands and feet was performed in a group of 34 patients affected by systemic lupus erythematosus (SLE), using low-dose mammographic film and Rank Xerox selenium plate, according to current diagnostic techniques. All patients presented articular symptoms (pain and arthralgia). The high incidence (38,8%) of patients with no radiographic evidence of bone damage-even though articular symptoms are present-is emphasized. In such cases, it is very difficult to distinguish SLE from rheumatoid arthritis, especially as far as therapeutic management and prognosis are concerned. The lack of any "pathognomonic" radiological sign of the lupus arthritis, in the hands as well as in the feet, is then stressed. Nevertheless, arthropathy in SLE is defined as a deforming non-erosive arthritis, with a typical symmetric distribution, affecting most commonly-according to incidence-the proximal interphalangeal and metacarpophalangeal joints. In the hand, arthropathy is referred to as Jaccoud's type arthritis, because it is characterized by joint deformities which can be corrected. In the foot, the main abnormalities include hallux valgus, subluxation of the metatarsophalangeal joints and widening of the forefoot.
1792630	[The clinico-prognostic assessment of DNA antibodies and antinuclear factors in rheumatoid	1991	As many as 195 patients with rheumatoid arthritis (RA) were examined for the clinical characteristics of the disease course depending on the presence or lack of antibodies to DNA or of antinuclear factor (ANF). Provided the patients' blood serum contained antibodies to DNA and ANF, RA was noted to run a graver course associated with a high-active process, marked erosive and destructive lesions of the joints, and the development of systemic manifestations. Excess production of the antibodies in question was accompanied by an increase of circulating immune complexes and rheumatoid factor, and a decrease of serum IgG. Glucocorticoids were demonstrated to be effective in suppression of autoimmune disorders. The presence of antibodies to DNA and of ANF is a prognostically unfavourable sign, indicating the development of systemic manifestations.
2734596	Diminished clearance of soluble aggregates of human immunoglobulin G in patients with rheu	1989	Investigation of the capacity of the mononuclear phagocyte system to remove immune complexes from the circulation was performed by the administration of 125I-labelled aggregates of human immunoglobulin G (AIgG) to patients with seropositive rheumatoid arthritis and healthy volunteers. It was found that the rate at which AIgG disappeared from the circulation was significantly prolonged in patients with RA, t1/2 61 +/- 49 min, versus 26 +/- 8 min in healthy volunteers (p less than 0.01). We were not able to establish a correlation between the t1/2 of AIgG and immune complex levels in the circulation, or between t1/2 and articular disease activity (Ritchie index). The sites of removal of AIgG from the circulation were analysed by determining radioactivity levels detectable over liver, spleen and heart. No correlation was found between t1/2 and liver/spleen uptake ratios. We have demonstrated that the removal of AIgG from the circulation of patients with RA is abnormal, though the biological significance of this finding remains to be determined.
3490228	Nailfold capillary microscopy in connective tissue disease: a quantitative morphological a	1986 Sep	Photomicrographs were taken of front line nailfold capillary loops in 18 healthy women (controls) and 42 women with established connective tissue disease (14 rheumatoid arthritis, 19 systemic lupus erythematosus, nine scleroderma). Measurements were made of apex width, maximum limb and loop widths, capillary length, interpeak distance, and frequency per linear millimetre. A numerical index for assessing capillary dilatation was derived, based on the mean of the apex plus maximum limb widths. Results show considerable overlap in subject means. Statistical analysis showed no difference between rheumatoid arthritis and control groups. Patients with systemic lupus erythematosus had slightly larger loops at a lower frequency (not statistically significant); three patients with an abnormal capillary index also had high titres of ribonucleoprotein antibody. Six scleroderma patients had abnormal indices, two of whom had high titre ribonucleoprotein antibody. No relation between capillary morphology and clinical features was found.