bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunogenetic factors in inflammatory eye disease. influence of hla–b27 and alpha1‐antitrypsin phenotypes on disease expression
Authors: Wakefield Denis , Breit Samuel N. , Clark Peggy , Penny Ronald
Published: February 2007

The relationship between the nature and severity of inflammatory eye disease was analyzed with respect to HLA antigens and alpha1‐antitrypsin phenotypes. Using standard ophthalmologic criteria, we divided patients with anterior uveitis into acute, chronic (>3‐month duration), bilateral, or recurrent disease. There was a significantly increased incidence of alpha1‐antitrypsin–deficient phenotypes in anterior uveitis, especially in those patients with severe (chronic, bilateral, or recurrent) disease. HLA–B27 acts as an independent predisposing factor: it was present in 22% of patients with their first attack of acute uveitis compared with 51% of patients with recurrent disease. Together, these genetic factors are present in 63% of patients with severe anterior uveitis and represent the most significant predisposing and prognostic factors so far detected.
Quantitation of cells secreting rheumatoid factor of igg, iga, and igm class after elution from rheumatoid synovial tissue
Authors: Egeland Torstein , Lea Tor , Saari George , Mellbye Ove J. , Natvig Jacob B.
Published: February 2007

In an indirect hemolytic plaque assay that used sheep erythrocytes coated with normal rabbit IgG or reduced/alkylated IgG anti–sheep erythrocytes, mononuclear cells eluted from rheumatoid synovial tissue of 7 of 11 patients with seropositive rheumatoid arthritis contained cells that secreted rheumatoid factor of IgG, IgA, and IgM classes. The number of rheumatoid factor–secreting cells varied from <1% to 53% of the total number of eluted immunoglobulin‐secreting cells. In contrast, immunoglobulin‐secreting cells and rheumatoid factor–secreting cells were scanty in blood compared with synovial tissue mononuclear cells.
Relationship between reduced b cell susceptibility to igm antibodies and reduced igd‐bearing b cells in patients with systemic lupus erythematosus
Authors: Suzuki Hiroshi , Sakurami Takehiko , Imura Hiroo
Published: February 2007

Peripheral blood lymphocytes from 14 patients with systemic lupus erythematosus, 5 patients with rheumatoid arthritis, and 10 normal subjects were cultured for 7 days with or without anti‐IgM or anti‐IgD antibodies, and IgG‐ and IgM‐secreting cells were assayed by reverse hemolytic plaque assay. Surface immunoglobulin (Ig) isotypes on peripheral blood B cells were also examined by a direct anti‐Ig resetting reaction. In normal subjects and rheumatoid arthritis patients, the spontaneous development of IgG‐ and IgM‐secreting cells was markedly suppressed by anti‐IgM or anti‐IgD antibodies. Over 50% of peripheral blood B cells were IgD‐ and/or IgM‐bearing cells in normal subjects and in most patients with rheumatoid arthritis. In lupus patients, however, the suppression of IgG and IgM production by anti‐IgM or anti‐IgD antibodies was remarkably reduced, especially in the active stage. Furthermore, the percentage of IgD‐bearing cells in peripheral blood B cells was remarkably reduced, especially in patients with active disease. There was a good correlation between reduced susceptibility of B cells to anti‐IgM antibody‐mediated suppression and reduced percentage of IgD‐bearing cells in lupus patients.
Effect of metal chelators and antiinflammatory drugs on the degradation of hyaluronic acid
Authors: Betts W. Henry , Cleland Leslie G.
Published: February 2007

Degradation of hyaluronic acid (measured viscometrically) by oxygen‐derived free radicals (ODFR) generated 1) by autoxidation of ferrous EDTA chelates and 2) enzymatically by xanthine oxidase and hypoxanthine (XO/HX) was studied. Degradation of hyaluronic acid by XO/HX was strongly inhibited by superoxide dismutase and catalase, whereas degradation of hyaluronic acid by autoxidation of ferrous ions was weakly inhibited by catalase and unaffected by superoxide dismutase. Both ODFR‐producing systems were inhibited by hydroxyl radical scavengers, suggesting that hydroxyl radical was the proximate damaging species in both systems. Penicillamine at concentrations of 1–5 mM stimulated hyaluronic acid degradation by ferrous EDTA chelates but inhibited degradation by the XO/HX system. Higher concentrations of penicillamine and all concentrations studied (1–100 mM) of other antiinflammatory drugs (chloroquine, gold sodium thiomalate, and salicylate) inhibited hyaluronic acid degradation by both the autoxidation and enzymatic ODFR‐producing systems, with inhibitory potency similar to that seen with known hydroxyl radical scavengers. Both systems serve as in vitro models of ODFR‐mediated tissue damage which may occur in vivo at sites of inflammation.
Quantitation and detection of isotypes of ANTI‐SS‐B antibodies by elisa and farr assays using affinity purified antigens
Authors: Venables PATRICK J. W. , Charles Peter J. , Buchanan RUSSELL R. C. , Yi Tung , Mumford Patricia A. , Schrieber Leslie , Room GERALDINE R. W. , Maini Ravinder N.
Published: February 2007

Affinity purified SS‐B was characterized as a protein with immunoreactive polypeptides of 40K and 29K. A modified Farr assay and an enzyme linked immunosorbent assay (ELISA) were 100‐ to 1,000‐fold more sensitive than immunodiffusion and showed an association with the systemic manifestations of primary sicca syndrome and Sjögren's syndrome with systemic lupus erythematosus. The ELISA was sufficiently sensitive to detect class specific antibodies in saliva and lymphocyte culture supernatants.
The effect of native and single stranded DNA on the platelet release reaction
Authors: Dorsch Carole A. , Killmayer Jody
Published: February 2007

Native (n) but not single stranded (ss) DNA was found to induce release of 3H‐serotonin (5‐HT) from platelets of the majority of normal individuals. However, ssDNA markedly enhanced 5‐HT release induced by heat‐aggregated IgG (aggIgG), while less enhancement was seen using nDNA. Similar enhancement was produced by polyinosinic acid but not by polyinosinic:polycytidylic acid. The ability of ssDNA to potentiate aggIgG‐induced 5‐HT release seemed specific for aggIgG, since no effect on ADP or epinephrine‐induced release was observed and thrombin‐induced release was inhibited. In contrast, nDNA in high concentrations (100 μg/ml) potentiated ADP, epinephrine, and thrombin‐induced 5‐HT release. These results suggest that ss‐and nDNA may interact with platelets by different mechanisms and provide a means by which DNA, released at sites of tissue injury, could modulate the role of platelets in the inflammatory response. The ability of DNA to enhance the aggIgG‐induced platelet release reaction may be important in immune complex diseases such as systemic lupus erythematosus.
An Evaluation of the Annual Meeting of The American Rheumatism Association
Authors: Meenan Robert F. , Mason John H. , Winfield John B.
Published: February 2007

Members of the American Rheumatism Association (ARA) were surveyed to determine their views on the content and quality of their annual meeting. Responses were received from 1,208 members. ARA members were generally positive about the major components of the annual meeting program, but there were significant differences in opinion between practitioners and academicians. Practitioners favored a reduction in basic science material and an increase in didactic clinical sessions. Academicians were more likely to feel that recent annual meetings have adequately addressed their educational needs. These findings have implications for the planning of future annual meetings of the ARA.
IgG and IgM Rheumatoid Factors in Rheumatoid Arthritis
Authors: Wernick Richard , Merryman Parvin , Jaffe Israeli , Ziff Morris
Published: February 2007

Penicillamine treatment of patients with rheumatoid arthritis (RA) leads to falling titers of agglutinating IgM rheumatoid factor (RF), but its effect on IgG RF has not been described. Using specific solid phase radio‐immunoassays, we have determined serial levels of IgM RF and IgG RF in 18 patients receiving penicillamine for 1 year, and correlated the results with the change in RA activity. Mean IgM RF levels fell to 76 ± 10% (mean ± SEM) after 3 months, and 30 ± 5% of the pretreatment value after 1 year of penicillamine treatment. This decline was greater than that for total IgM (P < 0.0001), indicating a selective reduction of RF. Patients receiving maintenance doses of 750 mg/day manifested more rapid and greater decreases than did those given 250 mg/day. In contrast, serial mean IgG RF levels did not change significantly, and actually increased in 6 of 18 cases. At onset, there was a significant correlation with erythrocyte sedimentation rate for both IgM RF (r = 0.535, P = 0.05) and IgG RF levels (r = 0.570, P = 0.02). But changes in RF concentration demonstrated no correlation with changes in either erythrocyte sedimentation rate or joint score over the 1‐year period, suggesting that circulating IgM RF or IgG RF levels may be unrelated to the degree of RA activity.
Decreased Complement Mediated Binding of Antibody/3H‐dsDNA Immune Complexes to the Red Blood Cells of Patients with Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Hematologic Malignancies
Authors: Taylor Ronald P. , Horgan Carol , Buschbacher Ralph , Brunner Carolyn M. , Hess Charles E. , O'Brien William M. , Wanebo Harold J.
Published: February 2007

The complement mediated binding of prepared antibody/3H‐dsDNA immune complexes to the red blood cells obtained from a number of patient populations has been investigated. Patients with solid tumors have binding activity similar to that seen in a normal group of individuals. However, a significant fraction of patients with systemic lupus erythematosus, rheumatoid arthritis, and hematologic malignancies have lowered binding activity compared with normal subjects. Quantitative studies indicate the lowered activity probably arises due to a decrease in complement receptors on the respective red blood cells. The potential importance and implications of these findings are briefly discussed.
Neurologic complications induced by gold treatment
Authors: Schlumpf U. , Meyer M. , Ulrich J. , Friede R. L.
Published: February 2007

Two patients developed a Guillain—Barre‐like syndrome and a third suffered neuropathy and myokymia during therapy with sodium aurothiomalate. The cumulative dose at the time of development of neuropathy was different in all 3 cases. Evidence for gold toxicity was suggested by clinical, electromyographic, and histologic findings, as well as the disappearance of symptoms and signs on cessation of gold injections.
Suppressor cell function and t lymphocyte subpopulations in peripheral blood of patients with progressive systemic sclerosis
Authors: Whiteside Theresa L. , Kumagai Yasuo , Roumm Alan D. , Almendinger Robin , Rodnan Gerald P.
Published: February 2007

Three different in vitro assays—immunofluorescence with monoclonal anti‐T cell reagents, enumeration of Tγ cells, and nonspecific suppressor cell function—were used for the analysis of suppressor lymphocytes in the circulation of 28 patients with progressive systemic sclerosis (PSS, scleroderma) and 20 normal individuals. Both OKT8+ and Tγ lymphocytes were significantly reduced (P < 0.001 and P < 0.02, respectively) in patients with PSS compared with controls. The OKT4/OKT8 ratio was increased (P < 0.02). However, the mean suppressor cell index (SCI) of 1.9 (range 0.4‐6.6) for patients with PSS was not significantly different (P > 0.05) from the SCI of 2.9 (range 1.2‐14) for controls. Eleven of the patients had depressed suppressor cell function as indicated by the index value of < 1.2. In only 5 of these patients, simultaneously measured Tγ and OKT8+ cells were reduced and OKT4+ lymphocytes were concomitantly increased. There were no significant correlations between the numbers of Tγ or OKT8+ cells and the SCI in patients and controls. Neither depressed suppressor cell function nor the OKT4+/OKT8+ ratio > 4.2 (>2 SD of normal) in the patients could be related to other immunologic findings, to disease duration and severity, or to involvement of internal organs. These results suggest that depressed suppressor cell activity and immunoregulatory T cell imbalance in PSS may not be directly related to the pathogenesis of the disease.
Collagenolytic activity and collagen matrix breakdown of the articular cartilage in the pond‐nuki dog model of osteoarthritis
Authors: Pelletier Jean‐Pierre , Martel‐Pelletier Johanne , Altman Roy D. , Ghandur‐Mnaymneh Latifa , Howell David S. , Frederick Woessner J.
Published: February 2007

Recent reports on the Pond‐Nuki model of osteo‐arthritis in the dog have provided evidence for partial disruption of the collagen network. The possibility of collagenase involvement in these localized changes was studied. Animals were killed 2, 4, 8, and 12 weeks after surgery. The left knee served as a sham‐operated control. Cartilages from femoral condyles were processed for light and electron microscopy and assayed for collagenolytic activity by a direct tissue assay, based on the measurement of digestion of endogenous cartilage collagen. Animals killed at 2 and 4 weeks showed fibrillation and mild erosion of femoral condyles, which usually progressed to ulceration by 8 and 12 weeks. Electron microscopy demonstrated fiber disruption of the midzone perilacunar collagen as early as 2 weeks after the operation. Total collagenolytic activity, measured after activation by aminophenylmercuric acetate, was significantly higher in diseased cartilage than in controls of 2, 4, and 8 weeks; the peak value was at 4 weeks. Collagenase was shown, by its specific action on type I collagen, to be present at 2 and 4 weeks; however, other metallo‐proteases may also contribute to the digestion. The correlation between increased collagenolytic activity and the early osteoarthritic changes in cartilage suggests a role of this enzyme activity in the disease process.
A new model of osteoarthritis in rabbits
Authors: Colombo C. , Butler M. , O'Byrne E. , Hickman L. , Swartzendruber D. , Selwyn M. , Steinetz B.
Published: February 2007

A partial lateral meniscectomy procedure has been developed for the induction of a predictable and reproducible degenerative joint disease in knees of rabbits. The procedure adopted involves section of the fibular collateral and sesamoid ligaments and removal of 4‐5 mm of the anterior lateral meniscus. In most experiments the animals are killed and tissues obtained for histologic examination at 6 weeks. Section of the ligaments alone (with or without penetration of the joint space) did not result in significant pathologic change. Significant degeneration was observed in tibial and femoral cartilage when the meniscus as well as the ligaments were cut, but the most extensive lesions were seen when a piece of the anterolateral meniscus was actually removed. These lesions included fibrillation, ulceration and erosion, “clone” and osteophyte formation, loss of chondrocytes, and loss of safraninophilic staining in the articular cartilage. The incidence and distribution of lesions with time following surgery were also investigated. Lesions were observed as early as 1‐2 weeks post‐surgery and increased in number and severity up to 12 weeks. A global scoring system has been devised to permit statistical comparisons of lesion incidence and severity in different groups of rabbits. This scoring system has enabled us to test drug efficacy in the rabbit lateral meniscectomy model of osteoarthritis.
Sustained improvement of intractable rheumatoid arthritis after total lymphoid irradiation
Authors: Field Elizabeth H. , Strober Samuel , Hoppe Richard T. , Calin Andrei , Engleman Edgar G. , Kotzin Brian L. , Tanay Amir S. , Jane Calin H. , Terrell Candace P. , Kaplan Henry S.
Published: February 2007

Total lymphoid irradiation (TLI) was administered to 11 patients who had intractable rheumatoid arthritis that was unresponsive to conventional medical therapy, including aspirin, multiple nonsteroidal antiin‐flammatory drugs, gold salts, and D‐penicillamine. Total lymphoid irradiation was given as an alternative to cytotoxic drugs such as azathioprine and cyclophosphamide. After radiotherapy, 9 of the 11 patients showed a marked improvement in clinical disease activity as measured by morning stiffness, joint tenderness, joint swelling, and overall functional abilities. The mean improvement of disease activity in all patients ranged from 40–70 percent and has persisted throughout a 13–28 month followup period. This improvement permitted the mean daily steroid dose to be reduced by 54%. Complications included severe fatigue and other constitutional symptoms during radiotherapy, development of Felty's syndrome in 1 patient, and an exacerbation of rheumatoid lung disease in another. After therapy, all patients exhibited a profound T lymphocytopenia, and a reversal in their T suppressor/cytotoxic cell to helper cell ratio. The proliferative responses of peripheral blood mononu‐clear cells to phytohemagglutinin, concanavalin A, and allogeneic leukocytes (mixed leukocyte reaction) were markedly reduced, as was in vitro immunoglobulin synthesis after stimulation with pokeweed mitogen. Alterations in T cell numbers and function persisted during the entire followup period, except that the mixed leukocyte reaction showed a tendency to return to normal values.
Heterogeneity of bone marrow‐directed immune mechanisms in the pathogenesis of neutropenia of felty's syndrome
Authors: Abdou Nabih I.
Published: February 2007

Twenty‐seven patients with Felty's syndrome were studied by the colony forming unit in culture (CFU‐C) assay for possible immune mechanisms within the bone marrow compartment that could contribute to the neutropenia. Depletion of bone marow suppressor T cells resulted in normal CFU‐C numbers in 7 patients. In 5 patients serum antiprecursor cell activity was detected. Blood monocytes failed to generate colony stimulating factor in 5 patients. Bone marrow‐directed immune mechanisms are heterogeneous and could play a role in the pathogenesis of neutropenia in some patients with Felty's syndrome.
67Gallium lung scans in progressive systemic sclerosis
Authors: Baron Murray , Feiglin David , Hyland Robert , Urowitz Murray B. , Shiff Bonnie
Published: February 2007

67Gallium lung scans were performed in 19 patients with progressive systemic sclerosis (scleroderma). Results were expressed quantitatively as the 67Gallium Uptake Index. The mean total pulmonary 67Gallium Uptake Index in patients was significantly higher than that in controls (41 versus 25), and 4 patients (21%) fell outside the normal range. There were no clinical or laboratory variables that correlated with the 67gallium uptake. Increased pulmonary 67gallium uptake in scleroderma may prove useful as an index of pulmonary disease activity.
The epidemiology of giant cell arteritis. Report of a Ten‐Year Study in Shelby County, Tennessee
Authors: Smith Carolyn A. , Fidler William J. , Pinals Robert S.
Published: February 2007

We have studied the epidemiology of giant cell arteritis (GCA) hi an urban population in south central United States. The incidence of GCA in Shelby County, Tennessee for the years 1971 through 1980 was determined for the total population and for age‐, sex‐, and race‐specific groups. Over this period 26 cases were identified. The average annual incidence was 0.35/100,000; This was increased to 1.58/100,000 for those over the age of 50. The incidence was 7 times greater in whites than in blacks and 7 times greater in females than in males. Clinical and laboratory features of the patients were reviewed and found to be similar to those in other populations. GCA is considerably less frequent in Shelby County, Tennessee than in other areas where similar epidemiologic studies have been performed. This difference can be accounted for only in part by racial distributions. Similar studies in southern geographic areas are needed to place our findings in perspective and point to specific factors which may have etiologic significance in GCA.
Polyarthritis in rats following the systemic injection of lactobacillus casei cell walls in aqueous suspension
Authors: Lehman Thomas J. A. , Allen Janice B. , Plotz Paul H. , Wilder Ronald L.
Published: February 2007

Postdysenteric Reiter's syndrome and the arthritis associated with jejunal bypass surgery for obesity suggest that the gastrointestinal tract is a possible source of bacterial products capable of initiating chronic inflammatory arthritis. Lactobacillus casei, a common component of the enteric flora, has a cell wall structure similar to that of arthritogenic streptococci. In this study we have demonstrated that a single intraperitoneal injection of an aqueous suspension of the cell walls of Lactobacillus casei induces a dose‐dependent, chronic, symmetric, erosive, peripheral polyarthritis in inbred LEW/N female rats. This model suggests that bacteria in the “normal enteric flora” may be a source of inflammatory products capable of inducing chronic erosive polyarthritis.
Lack of activation of C1, despite circulating immune complexes detected by two C1q methods, in patients with rheumatoid arthritis
Authors: Erik Hack C. , Eerenberg‐Belmer Anke J. M. , Lim Uwi G. , Haverman Joost , Aalberse Rob C.
Published: February 2007

The activation of C1 by circulating immune complexes in patients with rheumatoid arthritis was investigated. C\documentclass{article}\pagestyle{empty}\begin{document}$ \overline {{\rm{1r}}} $\end{document}C\documentclass{article}\pagestyle{empty}\begin{document}$ \overline {{\rm{1s}}} $\end{document}
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‐In)2 complexes in EDTA‐plasma, reflecting C1 activation in vivo, were slightly raised in 35 of 57 patients with rheumatoid arthritis, though most patients had elevated levels of circulating immune complexes as measured with either the 125I‐C1q binding test or the C1q solid phase assay. The activation of C1 by circulating immune complexes in vitro was investigated by measuring the generation of C\documentclass{article}\pagestyle{empty}\begin{document}$ \overline {{\rm{1r}}} $\end{document}
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‐In)2 complexes during 60 minutes at 37oC in diluted recalcified EDTA‐plasma. In 16 of the 57 patients, a slightly increased C1 activation in vitro was observed. These patients tended to have high levels of circulating immune complexes. However, the majority of the patients with high levels of circulating immune complexes showed a normal C1 activation in vitro. Therefore, it was concluded that measurement of circulating immune complexes by either of the two C1q methods in patients with rheumatoid arthritis does not imply that these circulating immune complexes are able to activate C1.
In vitro t lymphocyte proliferative response to yersinia enterocolitica in reiter's syndrome
Authors: Brenner Michael B. , Kobayashi Shigeto , Wiesenhutter Craig W. , Huberman Arthur K. , Bales Peter , Yu David T. Y.
Published: February 2007

We assessed the in vitro T lymphocyte tritiated thymidine (3HTdr) incorporation response of Reiter's patients in the United States to a serotype 3 strain of Yersinia enterocolitica. The mean 3HTdr incorporation response to the formalin killed form of this strain was 27,409 ± 5,488 counts per minute for 14 HLA‐B27 positive Reiter's patients compared with 5,414 ± 3,490 cpm for a control group of 11 HLA‐B27 positive normal individuals (P < 0.0005). This high response in Reiter's patients was observed with the formalin killed form of Y enterocolitica serotype 3, but not with a heat killed form or a rough mutant form derived from the same bacterial strain. Further, Y enterocolitica of a different serotype (serotype 8) which is not associated with reactive arthritis failed to induce the high proliferative response observed with the serotype 3 strain. This response indicates that T lymphocytes from spontaneous Reiter's patients are capable of recognizing and proliferating to determinant(s) on the formalin killed form of Y enterocolitica serotype 3. Since this bacterium is associated with Reiter's syndrome in Europe but not the United States, these data are consistent with the possibility that our patients have previously encountered these or similar determinants through unrecognized infection with other microorganisms.
The effects of a partially purified fraction of an ant venom in rheumatoid arthritis
Authors: Altman Roy D. , Schultz Duane R. , Collins‐Yudiskas Barbara , Aldrich Jose , Arnold Patricia I. , Arnold Patricia I. , Brown Harvey E.
Published: February 2007

A partially purified extract of an ant venom from the South American tree ant Pseudomyrmex sp. was tested in a double‐blind, controlled study of patients with rheumatoid arthritis. Venom treated patients demonstrated an improvement in global efficacy and a decrease in the number of tender/painful joints and swollen joints. Swollen joint index improved in 60% of venom treated patients. Other parameters did not demonstrate significant change. Reduction of joint swelling was followed by symptomatic improvement that was sometimes delayed by weeks. Reactions were limited to erythema at the injection site (all patients), local pruritis (two‐thirds of the patients), and fever with malaise (one‐third of the patients). Further study of this venom in rheumatoid arthritis appears warranted in view of its apparent favorable efficacy‐to‐toxicity ratio.
In Vivo and in Vitro Stimulation of Chondrocyte Biosynthetic Activity in Early Experimental Osteoarthritis
Authors: Sandy John D. , Adams Mark E. , Billingham Michael E. J. , Plaas Anna , Muir Helen
Published: February 2007

The biosynthesis of proteoglycans in the menisci and articular cartilages of the knee (stifle) of mature beagles was studied in the early stages of experimental osteoarthritis. The rate of proteoglycan synthesis, determined by systemic labeling in vivo at 21, 42, and 84 days after sectioning of the anterior cruciate ligament, was generally found to be 1.5—2.5‐fold higher than control in articular cartilages and 3—10‐fold higher than control in menisci. The medial meniscus was more stimulated than the lateral meniscus, and the medial tibial plateau under the meniscus was more stimulated than the adjacent tibial area. This area‐specific stimulation suggests the involvement of mechanical factors in the cellular response. The rate of proteoglycan synthesis determined in vitro at 7, 14, and 21 days after operation was also about 2‐fold higher than control in articular cartilages and about 3‐fold higher in menisci. This increase in biosynthetic activity in vitro was confirmed by 35S‐autoradiography and appeared to be due to general stimulation of existing chondrocytes, particularly in the middle and deep zones of the articular cartilage and throughout the meniscal cartilage. The rate of proteoglycan synthesis determined in vitro in cartilages from 2‐week and 3‐week sham operated joints was also increased relative to controls, suggesting that humoral as well as mechanical factors are involved in stimulating chondrocyte activity.
Cartilage Nucleoside Triphosphate (NTP) Pyrophosphohydrolase
Authors: Ryan Lawrence M. , Wortmann Robert L. , Karas Barbara , Mccarty Daniel J.
Published: February 2007

When 1 mM ATP was added to ambient media of canine cartilage in organ culture or canine chondrocytes in monolayer culture, PPi was generated linearly over 4 hours. The appearance of PPi was related to an ecto‐enzyme based upon its ability to act upon extracellular substrate, to generate extracellular products, failure to detect enzyme activity in supernatant media, failure to increase activity by cell disruption, and susceptibility to digestion by extracellular trypsin. The enzyme responsible for PPi generation is nucleoside triphosphate (NTP) pyrophosphohydrolase, which acts upon a number of purine and pyrimidine nucleoside triphosphates. This enzyme may play a role in generation of extracellular PPi which participates in calcium pyrophosphate dihydrate crystal formation.
HLA—‐DR4 is not a requisite for autoimmunity to collagen in rheumatoid arthritis
Authors: Kammer Gary M. , Trentham David E.
Published: February 2007

Immunogenetic studies in rheumatoid arthritis have demonstrated an increased frequency of the HLA—‐DR4 alloantigen in individuals with both the sporadic and familial forms of the disease. To investigate the significance of this association, we ascertained whether the possession of DR4 is necessary for the expression of cellular and humoral immunity to native human type II collagen. Our results indicate that the presence of DR4 is not required for the development of autoimmunity to collagen in rheumatoid arthritis.
Extracellular presence of the lysosomal proteinase cathepsin B in rheumatoid synovium and its activity at neutral pH
Authors: Mort John S. , Recklies Anneliese D. , Poole A. Robin
Published: February 2007

The presence of the lysosomal proteinases cathepsin B and cathepsin D at extracellular sites in rheumatoid synovium was demonstrated using the antibody capture technique. Unlike cathepsin D, the cysteine proteinase cathepsin B was commonly detected only at the edges of the synovial explants. Radioimmunoassay and enzyme activity assay of these proteinases demonstrated that both were released from rheumatoid synovial cells in comparable amounts. Since lysosomal cathepsin B is unstable and denatured at physiologic pH and the antibody used only recognizes inactivated enzyme, we believe the selective detection of cathepsin B at the edge of the synovium may be due to the proteinase maintaining a native conformation within the explant, where the pH may be low enough to permit this. By use of a fluorescent substrate in a sensitive, continuous enzyme assay, cathepsin B was shown to express significant activity at neutral and alkaline pH before being inactivated. This and earlier work from this laboratory indicate that cathepsin B secreted by rheumatoid synovial cells may possess extracellular activity in vivo and be involved in the degradation of connective tissue macro‐molecules.
The use of trained patient instructors for teaching and assessing rheumatologic care
Authors: Gall Eric P. , Meredith Keith E. , Stillman Paula L. , Rutala Paul J. , Gooden M. Annell , Boyer John T. , Riggs Gail E.
Published: February 2007

The training of professionals in rheumatologic care requires review and study. To improve teaching methods, 6 patients with stable rheumatic disease were trained to evaluate and teach medical students by using themselves as models for musculoskeletal examinations. Checklists for scoring performance and content were developed. Criteria established to give evidence of the validity of the checklists and of the reliability of the patient instructors in their scoring were met or exceeded. The patient instructors are now an integral part of the Preparation for Clinical Medicine curriculum at our institution and serve as resources for evaluation and teaching in the continuing education of practicing professionals.
Connective tissue activating peptide III induction of synthesis and secretion of plasminogen activator by synovial fibroblasts
Authors: Ragsdale Carol Godoshian , Castor C. William , Roberts Dedra J. , Swartz Kenneth H.
Published: February 2007

Connective tissue activating peptide III (CTAP‐III) is a platelet factor that induces, in cultured connective tissue cells, activities observed in chronic inflammation. In this study we measured plasminogen activator secretion by synovial fibroblasts after stimulation by CTAP‐III. Increased plasminogen activator secretion was observed 24—48 hours after stimulation. Induction was prevented by dexamethasone (10‐9—10‐7M), cycloheximide (1 μg/ml) and, variably, by actinomycin D (0.3 μg/ml), but not by cytosine arabinoside (10‐4M). This is the first evidence that CTAP‐III induces degradative as well as proliferative activity by connective tissue cells.
Susceptibility and resistance to 6‐sulfanilamidoindazole‐induced arthritis among inbred strains of rats
Authors: Samuelson Cecil O. , Griffiths Marie M. , Mathews Jeffrey L. , Clegg Daniel O. , Ward John R.
Published: February 2007

Inflammation induced by 6‐sulfanilamidoindazole (6‐SAI) in aged, outbred rats is predictably produced, but the pathogenesis is not understood. We demonstrate the variable resistance of 15 inbred rat strains to 6‐SAI arthritis. Susceptibility to 6‐SAI arthritis is not directly linked to the major histocompatibility complex, although resistance is related to the major histocompatibility complex in other experimental forms of rat arthritis. The genetic background of these inbred rat strains appears to have a major role in 6‐SAI arthritis susceptibility.
Rheumatoid myositis
Authors: Halla James T. , Koopman William J. , Fallahi Sohrab , Oh Shin J. , Gay Renate E. , Schrohenloher Ralph E.
Published: February 2007

Thirty‐one patients with rheumatoid arthritis were consecutively studied for evidence of muscle involvement, using muscle biopsy and electromyography. The patients were initially separated into 4 clinical categories: inactive peripheral joint disease (6 patients); active peripheral joint disease (10 patients); systemic disease and a disproportionately elevated sedimentation rate for the degree of mild synovitis (SERD) (11 patients); or elevated creatinine phosphokinase level (4 patients). In addition to routine histology, muscle tissue was examined for de novo synthesis of IgM and IgM rheumatoid factor, and by indirect immunofluorescence for the presence of immunoglobulin and complement deposits. Our results indicate that: 1) muscle fiber necrosis occurs frequently in patients with rheumatoid arthritis; 2) rheumatoid myositis, defined as muscle fiber necrosis and mononuclear cell infiltration, is a distinct entity and occurs particularly in patients with SERD or an elevated creatinine phosphokinase level; and 3) only muscle from patients with rheumatoid myositis exhibited de novo synthesis of rheumatoid factor and significant quantities of IgM, indicating that local immune events may be important in the pathogenesis of this entity.
Suppressor t cell function in patients with rheumatoid arthritis complicated by vasculitis
Authors: Abe Tohru , Takeuchi Tsutomu , Koide Jun , Hosono Osamu , Homma Mitsuo , Morimoto Chikao , Yokohari Ryuichi
Published: February 2007

Concanavalin A (Con A)—induced suppressor T cell activity was determined in 10 rheumatoid arthritis (RA) patients with vasculitis, 34 RA patients without vasculitis, and 10 healthy individuals. The percent Con A—induced suppression in RA patients with vasculitis was 24.6. In contrast, it was 68.4% in those RA patients without vascular lesions. Further, the proportion of T cells reactive with OKT8 monoclonal antibody was also decreased in RA patients with vasculitis. Accordingly, the reduced Con A—induced suppressor T cell activity in these RA patients resulted, in part, from the reduction in the number of cells of the suppressor T cell subset. Those patients with vascular lesions also had a higher percentage of positive antilymphocytotoxic antibodies than RA patients without vasculitis. Since the differences in Con A—induced suppressor T cell activity and frequency of positive antilymphocytotoxic antibodies were so great, we believe RA patients with vasculitis could be recognized as a disease group distinct from RA patients without vasculitis.
Collagen‐induced and adjuvant‐induced arthritis in rats
Authors: Phadke Kalindi , Fouts Rebecca , Parrish John E.
Published: February 2007

Immunization of Lewis rats with native type II collagen results in an inflammatory arthritis and increased humoral and cellular immune responses to type II collagen. The exposure of rats to native type II collagen at day 7 or 10 after immunization suppressed the incidence of arthritis and anticollagen antibody levels, although the cellular response was not affected. The exposure to denatured type II collagen offered partial protection, while type I collagen had no significant effect. Rats immunized with Mycobacterium tuberculosis also showed reduced arthritic response when subsequently treated with type II collagen. The common modalities between the 2 models and the possible role of type II collagen in the interference with the inflammatory arthritic events are discussed.
Quantitation of human synovial mast cells in rheumatoid arthritis and other rheumatic diseases
Authors: Godfrey Henry P. , Ilardi Carl , Engber William , Graziano Frank M.
Published: February 2007

We examined sections of synovial membranes from 14 patients with rheumatoid arthritis (RA), 7 with other rheumatic diseases, and 10 with no apparent joint disease. Patients with RA and other rheumatic diseases had significantly more synovial mast cells/vessel than patients with no joint disease (0.49 and 0.20, respectively, versus 0.03). They also had significantly more total mast cells/10 fields than patients with no joint disease (9.9 and 5.0, respectively, versus 0.4). Within the rheumatoid group, patients with active disease had more total mast cells/10 fields than patients clinically considered to have end‐stage disease (P < 0.05). Synovial basophils were not identified in any patient. Synovial vascularity was similar for all groups (2.3 vessels/field). The role of the synovial mast cell in RA and other rheumatic diseases remains to be determined.
Serum Clq levels as a prognostic guide to articular erosions in patients with rheumatoid arthritis
Authors: Ochi Takahiro , Yonemasu Kunio , Iwase Rokuro , Sasaki Takako , Tsuyama Kenichiro , Ono Keiro
Published: February 2007

C1q was measured serially by single radial immunodiffusion in 54 rheumatoid arthritis (RA) patients over a period of more than 5 years, and values were correlated with laboratory, radiographic, and clinical findings. The number of joints with erosion (NJE) was determined retrospectively from radiographs of patients who had RA of >7 years duration. In patients with clinically “burned out” RA, C1q levels were not statistically different from those of healthy adults. During the period of active disease, each patient's C1q level remained very constant, irrespective of erythrocyte sedimentation rate, C‐reactive protein (CRP) level, or whether the RA was active or in remission. No sustained correlation was found between the C1q level and the other 2 acute phase reactants, but patients with C1q levels of at least 250 μ g/ml showed a positive CRP over a period of years, in contrast to those with C1q levels below 250 μ/ml. Patients with an initial C1q above 250 μ/ml had more erosive RA when compared with those having C1q levels below 250 μ/ml. These data suggest that active RA can be classified into two subsets by C1q levels, one with persistent inflammation and a high NJE and another without persistent inflammation and with a low NJE.
Experimental synovitis induced by intraarticular administration of α2‐macroglobulin‐proteinase complexes
Authors: Steffen Carl , Borth Wolfgang , Susani Martin , Zischka‐Konorosa Wilhelm
Published: February 2007

Rheumatoid synovial collagenase was prepared from tissue cultures from rheumatoid arthritis patients, obtained after synovectomy. Alpha2‐macroglobulin was isolated from human plasma and complexed with collagenase or trypsin. Formation of both types of complexes was proven by sodium dodecyl sulfate and rate electro‐phoresis. Normal rabbits were injected intraarticularly into the right knee, on days 0, 3, and 6, with either α2‐macroglobulin‐collagenase or α2‐macroglobulin‐trypsin complexes. Control injections of α2‐macroglobu‐lin, trypsin, or rheumatoid synovial collagenase were applied to the left knee joint cavity. Groups of rabbits were killed 18 hours, 1 week, or 3 weeks after the last injection, and cellular exudation into synovial fluid and morphologic alterations of synovium were investigated. Joints injected with collagenase showed no synovitis, while joints injected with collagenase showed an experimental synovitis. Alpha2‐macroglobulin‐proteinase complexes, however, induced a synovitis, which was more severe than that occurring after injection of proteinases only. In the early stages, synovium showed perivascular accumulation of inflammatory cells, infiltration with neutrophils, proliferation of synovial cells, and exudation of inflammatory cells into synovial fluid. Later stages were characterized by infiltration with mononuclear cells and fibroplasia.
Changes in proteoglycan biosynthesis following leukocyte elastase treatment of bovine articular cartilage in culture
Authors: Bartholomew Jennifer S. , Lowther Dennis A. , Handley Christopher J.
Published: February 2007

Treatment of bovine articular cartilage in culture with a low molecular weight elastase purified from rabbit polymorphonuclear leukocytes resulted in degradation and release of proteoglycans from the tissue, coupled with a prolonged inhibition of proteoglycan biosynthesis. These observations are consistent with those seen in experimental arthritis induced in rabbits. Comparison of the size of the proteoglycan degradation products extracted from elastase‐treated cartilage in culture with that from arthritic cartilage showed marked similarities. The results strongly suggest that leukocyte elastase is a contributing factor in proteoglycan degradation and inhibition of synthesis in inflammatory joint disease.
A new serologic marker in ankylosing spondylitis
Authors: Lakomek Heinz‐Jürgen , Will Hans , Zech Michael , Krüskemper Hans Ludwig
Published: February 2007

Sera of patients with ankylosing spondylitis (AS) were screened for the presence of antibodies by indirect immunofluorescence staining of polytene chromosomes of Drosophila melanogaster. Thirty‐nine percent of the sera tested contained antibodies which selectively reacted with an antigen(s) present at the chromosomal locus 93D after heat shock treatment. This indicates a novel antibody specificity in a subgroup of AS patients and may provide a new aid in the diagnosis of AS.
Synthesis of electrophoretically restricted IgG by cultured rheumatoid synovium
Authors: Hoffman Wayne L. , Douglass Rita R. , Donald Smiley J.
Published: February 2007

IgG synthesized by excised rheumatoid (RA) synovia was separated according to isoelectric point using chromatofocusing and isoelectric focusing. Over 30% of the IgG synthesized by 9 of 11 synovia had an isoelectric point >8 (cathodal shift), while 55% of the synovia secreted IgG showing oligoclonal banding by isoelectric focusing. Oligoclonal serum IgG was seen in 17% of RA patients and in only 3% of hospitalized patients without RA. These results emphasize the selective character of the antigenic stimulus of the RA synovial lymphoid infiltrate.
Decreased pokeweed mitogen‐induced igm and igm rheumatoid factor synthesis in rheumatoid arthritis patients treated with gold sodium thiomalate or penicillamine
Authors: Olsen Nancy J. , Jasin Hugo E.
Published: February 2007

Prospective and retrospective analysis of data obtained on 119 patients with rheumatoid arthritis suggested a relationship between clinical response induced by gold salts or D‐penicillamine and decreased in vitro antibody synthesis by peripheral blood mononuclear cells. A subgroup of 21 patients with inactive disease receiving these drugs was found to have decreased pokeweed mitogen‐induced in vitro synthesis of IgM and IgM rheumatoid factor. Detailed analysis of the cellular mechanisms responsible for this decreased responsiveness demonstrated markedly decreased B cell function. Patients treated with D‐penicillamine also had altered T cell helper function manifested by incomplete reconstitution of the normal IgM response, while patients treated with gold salts had normal T cell function. Monocytes appeared not to have a major role in the decreased in vitro responsiveness. The results suggest that, in patients who respond to gold salts or D‐penicillamine, antibody synthesis by circulating B cells is profoundly decreased, probably due to an indirect effect of these disease‐modifying agents.
Increased biosynthesis of glycosaminoglycans by scleroderma fibroblasts in culture
Authors: Bashey Reza I. , Millan Alberto , Jimenez Sergio A.
Published: February 2007

Fibroblasts from normal and scleroderma skin, grown in culture, were incubated with radioactive glucosamine to study the biosynthesis of glycosaminoglycans (GAG). Incorporation of 3H‐glucosamine and GAG biosynthesis was increased in 6 of 9 scleroderma fibroblast cultures examined. This increase ranged from 26 to 96% over normal values and was reproducible. Over 70% of the 3H‐glucosamine incorporated was found in the medium of the cultures, and this fraction was used to isolate GAG. Characterization of media GAG from normal and control cultures showed that about 80% of the radioactive GAG could be degraded by a specific fungal hyaluronidase; therefore, it represented hyaluronic acid. Our findings indicate that the majority of scleroderma dermal fibroblasts display increased biosynthesis of GAG in culture and that this increase is mostly in the hyaluronic acid fraction.
Clinical and pathologic studies of synovitis in polymyalgia rheumatica
Authors: Chou Chung‐Tei , Ralph Schumacher H.
Published: February 2007

Clinically detectable joint swelling was found in 10 of 13 fully evaluated patients considered to have polymyalgia rheumatica. Five patients had some joint findings at disease onset. Knees were most commonly affected. Sternoclavicular involvement was seen in 3 patients. Joint effusions in 8 patients had 300–5,700 leukocytes/mm3 with a mean of 2,900. Six synovial biopsy specimens studied by light microscopy revealed mild to moderate synovial proliferation and chronic inflammation that was generally less severe than in typical rheumatoid arthritis. Electron microscopy identified microvascular changes and large amounts of vesicular and granular debris in lining cells. In 1 patient, a “fingerprint” pattern in the granular material was suggestive of the findings in some immune complexes. This still unexplained synovitis may, as previously suggested, be important in the pathogenesis of the polymyalgia rheumatica syndrome.
Inhibitory effect of igm rheumatoid factor on immune complex solubilization capacity and inhibition of immune precipitation
Authors: Balestrieri Genesio , Tincani Angela , Migliorini Paola , Ferri Clodoveo , Cattaneo Roberto , Bombardieri Stefano
Published: February 2007

Purified IgM rheumatoid factors (RF; 3 monoclonal and 2 polyclonal) were shown to inhibit, in a dosedependent manner, 2 complement‐mediated functions, i.e., the immune complex solubilization capacity and the inhibition of immune precipitation. Inhibition of immune complex solubilization capacity occurred only if RF was added at the same time as, but not after, addition of the complement source. Experimental evidence suggests that the effects of RFs were not related to their anticomplementary activity, but rather required the attachment of RF to the Fc region of the IgG molecule. Although no clinical data are available so far, it might be plausible that these newly described properties of RF have biologic relevance.
Cyclic nucleotides and calcium transport in cultured dermal fibroblasts from progressive systemic sclerosis and rheumatoid arthritis patients
Authors: Grozdova M. D. , Khokhlova J. V. , Panasyuk A. F. , Guseva N. G. , Trofimova T. M.
Published: February 2007

Levels of cAMP were decreased and cGMP increased in progressive systemic sclerosis (PSS) fibroblasts compared with normal fibroblasts. PSS cells took up unusually large quantities of Ca++. The epinephrine‐induced increases in cAMP were diminished sixfold and epinephrine‐induced Ca++ uptake was abnormal in PSS cells. Considerable heterogeneity was observed in rheumatoid arthritis fibroblasts. Membrane‐bound abnormalities in (PSS) cells may be of importance in the defective control of collagen production in progressive systemic sclerosis.