bluuebunny/crossref_metadata_2025 huggingface dataset:
Self‐associating igg rheumatoid factors in mrl/1 autoimmune mice
Authors: Nardella Francis A. , Teller David C. , Izui Shozo , Mannik Mart
Published: February 2007

Previous work has shown that the intermediate complexes isolated from the plasma of patients with rheumatoid arthritis are composed of self‐associating IgG rheumatoid factors. Mice of the MRL/1 strain develop spontaneous autoimmune disease with arthritis that is pathologically similar to human rheumatoid arthritis. Also, the sera of MRL/1 mice contain autoantibodies to nuclear antigens as well as IgM and IgG rheumatoid factors. The present studies were done to determine if the IgG rheumatoid factors isolated from these mice undergo self‐association. MRL/1 mouse sera were categorized into groups A and B based on serumserum precipitin interactions. Thirteen of 13 MRL/1 mice sera examined contained intermediate complexes sedimenting between the 6.6S and 19S components of normal serum by sedimentation velocity ultracentrifugation. There were no differences in the level of intermediate complexes between groups A and B. IgG rheumatoid factors were isolated from the sera of 9 other mice. Upon sedimentation equilibrium ultracentrifugation, these rheumatoid factors underwent concentration‐dependent self‐association similar to that described for human self‐associating IgG rheumatoid factors, although the precise stoichiometry of self‐association could not be determined. The IgG rheumatoid factors from group B had higher energies of self‐interaction than those from group A. These studies provide additional evidence that MRL/1 mice may be the best available animal model for the study of human rheumatoid arthritis.
An attempt to predict the response to gold therapy in rheumatoid arthritis
Authors: O'Duffy J. D. , O'Fallon W. M. , Hunder G. G. , Mcduffie F. C. , Moore S. B.
Published: February 2007

In 54 rheumatoid arthritis patients undergoing conventional chrysotherapy, we prospectively sought predictors of response, using strict clinical and laboratory criteria of improvement. Forty‐five patients who completed 6–12 months of therapy were classified into 3 outcome categories: group 0, not significantly improved (18 patients); group 1, improved (18 patients); and group 2, markedly improved (9 patients). Sixty‐two entry variables were tested in univariate and multivariate analysis for predictor function. No continuous variable was predictive. The discrete variables HLA‐A3 positivity and HLA‐DR4 negativity were the best predictors of response to gold. In a multivariate analysis using these 2 univariates (A3 and DR4) plus hemoglobin, we developed a discriminant function that correctly predicted outcome in 21 of 23 patients in groups 0 and 2. We also observed that of 15 DR blank patients (10 of whom were DR4 blank), none entered remission.
Zonal analysis of cytoplasmic components of articular cartilage chondrocytes
Authors: Brighton Carl T. , Kitajima Toshihiro , Hunt Robert M.
Published: February 2007

The cytoplasmic components of chondrocytes in the various zones of articular cartilage of the medial femoral condyle of adult male New Zealand white rabbits were quantitated from electron micrographs. A progressive increase in the content of endoplasmic reticulum, Golgi apparatus, mitochondria, and electrondense bodies (presumed to be lysosomes) from the tangential zone through the top half of the calcified zone was observed. These organelles then showed a decrease in content in the bottom half of the calcified zone. This was associated with an even greater increase in content of holes in the cytoplasm at that level, providing clear evidence of cellular swelling. Based on these quantitative morphologic studies, it is concluded that the chondrocytes in all zones of articular cartilage are metabolically active, but those cells in the calcified zone show signs of degeneration. The ultimate fate of the chondrocytes in the bottom of the calcified zone is not clear from this study.
Low C3B receptor reactivity on erythrocytes from patients with systemic lupus erythematosus detected by immune adherence hemagglutination and radioimmunoassays with monoclonal antibody
Authors: Minota Seiji , Terai Chihiro , Nojima Yoshihisa , Takano Kiyohide , Takai Emiko , Miyakawa Yuzo , Takaku Fumimaro
Published: February 2007

C3b receptor (CR1) on erythrocytes from 23 patients with systemic lupus erythematosus (SLE) and 124 normal controls was determined by immune adherence hemagglutination (IAHA) and radioimmunoassay. The binding of radiolabeled monoclonal anti‐CR1 to erythrocytes and their lysate was distributed continuously in a wide range. The majority of SLE patients showed low binding by both assays. CR1 sites on erythrocytes were determined also by Scatchard plot analysis and standardized by the number of similarly determined lectin‐binding sites that served as a measure of erythrocyte surface. The numbers of standardized CR1 sites were classified as high, intermediate, and low. Thirty‐six percent of control subjects had high numbers of CR1 sites, 53% had intermediate numbers, and 11% had low numbers. Of SLE patients, the numbers of CR1 sites were high in 0%, medium in 52%, and low in 48%. Negative IAHA was found in 10 controls (8%), all of whom had low numbers of standardized CR1 sites. Among 13 SLE patients with negative IAHA, 11 had low numbers of CR1 sites and the remaining 2 had low intermediate numbers. IAHA, therefore, was particularly efficient in detecting the low numbers of CR1 sites in SLE, which would impair the disposal of circulating immune complexes and accelerate the development of tissue injuries.
Abnormal calcium and magnesium stores in erythrocytes and granulocytes from patients with inflammatory connective tissue diseases. Relationship to inflammatory activity and effect of corticosteroid therapy
Authors: Hällgren Roger , Svenson Karin , Johansson Erland , Lindh Ulf
Published: February 2007

The mass fraction of Ca and Mg in isolated erythrocytes and granulocytes was measured using the nuclear microprobe technique. Conspicuous abnormalities were observed in cells from patients with rheumatoid arthritis and other inflammatory arthritides. Compared with the normal cellular content, total Ca was increased an average of 3 times in erythrocytes and 5 times in granulocytes. Total granulocyte Mg was increased about 3 times, whereas erythrocyte Mg was reduced to as much as 60% of normal. These abnormalities were less prominent or were absent in scleroderma patients, except for levels of granulocyte Ca, which were increased more than 3 times beyond normal in this patient group. A significant positive correlation was found between serum haptoglobin and erythrocyte or granulocyte Ca content among these patients, but not between haptoglobin and erythrocyte or granulocyte Mg values. During corticosteroid treatment, a significant increase in erythrocyte Mg and a significant reduction in erythrocyte Ca were noted, but normalization of these levels was not achieved. Granulocyte Ca was also significantly reduced, while granulocyte Mg remained unaltered. Serum levels of Ca and Mg were within normal ranges and were not influenced by corticosteroid therapy. The results indicate that at least Ca abnormalities in erythrocytes and granulocytes are associated with the intensity of the inflammatory process and that the amounts of Ca and Mg in these cells are influenced by potent antiinflammatory therapy.
Circulating natural killer cells in sjögren's syndrome
Authors: Ichikawa Yukinobu , Yoshida Miyoko , Takaya Masatoshi , Uchiyama Mitsuaki , Shimizu Hiroaki , Arimori Shigeru
Published: February 2007

Reduced natural killer (NK) cell activity of peripheral blood lymphocytes (PBL) has been reported in a number of diseases including Sjögren's syndrome (SS). In this study, we used 2 monoclonal antibodies directed toward NK cells (anti‐Leu‐7 and anti‐Leu‐11) for determining NK cell activity in 29 patients with SS (9 with primary SS and 20 with secondary SS). The NK activity of PBL was simultaneously determined by the 51Cr release method using K562 as target cells. Contrary to previous reports, we did not find reduced NK activity of PBL in our patients compared with sex‐ and age‐matched healthy controls. Although the percentage of Leu‐7+ cells was significantly higher in the patients than in the controls (P < 0.05), the absolute number of circulating Leu‐7+ cells was not different between the groups. The percentage of Leu‐11+ cells, however, was not significantly different between the patients and the controls, but the number of circulating Leu‐11+ cells was significantly fewer in the patients than in the controls (P < 0.05). Between the primary and secondary SS groups, no significant differences were found in NK cell activity or in the percentage of Leu‐7+ or Leu‐11+ cells. Furthermore, we found a significant correlation of NK activity with the percentage of Leu‐11+ cells (P < 0.05) in the controls as well as the SS patients, although a significant correlation was not identified between NK activity and the percentage of Leu‐7+ cells. These results are compatible with the known specificities of each monoclonal antibody: the anti‐Leu‐11 antibody is more specific for functionally active NK cells than is the anti‐Leu‐7 antibody. The NK activity of PBL, therefore, was proportional to the percentage of NK cells (Leu‐11+ cells) and was not impaired in our patients with SS, although the number of circulating NK cells was fewer in the patients than in the healthy controls.
Effects of long‐term procainamide therapy on immunoglobulin synthesis
Authors: Yu Chia‐Li , Ziff Morris
Published: February 2007

Procainamide is a potent inducer of autoantibodies. In order to evaluate the immunologic effects of this drug in vivo, 23 cardiac disease patients who had received procainamide for at least 6 months and an equal number of matched cardiac disease control subjects were studied, and percentage of circulating T cell subsets, concanavalin A‐induced suppressor cell activity, and pokeweed mitogen‐stimulated generation of immunoglobulin‐secreting cells was quantitated. There was no significant difference between patient and control groups in the percentage of T cell subsets defined by OKT4 and OKT8 monoclonal antibodies or in concanavalin A‐induced suppressor cell activity. The numbers of pokeweed mitogen‐induced immunoglobulinsecreting cells were markedly decreased in the patient group, as measured by the protein A‐augmented reverse hemolytic plaque assay (3,000 ± 644, mean ± SEM in patients versus 10,826 ± 1,529, mean ± SEM in control subjects, P < 0.005). Removal of the adherent cell fraction did not improve the hyporesponsiveness. When B and T cell fractions of 6 patients were mixed with normal T and B cell fractions, all of the patients demonstrated diminished B cell responses, and one‐half also had diminished T cell responses. Addition of patient adherent cells to a co‐culture of normal B cells with deficient patient T cells restored plaque formation to normal levels, suggesting that the T cell defect was correctable by a macrophage‐derived factor. The data obtained suggest that procainamide exerts an immunosuppressive action on both B and T cell function in patients receiving this drug.
Serum c‐reactive protein in polymyalgia rheumatica. A prospective serial study
Authors: Mallya R. K. , Hind C. R. K. , Berry H. , Pepys M. B.
Published: February 2007

A prospective serial study of 13 well‐documented, previously untreated cases of polymyalgia rheumatica was undertaken in order to assess the behavior of the nonspecific indices of disease activity, erythrocyte sedimentation rate and serum C‐reactive protein (CRP) concentration, during induction of disease remission by prednisolone therapy. The clinical manifestations of all patients responded rapidly and completely to steroids, and the serum CRP value, which was raised in all patients at presentation, fell to normal at a rate which precisely reflected the clinical improvement. The erythrocyte sedimentation rate also fell, but did so much more slowly than the CRP concentration and, in half the patients, was still not normal after 14 days. These results indicate that assay of serum CRP provides a precise means of objectively assessing the course of polymyalgia rheumatica during initial therapy with steroids, and suggest that routine measurements of CRP may make a useful contribution to the management of the disease.
Phagocytosis and intracellular killing by polymorphonuclear cells from patients with rheumatoid arthritis and felty's syndrome
Authors: Breedveld Ferdinand C. , Van den Barselaar Maria T. , Leijh Peter C. J. , Cats Arnold , van Furth Ralph
Published: February 2007

The present in vitro study concerned the phagocytosis and intracellular killing by polymorphonuclear cells (PMN) of 5 patients with rheumatoid arthritis (RA) and 12 patients with Felty's syndrome (FS). PMN phagocytosis was assessed by microbiologic and morphologic methods, and intracellular killing was measured independently of continuous phagocytosis of viable bacteria (Staphylococcus aureus). PMN from patients with RA or FS ingested S aureus opsonized with immunoglobulins and complement as effectively as did PMN from healthy donors. However, the capacity of patient PMN to ingest S aureus opsonized with sera lacking complement activity, e.g., heat‐inactivated donor serum and the sera of 2 patients with FS, was lower than that of healthy donor PMN. This decreased ingestion is associated with diminished expression of Fc receptors on the membrane of PMN from patients who have RA or FS. As with sera lacking complement activity, decreased capacity to ingest S aureus was observed after preloading donor PMN with immune aggregates, which also decreased the expression of Fc receptors. PMN from patients with RA or FS were found to be as active in killing S aureus as cells from healthy donors.
Human rheumatoid arthritic cartilage and its neutral proteoglycan‐degrading proteases. The effects of antirheumatic drugs
Authors: Martel‐Pelletier Johanne , Cloutier Jean‐Marie , Howell David S. , Pelletier Jean‐Pierre
Published: February 2007

Measurements were made of the neutral proteoglycan–digesting protease activity in the cartilage matrix breakdown observed in the rheumatoid arthritic process. Normal knee (tibial plateau) cartilage specimens were obtained from 7 fresh cadavers and 29 cartilage specimens were obtained from 23 patients diagnosed as having rheumatoid arthritis (RA). The total neutral metalloproteoglycan–degrading enzyme (NMPE) activity in RA cartilages exhibited roughly an eightfold elevation over that of control subjects. The active form of the NMPE for diseased cartilage was higher than that observed for normal cartilage, but was not statistically different. A very low level of activity was detected for serine proteases and no variation was observed between normal and diseased cartilages. Data obtained from RA cartilages were also analyzed with respect to the relationship between enzyme activities and the patients' medications. Four groups of patients were then selected according to their drug treatments: S + G patients received steroid and gold therapy; S patients received steroids only; NS + NG patients did not receive steroid or gold therapy; G patients received gold therapy alone. The total NMPE activity for each of these groups remained at a very high level. The active enzyme activity measured in S + G and S patients was decreased to a level not different from that of normal controls. Specimens from NS + NG patients presented a significantly higher level of the active form of the enzyme (P < 0.05) when compared with either normal controls, S + G, or S patients. No significant difference was noted in the level of serine protease activity between the RA cartilage and normal cartilage. These data strongly support the role of NMPE in the destruction of RA cartilage. Steroids, whether alone or associated with gold compounds, are able to suppress the activity of the active form of the NMPE.
Antibodies to human T cell leukemia virus are absent in patients with systemic lupus erythematosus
Authors: Koike Takao , Takabayashi Katsuhiko , Maruyama Naoki , Tomioka Hisao , Yoshida Sho
Published: February 2007

It has been anticipated that type C oncornaviruses, which participate in the pathogenesis of murine systemic lupus erythematosus (SLE), would be found to have a role in the development of SLE in humans. In studies of tissues from SLE patients, type C–related proteins have been identified. Using information obtained on the recent isolation of the human T cell leukemia virus (HTLV), together with that from studies of murine SLE, we attempted to clarify the role of antibodies to HTLV in the pathogenesis of human SLE. Using a solid‐phase enzyme‐linked immunosorbent assay and sodium dodecyl sulfate–polyacrylamide gel electrophoretic techniques, we were unable to find evidence of the participation of antibodies to HTLV proteins in the development of human SLE.
Nifedipine and esophageal dysfunction in progressive systemic sclerosis. A controlled manometric study
Authors: Kahan André , Bour Bruno , Couturier Daniel , Amor Bernard , Menkes Charles J.
Published: February 2007

We evaluated the effect of the calcium channel blocking agent, nifedipine, on esophageal dysfunction in 15 patients with progressive systemic sclerosis, using a double‐blind, randomized, crossover, placebo‐controlled manometric study. Nifedipine significantly decreased lower esophageal sphincter pressure in these patients; this reduced lower esophageal sphincter pressure may cause gastroesophageal reflux. Thus, nifedipine may have detrimental effects on progressive systemic sclerosis patients.
Selective inhibition of excessive scleroderma fibroblast collagen production by lymphokines from normal human mononuclear cells
Authors: Jimenez Sergio A. , McArthur William M. , Bashey Reza I. , Rosenbloom Joel
Published: February 2007

We studied the effects of lymphokines from mitogen‐stimulated normal human mononuclear cells on collagen production by confluent monolayer cultures of scleroderma dermal fibroblasts. We examined 10 cell lines obtained from patients with early onset, rapidly progressive disease. All cell lines exhibited increased collagen production, compared with cell lines from ageand sex‐matched normal individuals. We found that supernatants from phytohemagglutinin‐stimulated mononuclear cells caused >45% inhibition of collagen production by the cultured scleroderma fibroblasts; the degree of inhibition was concentration‐dependent. Partially purified lymphokine preparations produced 84–94% inhibition of collagen production by scleroderma cells. The lymphokine effects were shown to be selective for collagen, since the synthesis of noncollagenous proteins was not significantly affected. The results suggest that lymphokines from normal mononuclear cells can modulate the excessive collagen biosynthesis that is characteristic of scleroderma fibroblasts, and these lymphokines may have a place as possible therapeutic agents for this incurable disease.
Impaired killer cell generation in the autologous mixed leukocyte reaction by rheumatoid arthritis lymphocytes
Authors: Goto Makoto , Zvaifler Nathan J.
Published: February 2007

Natural killer‐like cells are generated along with interleukin‐2 (IL‐2) in the autologous mixed leukocyte reaction (AMLR). Patients with active rheumatoid arthritis (RA), but not those whose disease is in remission, are poor producers of AMLR killer cells. This defect cannot be explained by age, medications, or serum factors. The impaired generation of natural killer‐like cells was not influenced by γ‐interferon but could be partially restored by addition of indomethacin to the AMLR culture, or by culturing RA T cells with exogenous IL‐2. However, the response of RA T cells to IL‐2 was significantly less than that of controls. These results suggest that the defect in the generation of AMLR killer cells in patients with active RA may be due in part to defective production of IL‐2 and a lesser sensitivity of RA T cells to IL‐2.
Salicylate‐induced depletion of endogenous inorganic sulfate. Potential role in the suppression of sulfated glycosaminoglycan synthesis in murine articular cartilage
Authors: De Vries Bernard J. , van den Berg Wim B. , van de Putte Levinus B. A.
Published: February 2007

Sodium salicylate has been shown to suppress glycosaminoglycan (GAG) synthesis by articular hyaline cartilage in vitro. We investigated the in vivo effect of sodium salicylate on murine patellar cartilage, using incorporation of intraperitoneally administered 35S‐sulfate as a measure of sulfated GAG synthesis. Our results indicated that a single dose of sodium salicylate (200 mg/kg) inhibited in vivo sulfated GAG synthesis by 56%, compared with controls, and had no effect on sulfated GAG breakdown. A striking finding was that sodium sulfate treatment reduced the serum concentration of inorganic sulfate from 1.1 mM to approximately 0.3 mM, and that this serum reduction was associated with a twofold increase in urinary excretion of sulfate. Using anatomically intact patellar cartilage, in vitro studies clearly showed that, in concentrations reached in vivo (⩾1 mM), salicylate suppressed murine chondrocyte GAG synthesis. However, in the presence of serum, the effects of 1 mM salicylate were abolished. We also found that sulfated GAG synthesis was clearly inhibited at low concentrations of sulfate (<0.5 mM). Our data indicate that sodium salicylate can suppress articular chondrocyte sulfated GAG synthesis in vivo, and that this effect may particularly be due to a drug‐induced reduction of endogenous sulfate.
No demonstrable relationship between IgM and IgG antinuclear antibody levels and acetylator phenotype in patients with systemic lupus erythematosus
Authors: Portanova Joseph P. , Small Calvin J. , Kohler Peter F.
Published: February 2007

To ascertain the possible influence of acetylator phenotype on antinuclear antibodies in systemic lupus erythematosus (SLE), we assayed sera from 11 rapid acetylators and 10 slow acetylators for IgM and IgG antibodies to chromatin, histones, denatured DNA, and native DNA. Whereas the majority of SLE patients of both acetylator phenotypes had elevated levels of antibodies to all 4 antigens compared with normal controls, there was no difference in antibody activities between slow acetylator patients versus rapid acetylator patients for these antigens. We conclude that levels of antibody to chromatin, histones, and DNA in SLE patients are similar irrespective of acetylator phenotype, and that if a protective effect of slow acetylation on spontaneous development of antinuclear antibodies does occur, a prospective study of presymptomatic individuals at high risk for lupus may be required to reveal this effect.
MOrphologic and cytochemical changes in maturing and osteoarthritic articular cartilage in the temporomandibular joint of mice
Authors: Livne Erella , von der Mark Klaus , Silbermann Michael
Published: February 2007

We studied the light microscopic, ultrastructural, and cytochemical characteristics of the temporomandibular joints of male ICR mice, from early neonatal life until they reached senescence, when spontaneous osteoarthritis is a common phenomenon. Aging of mandibular condylar cartilage was accompanied by decreasing total proteoglycan content and by an unmasking of collagen fibers, with no shift in collagen type. Fibronectin was also commonly present on the articular surface of specimens from old animals. Chondrocytes of aged mice contained an increased number of lysosomes, and their adjacent matrix vesicles reacted positively for acid phosphatase and arylsulfatase, but not for alkaline phosphatase. Such vesicles were also found to be devoid of calcium complexes and, thus, did not appear to be involved in the mineralization process. Similar age‐related changes have been described in human mandibular condyles; hence, the male ICR mouse could serve as a useful model for studies of spontaneous osteoarthritis in the human mandibular joint.
Stress‐induced proteins in chondrocytes from patients with osteoarthritis
Authors: Kubo Toshikazu , Towle Christine A. , Mankin Henry J. , Treadwell Benjamin V.
Published: February 2007

Recent studies have shown that a specific set of proteins is produced by a variety of cells after the application of some forms of stress, including heat shock. Human chondrocytes isolated from cartilage with moderate to severe osteoarthritis synthesize at least 1 of these stress proteins (Mr 70, 000) at physiologic temperature (37°C), whereas chondrocytes isolated from non‐pathologic cartilage synthesize this protein only in response to incubation at temperatures above 39°C. The active synthesis of this protein (SP‐70) at 37°C is positively correlated with the severity of osteoarthritis and can be a characteristic indicator of this degenerative disease. We identified the active synthesis of stress proteins after incubating the cartilage tissue in medium containing 35S‐methionine and separating the cell‐associated proteins by sodium dodecyl sulfate–polyacrylamide gel electrophoresis. The radioactive proteins were visualized by autoradiography. Analysis of the longevity of cell‐associated proteins was determined by pulsing the tissue with 35S‐methionine, and after different periods of chase in medium, the proteins were separated by sodium dodecyl sulfate–polyacrylamide gel electrophoresis. Specific protein bands were then excised, and the radioactivity was determined by liquid scintillation counting.
Continuing medical education. Changing behavior and improving outcomes
Authors: Stross Jeoffrey K. , Schumacher H. Ralph , Weisman Michael H. , Spalding David M.
Published: February 2007

A study was undertaken to determine if an intensive continuing medical education program in rheumatology could improve patient care. Fifteen primary care practitioners, who fit the description of educationally influential physicians, completed a 2‐week academic medical center–based preceptorship. Improvement in physician knowledge, from a mean score of 65.3% to a mean of 82.9%, was documented using pre‐ and post‐tests. Significant changes in physician behavior were documented using chart audits and patient interviews. The use of diagnostic tests and corticosteroids, and physician–patient interactions were the areas of greatest improvement. Functional outcomes for patients, measured by the Sickness Impact Profile, also improved. These findings suggest that a well‐designed continuing medical education program can effect some changes in physician knowledge and behavior that will result in at least short‐term improvement in patient outcomes.
Lack of correlation between blood gold concentrations and clinical response in patients with definite or classic rheumatoid arthritis receiving auranofin or gold sodium thiomalate
Authors: Dahl Stephen L. , Coleman Miki L. , Williams H. James , Altz‐Smith Mary , Kay Donald R. , Paulus Harold E. , Weinstein Arthur , Kaplan Stanley
Published: February 2007

We investigated the correlation between whole blood gold concentrations and clinical outcomes in 59 auranofin‐treated patients and 51 gold sodium thioma‐late‐treated patients who completed a 21‐week, placebo‐controlled, multicenter parallel trial. Whole blood gold concentrations did not correlate with clinical outcome, as assessed by changes in joint tenderness, joint swelling, or Westergren erythrocyte sedimentation rate. They also did not correlate with toxic reactions necessitating withdrawal from the study.
IgA rheumatoid factor synthesis by dissociated synovial cells. Characterization and relationship to IgM rheumatoid factor synthesis
Authors: Koopman William J. , Schrohenloher Ralph E. , Crago Sylvia S. , Spalding David M. , Mestecky Jiri
Published: February 2007

We examined patterns of IgA rheumatoid factor (RF) and IgM‐RF synthesis by dissociated synovial cells obtained from 27 patients with seropositive rheumatoid arthritis. Synthesis of IgA‐RF was observed in 19 of 34 synovial cell preparations from these patients and constituted a mean of 16% of the total IgA produced. IgA‐RF expression correlated only weakly with IgM‐RF production (r = 0.385) and could be dissociated from production of IgA‐RF (and IgM‐RF) exhibited by simultaneously obtained peripheral blood plasma cells. While wide variations were observed in the ratio of IgA‐RF:IgM‐RF produced by synovial B cells in the patient sample studied, remarkable consistency in the relationship of IgA‐RF to IgM‐RF synthesis was observed overtime in different joints of the same patient. IgA‐RF synthesized by dissociated synovial cells was predominantly of the IgAl subclass and existed in both monomeric and polymeric forms. Our results are compatible with the view that local production of IgA‐RF and IgM‐RF are regulated independently of each other.
Suppression of hyaluronic acid synthesis in synovial organ cultures by corticosteroid suspensions
Authors: Myers Stephen L.
Published: February 2007

The effects of sparingly soluble corticosteroid suspensions prepared for intraarticular therapy, of their vehicles, and of hydrocortisone on synovial hyaluronic acid (HA) synthesis were compared in organ cultures of normal canine villous synovium. Both hydrocortisone and the corticosteroid suspensions suppressed HA synthesis, as did 2 vehicle components, polysorbate 80 and myristyl‐gamma‐picrolinium chloride. Cultures of synovium from joints of dogs which, 1 day previously, had been injected with methylprednisolone acetate suspension synthesized less HA than did control cultures from noninjected joints of the same animals. The results indicate that suppression of HA synthesis is a mechanism by which these drugs can act to reduce joint HA content and promote resolution of synovial effusions.
Effective patient education. A quasi‐experiment comparing an individualized strategy with a routinized strategy
Authors: Lorish Christopher D. , Parker Julia , Brown Sam
Published: February 2007

A quasi‐experiment was conducted on 127 hospitalized rheumatoid arthritis patients to determine the relative success of 3 patient teaching strategies—an individualized program, a routinized program, and a no‐planned‐instruction program—on patients' knowledge of their disease and treatment. Data analysis revealed that the individualized program produced a 100% greater learning gain than the routinized program in patients who had low pretest scores. The results suggest that maximum patient learning occurs when the teaching process accommodates important patient differences.
Assessment of radiologic progression in rheumatoid arthritis. A randomized, controlled trial
Authors: Fries James F. , Bloch Daniel A. , Sharp John T. , McShane Dennis J. , Spitz Patricia , Bluhm Gilbert B. , Forrester Deborah , Genant Harry , Gofton Philip , Richman Steven , Weissman Barbara , Wolfe Frederick
Published: February 2007

Radiologic assessment of progressive joint destruction in rheumatoid arthritis is generally considered to be the ultimate standard for evaluation of treatment. We compared alternative radiologic techniques by performing a randomized, controlled trial in which hand films of rheumatoid arthritis patients were read by several skilled observers. The number of joints evaluated (34 versus 18) was found to make relatively little difference, but the number of readers and their experience level was critical. Films should be read in pairs. Joint space narrowing and erosion scores were shown to contribute independent information. Use of recommended techniques can reduce the number of patients required and, thus, can reduce the cost of a clinical trial by more than half and can substantially increase the sensitivity and efficiency of a trial. Therefore, critical selection of the method of assessing study endpoint is of great importance.
The allopurinol hypersensitivity syndrome. Unnecessary morbidity and mortality
Authors: Singer Joyce Z. , Wallace Stanley L.
Published: February 2007

Patients receiving allopurinol are at risk of developing the allopurinol hypersensitivity syndrome, an immunologic reaction to the drug, characterized by multiple abnormalities such as fever, rash, decreased renal function, hepatocellular injury, leukocytosis, and eosinophilia. The records of 8 patients with the allopurinol hypersensitivity syndrome evaluated at the Downstate Medical Center hospitals and an additional 72 patients described in the literature were reviewed. All were seriously ill. Three of the 8 patients at the Down‐state Medical Center hospitals died as a result of allopurinol hypersensitivity; 19 of the 72 previously described patients also died from consequences of taking the drug. Only 1 of our 8 patients with allopurinol hypersensitivity was given allopurinol for an appropriate reason. Eight of the 59 previously described patients on whom there was adequate information had legitimate indications for allopurinol therapy. Severe, often fatal iatrogenic disease occurred unnecessarily in the others.
Immunofluorescence studies of florid rheumatic Aschoff lesions
Authors: Husby Gunnar , Arora Ramesh , Williams Ralph C. , Khaw Ban An , Haber Edgar , Butler Cooley
Published: February 2007

We studied cardiac tissues of a patient who died of severe rheumatic myocarditis. Multiple Aschoff lesions were present throughout both ventricles and auricles. Immunofluorescence studies showed large monocytoid cells staining with OKM1 and anti‐Leu M‐3 as well as anti‐Ia. Scattered T cells in areas of focal myocarditis stained with OKT3. Parallel staining for cardiac myosin‐heavy chain antigens showed patchy dissolution of cardiac muscle fibers and traces of cardiac myosin within large monocytoid Aschoff cells.
Experimental osteoarthritis induced by selective myectomy and tendotomy
Authors: Arsever Christiane L. , Bole Giles G.
Published: February 2007

A new model of osteoarthritis has been developed that utilizes an extraarticular surgical technique to alter gait and weight‐bearing capabilities in the hind limbs of experimental animals. Guinea pigs, averaging 650 gm in weight, were subjected to unilateral resection of a segment of the gluteal muscles at the sacral origin, to section of the infrapatellar ligament, or to both procedures. Progressive changes consistent with osteoarthritis developed over 10–24 weeks as judged by gross, radiologic, and microscopic findings. In addition, an increase in mean cartilage water content and 35SO4−2 incorporation into proteoglycans by 10 and 14 weeks, respectively, were consistent with the chemical changes observed in early osteoarthritis. Abnormalities developed not only in the operated hind limb, but in the contralateral, unoperated hind limb at a slightly later time. Thus, this animal model provided the opportunity to evaluate a mild gait abnormality and other biomechanical influences on the evolution of osteoarthritis which is uninfluenced by any intraarticular joint trauma.
Immunomodulatory effects of treatment with naproxen in patients with rheumatic disease
Authors: Ceuppens Jan L. , Robaeys Geert , Verdickt Wilfried , Vertessen Simonne , Deckmyn Hans , Dequeker Jan
Published: February 2007

We evaluated the effects of a nonsteroidal antiinflammatory drug, naproxen, on phytohemagglutinin (PHA)–induced lymphocyte proliferation. When added in vitro to cultures of peripheral blood mononuclear cells, naproxen enhanced the proliferative response toward PHA of lymphocytes from rheumatoid arthritis (RA) patients but not from healthy volunteers, and it reduced prostaglandin E2 (PGE2) synthesis in the cultures. Oral treatment for 7 days with naproxen also resulted in a significant enhancement of the in vitro PHA‐induced proliferation of lymphocytes from RA patients and from age‐matched control patients with noninflammatory rheumatic diseases, but not from young healthy controls. This enhancement of PHA‐induced lymphocyte proliferation after oral intake of naproxen was not accompanied by diminished in vitro PGE2 production in the cultures. It did occur when PGE2‐producing monocytes were removed and when in vitro PGE2 synthesis was blocked with indomethacin. We conclude that oral treatment with naproxen has an immunomodulatory effect and improves in vitro PHA‐induced proliferation of lymphocytes from rheumatic disease patients. This effect is not due to reduced PGE2 synthesis in the in vitro cultures, but reflects a more fundamental in vivo change in immunoregulation.
Low density lipoprotein inhibits the physical interaction of phlogistic crystals and inflammatory cells
Authors: Terkeltaub Robert , Smeltzer Dianne , Curtiss Linda K. , Ginsberg Mark H.
Published: February 2007

Low density lipoprotein (LDL) is the major plasma inhibitor of neutrophil oxidative and lytic responses to monosodium urate crystals and may function to modulate acute gouty inflammation. LDL inhibited apparent phagocytosis of urate crystals by human neutrophils, suggesting it may interfere with early events in the crystal‐induced stimulation of neutrophils. The effects were not specific for neutrophils, since human platelet secretory and membranolytic responses to urate crystals were also inhibited by purified LDL in doses as low as 10 μg/ml. As with neutrophils, the inhibitory activity of LDL was stimulus‐specific. Since LDL binds to urate crystals and specifically inhibits a range of cellular responses to them, including phagocytosis, we hypothesized that LDL interferes with the initial crystal‐cell interaction. We measured platelet interaction with urate crystals and found that LDL was a potent inhibitor of crystal‐induced platelet sedimentation and was 10–100‐fold more active than lipoprotein‐depleted plasma or purified high density lipoprotein. In summary, LDL inhibits a broad range of responses of a number of inflammatory cell types to certain inflammatory surfaces, and this effect appears to be due to inhibition of physical association of crystals with cell membranes.
Analysis of interleukin‐2 activity in patients with Behçet's disease. Ability of T cells to produce and respond to interleukin‐2
Authors: Sakane Tsuyoshi , Suzuki Noboru , Ueda Yuji , Takada Shinsuke , Murakawa Yohko , Hoshino Takashi , Niwa Yukie , Tsunematsu Tokugoro
Published: February 2007

We examined interleukin‐2 (IL‐2) activity in patients with Behçet's disease. T cells from all patients with Behçet's disease were able to produce normal levels of IL‐2 in response to phytohemagglutinin; however, responsiveness to IL‐2 was impaired in their concanavalin A‐activated lymphoblasts. This defect was due to decreased numbers of cells bearing IL‐2 receptors in patients with early active disease; in patients with chronic active or with inactive disease, there was a decrease in density of IL‐2 receptors on T cells bearing these receptors. Unresponsiveness of T cells to IL‐2 may thus contribute to immunologic aberrations in Behçet's disease.
Acute gout presenting in the manubriosternal joint
Authors: Kernodle G. Wallace , Allen Nancy B.
Published: February 2007

A 54‐year‐old black man developed acute pain and swelling of the manubriosternal joint. Acute gouty arthritis was diagnosed by arthrocentesis and polarizing microscopy. The histology of the manubriosternal joint and its involvement in other arthritides are briefly discussed.
Alpha1‐antitrypsin phenotypes, including M subtypes, in pulmonary disease associated with rheumatoid arthritis and systemic sclerosis
Authors: Michalski Joseph P. , McCombs Candace C. , Scopelitis Eve , Biundo Joseph J. , Medsger Thomas A.
Published: February 2007

Alpha1‐antitrypsin is a glycoprotein that functions as the major protease inhibitor in human serum. Many genetic variants of α1‐antitrypsin can be detected by electrophoretic techniques. We used isoelectric focusing on ultrathin gels to determine the common M subtypes as well as other variants of α‐antitrypsin in 62 white patients with rheumatoid arthritis (RA) and 51 white patients with systemic sclerosis (SSc). We found no increased prevalence of variant phenotypes in either disease group as a whole. In RA, however, the association between pulmonary interstitial fibrosis and α1‐antitrypsin variants was striking. Interstitial fibrosis was seen on chest roentgenogram in only 1 of 30 subjects apparently homozygous for M1 (the “wild type” or “normal” phenotype), compared with 13 of 32 patients with variant phenotypes. Seven of 15 patients with M1M2 (the most common variant phenotype) had pulmonary fibrosis. In contrast, there was no apparent association of variant phenotypes with pulmonary involvement in SSc. Our findings suggest a possible role of α1‐antitrypsin in the pathogenesis of interstitial fibrosis in patients with RA. The absence of such an association in SSc suggests that pulmonary involvement in these 2 rheumatic diseases may have different pathogeneses.
Serum amino‐terminal type III procollagen peptide in rheumatoid arthritis. Relationship to disease activity, treatment, and development of joint erosions
Authors: Hørslev‐Petersen Kim , Bentsen Kirsten D. , Junker Peter , Lorenzen Ib
Published: February 2007

Using 2 radioimmunoassays, increased serum levels of amino‐terminal type III procollagen peptide and its degradation products were demonstrated in rheumatoid arthritis patients. Patients with active disease showed higher serum propeptide levels than did patients with inactive disease. Unlike D‐penicillamine, azathioprine treatment suppressed the propeptide levels in patients with active disease. A 6‐month prospective study showed significantly higher initial serum propeptide levels in patients with erosive progression. The propeptide level reflects disease activity and may be a valuable prognostic marker in rheumatoid arthritis.
Impact of specific therapy upon rheumatoid arthritis
Authors: Fries James F. , Spitz Patricia W. , Mitchell Donald M. , Roth Sanford H. , Wolfe Frederick , Bloch Daniel A.
Published: February 2007

We performed a prospective, parallel, descriptive study of 737 consecutive new uses for 11 drugs prescribed for patients with definite or classic rheumatoid arthritis. The patients were from 5 geographically dispersed sites. Researchers used validated outcome assessment instruments to measure endpoints of disability, pain, patient global assessment, medication costs, laboratory costs, and number of physician visits. Patients were studied by strict prospective protocol at 6‐month intervals for 3 years. Controls included parallel results with other drugs, and before and after values for the individual patient. Beneficial effects were observed with the “disease‐modifying” drugs: intramuscular gold, pencillamine, and methotrexate. Of these, gold had the most apparent effect. An average of 9 months of gold therapy resulted in highly significant reductions in disability (P < 0.005), pain (P < 0.001), and patient global assessment (P < 0.005). However, patients receiving gold and methotrexate had nearly twice as many visits to physicians. In addition, drug costs increased strikingly with gold, and laboratory costs tripled. Relatively minor differences among nonsteroidal antiinflammatory agents were difficult to interpret. The outcome assessment techniques used in the study are sensitive measures, which confirm the results of experimental studies and extend observations to new outcomes, including cost and disability.
Effect of anti‐T cell auto antibodies from systemic lupus erythematosus sera upon T lymphocyte functions
Authors: Goldschmidt Leonard P. , Kresina Thomas F. , Kammer Gary M.
Published: February 2007

This study was undertaken to establish whether IgM and IgG anti‐T cell autoantibodies obtained from sera of patients with active systemic lupus erythematosus, impair normal T lymphocyte functions. Two in vitro models of T cell function were examined: (a) the capacity of cells to cap, endocytose, and regenerate the T3, T4, and T8 surface antigens; and (b) the adenosine‐induced T4 → T8 phenotype switch. The results demonstrated that autoantibody neither impaired the capping process, nor impeded the phenotypic switch. Thus, bound anti‐T cell autoantibodies do not appear to interfere with these specific T lymphocyte functions and cannot directly account for either the impaired T cell capping mechanism or the block in adenosine‐induced phenotype switch observed during active systemic lupus erythematosus.
Pulmonary amyloidosis associated with systemic lupus erythematosus
Authors: Nomura Shigeo , Kumagai Naoki , Kanoh Tadashi , Uchino Haruto , Kurihara Jiro
Published: February 2007

The association between amyloid and systemic lupus erythematosus is rarely reported. Our patient, a 26‐year‐old woman with systemic lupus erythematosus, developed steroid‐resistant exertional dyspnea and pulmonary fibrosis, without proteinuria or the nephrotic syndrome. Our studies showed that she had pulmonary amyloidosis.
Complement activation in rheumatoid arthritis evaluated by C3dg and the terminal complement complex
Authors: Mollnes Tom E. , Lea Tor , Mellbye Ove J. , Pahle Jan , Grand Øyvind , Harboe Morten
Published: February 2007

Complement activation was evaluated in plasma and synovial fluid from patients with rheumatoid arthritis. The activation fragment C3dg and the fluid‐phase terminal complement complex were used as indicators of initial and terminal activation, respectively. Considerable activation of the whole complement cascade was demonstrated in most synovial fluid samples and in one‐third of the plasma samples. No correlation was found between the level of activation products in synovial fluid and the level in plasma. Therefore, both compartments must be examined in order to evaluate local and systemic complement activation in rheumatoid arthritis.
Decreased expression of the C3b/C4b receptor (CR1) and the C3d receptor (CR2) on B lymphocytes and of CR1 on neutrophils of patients with systemic lupus erythematosus
Authors: Wilson James G. , Ratnoff William D. , Schur Peter H. , Fearon Douglas T.
Published: February 2007

Decreased numbers of complement receptor type 1 (CR1) have been observed on erythrocytes of patients with systemic lupus erythematosus (SLE) and on glomerular podocytes of patients having proliferative nephritis of SLE. In the present study, the analysis of the cellular expression of CR1 has been extended to include leukocytes. In addition, expression by B lymphocytes of the C3d receptor (CR2), which also serves as the receptor for the Epstein‐Barr virus, was assessed. Receptor expression was measured by 2‐color fluorescent flow cytometry of peripheral blood B cells, identified by the presence of the B1 antigen, that had also been stained with anti‐CR1 or anti‐CR2. B cells from 17 patients with SLE exhibited a mean relative fluorescence for CR1 that was 61% of that found in 17 normal individuals (P < 0.001). The expression of CR2 by the patients' B cells (n = 14) was 62% of that of the B cells from normal subjects (n = 17) (P < 0.001). The expression of CR1 correlated with that of CR2 among patients (r = 0.63; P < 0.01) but not with the expression of CR2 among normal individuals (r = 0.36; P > 0.1). The mean CR1 content of the patients' neutrophils was only 59% of the normal mean (P < 0.001). Thus, abnormalities of complement receptor expression occur on the leukocytes of patients with SLE. These deficiencies may be secondary to interaction of the cells with the products of complement activation, or, in some individuals, the deficiencies may be familial.
Reduced high‐energy phosphate levels in the painful muscles of patients with primary fibromyalgia
Authors: Bengtsson Ann , Henriksson K. G. , Larsson Jörgen
Published: February 2007

Muscle energy metabolism was studied by chemical analysis of biopsy samples from: 1) trigger points in the trapezius muscle from 15 patients with primary fibromyalgia (PF), 2) nonpainful, anterior tibial muscle from 6 patients with PF, and 3) the trapezius muscle from 8 healthy controls. We found a decrease in the levels of adenosine triphosphate, adenosine diphosphate, and phosphoryl creatine, and an increase in the levels of adenosine monophosphate and creatine, in the trapezius muscles from the patients. These findings support the notion that the pain in patients with PF is of muscular origin.