bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of synovial iron on the progression of rheumatoid disease
Authors: Blake D. R. , Gallagher P. J. , Potter A. R. , Bell M. J. , Bacon P. A.
Published: February 2007

Seventeen patients with early rheumatoid synovitis underwent synovial biopsy to assess the interrelationship between both ferritin (the intracellular iron storage protein) and Perls' positive iron (ferric iron in loose combination with protein), on the activity and course of rheumatoid disease. The amount of ferritin was associated to a significant degree with the activity of the disease at the time of biopsy, but showed no relation to the way the disease progressed over the following year. In contrast, the amount of Perls' iron bore no relation to the activity of the disease at biopsy, but its presence was associated with persistent disease. It is argued that this association is direct, that ferritin production may fail in a population of synovial macrophages, and that Perls' ferric iron may either be reduced to the ferrous form and promote the formation of toxic free radical species, or stimulate collagenase and prostaglandin release from synovial macrophages.
Extended haplotypes of chromosome 6 in adult rheumatoid arthritis
Authors: Raum D. , Awdeh Z. , Glass D. , Kammer G. , Khan M. A. , Coblyn J. S. , Weinblatt M. , Holdsworth D. , Strong L. , Rossen R. D. , Brewer E. , Yunis E. , Alper C. A.
Published: February 2007

In 46 patients with rheumatoid arthritis (RA) the allele C4B*3 occurred in 6 patients, while among 350 normal controls, it occurred 6 times (P < 0.00002). Among 9 white and 1 black families, each of which had 2 or more members with RA, there were 36 haplotypes associated with RA. An extended haplotype (specific HLA‐B, DR, complotype haplotypes in significant linkage disequilibrium) containing C4B*3: HLA—‐B15, DR4, BF*S, C2*C, C4A*3, C4B*3, was found twice (P < 0.001) among whites with the disease‐associated chromosomes.
Costs and outcomes in rheumatoid arthritis and osteoarthritis
Authors: Liang Matthew H. , Larson Martin , Thompson Mark , Eaton Holley , Mcnamara Elizabeth , Katz Robert , Taylor Jennifer
Published: February 2007

A prospective descriptive study was done on the direct and indirect costs to ambulatory patients with rheumatoid arthritis and osteoarthritis, stratified at study entry by level of function. Measures of health status over a 1‐year period were taken. On a yearly basis, in 1979 dollars, patients spent an average of $147 for arthritis medications, aids, and devices, and $207 for outpatient visits. A small number were hospitalized and incurred an average charge of $245, and an additional $84 for physician fees. In addition to direct monetary costs, patients averaged 6.8 days of restricted activity per month, in some cases so severe as to confine patients to bed for an average of 1.3 days per month. Among students and working patients, 2.5 workdays per month were lost due to arthritis, and 30% reported that they were unemployed or retired because of impaired health. Functional capacity and specific diagnosis on entry to the study were the most important determinants of arthritis‐related expenditures. Both direct and indirect costs varied considerably from the observed average. Twenty percent of patients incurred no costs for arthritis‐related purchases, 42% had no costs for outpatient visits, and 93% had no inpatient costs. Yet for some patients, the financial burden was very high.
Renal vein thrombosis and inferior vena cava thrombosis in systemic lupus erythematosus
Authors: Mintz Gregorio , Acevedo‐Vázquez Eduardo , Gutiérrez‐Espinosa Gaspar , Avelar‐Garnica Francisco
Published: February 2007

Phlebography of the inferior vena cava with selective study of the renal veins was performed in 43 patients with systemic lupus erythematosus (SLE). Inferior vena cava thrombosis (IVCT) or renal vein thrombosis (RVT) was found in 3 of 11 patients (27%) with nephrotic syndrome, in 8 of 13 (61.5%) with previous thrombophlebitis, and in 3 of 4 (75%) with suggestive acute clinical picture. In contrast, none of the 20 control patients with SLE had IVCT or RVT. These results show that SLE patients with thrombophlebitis have a very high risk of developing IVCT or RVT; patients with nephrotic syndrome have a smaller risk. Neither IVCT nor RVT was found in SLE patients without antecedent thrombophlebitis or nephrotic syndrome.
Specificity analysis of monoclonal anti‐DNA antibodies from B6‐1Pr/1Pr mice
Authors: Warren Robert W. , Sailstad Denise M. , Caster Sandra A. , Pisetsky David S.
Published: February 2007

The binding properties of B6‐lpr/lpr anti‐DNA monoclonal antibodies were characterized to evaluate the influence of genetic background on the diversity and specificity of lpr‐induced autoantibody responses. Six anti‐DNA antibodies were produced from fusions with B6‐lpr/lpr mice, while another was obtained from a fusion with a B6‐+/+ mouse immunized with lipopoly‐saccharide. Each antibody bound single‐stranded DNA in preference to double‐stranded DNA, with variation of over 300‐fold in relative binding activities. In terms of binding to a panel of synthetic polynucleotides, each antibody exhibited a unique antigenic specificity. This binding, however, was not dependent on recognition of a unique base or sugar moiety, since individual antibodies bound polymers of dissimilar composition. These results suggest a diversity of binding reactions for B6‐lpr/lpr anti‐DNA antibodies, with a clonal repertoire similar to that of mice from autoimmune backgrounds.
Rheumatoid arthritis and sterile corneal ulceration
Authors: Michels Mary L. , Cobo L. Michael , Caldwell David S. , Rice John R. , Haynes Barton F.
Published: February 2007

Tissue immune effector cells and epithelial surface antigens present in eye tissue of rheumatoid arthritis (RA) patients with sterile corneal ulceration were studied using a large panel of monoclonal antibodies. During periods of active corneal ulceration, conjunctivae and corneas of all RA patients studied contained numerous immune‐associated (Ia) antigen‐positive tissue macrophages. In 4 of 6 patients, conjunctival or corneal T cell infiltrations were present. In 2 patients, a T cell vasculitis was seen in conjunctival tissue. Conjunctival epithelial cells of all 6 RA patients expressed Ia antigens during active corneal ulceration. These data provide evidence for immune‐mediated mechanisms in the pathophysiology of corneal ulceration in RA. Moreover, the expression of Ia antigens by conjunctival epithelial cells may be a useful indicator of disease activity in RA patients with sterile corneal ulceration.
Fibronectin on the surface of articular cartilage in rheumatoid arthritis
Authors: Shiozawa Kazuko , Shiozawa Shunichi , Shimizu Shinichi , Fujita Takuo
Published: February 2007

The presence of fibronectin on the surface of articular cartilage in rheumatoid arthritis (RA) was investigated. Cartilage samples were stained by the immunoperoxidase method using anti‐human fibronectin antibody, and observed under light and electron microscopy. Fibronectin was present on the articular surface in 7 of 8 RA patients. The degree of staining varied greatly among the patients. Five of 8 patients were positive for fibronectin in 50% or more of the cartilage areas studied. In total, fibronectin was observed in 37 of 67 areas examined, giving a 55% positivity in RA. Fibronectin was not observed in cartilage samples of osteoarthritic joints or joints which were not diseased but had undergone trauma. Ultrastructurally, it was observed to be associated with collagen fibrils and amorphous substance in the matrix. The fibronectin‐negative surface of the rheumatoid cartilage was usually thick ultrastructurally, compared with the fibronectin‐positive surface, and the staining for fibronectin roughly correlated with decreased proteoglycans on the surface. The presence of fibronectin in the matrix appeared to be revealed by partial degradation of proteoglycans with proteolytic enzymes in the synovial fluid, as well as by the deposition of fibronectin onto the surface of rheumatoid cartilage. Fibronectin on the articular surface may play an important role in promoting pannus extension onto the articular surface in RA.
Female hormones reduce neutrophil responsiveness in vitro
Authors: Buyon Jill P. , Korchak Helen M. , Rutherford Lorene E. , Ganguly M. , Weissmann Gerald
Published: February 2007

Neutrophils were preincubated with 17 betaestradiol and progesterone to determine the effects of these hormones on chemotactic peptide‐stimulated superoxide anion (O2‐) generation and degranulation. At pharmacologic levels 17 beta‐estradiol was more active than progesterone with respect to inhibition of O2‐ generation as well as degranulation. An increase of preincubation time from 5 minutes to 25 minutes increased the percent inhibition. When 17 beta‐estradiol and progesterone were combined at levels which approximate those measured during gestation, there was small but significant inhibition of O2‐ generation. Dexamethasone at equal molar concentration inhibited O2‐ generation only after 25 minutes of preincubation and at no time reached the level of inhibition attained by either of the sex hormones alone. Both estradiol and progesterone at pharmacologic levels significantly inhibited betaglucuronidase and lysozyme release, whereas dexamethasone did not inhibit degranulation despite prolonged preincubation. Neutrophils isolated from women during various phases of the menstrual cycle and during the third trimester of pregnancy did not differ with respect to chemotactic peptide‐stimulated O2‐ generation. These data suggest that inhibition of neutrophil responses requires the continuous presence of pharmacologic levels of estradiol and progesterone.
Generation of C5‐derived peptides and other immune reactants in the sera of patients with systemic lupus erythematosus
Authors: Given William P. , Edelson Henry S. , Kaplan Howard B. , Aisen Paul , Weissmann Gerald , Abramson Steven B.
Published: February 2007

Activated complement components and immune complexes cause neutrophil aggregation in vitro and in vivo. We have previously demonstrated that sera of patients with active systemic lupus erythematosus (SLE) provoke the aggregation of normal neutrophils in vitro. In this study the serum or plasma of 4 such patients was fractionated on Sephadex G‐75. In 3 patients neutrophil aggregating activity (NAA) was detectable in fractions which coeluted with reference C5‐derived peptides (estimated molecular radius of 17,000). The activity of these fractions was inhibitable by antibodies to human C5. All patients also had activity that coeluted with reference immune complexes. In addition, material of apparent molecular radius under 12,000 that contributed to the neutrophil aggregating activity of SLE sera was detected. In separate experiments increased levels of C5a desarg were demonstrated during active disease by means of radioimmunoassay. These findings suggest that multiple neutrophil aggregants circulate during the course of active SLE. The formation of intravascular leukoaggregates may contribute to endothelial injury in this disease.
In vitro activation of human chondrocytes and synoviocytes by a human interleukin‐1‐like factor
Authors: Mcguire‐Goldring Mary B. , Meats Judith E. , Wood David D. , Ihrie Earl J. , Ebsworth Nicolette M. , Russell R. Graham G.
Published: February 2007

Monocytes have been shown to secrete factors which stimulate the destruction of cartilage. Since one of the monocyte products, interleukin‐1 (IL‐1), has been shown to stimulate the release of collagenase and prostaglandin E from synoviocytes, we have investigated whether IL‐1 is also responsible for chondrocyte activation. Purified preparations of IL‐1 derived from human blood monocytes stimulated the production of prostaglandin E and plasminogen activator by human articular chondrocytes. After Sephadex G‐75 chromatography, the lymphocyte‐activating and the chondrocyteactivating activities of IL‐1 eluted together in the regions corresponding to the void volume and to Kav = 0.2—0.3 (Mr 30,000—45,000) and Kav = 0.5—0.65 (Mr 12,000—17,000). The major peak of stimulating activity was the 12,000—17,000 dalton peak. Upon further analysis of the 12,000—17,000 dalton peak by isoelectric focusing, the major peak of lymphocyte‐activating factor activity was recovered at a pI of 6.3 with a minor peak at 4.6—5.3. Similar patterns of activity were observed when the fractions were assayed for the stimulation of the production of prostaglandin E and plasminogen activator by human chondrocytes and of prostaglandin E by human synoviocytes. Treatment of the partially purified lymphocyte activating factor with phenylglyoxal reduced the thymocyte‐stimulating activity 99% and the chondrocyte‐stimulating activity 100%. These results suggest that IL‐1 may stimulate the degradation of connective tissues during inflammation.
The influence of pituitary hormones on adjuvant arthritis
Authors: Berczi Istvan , Nagy Eva , Asa Sylvia L. , Kovacs Kalman
Published: February 2007

Adjuvant arthritis was induced in female Fisher rats by injecting their right hind paw with 0.1 ml Freund's complete adjuvant. The development of adjuvant arthritis was inhibited by hypophysectomy and by daily treatment of intact animals with the dopaminergic agent bromocriptine. Adjuvant arthritis developed normally if hypophysectomized or bromocriptine‐suppressed animals were treated with either prolactin or growth hormone. Additional treatment with adrenocorticotropic hormone inhibited this restoration. Treatment of hypophysectomized rats with follicle‐stimulating hormone, luteinizing hormone, and thyroidstimulating hormone had no effect. These results indicate that prolactin and/or growth hormone are necessary for the development of adjuvant arthritis, whereas adrenocorticotropic hormone has an inhibitory effect.
Serial observations and definition of mononuclear cell infiltrates in avian scleroderma, an inherited fibrotic disease of chickens
Authors: Water Judy Van De , Gershwin M. Eric , Abplanalp Hans , Wick Georg , Mark Klaus Von Der
Published: February 2007

University of California, Davis (UCD) line 200 chickens develop an inherited connective tissue disease which includes fibrosis, vascular occlusion, and lymphocytic infiltration of skin, comb, and viscera. To further identify the nature of these features, tissue from both affected and control chickens, aged 7 days to 12 months, was serially examined using hematoxylin‐eosin and Masson's trichrome stain. Mononuclear cell accumulations in skin were simultaneously characterized using mouse anti‐chicken T and B cell specific monoclonal antibodies in a solid‐phase immunoperoxidase assay; the same cells were also examined by direct immunofluorescence with fluoresceinated anti‐chicken IgM and IgG, and stained for esterase and acid phosphatase. At 6 weeks of age, the majority of line 200 chicks manifested dermal fibrosis, cellular infiltrates, and vessel anomalies. In contrast, visceral involvement did not reach maximum incidence until 5 months of age with involvement of small intestine (60%), lungs (60%), and kidneys (65%), and not until 1 year for esophagus (64%), heart (30%), and testes (66%). Moreover, and of particular interest, was the threefold increment of full‐thickness skin biopsies in line 200 birds. The cellular infiltrates in skin, found in 100% of affected line 200 chickens, were positive for B1, a mature B cell marker found on peripheral blood and bursal B cells; the majority of these same cells were found to bear surface IgM but not IgG. These data suggest that this syndrome may result from an alteration in collagen metabolism associated with a mature subpopulation of B lymphocytes.
Histopathology of the rheumatoid lesion
Authors: Bromley Michael , Woolley David E.
Published: February 2007

Histochemical and ultrastructural techniques were used to examine the cartilage—pannus junction of 49 rheumatoid joints. Whereas 24 showed relatively acellular, fibrous pannus tissue, 25 demonstrated “cellular” junctions with different cell types at sites of erosion. Macrophages and fibroblasts were commonly observed as majority cell types in most specimens, but others showed mast cells, polymorphonuclear leukocytes, dendritic, or plasma cells as the predominant cell type. Some showed local accumulations of different cell types at sites along each junction. Our findings show that the cellular composition at sites of cartilage erosion varies greatly and suggest that cells are subject to turnover and interchange.
Severe functional declines, work disability, and increased mortality in seventy‐five rheumatoid arthritis patients studied over nine years
Authors: Pincus Theodore , Callahan Leigh F. , Sale William G. , Brooks Arthur L. , Payne Lee E. , Vaughn William K.
Published: February 2007

Seventy‐five patients with rheumatoid arthritis (RA) were reviewed 9 years after an extensive evaluation which included quantitative measures of functional capacity. These patients had received multiple intraarticular injections of thiotepa with corticosteroids early in their course, but appear demographically and functionally similar to other RA patients who had not received this therapy. Severe morbidity was seen over the 9‐year period in the 55 surviving patients, including significantly lower overall functional capacity in 92% of patients studied, lower grip strength in 93%, and longer button test results in 84%. Work disability occurred in 85% of patients under age 65 who had been working full‐time at disease onset. There was increased mortality at the 9‐year review, similar to most reported series of RA patients from referral centers; however, a significant increase in neoplasia, which was of concern because of the use of intraarticular thiotepa, was not seen. In terms of functional capacity, including responses to questions about ability to perform activities, walking time, and the button test, those patients who had died prior to review had significantly lower baseline values than did those who survived. Of the 75 patients, 20 had died and 51 had lost significant functional capacity over a 9‐year period, documented by quantitative measures of functional capacity.
Characterization of synovial fluid fibronectin from patients with rheumatic inflammatory diseases and healthy subjects
Authors: Carnemolla Barbara , Cutolo Maurizio , Castellani Patrizia , Balza Enrica , Raffanti Stephen , Zardi Luciano
Published: February 2007

Synovial fluid fibronectin from normal subjects and from patients who have rheumatic inflammatory diseases has been studied and compared with plasma fibronectin. The average fibronectin concentration in synovial fluids from normal subjects was 172 ± 69 μg/ml; it was 721 ± 315 and 556 ± 349 μg/ml in synovial fluids from patients with rheumatoid arthritis and osteo‐arthritis, respectively. This is the first report on fibronectin concentrations in normal synovial fluids. Synovial fluid fibronectin from healthy subjects and patients with rheumatoid arthritis or osteoarthritis showed a molecular weight identical to that of plasma fibronectin. All normal and pathologic synovial fluid fibronectins showed a remarkably lower electrophoretic mobility compared with that of plasma fibronectin, when separated according to net molecular charge on agarose gel. Peptides from thermolysin digests of fibronectin from plasma and synovial fluid, when compared on sodium dodecyl sulfate‐polyacrylamide gel electrophoresis, showed distinct differences. These data demonstrate that synovial fluid fibronectin represents a molecular form which is structurally different from that of plasma fibronectin. This suggests that synovial fluid fibronectin is locally synthesized, possibly by a cell type which differs from that responsible for the production of the plasmatic fibronectin pool.
Induction of fibroblast proliferation by interleukin‐1 derived from human monocytic leukemia cells
Authors: Postlethwaite Arnold E. , Lachman Lawrence B. , Kang Andrew H.
Published: February 2007

Human interleukin‐1 (IL‐1), free of contaminating lymphokines, was isolated from cultures of purified monoblasts from a patient with acute monocytic leukemia. Partially purified IL‐1 (diafiltration, ultrafiltration, and isoelectric focusing) stimulated proliferation of subconfluent human fibroblasts in vitro. Further purification of IL‐1 by high‐resolution gel filtration‐ and anion exchange‐high performance liquid chromatography revealed that fibroblast proliferation activity could not be separated from IL‐1 activity (thymocyte proliferation), suggesting that both activities are the properties of a single molecule. Fibroblasts and thymocytes exhibited a similar sensitivity to the proliferative effects of IL‐1. These findings suggest that macrophages participating in inflammatory reactions in vivo might release IL‐1, which could function to expand fibroblast populations at sites of inflammatory reactions, by acting as a fibroblast growth factor.
The altered biomechanical state of human femoral head osteoarthritic articular cartilage
Authors: Broom Neil D.
Published: February 2007

In this study, the biomechanical characteristics of normal and osteoarthritic human femoral head articular cartilage are compared using both microcompression and notch propagation techniques, combined with simultaneous differential interference contrast microscopy. The latter permits examination of the process of matrix rupture occurring in a controlled manner at the notch root. The results provide new biomechanical insights into the differences between normal and osteoarthritic cartilage and draw particular attention to some areas of fundamental structural breakdown associated with the loss of load‐bearing function in this tissue.
Elevation of von willebrand factor is independent of erythrocyte sedimentation rate and persists after glucocorticoid treatment in giant cell arteritis
Authors: Federici Augusto B. , Fox Robert I. , Espinoza Luis R. , Zimmerman Theodore S.
Published: February 2007

Von Willebrand factor (vWF) antigen levels were measured in 39 patients with biopsy‐proven giant cell arteritis (GCA), 16 patients with polymyalgia rheumatica (PMR), 12 patients with Sjögren's syndrome, and 7 with choroiditis, as well as in 20 age‐ and sex‐matched controls. Among GCA patients, 31 (group A) had clinically inactive disease and were taking low‐dose glucocorticoids for at least 1 year; their vWF levels were high even in the presence of a normalized erythrocyte sedimentation rate (ESR). When the ESR and vWF were analyzed in another 8 GCA patients (group B) before and after treatment with glucocorticoids, vWF remained elevated even though the ESR returned to normal. Among the highest levels of vWF were those of 3 GCA patients who presented with ocular symptoms and positive temporal artery biopsies, but normal ESR. The presence of elevated vWF was not specific for GCA since elevated levels were also found in patients with PMR, Sjögren's syndrome, and choroiditis. The levels of vWF in GCA were significantly higher (P < 0.01) than in these other conditions associated with myalgias and eye symptoms. Elevation of vWF levels may help in the differential diagnosis of GCA, particularly when the ESR is normal and ocular symptoms are present.
Impaired release of a soluble natural killer cytotoxic factor in systemic lupus erythematosus
Authors: Sibbitt Wilmer L. , Mathews Paul M. , Bankhurst Arthur D.
Published: February 2007

Disease states characterized by abnormalities in immune regulation often demonstrate concomitant abnormalities in cytotoxicity mediated by natural killer (NK) cells. For example, some patients with systemic lupus erythematosus (SLE) have depressed NK activity despite the presence of normal numbers of effector cell:target cell conjugates. This study was designed to determine if defects in NK cell function were directly related to impaired release of a soluble cytotoxic factor. NK activity of peripheral blood mononuclear cells and large granular lymphocytes was measured using51Crlabeled K562 target cells in 4‐hour release assays. The SLE patients had significantly decreased NK activity relative to normal controls. However, the number of effector cell:target cell conjugates was not different in SLE patients versus control subjects. The release of a soluble natural killer cytotoxic factor (NKCF) by peripheral blood mononuclear cells was measured by cytotoxicity induced in K562 cells. NKCF was released preferentially by suspensions enriched in NK cells (large granular lymphocytes). At a 1:1 dilution, NKCF release was significantly lower in SLE patients than in controls. The release of NKCF correlated well with NK activity. Thus, this study shows that the defect in NK cell activity in SLE patients may be related to an impairment in release of a soluble cytotoxic factor with specificity for NK cell‐sensitive targets.
Trial of platelet‐inhibiting drug in scleroderma double‐blind study with dipyridamole and aspirin
Authors: Beckett Victoria L. , Conn Doyt L. , Fuster Valentin , Osmundson Philip J. , Strong Cameron G. , Chao Edmund Y. S. , Chesebro James H. , Michael O'Fallon W.
Published: February 2007

In a randomized, double‐blind, controlled study, 28 patients with early scleroderma received dipyridamole (225 mg/day) and aspirin (975 mg/day) or placebo for 1–2 years. No significant clinical or objective laboratory improvement was noted in either group. Platelet survival time, plasma renin activity, and coagulation tests were not predictive of disease course. Biomechanical and vascular tests of the hands correlated with clinical extent of skin induration and presence of finger ulcers, respectively.
Multiplicity of antibodies in myositis sera
Authors: Reichlin Morris , Arnett Frank C.
Published: February 2007

Serologic studies on 114 patients with polymyositis and dermatomyositis revealed that 89% had either a precipitating antibody to antigens in calf thymus extract or a positive immunofluorescent reaction on HEp‐2 cells, a human tissue culture line. Previously, the greatest proportion of polymyositis sera demonstrating positive serologic results (i.e., the proportion of patients' sera forming precipitates with calf thymus extract) was reported to be 60%. Use of the HEp‐2 cell as immunofluorescent substrate enabled the detection of antibody in 89 (78%) of the sera, providing the additional probe which demonstrated specific antibody. Nuclear, cytoplasmic, and nucleolar staining are the most common patterns of immunofluorescence. The immunofluorescent patterns and individual precipitin reactions are related to each other and to the clinical syndromes in which they appear.
Arthritis confined to knee joints synovial lymphocyte responses to microbial antigens correlate with distribution of HLA
Authors: Ford Denys K. , Da Roza Doreen M. , Ward Ryk H.
Published: February 2007

The responses of synovial lymphocytes to Chlamydia/Ureaplasma and to enteric antigens were studied in 31 patients with arthritis confined to knee joints, 15 patients with sexually‐transmitted Reiter's syndrome, 9 with enteric Reiter's syndrome, and 24 with rheumatoid arthritis. The frequency of HLA antigens was studied in 28 patients with knee joint arthritis; this group was characterized by elevated frequencies of HLA–A2 and DR1. A subgroup of 8 responders to Chlamydia/Ureaplasma was characterized by an increase of HLA–Bw44 and DR7 or 8, while a subgroup of 8 responders to enteric antigens was characterized by increases of HLA–A1 and DR5. The frequency of HLA–B27 in the groups responding to antigens was 25–30%, less than half the frequency in patients with Reiter's syndrome.
Characterization of the defective autologous mixed lymphocyte response in rheumatoid arthritis
Authors: Pope Richard M. , Mcchesney Linda , Talal Norman , Fischbach Michael
Published: February 2007

In order to characterize the autologous mixed lymphocyte response (AMLR) in patients with rheumatoid arthritis (RA) and to define the relationship with disease activity, peripheral blood T lymphocytes were stimulated with either a B lymphocyte‐enriched (B cells) or a macrophage‐enriched (macrophages) population. A significant reduction (P < 0.01 to P < 0.001) of T cell proliferation stimulated both by B cells and macrophages was observed in patients with active disease. The B lymphocytes were significantly less stimulatory (P < 0.02 to P < 0.001) than macrophages in the patients compared with the controls. In the normal controls, macrophages in higher concentrations were capable of suppressing the B lymphocyte‐stimulated AMLR, but macrophages from patients with RA were not excessively suppressive. A significant association (P < 0.02) was observed between disease activity and the AMLR. Using the B‐enriched population, the AMLR proliferative response was significantly associated (P < 0.001) with the production of interleukin‐2. Defects in proliferation could only be partially restored by the addition of interleukin‐2. These data indicate that the defective AMLR observed in patients with RA is related to disease activity and is associated with altered cellular interactions among T lymphocytes, macrophages, and the B lymphocyte‐enriched population.
Dr, C4, and BF allotypes in juvenile rheumatoid arthritis
Authors: Arnaiz‐Villena A. , Gómez‐Reino J. J. , Gamir M. L. , Regueiro J. R. , Vicario J. L. , Góamez‐Reino F. J. , Alonso A. , Fernandez‐Dapica M. P. , Irigoyen M. V. , Mateo I. , Zea A.
Published: February 2007

HLA‐DR, C4, and Bf typing was performed in 99 patients with juvenile rheumatoid arthritis (JRA). DR1 was found with higher frequency in patients with polyarticular JRA than in controls (P < 0.05). DR3 was more common in patients with fever and/or rash than in those without these manifestations (P < 0.05). A significant negative association between JRA and C4A6 (P < 0.05), C4BQ0 (P < 0.0005), and BfF1 (P < 0.05) was found. It is possible that a disequilibrium between DR and C4/Bf genes plays a role in the pathogenesis of JRA.
Effect of oral 1,25‐dihydroxyvitamin D and calcium on glucocorticoid‐induced osteopenia in patients with rheumatic diseases
Authors: Dykman Thomas R. , Haralson Kathleen M. , Gluck Oscar S. , Murphy William A. , Teitelbaum Steven L. , Hahn Theodore J. , Hahn Bevra H.
Published: February 2007

Twenty‐three rheumatic disease patients with glucocorticoid‐induced osteopenia (defined by measurement of forearm bone mass) completed an 18‐month double‐blind, randomized study to assess the effect of oral calcium and 1,25‐dihydroxyvitamin D (1,25‐OH2D) or calcium and placebo on bone and mineral metabolism. Intestinal 47Ca absorption was increased (P < 0.05) and serum parathyroid hormone levels were suppressed (P < 0.01) by 1,25‐OH2D (mean dose 0.4 μg/day); however, no significant gain in forearm bone mass occurred, and bone fractures were frequent in both groups. In the 1,25‐OH2D group, histomorphometric analysis of iliac crest biopsy specimens demonstrated a decrease in osteoclasts/mm2 of trabecular bone (P < 0.05) and parameters of osteoblastic activity (P < 0.05), indicating that 1,25‐OH2D reduced both bone resorption and formation. We conclude that 1,25‐OH2D should not be used for treatment of glucocorticoid‐induced osteopenia. Since patients receiving calcium and placebo did not exhibit a loss of forearm bone mass, elemental calcium supplementation of 500 mg daily might be useful to maintain skeletal mass in patients receiving long‐term glucocorticord therapy.
Outcome assessment in clinical trials evidence for the sensitivity of a health status measure
Authors: Meenan Robert F. , Anderson Jennifer J. , Kazis Lewis E. , Egger Marlene J. , Altz‐Smith Mary , Samuelson Cecil O. , Willkens Robert F. , Solsky Marilyn A. , Hayes Stanley P. , Blocka Kenneth L. , Weinstein Arthur , Guttadauria Maria , Kaplan Stanley B. , Klippel John
Published: February 2007

Health status measures are conceptually relevant to the assessment of clinical outcome in the rheumatic diseases, but their ability to detect meaningful changes in health has not been clearly demonstrated. This report describes the performance of a self‐administered health status questionnaire in a randomized, double‐blind, 21‐week comparison of placebo, oral gold, and injectable gold in rheumatoid arthritis patients. Outcome was assessed by standard clinical measures, including joint count, grip strength, and laboratory tests, and by the Arthritis Impact Measurement Scales, a reliable and valid health status measure that assesses physical disability, psychological status, and pain. Data from the clinical and health status measures produced highly similar conclusions: injectable and oral gold are more effective than placebo for rheumatoid arthritis, and injections are slightly more effective than oral gold. The health status measure was thus quite sensitive to clinically meaningful drug‐induced improvements. These findings provide justification for the further application of health status measures to clinical trials of chronic disease.
Fractures after rheumatoid arthritis a population‐based study
Authors: Hooyman Joseph R. , Joseph Melton L. , Nelson Audrey M. , Michael O'Fallon W. , Lawrence Riggs B.
Published: February 2007

In a population‐based study, the incidence of osteoporotic fractures in patients who have been diagnosed as having rheumatoid arthritis was investigated. This incidence was found to be increased, though not dramatically so: the relative risk for hip fracture, for example, was 1.5. Univariate analyses generally indicated increased risk associated with increasing age, earlier age at diagnosis of rheumatoid arthritis, disability, impaired ambulation, steroid use, and thinness, and decreased risk associated with obesity and estrogen use. In multivariate analyses, only aging, impaired ambulation, and thinness were identified as independent risk factors.
Increased von willebrand factor antigen in the plasma of patients with vasculitis
Authors: Nusinow Steven R. , Federici Augusto B. , Zimmerman Theodore S. , Curd John G.
Published: February 2007

The plasma concentrations of von Willebrand factor antigen (vWF:Ag) were determined in 101 patients who had the following diagnoses: vasculitis 8 patients, systemic lupus erythematosus (SLE) 51, rheumatoid arthritis (RA) 28, asthma 7, hereditary angioedema 7. The greatest mean concentration of vWF:Ag, 469% (normal 100% ± 50), was observed in patients with vasculitis, often without elevation of the erythrocyte sedimentation rate. The mean concentration of vWF:Ag was also increased in both SLE (277%) and RA (194%). Twenty‐four patients (15 with SLE, 6 with vasculitis, 3 with RA) had vWF:Ag concentrations >300%. Four of these patients died within 1 year of the date of the study. Of the 15 SLE patients, 9 had vasculitis and 2 had active glomerulonephritis. The 3 RA patients had severe disease associated with extraarticular manifestations. Elevated vWF:Ag may reflect vascular damage, while markedly elevated levels of vWF:Ag appear to indicate a poor prognosis.
Characterization of T Cells bearing HLA‐DR antigens in rheumatoid arthritis
Authors: Pincuxy Seth H. , Clegg Daniel O. , Ward John R.
Published: February 2007

It has been demonstrated that T cells bearing HLA‐DR antigens on their surface are actively involved in an immune response. In diseases of disordered immunoregulation, including rheumatoid arthritis (RA), there are elevated numbers of circulating HLA‐DR + T cells. In this study, we examined the cellular physiology of these T cells in RA patients. Using tritiated thymidine incorporation, we found that, in most patients, HLA‐DR + cells do not account for a significant amount of spontaneous proliferation found in peripheral blood T cells. RNA hybridization studies, using a cloned HLA‐DR alpha chain gene probe, indicate that the T cells actively synthesize HLA‐DR antigens rather than passively adsorbing them. The cell surface phenotype of the HLA‐DR + T cells was analyzed using double immunofluorescence and a variety of monoclonal antibodies. The expression of T cell differentiation antigens T4, T6, T8, and T10 varied markedly from patient to patient. In some patients, a significant number of cells expressed both T4 and T8 antigens. Most HLA‐DR + cells also express antigens defined by the following antibodies: anti‐Tac (the interleukin‐2 receptor), J2 (a glycoprotein found on T cell blasts), and ILR‐1 (a class II major histocompatibility complex antigen). Activated T cells bearing HLA‐DR antigens may play a role in the development of RA. Our data demonstrate that although these cells are not lymphoblasts, they possess a distinct cell surface phenotype.
Therapeutic value of graded aerobic exercise training in rheumatoid arthritis
Authors: Harkcom Thomas M. , Lampman Richard M. , Banwell Barbara Figley , Castor C. William
Published: February 2007

Women with rheumatoid arthritis performed 1 of 3 low intensity aerobic exercise protocols (15, 25, and 35 minutes) 3 times per week for 12 weeks. A nontraining group served as controls. All exercise groups improved their aerobic capacity, exercise time, and joint counts. Subjects described improvement in activities of daily living and reduced joint pain and fatigue. Exercise duration up to 35 minutes can be therapeutic, and as little as 15 minutes of exercise 3 times/week is sufficient to improve aerobic capacity in rheumatoid arthritis patients with severe limitations.
Spondylitic disease without radiologic evidence of sacroiliitis in relatives of HLA‐B27 positive ankylosing spondylitis patients
Authors: Khan Muhammad A. , van Der Linden Sjef M. , Kushner Irving , Valkenburg Hans A. , Cats Arnold
Published: February 2007

We report 2 independently‐conducted family studies of HLA‐B27 positive probands with ankylosing spondylitis (AS), both of which support the view that the clinical spectrum of AS is broader than ordinarily assumed, and should include individuals who have symptomatic disease but who do not show radiologic evidence of abnormalities of the sacroiliac joints or the spine. In the Cleveland study of 100 relatives of 30 B27 positive AS probands, 9 relatives did not show radiologic abnormalities of the sacroiliac joints or the spine but had symptoms of chronic inflammatory back pain previously reported to be characteristic of AS. These 9 relatives were all subsequently found to possess B27, in contrast with only 27 of 60 asymptomatic relatives (P < 0.01). In the Leiden study of 101 relatives of 20 randomly chosen B27 positive AS probands, 13 of 86 relatives without radiographic evidence of sacroiliitis reported “thoracic pain and stiffness,” as defined in the Rome criteria for AS. Twelve of these 13 symptomatic relatives were B27 positive. In contrast, among the remaining 73 relatives, only 33 were B27 positive (P < 0.01). The occurrence of these characteristic spondylitic symptoms in B27 positive, but not B27 negative, relatives of AS probands suggests that the spectrum of the clinical manifestations of AS may include individuals with symptomatic disease, but without radiographic evidence of abnormalities of the sacroiliac joints or the spine. The relatively large number of females we found in this group suggests that women are more likely to manifest this variety of disease than are men.
Surface antigen specificity of cold‐reactive IgM antilymphocyte antibodies in systemic lupus erythematosus
Authors: Yamada Akira , Shaw Melody , Winfield John B.
Published: February 2007

Monoclonal antibodies to known surface antigens on B cells and on resting and activated T cells of various types were used in several approaches to examine the specificity of IgM antilymphocyte antibodies in systemic lupus erythematosus (SLE). Surface determinants that were sought included: T3, T11, Leu‐1, Leu‐8 (pan‐T); T4, T8 (T subset); β2‐microglobulin (β2m); L243, Leu‐10 (DR and DS/DC framework, respectively); anti‐Tac (interleukin‐2 receptor); 5E9 (transferrin receptor); and 4F2, AA1 (other activation antigens). The first strategy was based on inhibition of rosette formation between mouse monoclonal antibody‐coated targets and antimouse IgG‐coated erythrocytes by SLE sera, either directly at 4°C or after modulation of IgM antilymphocyte antibody‐reactive target cell antigen at 37°C. Significant rosette inhibition, defined as > 2 standard deviations from the mean value for 10 control sera, was seen only for β2m (13 of 20 SLE sera were positive; inhibition = 15–58%). Next, relative fluorescence intensity of lymphocyte staining by monoclonal antibodies was assessed by flow microfluorometry after preincubation of cells with SLE serum at 4°C or after modulation of SLE antibody‐reactive antigen. Modulation markedly reduced or eliminated SLE antilymphocyte antibody IgM staining. Except for β2m, neither cold nor warm temperature preincubations altered the relative fluorescence intensity for the known surface antigens. These data confirm anti‐β2m as a common antibody specificity in SLE and suggest that antilymphocyte antibodies in this disorder are not directed to Ia or to certain other defined lymphocyte antigens of functional interest.
Lupus pregnancy. II. Unusual pattern of hypocomplementemia and thrombocytopenia in the pregnant patient
Authors: Lockshin Michael D. , Harpel Peter C. , Druzin Maurice L. , Becker Carl G. , Klein Renate F. , Watson Rosemarie M. , Elkon Keith B. , Reinitz Elizabeth
Published: February 2007

To explore the causes of complications in pregnant women with systemic lupus erythematosus (SLE), we prospectively evaluated 34 pregnancies in 28 SLE patients, and 2 additional pregnancies in patients with lupus anticoagulant and positive antinuclear antibody, but no other manifestations of SLE. Nineteen pregnancies (55%) were complicated by marked proteinuria, thrombocytopenia, and/or lupus anticoagulant. Hypocomplementemia occurred in 18 pregnancies (52%). Neither thrombocytopenia‐anticoagulant nor proteinuria was accompanied by an increase in antibody to double‐stranded DNA or by clinical signs of active SLE. Antibody to Ro antigen did not predict fetal death. Both thrombocytopenia and proteinuria appeared abruptly during pregnancy and disappeared quickly after delivery. Fetal death was the result in 7 of 9 (77%) pregnancies in patients with anticoagulant, 6 of 10 (60%) in patients with thrombocytopenia, 6 of 18 (33%) in patients with hypocomplementemia, and 3 of 11 (27%) in patients with proteinuria. Twenty of 29 (68%) children were identified as male. The pathogenesis of hypocomplementemia was evaluated by a new assay, C1s‐C1 inhibitor complex, which is thought to measure rate of complement activation by the classical pathway. Most pregnant patients with low CH50 levels and proteinuria had normal levels of C1s‐C1 inhibitor complex, whereas nonpregnant patients with equivalent proteinuria and hypocomplementemia had high levels, as did pregnant patients with hypocomplementemia who did not have SLE. Pregnant and nonpregnant hypocomplementemic patients with proteinuria had similar levels of C3 and C4. In pregnant patients with SLE, C1s‐C1 inhibitor complex was independent of CH50; in nonpregnant patients a linear relationship between C1s‐C1 inhibitor complex and CH50 was seen. We conclude that hypocomplementemia and probably thrombocytopenia (with anticoagulant) occur via different mechanisms in pregnant and nonpregnant patients with SLE.
Salmonella bacteremia in systemic lupus erythematosus. Eight‐year experience at a municipal hospital
Authors: Abramson Steven , Kramer Sara B. , Radin Allen , Holzman Robert
Published: February 2007

Non‐endemic Salmonella bacteremia tends to occur in patients with chronic disease. We reviewed all cases of Salmonella infection documented in adults at Bellevue Hospital during the years 1975–1982. Unexpectedly, the most frequent underlying disease found among bacteremic patients was systemic lupus erythematosus (SLE). Patients with SLE accounted for 6 of 30 Salmonella bacteremias as compared with 13 of 2,388 non‐Salmonella gram‐negative bacteremias. Salmonella was the single most frequent gram‐negative isolate from the blood of SLE patients. All lupus patients with Salmonella infection were bacteremic. In contrast, isolates from blood represented only 23% of all Salmonella infections documented in the non‐lupus population. Presentation was characterized by fever (>103°F) and abdominal pain. Four of the 6 patients were hypocomplementemic. All were receiving immunosuppressive therapy. We conclude that SLE patients in a municipal hospital setting are at increased risk for Salmonella sepsis. This should be considered when empiric antibiotic therapy is initiated.
Evolution of primary raynaud's phenomenon (raynaud's disease) to connective tissue disease
Authors: Gerbracht David D. , Steen Virginia D. , Ziegler Gayle L. , Medsger Thomas A. , Rodnan Gerald P.
Published: February 2007

Eighty‐seven patients diagnosed as having primary Raynaud's phenomenon (Raynaud's disease) were reexamined after this symptom had been present for a mean of 8.8 years (range 2.0–34.5). One or more additional clinical feature(s) suggesting an underlying connective tissue disease were found in 12 patients (14%) at first evaluation, and in 23 (26%) by the last evaluation. The most frequent findings were puffy fingers (10 patients), digital tip pitting scars (8 patients), and digital tip ulcerations (6 patients). Distal esophageal hypomotility and/or decreased pulmonary diffusing capacity for carbon monoxide were found in 12 patients. Only 4 individuals (5%) developed clear evidence of a connective tissue disease, and in all cases, the diagnosis was the CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias) syndrome variant of systemic sclerosis. This condition became obvious 8–17 years after the onset of Raynaud's phenomenon. One or more serologic test values were initially abnormal in 2 of these CREST syndrome patients, as well as in 12 patients who continued to have primary Raynaud's phenomenon at the last evaluation. The combination of puffy fingers, digital pitting scars, and serum anticentromere antibody, all consistent with CREST syndrome, occurred in a small group of patients. None of the 78 patients whose serologic tests were repeated during followup had a change in the serologic profile. These results suggest that only a small proportion of patients with primary Raynaud's phenomenon develop one of the connective tissue diseases during the first decade after onset. When such a disorder does appear, systemic sclerosis with the CREST syndrome variant is the most likely eventual diagnosis.
Plasma follicle‐stimulating hormone, luteinizing hormone, and sex hormones in patients with gout
Authors: Marinello Enrico , Riario‐Sforza Giuseppe , Marcolongo Roberto
Published: February 2007

Plasma levels of follicle‐stimulating hormone, luteinizing hormone, testosterone, progesterone, 17 beta‐estradiol, and cortisol were examined in normal subjects and gout patients under baseline conditions and after clomiphene stimulation. A significant decrease in follicle‐stimulating hormone, luteinizing hormone, and 17 beta‐estradiol was observed both in male and female gout patients; in the same patients, the plasma testosterone: 17 beta‐estradiol ratio was found to be significantly higher than in control subjects. The changes observed suggest a possible role played by 17 beta‐estradiol in the regulation of purine biosynthesis and uric acid metabolism.