bluuebunny/crossref_metadata_2025 huggingface dataset:
Glomerulonephritis in rheumatoid arthritis
Authors: Davis James A. , Cohen Arthur H. , Weisbart Richard , Paulus Harold E.
Published: February 2007

Glomerulonephritis is rarely a complication of rheumatoid arthritis (RA) despite the observation of significant amounts of circulating immune complexes in both glomerulonephritis and RA (1). Among 5,232 patients with a diagnosis of RA, hospitalized at the UCLA Center for the Health Sciences from 1955 to 1977, glomerulonephritis was diagnosed in only 4 patients, all of whom also met diagnostic criteria for systemic lupus erythematosus or mixed connective tissue disease. We present a well documented case of proliferative glomerulonephritis in association with RA in the absence of another immunologically mediated disease.
Lymphocytotoxic antibodies in systemic lupus erythematosus and clinically related diseases
Authors: Schocket Alan L. , Kohler Peter F.
Published: February 2007

Sera from patients with systemic lupus erythematosus (SLE) and clinically related diseases were examined for cold‐reactive lymphocytotoxic antibodies (LCA). The incidence of LCA was significantly increased in SLE (93%), discoid lupus (50%), and “lupuslike” syndromes associated with congenital complement deficiencies (63%) as compared to normal controls (3%) and patients with drug‐induced lupus (11%), mixed connective tissue disease (MCTD) (17%), and necrotizing vasculitis (19%). The diagnostic and pathogenetic implications of these differences are discussed.
Accelerated appearance of neoplasms in female nzb/nzw mice treated with high‐dose cyclophosphamide
Authors: Walker Sara E , Anver Miriam R
Published: February 2007

Prolonged immunosuppressive therapy with cyclophosphamide increases the prevalence of neoplasms in NZB/NZW mice, an animal model of systemic lupus erythematosus. The current study was designed to compare the oncogenic properties of high dose cyclophosphamide with a low dose therapeutic regimen. Female NZB/NZW mice received life‐long therapy with “high dose” cyclophosphamide, 16 mg/kg/day, or “low dose” cyclophosphamide, 5.7 mg/kg/day; control mice received saline. High dose therapy clearly accelerated appearance of neoplasms. Seventeen of 19 mice treated with high‐dose cyclophosphamide developed neoplasms at the mean age of 61 weeks. Fifty‐seven percent of these tumors were mammary carcinomas. Neoplasms appeared in all mice treated with low dose; mean longevity in this treatment group was 80 weeks (compared to high dose treated mice, P < 0.001). Carcinomas, pulmonary adenomas, and lymphomas were the most common tumors in mice receiving low dose therapy. Positive tests for ANA were suppressed in high dose treated mice. AntiDNA antibody levels and glomerulonephritis were decreased significantly in both groups of cyclophosphamide‐treated mice compared to controls. It was concluded that the high daily dose of immunosuppressive drug was related to early oncogenesis in autoimmune NZB/NZW mice.
Culture‐negative septic arthritis and bacterial endocarditis
Authors: Wofsy David
Published: February 2007

The capacity of bacterial endocarditis to mimic other systemic illnesses is well known. This report describes a patient with blood culture‐negative bacterial endocarditis who presented with features suggestive of rheumatoid arthritis. Despite sterile synovial fluid, synovial biopsy culture resulted in identification of the causative organism and led to specific antibiotic therapy and cure. This is the first report of such a case.
Altered regulation of epstein‐barr virus induced lymphoblast proliferation in rheumatoid arthritis lymphoid cells
Authors: Bardwick Peter A. , Bluestein Harry G. , Zvaifler Nathan J. , Depper Joel M. , Edwin Seegmiller J.
Published: February 2007

An empiric observation of the rapid development of B lymphoblast cell lines after in vitro infection with Epstein‐Barr virus (EBV) in peripheral blood mononuclear cells (PBM) from patients with rheumatoid arthritis (RA) led us to compare cellular regulation of EBV‐induced lymphoblast outgrowth in RA and normal lymphoid cell populations. We found that RA PBM developed proliferating B lymphoblast colonies in a median time of 10 days after exposure to an EBV containing culture supernatant, while normal PBM took 18 days to grow out under the same conditions. The more rapid outgrowth of RA cells was not due to therapy with antiinflammatory or antirheumatic drugs. The time to outgrowth of the normal cells decreased to 11 days after T cell depletion. T cell depletion of the RA cells had less effect on the time to outgrowth but it was shortened to 8 days. B lymphoblast cell lines were established from “purified” T cell populations from 18 of 20 RA patients, while populations of T cells from normal donors with the same percentage of T and B cells did not produce lymphoblast cell lines when infected with EBV. In addition, we found that the non‐ T lymphoid cells from 7 of 20 RA patients established permanent B lymphoblast cell lines spontaneously without EBV infection. Spontaneous outgrowth of lymphoid cells from normal donors occurred only once in 48 experiments. These results indicate abnormalities in cell‐mediated regulation of EBV‐induced cell proliferation in lymphoid cells from patients with RA.
A controlled study of plasma exchange in the treatment of severe rheumatoid arthritis
Authors: Rothwell Robert S. , Davis Paul , Gordon Phillip A. , Dasgupta Mrinal K. , Johny Kaivilayil V. , Russell Anthony S. , Percy John S.
Published: February 2007

To learn whether the removal of immune complexes from the circulation by plasma exchange could effect an improvement in disease activity in rheumatoid arthritis (RA) patients, we performed a controlled study of 20 patients with severe progressive disease which had not responded to previous therapy. Ten patients (Group 1) were hospitalized, continued on their regular antiinflammatory medication, and given a graded course of physiotherapy. A further 10 patients (Group 2) received the same treatment as the first group with the addition of a concurrent course of plasmapheresis. Clinical measurement of disease activity after treatment revealed little difference between the two groups with a statistically significant improvement in four measures in Group 1 and in five in Group 2. Laboratory studies suggested that the intensity of plasma exchange was sufficient to remove circulating immune complexes in these patients. Our results confirm that hospitalization in itself is of benefit in the treatment of acute exacerbations of rheumatoid arthritis. The marginal improvement achieved by the addition of plasma exchange in the management of these patients (despite the removal of circulating immune complexes) makes its short‐term use of questionable value in the treatment of severe rheumatoid arthritis.
Effect of atropine sulfate in pulmonary hypertrophic osteoarthropathy
Authors: Lopez‐Enriquez Edrick , Morales A. Raphael , Robert Francisco
Published: February 2007

A 49‐year‐old patient with pulmonary hypertrophic osteoarthropathy was treated with 0.4 mg of atropine sulfate every 4 hours for 14 days. A good clinical response was obtained as measured by handgrip strength, range of motion, and quantitative thermography. Chemical vagotomy supports the hypothesis of the vagal reflex as the pathophysiological mechanism in pulmonary hypertrophic osteoarthropathy.
Prospective evaluation of sacroiliac scintigraphy in chronic inflammatory back pain
Authors: Esdaile John M. , Rosenthall Leonard , Terkeltaub Robert , Kloiber Reinhard
Published: February 2007

To assess the usefulness in screening for sacroiliitis of a wide band profile cut which included the entire sacroiliac (SI) joint, 34 patients with chronic inflammatory back pain (IBP) underwent sacroiliac joint scintigraphy with 99mTc‐methylene diphosphonate while receiving no antiinflammatory therapy. The sacroiliac joint to sacrum (SIJ/S) ratios in those with back pain differed significantly from the ratios of an age‐matched control group. However, 12 of the 34 patients with inflammatory back pain had normal or equivocal sacroiliac radiographs and 4 of 12 had normal SIJ/S ratios. All 4 were HLA‐B27 positive, had diminished lumbar movement, and required antiinflammatory medication; 2 had diminished chest expansion; 1 has developed iritis. We conclude that this technique is not a reliable screening procedure. Therapy with antiinflammatory drugs was associated with a significant decrease in the SIJ/S ratios in 19 of the 34 who were reimaged.
The detection and identification of antibodies to saline extractable nuclear antigens by counterimmunoelectrophoresis
Authors: Keiser Harold D. , Weinstein Joshua
Published: February 2007

Sera containing antibodies to the saline extractable nuclear antigens RNP, Sm, and Ha can be identified with counterimmunoelectrophoresis (CIE) by matching their precipitin reactions to those of reference sera. The CIE reaction of Sm is unusual in that two preciptin lines are formed, one of which shows partial immunologic identity with the reaction to RNP. Sera were identified with the reaction to RNP. Sera were identified by CIE which reacted with additional acidic antigens in rabbit thymus extract, some of which had the same enzyme sensitivity profiles as RNP and Ha but were immunologically not identical and could not be detected by hemagglutination with red cells coated with calf thymus nuclear extract. Although the incidence of reactivity to RNP, Sm, and Ha was similar to previous reports, review of the clinical manifestations of 128 patients with systemic lupus erythematosus (SLE) did not provide statistically significant confirmation of previously to reactivity and particular patterns of disease expression. With due attention paid to technical artifacts, CIE is a sensitive and specific method for identifying sera reactive with acidic nuclear antigens that has practical advantages over alternative methods.
Chemotaxis in yersinia arthritis HLA‐B27 positive neutrophils show high stimulated motility in vitro
Authors: Leirisalo Marjatta , Repo Heikki , Tiilikainen Anja , Kosunen Timo U. , Laitinen Ossi
Published: February 2007

Chemotaxis, chemokinesis, and spontaneous locomotion of polymorphonuclear leukocytes (PMNs) of yersinia arthritis (YA) patients and healthy subjects with or without HLA‐B27 were studied by agarose assay and membrane filter technique. HLA‐B27 positive healthy control subjects and yersinia patients showed significantly higher response to chemotactic stimulus than HLA‐B27 negative controls. Consequently, the high response was associated with HLA‐B27 irrespective of YA. The high responder PMNs may contribute to the more severe inflammatory symptoms in YA patients with HLA‐B27.
Skeletal metabolism in paget's disease of bone
Authors: Krane Stephen M.
Published: February 2007

Paget's disease of bone is characterized by focal resorption of existing bone followed by the deposition of woven and lamellar bone in a characteristic pattern. Although bone turnover may be markedly increased, the coupling between formation and resorption is maintained. Metabolically there is increased efflux and influx of mineral ions in the involved areas. In addition, there is a parallel increase in resorption of matrix components, particularly collagen, with increased excretion of degradation products containing 4‐hydroxyproline, hydroxylysine, and its glycosides. A portion of the urinary 4‐hydroxyproline and hydroxylysine is in the form of peptides of approximately 5,000 daltons which appear to be related to collagen synthesis. Circulating levels of other organic matrix components are also increased such as procollagen fragments and the γ‐carboxyglutamic acid‐bone protein. The increased levels of most of these metabolites return toward normal with specific therapy. The pattern of change suggests that bone resorption is decreased initially with therapy followed by a coupled decrease information.
Radiologic observations on bone resorption in Paget's Disease
Authors: Doyle Frank H. , Banks Linda M. , Pennock Jacqueline M.
Published: February 2007

The diagnosis of Paget's disease of bone at its earliest osteolytic phase is difficult and requires radiographs of the highest quality. Calcitonin controls the bone resorption of uncomplicated Paget's disease but does not prevent disuse osteoporosis in normal and pagetic bones. Cessation of treatment leads to a recurrence of the osteolytic phase of the disease in some patients. Retreatment with human calcitonin arrests the bone resorption and permits bony consolidation of resorption clefts.
Carpal ankylosis in juvenile rheumatoid arthritis
Authors: Maldonado‐Cocco José A. , García‐Morteo Osvaldo , Spindler Alberto J. , Hübscher OSVALDO , Gagliardi Susana
Published: February 2007

Forty‐seven of 100 consecutive juvenile rheumatoid arthritis patients with wrist arthritis were found to have ankylosis at the carpal joints. This finding was significantly more frequent in juvenile than in adult rheumatoid arthritis patients. The carpometacarpal wrist segment was the most frequently ankylosed. Ankylosis was not related to any particular feature of the disease, but disease duration was longer in patients with ankylosis. A significant association was found between carpal ankylosis and cervical apophyseal joint fusion.
Natural cell mediated cytotoxicity in systemic lupus erythematosus
Authors: Goto Makoto , Tanimoto Kiyoaki , Horiuchi Yoshihiko
Published: February 2007

The significantly reduced natural killer (NK) cell activity was demonstrated in the peripheral blood lymphocytes (PBL) from 20 female patients with systemic lupus erythematosus (SLE) when compared with NK activity in the age and sex‐matched controls. The reduced NK activity did not correlate with clinical parameters including daily prednisolone doses, serum CH50, antinuclear antibody titers, antiDNA activities, circulating immune complex levels, and cytotoxic activities of antilymphocyte antibodies (ALA). The effects of prednisolone and aggregated human IgG on NK activity were only slightly suppressive in the in vitro studies. When normal PBL were pretreated with rabbit complement and SLE sera containing ALA, the NK activity of the surviving cells was markedly decreased. The decrease was specific and did not seem to be due to the physical hindrance of the dead cells. Other heterologous ALA of rabbit origin did not exert a suppressive effect on NK activity. These results suggest that the suppressed NK activity in SLE can be ascribed to an antiNK cell specific antibody in lupus sera, although the participation of circulating immune complexes was not completely excluded.
‘Navajo Arthritis’ reconsidered
Authors: Rate Robert G. , Morse Harold G. , Bonnell Mark D. , Kuberski Timothy T.
Published: February 2007

‘Navajo arthritis’ was described in 1971 as an acute, self‐limited, asymmetric polyarthritis of unknown etiology seen in Navajo Indian patients. This description was before published accounts relating HLA‐B27 to certain seronegative arthropathies. Review of 92 cases of arthritis seen between 1977 through 1979 in adult Navajo Indians revealed 16 cases of complete Reiter's syndrome, 6 cases of incomplete Reiter's syndrome, and 7 cases of ankylosing spondylitis. The phenotype frequency of HLA‐B27 in this Navajo population is 36% and, of the Reiter's syndrome and ankylosing spondylitis patients tested, 85% were found to be HLA‐B27 positive. We suggest that “Navajo arthritis” may not be a unique form of arthritis affecting only the Navajo, but a variant of either Reiter's syndrome or ankylosing spondylitis.
Efefct of long‐term treatment with circulating thymic factor on murine lupus
Authors: Bach Marie‐Anne , Droz Dominique , Noel Laure‐Helene , Blanchard Dominique , Dardenne Mireille , Peking A.
Published: February 2007

Mice from three different strains (NZB, B/W, and Swan) which spontaneously develop a lupus‐like disease and show a premature decline of their secretion of the circulating thymic factor, Facteur Thymique Serique (FTS), were treated repeatedly with FTS and followed for the evolution of their autoimmune disease. The autoimmune sialoadenoitis (Sjogren's syndrome) appearing in NZB and B/W mice, evaluated here by a scintigraphic method, was completely prevented or evencured by FTS treatment. The increase in antierythrocyte autoantibody production was transiently delayed in aged NZB mice. Conversely, antiDNA antibody production either remained unaffected or was accelerated (in B/W mice) by FTS treatment. These results demonstrate that the restoration of the failing thymic secretion does influence autoantibody production, in a manner depending primarily on the autoantigen eliciting the autoimmune response. However, caution is urged in the application of this approach to human lupus without further studies.
Functional renal involvement in normotensive patients with progressive systemic sclerosis. impaired sodium excretion during isotonic saline infusion
Authors: D'Angelo A , Messa P , Fiocco U , Fabris A , Morachiello P , Senesi G , Todesco S
Published: February 2007

An intravenous infusion of 2,000 ml isotonic saline was performed in 8 normotensive, normoreninemic patients with progressive systemic sclerosis. None of them had clinical evidence of renal disease. Total and proximal fractional excretion of sodium was reduced when compared with that of 8 normal subjects. No correlation was found with para‐aminohippurate (PAH) clearance values. Two years after this study was done, 4 patients developed arterial hypertension; interestingly, plasma renin activity remained within the normal range. Reduced sodium excretion is suggested as having a pathogenetic role in the hypertension of progressive systemic sclerosis.
“Milwaukee shoulder”—association of microspheroids containing hydroxyapatite crystals, active collagenase, and neutral protease with rotator cuff defects. ii. synovial fluid studies
Authors: Halverson Paul B. , Cheung Herman S. , Mccarty Daniel J. , Garancis John , Mandel Neil
Published: February 2007

Hydroxyapatite crystals in spheroid‐shaped masses 1.9–15.6m̈ in diameter were found in 12 of 13 synovial fluids obtained from the shoulder joints of 4 patients with rotator cuff tears and glenohumeral osteo‐arthritis. Two of 16 control joint fluids also showed these particles. Collagen types I, II, and III were identified in the joint fluid pellets from 3 of the 4 patients, and fibers with typical collagen periodicity were also seen on transmission electronmicroscopy. Collagenase and neutral protease activities were found in fluids from 5 joints in 3 patients, whereas active collagenase was found in only 1 of 10 fluids from rheumatoid arthritis patients and in none of 3 fluids from patients with osteoarthritis. Neutral protease activities were present in several rheumatoid joint fluids. These findings are compatible with the hypothesis of an enzymatic release of hydroxyapatite crystals from the synovium and endocytosis by synovial macrophage‐like cells with subsequent crystal‐stimulated release of collagenase and neutral protease into the joint fluid, completing a pathogenetic cycle.
Comparison of phosphohydrolase activities from articular cartilage in Calcium Pyrophosphate deposition disease and primary osteoarthritis
Authors: Tenenbaum Jerry , Muniz Ofelia , Ralph Schumacher H. , Good Armin E. , Howell David S.
Published: February 2007

One abnormality in calcium pyrophosphate deposition disease (CPDD) which fosters consistently high synovial fluid pyrophosphate ion (PPi) and large accumulations of calcium pyrophosphate dihydrate crystals (Ca pyrophosphate) might be an aberration in chondrocytes involving elaboration of PPi and failure of its hydrolysis within cartilage matrix. Exploration of this hypothesis required further information on the phosphohydrolases in relevant human articular cartilages. Triton X‐100 extracts of whole homogenized cartilage from 18 patients with primary osteoarthritis (OA), 10 patients with CPDD and secondary OA, as well as 6 “normal” subjects were partially purified by DE‐52 chromatography and eluates studied for phosphohydrolase activity in a variety of substrates, inhibitors, and environmental conditions. Almost all the protein as well as crude alkaline phosphatase and pyrophosphatase activities were clustered in peaks designated I and II. Findings in CPDD cartilage not observed in OA controls were: 1) consistent alkaline phosphatase activity in the void volume of DE‐52 columns, 2) high levels of 5′nucleotidase activity, 3) abundant generation of PPi by CPDD cartilage during in vitro incubation of cartilage extract fractions with ATP. This enzymatic behavior is likely to bear a regulatory relationship to PPi production by chondrocytes in CPDD.
Production of agglutinators and rheumatoid factors in plasma cells of rheumatoid and nonrheumatoid synovial tissues
Authors: Fehr Kurt , Velvart Magda , Rauber Monika , Knöpfel Margrit , Baici Antonio , Salgam Prathima , Böni Albert
Published: February 2007

Immunohistochemical studies were performed in synovial tissues from 40 patients with rheumatoid arthritis (RA), 9 with juvenile rheumatoid arthritis (JRA), 7 with psoriatic arthritis, and 4 with various rheumatic diseases. Overall synthesis of IgG– and/or IgM–rheumatoid factor (RF) was found in all patients with seropositive RA and JRA, in 75% of patients with seronegative RA, and in 1 patient with psoriatic arthritis. Agglutinator producing cells were found in 77% of the samples from seropositive RA and in 44% and 56% from seronegative RA and JRA patients, respectively. The percentage of IgG plasma cells synthesizing one or more of the 5 types of agglutinators studied was approximately 10% of plasma cells synthesizing IgG–RF. Intercellular and intracellular immune complex deposits were also found in patients with seropositive and seronegative RA and JRA. These findings suggest that synthesis of agglutinators by synovial tissue plasma cells of RA and JRA patients is a distinct—but definitely less prominent—function than that of RF synthesis.
Clearance of calcium pyrophosphate dihydrate crystals in VIVO
Authors: Mccarty Daniel J. , Palmer David W. , Garancis John C.
Published: February 2007

Synthetic triclinic calcium pyrophosphate dihydrate crystals, uniformly labeled with 85Sr and 45Ca, were injected into the knee joints of 2 normal adult rabbits and 2 rabbits previously injected repeatedly with autologous blood. The “half clearance time” of the injected crystal mass was 20.4 and 19 days from control joints, nearly identical to previously reported values in 6 rabbits (19.1 ± 1.4), and 28.8 and 34 days from the joints injected with blood, a significant difference (P < 0.05). Iron stains showed hemosiderin granules in the superficial synovium in these joints. Electron microscopy showed crystals with a molar calcium/phosphorus ratio of 1.0 and particles containing iron within synovial cells. We hypothesize that the decreased clearance rate from hemosiderotic synovium is due to inhibition of one or more intracellular pyrophosphatases by iron.
Pharmacology of human spontaneous monocyte‐mediated cytotoxicity
Authors: Kleinerman E. S. , Louie J. S. , Wahl L. M. , Muchmore A. V.
Published: February 2007

The effect of various antiinflammatory agents on the spontaneous cytotoxicity of human mononuclear cells in vitro was assessed. Acetylsalicylic acid (ASA) and hydrocortisone enhanced spontaneous monocyte‐mediated cytotoxicity compared to control values. This enhancement could not be mediated through inhibition of prostaglandin biosynthesis since indomethacin had no effect on cytotoxic function and since the direct addition of PGE2 to the cell cultures did not inhibit the expression of cytotoxicity. Likewise, salicylic acid (SA), which has no effect on prostaglandin biosynthesis, also enhanced monocyte cytotoxicity. Stimulation of monocyte‐mediated cytotoxicity resulting in more efficient antigen removal and thus decreasing antigen persistence may be an additional mechanism by which ASA, SA, and hydrocortisone modulate the destructive inflammatory response in rheumatoid arthritis.
Lymphokine‐mediated suppression of chondrocyte glycosaminoglycan and protein synthesis
Authors: Herman Jerome H. , Nutman Thomas B. , Nozoe Masaru , Mowery Clifford S. , Dennis Marie V.
Published: February 2007

Spontaneously released and T cell mitogen augmented lymphokine produced by human mononuclear cells has been shown to induce a concentration dependent reversible suppression of chondrocyte glycosaminoglycan and protein synthesis without significantly enhancing chondrocyte catabolic activity. The modulatory factor(s) is of T cell origin and is trypsin, pronase, and heat sensitive. Prostaglandin inhibitors failed to influence factor formation or activity. Although eluting from Sephadex G‐100 over a wide range, peak activity had an approximate molecular weight of 53,000 and appeared distinct from recognized forms of lymphotoxin.
Self‐nonself recognition by T and B lymphocytes and their roles in autoimmune phenomena
Authors: Weigle William
Published: February 2007

Evidence is presented which supports the suggestion that whether a given antigen is vulnerable to an autoimmune attack is dependent upon the specific immune status of B cells and T cells to that antigen which, in turn, is dictated by the concentration of self antigen in their microenvironment. That B cells require much higher concentrations of self antigens than do T cells for the maintenance of tolerance is supported by data presented using an experimental model of acquired tolerance to serum proteins. Depending on the immune status of T cells and B cells to self antigen, the following three models are suggested for the early events leading to autoimmunity: 1) polyclonal activation of competent B cells, 2) direct activation of competent T cells, and 3) bypass of specifically tolerant T cells and activation of competent B cells. The role of a regulatory network involving the suppressor cell circuit in the induction and regulation of autoimmunity is discussed.
Suppression of acute and chronic inflammation by orally administered prostaglandins
Authors: Kunkel Steven L. , Ogawa Hiroshi , Conran Philip B. , Ward Peter A. , Zurier Robert B.
Published: February 2007

Oral administration of a stable analog of prostaglandin E, (PGE1), 15‐(S)‐15‐methyl‐prostaglandin E1, can suppress both chronic adjuvant‐induced polyarthritis and acute immune complex‐induced vasculitis in a dose dependent manner. Histopathologic studies of tibiotarsal joints from rats with adjuvant disease showed suppression of arthritis in animals treated with the PGE, analog from time of adjuvant challenge. This study represents the first demonstration of suppressed experimental polyarthritis by an orally administered prostaglandin. Suppression of the acute immune complex‐induced vasculitis was demonstrated using 15‐methyl‐PGE, administered orally 12 hours prior to antigen‐antibody challenge. Diminution of tissue injury resulting from immune complex‐induced vasculitis is reflected by a decrease in vaso‐permeability, indicating suppressed vascular damage in animals treated with prostaglandin. These studies demonstrate the potential use of orally active prostaglandins as an antiinflammatory agent.
Decreased capacity to solubilize immune complexes in sera from patients with systemic lupus erythematosus
Authors: Aguado M. Teresa , Perrin L. H. , Miescher P. A. , Lambert P. H.
Published: February 2007

The capacity to solubilize immune complexes formed in vitro is significantly decreased in patients with systemic lupus erythematosus (SLE). This complement function correlates significantly with serum C3 levels and inversely with the presence of circulating immune complexes. Clinically, patients with a decreased capacity to solubilize complexes show a worse evolution and an increased incidence of renal involvement. In conclusion, the impaired solubilization capacity, related to low complement activity, which is observed in patients with SLE may favor the persistence of immune complexes in tissues.
THE EFFECT OF LEAD UPON URATE NUCLEATION
Authors: Tak Hyon‐Ki , Wilcox William R. , Cooper Sheldon M.
Published: February 2007

Lead urate was crystallized from solutions originally containing 0.595 mM (10 mg%) urate and 0.297 mM PbCl2. In the absence of lead, monosodium urate does not nucleate unless the urate concentration exceeds 80 mg%. Lead urate crystals were negatively birefringent and had a distinct x‐ray powder diffraction pattern. Crystals of monosodium urate nucleated on lead urate seed crystals when the urate concentration was 10 mg%. These studies indicate that with physiologic conditions of temperature, pH, and ionic strength, spontaneous nucleation of lead urate can be demonstrated.
Treatment Of NZB/NZW F1 Hybrid Mice with Mycobacterium Bovis Strain BCG or Type II Interferon Preparations Accelerates Autoimmune Disease
Authors: Engleman Edgar G. , Sonnenfeld Gerald , Dauphinee Michael , Greenspan John S. , Talal Norman , Mcdevitt Hugh O. , Merigan Thomas C.
Published: February 2007

NZB/NZW F1 hybrid mice develop a spontaneous autoimmune disease characterized by the appearance of antinuclear antibodies and premature death due to immune complex glomerulonephritis. To investigate the possible effects of cellular immune stimulation on this disorder, groups of female NZB/NZW mice, aged 2, 5, and 7 months, were treated either with the nonspecific immunostimulatory agent Mycobacterium bovis strain BCG or with saline. Mice treated with BCG at ages 5 and 7 months died sooner than age‐matched controls, and death was associated with severe glomerulonephritis, suggesting that BCG may have accelerated autoimmunity in these mice. Since BCG is known to stimulate the production of type II (or γ) interferon, a substance with potent immunoregulatory effects, a second study was carried out to assess the effects of type II interferon on NZB/NZW disease. A greater number of type II interferon‐treated mice died by 9 months of age when compared to controls, and the increased death rate was associated with a more rapid development of antinuclear antibodies and histologically confirmed glomerulonephritis. These data, together with a recent report of increases in the level of serum type II interferon in patients with active systemic lupus erythematosus, suggest that type II interferon may play a role in the pathogenesis of autoimmune disease.
Electromyographic findings in various forms of progressive systemic sclerosis
Authors: Hausmanowa‐Petrusewicz Irena , Jabłońska Stefania , Błaszczyk Maria , Matz Beżena
Published: February 2007

Electromyographic findings were studied in 32 women and 7 men with progressive systemic sclerosis. Among the 14 patients in group 1, 7 had the CREST syndrome in an early stage while the 14 patients in group 2 had advanced CREST‐type lesions. The 18 patients in group 3 had diffuse scleroderma with extensive visceral involvement. In all groups, the mean duration of single potentials was reduced and the percent of polyphasic potentials was above normal in groups 2 and 3. Distal muscles were more involved in group 1, and proximal muscles in group 2. In group 3, involvement of various muscles was nearly equal. Electromyographic changes correlated with the clinical condition of the patients. Overall, the findings in this study are similar to findings from other laboratories.
Activation of the classical pathway of complement by rheumatoid factors
Authors: Sabharwal Umesh K. , Vaughan John H. , Fong Sherman , Bennett Peter H. , Carson Dennis A. , Curd John G.
Published: February 2007

A simple, sensitive solid‐phase radioimmunoassay to quantitate the activation of the classical pathway of complement by rheumatoid factor (RF) is described. RF (purified, in serum or synovial fluid) was bound to reduced and alkylated IgG adsorbed to polyvinyl chloride microtiter plates and reacted with diluted normal human serum (complement). The activation and binding of C4 were quantitated with 125I‐Fab'2‐anti‐C4. Purified, polyclonal IgM–RF was 100‐ to 1,000‐fold more effective than purified IgG–RF in activating complement. The amount of complement activation produced by RF in each of the 57 sera and 2 synovial fluid samples correlated directly with the amount of IgM–RF present. The complement activating abilities of polyclonal IgM–RF in the sera of 15 rheumatoid arthritis patients were homogeneous. This novel technique is readily applicable to the investigation of complement activation by RF in disease.
Noncollagenous proteins in cartilage of normal subjects and patients with degenerative joint disease. a gel electrophoretic study
Authors: Chaminade F. , Stanescu V. , Stanescu R. , Maroteaux P. , Peyron J. G.
Published: February 2007

Normal articular cartilage from subjects of various ages and cartilage from patients with degenerative joint disease were extracted with 4M guanidinium chloride. After dialysis against 8M urea pH 6.8, a 0.2M NaCl fraction was obtained by ion exchange chromatography on DE‐52 in 8M urea. This fraction was concentrated, reduced, and analyzed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (7% gels). Six major noncollagenous protein bands (P1–P6) were found; 2 were identified as the link proteins. The approximate molecular weights of P1–P6 were: 87,000, 64,000, 56,000, 46,000, 41, 000, and 27,000. A similar sodium dodecyl sulfate–polyacrylamide gel electrophoresis pattern of P1–P6 was found in young baboons, in normal young and aged humans, and in patients with degenerative joint disease. Peaks corresponding to extracted collagen were decreased in older patients and increased in patients with degenerative joint disease, even those of advanced age.
Abnormal softening in articular cartilage. Its relationship to the collagen framework
Authors: Broom Neil D.
Published: February 2007

Abnormal softening in articular cartilage is related to the presence of collagen fibers strongly aligned in a radial direction. In this paper, a morphologic model is proposed that provides a mechanism by which these radial arrays can develop passively from the more random, 3‐dimensional network of fibers observed in normal articular cartilage.
Effect of purified growth factors on rabbit articular chondrocytes IN MONOLAYER CULTURE. I. DNA Synthesis
Authors: Prins A. Pieter A. , Lipman Jack M. , Sokoloff Leon
Published: February 2007

The ability of purified growth factors, insulin, ascorbate, and several other compounds to stimulate DNA synthesis by rabbit articular chondrocytes was studied in monolayer culture. Platelet‐derived growth factor (1 U/ml), pituitary fibroblast growth factor (1–100 ng/ml), and epidermal growth factor (1–50 ng/ml) were stimulatory in a basal medium supplemented with 1% heat‐inactivated fetal bovine serum. Insulin, 1–50 μg/ml, had small growth‐promoting effects but acted synergistically with platelet‐derived, pituitary fibroblast, and epidermal growth factors. Increasing concentrations of serum up to 10% enhanced the growth‐promoting action of the purified factors, but not of insulin. There were indications of cooperation between insulin and bovine serum albumin and dexamethasone. Ascorbate (0.2 mM) reduced or had little growth‐promoting action in the basal medium. At 5 and 10% serum concentrations, however, ascorbate promoted DNA synthesis as effectively as the purified growth factors. No significant stimulatory effect was shown by transferrin, thrombin, L‐glutamine, putrescine, selenous acid, dexamethasone, 7S nerve growth factor, or multiplication‐stimulating activity.
Adjuvant polyarthritis. vii. The role of type ii collagen in pathogenesis
Authors: Iizuka Yoshio , Chang Yi‐Han
Published: February 2007

The development of immune response in rats directed toward EL4 cells, after the injection of EL4 cells suspended in a saline/oil emulsion, was enhanced by the incorporation of Mycobacterium into the saline/oil emulsion; the incorporation of type II collagen into the saline–acetic acid/oil emulsion in concentrations ranging from 0.5–25 μg/ml had no apparent effect on the development of immune response. The incorporation of type II collagen into the saline–acetic acid/oil emulsion at higher concentrations (100 μg and 1.0 mg/ml) significantly suppressed both the humoral and the cell‐mediated immune response. Pretreatment of rats with the maximal subarthritogenic dose of complete Freund's adjuvant prevented the development of arthritis in response to a subsequent injection of an arthritogenic dose of the same adjuvant, but had no effect on the development of type II collagen–induced arthritis. These observations suggest that adjuvant arthritis and the type II collagen–induced arthritis are distinctly different diseases.
Natural killer cell activity of mononuclear cells from rheumatoid patients measured by a conjugate‐binding cytotoxicity assay
Authors: Reinitz Elizabeth , Neighbour P. Andrew , Grayzel Arthur I.
Published: February 2007

The natural killer cell activity of synovial fluid mononuclear cells and synovial membrane mononuclear cells from patients with rheumatoid arthritis was compared with that of paired peripheral blood mononuclear cells from many of these patients. Natural killer cell activity was measured by the use of a conjugate‐binding cytotoxicity assay with an erythroleukemic cell line, K562, as target. There was no significant difference when 15‐minute target binding by peripheral blood mononuclear cells was compared with synovial fluid mononuclear cells. Target binding of synovial membrane mononuclear cells was significantly greater (P < 0.05) than that of peripheral blood cells. Three‐hour target killing, however, was significantly greater when synovial fluid mononuclear cells were compared with the peripheral blood cells, P 7< 0.01, and when synovial membrane cells were compared with the peripheral blood cells (P < 0.05). The products of binding and 3‐hour killing, a reflection of the total number of mononuclear cells participating in cytotoxicity, were significantly greater when either synovial fluid or synovial membrane mononuclear cells were compared with peripheral blood mononuclear cells (both P < 0.01). Electron microscopy confirmed the presence of large granular lymphocytes, representing 20% of the peripheral blood cells and 37% of the synovial fluid mononuclear cells. Interferons were detected in 10/12 rheumatoid and 3/12 nonrheumatoid synovial fluid samples studied. These findings indicate that functional natural killer cells are selectively increased in the rheumatoid joint and may contribute to the overall increase in immunologic activity found in the joints of these patients.
Induction of fibroblast proliferation by human mononuclear leukocyte‐derived proteins
Authors: Postlethwaite Arnold E. , Kang Andrew H.
Published: February 2007

Human peripheral blood mononuclear leukocytes stimulated by T cell antigen or mitogen release soluble factors that induce mitogenesis of dermal fibroblasts in vitro. Fractionation of supernatants from antigen‐stimulated mononuclear leukocyte cultures by Sephadex G‐100 yielded 2 major peaks of fibroblast proliferation activity (∼︁60,000 and ∼︁16,000 MW). Both proliferation factors are heat stable (56°C for 45 minutes) proteins. These data show that mononuclear leukocytes, under appropriate conditions, can release soluble mediators that can stimulate fibroblast proliferation; such leukocytes may also play a role in expanding fibroblast populations adjacent to certain cell‐mediated immune reactions in vivo.
Clinical features of patients with antibodies directed against proliferating cell nuclear antigen
Authors: Fritzler Marvin J. , Mccarty Gale A. , Paul Ryan J. , Douglas Kinsella T.
Published: February 2007

The clinical and serologic features of 7 patients whose sera contained antibodies directed against proliferating cell nuclear antigen (anti‐PCNA) were studied. Five of the patients had systemic lupus erythematosus (SLE), 1 had idiopathic diffuse proliferative glomerulonephritis, and 1 had seronegative arthritis. In a study of various rheumatic diseases, anti‐PCNA was found in 2% of SLE sera but was not found in the sera of 100 rheumatoid arthritis patients, 20 mixed connective tissue disease patients, or 50 diffuse scleroderma patients. Patients with anti‐PCNA had no history of hemolytic anemia, leukopenia, thrombocytopenia, or pleuro‐pericarditis. Evidence that the production of anti‐PCNA antibodies is sensitive to corticosteroid therapy is also presented.
Separation and characterization of immune complexes containing 19S IgM rheumatoid factor‐IgG in juvenile arthritis
Authors: Moore Terry L. , Wayne Sheridan P. , Zuckner Jack , Dorner Robert W.
Published: February 2007

Sera from 10 patients with juvenile arthritis (JA), 2 seropositive and 8 with hidden rheumatoid factor (RF), were subjected to affinity chromatography on a rabbit anti‐human IgM column. Material retained by the column was eluted sequentially by 1M NH3 and 0.1M glycine‐HCl buffer, pH 3.0. The affinity fractions contained both 19S IgM RF and IgG, while corresponding fractions from healthy controls contained neither. Sera from 15 patients with JA, 1 seropositive and 11 with hidden RF, were subjected to 4% polyethylene glycol precipitation followed by acid dissociation of the precipitate. Ten of 15 resultant fractions contained both IgM RF and IgG, while corresponding fractions from healthy controls contained only traces of IgG. Sera from 7 of these JA patients were subjected to sucrose density gradient centrifugation and the resultant fractions analyzed for the presence of immune complexes by the Clq solid‐phase assay. Immune complexes were detected at and ahead of the IgM marker, as expected for IgM RF‐IgG complexes. These combined data show that the majority of JA patients with classic or hidden 19S IgM RF have immune complexes containing IgM RF and IgG in their sera.
Cytotoxicity of sera from patients with scleroderma
Authors: Cohen Stanley , Johnson Alice R. , Hurd Eric
Published: February 2007

Sera from patients with progressive systemic sclerosis were compared with sera from normal individuals and from patients with other connective tissue diseases for cytotoxic effects on cultured human cells. More than 40% of the sera from patients with active progressive systemic sclerosis were cytotoxic by several criteria for pulmonary arterial or umbilical venous endothelial cells, foreskin fibroblasts, and neuroblastoma cells. Cytotoxic sera caused morphologic changes, uptake of trypan blue dye, and a decrease in the incorporation of 3H‐thymidine into DNA. In contrast, only 4 sera from normal individuals or patients with other rheumatic diseases affected cell morphology, staining, or uptake of 3H‐thymidine. Partial characterization of the cytotoxic factor indicated that it is sensitive to proteolysis by trypsin. The molecular weight of the factor was estimated to be similar to that of albumin.
The Precipitating Antibody to an Acidic Nuclear Protein Antigen, the Jo‐1, in Connective Tissue Diseases
Authors: Yoshida Shunji , Akizuki Masashi , Mimori Tsuneyo , Yamagat Hajime , Inada Shinichi , Homma Mitsuo
Published: February 2007

The clinical significance of antibodies to the Jo‐1 antigen in connective tissue diseases was studied. Clinical diagnoses of 11 patients who had anti‐Jo‐1 antibody were: polymyositis 8, dermatomyositis 1, and overlap syndrome 2 (polymyositis‐systemic lupus erythematosus 1, polymyositis—scleroderma 1). All the patients who had anti‐Jo‐1 antibody showed interstitial pulmonary fibrosis, and in 2 patients anti‐Jo‐1 antibodies were detected before the appearance of lung disease.
Natural Killer Cells in Systemic Lupus Erythematosus
Authors: Egan Marianne L. , Mendelsohn Steven L. , Abo Toru , Balch Charles M.
Published: February 2007

A monoclonal antibody, HNK‐1, that detects a differentiation antigen on human granular lymphocytes with natural killer (NK) activity was used to enumerate this subpopulation in the peripheral blood of 14 patients with systemic lupus erythematosus (SLE). Nine patients had severely decreased numbers of HNK‐1+ cells, 3 patients had elevated levels of HNK‐1+ cells, and 2 patients had appropriate numbers of HNK‐1+ cells compared with the levels in 112 normal controls. All SLE patients exhibited low NK killing ability against K562 target cells compared with controls. An increased proportion of the HNK‐1+ cells was categorized as immature granular lymphocytes in over 50% of the SLE patients because their HNK‐1+ cells coexpressed the OKT3 antigen and contained a paucity of cytoplasmic granules. The numbers of HNK‐1+ cells or the HNK‐1+ OKT3+ subgroup did not correlate with steroid therapy. This evidence suggests that levels of HNK‐1+ lymphoctyes are abnormal and functionally immature in most SLE patients. Longitudinal studies conducted over several months on a number of SLE patients demonstrated fluctuations in the ratio of mature and immature HNK‐1+ cells and total HNK‐1+ cells. Additional patients tested over longer periods of time will have to be studied to determine whether the proportion of mature NK cells (HNK‐1+ OKT3‐) and immature NK cells (HNK‐1+ OKT3+) will be useful in predicting the clinical course of disease.
High Serum Beta‐2‐Microglobulin Levels and Circulating Immune Complexes Containing βm AND Anti‐βm Antibodies in Felty's Syndrome
Authors: Falus AndráS , Wiik Allan , Permin Henrik , Brandslund Ivan , Svehag Sven‐Erik
Published: February 2007

Serum beta‐2‐microglobulin (β2m) levels, incidence and levels of anti‐β2m autoantibodies, and quantity of circulating macromolecular complexes containing β2m were studied in patients with Felty's syndrome (FS), joint‐restricted rheumatoid arthritis (RA), and healthy controls. The serum β2m concentrations detected in the FS group (6.95 ± 2.9 mg/liter) greatly exceeded those of the RA group (3.4 ± 1.2 mg/liter) and the control group (1.42 ± 0.69 mg/liter). Autoantibodies to β2m were frequent in the FS group. Circulating complexes containing β2m, prepared by precipitation in 3% polyethylene glycol, were detected in 65% of FS and 35% of RA patients. In the majority of these cases the solid‐phase Clq purified immune complexes also contained βm. Detection of anti‐β2m antibodies in a significant part of complexes containing β2m suggests the presence of specific immune complexes in this fraction of FS and RA patients.
Incidence and specificity of antibodies to types I, II, III, IV, and V collagen in rheumatoid arthritis and other rheumatic diseases as measured by 125i‐radioimmunoassay
Authors: Stuart John M. , Huffstutter Eugene H. , Townes Alexander S. , Kang Andrew H.
Published: February 2007

Antibodies to human native and denatured types I, II, III, IV, and V collagens were measured using 125I‐radioimmunoassay. Mean levels of binding by sera from 30 rheumatoid arthritis patients were significantly higher than those from 20 normal subjects against all of the collagens tested. The relative antibody concentration was higher in synovial fluid than in simultaneously obtained serum. Many patients with gout or various other rheumatic diseases also had detectable anticollagen antibodies. With a few notable exceptions, the majority of the reactivity detected in all patient groups was directed against covalent structural determinants present on all of the denatured collagens, suggesting a secondary reaction to tissue injury.
Social and economic impacts of four musculoskeletal conditions
Authors: Kramer Jane S. , Yelin Edward H. , Epstein Wallace V.
Published: February 2007

The present study uses data from a national, community‐based survey to compare the social impact of and medical care use due to 4 musculoskeletal conditions: rheumatoid arthritis, osteoarthritis, lower back pain, and tendinitis. The study also compares the impacts experienced by persons with these conditions with those experienced by a sample of persons having a broader range of musculoskeletal conditions, and by an age‐adjusted sample representing the entire U.S. population. Rheumatoid arthritis leads to the most frequent use of physician services; lower back pain results in the most hospitalizations and surgery. Rheumatoid arthritis also causes the most restriction in activity. We found that as a broad group, persons with musculoskeletal disease experience about the same amount of restriction in activity and use about the same amount of medical care as U.S. citizens as a whole. This study demonstrates that health planning on the basis of specific musculoskeletal conditions is necessary to serve the disparate needs of persons with particular, discrete conditions.