bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromosome Breakage and Sister Chromatid Exchange Frequencies in Scleroderma
Authors: Sherer Glenn K. , Jackson Barbara B. , Leroy E. Carwile
Published: February 2007

Peripheral lymphocytes from 3 scleroderma patients with systemic disease and from 3 normal controls were examined for frequencies of chromosomal aberration and sister chromatid exchange (SCE). Significant increases in the levels of chromosomal anomaly and SCE were found for all 3 patients. These results are discussed in terms of the diagnostic potential of SCE in scleroderma and the possible etiologic role of cytogenetic instability in this disease.
Identification of Cartilage Wear Fragments in Synovial Fluid from Equine Joints
Authors: Tew William P. , Hackett Richard P.
Published: February 2007

Synovial fluids from 72 equine joints were examined for the presence of cartilage debris, and these findings were compared to findings from visual inspection of the articular cartilage surfaces at necropsy. Synovial fluids from 25 joints with visual cartilage damage contained one or more large particles of articular cartilage. Cartilage fragments were not found in synovial fluids from 42 of the 47 apparently normal joints; thus, a correlation may exist between cartilage debris in the synovial fluid and lesions of the articular surfaces.
Proteoglycan Structure and Metabolism in Normal and Osteoarthritic Cartilage of Guinea Pigs
Authors: Schwartz Edith R. , Leveille Cynthia R. , Stevens Jeff W. , Oh Won H.
Published: February 2007

Sulfated proteoglycan structure and metabolism in osteoarthritic articular cartilage from the hind‐limb joints of guinea pigs in which the disease had been surgically induced were evaluated and compared with those from nonoperated or sham‐operated controls. In these studies, conducted on animals receiving high and low dietary levels of ascorbic acid, the effect of vitamin C on these variables was also examined. Sulfated proteoglycan biosynthesis per unit of DNA as reflected by in vivo uptake of 35S‐sulfate was stimulated both by arthritic development and high dietary vitamin C. Under these conditions, the specific activities, 35S‐cpm/μg uronic acid, of the proteoglycans were elevated. Neither arthritic development nor variation in dietary levels of vitamin C altered the structure of the proteoglycans. Two species of proteoglycans that exhibited the same electrophoretic mobilities in agarose/acrylamide gels, the same elution profiles on high performance liquid chromatography, and the same galactosamine/glucosamine ratios were found in all normal and osteoarthritic cartilage specimens tested. The specific activities of these two species were dissimilar. In all samples, the larger of the two species had a higher specific activity.
An Unusual Morphologic Evolution of Paget's Disease of Bone
Authors: Mallette Lawrence E.
Published: February 2007

A patient with early Paget's disease of bone was treated for 12 months with calcitonin and 10 months with etidronate. During this time the cortex of each diseased bone showed a progressive 2‐ to 3‐fold increase in thickness. Lytic areas regressed and the new bone appeared radiographically very compact. No bowing deformity developed in 3 years of observation. This form of morphologic evolution differs markedly from those previously reported during treatment. For this patient, treatment was instituted very early during the course of the disease and moderately high doses of vitamin D were given during part of the treatment course. Observation of a larger number of patients will be needed to determine whether these factors actually modified the treatment outcome.
Pyrophosphate arthropathy in two swedish families
Authors: Bjelle Anders , Edvinsson Ulla , Hagstam ÅSa
Published: February 2007

A clinical and radiographic survey of 110 members of 2 families with hereditary pyrophosphate arthropathy was performed. The mode of inheritance was autosomal, dominant with a variable penetrance. Twenty‐two percent of the family members had joint involvement related to pyrophosphate arthropathy, 47% of those over 50 years of age had experienced acute attacks of arthritis and/or had joint calcifications. The majority of individuals with both arthritis and joint calcifications suffered from chronic pain that resulted in early retirement. A high frequency of back pain was observed, but no ankylosis or deformity. Surgery was performed for parathyroid hyperplasia on the propositus in 1 family, and several members of her family suffered from symptoms that suggested a disturbance of calcium phosphate metabolism. There were several differences between our patients and 50 cases of sporadic pyrophosphate arthropathy from the same area of Sweden. Familial cases had an earlier onset, a greater number of involved joints, and peripheral joint involvement more often. Back pain was more frequent, and calcifications of intervertebral discs were found only in the hereditary cases.
IgA nephropathy associated with seronegative spondylarthropathies
Authors: Charles Jennette J. , Ferguson Alfred L. , Moore Michael A. , Freeman Douglas G.
Published: February 2007

Three patients with a seronegative spondylarthropathy were found to have IgA nephropathy. Two patients had ankylosing spondylitis (one with psoriasis), and one had incomplete Reiter's syndrome. All three had a focal proliferative glomerulonephritis with IgA‐dominant mesangial immune deposits. One patient had a leukocytoclastic vasculitis. This association of IgA nephropathy with seronegative spondylarthropathies raises the possibility of a common or related pathogenesis. There is evidence to suggest that both diseases are mediated by genetically controlled immune responses to mucosal contact with etiologic antigens.
Differential patterns of in vitro IgM rheumatoid factor synthesis in seronegative and seropositive rheumatoid arthritis
Authors: Alarcón Graciela S. , Koopman William J. , Schrohenloher Ralph E.
Published: February 2007

The existence of a subpopulation of patients with rheumatoid arthritis (RA) who lack detectable rheumatoid factor (RF) is well documented. The cellular basis for nonexpression of RF in seronegative RA is not understood. In order to approach this problem, we compared mononuclear leukocytes (MNL) from 20 healthy adult controls, 20 seropositive RA and 22 seronegative RA patients to assess their capacity to synthesize IgM and IgM RF in vitro in the presence and absence of pokeweed mitogen (PWM). MNL from 10 of 20 seropositive RA patients spontaneously elaborated IgM RF (mean = 16.7 ng/106 cells), whereas this was not observed with MNL from either controls or seronegative patients. Small quantities of IgM were spontaneously released by MNL from the seropositive (68.1 ng/106 cells), seronegative (43.1 ng/106 cells), and control (142.3 ng/106 cells) groups. PWM induced IgM RF production by MNL from 10 of 20 controls (18.5 ng/106 cells) and 8 of 22 seronegative RA patients (13.5 ng/106 cells); however, this was significantly less than the production observed with seropositive RA MNL (13 of 20; 37.5 ng/106 cells). In contrast, IgM production in response to PWM was significantly less in both the seronegative (999.7 ng/106 cells) and seropositive RA groups (471.7 ng/106 cells) than in the control group (2,678 ng/106 cells). IgM RF constituted a significantly higher proportion of total IgM synthesized by seropositive RA MNL (10.7%) than either seronegative RA MNL (2.5%) or control MNL (1.2%). Differences in IgM RF production in vitro could not be explained by HLA—DR4 status. Hidden RF was not detected in seronegative MNL supernatants. The results indicate clear differences in the pattern of in vitro release of IgM and IgM RF by MNL from seronegative RA patients as compared to either seropositive RA MNL or control MNL. The similarity of seronegative RA MNL to control MNL with regard to in vitro expression of IgM RF suggests that regulatory mechanisms governing RF synthesis are relatively intact in patients who have seronegative RA.
Superoxide anion generation by human neutrophils exposed to monosodium urate. effect of protein adsorption and complement activation
Authors: Abramson Steven , Hoffstein Sylvia T. , Weissmann Gerald
Published: February 2007

We studied the capacities of naked and proteincoated monosodium urate (MSU) crystals to stimulate superoxide anion (O2\documentclass{article}\pagestyle{empty}\begin{document}$ \[\bar .\] $\end{document}) release by human polymorphonuclear leukocytes (PMN). Uncoated MSU stimulated significant O2\documentclass{article}\pagestyle{empty}\begin{document}$ \[\bar .\] $\end{document} production by cytochalasin B‐treated PMN. Precoating MSU with IgG caused an increase in mean O2\documentclass{article}\pagestyle{empty}\begin{document}$ \[\bar .\] $\end{document} production, whereas precoating heated MSU with serum or plasma inhibited O2\documentclass{article}\pagestyle{empty}\begin{document}$ \[\bar .\] $\end{document} release. Unheated MSU crystals, which activate complement to a greater extent than heated crystals, also provoked O2\documentclass{article}\pagestyle{empty}\begin{document}$ \[\bar .\] $\end{document} generation, an effect again abrogated by precoating with serum but not with plasma. Coincubation of unheated MSU and plasma resulted in an enhancement of O2\documentclass{article}\pagestyle{empty}\begin{document}$ \[\bar .\] $\end{document} generation. The results of these experiments support the hypothesis that adsorbed proteins modulate the phlogistic potential of MSU and that the surface activation of humoral mediators contributes to the local inflammatory response.
Rheumatoid factor inhibition of in vitro binding of IgG complexes in the human glomerulus
Authors: Bolton W. Kline , Schrock Jon H. , Davis John S.
Published: February 2007

We studied the effects of rheumatoid factor (RF) on binding of immune complexes to activated C3 (C3b) receptors in vitro. IgM fraction of serum containing RF activity (IgM‐RF), IgM isolated from pooled normal human serum and having no RF activity (IgM‐control), bovine serum albumin, and Veronal buffered saline solutions were used in a C3b assay system consisting of aggregated human IgG (AggHuIgG) coupled to sheep erythrocytes (SRBC) with guinea pig and normal human serum complement. The number of glomerular bound AggHuIgG‐SRBC with IgM‐control and bovine serum albumin or Veronal buffered saline was similar, while the number of bound cells with IgM‐RF was reduced significantly. This effect was seen with both guinea pig and normal human serum complements. Supernatant hemolytic complement activity was maintained with IgM‐RF, but reduced with control solutions. The blocking factor was shown to be RF by serial dilutions of IgM‐RF resulting in inverse correlations with latex flocculation and inhibition of SRBC binding, absorption of blocking from IgM‐RF with insolubilized AggHuIgG, and failure of IgM‐control to block binding. IgM‐RF did not directly interfere with activation of complement, but blocked attachment of C3 to AggHuIgG and formation of C3b capable of reacting with glomerular receptors. These results showed that IgM‐RF can inhibit binding of AggHuIgG complexes to human glomeruli. This in vitro phenomenon may represent a possible protective mechanism of RF in vivo in diseases with immune complexes.
Histone antibodies in systemic lupus erythematosus. A possible diagnostic tool
Authors: Gioud M. , Kaci M. Ait , Monier J. C.
Published: February 2007

Antibodies to total histones and histone fractions H1, H2a‐H4, H2b, and H3 were measured in serum samples from 61 patients with systemic lupus erythematosus (SLE), 33 with rheumatoid arthritis, 17 with systemic sclerosis, and 20 with various other diseases by use of a sensitive immunoenzymatic assay. Histone antibodies were present in 52.4% of the SLE samples whereas only 1 of the samples from other diseases was positive (systemic sclerosis). The presence of these antibodies in SLE patients was not associated with any specific clinical manifestations, but was correlated with activity of the disease: 87% (20 of 23) of patients with active SLE, in particular 9 of 9 not yet treated, showed histone antibody whereas only 18% (4 of 22) of samples from patients with inactive SLE were positive. We believe that the measurement of histone antibodies would be a useful addition to the present laboratory parameters (antinuclear and double‐stranded DNA antibodies and circulating immune complexes) for the diagnosis and progression of systemic lupus erythematosus, particularly since they seem to appear during or just before the onset of an active phase and tend to be absent during remission.
Natural killer augmentation in systemic lupus erythematosus via a soluble mediator derived from human lymphocytes
Authors: Kaufman Donald B.
Published: February 2007

Seventeen patients with diagnosed systemic lupus erythematosus were studied for natural killer activity and the ability of a human soluble immune‐response factor to modify this activity. Defective natural killer activity was found in patients with systemic lupus erythematosus regardless of the stage of disease, medication, or organ system involvement (24.6% versus 47.8% cytotoxicity). After treatment with the immune‐response factor, the natural killer activity increased in all patients, with a mean of 47.3% compared with 24.6% before treatment. This product has other immunologic activities and was shown to be free of interferon. The mechanism of action is not yet known, but such an immune‐response factor has potential use in the treatment of systemic lupus erythematosus.
Chronic arthritis of rabbits induced by mycoplasmas. III. Induction with nonviable mycoplasma arthritidis antigens
Authors: Washburn Leigh Rice , Cole Barry C. , Ward John R.
Published: February 2007

Preexposure of rabbits to Mycoplasma arthritidis predisposed them to subsequent development of chronic inflammation in knee joints challenged with nonviable M arthritidis antigens. Rabbits sensitized by hyperimmunization developed a more severe arthritis than those sensitized by infection. Unsensitized rabbits responded minimally to intraarticular injection of nonviable organisms. These results suggested that an immune response to a persisting mycoplasmal antigen might be capable of sustaining chronic inflammation in rabbits with arthritis induced by viable M arthritidis.
Frequencies of epstein‐barr virus—inducible IgM anti‐IgG B lymphocytes in normal children and children with juvenile rheumatoid arthritis
Authors: Fong Sherman , Miller John J. , Moore Terry L. , Tsoukas Constantine D. , Vaughan John H. , Carson Dennis A.
Published: February 2007

The relative frequencies of IgM antilgG autoantibody (rheumatoid factor) producing cells induced by the polyclonal B cell activator Epstein‐Barr virus were measured in peripheral blood lymphocyte cultures of normal children and patients with juvenile rheumatoid arthritis. The frequencies of rheumatoid factor precursor B cells in normal children were lower than adults, but higher than neonates. The frequency increased with the age of the donor. In seronegative children with the systemic‐onset or pauclarticular‐onset types of juvenile rheumatoid arthritis, the number of IgM antiIgG inducible B cells was not significantly different (P>0.05) from age‐matched controls. Patients with seropositive juvenile rheumatoid arthritis or seropositive adult rheumatoid arthritis had significantly higher IgM antiIgG precursor cell frequencies than age‐matched normal subjects (P<0.01 and P<0.02, respectively). In contrast, the patients with seronegative polyarticular‐onset juvenile rheumatoid arthritis had an average precursor frequency significantly lower than normal age‐matched controls (P<0.05), analogous to results previously noted in adult seronegative rheumatoid arthritis. Thus, both children and adults with seronegative polyarticular rheumatoid arthritis had a deficiency in B cells that produce IgM antiIgG and that are induced by Epstein‐Barr virus. This distinguished them from seropositive juvenile rheumatoid arthritis and rheumatoid arthritis patients, normal subjects, and patients with the pauciarticular‐onset and systemic‐onset types of seronegative juvenile rheumatoid arthritis.
Factors influencing articular cartilage wear in vitro
Authors: Radin Eric L. , Swann David A. , Paul Igor L. , Mcgrath Paul J.
Published: February 2007

The in vitro wear of articular cartilage in oscillating and impulsively loaded bovine metatarsophalangeal joints was studied. Articular cartilage scarification had little effect on cartilage wear, but stiffening of the subchondral bone with methyl methacrylate greatly increased the rate of cartilage loss, whether or not it had previously been scarified. Glutaraldehyde treatment of articular cartilage for 30 minutes decreased its wear rate. Guanidinium chloride extraction of the cartilage before wear testing caused it to peel off its subchondral bed. This effect could be spared by prior glutaraldehyde fixation.
Induction of human rheumatoid factor producing cells by aggregated igg
Authors: Pisko Edward J. , Turner Robert A. , Foster Susan L.
Published: February 2007

Normal human peripheral blood mononuclear leukocytes were induced to become cells that secrete rheumatoid factor after culture with aggregated IgG, but not monomeric IgG. A plaque‐forming cell assay was used to detect cells that secrete antibodies to IgG. Anti‐haptenated–sheep red cell plaque‐forming cells were also induced by aggregated IgG, suggesting that aggregated IgG may have induced plaque‐forming cells polyclonally. Polyclonal stimulation of mononuclear leukocytes by aggregated IgG may be a mechanism for the in vivo stimulation of cells that produce rheumatoid factor.
Ultrastructure of the esophagus in scleroderma
Authors: Russell M. Lynn , Friesen Dianne , Henderson R. D. , Hanna Wedad M.
Published: February 2007

The ultrastructure of the esophageal wall in progressive systemic sclerosis (scleroderma) was studied in 7 patients and compared with other esophageal diseases. In scleroderma, fibrosis and capillary basement membrane changes were the most characteristic abnormalities. Muscle fibers of patients with scleroderma showed thickened dense bodies and plaques and increased cell organelles in comparison with other disease groups, while neural structures were normal. Our data supported a primary vascular cause, rather than a neurogenic or myopathic process, for esophageal dysfunction in scleroderma.
Experimental hydroxyapatite synovial and articular cartilage calcification. light and electron microscopic studies
Authors: Reginato Antonio J. , Schumacher H. Ralph , Brighton Carl T.
Published: February 2007

Intraarticular calciphylaxis with cartilage and synovial calcification was produced in rabbits by oral administration of a single dose of dehydrotachysterol followed by an intraarticular injection of ferrous chloride. Synovial membrane apatite deposits were seen in the interstitium, on collagen fibers, and within cell vacuoles. In contrast, long‐term administration of dehydrotachysterol alone induced only articular cartilage calcification. Such calcification was limited to the mid and deep zone of cartilage. Most calcium deposits were apatite‐like crystals. Acute crystal‐associated inflammation was not demonstrated in these specimens with crystals sequestered in synovial or cartilage tissue. Further studies on these models will examine the relation of apatite to joint disease.
Aspirin aggravates the degeneration of canine joint cartilage caused by immobilization
Authors: Palmoski Marshall J. , Brandt Kenneth D.
Published: February 2007

The effect of aspirin on the degeneration of knee cartilage caused by immobilization was examined. If dogs were fed aspirin daily (serum salicylate = 20–25 mg/dl) for 6 weeks while one hind limb was immobilized in a cast, the decreases in uronic acid content and net proteoglycan synthesis in cartilage from the immobilized knee were significantly greater than the decreases in cartilage from immobilized knees of dogs that had not received aspirin (P<0.01). Furthermore, neither aspirin administration nor immobilization alone affected the extractability of proteoglycans from the cartilage. However, in organ cultures of cartilage from the immobilized knee of dogs fed aspirin, the proportion of the total 35S‐proteoglycans present in the culture medium was nearly twice that from cultures of cartilage of the contralateral knee. Also, more than twice as many of the total tissue proteoglycans (uronic acid) were extractable with 0.4M guanidinium chloride, a nondissociating solvent (P<0.01). Regardless of whether the dogs received aspirin, the in vitro interaction of proteoglycans with hyaluronic acid from cartilage of the immobilized knee was diminished, apparently due to an abnormality in the hyaluronate‐binding region of the core protein. Although these results indicate that aspirin had an adverse effect in vivo on articular cartilage of immobilized joints, aspirin administration did not preclude reversal of all of the above changes if the dog was allowed to walk about in a pen for 3 weeks after cast removal. If, however, the dog was run daily on a treadmill for 3 weeks after cast removal, the decrease in uronic acid content in cartilage from the immobilized knee persisted and was more profound if the animal had received aspirin than if it had not (P<0.01).
Digital sclerosis in children with insulin‐dependent diabetes mellitus
Authors: Seibold James R.
Published: February 2007

Palpable thickening and induration of the skin of the fingers were found in 47 (34%) of 137 children with insulin‐dependent diabetes mellitus and in none of 52 normal children. Mild flexion contractures of the interphalangeal joints were seen in 26 (19%), mainly in those children with more extensive and severe skin changes. Such contractures have been linked to microvascular complications of diabetes. The clinical and pathogenic similarities to progressive systemic sclerosis make the digital sclerosis of childhood diabetes a promising model for further rheumatologic study.
Circadian variations of serum myoglobin levels in normal subjects and patients with polymyositis
Authors: Bombardieri Stefano , Clerico Aldo , Riente Lucrezia , Chicca Maria Grazia Del , Vitali Claudio
Published: February 2007

Circadian variations in myoglobin levels were determined in 18 normal volunteers and in 10 patients with active polymyositis. In all the controls and in 9 of the 10 patients, serum myoglobin concentrations were highest at 9 AM, fell significantly during the day to reach a nadir between 6 and 12 PM, remained constant until midnight, and then rose again at 3 AM. The percent differences between the highest and lowest values ranged from 21–66%. This pattern was observed in both untreated patients and patients receiving 6‐methyl‐prednisolone, which was given either in a single dose at 8 AM or in divided doses (8 AM and 8 PM). These data demonstrate that the time of sample collection must be taken into account when myoglobin levels are used as a marker of muscle damage.
Circulating dna in polyarteritis nodosa and related syndromes
Authors: Steinman Charles R.
Published: February 2007

Patients with systemic lupus erythematosus (SLE) were previously reported to have a high prevalence of circulating DNA in association with systemic vasculitis. The present study was designed to determine whether circulating DNA also characterizes forms of systemic arterial inflammation other than those associated with SLE. A specific counterimmunoelectrophoresis assay capable of detecting 20–50 ng/ml of doublestranded DNA (dsDNA) in plasma was used. Of a total of 16 patients studied, 15 (94%) had circulating DNA. Similarly, 89% of the 47 plasmas from vasculitis patients contained DNA. In each of the 3 control groups, which consisted of normal individuals, patients with nonvasculitic systemic inflammation, and patients receiving high dose corticosteroid and/or cytostatic agents, no more than 8% had plasma DNA. This difference was significant with P < 0.001. Relevance of this observation to etiologic, pathogenetic, and clinical considerations in the systemic arteritides is discussed. It is suggested that clinical detection of circulating plasma DNA may be useful for the diagnosis and management of systemic polyarteritis nodosa and related syndromes.
Effects of gold compounds on the function of phagocytic cells
Authors: Davis Paul , Johnston Carol , Miller Cindy L. , Wong Ken
Published: February 2007

The effect of sodium aurothiomalate and triethyl‐phosphine gold on the generation of superoxide radicals by chemotactic tripeptide‐activated polymorphonuclear leukocytes has been investigated using a cytochrome C reduction technique. Neither gold compound inhibited the binding of the tripeptide to cells. Sodium aurothiomalate in concentrations ranging from 1 to 100 μg/ml produced mild, nonsignificant inhibition of the generation of superoxide radicals. In contrast, triethylphosphine gold at a concentration of 0.25 μg/ml was associated with a mild enhancement of superoxide radical production, but the enhancement was not statistically significant. At concentrations of 1.25 μg/ml and above, there was a profound inhibition of superoxide radical production by these activated cells. Since the products of the respiratory burst, including superoxide, are thought to be inflammatory mediators, it is postulated that the inhibition of superoxide radical generation by gold compounds may be another mechanism by which the compounds modulate their antiinflammatory effects in patients with rheumatoid disease.
Diet therapy for rheumatoid arthritis
Authors: Panush Richard S. , Carter Randy L. , Katz Paul , Kowsari Badri , Longley Selden , Finnie Sheryl
Published: February 2007

Although diet therapy for arthritis has received considerable publicity, there is little objective information about its efficacy. We undertook a 10‐week, controlled, double‐blind, randomized trial of patients with active rheumatoid arthritis (RA). Twenty‐six patients completed the study; 11 were on an experimental diet (a specific popular diet free of additives, preservatives, fruit, red meat, herbs, and dairy products) and 15 were on a ‘placebo’ diet. Of 183 variables analyzed, there were no clinically important differences among rheumatologic, laboratory, immunologic, radiologic, or nutritional findings between patients on experimental and placebo diets. Six RA patients on the placebo and 5 on the experimental diet improved by objective criteria. Improvement averaged 29% for patients on placebo and 32% for patients on experimental diets. Two patients on the experimental diet improved notably, elected to remain on the experimental diet following the study period, have continued to improve, and noted exacerbations of disease upon consuming nonexperimental diet foods. Our study failed to provide evidence of objective overaii clinical benefit of this diet as followed by a group of patients with longstanding, progressive, active RA. However, our data are not inconsistent with the possibility that individualized dietary manipulations might be beneficial for selected patients with rheumatic disease.
Fibrin and fibronectin in rheumatoid synovial membrane and rheumatoid synovial fluid
Authors: Clemmensen Inge , Hølund BERIT , Andersen Rasmus Bach
Published: February 2007

Normal synovial membranes and synovial membranes from patients with classic rheumatoid arthritis were investigated for the presence of fibrin and fibronectin by an indirect immunoperoxidase technique. In normal synovial membranes, fibronectin was found around the monolayer of the synovial lining cells. Staining was most intense on the surface and beneath the lining cells, but not detectable in the cytoplasm. Fibronectin was also found in the cytoplasm of the endothelial cells. No staining for fibrin was found in the normal synovial membrane. In synovial membranes from patients with rheumatoid arthritis, large amounts of fibronectin were found around the multilayer of synovial lining cells, in the cytoplasm of the endothelial cells, and in argyrophilic fiber‐rich connective tissue. In superficial areas denuded of synovial lining cells, high amounts of fibronectin were found incorporated in fibrin. In some areas with noninjured synovial lining cells, fibrin was also found, but in this case no fibronectin was incorporated. No fibronectin was found in connective tissue in areas with infiltration of inflammatory cells. After treatment of normal and rheumatoid synovial membranes with hyaluronidase, fibronectin was still present around the lining cells but the staining was found to be more distinct. This study relates the presence of fibrin and fibronectin in the rheumatoid synovial membrane to the high amount of these proteins, recently described, in rheumatoid synovial fluid. It also suggests that fibronectin present in the synovial membrane is produced and secreted by the endothelial cells.
Reactivity of serum antibodies to the keratin layer of rat esophagus in patients with rheumatoid arthritis
Authors: Quismorio Francisco P. , Kaufman Ronald L. , Beardmore Thomas , Mongan Edward S.
Published: February 2007

Serum antibodies reactive with the keratin layer of rat esophagus (AKA) were found in 46 of 80 (57.5%) rheumatoid arthritis (RA) patients. In contrast, AKA were present in only 7 of 82 (9.5%) patients with other types of rheumatic disorders and in 2 of 47 (4.2%) healthy subjects. AKA were not specific for RA, however, because in the former group, AKA were present in 4 of 20 (20%) systemic sclerosis patients and in 3 of 12 (25%) ankylosing spondylitis patients. AKA belong predominantly to the IgG class and are complement fixing. Although found in some RA joint fluids, AKA were not selectively concentrated in the joint fluid. Absorption of RA serum with type I human collagen or with human epidermal keratin did not remove AKA activity. The frequency of AKA in RA patients both negative and positive for DR4 was equal. There was no relationship between the frequency of AKA and the occurrence of other serum autoantibodies such as antibodies to intermediate filaments, smooth muscle, and nuclear antigens. Serum antibody reactive with human stratum corneum found in patients with psoriatic arthritis was shown to be different from AKA. Rabbit antiserum to human keratin did not inhibit the reaction of AKA against the keratin layer of rat esophagus. Autoimmunity to structural proteins including collagen, vimentin intermediate filaments, smooth muscle antigens, and keratin is a characteristic feature of RA.
Low‐Dose D‐Penicillamine Therapy in Rheumatoid Arthritis
Authors: Williams H. James , Ward John R. , Reading James C. , Egger Marlene J. , Grandone John T. , Samuelson Cecil O. , Furst Daniel E. , Sullivan James M. , Watson Margaret A. , Guttadauria Maria , Cathcart Edgar S. , Kaplan Stanley B. , Halla James T. , Weinstein Arthur , Plotz Paul H.
Published: February 2007

Two hundred twenty‐five patients with active severe rheumatoid arthritis were admitted to a multiclinic, controlled, double‐blind trial comparing the use of 500 mg D‐penicillamine per day, 125 mg D‐penicillamine per day, and placebo. One hundred seventy‐one patients completed at least 30 weeks of therapy. The 500 mg D‐penicillamine group demonstrated statistically significant improvement over the placebo group in grip strength, average circumference of swollen proximal interphalangeal joints, and patient assessment. While the trend was for greater improvement with the larger dose of D‐penicillamine, there was no statistically significant difference among the 3 groups in duration of morning stiffness, walking time, physician's assessment, number of swollen joints, or scores for tender and swollen joints. The slight increase in efficacy of higher dose D‐penicillamine was associated with increased toxicity.
A Search for Rheumatoid Arthritis‐Associated Nuclear Antigen And Epstein‐Barr Virus Specific Antigens or Genomes in Tissues and Cells from Patients with Rheumatoid Arthritis
Authors: Alspaugh Margaret A. , Shoji Hiromu , Nonoyama Meihan
Published: February 2007

Pannus extracts and/or cells and tissues from rheumatoid arthritis (RA) patients and controls were tested for the presence of RA‐associated nuclear antigen (RANA), anti‐RANA, Epstein‐Barr virus (EBV)‐specific antigens, and EBV genomes. Using our present rather insensitive methods, RANA was rarely detected in RA pannus extracts or tissues, whereas anti‐RANA was commonly found. EBV‐specific antigens or genomes could not be detected in a limited number of tissues tested using our present methods. The data suggest that EBV may not be the primary event causing RA through direct infection and transformation of synovial tissues.
Plasma Protein Binding by Monosodium Urate Crystals
Authors: Terkeltaub Robert , Tenner Andrea J. , Kozin Franklin , Ginsberg Mark H.
Published: February 2007

Using 2‐dimensional O'Farrell gel electrophoresis, we have mapped the proteins from undiluted plasma and serum which bind to monosodium urate (MSU) crystals. More than 30 crystal‐associated polypeptides were visualized, including anionic and cationic species. Proteins increased on the crystals relative to plasma included C1q, C1r, C1s, fibronectin, fibrinogen, and kininogen. Crystal‐bound polypeptides derived from IgG, albumin, and transferrin were recovered in decreased amounts relative to plasma. Direct evidence for activation of the complement and coagulation systems in plasma was provided by the identification of crystal‐associated activation fragments of C1 and kininogen. Plasmas deficient in selected proteins (e.g., C1q and IgG) were used to define the role of these proteins in such activation events and confirmed activation of C1 in immunoglobulin‐deficient plasma by MSU crystals. In summary, we have described a high resolution, semi‐quantitative approach to analyze protein binding to crystals, have documented the complexity of crystal‐plasma protein interaction, and have provided direct evidence for the binding of coagulation system proteins and binding and activation of complement by MSU crystals, in whole plasma and IgG‐deficient plasma.
Antibodies to SM and RNP
Authors: Munves Ellen Field , Schur Peter H.
Published: February 2007

The charts of 150 consecutive patients found to have antibodies to Sm, ribonucleoprotein (RNP), or both were examined to determine these antibodies' possible associations with certain clinical conditions as well as their diagnostic specificities. Patients with anti‐Sm were more likely to have renal disease and antibodies to double‐stranded DNA, single‐stranded DNA, and nuclear protein than were patients with anti‐RNP. No clinical associations were found for anti‐RNP. Although most of the patients with antibodies to Sm, RNP, or both had systemic lupus erythematosus, some had other diagnoses, including cutaneous lupus, drug‐induced lupus, rheumatoid arthritis, juvenile arthritis, mixed connective tissue disease, Raynaud's disease, progressive systemic sclerosis, miscellaneous rheumatic and non‐rheumatic diseases, and undifferentiated connective tissue disease syndromes. These findings suggest that these antibodies may be associated with some diseases, but are not disease‐specific.
Penetration and effect of topically applied dimethylsulfoxide or indomethacin on adjuvant arthritis in the rat
Authors: Francis Marion D. , Horn Patricia A. , Mccreary Lionel D.
Published: February 2007

The present study, using 14C‐DMSO, established the systemic and local load and distribution of topically applied DMSO in adjuvant arthritic rats. Under equivalent conditions, the antiinflammatory effects (systemic and local) of topical DMSO treatments were compared with a topical treatment of a control vehicle or of indomethacin, a known effective antiinflammatory agent. No significant systemic or local antiinflammatory effect of topical DMSO was seen in the adjuvant arthritic rats. Indomethacin, applied topically, had a significant systemic antiinflammatory effect; however, no significant local antiinflammatory effect of indomethacin was observed.
Characterization of latent and active forms of cartilage proteinases produced by normal immature rabbit articular cartilage in tissue culture
Authors: Cartwright Elizabeth C. , Campbell Ian K. , Britz Margaret L. , Sandy John D. , Lowther Dennis A.
Published: February 2007

Cultured tissue slices from normal immature rabbit articular cartilage released latent neutral metal‐loproteinases into serum‐free medium. On activation with 4‐aminophenylmercuric acetate, these metalloproteinases could degrade collagen, proteoglycan, and gelatin. Also produced were an acid proteinase with the properties of cathepsin D and an inhibitor of the neutral metalloproteinases. The appearance of both the proteinases and the inhibitor in the culture medium could be prevented by incubation of cultures with cycloheximide. The active and latent forms of the proteinases were characterized using Ultrogel AcA 54 chromatography.
HLA‐B27 haplotypes in family studies of ankylosing spondylitis
Authors: Lochead John A. , Chalmers Ian M. , Marshall William H. , Larsen Bodil , Skanes Verna M. , Payne Ronald H. , Barnard John M.
Published: February 2007

Although HLA‐B27 carries a high relative risk for development of ankylosing spondylitis (AS), most B27 positive individuals do not have spondylitis. One interpretation of this observation is that there may be 2 types of B27, 1 which carries the risk factor and 1 which does not. If this were the case, then with the help of markers closely linked to HLA‐B, it might be possible to detect differences between the B27 haplotypes in AS patients and those in healthy probands. We studied 197 members of 18 families with known AS and 110 members of 19 families in which HLA‐B27 was present without any known inflammatory spinal disease. HLA antigens A, B, and C and alleles of complement components C2, C4, and Factor B and glyoxalase‐1 were determined in all cases. Detailed haplotypes were assigned and their associations with development of the disease were examined. We were unable to identify any distinct HLA‐B27 haplotype associated with AS; 2 common haplotypes and several miscellaneous ones were found in both groups. Thinking that the development of AS might be influenced by the other, non‐B27 haplotype, we analyzed this and found that there was no detectable influence. The data do not contradict the notion that B27 in whites is a single entity and is itself the susceptibility factor predisposing to the development of ankylosing spondylitis.
The epidemiology of juvenile arthritis in rochester, minnesota 1960–1979
Authors: Towner Ba Steven R. , , Michet Clement J. , M. O'Fallon William , Nelson Audrey M.
Published: February 2007

A 20–year community‐based study of the epidemiology of juvenile arthritis in Rochester, Minnesota from January 1, 1960 to January 1, 1980 is described. Cases were identified using the 1977 revised American Rheumatism Association criteria for juvenile arthritis. Higher incidence and prevalence rates and a greater predominance of pauciarticular disease were observed than previously reported. Lower rates were observed when a minimum of 3 months' disease duration was used to identify incidence.
Crystal populations in human synovial fluid. Identification of Apatite, Octacalcium Phosphate, and Tricalcium Phosphate
Authors: Mccarty Daniel J. , Lehr James R. , Halverson Paul B.
Published: February 2007

Defatted joint fluid pellets from 4 patients with the “Milwaukee shoulder” syndrome, an aspirate of milky fluid from subcutaneous tissue of a girl with dermatomyositis/calcinosis, and 2 rabbit synovial membranes calcified by calciphylaxis were studied by Fourier transform infrared analysis. This method permits sequential electronic subtraction (“stripping”) of known patterns of highly characterized reference compounds from an unknown sample pattern. Collagen and hydroxyapatite, with carbonate partially (1–3%) substituted for phosphate, and to a lesser extent hydroxyl, were found in all samples. Octacalcium phosphate (OCP) was found in all samples except that from a patient with synovial chondromatosis which contained tricalcium phosphate (TCP). Sulfate was found in 2 of the shoulder joint fluid specimens. An unidentified organic phase was present in all samples. This study confirms recent observations by others that pathologic calcifications contain several mineral phases. These data raise the possibility that hydroxyapatite nucleation may be controlled by hydrolytic alteration of precursor calcium phosphate phases such as OCP or TCP. Studies of the biologic effects of synthetic calcium phosphate crystals must take into account the existence of several crystalline phases in natural pathologic calcifications.
Aspirin causes in vivo synthesis of type i collagen by atrophic articular cartilage
Authors: Gay Renate E. , Palmoski Marshall J. , Brandt Kenneth D. , Gay Steffen
Published: February 2007

We have previously shown that aspirin, when fed to dogs daily for 6 weeks in amounts sufficient to maintain serum levels at 20–25 mg/dl, worsens the degeneration of knee cartilage caused by immobilization of the limb in a cast. Thus, there is a greater decrease in proteoglycan content and synthesis and an increase in proteoglycan extractability in cartilage from immobilized limbs of dogs fed aspirin, compared with dogs not fed aspirin. The present study was designed to examine whether phenotypic changes in cartilage collagen also occur under these conditions. Cartilage samples from the immobilized and contralateral control limbs of 3 dogs killed after 6 weeks of casting showed no reaction with specific fluorescein‐labeled rabbit antibody to human type I collagen. However, if dogs were fed aspirin during the casting period, cartilage from immobilized limbs showed marked staining of the chondrocytes with antibody to type I collagen and weak fluorescence of the interterritorial matrix. In 4 dogs the cast was removed after 6 weeks: 2 were allowed to ambulate in a pen for 3 weeks and 2 were subjected to treadmill running for 3 weeks after cast removal. The animals were maintained on aspirin for the entire 9 weeks. In all 4 dogs, cartilage from the previously immobilized limbs showed marked fluorescence for type I collagen. Cartilage from the non‐immobilized knees, regardless of whether the dog received aspirin, did not react with the antibody, showing that the presence of type I collagen was not due to aspirin feeding alone.
Type ii collagen‐induced arthritis. A Morphologic and Biochemical Study of Articular Cartilage
Authors: Desimone Daniel P. , Parsons Diane B. , Johnson Kurt E. , Jacobs Robert P.
Published: February 2007

Articular cartilage was obtained from type II collagen‐induced arthritic rat joints. Transmission electron microscopy showed a gradual degeneration of chondrocytes, disorganization of the collagenous extracellular matrix, and formation of microscars. Biochemical analyses indicated that type II collagen was the only collagen present and that it was normal in regard to hydroxylation of lysine and glycosylation of hydroxylysine. Analyses of the proteoglycan in the extracellular matrix revealed a 50% loss of chondroitin sulfate and keratan sulfate.
Probable depiction of juvenile arthritis by sandro botticelli
Authors: Alarcön‐Segovia Donato , Laffön Armando , Alcocer‐Varela Jorge
Published: February 2007

There is a question whether rheumatoid arthritis is a disease of recent or ancient onset since it was only first described in 1800. In support of its earlier appearance are depictions of rheumatoid hands in Flemish paintings of the fifteenth through eighteenth centuries. The first description of juvenile arthritis is attributed to Cornil in 1864, making the question of its antiquity also pertinent. We show here that the “Portrait of a Youth,” painted in 1483 by the Florentine artist Sandro Botticelli, has features of rheumatoid arthritis in the hand of the subject, who would be young enough to be considered as having juvenile arthritis. A review of all of Botticelli's paintings revealed that these changes could not be attributed to stylistic traits. Neither could they be attributed to lack of technique, for he has been considered a superb artist. If the “Portrait of a Youth” does indeed represent juvenile arthritis, it would mean that this disease is older than its initial description would indicate.
Phenotypic characterization of cells within subcutaneous rheumatoid nodules
Authors: Hedfors Eva , Klareskog Lars , Lindblad Staffan , Forsum Urban , Lindahl Göran
Published: February 2007

An immunohistochemical double‐staining technique was applied to frozen sections of biopsies from subcutaneous rheumatoid nodules. Material within the central necrosis reacted with anti‐immunoglobulin and anti‐HLA‐DR antibodies. Cells within the palisading layer were “macrophage‐like,” as indicated by staining for anti‐HLA‐DR and OKM1, and showed a high proliferative activity as seen by OKT9 reactivity. The granulation zone contained many (αLeu‐1+) T cells in close contact with HLA‐DR‐expressing non‐T cells.
Changes in vascular endothelium related to lymphocyte collections in diseased synovia
Authors: Freemont Anthony J. , Jones Carolyn J. P. , Bromley Michael , Andrews Paul
Published: February 2007

A population of small blood vessels are described in the synovia of patients with a number of different arthropathies. These vessels are identical to the high endothelial venules (HEV) of lymph node paracortex, known to be the site of lymphocyte diapedesis from blood to tissues. The significance of this finding and its possible role in the pathogenesis of inflammatory arthritides are discussed.
The pathogenesis of group a streptococcal cell wall‐induced polyarthritis in the rat comparative studies in arthritis resistant and susceptible inbred rat strains
Authors: Wilder Ronald L. , Allen Janice B. , Wahl Larry M. , Calandra Gary B. , Wahl Sharon M.
Published: February 2007

This report addresses the host mechanisms which regulate susceptibility and resistance to group A streptococcal cell wall‐induced polyarthritis in the rat. We have compared cell wall tissue distribution and persistence following a single intraperitoneal injection of an aqueous suspension of the cell walls into arthritis susceptible LEW/N and resistant F344/N female rats. Selected aspects of the induced inflammatory reaction were also compared. Our results suggest that development of chronic erosive polyarthritis in this model is dependent, in variable degrees, upon 1) deposition and persistence of the cell walls in synovial tissues, and 2) a relative inability of arthritis susceptible rats to neutralize the proinflammatory properties of the cell walls.
Prealbumin and retinol binding protein serum concentrations in the indiana type hereditary amyloidosis
Authors: Benson Merrill D. , Dwulet Francis E.
Published: February 2007

Serum prealbumin and retinol binding protein (RBP) concentrations were determined for 68 members of a kindred in Indiana with a familial type of systemic amyloidosis. Immunohistochemical studies on rectal and muscle biopsy material from individuals with this type of amyloidosis revealed staining of amyloid deposits with anti‐prealbumin. Both the serum prealbumin and RBP concentrations were significantly depressed in 9 patients with amyloidosis when compared with normal controls and unaffected kin. In addition, the mean RBP serum concentration of 21 offspring of the patients with amyloidosis was significantly depressed. A more significant finding was that on the basis of the serum RBP concentrations, the offspring could be divided into 2 distinct groups. One group represented approximately 50% of the children and had serum prealbumin and RBP concentrations not significantly different from their afflicted parents. The second group had serum prealbumin and RBP concentrations not significantly different from those of normal controls and non‐affected kin. These findings show that prealbumin and RBP serum concentrations are depressed in patients with the Indiana type of hereditary amyloidosis and that these serum abnormalities may be present long before development of clinical disease. They suggest that individuals with this genetic abnormality may be identified prior to clinical expression of the disease.