bluuebunny/crossref_metadata_2025 huggingface dataset:
Deposition of antibodies to a soluble cytoplasmic antigen in the kidneys of patients with systemic lupus erythematosus
Authors: Maddison Peter J. , Reichlin Morris
Published: February 2007

Two patients with systemic lupus erythematosus were studied whose sera contained precipitating anti‐bodies to a soluble cytoplasmic antigen, termed Ro. A reduction in the amount of these antibodies in each case was accompanied by a deterioration in the clinical status with the development of nephritis leading to death. Acid elution of gamma globulin was performed from homogenates of the renal cortex, and in both instances antibodies to Ro were demonstrated in the eluates by double immunodiffusion. The titer of these antibodies was measured in both sera and eluates, and specific enrichment of anti‐Ro in the eluates was demonstrated in both patients. This strongly suggests the direct participation of Ro‐anti‐Ro immune complexes in the progressive renal disease and may underlie the association seen here between the decreasing serum titers of antibodies to Ro and the clinical deterioration in these two cases.
Glycosaminoglycan synthesis and glucose uptake by rheumatoid and nonrheumatoid fibroblastic cells in culture
Authors: Anastassiades Tassos P. , Ley Janice , Wood Anne
Published: February 2007

Glycosaminoglycan (GAG) synthesis and glucose uptake by rheumatoid (R) and nonrheumatoid (NR) synovial cells were studied at the second subculture during four different sets of nutritional conditions and at sequential, defined intervals of the growth cycle. Synovial fibroblastic cells in monolayer cultures secrete both hyaluronic acid and sulfated GAGs in a ratio of about 8:1. With increasing cell density the ability to sulfate GAGs appears to decrease. No significant differences in GAG synthesis between rheumatoid and nonrheumatoid lines on a per cell basis could be detected during any interval in the growth cycle. Similarly, no significant differences of glucose uptake per cell could be demonstrated between rheumatoid and nonrheumatoid lines under the various protocols applied throughout the growth cycle. The most important factor determining glucose uptake per cell is the availability of glucose in the medium which is in turn closely correlated with cell number.
Platelet aggregation and aggregation inhibition by different antiglobulins and antiglobulin complexes from sera of patients with rheumatoid arthritis
Authors: Fink P. C. , Piening U. , Fricke M. , Deicher H.
Published: February 2007

Antiglobulin complexes were isolated from rheumatoid arthritis (RA) sera in order to investigate their ability to aggregate human platelets and to influence platelet aggregation induced by heat‐aggregated IgG. Eleven of 38 seropositive RA sera showed a significant platelet aggregation (PA) titer as compared to 40 normal control sera. No correlation was observed between sheep T cell agglutination titers and PA titers of individual sera. Ten of 22 RA antiglobulin preparations containing IgG, IgM, and IgA antiglobulins and antiglobulin complexes also showed positive PA tests. Such preparations were able to inhibit PA brought about by heat‐aggregated human IgG. When IgG and IgM antiglobulins were tested separately, only IgM antiglobulins showed this inhibitory effect, whereas IgG antiglobulins were inactive. Neither IgG nor IgM antiglobulins induced PA alone. Reassociated IgG antiglobulin complexes consisting of carefully prepared IgG and isolated IgG antiglobulins were able to induce PA. Platelet aggregation by RA sera was thus shown to be due to IgG antiglobulin complexes present in the sera. It can be concluded from these experiments that the composition of antiglobulin complexes in individual sera comprised of antiglobulins of different classes and IgG “antigen” is responsible for PA results in vitro. In pathophysiologic terms, the reaction of IgG antiglobulin complexes with thrombocytes in vivo may be an important step in the chain of events leading to generalized vascular damage and deposition of immune complexes in vessel walls which is thought to be responsible for the development of generalized vasculitis in RA.
Immunoblastic sarcoma with features of sjögren's syndrome and systemic lupus erythematosus in a patient with immunoblastic lymphadenopathy
Authors: Pierce Donald A. , Stern Robert , Jaffe Ronald , Zulman Jules , Talal Norman
Published: February 2007

A patient with immunoblastic lymphadenopathy and features of Sjögren's syndrome and systemic lupus erythematosus is presented. Clinical features included generalized lymphadenopathy, rash, alopecia, and synovitis, with associated laboratory abnormalities of a positive antinuclear factor and double‐stranded DNA antibodies, positive lupus band test, and hemolytic anemia. Symptoms of Sjögren's syndrome included dry eyes and mouth and swollen parotid gland; biopsy results of the accessory salivary glands were positive. At autopsy immunoblastic sarcoma was found that involved the myocardium, which stained for both K and X light chains by immunoperoxidase techniques.
Does corticosteroid therapy affect the survival of patients with systemic lupus erythematosus?
Authors: Albert Daniel A. , Hadler Nortin M. , Ropes Marian W.
Published: February 2007

The hypothesis that corticosteroid therapy is responsible for the striking improvement in survival of patients with systemic lupus erythematosus (SLE) was investigated with two approaches: Of 250 published papers on SLE, 52 were chosen for the first analysis because they included sufficient information on diagnostic criteria and survival but were not limited to patients selected for a particular target organ. From each article percent survival by series, average duration to death, and 1 and 5 year survival curves were abstracted. Each statistic showed linear improvement in survival since the 1930s without a significant change (P > 0.10) in slope for the time period following the introduction of corticosteroids. The second analysis examined the effect of corticosteroid therapy on 142 patients with SLE followed at the Massachusetts General Hospital between 1922 and 1966. Although the steroid use was conservative, the patients' survival, from year of entry, was comparable to the 52 abstracted series. A prognostic index was used to stratify patients admitted in the steroid era (after 1950) for life table analysis of survival with and without steroids. Steroids had no discernible effect on overall survival in low and medium risk groups. Use of steroids was associated with improved survival among high risk patients (P < 0.05).
Antigenic bacterial polysaccharide in rheumatoid synovial effusions
Authors: Bartholomew Lee E. , Bartholomew Frances N.
Published: February 2007

Phenol‐water extracted rheumatoid synovial fluids and synovial fluid leukocytes contain an antigen immunologically identical to the Proprionibacterium group bacteria. The antigen was identified by counter‐immunoelectrophoresis in 70% of rheumatoid synovial fluid leukocyte pellets and in 60% of rheumatoid synovial fluids. It was also present in 6% of nonrheumatoid fluids and in 22% of nonrheumatoid inflammatory fluid leukocytes. Antigen was not detectable in synovial samples before extraction. Synovial and bacterial antigens were further purified by proteolytic digestion and Sepharose 4B column chromatography. Biochemical and enzymatic studies of bacterial and synovial antigens were similar and consistent with a high molecular weight polysaccharide. Serum antibody to bacterial and synovial antigens was significantly less frequent in rheumatoid sera than in normal controls. The significance of demonstrating a bacterial polysaccharide primarily in rheumatoid synovial effusions is discussed.
Increase in fibronectin in the deep dermis of involved skin in progressive systemic sclerosis
Authors: Cooper Sheldon M. , Keyser Anthony J. , Beaulieu Andre D. , Ruoslahti Erkki , Nimni Marcel E. , Quismorio Francisco P.
Published: February 2007

The distribution and amount of fibronectin in both involved and uninvolved skin from scleroderma patients and controls were compared by indirect immunofluorescence. A marked increase in fibronectin was found in the deep dermis of involved scleroderma skin, while the subepidermal papillary regions of all specimens revealed little variation in fibronectin content. The distribution of the accumulated fibronectin appeared to parallel that of the accumulated collagen in the involved reticular dermis.
In vitro hexosamine depletion of intact articular cartilage by e‐prostaglandins
Authors: Fulkerson John P. , Ladenbauer‐Bellis Inge‐Maria , Chrisman O. Donald
Published: February 2007

Short‐term incubations of intact canine articular cartilage slices with prostaglandins E1 and E2 caused significant losses of hexosamine from cartilage matrix compared to controls. Chloroquine, an inhibitor of DNA primer, prevented this prostaglandin‐induced hexosamine depletion. These data suggest that E‐prostaglandins may degrade articular cartilage directly through DNA‐dependent RNA synthesis of cathepsinlike proteases. Catabolism of articular cartilage probably involves degradation of existing matrix in addition to inhibition of synthesis.
Identification of human h‐y antigen and its testis‐organizing function
Authors: Iwata Hikaru , Nagai Yukifumi , Stapleton Dwight D. , Smith Richard C. , Ohno Susumu
Published: February 2007

In a mutational absence of the proposed plasma membrane anchorage sites of H‐Y antigen, the original pseudodiploid line of β+2microglobulin (—), HLA (—) Daudi human male Burkitt lymphoma cells proved themselves incapable of stably maintaining H‐Y antigen on their plasma membrane. Instead, H‐Y antigen was excreted into the culture medium. Human H‐Y antigen so excreted was identified as a series of polymers of molecular weight (MW) 18,000 subunit formed by interchain disulfide bridges. MW 18,000 H‐Y antigen subunit and other equally hydrophobic protein subunits excreted by Daudi cells were characterized by half‐lives longer than 20 hours. Human H‐Y antigen excreted by Daudi demonstrated a specific binding affinity toward unoccupied gonad‐specific H‐Y receptor sites residing on the plasma membrane of XX bovine embryonic gonadal cells, and this interaction induced the precocious testicular transformation in XX bovine embryonic indifferent gonads. In this experiment reported here, the variant pseudotetraploid line of Daudi produced an altered form of MW 18,000 subunit which was no longer capable of polymerizing via interchain disulfide bridges. Most of the altered H‐Y antigen subunit remained on the plasma membrane, but a small amount of it was excreted and demonstrated no binding affinity toward unoccupied gonad‐specific H‐Y receptor sites. However, this altered, monomeric H‐Y antigen subunit still readily absorbed the male‐specific cytotoxicity contained in H‐Y antibody.
High sensitivity to androgen as a contributing factor in sex differences in the immune response
Authors: Cohn D. A.
Published: February 2007

The factors responsible for sex differences in the immune response remain poorly understood despite the numerous, often conflicting reports published on the effects of the sex chromosomes or sex hormones on immune responsiveness. In the first part of this work, attempts are made to draw together some of the findings reported from different laboratories and to review briefly the work on sex differences in the immune response. In the second part, data from our laboratory are presented which suggest that in healthy, intact, untreated male mice a correlation exists between high sensitivity to androgen and low immune performance. We show that sex differences in the immune response do not invariably occur, but they do occur primarily in mouse strains with high target organ responsiveness to androgen, the C57L/J and the RF/J. In these strains males appear to be at a disadvantage immunologically in that they have lower plasma immunoglobulin levels and lower specific immune responses than females of the same strains or males of low androgen responder strains, the A/J and the 129/J. The low immune status of these high androgen responder (HAR) males is not influenced by altering postnatal concentrations of circulating androgen, indicating that it is high sensitivity to androgen, not a high concentration of circulating androgen, that correlates with poor immune performance. The low responses of HAR males to a variety of unrelated antigens and the fact that HAR males produce low antibody responses to bovine IgG even when they carry the H‐2 type for high immune responses suggest that high sensitivity to androgen may act as a nonspecific modulator of the immune response. Possible mechanisms of action are discussed.
Gold‐induced changes in the morphology and functional capabilities of human monocytes
Authors: Ugai Kazuhiro , Ziff Morris , Lipsky Peter E
Published: February 2007

The capacity of gold compounds to induce morphologic changes and alterations in the functional activity of human mononuclear phagocytes (MΦ) in vitro was examined. Human peripheral blood mononuclear cells were incubated with gold sodium thiomalate (25 μg/ml) for 96 hours. As a result, MΦ developed electron dense precipitates within phagolysosomes, as well as marked dilatation of these organelles. Gold incubation also altered a number of MΦ functions. While viability and adherence were unaffected, the capacity to spread on surfaces was diminished. Pinocytosis of soluble proteins and phagocytosis of opsonized sheep erythrocytes were impaired, but Fc mediated particle binding was not. These data indicate that gold can alter certain functional activities of MΦ and support the idea that the major action of gold in rheumatoid arthritis results from its capacity to alter MΦ function.
Collagen types synthesized in dermal fibroblast cultures from patients with early progressive systemic sclerosis
Authors: Gay Renate E. , Buckingham Robert B. , Prince Robert K. , Gay Steffen , Rodnan Gerald P. , Miller Edward J.
Published: February 2007

Fibroblast cultures were established by explant culture from upper and lower dermis of 7 normal donors and 10 patients with early progressive systemic sclerosis (PSS). Antibodies against collagens containing the A and B chains, collagens which occur largely in vascular structures, were isolated and used for immunofluorescence studies. Cultures from lower PSS dermis accumulated significantly more of these collagens than fibroblast cultures from upper PSS dermis or cultures from upper or lower dermis of normal skin. These data indicate that the collagens containing the A and B chains in early PSS lesions are produced by cells of vascular origin and support the concept that alterations in vascular tissue play a prominent role in the pathogenesis of PSS.
In vitro synthesis of tissue‐specific type ii collagen by healing cartilage
Authors: Cheung Herman S. , Lynch Kenneth L. , Johnson Roger P. , Brewer Bruce J.
Published: February 2007

The healing of surgically induced defects in mature rabbits' hyaline cartilage was examined histologically and biochemically. The subchondral bone underneath the lesion was the source of repair. At the end of the first month, mushroom‐shaped chondroid buds were seen sprouting from the subchondral bone. By the tenth week, these buds fused to a cartilagenous plug filling the lesion. The repaired cartilage synthesized Type II collagen.
Left atrial myxoma presenting as a systemic vasculitis
Authors: Byrd William E. , Matthews Oliver P. , Hunt Robert E.
Published: February 2007

Left atrial myxoma has often simulated systemic vasculitis or a connective tissue disease, but the diagnosis is usually suggested by cardiac symptoms or signs. The present case report is both unusual and instructive in that the patient presented with a painless left foot drop followed by digital vasculitis. Laboratory findings included depressed total hemolytic complement and elevated anti‐double‐stranded DNA. Despite frequent and careful observation, a heart murmur was not appreciated. Because of the unusual features and the patient's frequent military travels, the diagnosis of left atrial myxoma was not established for 8 months. This case history stresses the importance of considering the possibility of atrial myxoma in patients with heart murmurs whose symptoms, physical findings, and laboratory studies could be compatible with a systemic vasculitis.
Lymphocytotoxic antibodies in systemic lupus erythematosus patients and their relatives
Authors: Messner Ronald P. , Horatius Raphael De , Ferrone Soldano
Published: February 2007

Lymphocytotoxic activity of sera from systemic lupus erythematosus (SLE) patients and their families was inhibited by 50% or more by preincubation of target cells with Fab2 fragments of xenoantisera against β2 microglobulin or the heavy chain of the HLA‐A,B,C antigenic molecular complex. An antiHLA‐DR xenoantiserum had less blocking effect on peripheral blood mononuclear cells but was effective at blocking reactivity of these sera against cultured B lymphoid cell lines. The repertoire of specificities in family members' sera differed from each other and their respective proband with respect to their reactions with cultured lymphoid cell lines. These data indicate that lymphocytotoxic antibodies (LCA) found in most patients with SLE and some of their relatives include a subpopulation with specificity for determinants present on major histocompatibility gene products. They also suggest that LCA in relatives represent a defect in immune regulation which allows expression of existing autoimmune potentials rather than immunization with a single ‘lupus’ antigen.
Synovial pathologic changes in spontaneous canine rheumatoid‐like arthritis
Authors: Schumacher H. Ralph , Newton Charles , Halliwell Richard E. W.
Published: February 2007

The synovial fluid and membrane were studied in 10 dogs meeting the American Rheumatism Association criteria for classic human rheumatoid arthritis (RA). Light microscopic pathologic features were consistent with those found in the human disease. Neutrophilic infiltration of synovium was somewhat more prominent than in chronic human RA, and activated lymphocytes in fluid or membrane were less frequent. The proliferative and plasma cell reaction seemed identical. Electron microscopy (EM) suggested microvascular injury with findings which included electron dense deposits in the vessel walls of 2 dogs. Seven dogs had meshworks of 20‐25 mm tubules in tubuloreticular structures (TRS) similar to those seen in human systemic lupus erythematosus and only occasionally in human RA. There were also crystalline arrays of tubules, a configuration previously reported in tumors and virus infections and possibly suggestive of a cellular reaction to virus infection. To date no initiating agent has been identified, but this spontaneous canine disease which is very similar to human RA can provide a valuable model in which to examine pathogenesis of chronic arthritis.
Resistance to therapy in mature palmerston north mice treated with cyclophosphamide or hydrocortisone sodium succinate
Authors: Walker Sara Ellen , Schnitzer Bertram
Published: February 2007

Inbred Palmerston North (PN) mice are a newly reconized model of systemic lupus erythematosus.In this study PN mice with established autoimmune disease were treated until death with cyclophosphamide (8 mg/kg/day) or hydrocortisone (10 mg/kg/day). These doses had previously been found to prevent or suppress disease in another lupus model, the NZB/NZW mouse. In the PN strain, autoantibodies, severity of glomerulo‐nephritis, and longevity were not influenced by treatment. Furthermore, the incidence of neoplasms was not increased in PN mice receiving prolonged therapy with immunosuppressive drugs. Unlike NZB/NZW mice, PN mice were resistant to the effects of cyclophomide and hydrocortisone.
Elevated levels of collagenase and prostaglandin e2 from synovium associated with chronic lyme arthritis
Authors: Steere Allen C. , Brinckerhoff Constance E. , Miller Denis J. , Drinker Henry , Harris Edward D. , Malawista Stephen E.
Published: February 2007

A patient with chronic Lyme arthritis and roentgenographic evidence of bony erosion underwent a synovectomy; proliferative synovium (pannus), containing aggreagates of small lymphocytes, was found adherent to eroded cartilage and bone. During 8 days in tissue culture, the synovial cells produced large amounts of collagenase and prostaglandin E2, but only low levels of both neurtral and acid proteinases. Sixty‐seven percent of the lymphocytes from the synovium were T cells; 19% were B cells. Attempts to identify agent/antigen in the synovial cells were unsuccessful. Thus, the synovium of this patient, whose disease appears to be tick‐transmitted, resembles that of rheumatoid arthritis. This finding further supports the hypothesis that many possible agents, including infectious ones, trigger a common pathway in synovium, which leads to joint destruction.
Immune complexes in sjögren's syndrome
Authors: Fischbach Michael , Char Devron , Christensen Mary , Daniels Troy , Whaley Keith , Alspaugh Margaret , Talal Norman
Published: February 2007

Sera from 48 patients with Sjögren's syndrome were examined for immune complexes by the Raji cell assay. There was no correlation between levels of immune complexes and the degree of lymphocytic infiltration of the labial salivary glands. Serum complement levels were normal. Five patients were serially followed during the development of pseudolymphoma or malignant lymphoma. Immune complex levels in 4 of the 5 patients were generally unchanged throughout the illness and did not parallel disease activity, rheumatoid factor, or SS‐A and SS‐B concentrations. Possible roles for immune complexes in Sjögren's syndrome are discussed.
Platelet‐activating activity in synovial fluids of patients with rheumatoid arthritis, juvenile rheumatoid arthritis, gout, and noninflammatory arthropathies
Authors: Shapleigh Christine , Valone Frank H. , Schur Peter H. , Goetzl Edward J. , Austen K. Frank
Published: February 2007

The predominant activating activity in rheumatoid synovial fluid for human platelets, as assessed by the release of 11C serotonin, was previously isolated and shown to be a complex of IgG of molecular weight 450,000. Thus, a pooled 5 ml concentrate of the 450,000 molecular weight fraction obtained by Sepharose 66 gel filtration of 1 ml of synovial fluid was used to compare the platelet‐activating activity (PAA) of fluids from 28 patients with inflammatory and noninflammatory ar‐thropathies. One unit of PAA was arbitrarily defined as that volume of the 5 ml concentrate required to obtain release equal to that obtained with a standard dose of thrombin, and total units per milliliter of synovial fluid were calculated as the reciprocal of the volume of concentrate in milliliters containing one unit multiplied by five. A platelet‐activating activity of >766 units/ml of synovial fluid was arbitrarily defined as elevated, since this value represents two standard deviations above the mean for the noninflammatory synovial fluids. Each of 7 noninflammatory fluids (range <50 to 695) and 3 of 4 gouty fluids (range <50 to 1,250) fell within the normal range, whereas 9 of 13 adult rheumatoid fluids (range <50 to 11,880), and 4 of 4 JRA fluids (range 1,299 to 5,100) had elevated levels of PAA per ml of synovial fluid. The finding that the purified synovial fluid 450,000 molecular weight complex of IgG was inhibited in its platelet‐activating capacity by purified monoclonal rheumatoid factor suggests that a role for IgM rheumatoid factor could be to block IgG complex Fc receptor‐dependent proinflammatory effects on platelets, and perhaps other cells.
Chronic arthritis of rabbits induced by mycoplasmas II.antibody response and the deposition of immune complexes
Authors: Washburn Leigh Rice , Cole Barry C. , Ward John R.
Published: February 2007

Chronic mycoplasma‐induced arthritis of rabbits was accompanied by a highly active humoral immune response. Peak antibody liters coincided with the “disappearance” of mycoplasmas from joint tissues at 7 weeks. High synovial fluid antibody liters and immuno‐globulin‐producing cells in frozen sections of synovial membrane suggested local antibody production. Persistence of granular deposits containing IgG and complement in synovium and cartilage may be a mechanism for continuing inflammation in the apparent absence of cultivable mycoplasmas.
Efficient induction of collagen arthritis by the use of a synthetic muramyl dipeptide
Authors: Koga Toshitaka , Sakamoto Shigeru , Onoue Kauro , Kotani Shozo , Sumiyoshi Akinobu
Published: February 2007

We developed an efficient method for production of experimental polyarthritis. Native collagen (type II) from human costal cartilage was emulsified with incomplete Freund's adjuvant (IFA) containing the synthetic adjuvant N‐acetylmuramyl‐L‐alanyl‐D‐isoglutamine (MDP), and injected into one hind footpad of the PVG/c rat. This method reproducibly induced severe arthritis with high incidence, whereas the collagen alone in IFA produced mild arthritis with low incidence. MDP alone in IFA was shown to be minimally arthritogenic under identical conditions.
Circulating immune complexes in giant cell arteritis and polymyalgia rheumatica
Authors: Papaioannou Christos C. , Gupta Ramesh C. , Hunder Gene G. , Mcduffie Frederic C.
Published: February 2007

Sera from 74 patients with polymyalgia rheumatica or giant cell arteritis or both were tested for immune complexes by using the Raji cell radioimmunoassay. Levels in patients with active disease were higher than in patients whose disease had become inactive. There was no difference in levels of immune complexlike materials between patients with polymyalgia rheumatica alone and those with giant cell arteritis. Density gradient analysis of one serum showed immune complex‐like materials mainly in the 19S region. Immune complexes may be important in the pathogenesis of these conditions.
The action of the main therapeutic regimes on paget's disease of bone, with a note on the effect of vitamin d deficiency
Authors: Nagant Deuxchaisnes C. De , Maldague B. , Malghem J. , Devogelaer J. P. , Huaux J. P. , Rombouts‐Lindemans C.
Published: February 2007

The effect of vitamin D deficiency was studied in 3 patients with Paget's disease of bone. The biochemical parameters of bone turnover strikingly increased, while the pagetic bone became radiolucent. This occurred whether the nonpagetic bones were osteomalacic or not. All the observed changes were reversed upon correction of the deficiency. The effects of mithramycin and calcitonin on the biochemical parameters of bone turnover were compared sequentially in three cases. No treatment proved definitely superior in this regard. The effectiveness of calcitonin to induce a positive focal bone balance in osteolytic Paget's disease was studied radiologically and compared to the effects of the diphosphonate EHDP, and to the combined therapy of EHDP and calcitonin. Calcitonin showed a constructive action in 100% of the cases. EHDP, administered at low dosages (7.0 mg/kg/24 hr during a period of 7.4 months) did not demonstrate a uniformly constructive action in any patient. Radiolucent lesions appeared in 56%, “dissociated” effects (both a constructive and a destructive action) were seen in 33%, and no effect in 11% of the cases. Combined therapy was intermediate in its action between calcitonin and EHDP. After discontinuation of combined therapy, an EHDP‐like effect was often apparent.
19S IgM forssman‐type heterophhile antibodies in juvenile rheumatoid arthritis
Authors: Moore Terry L. , Dorner Robert W.
Published: February 2007

Fifty‐four sera from children with juvenile rheumatoid arthritis (JRA) were separated by gel filtration at pH 4.05. The serum and IgM and IgG‐containing fractions were analyzed for heterophile antibodies by subjecting them to a hemolytic assay in tubes with the target cell a 1% washed sheep erythrocyte (SRBC) or beef erythrocyte (BRBC) in suspension. Thirty‐three of 54 sera showed hemolytic antibody titers >1:640 against SRBC alone and 4 of 54 had titers >1:320 against SRBC and BRBC. All positive titers against SRBC and BRBC were associated with the IgM fraction. Differential absorption with SRBC, BRBC, and tissue sediment of homogenized guinea pig kidney revealed a Forssman specificity in 33 sera and Forssman and Hanganutziu‐Deicher specificity in 4. The presence of heterophile antibodies in JRA correlated with the presence of hidden rheumatoid factor. There was also an increased incidence in patients with positive antinuclear antibodies and in teenaged females with polyarticular disease.
Anti‐tetanus toxoid antibody synthesis after booster immunization in systemic lupus erythematosus
Authors: Nies Kenneth , Boyer Richard , Stevens Ronald , Louie James
Published: February 2007

The in vivo and in vitro synthesis of anti‐tetanus toxoid antibody (anti‐tet) was measured after booster immunization with tetanus toxoid in 9 patients with systemic lupus erythematosus (SLE) and 9 controls. In vitro culture of peripheral blood lymphocytes (PBL) from both patients and controls showed maximal antitet synthesis 7 days after booster immunization, and maximal serum titers occurred by day 14. The initial in vitro burst of anti‐tet synthesis was not dependent upon pokeweed mitogen (PWM) stimulation, whereas later synthesis was PWM dependent. Two differences between patients and controls were observed:1) patients with SLE had a lower mean pre‐boost serum titer of anti‐tet, and 2) one‐third of the patients showed a blunted serum anti‐tet response. To study whether these abnormalities were a result of altered immune regulation, anti‐tet synthesis was measured by the coculture of separated SLE‐B or control‐B cells and separated SLE‐T or control‐T or control‐T cell populations (± irradiation to remove suppressor T cell activity). These coculture studies showed that both abnormalities were due to a lack of SLE‐B cell response, not to abnormalities of SLE‐helper T or SLE‐ suppressor T cell function.
Total lymphoid and local joint irradiation in the treatment of adjuvant arthritis
Authors: Schurman David J , Paul Hirshman H , Strober Samuel
Published: February 2007

Total lymphoid irradiation (TLI) with 3,400 rads delivered in 17 divided doses, 600 rads at local paw irradiation in 3 divided doses, or both TLI and local irradiation were used to treat Lewis rats with adjuvant arthritis. Either TLI alone or local paw irradiation modestly reduced the severity of arthritis compared to a control group (P < 0.05). TLI treated animals had more initial suppression of inflammation. Adjuvant rats treated with a combination of both TLI and local paw irradiation had a profound and long lasting reduction in inflammation and permanent arthritis (P < 0.001).
Ineffectiveness of levamisole in systemic lupus erythematosus. a controlled trial
Authors: Hadidi Tahsin , Decker John L , El‐Nagdy Lene , Samy Mahmoud
Published: February 2007

Twenty‐six patients with active systemic lupus erythematosus partially controlled by prednisone 30 mg daily or less were randomly selected to receive levamisole 150 mg weekly or placebo. Many patients showed increased disease activity over the 6‐month trial period, and most required increased steroid dosage. Those on levamisole did no better than those on placebo.
Flow cytometry and cytoadherence studies of sera from children with juvenile rheumatoid arthritis and normal controls
Authors: Froelich Christopher J. , Bankhurst Arthur D. , Crowe William E. , Williams Ralph C. , Warner Noel L. , Levinson Joseph E.
Published: February 2007

Recently, antibodies reactive with T cell subpopulations have been reported to exist in children with active juvenile arthritis (JRA). In an attempt to verify and extend these observations, we have studied children with JRA for the presence of anti‐T cell antibodies by flow cytometry and cytoadherence rosette techniques. T cells were isolated from peripheral blood mononuclear cells (PBL) by two methods: 1) Differential sedimentation of PBL rosetted with neuraminidase‐treated sheep erythrocytes, and 2) removal of immunoglobulin positive PBL by rosetting with rabbit anti–human F(ab′)2 coated bovine erythrocytes and differential sedimentation. Utilizing these methods to detect lymphoreactivity of JRA sera to either population of T cell isolates, we observed the binding of ultracentrifuged normal human sera (NHS) to be comparable to JRA sera (active and quiescent). NHS reacted with 15–25% of T cells. Further studies demonstrate that monomeric IgG was chiefly responsible for lymphoreactivity. The results of these studies are discussed in the context of previous observations.
Interaction between rheumatoid factor and antibody/DNA COMPLEXES
Authors: Birchmore Daniel A. , Taylor Ronald P. , Waller Steven J. , Davis John S. , Morley Kathi W.
Published: February 2007

The influence of rheumatoid factor (RF) on the complement mediated binding of antibody/double‐stranded DNA immune complexes to red blood cells has been investigated. Our results indicate that RF enhances this binding reaction, apparently by fixing complement via its own Fc region. These findings suggest that under certain circumstances, RF may play an exacerbating role in the antibody/DNA induced glomeru‐lonephritis of systemic lupus erythematosus.
Fatal thrombotic thrombocytopenic purpura in a patient with systemic lupus erythematosus
Authors: Cecere Fred A. , Yoshinoya Sadyoshi , Pope Richard M.
Published: February 2007

An immunologic mechanism, possibly immune complex mediated, has been suggested as the basis for the pathogenesis of thrombotic thrombocytopenic purpura (TTP). The evidence supporting this concept has been the association of TTP with systemic lupus erythematosus and the successful therapy of TTP by plasmapheresis. However, most investigators have failed to demonstrate elevated circulating immune complexes during the course of TTP. This report describes a young woman with systemic lupus who developed TTP as a terminal event. Elevated levels of immune complexes were associated with periods of active lupus but were not detectable at the time she developed TTP.
Tγ cell subset specificity of lymphocyte reactive factors in juvenile rheumatoid arthritis and systemic lupus erythematosus sera
Authors: Williams R. C. , Froelich C. J. , Kilpatrick K. , Crowe W. E. , Levinson J. E.
Published: February 2007

Sera from 34 patients with juvenile rheumatoid arthritis (JRA), 31 patients with systemic lupus erthematosus (SLE), and 22 normal controls were studied for microcytotoxicity before and after clearing in the ultracentrifuge. Normal T cells as well as Tγ and non‐Tγ subpopulations were used. Before ultracentrifugation all test sera showed apparent Tγ cell specificity in the microcytotoxicity assay where rabbit complement was added. JRA and SLE sera produced much higher proportions of cell killing than normal controls. Ultracentrifugal clearing resulted in marked diminution in microcytoxicity of JRA and some SLE sera. However, a considerable proportion of lupus sera continued to show T cell subset cytotoxicity after ultracentrifugal clearing. No evidence for significant alteration of Tγ resetting capacity was recorded when ultracentrifuge‐cleared test sera were preincubated with T cells prior to Tγ EA rosette formation. Apparent Tγ cytotoxic specificity in some uncleared JRA and SLE sera may relate to high molecular weight materials (IgM and immune complexes) present in such samples, whereas in others it relates to lymphocyte reactive antibody with subset reactivity.
Cold dependent activation of complement in systemic lupus erythematosus
Authors: Atkinson John P. , Gorman John C. , Curd John , Hyla James F. , Deegan Michael J. , Keren David F. , Abdou Nabih I. , Walker Sara Ellen
Published: February 2007

A 31‐year‐old woman with systemic lupus erythematosus (SLE) was studied because she developed markedly reduced total hemolytic complement activity at a time when her disease was clinically inactive. Functional assays demonstrated reduced activities of C1, C4, and C2, but normal concentrations of C3 and the terminal (C5–9) components were present. Antigenic concentrations of C1, C4, and C2 were normal. Plasma or serum obtained from blood allowed to clot at 37°C had normal complement activity. Complement activity was depleted when the patient's serum was incubated in the cold. At reduced temperatures, the patient's serum (or purified IgG) depleted complement activity of normal human sera. A second patient with SLE was also demonstrated to have this same phenomenon. Cryoglobulins were not detectable in these patients. These data indicate that in vivo the patients' complement was normal and that the observed in vitro reduction was caused by cold dependent activation of the classical pathway.
Increased incidence of cervical atypia in women with systemic lupus erythematosus treated with chemotherapy
Authors: Nyberg Gudrun , Eriksson Olof , Gunnar Westberg N.
Published: February 2007

In a retrospective study we found that 19 of 80 women with systemic lupus erythematosus had atypical cervical smears as compared to only 9 of 80 age‐matched women without the disease. This increased incidence occurred mainly among women receiving cytotoxic drugs. Cervical atypia in women with lupus was not morphologically different from cervical atypia in general. Possible mechanisms responsible for the increased incidence are discussed. It is concluded that women with lupus who receive chemotherapy should have cervical smears taken regularly.
Tγ lymphocytes of peripheral blood and synovial fluid in rheumatoid arthritis
Authors: Mathieu Alessandro , Mereu Maria Cristina , Pisano Luisa
Published: February 2007

The distribution of Tγ lymphocytes in the peripheral blood of one group of rheumatoid patients and in the synovial fluid in a second group was determined. The results were compared to those found for peripheral blood (PB) lymphocytes of normal subjects and for synovial fluid lymphocytes of osteoarthrosis and meniscitis patients. Besides recording percentage and absolute number, we also used cytofluorographic analysis to determine individual capacity of PB Tγ cells to bind heat‐aggregated IgG (agg‐IgG). The following results were found: 1) there is no significant difference between the percentage and absolute number of PB Tγ lymphocytes of rheumatoid arthritis (RA) patients and those of controls, 2) individual RA PB Tγ cells had a greater number and/or avidity of Fc receptor for IgG than those cells of controls, and 3) the percentage of RA Tγ lymphocytes in synovial fluid, revealed by IgG‐EA ox rosetting, is significantly lower than that found in control patients. The factors that may determine a similar lymphocyte picture in RA are discussed.
Association of myositis and myocarditis in progressive systemic sclerosis
Authors: West Sterling G. , Killian Paul J. , Lawless Oliver J.
Published: February 2007

A retrospective review of 47 patients with progressive systemic sclerosis revealed a highly significant (P < 0.001) association between myositis and myocarditis. Three patients developed clinically overt myocarditis as an early feature of their disease. These patients had an inflammatory myopathy indistinguishable from polymyositis. Despite an excellent clinical response to steroids, the late occurrence of life‐threatening conduction system defects appeared while they were receiving therapy. Consequently, patients with progressive systemic sclerosis and myositis should be evaluated for a coexisting myocarditis. The findings in these patients lend further support to the concept of a generalized myopathic process among the connective tissue diseases.
Assessment and interpretation of radiopharmaceutical joint imaging in an animal model of arthritis
Authors: Rosenspire Karen L. , Blau Monte , Kennedy Alastair C. , Green Floyd A.
Published: February 2007

An animal model of arthritis in the rabbit was employed to assess the radioactivity contribution of joint tissues to externally monitored scintigram positivity. Bone contained the greatest total amount of radioactivity whether the imaging agent was technetium pertechnetate or pyrophosphate, although the greatest percent increase in the arthritis joints over control joints was seen in synovium. Mid‐shaft bone in the same region as the arthritic joint also showed increased radioactivity compared with control.
Low molecular weight IgM in rheumatoid arthritis and other rheumatic diseases
Authors: Roberts‐Thomson Peter J. , Wernick Richard M. , Ziff Morris
Published: February 2007

Low molecular weight (LMW) IgM was measured in the serum and synovial fluid of patients with rheumatoid arthritis (RA) and other rheumatic diseases. High levels were seen in RA, particularly in rheumatoid vasculitis and Felty's syndrome, and significant correlations occurred between LMW IgM and the rheumatoid factor (RF) level and other indices that reflected active or severe disease. LMW IgM‐RF, measured by radio‐immunoassay in those column fractions containing LMW IgM, correlated significantly with LMW IgM (P < 0.005); preliminary experiments suggested that in some sera, a considerable proportion of the LMW IgM consisted of LMW IgM‐RF. We conclude that LMW IgM and LMW IgM‐RF may have important implications in the immunopathogenesis of RA and other rheumatic diseases.
Experimental siderosis of articular chondrocytes cultured in vitro
Authors: Choi Ye‐Chin , Hough Aubrey J. , Morris Gregory M. , Sokoloff Leon
Published: February 2007

Siderosis of rabbit articular chondrocytes was produced in vitro as a model for the cartilage damage of hemophilic arthropathy. Both FeSO4 0.1–2.5 mM and rabbit hemoglobin (as hemolyzed serum, 14 mg/ml) caused iron storage in cell and organ culture. FeSO4 was far more effective. The fine structure of the siderosomes resulting from both iron sources was comparable to that observed in hemophilic and other forms of hemosiderosis. Particles resembling ferric oxyhydroxide were included in the FeSO4 but not the hemoglobin derived siderin. Iron storage following FeSO4 was enhanced 5‐fold by culturing with rabbit rather than fetal calf serum. Despite repeated washing of the cultures and detachment with trypsin, an extracellular pool of Fe3+ persisted in the cell pellets. Cytotoxicity of Fe was manifested by formation of myelin bodies and a dose‐dependent reduction of cell number. There was an inverse relationship betweeen cytotoxicity and iron storage following administration of FeSO4 to five other cell types. Ascorbate 40 μg/ml stimulated DNA synthesis but had no protective effect against the cytotoxicity of FeSO4. Little erythrophagocytosis was shown by the chondrocytes. Desferrioxamine (0.01–2.5 mM) was markedly toxic for dividing but not for stationary chondrocytes. Administered after iron storage had been induced with FeSO4, 1.0–2.5 mM desferrioxamine removed stainable siderin granules over the course of 4 days.
ULTRASTRUCTURE OF THE MOUSE SYNOVIAL MEMBRANE
Authors: Okada Yasunori , Nakanishi Isao , Kajikawa Kinichiro
Published: February 2007

The synovial membrane of the mouse knee joint was examined by electron microscopy and electron microscopic histochemistry, with special reference to the development of the extracellular matrix. In the embryonic synovium, the intercellular spaces were filled with hyaluronate and chondroitin sulfate. The formation of the early joint cavity appeared to be initiated by accumulation of hyaluronate and chondroitin sulfate in the synovial primordium. At the postnatal stage, the synovial primordium differentiated into a true synovial intima that could be easily identified by the presence of two distinct lining cells: fibroblast‐like cells (B cells) and phagocytic cells (A cells). Simultaneously, the synovial intima provided the specialized extracellular matrix that was characterized by organized structures of micro‐fibrils, collagen fibers, and fibrous long spacing fibers embedded in a large number of glycoproteins.
Enhanced neutral protease activity in proliferating rheumatoid synovial cells
Authors: Hatcher Victor B. , Borg Joanne P. , Levitt Mindy , Smith Carol
Published: February 2007

Proteolytic enzymes associated with rheumatoid synovial cells (RSC) have been implicated in the degradation of articular cartilage. Proteases have been measured in proliferating rheumatoid synovial cells (P‐RSC), proliferating nonrheumatoid synovial cells (P‐NSC), and their nonproliferating counterparts (NP‐RSC and NP‐NSC). The P‐RSC and P‐NSC exhibit enhanced total surface‐associated plus secreted neutral protease activity, as compared with NP‐RSC and NP‐NSC. The P‐RSC exhibited significantly higher protease activity in this category compared to P‐NSC. The RSC also secreted higher levels of secreted proteases alone compared to NSC. The secreted protease activity alone was not related to the proliferative state of the cells. Extractable protease activity was measured in early‐passaged and serially‐passaged P‐RSC, NP‐RSC, P‐NSC, and NP‐NSC. Extractable cellular protease activity measured at pH ranges from 5.0 through 8.0 was not significantly different between P‐RSC and NP‐RSC or between P‐NSC and NP‐NSC. The RSC contained elevated extractable cellular protease activity measured at pH ranges from 5.0 through 8.0 compared to extracts from later‐passaged cells. The neutral protease activity in the early‐passaged RSC was also higher than that measured at pH 6.0 or 8.0. In synovial cells cellular protease activity was related to the proliferative state and the origin of the cells. The P‐RSC exhibited the highest levels of surface associated plus secreted neutral protease activity. The RSC also possessed the highest levels of extractable protease activity compared to NSC.
Pharmacogenetic studies on the drug‐related lupus syndrome. differences in antinuclear antibody development and drug‐induced DNA damage in rapid and slow acetylator animal models
Authors: Weber W. W. , Tannen R. H.
Published: February 2007

Pharmacogenetic study of an inbred mouse model system derived from A/J (slow acetylator) and C57BL/6J (rapid acetylator) parental strains shows that spontaneous occurrence of antinuclear antibodies is associated with the slow acetylator phenotype although the development of spontaneous and procainamide‐induced antinuclear antibodies is a dissociable process. In another study using primary cultures of intact hepatocytes obtained from slow and rapid acetylator rabbits, observations indicate that the amount of DNA damage induced by exposure to hydrazine and arylamine containing foreign compounds depends on the concentration of the foreign compound used as well as on the acetylator phenotype. Exposure to hydralazine induced greater DNA damage in slow acetylator hepatocytes whereas exposure to the arylamine carcinogen, 2‐aminofluorene, induced greater DNA damage in rapid acetylator hepatocytes.
Relationship between immune response to hydralazine and to deoxyribonucleoprotein in patients receiving hydralazine
Authors: Mcduffie Frederic C.
Published: February 2007

In a prospective study of 21 hypertensive patients receiving hydralazine for 1 year, we found a close relationship between development of antibodies to deoxyribonucleoprotein (DNP) and to hydralazine but no evidence for cross‐reactivity between antibodies to these two antigens. Of 8 patients who developed increased levels of antiDNP, 7 also developed antibodies to hydralazine. Inhibition of the reaction between DNP and antiDNP as measured by radioimmunoassay in 3 patients with hydralazine lupus could not be achieved with large amounts of hydralazine. However, antibodies to DNP produced in guinea pigs immunized with hydralazine conjugates could be inhibited with hydralazine in accordance with previous studies by others on rabbits. In the human, antibodies to DNP which develop during hydralazine administration are not due to cross‐reactive antibodies nor do they appear as a result of immune response to an in vivo hydralazine DNP conjugate.