bluuebunny/crossref_metadata_2025 huggingface dataset:
Connective tissue activation
Authors: William Castor C. , Pek Sumer
Published: February 2007

Connective tissue activating peptides from lymphocytes (CTAP‐I) and platelets (CTAP‐III) are known to stimulate glycosaminoglycan synthesis, glycolysis, and mitogenesis in connective tissue cell cultures. Direct evidence suggested that increased accumulation of cyclic AMP was involved in the action of these peptide agonists, and increased prostaglandin E synthesis was postulated on the basis of indirect evidence. In the present experiments, CTAP‐I and ‐III were incubated with human and murine cells in culture, and prostaglandin E was measured by radioimmunoassay using antibody directed primarily to prostaglandin E2. Both CTAP‐I and ‐III markedly stimulated the elaboration of prostaglandin E into culture medium, the earliest evidence of increased synthesis occurring at 4 hours with maximal concentrations found at 24 hours. Substantial residual stimulation persisted at least through 48 hours. Indo‐methacin (13.0 m̈g/ml) obliterated basal and incremental synthesis of prostaglandin in the presence of mediators. Cycloheximide (8.7 m̈g/ml) did not affect the stimulation of prostaglandin synthesis by CTAP‐I and ‐III. Three nonrheumatoid and 3 rheumatoid synovial cell strains showed similar basal levels of prostaglandin E and similar responses to CTAP‐I. A murine fibroblast cell strain (3T3) showed increased prostaglandin E synthesis on exposure to CTAP‐I, and the KB tumor cell strain was markedly stimulated by CTAP‐III. These studies confirm the increased synthesis of E series prostaglandins postulated to occur in human connective tissue cells on exposure to CTAP‐I and ‐III, and clarify the mechanism of action of these agonists on “activated” target cells. The importance of elevated extracellular concentrations of prostaglandins is uncertain, although they may act directly on sensitive cell types as well as potentiate the actions of CTAP‐I and ‐III on neighboring cells.
Familial articular chondrocalcinosis in quebec
Authors: Gaudreau André , Camerlain Monique , Pibarot Marie‐Laure , Beauregard Germain , Lebrun André , Petitclerc Claude
Published: February 2007

The existence of articular chondrocalcinosis was documented in 9 members of 3 generations of a Quebec family. No associated or secondary forms of the disease were found. The clinical manifestations appeared early in life, and extensive radiologic involvement was apparent. We determined that genetic transmission was dominant, either autosomal or sex‐linked, and not related to the HLA system.
Investigation of type i and type iii collagens of the lung in progressive systemic sclerosis
Authors: Seyer Jerome M. , Kang Andrew H. , Rodnan Gerald
Published: February 2007

The interstitial collagens, type I and type III, were investigated in lung tissue from patients with progressive systemic sclerosis (PSS) with pulmonary involvement. By use of CNBr digestion of whole tissue, the relative content of type I versus type III collagen was unchanged. This contrasts with idiopathic pulmonary fibrosis. Limited pepsin digestion released greater amounts of collagen (55%) than normal (16%), but the individual collagen chains were chemically indistinguishable. A reduced amount of the more stable collagen crosslink, hydroxylysinonorleucine, was observed which was consistent with the relatively greater degree of solubilization.
HLA and rheumatoid arthritis in the japanese
Authors: Nakai Yuko , Wakisaka Akemi , Aizawa Miki , Itakura Katsuaki , Nakai Hidenori , Ohashi Akira
Published: February 2007

Sixty‐three Japanese patients with rheumatoid arthritis (RA) were typed for HLA‐A, ‐B, and ‐DR locus specificities. A significant association was found only with increased frequency of HLA‐DR4 in the patients (71.4%) compared with controls (41.8%) (corrected P = 0.007, relative risk = 3.5). No association was found with HLA‐A9 or HLA‐Bw54, which are in linkage disequilibrium with HLA‐DR4 in the Japanese. The association between HLA‐DR4 and RA observed in these Japanese patients has also been demonstrated in the white population.
Avidity indices of anti‐IgG antibodies in diseases
Authors: Chia D. , Nasu H. , Yamagata J. , Barnett E. V.
Published: February 2007

Anti‐IgG antibodies were detected in 69% of 235 sera tested. A simple and reproducible method was developed to measure the avidity index of anti‐IgG antibodies. It was found that subjects with systemic lupus erythematosus and progressive systemic sclerosis and normal controls had antibodies with lower avidity index than those with rheumatoid arthritis and Down's syndrome. The difference in avidity seems to be disease specific. Avidity does not correlate with antibody titers, but all sera with high avidity antibody are positive in the latex test. The anti‐IgG as measured by this method was shown to be mainly of IgM class. The avidity indices of whole sera and purified IgM fractions were similar.
A preliminary ferrographic survey of the wear particles in human synovial fluid
Authors: Evans Christopher H. , Mears Dana C. , Mcknight Jennifer L.
Published: February 2007

The technique of ferrography has been applied to the analysis of wear particles in human synovial fluid aspirates. A number of discrete, identifiable classes of wear particles were found, including particles indicative of cutting wear and rubbing wear. The spectrum of particles varied among different groups of patients, suggesting an eventual diagnostic use for this method.
EVALUATION OF A PILOT PROGRAM FOR RHEUMATIC DISABILITY IN AN URBAN COMMUNITY
Authors: Liang M. H. , Phillips E. E. , Scamman M. D. , Lurye C. S. , Keith A. , Cohen L. , Taylor G.
Published: February 2007

A program for the systematic detection and management of arthritis disability was developed for an urban population. A survey identified 601 persons with rheumatic disability in a population of 9,500–10,550. Seventy‐eight persons were evaluated and given recommendations. An ombudsman assisted the clients in obtaining health services and coordinated care. An evaluation 6–8 months later showed increased utilization of and referrals to relevant services but, on the whole, little improvement in functional capacity was noted. However, the small numbers do not permit more definite conclusions.
Cytotoxic T cell interactions with antigen. potential relevance for drug‐related lupus
Authors: Shaw Stephen , Shearer Gene M.
Published: February 2007

Understanding of cytotoxic T cell recognition may be relevant to the study of drug‐related lupus because either cell‐mediated cytotoxicity (CMC) contributes to triggering the disease or CMC provides an informative model to study T cell recognition of foreign antigen. As a model, CMC demonstrates the following: 1) Antigen presentation can occur by membrane insertion of the antigen, covalent modification of the cell surface, or cell surface adsorption of the antigen; these may be modes of presentation by which drug‐related antigens induce adverse responses. 2) HLA antigens regulate a wide variety of immune responses; this may be crucial in drug‐related lupus since HLA antigens may regulate autoimmune responses, may affect an individual' susceptibility to lupus, and may increase the risk for other specific adverse drug reactions.
Regulation of immune reactivity to collagen in human beings
Authors: Solinger A. M. , Stobo J. D.
Published: February 2007

Denatured beef collagen was tested for its ability to induce the production of leukocyte inhibition factor among the peripheral blood mononuclear cells from patients with rheumatoid arthritis and normal individuals. Responsiveness, defined as the production of leukocyte inhibition factor sufficient to cause greater than 20% inhibition of leukocyte migration, was significantly (P < 0.001, x2 = 31.1) associated with HLA‐DR4. All HLA‐DR4 positive individuals, including subjects without any evidence of synovitis, were collagen responders. There was no significant (P = 0.3) difference in the absolute reactivity of HLA‐DR4+ versus HLA‐DR4− individuals to respond to another antigen, Candida albicans. Collagen reactivity required interactions between macrophages and T cells and was directed against determinants inherent in the linear polypeptide, (Gly‐Pro)n. In 5 normal HLA‐DR4− nonresponders tested, absence of discernable reactivity to collagen was associated with the presence of antigen‐specific, radiosensitive suppressive T cells. These studies suggest that during the physiologic metabolism of collagen all individuals are exposed to Gly‐Pro determinants normally buried in the interstices of the collagen triple helix. In individuals whose major histocompatibility complex contains genes linked to those coding for HLA‐DR4, this results in the activation of reactive T cells. Conversely, in individuals lacking these genes, collagen‐specific suppressive cells predominate.
Immunologic effects of hydralazine in hypertensive patients
Authors: Litwin Allen , Adams Louis E. , Zimmer Hans , Hess Evelyn V.
Published: February 2007

Twenty‐seven hypertensive patients (23 blacks, 4 whites) treated with hydralazine had frequent serologic evidence of autoimmunity. However, only 1 patient developed a lupus syndrome. Acetylator phenotype influenced the autoimmune response; slow acetylators had a higher incidence and titers of autoantibodies. The lupus patient not only had high titers of autoantibodies but they were predominantly IgG in contrast to the predominant IgM antibodies found in other slow acetylators. Hydralazine treatment did not alter cell‐mediated immune responses and hydralazine antibodies were not detected. However, half the patients tested who received hydralazine had positive lymphoproliferative responses to the drug.
Differences in immunoregulatory t cell circuits between diphenylhydantoin‐related and spontaneously occurring systemic lupus erythematosus
Authors: Alarcón‐Segovia Donato , Palacios Ronald
Published: February 2007

We studied T cell surface markers, concanavalin A–induced, and spontaneously expanded suppressor cell function and the functions of postthymic precursor (Tar) cells in 3 patients with diphenyl‐hydantoin (DPH)‐related systemic lupus erythematosus (SLE). The findings were compared with those in 6 patients with spontaneously occurring SLE, 3 with active and 3 with inactive disease as well as with those in 3 normal volunteers. All 4 groups were age and sex matched. Findings were also compared to studies made in a group of 32 untreated idiopathic SLE patients and 32 normal controls. All T cell markers and immuno‐regulatory functions were normal in the DPH‐related SLE patients whereas all groups of patients with spontaneously occurring SLE had low numbers of Tγ cells, and Tar cells, and decreased concanavalin–A and spontaneously expanded suppressor, human feedback inhibition and generation of suppression functions. Since consanguineous relatives of patients with spontaneously occurring SLE have been shown to have decreased suppressor cell function and patients with long‐inactive spontaneous SLE continue to have defects in their T cell circuits, our findings may indicate that, in patients who develop SLE upon DPH intake the lupus diathesis uncovered by the drug probably resides in a site of immunoregulation different from that involved in spontaneously occurring lupus.
The nature of u.s. rheumatology practice, 1977
Authors: Epstein Wallace V. , Henke Curtis J.
Published: February 2007

A description of academic and community rheumatologist practice activities in the United States has been assembled from 826 responses to a 1977 survey of American Rheumatism Association members. Reported work hours and patient load are similar to other medical subspecialists, and three‐fourths of the clinical time is devoted to persons with predominantly rheumatic disease problems. Significant differences in activities occur between academic and community practices and among rheumatologists with different training backgrounds. Few characteristics vary significantly across geographic regions containing divergent rheumatologist‐population ratios. Descriptive productivity measures such as these are necessary for planning; they provide part of the empirical analysis required to give reality to manpower policies.
HEREDITARY DEFICIENCY OF THE THIRD COMPONENT OF COMPLEMENT IN TWO SISTERS WITH SYSTEMIC LUPUS ERYTHEMATOSUS‐LIKE SYMPTOMS
Authors: Sano Yuji , Nishimukai Hiroaki , Kitamura Hajime , Nagaki Kazuyoshi , Inai Shinya , Hamasaki Yasuteru , Maruyama Ikuro , Igata Akihiro
Published: February 2007

We observed two sisters with lupus‐like syndrome with homozygous C3 deficiencies. A 19‐year‐old woman and her 15‐year‐old sister developed malar rash, arthralgia, and photosensitivity, but antinuclear antibodies and LE cell preparations were negative. The older sister experienced recurrent bronchitis in her childhood, but the younger sister had no recurrent infections. Serum C3 was not detected immunochemically in either sister, and total complement activity and C3 hemolytic activity were extremely low.
Monocyte receptor function in patients with rheumatoid arthritis
Authors: Hoch Susan , Schur Peter H.
Published: February 2007

Monocytes from patients with rheumatoid arthritis (RA), osteoarthritis (OA), and normal volunteers were studied for abnormalities of Fc and C3 receptor function. Monocytes from the majority of 22 patients with active RA showed enhanced EA‐rosette formation and EA phagocytosis compared to monocytes from 20 normal volunteers and 10 OA patients. However, no significant differences in binding of EAC or uptake of iodinated aggregated gamma globulin were found among the 3 groups. Corticosteroid‐treated RA patients exhibited significant depression of EA‐rosette formation and phagocytosis. These results suggest that there is modulation of EA receptor function in monocytes from RA patients.
The private practice of rheumatology. the first 1,000 patients
Authors: Bohan Anthony
Published: February 2007

Although this report of the first 1,000 patients in a rheumatologic consultative private practice cannot necessarily reflect the general experience of rheumatology, certain conclusions may be valid and may help to guide the rheumatologist‐in‐training. Approximately 70% of our patients were categorized as having “inflammatory” or “connective tissue” disorders, rather than degenerative disorders. Internists and general practitioners were the principal referral sources. Over 80% of referrals came from a relatively small geographic radius of 10—15 miles. A population base of perhaps 200,000 people, therefore, may be necessary to support a purely rheumatologic practice. A relatively steady flow of 2 new patients per day was not significantly influenced by subsequent additional rheumatologists moving into the area. However, the pattern of referrals clearly changed to include more patient‐to‐patient referrals (nearly 30%), perhaps reflecting both loss of physician referral sources and the increasing number of referrals from satisfied patients over a period of time.
Titers of Antibodies to Rana in Rheumatoid Arthritis and Normal Sera
Authors: Venables Patrick J. W. , Roffe Lindsay M. , Erhardt Christopher C. , Maini Ravinder N. , Edwards Joan M. B. , Porter Anne D.
Published: February 2007

The disease specificity of antibodies to rheumatoid arthritis nuclear antigen (RANA) was examined by comparing anti‐RANA titers in sera from 100 patients with rheumatoid arthritis (RA) with sera from 93 healthy controls. Anti‐RANA antibodies were found in 86% of the RA sera and 56% of the controls. The higher titers in the RA sera were unrelated to clinical features or to measurements of circulating immune complexes or rheumatoid factors. To study the relationship of these antibodies to previous Epstein—Barr virus (EBV) infection, antibodies to the EB virus capsid antigen (VCA) were examined and found in 94% of the RA sera and 97% of the adult controls. Four of the six RA sera without anti‐VCA antibodies had detectable anti‐RANA antibodies, so that we might suggest anti‐RANA can arise in the absence of EBV infection. From absorption experiments with non‐EBV transformed extracts, we inferred that high anti‐RANA titers could be due to reactions with non‐Epstein—Barr virus related nuclear antigens. These data cast doubt on current speculation about a possible pathogenic role for Epstein—Barr virus in this disease.
Antibodies to Epstein—Barr Viral Antigens in Early Rheumatoid Arthritis
Authors: Silverman Stuart L. , Schumacher H. Ralph
Published: February 2007

Antibodies to Epstein—Barr viral (EBV) antigens were studied in 12 patients with early (less than 6 weeks) rheumatoid arthritis (RA) and compared to controls. Geometric mean antibody titers to viral capsid antigen, early antigens, and Epstein—Barr‐associated nuclear antigen (EBNA) were not elevated. Rather, they were comparable to titers in healthy volunteers and in patients with recent onset arthritis (less than 6 weeks) that did not develop into RA. In one patient with early RA, no serologic evidence of prior EBV infection or antibody to rheumatoid arthritis—associated nuclear antigen (RANA) was detected. Anti‐RANA was not seen in all patients with anti‐EBNA. These data do not support a primary role for EBV in the etiology of RA.
Clinical Trial of Penicillamine in Rheumatoid Arthritis
Authors: Rothermich Norman O. , Thomas Marvin H. , Phillips Vol K. , Bergen Waldemar
Published: February 2007

The medical records of our first 200 consecutive rheumatoid arthritis patients treated with penicillamine were analyzed retrospectively. All but 5 patients (97.5%) had undergone earlier chrysotherapy that resulted in either therapeutic failure or toxicity. Only 57 patients (28.5%) were still receiving penicillamine on January 1, 1981, and the duration of therapy ranged from 23 to 62 months. The dropout rate due to toxicity, therapeutic failure, relapse, or other reasons was very high (71.5%). Toxic effects required permanent discontinuance in 56 patients (28%). Therapy was discontinued for 36 patients (18%) because of no benefit. A striking number (20) had relapse after therapeutic success and while continuing to take penicillamine, and the therapy had to be discontinued, a relapse rate of 10%. Therapy for the remaining 15.5% was discontinued for miscellaneous reasons that were not related to penicillamine per se: patient anxiety (6%), lost to followup (5%), hospitalization for reasons unrelated to penicillamine therapy (2%), lack of cooperation and study protocol (1% each), or pregnancy (0.5%). By our criteria, 142 patients (71%) received benefit (remission or improvement). Therapy results for these patients were as follows: still on penicillamine on January 1, 1981 (28.5%); no longer receiving the drug due to toxicity (19.5%); no longer receiving penicillamine due to relapse while on continuing therapy (10%); no longer receiving penicillamine due to miscellaneous reasons not related to penicillamine therapy (13%). This study shows that penicillamine is a valuable drug in the treatment of rheumatoid arthritis, but its value in clinical practice is limited by a rather high incidence of both toxicity and relapse during treatment.
Decreased Platelet Serotonin Levels in Systemic Lupus Erythematosus
Authors: Meyerhoff John , Dorsch Carole A.
Published: February 2007

Platelet serotonin levels were measured in 41 patients with systemic lupus erythematosus (SLE) and 36 normal controls. SLE patients had significantly lower mean serotonin levels (243 ± 131 versus 414 ± 175 ng/ 109 platelets, P < 0.001); the lowest levels occurred in those patients with active disease. No differences in mean platelet serotonin levels were found when we compared patients with or without a history of renal disease, thrombocytopenia, or neuropsychiatric involvement. Decreased platelet serotonin did not correlate with increased release of platelet granule constituents, as measured by plasma levels of the α‐granule protein, β‐thromboglobulin.
Serum IgG and IgM Rheumatoid Factors by Solid Phase Radioimmunoassay
Authors: Wernick Richard , Lospalluto Joseph J. , Fink Chester W. , Ziff Morris
Published: February 2007

In this report, solid phase radioimmunoassays that specifically measure IgG rheumatoid factor (RF) and IgM RF in absolute concentrations are described. Polyclonal RF preparations were utilized as standards, and as little as 40 ng/ml of IgG RF and 1 ng/ml of IgM RF were detected. The IgG RF concentration of 26 seropositive rheumatoid sera was 439 ± 755 μg/ml (mean ± 1 SD), a level 107 times that of normal controls (P < 0.001). In contrast, levels for 49 children with juvenile rheumatoid arthritis (JRA) were 6.1 ± 3.7 μg/ ml for those with a polyarticular onset (JRA‐Po), 27.3 ± 113 μg/ml for the pauciarticular group (JRA‐Pa), and 12.6 ± 20.7 μg/ml for the group with a systemic onset (JRA‐S). None of these values differed significantly from the value of 6.0 ± 3.9 μg/ml measured in a juvenile control group. The IgM RF level in adult rheumatoid arthritis (RA) of 175 ± 221 μg/ml was also significantly elevated compared to controls (P < 0.001). In JRA, however, mean levels of 1.4 ± 2.0 μg/ml (JRA‐Po), 2.8 ± 8.3 μg/ml (JRA‐Pa), and 1.1 ± 0.7 μg/ml (JRA‐S) were not elevated significantly above the value of 1.2 μ 1.2 μg/ml measured in the juvenile control group. Hidden IgM RF was not found in 9 JRA sera tested. These marked differences in RF levels provide another indication that adult RA and JRA are distinct diseases.
Occurrence of Erythema Chronicum Migrans and Lyme Disease Among Children in Two Noncontiguous Connecticut Counties
Authors: Kaslow Richard A. , Samples Cathryn L. , Simon David G. , Lewis John N.
Published: February 2007

In May—November 1977 erythema chronicum migrans or Lyme arthritis occurred in at least 12 children in New London County, Connecticut, east of the original 3‐town epidemic focus. The attack rate (0.15 cases per 1,000 persons under 18) was considerably lower than within the focus itself but similar to the rate in towns west of the focus. No cases were identified in Litchfield County in northwest Connecticut. Observed rates of Lyme disease varied markedly within Connecticut in 1977.
Release of Pyrophosphate by Normal Mammalian Articular Hyaline and Fibrocartilage in Organ Culture
Authors: Ryan Lawrence M. , Cheung Herman S. , Mccarty Daniel J.
Published: February 2007

Calcium pyrophosphate dihydrate crystals are found most frequently in fibrocartilaginous tissue and to a lesser extent in hyaline articular cartilage. Previous investigators found that pyrophosphate (PPi) was released into the medium by immature rabbit hyaline cartilage and osteoarthritic human cartilage in organ culture but not by normal human or mature rabbit cartilage. By employing a sensitive fluorometric assay for PPi and correcting for hydrolysis of PPi during the incubations, we detected PPi release by all normal mammalian cartilage studied. PPi release per mg wet weight of lapine and canine cartilage was paralleled by uronic acid production. Meniscal fibrocartilage, the most common site of calcium pyrophosphate deposits, also elaborated PPi.
Amyloid Deposition in The Articular Structures of Akr Senescent Mice
Authors: Shimizu Katsuji , Kasai Ryuichi , Yamamuro Takao , Hosokawa Masanori , Takeshita Shuji , Takeda Toshio
Published: February 2007

Amyloid deposition in the articular structures occurred with high frequency in a strain of mice now being established as an animal model of senescence in this laboratory. The changes were most evident in the knee joint. Peripheral joints were always spared. The lesions appeared after 7 months of age, and the incidence reached 88% (7 of 8) in autopsied mice over 8 months of age. This is the first report of amyloid deposition in the joints of laboratory animals.
Association between endogenously activated t cells and immunoglobulin‐secreting b cells in patients with active systemic lupus erythematosus
Authors: Cohen Philip L. , Litvin David A. , Winfield John B.
Published: February 2007

Systemic lupus erythematosus (SLE) is characterized by increased numbers of circulating B cells activated polyclonally to secrete immunoglobulin. Because T cells secrete, or shed, various factors that are functionally important in regulating immunoglobulin production by B cells, a reverse hemolytic plaque assay was developed to quantitate such activated T cells. In this technique, we used a rabbit antiserum raised to supernatants of concanavalin‐A–stimulated human lymphocytes. The relevant antigenic specificity of this antiserum is directed toward the shed surface membrane determinant(s) preferentially expressed on activated T cells. Freshly isolated peripheral blood mononuclear cells from 14 SLE patients contained more than 10 times the number of endogenously activated T cells than cells from normal subjects. Within the SLE group, plaqueforming T cells were particularly increased in patients with active disease. By linear regression analysis, a significant positive correlation was revealed between such activated T cells and immunoglobulin‐secreting B cells, also measured by a reverse plaque assay (r = 0.83). It appears that both activated B cells and T cells circulate in increased numbers in SLE. Additional investigation will be required to define the molecular nature of the T cell product(s) being measured and to clarify the relationship of these findings to the immunoregulatory abnormalities in this disorder.
Stimulation of the respiratory burst in human neutrophils by crystal phagocytosis
Authors: Simchowitz Louis , Atkinson John P. , Spilberg Isaias
Published: February 2007

Exposure to monosodium urate crystals (MSU) stimulated the respiratory burst of human neutrophils as measured by increased O2 consumption and the generation of superoxide radicals (O2\documentclass{article}\pagestyle{empty}\begin{document}$ \[\bar .\] $\end{document}). From the comparison of data derived from nitroblue tetrazolium and cytochrome C reduction (two methods of detecting O2\documentclass{article}\pagestyle{empty}\begin{document}$ \[\bar .\] $\end{document} release), it appears that O2\documentclass{article}\pagestyle{empty}\begin{document}$ \[\bar .\] $\end{document} production in response to MSU may be compartmentalized, i.e., occur predominantly in the intracellular space. After exposure to MSU, neutrophils from patients with chronic granulomatous disease lost viability at the normal rate; thus products of the respiratory burst are not likely to be responsible for cell death.
The association of amyloid deposits and osteoarthritis
Authors: Egan Michael S. , Goldenberg Don L. , Cohen Alan S. , Segal David
Published: February 2007

Ten of eighteen consecutive patients who underwent total knee or hip arthroplasty for osteoarthritis had amyloid present in the surgically removed articular tissues. It was found in 6 of 13 cartilage specimens, 4 of 18 articular capsules, and 2 of 16 synovial membranes. In 3 of the cartilage specimens, the amyloid was adjacent to focal deposits of calcium pyrophosphate dihydrate crystals. Therefore, deposits of amyloid are not uncommon in osteoarthritis and may be more than incidental findings.
Antibody to cytomegalovirus in patients with sjögren's syndrome. As determined by an enzyme‐linked immunosorbent assay
Authors: Shillitoe Edward J. , Daniels Troy E. , Whitcher John P. , Strand C. Vibeke , Talal Norman , Greenspan John S.
Published: February 2007

By use of an enzyme‐lined immunosorbent assay (ELISA), patients with Sjögren's syndrome were found to have levels of serum IgG antibody to cytomegalovirus twice those of matched control subjects, and IgM antibody levels which were three times as high. It may be relevant that features of cytomegalovirus infection are similar to those of Sjögren's syndrome.
Gold inhibition of the production of the second complement component by lymphokine‐stimulated human monocytes
Authors: Littman Bruce H. , Schwartz Pamela
Published: February 2007

The ability of gold sodium thiomalate to inhibit production of the second complement component (C2) by monocytes stimulated by a lymphokine (monocyte complement stimulator) is demonstrated. This gold salt inhibits C2 production irreversibly if monocytes are incubated with it before or during lymphokine stimulation. Thiomalic acid is not inhibitory. Monocytes already stimulated by lymphokine are resistant to inhibition of C2 production by gold sodium thiomalate. Gold salts do not reduce monocyte viability, phagocytic ability (latex beads), accessory cell function (as measured by the ability to present antigen to autologous lymphocytes), or capacity to act as stimulating cells in mixed leukocyte culture. Gold sodium thiomalate's inhibition of monocyte responsiveness to lymphokine may be significant in explaining the therapeutic benefit of gold salts in rheumatoid arthritis.
Stimulation of dna synthesis by ascorbate in cultures of articular chondrocytes
Authors: Krystal Geoffrey , Morris Gregory M. , Sokoloff Leon
Published: February 2007

The addition of 0.2 mM Na L‐ascorbate increased the incorporation of 3H‐thymidine by rabbit articular chondrocytes in cell and organ culture. The stimulatory response of explants to ascorbate was potentiated by pretreatment of the cartilage with 0.2% clostridial collagenase (type 1) or trypsin for 15–30 minutes. In explants there was a latent period of 3 to 4 days before increased labeling of the nuclei could be detected. The effect was transient and declined after 8 days of culture. It was more evident in organ cultures of immature (3‐month‐old) than 2‐ to 3‐year‐old rabbits. Age differences were not detected in cell cultures. Explants of adult human articular cartilage were stimulated by ascorbate when the medium was supplemented with 10% fresh human serum but not by fetal bovine serum. The findings indicated that synthesis of DNA by articular chondrocytes in situ is regulated by responsiveness of the cells proper to compounds such as vitamin C, by properties of the extracellular matrix, and by factors in the serum. Ascorbate was cytotoxic at concentrations >0.2 mM in the presence of certain batches of serum and when added to monolayers before the cells attached to the surface of the flask.
Quantitation of rat liver xanthine oxidase by radioimmunoassay. A mechanism for sex‐specific differences
Authors: Decker Douglas E. , Levinson Dennis J.
Published: February 2007

To further delineate the mechanism responsible for the differences in xanthine oxidase activity in male and female Sprague—Dawley rats, a sensitive and specific radioimmunoassay (RIA) was developed for the measurement of hepatic xanthine oxidase. The RIA could detect as little as 5 ng of liver enzyme. Specificity of the RIA was confirmed by 1) Ouchterlony double immuno‐diffusion in which a single precipitin band exhibited xanthine oxidase activity, when crude liver homogenate and an enzyme‐specific stain were used; 2) parallelism between purified 125I‐labeled xanthine oxidase and serial dilutions of crude liver homogenate; 3) a linear correlation between xanthine oxidase activity and the level of enzyme protein; and 4) a single protein band coincident with purified xanthine oxidase, when an immunoprecipitate prepared from antisera and crude liver homogenate was analyzed on sodium dodecyl sulfate (SDS) polyacrylamide gels. Whether xanthine oxidase activity was assayed in the absence of nicotinamide adenine dinucleotide (NAD+) (oxidase form) or in the presence of NAD+ (dehydrogenase), male values were consistently higher, and both forms of the enzyme correlated significantly with each other. When purified to homogeneity, neither form of the enzyme was appreciably affected by 17β‐estradiol or testosterone propionate. When the RIA was employed, levels of hepatic xanthine oxidase were significantly greater in male than in female rats. We concluded from these data that increased xanthine oxidase activity in the male corresponds to a greater quantitative complement of xanthine oxidase protein. Furthermore, lower xanthine oxidase activity in the female cannot be explained by immunologically cross‐reactive material without enzyme activity nor by a direct sex—steroid enzyme interaction.
Antibodies to and elevations of beta 2 microglobulin in the serum of ankylosing spondylitis patients
Authors: Curry Russell , Thoen Jorn , Shelborne Charles , Gaudernack Gustav , Messner Ronald
Published: February 2007

Antibodies to beta 2 microglobulin are found in systemic lupus erythematosus patients and are important in the lymphocytotoxic reactions of sera from such patients. In this study, beta 2 microglobulin antibodies were measured with the use of an enzyme‐linked immunosorbent assay with purified beta 2 microglobulin antigen and peroxidase‐labeled anti‐human IgG or IgM. IgG antibodies to beta 2 microglobulin were found in 68% of 22 patients with ankylosing spondylitis. This incidence was higher than the 5% in 80 controls (P < 0.01) and similar to the 71% incidence found in 35 patients with systemic lupus erythematosus. Eleven (27%) of 41 patients with rheumatoid arthritis had elevated levels of antibodies to beta 2 microglobulin (P < 0.01). The mean antibody levels expressed in enzyme units were 0.125 for patients with ankylosing spondylitisis, 0.157 for those with systemic lupus erythematosus, 0.101 for those with rheumatoid arthritis, and 0.067 for controls. IgM anti—beta 2 microglobulin was not significantly different from controls. A competitive binding assay with enzyme‐labeled beta 2 microglobulin was used to determine serum beta 2 microglobulin. These values were also found to be elevated in 48% of patients in all 3 disease categories (P < 0.01). Beta 2 microglobulin antibodies and serum beta 2 microglobulin did not correlate with each other, renal diseases or antinuclear antibodies in patients with systemic lupus erythematosus, with rheumatoid factor or severity of articular disease in patients with rheumatoid arthritis, or with peripheral arthritis or iritis in those with ankylosing spondylitis. Although antibodies to beta 2 microglobulin might reflect a general disturbance of immune regulation in patients with systemic lupus erythematosus, their presence in those with ankylosing spondylitis, a disease closely associated with a specific HLA allotype and not usually associated with formation of autoantibody, suggests that they might play a role in the pathogenesis of the latter disease.
Stimulation of the plasminogen activator activity of human synovial fibroblasts by retinoids
Authors: Hamilton John A.
Published: February 2007

Nonrheumatoid human synovial fibroblasts in culture, while having low basal plasminogen activator levels, were stimulated to produce much more of this protease activity by low concentrations of a series of retinoids. The most potent retinoid tested, all‐trans retinoic acid, was active over the range 10‐11–10–6M. The increased plasminogen activator activity in the presence of 10–6M retinoic acid was first observed within 40 minutes under appropriate experimental conditions, required RNA and protein synthesis, and was reversible after short incubation periods. This stimulation was suppressed by low concentrations of antiinflammatory glucocorticoids such as dexamethasone.
Improving patient cooperation with arthritis treatment regimens
Authors: Jette Alan M.
Published: February 2007

This review of the literature on patient cooperation with arthritis treatment recommendations is categorized into 2 sections—involuntary and voluntary lack of cooperation. Extrapolating primarily from investigations of patients with other chronic diseases, 5 stategies for reducing involuntary patient noncooperation and 4 recommendations for improving voluntary patient cooperation are discussed. Although much remains to be learned about factors that influence patient cooperation with arthritis treatment recommendations, the application of existing knowledge can improve current levels. Determined efforts by health professionals are necessary if the excessive waste resulting from patient noncooperation is to be reduced. Shortcomings of past research and fruitful avenues for future empirical work in this important area are discussed.
Antibodies to collagen in scleroderma
Authors: Mackel Anne M. , Delustro Frank , Harper Frank E. , Roy E. Carwilele
Published: February 2007

Using the enzyme‐linked immunosorbent assay (ELISA), we detected antibodies to interstitial (type I) and basement membrane (type IV) collagens in the sera of patients with scleroderma (systemic sclerosis). Antibodies against type IV collagen were found in significant levels in these patients and correlated with the presence of abnormal pulmonary diffusion capacity. Levels of antibodies to type I collagens also correlated significantly with pulmonary diffusion capacity. Absorption of sera with type I or type IV collagens before analysis in the ELISA eliminated reactivity in an antigen‐specific pattern, indicating that these antibodies reacted with determinants specific for either type I or type IV collagens. The removal of immune complexes by ultracentrifugation had no effect on serum antibody levels. Autoantibodies to basement membrane and interstitial collagens may participate in the pathogenesis of scleroderma.
Aspirin survival in human blood modulated by the concentration of erythrocytes
Authors: Costello Patrick B. , Green Floyd A.
Published: February 2007

In vitro aspirin hydrolysis rates were measured in fresh human whole blood and in its separate components. The half‐life of aspirin in whole blood was relatively rapid (mean 22.2 ± 3.9 minutes) and exhibited a significant negative correlation with hematocrit (r = −0.96). Hydrolysis of aspirin in buffer that contained only washed red blood cells (40%) was significantly more rapid (mean half‐life 17.5 ± 2.0 minutes) than that in whole blood. When aspirin was incubated in solutions of washed red blood cells that contained human serum albumin in various concentrations, the aspirin half‐life was found to vary directly with the concentration of albumin used; at normal levels of albumin, the hydrolysis rate of aspirin approximated that measured in whole blood. The presence of diisopropyl fluorophosphate in low concentrations (0.02–0.05 mM) markedly inhibited the rate of aspirin hydrolysis in washed red blood cells and whole blood. We conclude that enzyme(s) linked to the erythrocyte, probably membrane‐bound acetylcholinesterase, control the survival of aspirin in blood.
Gonococcal arthritis–dermatitis syndrome. study of serum and synovial fluid immune complex levels
Authors: Manicourt Daniel H. , Orloff Serge
Published: February 2007

Immune complexes from serum and synovial fluid were detected by the C1q binding assay in 12 patients with disseminated gonococcal infection. Since immune complexes were regularly higher in synovial fluids than in paired sera and were not detected by the monoclonal rheumatoid factor radioimmunoassay, we suggest that IgM may be present in these complexes and that this represents a primary immune response. In contrast, only 2 of 10 patients with local gonococcal infection were slightly positive both with the C1q assay and the monoclonal rheumatoid factor assay. In patients with disseminated gonococcal infection, immune complexes closely paralleled the disease activity and negatively correlated with complement levels. Synovial fluid immune complexes seem to occur in the early and aseptic phase of polyarthritis and to aid the entrance of circulating gonococcal organisms. From the results of our study, it seems that immunologic processes initiate and/or sustain inflammation in disseminated gonococcal infections that appear, at least in part, as a form of reactive arthritis.
GAMMA‐carboxyglutamate excretion and calcinosis in juvenile dermatomyositis
Authors: Lian Jane B. , Pachman Lauren M. , Gundberg Caren M. , Partridge RAYMOND E. H. , Maryjowski Mona C.
Published: February 2007

Proteins containing gamma‐carboxyglutamic acid (Gla) are present in subcutaneous calcifications of adults with dermatomyositis or scleroderma. Sixteen children with juvenile dermatomyositis, including 7 with subcutaneous calcifications, were studied to determine if abnormal synthesis or turnover of Gla‐containing proteins occurred. All study children had increased excretion of the amino acid that was greater than that of age‐and sex‐matched controls. Patients who had juvenile dermatomyositis with calcifications had a 3‐fold increase in Gla excretion, and those without calcinosis had a 2‐fold increase. Five other children with various connective tissue disorders and subcutaneous calcification had 2‐fold increased Gla excretion. Decreased excretion of this amino acid was associated with salicylate therapy (80 mg/kg/24 hours). The data suggest an abnormal turnover of Gla‐containing proteins in juvenile dermatomyositis. Metabolism of these proteins may be involved in the pathophysiology of soft‐tissue calcification in children.
Susceptibility to adjuvant arthritis in da and F344 RATS. A dominant trait controlled by an autosomal gene locus linked to the major histocompatibility complex
Authors: Battisto Jack R. , Smith R. N. , Beckman Karla , Sternlicht Mona , Welles Wanda L.
Published: February 2007

The heritability of adjuvant‐induced arthritis in rats of the DA and Fisher 344 strains was examined. Development of arthritic lesions in response to a single injection of supplemented Freund's complete adjuvant has been found to be controlled by an autosomal, dominant gene locus, Ar. The capacity to respond was present in DA rats and absent in our Fisher rats. Ar has been found to be linked to the major histocompatibility complex genes with which it exhibits a high rate of recombination.
Skin response to intradermal dna and rna in systemic lupus erythematosus
Authors: Konttinen Yrjöt. , Tolvanen Erkki , Johansson Eija , Reitamo Sakari , Wegelius Otto
Published: February 2007

The local response of 18 patients with active systemic lupus erythematosus to 0.1 ml of intradermally injected 0.1% polymerized calf thymus DNA and synthetic double‐stranded polyinosinic‐polycytidylic acid was studied. In 14 patients positive for DNA, 61 ± 8% of the inflammatory cells in the subepidermis at 24 hours were acid alpha‐naphthyl acetate esterase–positive T lymphocytes. A leukocytoclastic vasculitis was observed in the deeper dermis. Rheumatoid arthritis patients and acne patients had negative responses. These results indicated an abnormal cellular and humoral in vivo response by patients with systemic lupus to DNA. It is suggested that the epidermal Langerhans cells were responsible for the topographic dichotomy of the local DNA response. Test results were positive for polyinosinic‐polycytidylic acid in 12 patients, for DNA in 14 patients, and for both in 9 patients. In the 9 patients with positive results for both tests, comparison of responses to each test indicated that the reaction intensity was dependent on the patient and not on the type of polynucleotide acid that was injected.
Prolonged lifespans in female nzb/nzw mice treated with the experimental immunoregulatory drug frentizole
Authors: Walker Sara Ellen , Solsky Marilyn , Schnitzer Bertram
Published: February 2007

Autoimmune female New Zealand Black/New Zealand White mice were treated with frentizole, an experimental immunosuppressive drug. Three groups of “young,” 8‐week‐old mice received high‐dose frentizole (80–84 mg/kg/day), low‐dose frentizole (8 mg/kg/day), or no drug (controls); these mice were followed until spontaneous death. Three groups of “old,” 24‐week‐old mice with established lupus‐like disease were treated with high or low doses of frentizole. Old control mice received no drug. After 12 weeks of therapy, surviving old mice were killed. Beneficial therapeutic response was achieved when high‐dose treatment was started at an early age; antiDNA values were suppressed, and longevity was prolonged significantly. Frentizole did not arrest the progression of renal disease in old mice. Glomerulonephritis and vasculitis were the most common causes of death in young and old animals. Twenty‐nine percent of young, high‐dose‐treated mice died with neoplasms. Large glomerular deposits of IgG, IgM, and C3 were present in renal tissue from treated and control mice. Peripheral lymphocyte counts and mitogenic responses of spleen cells were not changed by treatment. The efficacy of frentizole in a murine model of lupus supports its usefulness as an immunoregulatory drug.
Igm and igg anti‐f(ab )2 antibodies in rheumatoid arthritis and systemic lupus erythematosus
Authors: Heimer Ralph , Wolfe Lawrence D. , Abruzzo John L.
Published: February 2007

Radioimmunoassays for anti‐F(ab )2 antibodies, which feature the use of goat anti‐human Fc antibody for correcting potentiation of IgM anti‐F(ab )2 antibody titers by endogenous IgM anti‐Fc antibodies (rheumatoid factors), are described. Individuals with classic rheumatoid arthritis had significantly more IgM anti‐F(ab )2 antibody (P < 0.001) and IgG anti‐F(ab )2 antibody (P = 0.05) than did individuals with systemic lupus erythematosus or normal volunteers. There is some similarity in patterns of isotype distribution of anti‐F(ab )2 antibodies and rheumatoid factors.
Cytotoxic activity of sera from scleroderma and other connective tissue diseases. lack of cellular and disease specificity
Authors: Shanahan William R. , Korn Joseph H.
Published: February 2007

It has been suggested that serum‐mediated endothelial cell injury in scleroderma might contribute to disease pathogenesis. We compared the effect of serum from 28 scleroderma patients on human umbilical cord vein endothelial cell and human foreskin fibroblast proliferation with sera from 28 healthy controls, 13 patients with isolated Raynaud's disease, 22 patients with systemic lupus erythematosus, 19 patients with rheumatoid arthritis, and 15 patients with other connective tissue diseases. Five sera (2 scleroderma, 1 morphea, 1 rheumatoid arthritis, 1 systemic lupus erythematosus) markedly suppressed 3H‐thymidine incorporation into both endothelial cells and fibroblasts (to > 3 SD below the mean of the control group). These sera were also cytotoxic to endothelial cells and fibroblasts in a 51Cr release assay. Three additional sera (1 Raynaud's, 2 controls) suppressed endothelial cell proliferation moderately (>2 SD but <3 SD from control mean) but did not affect fibroblasts. Mean 3H‐thymidine incorporation by endothelial cells and fibroblasts in scleroderma serum was comparable to that of the other disease and control groups. In contrast to previous studies, we found serum‐mediated endothelial cell cytotoxicity occurred infrequently in scleroderma, occurred also in other connective tissue diseases, and was without target cell specificity. Furthermore, scleroderma serum did not appear to stimulate fibroblast proliferation.
Evidence for pseudomonas antigen in immune complexes in pseudomonas osteomyelitis
Authors: Rahn Daniel W. , Steere Allen C. , Grodzicki Robert L. , Levine Joseph H. , Hardin John A.
Published: February 2007

In infections associated with immune complex disease, microbial antigens have rarely been found in the complexes. Using an enzyme‐linked immunoassay, we studied the immune complexes of a patient who had hematogenous Pseudomonas aeruginosa osteomyelitis associated with palpable purpura, arthritis, and microscopic hematuria. After separation of the complexes into high and low molecular weight fractions, a 6hyphen;fold selective concentration of P aeruginosa antibody was found in the low molecular weight fraction compared with the concentration in the serum. Following disruption of immunoglobulin, the high molecular weight fraction competed with solid‐phase P aeruginosa antigen for P aeruginosa antibody from another source. After successful treatment of the infection, the patient's symptoms resolved, and the complexes disappeared. These findings strongly suggest that immune complexes in this patient contained P aeruginosa antigen and antibody that may have been pathogenetic in his disease.