bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies of immune functions of patients with systemic lupus erythematosus
Authors: Sakane Tsuyoshi , Steinberg Alfred D. , Arnett Frank C. , Reinertsen James L. , Green Ira
Published: February 2007

In normal individuals T cells are stimulated to proliferate by autologous non‐T cells; this is called the autologous mixed lymphocyte reaction (MLR). Previous studies demonstrated that such an autologous MLR was markedly impaired in patients with active systemic lupus erythematosus (SLE). To determine whether the defect resided in the responding cell or the stimulating cell, mixing experiments were performed using cells from identical twins. We identified two sets of identical twins discordant for SLE activity and correspondingly discordant in their degree of responsiveness in the autologous MLR. Reciprocal mixing experiments were performed in which T cells from one twin of each pair were mixed with non‐T cells from the other twin of that pair. These studies indicated that patients with active SLE have a defect in the ability of non‐T cells to stimulate as well as a defect in the ability of both Tγ and Tnonγ cells to respond in the autologous MLR. Patients with inactive SLE have a defect only in responsiveness of Tγ cells.
The arthropathy of fabry disease
Authors: Sheth Kumudchandra J. , Bernhard Gerson C.
Published: February 2007

Fabry disease, an X‐linked recessively inherited glycosphingolipidosis, results from defective activity of the lysosomal enzyme ceramide trihexosidase termed α‐galactosidase A (1). The cumulative deposition of the substrate ceramide trihexose (CTH) in various tissues accounts for the clinical manifestations of the disease (2). Although excruciating pains in the extremities are frequently present, pains localized in joints are uncommon. There is a characteristic arthropathy of the distal interphalangeal joints of the fingers with limitation of extension and degenerative changes which are evident on radiologic examination (3). Because patients with Fabry disease have attacks of fever, pains in extremities, and elevated ESR, rheumatic fever or rheumatoid arthritis is frequently the initial diagnosis (3). We wish to report synovial and joint capsule biopsies from a male who was initially diagnosed as having rheumatoid arthritis and was later confirmed to have Fabry disease by low plasma α‐galactosidase level.
Ankylosing spondylitis and multiple sclerosis
Authors: Khan Muhammad A. , Kushner Irving
Published: February 2007

In a retrospective study of 196 patients with long‐standing ankylosing spondylitis, 2 patients were found who had multiple sclerosis as well. This observation supports the recently proposed existence of an association between these diseases.
Elastofibroma: A rare cause of periscapsular pain
Authors: Prete Pamela , Thorne Roger P.
Published: February 2007

In 1961 Järvi and Säxen reported 4 cases of a previously undescribed connective tissue tumor containing elastinophilic fibers which they termed elastofibroma dorsi (1). Their patients were elderly, and the tumors were all located in the subscapular space adjacent to the apex of the scapula and beneath the rhomboid and latissimus dorsi muscles. One of the four had bilateral tumors.

Since the original description, over 60 cases have been reported (1–30). The true incidence of this unique soft tissue tumor is probably underestimated because of its obscure location and benign and usually silent course. Elastofibroma has not been recognized as a cause of periscapular complaints despite its characteristic scapular location.

The purpose of this report is to present a case of bilaterally occurring elastofibromas that caused periscapular pain in a 61‐year‐old man and review the salient features of this rare lesion.
Resolution of the identity of certain antigen‐antibody systems in systemic lupus erythematosus and sjögren's syndrome: An interlaboratory collaboration
Authors: Alspaugh Margaret , Maddison Peter
Published: February 2007

The Ouchterlony technique of double immunodiffusion, combined with some physicochemical characterization of the antigens involved, has been used to characterize several antigen‐antibody systems of importance in certain connective tissue diseases, notably systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), Sjögren's syndrome, rheumatoid arthritis, scleroderma, and poly‐ and dermatomyositis (1–12). These systems appear to have not only considerable diagnostic significance but also importance in determining prognosis and disease course.
Ophthalmologic safety of long‐term hydroxychloroquine treatment
Authors: Rynes Richard I. , Krohel Gregory , Falbo Anthony , Reinecke Robert D. , Wolfe Bruce , Bartholomew Lee E.
Published: February 2007

Ocular toxicity of long‐term hydroxychloroquine treatment was assessed by regular ophthalmologic examinations in 99 patients. No patient developed significant loss of vision or visual field constriction to a white test object. Three patients had evidence of toxicity, but the medication had to be permanently discontinued in only one who subsequently had regression of all abnormalities except visual field constriction to a red test object. Neither duration of treatment nor the diagnosis of systemic lupus erythematosus predisposed patients to toxicity.
Simultaneous immunologic studies of skin and kidney in systemic lupus erythematosus
Authors: Morris Richard J. , Guggenheim Stephen J. , Mcintosh Rawle M. , Rubin Robert L. , Kohler Peter F.
Published: February 2007

Thirty‐two biopsies of kidneys and of normal skin were performed simultaneously on patients with systemic lupus erythematosus (SLE) to determine whether the deposition of immune reactants in skin was correlated with the severity of renal injury or with several serologic measures of systemic disease activity. Immunofluorescent deposits at the dermal‐epidermal junction (lupus band test) did not correlate with any clinical or histologic measures of glomerulonephritis or with serologic abnormalities. Immune deposits in dermal venules were found in 56% of the skin biopsies and were correlated with hypocomplementemia and higher levels of immune complexes in serum, and possibly with glomerular subendothelial electron dense deposits. Azathioprine therapy was correlated with absence of both subepidermal and vascular immune deposits. Immunofluorescent findings on serial skin biopsies on 13 patients were highly inconsistent. It is concluded that the lupus band test is clinically useful only as a diagnostic aid but not helpful in assessing renal or serologic activity of lupus, and that dermal vascular deposits of immunoglobulin or complement are more frequent than previously recognized and correlate with measures of circulating immune complexes.
A tissue culture model of cartilage breakdown in rheumatoid arthritis
Authors: Steinberg James , Tsukamoto Soichiro , Sledge Clement B.
Published: February 2007

The effects of hydrocortisone, indomethacin, and gold thiomalate on proteoglycan release were assessed in bovine nasal cartilage‐rheumatoid synovium cocultures. Of the three agents, only hydrocortisone consistently inhibited both basal and synovium‐stimulated cartilage breakdown. Hydrocortisone responsivity was a direct function of the degradative capacity of synovial specimens, and this was equally well demonstrated both in patients receiving long‐term therapy and those given perioperative glucocorticoid therapy. The data are consistent with significant hydrocortisone inhibition of lysosomal enzyme‐mediated degradation of cartilage.
Quantification of human plasma inorganic pyrophosphate
Authors: Ryan Lawrence M. , Kozin Franklin , Mccarty Daniel J.
Published: February 2007

Plasma inorganic pyrophosphate (PPi) levels rose predictably (28%) after vigorous systemic exercise and returned to baseline values after 30 minutes of rest. Plasma PPi levels were greater (36%) in femoral venous blood than in femoral arterial blood. Forearm muscular exercise, however, did not result in a detectable rise in plasma PPi levels in antecubital veins. The physiologic reasons for both the systemic exercise effect and the arteriovenous differences remain unknown. Measurement of plasma PPi for 10 consecutive days in a single normal subject under basal conditions, where these and other previously identified biologic variables (fasting and diurnal variation) were controlled, showed a coefficient of variation of 12.7%. Thus biologic variability contributed less to observed variation in plasma PPi than did methodologic errors (coefficient of variation of method = 8%). The striking reproducibility of plasma PPi in this subject suggests that this important metabolite is under rather tight homeostatic control.
A review of the use, evaluations, and criticisms of the preliminary criteria for the classification of systemic lupus erythematosus
Authors: Canoso Juan J. , Cohen Alan S.
Published: February 2007

The use of the Preliminary Criteria for the Classification of Systemic Lupus Erythematosus (SLE) has been reviewed. Most authors describing 10 or more patients have used the criteria. Although originally designed for classification of patients, the criteria have often been used for the diagnosis of SLE. The sensitivity of the criteria was evaluated and found to be similar to the 90% reported in the original ARA trial. Studies on specificity yielded conflicting results. Various suggestions to improve the criteria have been made, including a more detailed description of some of the organ involvements and the adoption of laboratory tests that have been improved since or were unavailable at the time of original publication of the criteria.
Serum complement abnormalities in the antinuclear antibody‐positive relatives of children with systemic lupus erythematosus
Authors: Lehman Thomas J. A. , Hanson Virgil , Singsen Bernhard H. , Kornreich Helen K. , Bernstein Bram , King Karen K.
Published: February 2007

Serum C3, C4, and total hemolytic complement (CH50) levels were measured for 21 children with systemic lupus erythematosus (SLE) and 81 first degree relatives. The mean serum C4 and CH50 levels of the 12 relatives with antinuclear antibodies (ANA) were depressed to levels equal to those of the index cases. A similar depression was not found for C3, nor was there a depression of C3, C4, or CH50 in the relatives without ANA. If preexistent depression of C4 levels can be documented in the ANA‐positive relatives of index cases, it may provide an explanation for the inherited predisposition to SLE in some families.
Cardiac involvement in polymyositis
Authors: Denbow Charles E. , Lie J. T. , Tancredi Robert G. , Bunch Thomas W.
Published: February 2007

Cardiac involvement in polymyositis was investigated in 20 autopsied cases. Clinically, 13 of 18 patients had abnormal electrocardiograms, and 9 of the 20 patients had previous evidence of congestive heart failure. Histologically documented myocarditis was detected in 6 patients (4 with congestive heart failure and 2 without), 4 of whom also had small vessel disease of the myocardium. Patients with polymyositis may have a cardiopathy in the absence of overt myocardial inflammatory disease.
Collagenase production by synovial fibroblasts treated with phorbol myristate acetate
Authors: Brinckerhoff Constance E. , Mcmillan Rodger M. , Fahey John V. , Harris Edward D.
Published: February 2007

A series of intracellular events occurring after treatment of rabbit synovial fibroblasts with 0.01 μg/ml phorbol myristate acetate (PMA) were measured. Ten minutes after addition of PMA, there was a temporary increase in intracellular cyclic AMP levels, followed by a transient decrease in incorporation of 3H‐thymidine into DNA. Approximately 500 ng/mg cell protein of PGE2 were found in culture medium from the 12‐ to 24‐ hour incubation period, but significant collagenase was not detectable until 24 to 36 hours. Treatment with aspirin or indomethacin abolished PGE2 production but did not affect collagenase levels. Production of enzyme was associated with a cessation of cell proliferation, measured by protein content/culture and cell number. No enzyme was detectable in untreated cultures. Synovial fibroblasts treated with phorbol myristate acetate may provide a good model for studies on the mechanism of induction of collagenase production.
Sex hormone modulation of autoimmunity in NZB/NZW mice
Authors: Roubinian Jirayr , Talal Norman , Siiteri Pentti K. , Sadakian Jacqueline A.
Published: February 2007

Prepubertal castration of female NZB/NZW (B/W) hybrid mice did not influence mortality, whereas prepubertal castration of male B/W mice caused premature death and enhanced autoantibody formation. Prepubertal castration combined with the administration of sustained estradiol‐17‐β (E‐2) enhanced mortality and autoantibody development and promoted immune complex nephritis in both sexes. The enhanced mortality observed in castrated males was significantly reduced if they were treated with sustained progesterone (P). Mice of both sexes receiving P had the highest levels of autoantibodies. By contrast, sustained 5‐α‐dihydrotestosterone (DHT) and testosterone (T) suppressed these autoimmune parameters. The suppressive effect of androgens was not a nonspecific anabolic property, since danazol (a compound with attenuated masculinizing but intact anabolic properties) was ineffective in suppressing disease. AntiDNA antibody formation developed prematurely in males given cyproterone acetate, an antiandrogen. However, this metabolic blocker did not influence mortality or proteinuria. Unexpected early enhancement of mortality was observed in female and male mice castrated and given both E‐2 and DHT (when compared to sham‐operated controls or mice given E‐2 alone). When castration was combined with the administration of both E‐2 and P, mortality was enhanced in males but was similar to E‐2 alone in females. Androgen therapy was also suppressive when it was delayed and given to female mice with more advanced disease. DHT given to intact 3‐month‐old or castrated 6‐month‐old B/W females significantly improved survival without affecting the serum levels of anti‐DNA antibodies. These observations demonstrate that sex hormones significantly modify disease in B/W mice and may have therapeutic potential.
Approach to the study of the role of sex hormones in autoimmunity
Authors: Steinberg Alfred D. , Melez Kathleen A. , Raveche Elizabeth S. , Reeves J. Patton , Boegel William A. , Smathers Patricia A. , Taurog Joel D. , Weinlein Lisa , Duvic Madeleine
Published: February 2007

Investigators from this laboratory have been studying sex hormones in normal and autoimmune mice for the past 10 years. We have found that immune responses to DNA are influenced by sex hormones. Androgens reduce and estrogens increase both spontaneous and immunization‐induced antibodies to single‐stranded DNA in NZB x NZW, NZB x C3H, NZB x CBA, NZB x DBA mice. Treatment of female NZB/W mice with testosterone or 5 α dihydrotestosterone retards the progress of autoimmunity. Castration is not necessary for this effect. In contrast, danazol has no favorable effect on the disease process. Estrogens cause a marked acceleration of autoimmunity and a reduction in thymus weight. During the course of these studies, we found that a number of problems or variables arise in studying sex hormone effects, including: 1) X‐linked genes, 2) metabolism of testosterone to estrogens, 3) dose of hormone, 4) age at which administration is initiated, 5) differential effects of sex hormones on different autoantibodies and various immune responses.
Alterations of estrogen metabolism in systemic lupus erythematosus
Authors: Lahita Robert G. , Leon Bradlow H. , Kunkel Henry G. , Fishman Jack
Published: February 2007

Estradiol metabolism in 10 patients with systemic lupus erythematosus (SLE) and 29 normal controls was studied by measurement of urinary metabolites after injection of labeled 3H‐estradiol. Patients with SLE manifested increased 16‐hydroxylation of estrone. Diseased men differed from diseased women to the extent that only 16α‐hydroxyestrone was elevated in men, whereas women had elevations of both 16α‐hydroxyestrone and estriol. These data suggest that patients with SLE have abnormal patterns of estradiol metabolism, leading to increased estrogenic activity.
Glucocorticoids and immune responses
Authors: Crabtree Gerald R. , Gillis Steven , Smith Kendall A. , Munck Allan
Published: February 2007

We describe a series of investigations on mechanisms of antiinflammatory and immunosuppressive actions of glucocorticoids. Glucocorticoid receptors and primary mechanisms of action have been studied with isolated rat thymus cells. When added to these cells glucocorticoids immediately form cytoplasmic hormone‐receptor complexes which after activation bind to the nuclei where they apparently induce mRNA for specific proteins that rapidly inhibit glucose transport and acetate incorporation into lipids. Protein and RNA metabolism are inhibited more slowly and eventually the cells die. With normal peripheral human lymphocytes, similar but slower effects are produced. A dramatic increase in receptor sites per cell is seen in lymphocytes stimulated with concanavalin A or antigen. This increase is probably associated with preparation for mitosis. We do not find, contrary to widespread belief, that these stimulated cells are insensitive to glucocorticoids. Such insensitivity has been invoked to explain the insensitivity to glucocorticoid suppression of secondary compared to primary immune responses. An alternative explanation emerges from our experiments with T‐cell growth factor. T‐cell growth factor, produced by mitogen or antigen stimulated spleen cells, is necessary for the proliferation of T‐lymphocytes in culture and may be responsible for clonal expansion of antigen‐responsive T‐cells. Treatment of Con A‐stimulated rat spleen cells or human peripheral mononuclear cells with 100 nMdexamethasone inhibits the production of the growth factor by 95%. This effect is specific for glucocorticoids. Addition of T‐cell growth factor completely reverses the inhibition by glucocorticoid of mitogen‐induced blastogenesis. We propose that the inhibitory actions of glucocorticoids on antigen‐ or mitogen‐induced T‐cell blastogenesis are related to inhibition of production of T‐cell growth factor and that the reason the primary immune response is more sensitive to glucocorticoids is that by inhibiting production of T‐cell growth factor, glucocorticoids block the clonal expansion necessary to amplify the primary response. We have also studied effects of glucocorticoids on Fc receptors, which play important roles in phagocytosis and other aspects of immune responses. Treatment of the human progranulocytic cell line HL‐60 with dexamethasone for 72 hours reduces by 35‐50% the Fc receptors per cell with no effect on cell viability or proliferation and slight increase in leucine incorporation. The effect is specific for glucocorticoids. These findings indicate that an important component in glucocorticoid‐induced immunosuppression may be a reduction in Fc receptors, and with the results on T‐cell growth factor, suggest that glucocorticoids regulate immune processes via effects on lymphokines and other immunologically important proteins.
Sex differences in response to hepatitis b virus
Authors: Blumberg Baruch S.
Published: February 2007

Sex differences related to responses to hepatitis B infection are reviewed. In most human populations there is a higher prevalence of chronic carriers of hepatitis B virus (persistently HBsAg+) among males than females. Females are more likely than males to produce anti‐HBs in response to infection. Diseases associated with increased frequencies of carriers are more prevalent among males. The response of parents to hepatitis B virus (HBV) infection appears to affect the sex ratio at birth of their offspring. Couples in which either parent is a carrier have higher sex ratios (higher proportion of males) compared with couples in which neither parent is HBsAg+. Couples in which the mother is anti‐HBs+ have children with lower sex ratios than either carriers or uninfected couples.
Infection in patients with systemic lupus erythematosus
Authors: Perez H Daniel , Andron Richard I , Goldstein Ira M
Published: February 2007

We have found subnormal amounts of chemotactic activity in zymosan‐treated sera from 13 of 29 patients with systemic lupus erythematosus (SLE). As an explanation for this abnormality, the presence of a uniquely specific, heat‐stable inhibitor of complement (C5)‐derived chemotactic activity has been documented in sera from 11 of these patients. Sera from 2 other patients contained elevated levels of nonspecific, heat‐labile chemotactic factor inactivator (CFI) activity. The serum from 1 patient contained the heat‐stable inhibitor as well as elevated levels of CFI. Patients with SLE whose sera contained the heat‐stable inhibitor had more active disease clinically, but otherwise they were indistinguishable from patients without the inhibitor. When patients with the heat‐stable inhibitor improved clinically, this usually was accompanied by a decrease in serum inhibitory activity. Only one episode of bacterial infection was observed among 16 patients with SLE whose sera yielded normal amounts of chemotactic activity after treatment with zymosan. In contrast, 7 of 11 patients with SLE whose sera contained the heat‐stable inhibitor suffered serious bacterial infections. The presence of this heat‐stable inhibitor in sera from some patients with SLE may contribute, in part, to their increased susceptibility to infection.
Collagen‐induced arthritis in rats
Authors: Stuart John M , Cremer Michael A , Kang Andrew H , Townes Alexander S
Published: February 2007

When rats were injected intradermally with an oil emulsion of native type II collagen, they developed an inflammatory polyarthritis. The incidence and severity of arthritis increased as the amount of collagen injected was increased. Rats 4 1/2 weeks old were the most susceptible to the development of arthritis, whereas weanling and older animals were relatively resistant. There was no difference in incidence between males and females. Mononuclear cells from peripheral blood, lymph nodes, and spleen were cultured with type II collagen and responded maximally to a collagen concentration of 25 μg/ml. The earliest detectable response was in peripheral blood mononuclear cell cultures obtained 6 to 8 days after immunization. The response of lymph node and spleen cells tended to lag behind that of peripheral blood cells at the earlier time intervals. Antibodies were detected in sera by hemagglutination at 8 days postimmunization. Quantitation of IgM and IgG antibodies by radioimmunoassay showed good correlation with hemagglutination titers and increased binding of collagen by both classes of antibody in arthritic as compared to nonarthritic animals. It is clear that the development of both humoral and cellular immunity to type II collagen is associated with the development of arthritis and may be important in the pathogenesis of this disease.
Reaction of superficial bursae in response to specific disease stimuli
Authors: Canoso Juan J , Yood Robert A
Published: February 2007

Although microscopic studies have shown similarities between bursal and joint membranes, little is known about bursae and their response to disease states. Eighty‐six cases of superficial bursitis due to trauma, bacterial infection, or gout were reviewed and compared with cases of joint inflammation due to the same etiologies. In traumatic bursitis the bursal fluid mucin test was more abnormal and the viscosity lower than that of joint fluid in traumatic arthritis. The bursal fluid total leukocyte count of septic bursitis was less than 20,000/mm3 in 8 of 13 cases but in only 1 of 21 synovial fluids from cases of septic arthritis (P = 0.005). In gouty bursitis the mean total leukocyte count of bursal fluid was 2800/mm3, compared with a mean synovial fluid total leukocyte count of 28,700 in gouty arthritis (P < 0.02). These findings indicate that superficial bursae react less intensely than diarthrodial joints to specific disease stimuli and that a relatively low bursal fluid leukocyte count is often present in cases of septic and gouty bursitis.
Effects of naproxen on connective tissue changes in the adjuvant arthritic rat
Authors: Ackerman N R , Rooks W H , Shott L , Genant H , Maloney P , West E
Published: February 2007

The Freund's adjuvant‐injected rat shares a number of features with the arthritis patient, viz the presence of a proliferative synovitis, joint swelling, and cartilage and bone erosion. Naproxen, a prostaglandin synthetase inhibitor which is an effective antiinflammatory agent in laboratory animals and humans, was evaluated as an inhibitor of connective tissue destruction in this model by use of radiologic and histopathologic analyses. Sixteen days after rats were injected with Freund's complete adjuvant, marked joint swelling was noted. On day 17, vehicle or naproxen, 7 mg/kg/day, was administered orally. Twenty‐eight days later, vehicle‐treated animals demonstrated the following pathologic changes in their hindpaws: swelling, cartilage loss, large amounts of pannus within the joint spaces, osteoporosis, bone erosions, periosteal new bone formation, heterotopic ossification, and bony ankylosis. Rats treated 28 days with naproxen had significantly milder disease than the vehicle controls. The incidence of severe juxtaarticular bone destruction was 10/10 in the vehicle controls versus 2/10 of the drug‐treated group (P < 0.01). A comparable reduction in cartilage erosion, incidence of pannus, and new bone formation was noted in the drug‐treated group. These effects may relate to an inhibition of prostaglandin biosynthesis; prostaglandins have been shown to: 1) stimulate collagenase secretion from macrophages, 2) stimulate bone resorption in vivo and in vitro, and 3) diminish proteoglycan synthesis in cartilage.
Chronic tenosynovial hand infection from mycobacterium terrae
Authors: Halla James T , Gould John S , Hardin Joe G
Published: February 2007

A 23‐year‐old healthy man suffered a puncture wound from the fin of a catfish. Chronic tenosynovitis subsequently developed. Synovectomy was performed and cultures yielded Mycobacterium terrae. This organism, usually considered nonpathogenic, has only rarely been associated with human disease. This case further supports the role of this organism as a potential human pathogen and further suggests that M terrae should be considered in aquatic‐associated hand tenosynovitis.
Natural killer function in systemic lupus erythematosus
Authors: Hoffman Thomas
Published: February 2007

Peripheral blood lymphocytes from patients with systemic lupus erythematosus (SLE) demonstrated significantly less cytotoxicity against two different lymphoblastoid cell lines and one myeloid cell line than peripheral blood lymphocytes from normal individuals. Short‐term culture and other attempts to remove interfering immune complexes failed to restore low natural killer (NK) function. Six day culture in fetal calf serum resulted in increased cytotoxicity by mononuclear cells from normal individuals and some SLE patients, but this effect was shown to be dependent on Fc−, not Fc+, effector cells. Suppressor cells were not demonstrable as a cause for decreased NK activity.
Correlative histologic and serologic findings of sicca syndrome in patients with systemic lupus erythematosus
Authors: Moutsopoulos Haralampos M. , Klippel John H. , Pavlidis Nicholas , Wolf Robert O. , Sweet James B. , Steinberg Alfred D. , Chu Fred C. , Tarpley Thomas M.
Published: February 2007

We prospectively evaluated 24 patients with systemic lupus erythematosus for clinical, histologic, and serologic evidence of sicca syndrome. Abnormalities suggestive of sicca syndrome in patients with systemic lupus were identified by parotid scan (58%), questionnaire (54%), labial biopsy (50%), Schirmer's test (21%), and parotid flow rate (13%). An increased frequency of autoantibodies to gamma globulin and cellular antigen SS‐A was detected in lupus patients with histologic changes on labial biopsy. The serologic findings are similar to those of patients with sicca syndrome alone with the exception of the reduced incidence of anti‐SS‐B in patients with systemic lupus.
Adjuvant polyarthritis iv. induction by a synthetic adjuvant: immunologic, histopathologic, and other studies
Authors: Chang Yi‐Han , Pearson Carl M. , Abe Chiyuki
Published: February 2007

A solution of an apparently nonimmunogenic synthetic compound, N,N‐dioctadecyl‐N',N'‐bis(2‐hydroxyethyl) propanediamine (CP‐20961), suspended in mineral oil or olive oil (50 mg/ml), induced an acute, as well as a chronic, polyarthritis when single intradermal injections (0.2 ml) were made in the tail or hindpaw of Lewis rats. The polyarthritis was morphologically almost indistinguishable from classic adjuvant arthritis induced by Freund's complete adjuvant (FCA), a disease generally thought to be the result of a delayed hyper‐sensitivity reaction to a constituent(s) of the injected tubercle bacilli. The disease induced by CP‐20961 and that induced by Freund's complete adjuvant followed the same time course and almost identical pattern of development of clinical and histopathologic features. Like the classic adjuvant arthritis, CP‐20961 induced arthritis is suppressed by an immunosuppressive agent (cyclophos‐phamide) or an antiinflammatory drug (phenylbutazone). The alkyldiamine (CP‐20961) was found to be a potent adjuvant; a dispersion or a solution of the compound in mineral oil administered intraperitoneally enhanced the development of both the cell‐mediated and the humoral immune responses to EL4 cells in the rat. These findings suggest that the immunogen responsible for the development of adjuvant arthritis is endogenous, e.g., a constituent of host tissue, a viral protein, or some complex of the two.
Rat hepatic xanthine oxidase activity
Authors: Levinson Dennis J. , Chalker Deborah
Published: February 2007

The effect of maturation, castration, and sex hormonal treatment on hepatic xanthine oxidase activity (XOA) was evaluated in Sprague‐Dawley rats. In mature rats XOA was 59% greater in males than in females, whereas in the immature animal the differences between sexes were insignificant. Pubescence resulted in a twofold increase in activity in the male which was prevented by prepubertal orchiectomy. Conversely, prepubertal oophorectomy caused a twofold increase in XOA in females. Urinary uric acid excretion paralleled XOA in rats fed 1% oxonic acid. XOA was significantly elevated in females after postpubertal castration or testosterone treatment while orchiectomy or estradiol‐17 β treatment in the mature male showed no effect. In summary, these data suggest that androgens are required during puberty for full expression of hepatic XOA, and furthermore, an ovarian suppressive effect is evident. In the adult rat only the female responds appreciably to hormonal manipulation.
Marked suppression by salicylate of the augmented proteoglycan synthesis in osteoarthritic cartilage
Authors: Palmoski Marshall J. , Colyer Robert A. , Brandt Kenneth D.
Published: February 2007

In osteoarthritis a net increase in proteoglycan synthesis has been noted until the disease is far advanced and presumably reflects an attempt by the chondrocyte to repair the defect in the cartilage matrix. Because salicylates are the agents most commonly employed in treatment of osteoarthritis and because we recently showed that 10−3M sodium salicylate (i.e., approximately 20 mg%) suppresses proteoglycan synthesis in normal canine knee cartilage in vitro, we have studied the effects of this compound on osteoarthritic knee cartilage from dogs whose anterior cruciate ligament had been transected 9 weeks previously. The data indicated that the augmented synthesis of glycosaminoglycans in the degenerating cartilage was suppressed to a much greater degree by 10−3M sodium salicylate than the lower level of glycosaminoglycan synthesis in control cartilage from the contralateral knee of the same animal. Uptake of 14C‐acetylsalicylic acid was increased about 35% in osteoarthritic cartilage, suggesting that the drug permeated it more readily than normal cartilage. The salicylate‐induced suppression of proteoglycan synthesis in the osteoarthritic cartilage was not accompanied by reversal of the defect in proteoglycan aggregation or by improvement in the (presumed) defect in proteoglycan‐collagen interaction in the matrix, as reflected by the abnormally high proportion of 35S‐proteoglycans present in the culture medium.
Measuring health status in arthritis
Authors: Meenan Robert F. , Gertman Paul M. , Mason John H.
Published: February 2007

A multidimensional index that measures the health status of individuals with arthritis has been developed. The Arthritis Impact Measurement Scales (AIMS) are a combination of previously studies and newly created health status scales which assess physical, emotional, and social well‐being. The self‐administered AIMS questionnaire has been pilot tested in a mixed arthritis population. Results indicate that the instrument is practical and that it generates scalable, reliable, and valid measures of both aggregated and disaggregated health status. The AIMS approach to health status measurement should prove useful for evaluating the outcomes of arthritis treatments and programs.
The toxicity pattern of d‐penicillamine therapy
Authors: Kean Walter F. , Dwosh Isaac L. , Anastassiades Tassos P. , Ford Peter M. , Kelly H. Garfield
Published: February 2007

One hundred and one patients with rheumatoid arthritis were followed prospectively to assess the efficacy and toxicity of therapy with D‐penicillamine. After a mean total followup of 11.5 months (38 patients have completed 2 years of followup) there was a 70% overall improvement rate with 2 complete remissions. Sixty‐one patients developed 84 separate toxic reactions, 36 of which required drug withdrawal. Skin rashes (27/84), proteinuria (15/84), low platelets (14/84), and taste abnormalities (10/84) were the most common side effects of therapy at a mean D‐penicillamine dose of 463 mg/ day. The majority of toxic reactions (85%) occurred in the first 6 months, but proteinuria and thrombocytopenia were more common in the 6 to 12 month treatment period. Previous gold toxicity was a risk factor for developing D‐penicillamine toxicity (10/13). Our observations suggest that D‐penicillamine related toxicity is a major problem even at 500 mg/day, but the drug can be used with an increased safety margin after 9 months of continuous therapy.
Double‐blind placebo controlled crossover evaluation of levamisole in rheumatoid arthritis
Authors: Miller Bruce , Merieux Paula De , Srinivasan Ramachandran , Clements Philip , Fan Peng , Levy Joshua , Paulus Harold E.
Published: February 2007

During levamisole therapy, 14 of 20 patients with previously unresponsive rheumatoid arthritis had significant improvement (P < 0.05) in clinical measures of disease activity, erythrocyte sedimentation rate, and rheumatoid factor titer in a 32‐week double‐blind placebo controlled crossover trial. Levamisole was shown to alter antibody responses to tetanus and typhoid antigens, lymphocyte blastogenesis to phytohemagglutinins, and the number of null cells in peripheral blood. Agranulocytosis and rash resulted in discontinuation of the drug in one patient in each group. Though clearly effective, routine use of levamisole as a disease suppressant in rheumatoid arthritis must await more complete clarificatio of its association with agranulocytosis.
Effect of platelet lysate on growth and sulfated glycosaminoglycan synthesis in articular chondrocyte cultures
Authors: Choi Ye Chin , Morris Gregory M. , Sokoloff Leon
Published: February 2007

Human platelet lysate (PL) has a strong growth promoting action on rabbit articular chondrocytes in monolayer culture. The responsible factor is heat stable (56°C, 30 minutes) and above 10,000 MW. PL (80 μg protein/ml) reduces cell protein content and sulfated glycosaminoglycan synthesis. Synthesis of DNA is stimulated within the first 12 hours of culture but the decline in radiosulfact incorporation lags. PL acts to a slight extent on chondrocytes in serum‐free media, but its effect is potentiated by “platelet‐poor human serum” or fetal bovine serum. PL is one of several agents having such effects on chondrocytes cultured in serum‐containing media. Stimulation of growth in this cell type thus reduces nonreplicative biosynthetic activity nonspecifically. In the epiphyseal growth plate and in pathologic alterations of permeability of the martix of articular cartilage, platelet‐derived factors, together with somatomedin or other cofactors in serum, may be the principal mediator of growth of chondrocytes in vivo.
Clinical and laboratory features of canine lupus syndromes
Authors: Monier J. C. , Dardenne M. , Rigal D. , Costa O. , Fournel C. , Lapras M.
Published: February 2007

Determination of the specificities of antinuclear antibodies in the sera of 20 dogs presenting with symptoms of a lupus‐like syndrome permitted their separation into 2 groups. The first group of 14 dogs all had antibody activity to DNA‐histone antigen(s), and 4 of them also had antibodies to native DNA (nDNA). The Farr test with standard buffer was found to be unsatisfactory for the measurement of anti‐nDNA antibodies in dog sera due to a high incidence of false positive reactions; these could be eliminated by the inclusion of sodium dodecyl sulfate in the buffer system. The second group of 6 dogs was characterized by the presence of antibodies to extractable nuclear antigen. In every serum tested diseased dogs had a diminished level of circulating thymic factor as compared to controls of the same age, suggesting that a diminution of suppressor T cells may be an etiologic factor.
Reiter's disease in women
Authors: Smith David L. , Bennett Robert M. , Regan Martha G.
Published: February 2007

Reiter's disease in its classic form is defined by the triad of arthritis, conjunctivitis, and urethritis and occurs predominantly in men. Recent descriptions have emphasized other ancillary findings: mucocutaneous lesions, plantar fasciitis, Achilles tendinitis, sausage digits, asymmetrical sacroiliitis, and an association with HLA‐B27. This study describes 29 women followed over the past 4 years who have a rheumatic disorder most consistent with Reiter's disease. All 29 patients were seronegative, 72% presenting with an asymmetrical pauciarticular arthritis, and the majority evidenced lower extremity involvement. During the course of their illness, 52% of the patients developed either eye and/or urinary tract involvement. Additional features were mucocutaneous lesions in 8 patients, heel pain or Achilles tendinitis in 15 patients, sausage digits in 20 patients, and clinical sacroiliitis in 20 patients. HLA‐B27 was positive in 59% of patients, and radiographic bone and joint abnormalities were present in 52% of the patients. The recognition of this group of patients has both therapeutic and prognostic implications, because they preferentially respond to indomethacin or phenylbutazone and often pursue a chronic course, albeit without widespread joint destruction.
Depressed T cell colony growth in systemic lupus erythematosus
Authors: Bernstein Mark L. , Winkelstein Alan , Dobson Sue A.
Published: February 2007

Phytohemagglutinin‐stimulated peripheral blood T lymphocytes, plated in agar, are capable of forming discrete lymphoid colonies. In 35 normal subjects, the average number of colonies was 6,020 ± 351 (SEM). By contrast, in 39 patients with systemic lupus erythematosus (SLE), the mean colony number was 2,774 ± 384, a value significantly less than controls (P<0.001). Normal responses were measured in 5 patients with progressive systemic sclerosis and in 7 of 8 patients with rheumatoid arthritis. Colony growth in SLE showed a strong correlation with disease activity but did not correlate with responses of blood lymphocytes to phytohemagglutinin in suspension cultures, the number of circulating T cells, or serologic abnormalities.
Restricted subpopulations of DNA antibodies in kidneys of mice with systemic lupus
Authors: Ebling Fanny , Hahn Bevra H.
Published: February 2007

Sera from MRL/1, BXSB, and NZB/NZW mice, which develop IgG antibodies to DNA and glomerular deposits of DNA‐antiDNA immune complexes, were studied by isoelectric focusing. A large array of IgG antibodies with isoelectric points ranging from pH 5.5‐9.0 were found to bind double‐stranded DNA. Antibodies with isoelectric points from 8.0‐8.5 were significantly more frequent than antibodies focusing in all other pH ranges. In contrast, glomerular eluates from MRL/1 and NZB/NZW mice contained a restricted number of DNA‐binding bands, all of which focused at pH 8.0‐9.0. Anti‐DNA with isoelectric points from pH 8.0‐9.0 may be more pathogenic for the kidney than other subpopulations.
Antigen‐induced arthritis
Authors: Sandy John D. , Lowther D. A. , Brown Heather L. G.
Published: February 2007

During the acute phase of antigen‐induced arthritis, cartilage was obtained from five different sites within the joint, and chondrocyte activity was assessed by autoradiography of sections labeled with 35S‐sulfate. There was a marked inhibition of chondrocyte proteoglycan synthesis in all weight‐bearing areas; in addition, the complete superficial layer of cells and many mid‐zone cells in these areas were completely inactive. Electron microscopy showed that the inactive surface cells had degenerated completely, and that many midzone cells contained an accumulation of intracytoplasmic filaments and were depleted in biosynthetic organelles. A biochemical study of the inhibition showed that: 1) the incorporation of 35S‐sulfate and 3H‐acetate into glycosaminoglycans was inhibited to a similar extent; 2) the inhibition of glycosaminoglycan synthesis could not be reversed either by the addition of benzyl‐β‐D‐xyloside to incubations or by maintenance of the cartilage in organ culture for 6 days; 3) the inhibited chondrocytes exhibited a decreased ability to secrete proteoglycans into the extracellular fraction of the cartilage.
Induction of the synthesis of latent collagenase and latent neutral protease in chondrocytes by a factor synthesized by activated macrophages
Authors: Ridge Susan C. , Oronsky Arnold L. , Kerwar S. S.
Published: February 2007

The spent medium of stimulated peritoneal macrophages contains a factor or factors that induce the de novo synthesis of collagenase and neutral protease(s) in primary cultures of articular chondrocytes. The synthesis of this inducing factor by stimulated macrophages is inhibited by cycloheximide, indicating that the factor is a protein. The inducing factor is heat stable and stable to tryspin treatment, but it is partially inactivated on treatment to pH 2.0. The inducing factor is not retained on concanavalin Sepharose, is stable to reductive alkylation, and has an apparent molecular weight of approximately 30,000. Addition of the inducing factor to cartilage slices also results in the synthesis of both collagenase and neutral protease by the slices. Both of these enzymes synthesized by chondrocytes are in the latent form and are activated by either trypsin or plasmin. The neutral protease (MW 22,000) is a metalloprotease and is inhibited by o‐phenanthroline and by D‐penicillamine but not by phenylmethane sulfonylfluoride or iodoacetic acid. Induction of these latent enzymes in chondrocytes occurs between 8 and 16 hours after exposure to the inducing factor and is completely blocked by cycloheximide. The spent medium of stimulated lymphocytes (concanavalin A) does not induce the synthesis of these enzymes in chondrocytes, suggesting that the synthesis of the inducing factor may be a property specific to stimulated macrophages.
Effect of oxygen‐derived free radicals on hyaluronic acid
Authors: Greenwald Robert A. , Moy Wai W.
Published: February 2007

To investigate possible mechanisms of hyaluronic acid depolymerization, superoxide anion and other secondary oxygen‐derived free radicals were generated in vitro and allowed to act upon a hyaluronate substrate. Superoxide, generated either enzymatically with xanthine oxidase or by stimulation of polymorphonuclear leukocytes, reduced the viscosity of hyaluronate solutions dramatically while the chromatographic profiles of the glycosaminoglycan shifted toward lower molecular weights. Superoxide‐treated hyaluronate also became susceptible to further degradation by β‐N‐ace‐tylglucosaminidase A. Experiments with scavengers of various toxic oxygen‐derived free radicals clearly implicated these reactants as mediators of hyaluronate depolymerization. Generation of superoxide by leukocytes in vivo may account for the loss of synovial fluid viscosity that accompanies inflammatory joint disease.
The specificity and clinical usefulness of the lupus band test
Authors: Harrist Terence J. , Mihm Martin C.
Published: February 2007

Granular deposition of immunoglobulin at the dermoepidermal junction is characteristic, but not pathognomonic, of lupus erythematosus. When rigid criteria for the lupus band test are used, a positive result is highly specific. A positive band test is found in clinically normal skin and lesional skin of systemic lupus patients, and in lesional skin of discoid lupus patients. A positive band test is found infrequently in clinically normal skin of patients with other connective tissue disorders. Cutaneous lupus may be difficult to separate from other morphologically similar disorders. The lupus band test is useful in differential diagnosis because other disorders have either a specific pattern of immunoglobulin deposition or no immunoglobulin deposition. The mechanisms of immunoglobulin deposition at the epidermal basement membrane zone are discussed as well as pertinent clinical correlations of the positive band test.
Characteristics of antinuclear antibodies in rheumatoid. arthritis
Authors: Aitcheson Carol T. , Peebles Carol , Joslin Fenneke , Tan Eng M.
Published: February 2007

The immunologic specificities of antinuclear antibodies (ANA) in sera from 97 patients with rheumatoid arthritis (RA) were studied. The frequency of ANA detected by immunofluorescence with mouse kidney sections as substrate was 60% (59/97) compared to 13% (7/55) in controls. IgM ANA was positive in 41% (40/97) of RA sera, IgG ANA in 40% (39/97), and IgA ANA in 33% (32/97). Specificities of antibodies in the ANA positive sera were examined by radioimmunoassay for antibodies to DNA and by immunodiffusion for antibodies to Sm antigen, nuclear ribonucleoprotein, and the SS‐A and SS‐B nuclear antigens. Antibodies to these nuclear antigens were found infrequently (1.7% to 6.8%). Sera were further investigated for antibodies to histones by an immunofluorecent method previously described using acid‐extraced and histone reconstituted tissue section. Twinty‐four percent of the ANA positive sera (14/55) reacted with a histone‐dependent nuclear antigen. The relationship of rheumatoid factor to ANA was studied by isolating rheumatoid factors (RF) from aggregated IgG absorbant columns. Ten of 19 isolated RF showed ANA activity, which did not result from complexes of rheumatoid factor with IgG ANA since IgM rheumatoid factor, dissociated from IgG under acid conditions, continued to show ANA activity. In 8 of 16 RA sera tested, both ANA and rheumatoid factor activity could be inhibited by aggregated IgG. Five of the cross‐reacting rheumatoid factors reacted specifically with a histone‐dependent antigen in the reconstitution assay. These findings show that approximatley 50% of rheumatoid factors possess cross‐reactivity with nuclear components, and histones are involved in a significant number of these reactions.