scispace - formally typeset
Search or ask a question

Showing papers in "Arthritis & Rheumatism in 1982"


Journal ArticleDOI
TL;DR: The 1971 preliminary criteria for the classification of systemic lupus erythematosus (SLE) were revised and updated to incorporate new immunologic knowledge and improve disease classification and showed gains in sensitivity and specificity.
Abstract: The 1971 preliminary criteria for the classification of systemic lupus erythematosus (SLE) were revised and updated to incorporate new immunologic knowledge and improve disease classification. The 1982 revised criteria include fluorescence antinuclear antibody and antibody to native DNA and Sm antigen. Some criteria involving the same organ systems were aggregated into single criteria. Raynaud's phenomenon and alopecia were not included in the 1982 revised criteria because of low sensitivity and specificity. The new criteria were 96% sensitive and 96% specific when tested with SLE and control patient data gathered from 18 participating clinics. When compared with the 1971 criteria, the 1982 revised criteria showed gains in sensitivity and specificity.

14,272 citations


Journal ArticleDOI
TL;DR: The results confirmed the reliability and validity of the AIMS instrument and suggested that the instrument will prove useful as a tool to assess arthritis outcome in a wide variety of clinical settings.
Abstract: The Arthritis Impact Measurement Scales (AIMS) have been developed to assess the health status of arthritis patients. In this study, the self-administered AIMS questionnaire, which includes scales designed to measure the physical, psychologic, and social aspects of health status, was completed by 625 patients with various forms of arthritis. A comprehensive battery of analytic techniques was used to investigate the performance of these scales in this large sample. The results confirmed the reliability and validity of the AIMS instrument. They also showed that AIMS performs well in at least 4 major types of arthritis, in a range of sociodemographic groups, and across time. These findings emphasize the strengths of the AIMS approach and suggest that the instrument will prove useful as a tool to assess arthritis outcome in a wide variety of clinical settings.

398 citations


Journal ArticleDOI
TL;DR: A retrospective study of factors influencing survival in 1,103 patients with systemic lupus erythematosus was carried out at 9 university centers diverse in geographic, socioeconomic, and racial characteristics.
Abstract: A retrospective study of factors influencing survival in 1,103 patients with systemic lupus erythematosus (SLE) was carried out at 9 university centers diverse in geographic, socioeconomic, and racial characteristics. The mortality and disease characteristics of the patients at study entry varied widely among centers. The survival rates from the time patients with a diagnosis of SLE were first evaluated at the participating center was 90% at 1 year, 77% at 5 years, and 71% at 10 years. Patients with a serum creatinine greater than 3 mg/dl at study entry had the lowest survival rates: 48%, 29%, and 12% at 1, 5, and 10 years, respectively. Survival rate also correlated independently with the entry hematocrit, degree of proteinuria, number of preliminary American Rheumatism Association criteria for SLE satisfied, and source of funding of medical care. When data were corrected for socioeconomic status, race/ethnic origin did not significantly influence survival. Survival rates varied widely at different participating institutions, generally due to differences in disease severity. Place of treatment was independently associated with survival only in the second year after study entry. Disease duration before study entry did not account for the differences in disease severity.

378 citations


Journal ArticleDOI
TL;DR: Levels of interferon were measured in 81 serum samples from 23 patients with systemic lupus erythematosus by a plaque-reduction method and correlated retrospectively with clinical records of disease activity, anti-DNA binding, and serum complement measurements, which characterized the IFN found in the present study as IFN-alpha.
Abstract: Levels of interferon (IFN) were measured in 81 serum samples from 23 patients with systemic lupus erythematosus (SLE) by a plaque-reduction method and correlated retrospectively with clinical records of disease activity, anti-DNA binding, and serum complement measurements. IFN titers were found to correlate with both clinical disease activity and anti-DNA binding, but no relation was found to serum complement. Most (76.6%, 31 of 41) serum samples obtained during periods of active disease contained measureable amounts of IFN, but only 9.1% (2 of 22) of results of tests on samples obtained during periods of disease quiescence were positive (P less than 0.005). Of samples with clearly elevated anti-DNA binding (greater than 40%), 69.7% (23 of 33) had positive results for IFN, but 57.1% (8 of 14) had negative results when the anti-DNA binding was normal (less than 20%) (P less than 0.005). Measurement of serum IFN titers in patients with SLE, therefore, provides another serologic marker of disease activity. Contrary to the findings of previous studies, the IFN found in the present study was characterized as IFN-alpha, or Type I IFN, on the basis of acid stability and neutralization by antibody to IFN-alpha. Of interest are the questions raised about the origin of IFN in the sera of patients with SLE and what role IFN might have in the pathogenesis of the autoimmune disease in view of the many documented immunomodulating effects of IFN.

365 citations


Journal ArticleDOI
TL;DR: Causes of death were examined for 1,103 systemic lupus erythematosus patients who were followed from 1965 to 1978 at 9 centers that participated in the Lupus Survival Study Group.
Abstract: Causes of death were examined for 1,103 systemic lupus erythematosus patients who were followed from 1965 to 1978 at 9 centers that participated in the Lupus Survival Study Group. A total of 222 patients (20%) died. Lupus-related organ system involvement (mainly active nephritis) and infection were the most frequent primary causes of death. Causes of death were similar throughout the followup period. Hemodialysis had little impact on the length of survival for patients with nephritis. Active central nervous system disease and myocardial infarction were infrequent causes of death. There were no deaths from malignancy.

314 citations


Journal ArticleDOI
TL;DR: Major significant differences in racial distribution included 1) a higher incidence of serositis in older whites and in blacks regardless of age, and 2) more frequent hypocomplementemia in younger patients within both racial groups.
Abstract: We compared the frequency of clinical features of systemic lupus erythematosus (SLE) and determined survival in 113 patients with younger-onset lupus (age less than 55 at clinical diagnosis) and 25 patients with older-onset disease (age greater than or equal to 55 at diagnosis). The most striking difference was in the racial distribution; 59% of the younger patients were black, compared with only 20% of the older-onset patients (P less than 0.001). Major manifestation of lupus (including clinically evident renal disease, central nervous system involvement, cutaneous involvement, and hemocytopenia) occurred with similar frequency in both age groups. Antibodies to DNA were detectable equally often in both groups, but hypocomplementemia was more common in the younger patients. Five-year survival in the younger-onset group (79%) was similar to that of the older-onset group (72%); there was a tendency toward relatively improved survival in patients survival of appropriately matched control populations. Major significant differences in racial distribution included 1) a higher incidence of serositis in older whites and in blacks regardless of age, and 2) more frequent hypocomplementemia in younger patients within both racial groups.

288 citations


Journal ArticleDOI
TL;DR: Oral contraceptive therapy that used estrogens, even at low doses, often induced exacerbation of systemic lupus erythematosus activity, and pure progestogens, which were effective and devoid of such unfavorable effects, may be preferred in these patients.
Abstract: Since harmful effects of estrogens in murine lupus are well established, we studied the influence of oral contraceptive therapy on systemic lupus erythematosus activity in 26 female patients with lupus nephropathy. Combined preparations containing either 50 micrograms (14 patients) or 30 micrograms (7 patients) of ethinyl-estradiol were used in 21 courses in 20 patients. Initial manifestations or exacerbations of systemic lupus activity appeared within 3 months of beginning hormonal therapy in 9 patients, an overall incidence of lupus flare-up of 43%; there was major renal involvement in 4 patients. Conversely, evidence of lupus exacerbation did not develop in any of 11 patients who received pure progestogen oral contraceptive therapy with either continuous low-dose norsteroids (6 patients) or discontinuous progestogens at normal dosage (5 patients). These patients were followed for 5--30 months. Our data indicated that oral contraceptive therapy that used estrogens, even at low doses, often induced exacerbation of systemic lupus erythematosus activity. Pure progestogens, which were effective and devoid of such unfavorable effects, may be preferred in these patients.

265 citations



Journal ArticleDOI
TL;DR: Patients who were HLA-B27 positive had a more severe acute disease (more frequent back pain, urologic symptoms, mucocutaneous manifestations, and a longer duration of the disease) and more frequent chronic back pain and sacroiliitis.
Abstract: An analysis of 160 patients with Reiter's disease, 144 with yersinia arthritis, and 9 with salmonella arthritis was performed, Complete or incomplete Reiter's syndrome was observed in one-third of the patients with yersinia arthritis and in most of those with salmonella arthritis. During the followup period, chronic back pain and joint symptoms were frequent in all the patient groups. Patients who were HLA-B27 positive had a more severe acute disease (more frequent back pain, urologic symptoms, mucocutaneous manifestations, and a longer duration of the disease) and more frequent chronic back pain and sacroiliitis.

212 citations



Journal ArticleDOI
TL;DR: The findings indicated that 2 or more genetic loci, as well as sex-related factors, played a major role in determining susceptibility to arthritis in this model, and breeding studies demonstrated that susceptibility was a dominant or codominant trait.
Abstract: Sixteen inbred rat strains were examined for susceptibility and resistance to group A streptococcal cell wall-induced polyarthritis. The findings indicated that 2 or more genetic loci, as well as sex-related factors, played a major role in determining susceptibility to arthritis in this model. Breeding studies demonstrated that susceptibility was a dominant or codominant trait. A positive association between the severity of arthritis and the development of chronic inflammation in multiple tissues was also observed. In strains that were relatively resistant to arthritis, chronic inflammation was generally limited to the spleen. Since translocation of the poorly degradable and phlogogenic streptococcal cell walls to the synovium and other tissues appears to initiate inflammation, these studies suggested that susceptibility might be the result of a defect in host mechanisms limiting cell wall dissemination.

Journal ArticleDOI
TL;DR: Attempts to characterize the interferon in the sera of patients with systemic lupus erythematosus and vasculitis revealed that antibody to alpha (leukocyte) interferons, but not to beta (fibroblast)interferon, partially or completely neutralized the antiviral activity.
Abstract: Recently, we found interferon in the sera of patients with systemic lupus erythematosus, rheumatoid arthritis, scleroderma, and Sjogren's syndrome. In this study, we surveyed a variety of other immunologically mediated diseases. We did not find interferon in the sera of patients with Wegener's granulomatosis, sarcoidosis, infectious mononucleosis, minimal change nephritis, kidney transplants, myasthenia gravis, or uveitis, but we did find this protein in the sera of patients with active systemic and cutaneous vasculitis. Attempts to characterize the interferon in the sera of patients with systemic lupus erythematosus and vasculitis revealed that antibody to alpha (leukocyte) interferon, but not to beta (fibroblast) interferon, partially or completely neutralized the antiviral activity. The failure of antibody to alpha interferon to completely neutralize the antiviral activity in certain specimens and the lability of the antiviral activity in some specimens to pH 2.0 treatment both suggest that more than one type of interferon was present.

Journal ArticleDOI
TL;DR: Observations support a central role for endothelial cell injury in the pathogenesis of childhood dermatomyositis, suggest a basis for assessing the efficacy of therapy, and provide a focus for investigation of basic mechanisms.
Abstract: Childhood dermatomyositis is a distinct subset of dermatomyositis with highly variable outcome. We reviewed our experience with 29 patients observed over a period of 22 years and attempted to correlate tissue manifestations with outcome. Distinctive vascular lesions included non-necrotizing lymphocytic vasculitis and a unique spectrum of endovascular injury producing temporary or permanent occlusion of small arteries and capillaries. Vessels with noninflammatory endovasculopathy were often reactive with fluorescein-conjugated antisera to IgM, C3d, and/or fibrin. Lesions linked to endovascular injury include infarction, zonal myopathy, and loss of capillary network. We were able to identify half of the children destined to have persistent morbidity on the basis of severity of vasculopathy in pretreatment muscle-biopsy specimens. Our observations support a central role for endothelial cell injury in the pathogenesis of childhood dermatomyositis, suggest a basis for assessing the efficacy of therapy, and provide a focus for investigation of basic mechanisms.

Journal ArticleDOI
TL;DR: This syndrome is distinguishable from other childhood rheumatic disorders, including juvenile rheumatoid arthritis, and its recognition may reliably identify children with the prodromal manifestations of seronegative spondylarthropathies.
Abstract: Thirty-nine children with a syndrome of seronegative enthesopathy and arthropathy were evaluated The group included 25 patients with no apparent underlying primary disease and 13 with either ankylosing spondylitis, inflammatory bowel disease, reactive arthritis, or Reiter's syndrome Significant distinguishing characteristics of the group included male predominance, late age at onset, positive family histories of arthritis, oligoarthropathy, axial skeleton involvement, and the presence of the B27 histocompatibility antigen This syndrome is distinguishable from other childhood rheumatic disorders, including juvenile rheumatoid arthritis Its recognition may reliably identify children with the prodromal manifestations of seronegative spondylarthropathies

Journal ArticleDOI
TL;DR: Patients with fibrositis differed in both elevation and variability in their MMPI profiles, indicating that they were more psychologically disturbed than patients with rheumatoid or other types of arthritis.
Abstract: Thirty patients with fibrositis and 2 control groups, one of rheumatoid arthritis patients and the other of arthritis patients with other than rheumatoid arthritis, were compared on the basis of the Minnesota Multiphasic Personality Inventory (MMPI) to assess the role of psychologic factors in fibrositis. Patients with fibrositis differed in both elevation and variability in their MMPI profiles, indicating that they were more psychologically disturbed than patients with rheumatoid or other types of arthritis. The fact that almost all of the fibrositis patients' MMPI scales were higher suggests that we might be dealing with a number of different psychologic disturbances that have stiffness and musculoskeletal pain as principal and common symptoms.

Journal ArticleDOI
TL;DR: Human preputial skin fibroblasts were cloned in vitro, and studies in 21 clones were shown to exhibit a 3-fold difference in collagen synthesis; this heterogeneity of phenotypic expression was conserved over multiple population doublings, raising the possibility that scleroderma represents a process of selection of fibroblast programmed to produce increased amounts of collagen.
Abstract: Human preputial skin fibroblasts were cloned in vitro, and studies in 21 clones were shown to exhibit a 3-fold difference in collagen synthesis; this heterogeneity of phenotypic expression was conserved over multiple population doublings. When the clones were exposed to sera from 10 scleroderma patients, selective growth of high-collagen-producing fibroblasts was observed. Prostaglandin E2 abrogated the selective effect of scleroderma serum on high-collagen-producing fibroblast clones. Besides enhanced collagen synthesis, these clones of normal fibroblasts shared an insensitivity to feeding schedule with fibroblasts from scleroderma skin. These data raise the possibility that scleroderma represents a process of selection of fibroblasts programmed to produce increased amounts of collagen.

Journal ArticleDOI
TL;DR: DR2 and DR3 may be markers of a major histocompatibility complex–mediated immune hyperresponsiveness that affects expression of systemic lupus erythematosus.
Abstract: The interrelationships of serologic and clinical features and the HLA–DR, MB, and MT specificities were examined in 70 white patients with systemic lupus erythematosus. HLA–DR2 and MB1 were significantly increased when compared with controls from the Eighth International Histocompatibility Testing Workshop but not with local controls. DR2 and DR3 correlated with increased seroreactivity (anti-Ro, antiDNA, rheumatoid factor, and hyperglobulinemia), and anti-Ro with clinically overt sicca complex. Thus, DR2 and DR3 may be markers of a major histocompatibility complex–mediated immune hyperresponsiveness that affects expression of systemic lupus erythematosus.

Journal ArticleDOI
TL;DR: The identification of peripheral blood lymphocyte subsets by use of monoclonal antibodies and the relationship of these subsets to tissue infiltrates and autoantibody production provide further insight into the pathogenesis of primary Sjögren's syndrome.
Abstract: Using monoclonal antibodies to cell surface antigens, we studied lymphocyte subsets in 15 patients with primary Sjogren's syndrome. The absolute number of OKT8-positive cells (reactive with T suppressor/cytotoxic cells) was significantly decreased in such patients (353 +/- 186/mm3) compared to age-matched controls (631 +/- 150/mm3) (P less than 0.001). The number of OKT4-positive cells (reactive with T helper/inducer cells) was comparable in both groups (932 +/- 588/mm3 versus 1.073 +/- 290/mm3). The ratio of OKT4/OKT8-reactive peripheral blood lymphocytes was increased (greater than 2.4) in 67% of these patients and ranged from 1.0 to 6.4 (normal = 1.8 +/- 0.3). OKT4-positive cells were the predominant subset in lip biopsy specimens stained with immunofluorescence or immunoperoxidase techniques; the OKT4/OKT8 ratio exceeded 3.0 in all 5 patients examined. In 1 patient with pseudolymphoma, a lymph node biopsy specimen contained 80% T cells with an OKT4/OKT8 ratio of 3.2. Thus, OKT4-positive cells predominated in the peripheral blood lymphocytes as well as in sites of inflammation in primary Sjogren's syndrome. The decreased number of OKT8-positive cells in primary Sjogren's syndrome was probably not caused by circulating autoantibody, since patients' sera did not react with normal OKT8-positive cells. Functional studies using pokeweed mitogen demonstrated that T helper cell activity for immunoglobulin synthesis was contained in the OKT4-positive subset in both normal and patients' peripheral blood lymphocytes. Removal of OKT8-positive cells by complement-mediated lysis did not lead to increased immunoglobulin synthesis or production of rheumatoid factor. The identification of peripheral blood lymphocyte subsets by use of monoclonal antibodies and the relationship of these subsets to tissue infiltrates and autoantibody production provide further insight into the pathogenesis of primary Sjogren's syndrome.



Journal ArticleDOI
TL;DR: The clinical and laboratory features as well as the long-term course of adult- and juvenile-onset systemic Still's disease are similar, but further studies of genetic markers and immunopathology are required to establish a common pathophysiology.
Abstract: Eleven female patients with adult-onset Still's disease were followed for 7-36 years (mean 20.2 years) after the onset of their illness. Ten of these patients had a chronic course characterized by remissions and exacerbations of arthritis associated with fever and rash. Five patients had terminal interphalangeal involvement, and carpal ankylosis was demonstrated on x-ray film in 10. Two patients developed a widespread polyarthritis, and renal amyloidosis was diagnosed 10 years after disease onset in the most severely affected patient. In 4 patients studied during an exacerbation of the disease, circulating immune complexes were detected by the staphylococcal A binding assay, but not by the C1q binding assay. Synovial fluid analysis in 1 patient revealed a low C3 level and total hemolytic complement (CH50) together with immune complexes and IgG rheumatoid factor. Immune complexes were not identified in the characteristic Still's rash by immunofluorescence or electron microscopy, although mast cell degranulation, neutrophil lysis, and perivascular fibrin deposition were reminiscent of immune complex--mediated vascular injury. The clinical and laboratory features as well as the long-term course of adult- and juvenile-onset systemic Still's disease are similar, but further studies of genetic markers and immunopathology are required to establish a common pathophysiology.

Journal ArticleDOI
TL;DR: The hypothesis that adsorbed proteins modulate the phlogistic potential of MSU and that the surface activation of humoral mediators contributes to the local inflammatory response is supported.
Abstract: We studied the capacities of naked and protein-coated monosodium urate (MSU) crystals to stimulate superoxide anion (O(2)) release by human polymorphonuclear leukocytes (PMN). Uncoated MSU estimated significant O(2) production by cytochalasin B-treated PMN. Precoating MSU with IgG caused an increase in mean O(2) production, whereas precoating heated MSU with serum or plasma inhibited O(2) release. Unheated MSU crystals, which activate complement to a greater extent than heated crystals, also provoked O(2) generation, an effect again abrogated by precoating with serum but not with plasma. Coincubation of unheated MSU and plasma resulted in an enhancement of O(2) generation. The results of these experiments support the hypothesis that adsorbed proteins modulate the phlogistic potential of MSU and that the surface activation of humoral mediators contributes to the local inflammatory response.

Journal ArticleDOI
TL;DR: The specificity of antinucleolar antibodies in sera from 54 patients with various rheumatic diseases was analyzed by immunoprecipitation of 32P- or 35S-methionine-labeled HeLa cell extracts and correlation of these molecularly defined antinuclear antibody specificities with immunofluorescence patterns and rhematic diseases is discussed.
Abstract: The specificity of antinuclear antibodies in sera from 54 patients with various rheumatic diseases was analyzed by immunoprecipitation of 32P- or 35S-methionine-labeled HeLa cell extracts. Of 35 sera giving a speckled and/or homogeneous immunofluorescence pattern in rat liver nuclei, 20 contained antibodies to nuclear ribonucleoproteins, which are defined by their ribonucleic acid and protein components. Four sera reacted with a nuclear antigen (Ga) which has not been described so far. Of 19 sera with antinucleolar antibodies, 18 did not react with nuclear or nucleolar ribonucleoproteins. Correlation of these molecularly defined antinuclear antibody specificities with immunofluorescence patterns and rheumatic diseases is discussed.




Journal ArticleDOI
TL;DR: Suspended normal synoviocytes equaled peripheral blood non-T lymphocytes as stimulators of mixed lymphocyte reactions, whereas adherent rheumatoid synovial cells were extremely efficient as such stimulators and in presenting soluble antigens to autologous T lymphocytes.
Abstract: Normal and rheumatoid synovial cells have been analyzed in frozen sections and in suspension. HLA-DR-expressing, macrophage-like cells are demonstrated in normal synovial intima and in rheumatoid tissue. Suspended normal synoviocytes equaled peripheral blood non-T lymphocytes as stimulators of mixed lymphocyte reactions, whereas adherent rheumatoid synovial cells were extremely efficient as such stimulators and in presenting soluble antigens to autologous T lymphocytes. This HLA-DR-dependent T lymphocyte regulation might provide a cellular basis for the HLA-D haplotype-arthritis associations.

Journal ArticleDOI
TL;DR: Using the enzyme-linked immunosorbent assay (ELISA), antibodies to interstitial (type I) and basement membrane (type IV) collagens in the sera of patients with scleroderma (systemic sclerosis) were detected and correlated significantly with pulmonary diffusion capacity.
Abstract: 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

Journal ArticleDOI
TL;DR: The measurement of histone antibodies would be a useful addition to the present laboratory parameters (antinuclear and double-stranded DNA antibodies and circulating immune complexes) for the diagnosis and progression of systemic lupus erythematosus, particularly since they seem to appear during or just before the onset of an active phase and tend to be absent during remission.
Abstract: Antibodies to total histones and histone fractions H1, H2a-H4, H2b, and H3 were measured in serum samples from 61 patients with systemic lupus erythematosus (SLE), 33 with rheumatoid arthritis, 17 with systemic sclerosis, and 20 with various other diseases by use of a sensitive immunoenzymatic assay Histone antibodies were present in 524% of the SLE samples whereas only 1 of the samples from other diseases was positive (systemic sclerosis) The presence of these antibodies in SLE patients was not associated with any specific clinical manifestations, but was correlated with activity of the disease: 87% (20 of 23) of patients with active SLE, in particular 9 of 9 not yet treated, showed histone antibody whereas only 18% (4 of 22) of samples from patients with inactive SLE were positive We believe that the measurement of histone antibodies would be a useful addition to the present laboratory parameters (antinuclear and double-stranded DNA antibodies and circulating immune complexes) for the diagnosis and progression of systemic lupus erythematosus, particularly since they seem to appear during or just before the onset of an active phase and tend to be absent during remission

Journal ArticleDOI
TL;DR: The effect of immobilization of the knee in flexion on the development of osteoarthritis was studied in dogs that had undergone transection of the anterior cruciate ligament and in cartilage from all operated and/or immobilized joints the proportion of proteoglycans that interacted with hyaluronic acid in vitro was diminished.
Abstract: The effect of immobilization of the knee in flexion on the development of osteoarthritis was studied in dogs that had undergone transection of the anterior cruciate ligament. Knees of dogs that were permitted ad libitum ambulation in a pen for 12 weeks after transection of the ligament showed osteophytes and fibrillation and a decrease in proteoglycan (uronic acid) content, although thickness of the articular cartilage was normal. Proteoglycan synthesis was 80% greater (P less than 0.01) than that in cartilage from the contralateral knee, and more than twice the normal proportion of the total proteoglycans was present in the medium of cultures of cartilage from the unstable knee (P less than 0.01). Similarly, the proportion of total tissue proteoglycans extracted with 0.4M guanidinium chloride was 3 times greater than normal (P less than 0.01). In contrast, osteophytes were not seen when the leg was immobilized in flexion immediately after transection of the ligament, and the articular surface remained intact. The cartilage became atrophic, however, and its proteoglycan content (uronic acid) was diminished; proteoglycan synthesis was decreased to 61% of the level in cartilage from the contralateral knee, although proteoglycan extractability was normal. Knee cartilage from these legs that were immobilized after transection, therefore, resembled that from dogs whose leg had been immobilized without cruciate ligament transection. In cartilage from all operated and/or immobilized joints the proportion of proteoglycans that interacted with hyaluronic acid in vitro was diminished, because of a defect in the hyaluronate-binding region of the proteoglycan.