bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between matrix proteoglycan content and the effects of salicylate and indomethacin on articular cartilage
Authors: Palmoski Marshall J. , Brandt Kenneth D.
Published: February 2007

When 160 γg/ml sodium salicylate was added to the culture medium, glycosaminoglycan synthesis in slices of normal articular cartilage from habitually loaded areas of canine femoral condyles was diminished by 24% (P ≤ 0.01). Although glycosaminoglycan synthesis in cartilage from habitually unloaded regions of the same joints was similar to that in cartilage from loaded sites, the mean uronic acid content of the former was about 25% less, and salicylate suppressed glycosaminoglycan synthesis in unloaded cartilage to a much greater extent (42% of control) than it did in loaded cartilage (P ≤ 0.01). Furthermore, 1.5 γg/ml indomethacin, which had no effect on cartilage from loaded regions, suppressed glycosaminoglycan synthesis in cartilage from unloaded regions by 31%. However, if cartilage from loaded regions was treated with testicular hyaluronidase, indomethacin inhibited glycosaminoglycan synthesis, and inhibition of glycosaminoglycan metabolism by salicylate in hyaluronidase‐treated cartilage was greater than in untreated cartilage. The data suggest that the effects of nonsteroidal antiinflammatory drugs on glycosaminoglycan metabolism in articular cartilage are dependent on proteoglycan content of the extracellular matrix.
Neutrophil Aggregation Induced by Sera from Patients with Active Systemic Lupus Erythematosus
Authors: Abramson Steven B. , Given William P. , Edelson Henry S. , Weissmann Gerald
Published: February 2007

Activated complement components and immune complexes cause neutrophil (PMN) aggregation in vitro and in vivo, as in dialysis‐induced neutropenia and adult respiratory distress syndrome. To investigate the possible role of PMN aggregation in systemic lupus erythematosus (SLE), we studied the capacity of 59 sera from 53 patients to induce aggregation of normal PMN in vitro. Neutrophil aggregating activity (NAA) was present in the sera of 26 of 28 patients with active SLE. The mean NAA in this group was significantly greater than that found in 13 patients with inactive SLE, 20 patients with rheumatoid arthritis, and 17 normal controls. In patients with SLE there was a positive correlation between disease severity and the quantitative measure of NAA. NAA did not correlate with serum C3 or C4 nor with the presence or absence of circulating immune complexes. High levels of NAA were particularly characteristic of central nervous system lupus. These data suggest that the formation of intravascular leukoaggregates may contribute to morbidity in SLE.
Arthropathy of Lowe's (Oculocerebrorenal) Syndrome
Authors: Athreya Balu H. , Schumacher H. Ralph , Getz Harry D. , Norman Michael E. , Iv Spencer Borden, , Witzleben Camillus L.
Published: February 2007

We describe 3 children with Lowe's syndrome who developed joint manifestations—‐a previously rarely recognized feature. Two children had swelling and contractures of large and small joints; the third child had a small joint effusion and hypermobile joints. None of them had antinuclear antibody or rheumatoid factor; synovial effusions and biopsies showed no evidence of inflammatory cell infiltration. By light microscopy, profuse fibrous tissue and sparse synovial lining cells were found. Electron microscopy of the synovium of 2 patients showed large amounts of normal appearing collagen, unidentified thin fibrils, and focal profuse granular and fibrillar basement membrane‐like material around small vessels, similar to findings described in other tissues in this syndrome. Whether these clinical and pathologic findings are results of the still incompletely understood basic metabolic defect or not, they should be recognized as features that may be seen in patients with Lowe's syndrome.
T Lymphocyte Subsets in Systemic Lupus Erythematosus
Authors: Bakke Antony C. , Kirkland Purnell A. , Kitridou Rodanthi C. , Quismorio Francisco P. , Rea Thomas , Ehresmann Glenn R. , Horwitz David A.
Published: February 2007

The contribution of immune regulation to the etiology of systemic lupus erythematosus (SLE) is poorly understood. Using the monoclonal antibodies OKT4 and OKT8, we quantitated, by flow cytometry, T inducer/helper and T cytotoxic/suppressor cells in patients with SLE. Serologically active patients, who had clinical manifestations such as arthritis or rash and were not receiving prednisone, were characteristically lymphopenic due to a marked reduction in OKT4+ cells. Prednisone therapy produced the same phenomenon. Untreated patients, who were serologically inactive, demonstrated no abnormalities. These studies have thus revealed two presumably independent factors that can produce similar immunoregulatory aberrations.
Spinal Fractures Complicating Ankylosing Spondylitis
Authors: Hunter Thomas , Dubo Hyman I. C.
Published: February 2007

Twenty‐two spinal fractures in 20 patients with chronic ankylosing spondylitis are reported. Nineteen fractures occurred in the cervical region. Fourteen of the fractures were caused by minor falls, 3 by falls down steps, 4 by motor vehicle accidents, and 1 by cardiopulmonary resuscitation. Long‐term followup (mean 3.2 years) of 9 fractures diagnosed early and managed conservatively showed bony union of all fractures. No patient deteriorated neurologically and 3 patients made major recovery. Long‐term followup is also reported on 6 patients in whom the diagnosis was delayed. The difficulties in diagnosis and management are discussed.
The Radiographic Diagnosis of Sacroiliitis
Authors: Ryan Lawrence M. , Carrera Guillermo F. , Lightfoot Robert W. , Hoffman Raymond G. , Kozin Franklin
Published: February 2007

Conventional radiography is the standard method of objectively identifying sacroiliitis. Single views of the sacroiliac joints can be unequivocally interpreted in 70‐80% of patients with low back pain. A series of views usually correctly resolves the ambiguity in the remaining 20—30% of patients (67% correct). Computed tomography will be helpful in the few patients in whom a series of views produces equivocal interpretation.
Hyaluronate Synthesis by Synovial Villi in Organ Culture
Authors: Myers Stephen L. , Christine Theresa A.
Published: February 2007

Individual canine synovial villi were used to establish short‐term synovial organ cultures. These villi incorporated 3H‐glucosamine into highly‐polymerized 3H‐hyaluronic acid (3H‐HA), which was the only 3H‐glycosaminoglycan identified in the culture medium. Some 3H‐HA, and larger amounts of other 3H‐glycosaminoglycans, were recovered from cultured tissues. Culture medium 3H‐HA content was proportional to the surface area of cultured villi. Organ cultures of nonvillous synovium were compared with villi; nonvillous cultures synthesized less 3H‐HA per mm2 of their synovial intimal surface than villi. These cultures complement cell culture techniques for in vitro studies of synovial lining cell function.
Benoxaprofen stimulates proteoglycan synthesis in normal canine knee cartilage in vitro
Authors: Palmoski Marshall J. , Brandt Kenneth D.
Published: February 2007

Several nonsteroidal antiinflammatory drugs which are cyclooxygenase inhibitors (e.g., salicylates, fenoprofen, ibuprofen) have been shown to suppress proteoglycan synthesis by normal joint cartilage in vitro. We examined the effect of benoxaprofen, a long‐acting proprionic acid derivative which inhibits lipoxygenase in addition to causing moderate cyclooxygenase inhibition. When added to the culture medium in concentrations comparable with those obtainable in serum of patients treated with the drug (e.g., 10 and 50 μg/ml), benoxaprofen increased proteoglycan synthesis in slices of normal canine knee cartilage to 126% and 135%, respectively, of control levels. These concentrations of the drug augmented net protein synthesis to 154% and 123%, respectively, of control levels. Incorporation of 3H glucosamine into 9‐aminoacridine precipitable material was increased by benoxaprofen, showing that it stimulates net proteoglycan synthesis, and not merely sulfation. At concentrations of either 10 or 50 μg/ml, the drug had no effect on proteoglycan catabolism or on the ability of proteoglycans to interact with cartilage hyaluronic acid to form macromolecular aggregates. Nordi‐hydroguaiaretic acid, a free radical scavenger which, like benoxaprofen, inhibits the lipoxygenase as well as cyclooxygenase pathways of arachidonic acid metabolism, also increased 35S glycosaminoglycan synthesis in cartilage slices. The stimulation of glycosaminoglycan and protein synthesis by benoxaprofen suggests that its action on the chondrocyte may be different from that of most other nonsteroidal antiinflammatory drugs.
Clinical characteristics of fibrositis
Authors: Campbell Stephen M. , Clark Sharon , Tindall Elizabeth A. , Forehand Mary E. , Bennett Robert M.
Published: February 2007

Twenty‐two patients with fibrositis, selected from a general medical outpatient population by a screening questionnaire and subsequent evaluation, were compared with age‐, sex‐, and clinic‐matched patients without fibrositis. Although there was a high prevalence of musculoskeletal complaints in both groups, the fibrositis patients had a uniform constellation of symptoms, including axial pain, severe aching and stiffness, morning fatigue, and modulation by specific factors. They also had a higher incidence of tension headache and irritable bowel syndrome. The use of a dolorimeter demonstrated that fibrositis patients had many more areas of localized tenderness than control patients, but also that fibrositis patients did not have diffusely diminished pain threshold and tolerance. Using the criteria of this study, fibrositis appears to be a common and readily definable syndrome within the spectrum of soft tissue rheumatism.
Biochemical and morphologic studies of cartilage from the adult human sacroiliac joint
Authors: Paquin Julie D. , Rest Michel Van Der , Marie Pierre J. , Mort John S. , Pidoux Isabelle , Robin Poole A. , Roughley Peter J.
Published: February 2007

The cartilage of the adult sacroiliac joint contains type II collagen and a high concentration of glycosaminoglycan. Furthermore, large aggregating proteoglycans and link proteins were extracted from the sacral cartilage. In these respects the sacroiliac cartilage is similar to that in the peripheral joints. However, while the organization of the collagen in the sacral cartilage is typical of an articular cartilage, the organization of the ilial cartilage is very different, and throughout its depth it possesses narrow collagen fibrils arranged parallel to the articular surface.
The pathology of the involved tendons in patients with familial arthropathy and congenital camptodactyly
Authors: Ochi Takahiro , Iwase Rokuro , Okabe Norikazu , Fink Chester W. , Ono Keiro
Published: February 2007

In 2 sisters with congenital camptodactyly and joint effusions, abnormalities in tendons were restricted to the portion within synovia sheaths. This implied a disease of the tenosynovium, rather than one of the tendon itself. In areas of chronic involvement, some tendons were replaced by fibrous tissue. Significant portions of the tendons in fingers with camptodactyly were replaced by hard scars. Congenital camptodactyly is probably the result of an intrauterine tenosynovitis, rather than an isolated congenital anomaly.
Natural killing activity in sjögren's syndrome
Authors: Miyasaka N. , Seaman W. , Bakshi A. , Sauvezie B. , Strand V. , Pope R. , Talal N.
Published: February 2007

Natural killing (NK) by peripheral blood mono‐nuclear cells (PBMC) against K562 cells was examined in 27 patients with Sjögren's syndrome and 17 normal controls. NK activity in the patients was significantly reduced compared with normal controls (34.6 ± 3.4% versus 52.2 ± 3.4%, P < 0.001). Patients with secondary Sjögren's had lower cytotoxicity compared with those who had primary Sjögren's (28.5 ± 5.5% versus 37.3 ± 4.2%, P < 0.01). The proportion of PBMC with characteristics of NK cells was not decreased in the patients. NK by normal PBMC was diminished both in the presence of sera from patients with reduced NK and when the effector cells were pretreated with the sera. Pretreatment of target K562 cells did not alter NK activity. Suppression of NK by sera from patients did not correlate with levels of immune complexes or with antilymphocyte antibodies. Some patients had adherent cells which inhibited NK function. Addition of either indomethacin or catalase partially restored NK activity in such patients, indicating that both prostaglandins and hydrogen peroxide play a role in suppression. These data suggest that multiple mechanisms are involved in the defective NK activity seen in patients with Sjögren's syndrome. The reduction of NK activity in Sjögren's syndrome may contribute to the increased incidence of lymphoid malignancy.
Esophageal abnormalities and dysphagia in polymyositis and dermatomyositis
Authors: Merieux Paula De , Anthony Verity M. , Clements P. J. , Paulus Harold E.
Published: February 2007

Structural or functional abnormalities of the distal esophagus were demonstrated by cineradiography in 14 of 16 patients with polymyositis or dermatomyositis who had been incompletely responsive to high dose corticosteroids and, in some cases, immunosuppressive therapy, or who had adverse effects associated with these therapies. These distal abnormalities occurred in the absence of proximal esophageal skeletal muscle dysfunction in 70% of patients, usually were more frequent with increasing disease duration, and were functionally similar to abnormalities reported in scieroderma. Symptomatic improvement occurred in some patients with administration of antacids and measures designed to decrease esophageal reflux, but improved esophageal symptoms did not correlate with improvement in the myositis. In 18 autopsy subjects with similar histories, distal esophageal smooth muscle atrophy and fibrosis occurred in only 1 and 2 cases, respectively. Of 5 in whom distal esophageal dysmotility had been documented ante‐mortem, only 1 had fibrosis and none had smooth muscle atrophy. These findings suggest that factors other than fibrosis and muscle atrophy may contribute to distal esophageal dysmotility in polymyositis and dermatomyositis.
Isolation of an interleukin‐1‐like factor from human joint effusions
Authors: Wood D. D. , Ihrie E. J. , Dinarello C. A. , Cohen P. L.
Published: February 2007

Interleukin‐1 (IL‐1) is a macrophage derived mediator whose properties suggest that it could play a role in the pathology of arthritis. To test this hypothesis, joint fluids from patients with several different arthritides were tested. Small amounts of IL‐1‐like activity were recovered from many of these joint fluids after affinity chromatography over a column of rabbit anti‐human IL‐1. Positive fluids were obtained from patients with rheumatoid arthritis, psoriatic arthritis, Reiter's syndrome, osteoarthritis, gout, and traumatic arthritis. Upon gel filtration, the joint derived factor displayed a molecular weight distribution similar to that of IL‐1 derived from human monocytes stimulated in vitro. These results suggest that IL‐1 is present in joint effusions and, therefore, might contribute to joint destruction.
Pain in the rheumatic diseases
Authors: Kazis Lewis E. , Meenan Robert F. , Anderson Jennifer J.
Published: February 2007

The importance of pain in the health status and health behavior of patients with chronic rheumatic disease was evaluated. The Arthritis Impact Measurement Scales were used to estimate physical disability, psychological status, and pain in a large set of rheumatic disease patients. Explanatory regression models were built to explore the contribution of pain in physician and patient assessments of overall health, medication usage, and changes in health status over time. Results confirm that pain makes a highly significant contribution to explaining both physician and patient overall health assessments (P < 0.001). Pain is also the most important of the 3 health status components in explaining medication usage (P < 0.001). Finally, using prospective data, it is shown that current pain, rather than current physical or psychological disability, is the best predictor of subsequent pain (P < 0.001). Current pain also is most associated with subsequent physical disability (P < 0.05). These findings confirm the importance of pain in determining the health status and health behavior of individuals with chronic rheumatic disease, and suggest that doctors and other health professionals should continue to solicit and address the patient's complaints of pain.
The significance of thrombocytopenia in systemic lupus erythematosus
Authors: Miller Marian H. , Urowitz Murray B. , Gladman Dafna D.
Published: February 2007

The significance of thrombocytopenia in systemic lupus erythematosus (SLE) is unclear. Some researchers have found it associated with severe disease, others with mild disease. Thrombocytopenia (platelets < 100,000) occurred in 21 patients seen at an SLE clinic over 18 months. Prospective assessment of 19 (non‐SLE causes excluded) revealed 2 distinct subgroups. Seven were thrombocytopenic only during severe multisystem flares. Twelve had chronic thrombocytopenia with intermittent mild flares in other systems. Serious bleeding was rare in both subgroups. It was concluded that thrombocytopenia clearly is not a prognostic indicator.
Impaired natural killer cell function in systemic lupus erythematosus
Authors: Sibbitt Wilmer L. , Likar Laura , Spellman Craig W. , Bankhurst Arthur D.
Published: February 2007

Immune regulation requires clonal expansion of regulatory T cells which is dependent on the presence of interleukin‐2 (IL‐2). Previously, both natural killer (NK) cell function and IL‐2 production were found to be depressed in systemic lupus erythematosus (SLE). This study was designed to determine the relationship between IL‐2 production and NK cell activity in SLE. NK activity as determined by a standard 4‐hour51Cr‐release assay was impaired in SLE (11.0 ± 5.1 lytic units/107cells) compared with controls (25.1 ± 7.1 lytic units/107cells) (P< 0.05). IL‐2 production was induced with concanavalin A and phorbol ester and quantitated using the IL‐2 dependent cell line HT‐2. IL‐2 production was impaired in only 1 SLE patient, despite concomitant abnormalities in NK function in the SLE group as a whole. Moreover, in patients with impaired NK activity, incubation of lymphocytes with exogenous IL‐2 did not restore NK activity to normal levels. These findings demonstrate that impaired NK activity in SLE is independent of IL‐2 production and that defects in IL‐2 production in SLE may not be as common as previously reported.
Connective tissue activation
Authors: Cabral A. , Castor C. W.
Published: February 2007

Four normal (NF) and 4 scleroderma skin fibro‐blast (SF) strains were compared with respect to 1) basal 14C‐glucosamine and 35SO4‐labeled glycosaminoglycan (GAG) synthesis, 2) responsiveness to autacoid mediators, and 3) performance following maximal stimulation. Under basal conditions, SF synthesized and secreted 2–3 times more radioactive hyaluronic acid than the NF (P < 0.001); molecular volume by gel chromatography was similar and suggested a high molecular weight product. SF were essentially as responsive to normal lymphoid and platelet factors as were NF. No consistent qualitative or quantitative differences in sulfated GAG synthesis were noted between the 2 groups of cells. Incubation of NF and SF with a false “core protein” such as p‐nitrophenyl‐β‐D‐xyloside suggested that synthesis of the core protein was rate limiting; SF and NF were equally facile in SO4‐GAG chain synthesis in the presence of a β‐xyloside. SF appear to retain in vitro a partially activated state for many generations, at least with respect to hyaluronic acid synthesis.
Morphologic and mitogenic responses of rabbit synovial fibroblasts to transforming growth factor β require transforming growth factor α or epidermal growth factor
Authors: Brinckerhoff Constance E.
Published: February 2007

We tested the hypothesis that normal synovial fibroblasts might proliferate in response to transforming growth factors (TGFs), peptides that are extracted with acid‐ethanol from bovine kidney or salivary gland and that cause anchorage‐independent growth of normal cells. A 72‐hour exposure of confluent monolayers of rabbit synovial fibroblasts in 10% fetal calf serum to partially purified TGF‐β in the presence of TGF‐β gave a 2‐ to 5‐fold increase in incorporation of 3H‐thymidine, protein content, and cell number. Similar results were obtained with high pressure liquid chromatography‐purified TGF‐β in the presence of epidermal growth factor (EGF) (a type of TGF‐β). By itself, purified TGF‐β was not mitogenic; it depended absolutely on EGF. However, only TGF‐β along with EGF, and not EGF alone, induced a marked morphologic change: a piling up of cells into foci resembling those commonly seen in primary cultures of rheumatoid synovial cells. Mitogenic responses induced by the TGF‐β‐EGF combination were prevented by all‐trans‐retinoic acid but not by indomethacin or dexamethasone. The data indicate that TGF‐β, a peptide extracted from normal cells, can act in concert with EGF to cause proliferation and piling up of synovial cells and raise the possibility that these factors may play a role in rheumatoid arthritis and other proliferative but nonmalignant diseases as well.
A new model of osteoarthritis in rabbits
Authors: Butler M. , Colombo C. , Hickman L. , O'Byrne E. , Steele R. , Steinetz B. , Quintavalla J. , Yokoyama N.
Published: February 2007

A battery of steroidal and nonsteroidal antirheumatic drugs and protease inhibitors were tested by intraarticular injection for effects on osteoarthritis of the knees of rabbits subjected to partial lateral meniscectomy and section of the sesamoid and collateral fibular ligaments. Among the standard drugs, only the glucocorticoid, triamcinolone hexacetonide, and the protease inhibitor, tranexamic acid, exhibited significant anti‐osteoarthritic activity. An experimental drug, GPA 2163, also offered some protection against joint degeneration. The nonsteroidal antiinflammatory drugs had no effect on the development of osteoarthritis in the model.
Abnormal interferon modulation of natural cytotoxicity in systemic lupus erythematosus relation to suppressive serum factors
Authors: Sibbitt W. L. , Froelich C. J. , Bankhurst A. D.
Published: February 2007

In the present study we examined one aspect of the derangement in natural cytotoxicity (natural killer, NK) activity observed in some patients with systemic lupus erythematosus (SLE), i.e., the lack of enhancement of NK activity usually seen with interferon (IFN). NK activity of SLE patients as a group was 23.0 ± 3.9 lytic units (LU)/107cells (mean ± SE). This contrasted with the NK activity found in normal controls (45.0 ± 3.8 LU/107cells) (P< 0.05). The enhancement seen with IFN was an increase of 15.4 ± 4.0 LU/107cells in SLE patients compared with 104.6 ± 192 LU/107cells in control subjects (P< 0.05). SLE sera and aggregated IgG (Agg‐IgG) also inhibited the increase in NK activity of normal peripheral blood mononuclear cells after IFN priming. The results reported here support the hypothesis that the impaired baseline NK activity and poor response to IFN noted in SLE are secondary, in part, to the presence of inhibitory serum factors and preactivation by IFN.
Genetic differences between b27 positive patients with ankylosing spondylitis and b27 positive healthy controls
Authors: Calin Andrei , Marder Amy , Becks Elena , Burns Thomas
Published: February 2007

In a controlled study of the 499 available first degree relatives of 79 consecutive HLA‐B27 positive patients with ankylosing spondylitis and 69 HLA‐B27 positive healthy blood donors, 19 cases of ankylosing spondylitis were found: 16 (15 B27 positive) among the 282 relatives of the patients with ankylosing spondylitis, and 3 (1 B27 positive, 1 B27 negative, 1 unknown) among the 217 relatives of healthy donors (Xc2 = 5.11; P < 0.025). However, if all cases of possible spondyl‐arthritis are included, 48 cases of ankylosing spondylitis were found: 37 of 282 relatives of patients with ankylosing spondylitis and 11 of 217 relatives of healthy donors (Xc2 = 8.29; P < 0.01). Assuming that 50% of relatives of B27 positive individuals carry this antigen, 15 of 142 (10.6%) B27 positive relatives of patients and 2 of 108 (1.9%) B27 positive relatives of healthy subjects (Xc2 = 5.91; P < 0.025) have ankylosing spondylitis. The relative risk of spondylarthropathy for B27 positive relatives of B27 positive patients compared with relatives of B27 positive healthy subjects is 5.6. Assuming all subjects were evaluated in a similar manner, analysis of these data suggests genetic differences between B27 positive diseased individuals and B27 positive healthy subjects.
Synovial fluid lactic acid in septic and nonseptic arthritis
Authors: Eugene Arthur R. , Stern Mark , Galeazzi Mauro , Baldassare Andrew R. , Weiss Terry D. , Rogers John R. , Zuckner Jack
Published: February 2007

We determined lactic acid levels by the lactic dehydrogenase method in synovial fluid of 41 patients with various rheumatic diseases, to test the concept that significantly elevated values were diagnostic of septic arthritis. Nine patients had septic arthritis, 15 rheumatoid arthritis (RA), and the remainder miscellaneous conditions. In another 9 patients with different rheumatic diseases, including 1 with septic arthritis, synovial fluid lactic acid was determined by both the lactic dehydrogenase and gas‐liquid chromatography methods. There was a wide scatter of values among patients with septic and nonseptic inflammatory arthritis, and much overlap occurred. We could not differentiate septic arthritis from RA on the basis of synovial fluid lactic acid levels. Results were similar with both procedures for determining lactic acid levels.
Clinical spectrum of connective tissue disease after cosmetic surgery
Authors: Kumagai Yasuo , Shiokawa Yuichi , Medsger Thomas A. , Rodnan Gerald P.
Published: February 2007

Connective tissue disease has been reported to occur following cosmetic surgery with injection of the foreign substances paraffin and silicone (human adjuvant disease). The clinical findings in 18 such patients and a review of 28 additional cases from the Japanese literature are presented. The patients were classified into 2 major groups: group I consisted of 24 patients with definite connective tissue disease—12 with scleroderma, including 8 with progressive systemic sclerosis (PSS), 6 with rheumatoid arthritis, 5 with systemic lupus erythematosus, and 1 with polymyositis; group II consisted of 22 patients with human adjuvant disease with some symptoms, signs, and laboratory abnormalities suggestive, but not diagnostic of a connective tissue disease. The occurrence of PSS is approximately three‐fold greater than expected for all women believed to have undergone such surgery, and PSS developed primarily in individuals injected with paraffin. Prolonged exposure to the injected substance may play a role in the induction of these immunologic disorders.
The psychosocial impact of systemic lupus erythematosus and rheumatoid arthritis
Authors: Liang Matthew H. , Rogers Malcolm , Larson Martin , Eaton Holley M. , Murawski Benjamin J. , Taylor Jennifer E. , Swafford Julie , Schur Peter H.
Published: February 2007

Seventy‐six ambulatory patients with systemic lupus erythematosus and a comparison group of 23 ambulatory patients with rheumatoid arthritis were given a structured interview and standard psychological tests, including the Minnesota Multiphasic Personality Inventory, to determine the psychosocial impact of the illness. Both groups had significantly elevated scores on 3 Minnesota Multiphasic Personality Inventory scales: Hypochondriasis, Depression, and Hysteria. Psychological difficulties are an integral part of systemic lupus erythematosus and are as common as most other manifestations. The implications for clinical practice are discussed.
Immunohistologic characterization of synovial membrane lymphocytes in rheumatoid arthritis
Authors: Young Carol L. , Adamson Thomas C. , Vaughan John H. , Fox Robert I.
Published: February 2007

Synovial membrane biopsy specimens from 15 rheumatoid arthritis patients were examined using routine histologic stains and monoclonal antibodies directed against cell surface antigens. Three patterns of lymphoid cell infiltrates were recognized: 1) diffuse infiltration of T cells that surrounded clusters of germinal center B cells (3 patients); 2) diffuse T cell infiltration, lacking germinal centers (8 patients); and 3) proliferation of subsynovial fibroblasts, with relatively few lymphoid cells (4 patients). The synovial, subsynovial, and perivascular tissues in each of the patterns exhibited a high frequency of HLA‐DR antigen, HLA‐DS antigen, transferrin receptor, and/or epidermal growth factor receptor. In contrast, normal or osteoarthritic synovial tissues did not display a marked increase of these antigens or receptors. Cells bearing natural killer antigen were infrequent in each of these patterns. Active synovitis, synovial effusions, anemia, and elevated sedimentation rate were present in rheumatoid arthritis patients with each of the three histologic patterns. Immunohistologic characterization of synovial membrane infiltrates by these monoclonal antibodies provides additional information about pathogenesis of rheumatoid arthritis and may help in predicting responses to different therapeutic modalities.
The effects of in vivo hydrocortisone on lymphocyte‐mediated cytotoxicity
Authors: Katz Paul , Zaytoun Annette M. , Lee Jr. James H. ,
Published: February 2007

To examine the effects of in vivo hydrocortisone sodium succinate (HC) on natural killer (NK) cell and antibody‐dependent cellular cytotoxicity (ADCC), 11 normal adults received a single intravenous bolus of 400 mg hydrocortisone. Lymphocytes were tested for NK activity and ADCC using 51chromium (51Cr)‐release and single cell cytotoxicity assays against Molt‐4 and sensitized RL ˆ→ target cells; respectively. Four hours after injection, both NK and ADCC activity were transiently increased in the 51Cr‐release system (P < 0.05). At 4 hours, there was a twofold increase in the relative frequency of potentially cytotoxic target binding cells (P < 0.001) but the absolute number of these cells did not change (P < 0.1). However, the percentage lysis of bound targets at 4 hours was not altered (P > 0.1). These data suggest that: 1) lymphocytes participating in NK and ADCC reactions are refractory to the kinetic and functional effects of HC; 2) the increased lytic activity observed at 4 hours is due to a selective depletion of noncytotoxic cells from the circulation; and 3) NK and ADCC activity did not differ in their responses to HC.
Nailfold biopsy in scleroderma and related disorders
Authors: Thompson Robert P. , Harper Frank E. , Maize John C. , Ainsworth Sterling K. , Carwile Leroy E. , Maricq Hildegard R.
Published: February 2007

Although nailfold capillary abnormalities associated with connective tissue disease (CTD) have been studied by direct in vivo microscopy, little is known of the underlying histology and morphology of this tissue. This report summarizes light microscopic study of glycolmethacrylate embedded nailfold biopsies from 13 CTD patients (9 scleroderma, 2 CREST, 2 undifferentiated CTD), 2 subjects with Raynaud's phenomenon alone, and 9 normal volunteers of similar age and sex distribution. The most striking and consistent finding was the presence of globular, eosinophilic, PAS‐positive deposits in the cuticles of 14 of 15 patients and none of the controls. This material, identified by immunofluo‐rescent staining as serum protein exudates, was associated with pronounced parakeratosis and elevated epithelial mitotic activity. Capillary ectasia with thinning of the basement membrane was often present in CTD biopsies. Occasional signs of endothelial swelling and proliferation were encountered in both populations. Inflammatory changes were rarely seen. In quantitative comparison with control tissues, the superficial dermis from CTD patients contained significantly fewer capillaries, cutaneous nerve bundles, and interstitial fibroblasts per unit area and fewer papillary capillaries per unit of epidermal length. Measures of capillary density in sectioned tissue correlated well with the results of in vivo microscopic examination.
A long‐term longitudinal study of anticentromere antibodies
Authors: Tramposch Helen D. , Douglas Smith C. , Senecal Jean‐Luc , Rothfield Naomi
Published: February 2007

A longitudinal retrospective study of 37 patients previously tested for anticentromere antibodies (ACA) in 1982 was carried out. No ACA were found in stored sera from 22 ACA‐negative patients including 1 patient with CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia). All ACA‐positive patients, with 1 exception, were found to have ACA in their sera over prolonged periods of time. One patient developed ACA for the first time when the third feature of the CREST syndrome (Raynaud's phenomenon) was noted. Anticentromere antibodies were IgG, and no consistent change in titer over time was found.
Multiple serologic reactions and their relationship to clinical activity in systemic lupus erythematosus
Authors: Isenberg David A. , Shoenfeld Yehuda , Schwartz Robert S.
Published: February 2007

Analysis of the binding of serum from 56 systemic lupus erythematosus patients to native DNA (nDNA), denatured DNA (dDNA), poly I, poly(dT), RNA, and cardiolipin revealed multiple antigen binding in many of the sera. Raised levels of antibodies (IgG and/or IgM) to denatured DNA were found in the highest percentage (68%) of patients. A small subset of patients with multiple raised IgM antibodies, renal disease, and vasculitic skin rash was identified. No correlation between multiple serologic activity and clinical disease was found.
Sjögren's syndrome in MRL/l and MRL/n mice
Authors: Hoffman Robert W. , Alspaugh Margaret A. , Waggie Kim S. , Durham James B. , Walker Sara Ellen
Published: February 2007

Six autoimmune murine models (MRL/l, MRL/n, NZB, NZB/NZW, PN, C57BL/6J‐lpr/lpr) were compared with normal control C57BL/6J and DBA/2 mice to determine if spontaneous autoimmune disease was associated with evidence of Sjögren's syndrome. Schirmer tests documented dry eyes in NZB/NZW and PN mice; other autoimmune strains and controls had normal tear formation. All autoimmune mice had conjunctivitis, but this abnormality was most severe in the PN strain. Ninety‐eight percent of MRL/1 and MRL/n mice had mononuclear cell infiltrates in lacrimal glands, and salivary glands were involved to a lesser degree. New Zealand mice and PN mice had smaller gland lesions. The extensive gland destruction in MRL/l and MRL/n mice suggested that these substrains merit further studies as animal models of Sjögren's syndrome.
The importance of tissue substrate in the SS‐A/Ro antigen‐antibody system
Authors: Harmon Catherine E. , Deng Jau‐Shyong , Peebles Carol L. , Tan Eng M.
Published: February 2007

Using highly monospecific anti‐SS‐A containing sera and specific antibody to SS‐A antigen dissociated from immune precipitates, tissue sections and cell culture lines were evaluated by the indirect immunofluorescence technique to determine the intracellular location, tissue distribution, and species specificity of the SS‐A/Ro antigen. The SS‐A/Ro antigen is predominantly a nuclear antigen giving an immunofluorescence staining pattern of discrete nuclear speckles. The SS‐A/Ro antigen is present in a wide variety of human tissue, including kidney and liver parenchymal cells, lymphocytes, fibroblasts, and epithelioid cells. However, the SS‐A/Ro antigen does appear to have a variable species distribution, with significant quantities of the antigen detected by immunofluorescence in cells of human, monkey, dog, and guinea pig, but absent to low amounts detected in cells of mouse, rat, rabbit, hamster, and chicken.
Experimental arthritis induced by intraarticular injection of allogenic cartilaginous particles into rabbit knees
Authors: Evans Christopher H. , Mazzocchi Raphael A. , Nelson D. Dirk , Rubash Harry Edward
Published: February 2007

Human synovial fluid often contains small cartilaginous “wear particles.” Previous in vitro experiments have indicated the potential involvement of these particles in the pathophysiology of arthritis. To determine whether this potential is realized under the conditions existing within joints, standard suspensions of lapine articular cartilage were injected intraarticularly into the knee joints of rabbits. Thrice‐weekly injections of 1 mg allogenic cartilage produced an inflammatory arthritis, accompanied by a marked cellular effusion, in all rabbits within 5 months. The synovium became hyperplastic, discolored, and infiltrated with mononuclear inflammatory cells. Embedded particles of the injected material were seen in histologic preparations of these synovia. Organ cultures of such synovia produced 4 to 5 times more collagenase, plasminogen activator, “Pz‐peptidase,” neutral and acid azocaseinase, and β‐glucuronidase than did cultures of synovia from control knees injected with saline. Furthermore, the articular cartilage of knees injected with cartilaginous particles showed elevated intrinsic collagenolytic activity. Histologic examination of the articular cartilage revealed an attendant loss of metachromasy, resulting in friability, pitting, and discoloring of the cartilage. Preliminary immunoassays failed to demonstrate a systemic immune response to the injected material.
Sexual problems in rheumatoid arthritis and ankylosing spondylitis
Authors: Elst P. , Sybesma T. , Van Stadt R. J. Der , Prins A. P. A. , Hissink Muller W. , Den Butter A.
Published: February 2007

In this study, scores on the sexual motivation scale (which measures the tendency to engage in sexual interaction versus the tendency to be averse to sexual interaction) were determined, by interview, in ankylosing spondylitis (AS) and rheumatoid arthritis (RA) patients and compared with the scores of healthy matched controls. AS patients did not score differently from the healthy population, but scores of men and women with RA were more in the direction of sexual aversion than those of healthy men and women. In female RA patients, some relationship was found between disease variables such as joint index and erythrocyte sedimentation rate and the score on the sexual motivation scale. In the second part of the interview, preference for certain coital positions was investigated, and the demand for help with sexual problems was explored. The percentage of RA patients expressing a need for advice was considerably greater than the percentage of AS patients.
Controlled trial of hydroxychloroquine and d‐penicillamine singly and in combination in the treatment of rheumatoid arthritis
Authors: Bunch Thomas W. , O'Duffy J. Desmond , Tompkins Richard B. , O'Fallon W. Michael
Published: February 2007

A 2‐year, controlled, double‐blind trial of D‐penicillamine and hydroxychloroquine either alone or in combination was conducted on patients with progressive rheumatoid arthritis. The group given D‐penicillamine alone improved most, but a linear fall‐off in efficacy occurred. Surprisingly, the group receiving combination drug therapy did not fare as well as the group receiving D‐penicillamine therapy. A subset of patients receiving hydroxychloroquine therapy had prolonged benefit. Toxicity, though not uncommon, was generally not severe.
Polymyositis/dermatomyositis and pregnancy
Authors: Gutiéarrez Gaspar , Dagnino Rogelio , Mintz Gregorio
Published: February 2007

Eighteen women with polymyositis/dermatomyositis (PM/DM) were studied to determine the possible influences of pregnancy on the disease and the influence of the disease on pregnancy. Before the onset of PM/DM there were 77 pregnancies: 7 (9%) ended in abortion, 2 (2.5%) in perinatal deaths, with a total fetal loss of 11.5%. There were 3 (3.8%) premature newborns that survived. These figures are equivalent to those of the general population. There were 10 pregnancies in 7 patients coinciding with PM/DM, 1 of them with twins; 3 (30%) ended in abortion, 3 (25%) in perinatal deaths, with a total fetal loss of 55%, and 5 (50%) pregnancies ended prematurely. Four of the 7 women had onset of PM/DM during pregnancy, and 3 others with previously inactive disease had an exacerbation during pregnancy. There were no maternal deaths, nor was there any correlation between activity of PM/DM and fetal loss. These results together with those previously reported suggest that pregnancy in PM/DM should be considered high‐risk for both the mother and the baby.
Pregnancy and systemic sclerosis
Authors: Ballou Stanley P. , Morley John J. , Kushner Irving
Published: February 2007

Pregnancy has been reported infrequently in patients with systemic sclerosis. Consequently, the outcome and appropriate management of such patients is uncertain. We review the obstetric experience of 19 female patients with systemic sclerosis, and report 2 women in whom 3 pregnancies occurred during the course of disease. Maternal complications included hypertension during 2 of these pregnancies and congestive heart failure during 1. There were 2 premature deliveries, although all 3 infants survived. Our experience with these patients and a review of the available literature suggest that, in patients with systemic sclerosis, fertility may be reduced and complications of pregnancy may be more frequent.
Autoreactivity to collagen in a murine lupus model
Authors: Phadke Kalindi , Fouts Rebecca , Parrish John , Baker Robert S.
Published: February 2007

MRL/1 mice exhibit many characteristics of human systemic lupus erythematosus including antinuclear antibodies, circulating immune complexes, glomerulonephritis, and death secondary to renal failure. In addition, these mice have elevated levels of rheumatoid factor and spontaneously develop arthritis that has many similarities to human rheumatoid arthritis. Our present studies indicate that, with age, they also develop reactivity to types I and II collagen. The levels of antibodies against native or denatured types I and II collagen in the sera of 4–5‐month‐old MRL/1 mice are significantly higher than those in the sera of age‐matched Balb/c or MRL/n mice. The specificity of these antibodies for collagen was demonstrated by a competitive binding assay. The T cells from 1‐ or 2‐month‐old MRL/1 mice exhibited a significant proliferative response in the presence of type I collagen and a mild or no response to type II collagen. Both antigenic and mitogenic responses decreased with age. The results suggest that the development of autoimmunity to collagen may play an important role in the perpetuation of arthritis, vasculitis, and glomerulonephritis in MRL/1 mice.
Evaluation of Diagnostic Criteria for Ankylosing Spondylitis
Authors: Linden Sjef Van Der , Valkenburg Hans A. , Cats Arnold
Published: February 2007

The New York and the Rome diagnostic criteria for ankylosing spondylitis (AS) and the clinical history screening test for AS were evaluated in relatives of AS patients and in population control subjects. The New York criterion of pain in the (dorso) lumbar spine lacks specificity, and the chest expansion criterion is too insensitive. The Rome criterion of low back pain for more than 3 months is very useful. Our study showed the clinical history screening test for AS to be moderately sensitive, but it might be better in clinical practice. As a modification of the New York criteria, substitution of the Rome pain criterion for the New York pain criterion is proposed.
Randomized, Double‐Blind, Placebo Controlled Trial of Low‐Dose Pulse Methotrexate in Psoriatic Arthritis
Authors: Willkens Robert F. , Williams H. James , Ward John R. , Egger Marlene J. , Reading James C. , Clements Philip J. , Cathcart Edgar S. , Samuelson Cecil O. , Solsky Marilyn A. , Kaplan Stanley B. , Guttadauria Maria , Halla James T. , Weinstein Arthur
Published: February 2007

Thirty‐seven patients with psoriatic arthritis were entered into a 12‐week prospective, controlled, double‐blind multicenter trial comparing placebo and oral pulse methotrexate therapy. Methotrexate was given in a dose of 2.5—5.0 mg every 12 hours in 3 consecutive doses per week. A stable background medication program with nonsteroidal antiinflammatory drugs was allowed. Methotrexate was superior to placebo only in physician assessment of arthritis activity and in improvement of the amount of skin surface area with psoriasis. A small but statistically significant rise of serum total bilirubin occurred in the methotrexate‐treated patients. No patients were withdrawn from the study for adverse drug effects.
The Relative Roles of Hydrolases of the Erythrocyte and Other Tissues in Controlling Aspirin Survival in Vivo
Authors: Costello Patrick B. , Caruana Joseph A. , Green Floyd A.
Published: February 2007

The rate of aspirin (acetyIsalicylic acid, ASA) deacetylation to salicylate in vivo determines the availability of the intact molecule for therapeutically important transacetylation reactions. Experiments were carried out to assess the relative contribution of a previously isolated human erythrocyte ASA esterase to the overall hydrolysis rate in vivo, as opposed to similar enzymes in other tissues. In vitro, the rates of ASA hydrolysis were relatively slow in plasma from humans and dogs. The hydrolysis rates were significantly greater in whole blood in dogs, rabbits, and humans. In human and canine whole blood, the rate of hydrolysis correlated positively with hematocrit. In vivo studies with dogs showed that ASA decay rates conform to a 2‐compartment model. After reduction of hematocrit by a mean of 49% in 4 dogs without previous splenectomy, the “availability” of ASA increased. In 4 dogs with previous splenectomy, this measurement was increased even more after comparable hematocrit reduction. In 2 dogs that underwent a sub‐total hepatectomy, ASA availability increased by only 35% and 12.8%, respectively. These results suggest a significant role for the erythrocyte esterase in vivo in the dog and possibly in humans.
Total lymphoid irradiation therapy in refractory rheumatoid arthritis
Authors: Brahn Ernest , Helfgott Simon M. , Belli James A. , Anderson Ronald J. , Reinherz Ellis L. , Schlossman Stuart F. , Austen K. Frank , Trentham David E.
Published: February 2007

Twelve patients with refractory rheumatoid arthritis were treated with total lymphoid irradiation (TLI) to a total cumulative dose of 3,000 rads. Post‐TLI morbidity/mortality included 8 patients with xerostomia, 4 with weight loss of >10 kg, 3 with loss of 4 or more teeth, 3 with herpes zoster, 4 with bacterial infection that was fatal in 2, 3 with hypothyroidism, 1 with cutaneous vasculitis, and death from myocardial infarction in 1 patient and cardiorespiratory arrest in another. Ten of the patients were reevaluated 15–40 months (mean ± SE, 30 ± 2) after completion of TLI, and significant improvement was noted in several disease parameters including number of swollen joints, duration of morning stiffness, and 50‐foot walking time. Blood lymphopenia and a decrease in helper T cells (T4) were also noted. These data suggest that changes in immunoregulation induced by TLI can produce long‐lasting alterations in rheumatoid arthritis, although adverse effects may limit its efficacy.