bluuebunny/crossref_metadata_2025 huggingface dataset:
Autoantibodies to nonhistone chromosomal proteins HMG‐1 and HMG‐2 in sera of patients with juvenile rheumatoid arthritis
Authors: Wittemann Bettina , Neuer Gunter , Michels Hartmut , Truckenbrodt Hans , Bautz Friedlinde A.
Published: February 2007

IgG antibodies against the high mobility group (HMG) nonhistone chromosomal proteins HMG‐1 and/or HMG‐2 were detected in the sera of 49 (39%) of 126 antinuclear antibody (ANA)‐positive patients with juvenile rheumatoid arthritis (JRA), by immunoblotting. Clinical diagnosis classified these patients in 2 major groups, 105 with pauciarticular‐onset JRA and 21 with polyarticular‐onset JRA. Anti‐HMG‐1 and/or anti‐HMG‐2 antibodies were found in 8 (25%) of 32 pauciarticular‐onset JRA patients with uveitis and in 34 (47%) of 73 patients without uveitis, whereas anti‐HMG‐1 and/or anti‐HMG‐2 antibodies were found in 4 (24%) of 17 children with polyarticular‐onset JRA without uveitis. Among 53 sera from ANA‐negative JRA patients, 3 (6%) were positive for anti‐HMG‐1 and/or anti‐HMG‐2 antibodies, whereas no reactivity to HMG‐1 or HMG‐2 proteins was observed in 48 sera from age‐matched children with nonrheumatic diseases.
Gonococcal pericarditis with tamponade in a patient with systemic lupus erythematosus
Authors: Coe Marcia D. , Hamer Davidson H. , Levy Charles S. , Milner Mark R. , Nam Myong Ho , Barth Werner F.
Published: February 2007

Pericarditis is one of the most frequent manifestations of systemic lupus erythematosus; however, purulent pericarditis and tamponade are rare. We describe a patient with systemic lupus erythematosus and culture‐proven gonococcal arthritis who developed purulent pericarditis with intracellular gram‐negative diplococci. Evidence of tamponade was seen on echocardiography. There has not been a reported case of Neisseria gonorrhoeae in pericardial fluid or tissue since the introduction of antibiotics.
Diminished incidence of severe rheumatoid arthritis associated with oral contraceptive use
Authors: Zeben Derkjen Van , Hazes Johanna M. W. , Vandenbroucke Jan P. , Dijkmans Ben A. C. , Cats Arnold
Published: February 2007

It has been suggested that the negative association between rheumatoid arthritis (RA) and oral contraceptive (OC) use might be limited to the more severe forms of RA. To investigate this further, we studied 121 consecutive female patients with definite RA, 52 female patients with probable RA, and 378 female controls. All patients had RA symptoms of recent onset. After a mean followup period of 6 years, patients with definite RA were classified as having either a severe disease course (n = 76) or a mild disease course (n = 45). The negative association between OC use prior to the onset of RA symptoms and the development of RA was limited to those patients with definite RA who had a severe disease course. We therefore conclude that OC use prior to the onset of RA symptoms is only associated with a reduction in the incidence of severe RA. This may explain the divergent results of previous studies.
Collagen‐collagen versus collagen‐proteoglycan interactions in the determination of cartilage strength
Authors: Broom Neil D. , Silyn‐Roberts Heather
Published: February 2007

For articular cartilage to function as a stress‐reducing layer in the joint, it must both deform to an appropriate level to achieve load‐spreading as well as remain structurally coherent. Combined micromechanical and enzymatic studies of cartilage have demonstrated that the bulk of the extractable proteoglycans, while essential to the maintenance of compressive stiffness, contribute little to its cohesive strength. The study reported here clarifies fundamental aspects of the relationship between matrix components and the biomechanical function of cartilage.
Increased expression of platelet‐derived growth factor type b receptors in the skin of patients with systemic sclerosis
Authors: Klareskog Lars , Gustafsson Rolf , Scheynius Annika , Hällgren Roger
Published: February 2007

The expression of B‐type receptors for platelet‐derived growth factor (PDGF) was investigated in skin biopsy samples from patients with systemic sclerosis (SSc), by immunohistochemical staining using monoclonal antibodies specific for the receptor. Whereas skin from healthy individuals lacked expression of PDGF‐B receptors, receptor expression was seen in sclerodermatous skin lesions from 13 of 14 patients. Increased receptor expression was observed in dermal vessels, as well as on many stromal fibroblast‐like cells close to these vessels. PDGF‐B receptor expression was most pronounced within and around dermal vessels in which perivascular infiltrates of Leu‐4‐positive T lymphocytes and HLA‐DR‐positive, RFD7‐positive activated macrophages were present. Both perivascular inflammatory cell infiltrates and PDGF‐B receptor expression were generally also seen in macroscopically normal areas of the skin of the SSc patients, indicating that the observed phenotypic alterations may precede the macroscopically observable features of scleroderma in the skin. The observed induction of PDGF‐B receptors, together with indirect indications of increased synthesis and release of PDGF, would be compatible with altered PDGF‐mediated control of connective tissue cell growth as part of the molecular basis for development of the skin lesions in SSc.
Major histocompatibility complex genes and susceptibility to systemic lupus erythematosus
Authors: Fronek Zdenka , Timmerman Luika A. , Alper Chester A. , Hahn Bevra H. , Kalunian Kenneth , Peterlin B. Matija , Mcdevitt Hugh O.
Published: February 2007

Susceptibility to systemic lupus erythematosus is associated with major histocompatibility complex (MHC)‐encoded genes. We have used nucleotide sequence analysis to better define the disease‐associated MHC alleles. HLA‐DR2, DQw1, and especially the rare allele DQβ1.AZH confer high relative risk (RR = 14) for lupus nephritis in a Caucasian population of patients. Pilot studies using historical controls suggest that these genes also confer a high risk in non‐Caucasian ethnic groups (RR = 24–78). We have found that DR4 is significantly decreased in patients with lupus nephritis. Fifty percent of the patients with lupus nephritis had either the DQβ1.1, the DQβ1.AZH, or the DQβ1.9 alleles. These alleles share amino acid residues that have been predicted to be the contact points for antigen and the T cell receptor. These HLA alleles appear to have a direct role in the predisposition to lupus nephritis, whereas DR4 may have a “protective” effect.
The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand
Authors: Altman R. , Alarcon G. , Appelrouth D. , Bloch D. , Borenstein D. , Brandt K. , Brown C. , Cooke T. D. , Daniel W. , Gray R. , Greenwald R. , Hochberg M. , Howell D. , Ike R. , Kapila P. , Kaplan D. , Koopman W. , Longley S. , Mcshane D. J. , Medsger T. , Michel B. , Murphy W. , Osial T. , Ramsey‐Goldman R. , Rothschild B. , Stark K. , Wolfe F.
Published: February 2007

Clinical criteria for the classification of symptomatic idiopathic (primary) osteoarthritis (OA) of the hands were developed from data collected in a multi‐center study. Patients with OA were compared with a group of patients who had hand symptoms from other causes, such as rheumatoid arthritis and the spondylar‐thropathies. Variables from the medical history, physical examination, laboratory tests, and radiographs were analyzed. All patients had pain, aching, or stiffness in the hands. Patients were classified as having clinical OA if on examination there was hard tissue enlargement involving at least 2 of 10 selected joints, swelling of fewer than 3 metacarpophalangeal joints, and hard tissue enlargement of at least 2 distal interphalangeal (DIP) joints. If the patient had fewer than 2 enlarged DIP joints, then deformity of at least 1 of the 10 selected joints was necessary in order to classify the symptoms as being due to OA. The 10 selected joints were the second and third DIP, the second and third proximal interphalangeal, and the trapeziometacarpal (base of the thumb) joints of both hands. Criteria derived using the “classification tree” method were 92% sensitive and 98% specific. The “traditional format” classification method required that at least 3 of these 4 criteria be present to classify a patient as having OA of the hand. The latter sensitivity was 94% and the specificity was 87%. Radiography was of less value than clinical examination in the classification of symptomatic OA of the hands.
Polymorphism and expression of the galactosyltransferase‐associated protein kinase gene in normal individuals and galactosylation‐defective rheumatoid arthritis patients
Authors: Delves Peter J. , Lund Torben , Axford John S. , Alavi‐Sadrieh Azita , Lydyard Peter M. , Mackenzie Lorna , Smith Mark D. , Kidd Vincent J.
Published: February 2007

We used restriction endonuclease digestion of leukocyte DNA to assess the structural integrity of an N‐acetylglucosamine β1→4 galactosyltransferase (GalTase)‐associated (GTA) protein kinase gene in rheumatoid arthritis (RA) patients. This analysis provides evidence that the gross structure of the GTA protein kinase gene locus remains intact in patients with defective galactosylation and that this gene locus is polymorphic both in normal individuals and in patients with RA, although no polymorphisms unique to RA patients were observed. Initial data on the expression of this gene indicate that comparable levels of GTA protein kinase messenger RNA are present in the lymphocytes of normal individuals and RA patients, irrespective of whether lymphocytes were obtained from patients with decreased or normal levels of galactosylation.
Dermal mast cell degranulation in systemic sclerosis
Authors: Seibold James R. , Giorno Ralph C. , Claman Henry N.
Published: February 2007

Paired biopsy samples from involved and uninvolved skin were obtained from 19 patients with generalized scleroderma (11 with early, progressive disease and 8 with late, improving disease). Skin biopsy samples were double stained for mast cell granules and for mast cell membrane. The number of mast cells was increased in patients with systemic sclerosis (SSc), in both involved and uninvolved skin and in both early and late disease. There was an increase in the number of degranulated mast cells in the involved skin of patients with both early and late disease and in the not‐yet‐involved skin of patients with early disease; however, there was no increase in the number of degranulated mast cells in areas of previously involved but now normal skin of patients with late disease. Increases in mast cell number and degranulation precede clinically apparent dermal fibrosis in SSc. These observations and the absence of mast cell degranulation in regressing skin suggest a participatory role of the mast cell in the clinical progression of skin changes in SSc.
Outbreak of spontaneous staphylococcal arthritis and osteitis in mice
Authors: Bremell Tomas , Lange Stefan , Svensson Lena , Jennische Eva , Gröndahl Kerstin , Carlsten Hans , Tarkowski Andrzej
Published: February 2007

Staphylococcus aureus is the most common bacterial species found in association with nongonococcal bacterial arthritis in humans. We present here the first description of spontaneous bacterial arthritis and osteitis in mice. Clinically, the most obvious findings were swelling and/or ankylosis of hindpaws and nodose changes of the tail. The prevalence of arthritis and osteitis ranged from 0% to >50% of the mice studied, depending on the mouse strain. The most prominent histopathologic feature of the arthritis was hypertrophy of the synovial tissue and destruction of cartilage and underlying bone. Most of the S aureus‐infected mice displayed an identical phage type, which was also the only S aureus phage type found in skin isolates from clinically healthy mice. However, a few S aureus isolates were not typeable, indicating that an additional strain(s) might cause bacterial arthritis in mice.
Magnetic resonance imaging of sacroiliac joint inflammation
Authors: Ahlström H. , Feltelius N. , Nyman R. , Hällgren R.
Published: February 2007

A consecutive series of 27 patients with symptoms compatible with sacroiliitis underwent magnetic resonance imaging (MRI) of the sacroiliac joints. The diagnostic sensitivity of MRI was similar to that of computed tomography or conventional radiography. However, MRI seems to have the potential of providing unique information about the disease process in sacroiliitis by demonstrating abnormalities in subchondral bone and periarticular bone marrow. The results of this study suggest that early inflammatory changes in sacroiliitis occur in the subchondral structures of the sacroiliac joints.
Hla antigens in juvenile Arthritis
Authors: Fernandez‐Viña Marcelo A. , Fink Chester W. , Stastny Peter
Published: February 2007

Using DNA techniques, we investigated the role of HLA—DR, DQ, and DP alleles in susceptibility to juvenile arthritis (JA). We studied 2 groups of patients with JA having a different disease prognosis and course. The pauciarticular form is usually benign, while the polyarticular disease frequently leads to joint destruction and disability. Persistent pauciarticular disease developed preferentially in patients having HLA—DRw13‐Dw18 and DQw6‐Dw18, but these antigens did not confer susceptibility in patients whose disease converted to the polyarticular form. HLA—DPw2.1 was an additional susceptibility factor for patients with JA of pauciarticular onset. In the polyarticular form of JA, HLA—DPw3 was the major factor for susceptibility, giving a relative risk of 10.3 (P < 0.0001). In addition, we found that DRw8.1 and DQw4 were increased, and HLA—DR4 was markedly decreased, in patients with pauciarticular and polyarticular disease. These results indicate that in addition to some shared factors, distinct HLA class II alleles are important in pauciarticular or polyarticular JA. We conclude that typing with oligonucleotide probes may be useful in predicting the outcome in some children with arthritis.
Modulation of the effects of interleukin‐1 on glycosaminoglycan synthesis by the urine‐derived interleukin‐1 inhibitor, but not by interleukin‐6
Authors: Seckinger Philippe , Yaron Ilana , Meyer Frank A. , Yaron Michael , Dayer Jean‐Michel
Published: February 2007

Interleukin‐1 (IL‐1) has been shown to regulate glycosaminoglycan (GAG) synthesis. We therefore investigated whether an IL‐1 inhibitor or IL‐6 modulates IL‐1 biologic activities in human synovial cells and cultured articular cartilage. We found that in the presence of a constant amount of IL‐1β, stimulation of hyaluronic acid (HA) synthesis by the IL‐1 inhibitor was inhibited in a dose‐dependent manner. Similarly, the decrease in sulfated GAG synthesis induced by IL‐1 was reversed by the addition of the IL‐1 inhibitor. In contrast, IL‐6 did not affect the production of HA, prostaglandin E2, or collagenase in synovial cells, nor did it affect GAG in organ cultures when tested in the presence or absence of IL‐1β. Hence, IL‐6 was ineffective in modulating IL‐1 bioactivities on HA or sulfated GAG synthesis. These results emphasize the importance of IL‐1 and IL‐1 inhibitor in connective tissue destruction and raise questions concerning the role of IL‐6 in this pathogenesis.
Organ distribution of the ro (SS‐A) antigen in the guinea pig
Authors: Itoh Yasuhiko , Kriet John D. , Reichlin Morris
Published: February 2007

Using an anti—Ro (SS‐A—specific “sandwich” enzyme‐linked immunosorbent assay (ELISA) and Western immunoblotting, we determined the Ro (SS‐A) content (both quantitative and qualitative) in saline‐perfused organs of the guinea pig. All tissue extracts contained substantial concentrations of Ro (SS‐A) antigen and could be grouped into 3 categories based on quantitative reactivity in the sandwich ELISA. The 60‐kd and 52‐kd molecular forms of Ro (SS‐A) present in tissue extracts were similar to those described in Wi‐L2 extracts, and the 54‐kd molecular form of Ro (SS‐A) in guinea pig erythrocytes was similar to that found in human erythrocytes. The tissue distribution of the isoforms of Ro (SS‐A) was shown by Western immunoblotting to vary in different tissues, and the reactivity to the 60‐kd Ro (SS‐A) was correlated with the activity seen in the ELISA. Both the 60‐kd and 52‐kd Ro (SS‐A) bands in guinea pig liver extracts were very weak on Western immunoblots, in contrast to the high concentration of Ro (SS‐A) antigen in the ELISA. Other data suggest the possible existence of a unique form of Ro (SS‐A) in the liver. Guinea pig tissues have 4 Y RNA that are equivalent to the 4 human RNA—hY1, hY3, hY4, and hY5—present in HeLa cells, while guinea pig red blood cells have only one Y RNA, which is equivalent in size to human hY4. This heterogeneity of the Ro (SS‐A) antigen suggests that there is differential expression of the various Ro (SS‐A) genes in different tissues and expands the possibilities for tissue‐specific pathologic events involving the Ro (SS‐A)/anti—Ro (SS‐A) system.
Cutaneous vasculitis associated with Pheochromocytoma
Authors: Kulp‐Shorten Carol L. , Rhodes Richard H. , Peterson Hugh , Callen Jeffrey P.
Published: February 2007

We describe a patient who presented with constitutional symptoms, severe hypertension, and purpuric lesions over the knees, thighs, and penis. The patient was eventually diagnosed as having multiple endocrine neoplasia type II, with cutaneous leukocytoclastic vasculitis. The cutaneous vasculitis persisted despite treatment with high‐dose systemic corticosteroids, but rapidly resolved after the removal of bilateral pheochromocytomas. This case demonstrates cutaneous leukocytoclastic vasculitis in association with pheochromocytoma.
Progression of osteoarthritis of the hand and metacarpal bone loss. A twenty‐year followup of incident cases
Authors: Sowers Maryfran , Zobel Donna , Hawthorne Victor M. , Carman Wendy , Weissfeld Lisa
Published: February 2007

We examined the prospective relationship between metacarpal bone mass and osteoarthritis (OA) of the hand, using incidence data from the historical cohort in the Tecumseh Community Health Study (Tecumseh, MI). Women were examined for radiographic evidence of OA and for bone mass twice, 20–23 years apart (1962–1965 and 1985; 683 subjects with an age range of 55–74 in 1985). Two measures of OA were evaluated: the highest score assigned to any of the 32 wrist/hand joints, and the sum of scores for all wrist/hand joints. After adjustment for age, women who were classified as having OA (by either measure of OA) in 1985 were more likely to have more cortical area at baseline, which indicates greater bone mass. Women who developed OA in the 23‐year period were more likely to experience a significantly greater widening of the medullary cavity over time, an indicator of increased bone resorption. Women with increasing levels of OA involvement also had an increased likelihood of greater cortical area loss. We conclude that women who later developed OA were more likely to have higher baseline bone mass than women who did not develop OA, but these women also had a greater likelihood of bone loss over time.
Association of HLA–Dw16 with rheumatoid arthritis in Yakima Indians. Further evidence for the “shared epitope” hypothesis
Authors: Willkens Robert F. , Nepom Gerald T. , Marks Cara R. , Nettles James W. , Nepom Arbara S.
Published: February 2007

Rheumatoid arthritis (RA) is prevalent in Yakima Indians, a Native American tribe. HLA–DR4, the HLA specificity commonly associated with RA in Caucasians, is rare among the Yakima. Using a specific oligonucleotide probe that recognizes DR4 nucleotide sequences associated with RA, a rare HLA–Dw16 gene was identified in 83% of Yakima patients with RA and in 60% of Yakima control subjects. This shared sequence encodes a discrete class II epitope that is highly correlated with RA in both DR4 positive and DR4 negative individuals.
Application of the polymerase chain reaction and immunofluorescence techniques to the detection of bacteria in Yersinia‐triggered reactive arthritis
Authors: Viitanen Anna‐Mari , Arstila T. Petteri , Lahesmaa Riitta , Granfors Kaisa , Skurnik Mikael , Toivanen Paavo
Published: February 2007

Leukocytes in synovial fluid and peripheral blood samples from patients with Yersinia‐triggered reactive arthritis were analyzed after DNA amplification using the polymerase chain reaction. The primers applied were specific for the virulence plasmid–coded 1crE genes of Yersinia enterocolitica O:3 and Yersinia pseudotuberculosis III. No Yersinia DNA was observed within the synovial fluid cells or peripheral blood cells by polymerase chain reaction techniques. However, Yersinia antigens were detected in the synovial fluid cells by immunofluorescence techniques. These results suggest that only parts of the causative agents, not the entire microbe, can enter the joint and initiate the inflammation that leads to a reactive arthritis.
Systemic lupus erythematosus in a boy with chronic granulomatous disease: Case report and review of the literature
Authors: Manzi Susan , Urbach Andrew H. , McCune Ann B. , Altman Harold A. , Kaplan Sandra S. , Medsger Thomas A. , Ramsey‐Goldman Rosalind
Published: February 2007

We describe a patient with X‐linked chronic granulomatous disease (CGD) who developed systemic lupus erythematosus, which was characterized by photosensitivity, malar rash, glomerulonephritis, leukopenia, hypocomplementemia, antinuclear antibodies, and anti–double‐stranded DNA antibodies, at age 3. The patient's mother is an asymptomatic carrier of CGD, and her other son (the patient's half‐brother) also has CGD. Neither the mother nor the brother has clinical or serologic evidence of systemic lupus erythematosus. Previous cases of discoid lupus–like skin lesions have been reported both in carriers and in patients with CGD. Our patient represents the first reported case of an individual with convincing clinical, serologic, and pathologic evidence of systemic lupus erythematosus. The association between defective host defense mechanisms and autoimmune phenomena has been described previously in patients with Job's syndrome and in patients with B cell and T cell deficiency disorders, including the acquired immunodeficiency syndrome. The relationship between the known leukocyte defects in CGD and the pathogenesis of a lupus‐like illness is unclear.
Seronegative juvenile rheumatoid arthritis and mast cell–associated gastritis
Authors: Lindsley Carol B. , Miner Philip B.
Published: February 2007

We describe 4 children with seronegative inflammatory arthritis who had persistent, severe nausea and abdominal pain over several months, in spite of vigorous medical therapy, including antacids and histamine H2 receptor antagonists. Endoscopy and biopsy of gastric and duodenal mucosa showed antral gastritis and an increased number of mast cells in 3 of the 4 patients. In the fourth patient, urinary histamine levels were elevated. These findings suggest an association between inflammatory arthritis and localized mast cell disease in some individuals. Further studies are needed to determine whether this association represents an independent syndrome or whether mast cell–related disease is secondary to long‐term treatment with nonsteroidal antiinflammatory drugs in children with mild arthritis.
Synovial membrane histology and immunopathology in rheumatoid arthritis and osteoarthritis. In vivo effects of antirheumatic drugs
Authors: Haraoui Boulos , Pelletier Jean‐Pierre , Cloutier Jean‐Marie , Faure Marie‐Pierre , Martel‐Pelletier Johanne
Published: February 2007

We examined the histologic and immunopathologic features of the synovial membrane of 18 patients with rheumatoid arthritis (RA) and 12 patients with osteoarthritis (OA) who had undergone total knee arthroplasty. Patients were classified into 5 groups according to therapeutic regimen and disease: RA treated with nonsteroidal antiinflammatory drugs (NSAIDs), RA treated with NSAIDs and prednisone, RA treated with NSAIDs and methotrexate (MTX), OA treated with analgesics, and OA treated with NSAIDs. There were no significant between‐group differences in the percentages or the distribution pattern of the infiltrating T cell subsets (CD4, CD8), HLA–DR, or interleukin‐2 receptor‐bearing cells. However, inflammatory indices, which included the thickness of the lining cell layer and the density of the mononuclear cell infiltrate, were significantly higher in the RA patients treated with prednisone and those treated with MTX (P < 0.05). Similarly, fibrosis was markedly reduced in these 2 groups. The RA patients treated with NSAIDs alone and the 2 groups of patients with OA demonstrated similar profiles. These data suggest that prednisone and MTX may inhibit the development of fibrosis without altering the subsets of the inflammatory cell population. This observation raises the possibility that the action of these 2 drugs may be partly mediated by the suppression of inflammatory mediators that are responsible for fibroblast activation.
Temporal arteritis with normal erythrocyte sedimentation rates presenting as occipital neuralgia
Authors: Jundt Jeffrey W. , Mock David
Published: February 2007

A retrospective review of 46 patients with biopsy‐proven giant cell (temporal) arteritis revealed 8 (17%) whose initial presentation was occipital pain. The most likely etiology of occipital pain in these patients was occipital artery inflammation. A Westergren erythrocyte sedimentation rate < 40 mm/hour was noted at presentation in 6 of these 8 patients. Giant cell arteritis should be considered in the differential diagnosis of elderly patients who present with occipital pain and demonstrate a normal erythrocyte sedimentation rate.
Association of the complement allele c4aq0 with primary Sjögren's syndrome in japanese patients
Authors: Moriuchi Junko , Ichikawa Yukinobu , Takaya Masatoshi , Shimizu Hiroaki , Arimori Shigeru , Tsuji Kimiyoshi , Wakisaka Akemi , Dawkins Roger
Published: February 2007

We studied allotypes of the fourth component of complement (C4) and factor B in 76 patients with Sjögren's syndrome (SS) and in 63 normal subjects. C4A‐null (C4AQO) was found in 10 of 28 patients who had primary SS, compared with 1 of 63 control subjects (P ⩽ 0.005). In contrast, no significant difference in the frequency of any C4 allotype was observed between patients with secondary SS and control subjects. An association of HLA–DRw53 with primary SS in Japanese patients has been reported. Since there is no linkage disequilibrium between DRw53 and C4AQO, it is possible that at least 2 genes in the major histocompatibility complex may determine susceptibility to the development of primary SS in the Japanese population.
Fatal pulmonary venoocclusive disease secondary to a generalized venulopathy: A new syndrome presenting with facial swelling and pericardial tamponade
Authors: Liang Matthew H. , Stern Steve , Fortin Paul R. , Louie Diane C. , Marsh James D. , Mudge Gilbert H. , Murphy George
Published: February 2007

We describe a patient who developed fatal pulmonary artery hypertension secondary to diffuse venulitis. This otherwise healthy young woman first presented with generalized venulopathy, with chemosis, facial swelling, pleural effusions, and pericardial tamponade. The symptoms partially responded to steroid therapy, but over a 2‐year course, a rapidly progressive and fatal venoocclusive disease developed. No other primary condition was diagnosed, and at autopsy, the patient had striking venulitis throughout, including the pulmonary bed. We believe that this is a unique case of pulmonary hypertension resulting from a generalized venulopathy.
Symptoms of Raynaud's syndrome in patients with fibromyalgia. A study utilizing the Nielsen test, digital photoplethysmography, and measurements of platelet α2‐adrenergic receptors
Authors: Bennett Robert M. , Clark Sharon R. , Campbell Stephen M. , Ingram Shirley B. , Burckhardt Carol S. , Nelson Donna L. , Porter John M.
Published: February 2007

Twenty‐nine female patients with fibromyalgia were questioned about symptoms of cold intolerance and Raynaud's syndrome; objective documentation of cold‐induced vasospasm was obtained by a Nielsen test. Twelve patients (41%) had abnormal Nielsen test results, and 11 patients (38%) had elevated levels of platelet α2‐adrenergic receptors. There was a positive correlation between the percentage of change in finger systolic pressure on cooling (Nielsen test) and the number of α2‐adrenergic receptors. There was poor correlation between Raynaud's syndrome symptoms and an abnormal Nielsen test result. Digital photoplethysmography showed a normal waveform in 2 of 3 patients. We hypothesize that a subgroup of patients with fibromyalgia syndrome have an up‐regulation of α2‐adrenergic receptors as a cause of their exaggerated reaction to cold.
In vitro regulation of B cell differentiation by interleukin‐6 and soluble CD23 in systemic lupus erythematosus B cell subpopulations and antigen‐induced normal B cells
Authors: Klashman David J. , Martin Robert A. , Stevens Ronald H. , Martínez‐Maza Otoniel
Published: February 2007

Polyreactive systemic lupus erythematosus (SLE) B cells were compared with antigen‐induced SLE and normal B cells for their interleukin‐6 (IL‐6) and soluble CD23 requirements. Unlike normal B cells, secretion of antibody by SLE B cells in serum‐free medium was not enhanced by exogenous IL‐6. Anti–IL‐6 antibodies inhibited immunoglobulin production in cultures of normal and SLE B cells, which suggests that IL‐6 is required for B cell differentiation. SLE culture supernatants had elevated levels of IL‐6, which explains the poor response of the SLE cells to exogenous IL‐6. Soluble CD23 enhanced the responses of cells from normal subjects and SLE patients.
A double‐blind study of deflazacort and prednisone in patients with chronic inflammatory disorders
Authors: Gray Richard E. S. , Doherty Sheelagh M. , Galloway John , Coulton Les , Kanis John A. , de Broe Marc
Published: February 2007

Deflazacort and prednisone were given to 26 patients with rheumatoid arthritis, polymyalgia rheumatica, or other chronic inflammatory diseases, in a double‐blind study. Deflazacort rapidly and effectively suppressed disease activity in a manner supporting its assumed therapeutic potency of 83% that of prednisone. Prednisone induced a rapid increase in the level of daily calcium excretion that was not evident with deflazacort. Cortisol secretion was acutely inhibited by prednisone, but not by deflazacort. Neither corticosteroid had a significant effect on glucose metabolism, at the doses studied. Treatment with deflazacort may be an effective alternative to prednisone treatment, with fewer adverse effects on levels of calcium and cortisol, in patients with severe inflammatory conditions warranting the use glucocorticoids.
Induction of neutrophil‐mediated cartilage degradation by interleukin‐8
Authors: Elford Peter R. , Cooper Philip H.
Published: February 2007

Neutrophil influx into the inflamed joint is a characteristic feature of disease flares in patients with rheumatoid arthritis. Recently, a protein produced by monocytes and fibroblasts that has chemoattractive/activating properties for neutrophils has been identified and characterized. This protein has been called interleukin‐8 (IL‐8). In this study, we cocultured neutrophils with 35S‐sulfate–labeled cartilage and found that the addition of recombinant human IL‐8 (rHuIL‐8) caused rapid, neutrophil‐mediated cartilage degradation that was the result of induction of neutrophil degranulation by the cytokine. With 10−7M rHuIL‐8, 23% of the radiolabel was released into the culture medium in 4 hours, compared with a 9% release without the factor. At concentrations of up to 10−6M, rHuIL‐8 had no direct effect upon cartilage breakdown. These findings indicate that IL‐8 may participate in the pathogenesis of rheumatoid arthritis through the induction of neutrophil‐mediated cartilage damage.
Epidemiologic and immunogenetic aspects of polymyalgia rheumatica and giant cell arteritis in northern Italy
Authors: Salvarani Carlo , Macchioni Pierluigi , Rossi Fulvia , Castri Concetta , Capozzoli Nicholas , Baricchi Roberto , Boiardi Luigi , Chiaravalloti Franco , Portioli Italo , Zizzi Fabio , Mantovani Wilma
Published: February 2007

We studied the epidemiology of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) in a Mediterranean population. Ninety‐nine patients with PMR and/or GCA were identified over a 9‐year period (1980–1988) in Reggio Emilia, Italy. The average annual incidence of PMR and GCA was 12.7/100,000 and 6.9/100,000, respectively, in a population aged 50 years or older. Frequencies of HLA antigens were determined in 49 patients with PMR and/or GCA who were followed by staff at our rheumatology unit during the 1980–1988 period. When compared with HLA findings in 242 healthy controls, DR4 was not found to be significantly associated with PMR (24% in PMR patients versus 14% in controls). Patients with GCA also showed an increased frequency of DR4 compared with controls (36% versus 14%), but this difference was also not statistically significant. The immunogenetic features of PMR and GCA and the relationship between the immunogenetic and epidemiologic patterns in different populations are discussed.
Serum keratan sulfate. Quantitative and qualitative comparisons in inflammatory versus noninflammatory arthritides
Authors: Mehraban Fuad , Finegan Candace K. , Moskowitz Roland W.
Published: February 2007

The concentration of keratan sulfate (KS) epitope was measured in the serum of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) by enzyme‐linked immunosorbent assay and compared with that in the serum of patients with primary fibromyalgia syndrome (PFS) and of controls who had no joint disease. By Student's t‐test, the mean serum KS concentrations in OA and RA patients measured with monoclonal antibodies (MAb) 5‐D‐4 and 2‐D‐3 were significantly increased over those in the PFS and normal groups; similar findings were observed using a nonparametric test, except that levels in RA patients showed no difference from those in PFS patients and normal subjects. There was no significant correlation between joint scores or disease duration and KS levels in OA or RA patients. Gel filtration of sera revealed mainly large, polydisperse KS‐bearing fragments which eluted in a broad profile. KS purified from sera by immunoaffinity chromatography consisted mainly of high‐density proteoglycans. Electrophoresis of pooled high‐density KS fractions in polyacrylamide‐agarose gels followed by Western blotting with MAb 5‐D‐4 showed diffuse bands with relative mobilities corresponding to large proteoglycans. These findings are consistent with attachment of KS to protein core fragments of various sizes; KS in patient sera is comparable in size with that in normal sera. Elevations of serum KS levels occur in the presence of cartilage degradation, but do not quantitatively define the extent or duration of articular involvement.
Predictors of survival in systemic sclerosis (Scleroderma)
Authors: Altman Roy D. , Medsger Thomas A. , Bloch Daniel A. , Michel Beat A.
Published: February 2007

We conducted followup of 264 patients with definite systemic sclerosis (SSc) who were entered into the multicenter Scleroderma Criteria Cooperative Study (SCCS) during 1973–1977. At the end of the study (average 5.2 years of followup), 38% were known to be alive, 50% were dead (68% of these deaths definitely related to SSc), and 12% were lost to followup. Survival analyses of 484 demographic, clinical, and laboratory items recorded at entry into the SCCS (within 2 years of physician diagnosis of SSc) were performed. Survival declined linearly, and the cumulative survival rate was <80% at 2 years, 50% at 8.5 years, and 30% at 12 years after entry. Analysis using combinations of entry variables identifying organ system involvement confirmed that renal, cardiac, pulmonary, and gastrointestinal involvement in SSc predicted reduced survival; however, data on organ system involvement at study entry could not be used to consistently predict which organ system would ultimately be involved as the primary cause of death. By survival tree analysis, the individual entry variables best predicting reduced survival included older age (>64 years), reduced renal function (blood urea nitrogen >16 mg/dl), anemia (hemoglobin ≤11 gm/dl), reduced pulmonary diffusing capacity for carbon monoxide (≤50% of predicted), reduced total serum protein level (≤6 gm/dl), and reduced pulmonary reserve (forced vital capacity <80% with hemoglobin >14 gm/dl or forced vital capacity <65% with hemoglobin ≤14 gm/dl). Cox proportional hazards model analysis confirmed these results. Different combinations of variables led to markedly different survival rates. The poorest prospects for survival were in patients with SSc who were ≤64 years old with a hemoglobin level ≤11 gm/dl, and in those >64 years old with a blood urea nitrogen level >16 mg/dl. These results may be useful in predicting individual patients at risk for shortened survival.
Magnetic resonance imaging of central nervous system lesions in patients with lupus erythematosus. Correlation with clinical remission and antineurofilament and anticardiolipin antibody titers
Authors: Bell Carolyn L. , Robbins Mark , Graziano Frank , Partington Curtis , Turski Patrick , Kornguth Steven
Published: February 2007

Clinical, magnetic resonance imaging (MRI), and serologic studies were performed on 11 patients with diffuse central nervous system (CNS) systemic lupus erythematosus and 8 patients with focal CNS lupus. MRI of patients with diffuse clinical disease showed symmetrically distributed areas of increased signal intensity in the subcortical white matter; these resolved after treatment with high‐dose methylprednisolone. These patients' sera contained elevated levels of antineurofilament antibodies. Patients with focal CNS lupus had areas of increased signal intensity and atrophic changes in regions corresponding to the major cerebral vessels. These MRI abnormalities did not improve after treatment with high‐dose steroids. The sera of patients with focal CNS lupus had elevated levels of cardiolipin and lupus anticoagulant but normal levels of antineurofilament antibody. Our findings suggest that results of a combined clinical, MRI, and serologic evaluation of patients with CNS lupus may predict the response of patients to high‐dose steroid therapy.
Association of immunoglobulin Km and Gm allotypes with specific antinuclear antibodies and disease susceptibility among connective tissue disease patients
Authors: Hoffman Robert W. , Sharp Gordon C. , Irvin William S. , Anderson Sharon K. , Hewett John E. , Pandey Janardan P.
Published: February 2007

The distribution of the immunoglobulin Km(1) and Gm phenotypes was examined in patients with connective tissue diseases, including systemic lupus erythematosus, mixed connective tissue disease, and scleroderma, whose sera were characterized for antibodies against nuclear antigens and polypeptides of U small nuclear ribonucleoproteins. We found a strong association between the Km(1) phenotype and susceptibility to systemic lupus erythematosus (P < 0.00001, relative risk = 17). We also found a positive association between the Km(1) phenotype and the presence of anti–double‐stranded DNA antibodies. The presence of certain immunoglobulin genes or gene families may have a role in susceptibility to the development of autoantibodies and/or of connective tissue disease.
Restriction fragment length polymorphism of the tumor necrosis factor region in patients with ankylosing spondylitis
Authors: Verjans Georges M. G. M. , Kijlstra Aize , Van Linden Sjef M. Der , van Eys Guillaume J. J. M. , de Waal Leo P.
Published: February 2007

Although ankylosing spondylitis (AS) is known to be strongly associated with the class I major histocompatibility complex antigen HLA–B27, B27 is probably not the only genetic factor involved in the pathogenesis of AS. Because of the involvement of tumor necrosis factor (TNF) in cartilage damage and the localization of the TNF genes in the proximity of the HLA–B locus, we investigated the association between AS and TNF alleles. The frequencies of the restriction fragment length polymorphisms linked to the TNF genes were determined in 73 AS patients and 81 controls. No differences were observed between AS patients and controls with respect to the frequencies of the TNF restriction fragment length polymorphisms.
Treatment of rheumatoid arthritis with monoclonal CD4 antibody M‐T151. Clinical results and immunopharmacologic effects in an open study, including repeated administration
Authors: Reiter Christian , Kakavand Bahram , Rieber Ernst Peter , Riethmüller Gert , Schattenkirchner Manfred , Krüger Klaus
Published: February 2007

Recent experimental and clinical data point to the T helper lymphocyte subset as playing a central role in the pathogenesis of rheumatoid arthritis (RA). Thus, a therapeutic strategy aimed specifically at the CD4 T cell subset is warranted. We treated patients with active RA for 7 days with a daily dose of 20 mg of CD4 monoclonal antibody M‐T151, administered intravenously over 30 minutes. There were no negative side effects. According to changes in the combined parameters of Ritchie articular index, pain assessment, grip strength, and morning stiffness, 6 patients had a good response. Clinical improvement was greatest approximately 2 weeks after termination of the therapy and lasted from 4 weeks to 6 months. Of the serologic parameters of inflammation, only the C‐reactive protein level improved in the patients with a favorable response. Close immunologic monitoring revealed a transient, selective depletion of CD4+ T cells after each infusion. During the entire treatment period, residual circulating CD4+ cells were found to be coated with CD4 antibody, whereas free antibody was detected in the serum only for approximately 8 hours after each infusion. Immediately after infusion, soluble CD4 antigen appeared in the serum. In addition to the cell‐bound CD4 antibody, complement components could be detected on the surface of the remaining CD4+ cells. The proliferative response of peripheral blood mononuclear cells to purified protein derivative was significantly diminished 4 weeks after cessation of antibody treatment. Six patients showed a weak antibody response to mouse immunoglobulin. In 4 of the responders who received a second course of therapy (2 of them as outpatients), a therapeutic effect was noted that was similar to that after the first course. Only 1 patient, who had low titers of serum IgE anti‐mouse Ig antibodies, showed a mild anaphylactic reaction at the end of the second course of therapy. Treatment of RA with the monoclonal CD4 antibody M‐T151 seems to be a promising alternative, although the optimal dose and the regimen of administration are still to be defined.
A variant of HLA–DR4 determines susceptibility to rheumatoid arthritis in a subset of Israeli Jews
Authors: Gao Xiaojiang , Stastny Peter , Brautbar Chaim , Naparstek Y. , Gazit Ephraim , Livneh A. , Segal Raphael
Published: February 2007

HLA–DR4 is associated with risk for developing rheumatoid arthritis (RA) in most populations. In Israeli Jews, in whom the Dw10 subtype of DR4 predominates, no association of RA with DR4 has been found. The inability to detect an association could be due to the high frequency of DR4‐Dw10. We used DNA typing with amplification by the polymerase chain reaction and dot‐blotting with allele‐specific oligonucleotides to determine DR4 variants in 131 Jewish RA patients living in Israel and 134 controls. In both Ashkenazi Jews and non‐Ashkenazi Jews, the rare variant Dw15 (previously identified in Japanese populations and in Japanese patients with RA) was found to be the main allele associated with the risk of developing RA (relative risk = 9.2, corrected P < 0.001). However, this low‐frequency allele could be responsible for susceptibility in only 11.5% of the patients. Susceptibility for rheumatoid factor–positive RA was associated with Dw4 and Dw15; the risk for rheumatoid factor–negative RA was associated only with Dw14. The distribution of the HLA–DQ alleles associated with DR4 showed that more than half of the RA patients with Dw15 also had HLA–DQw2. The frequencies of DQw7 and DQw8 were not different in RA patients compared with controls. The results suggest that, as in other populations, susceptibility for the development of RA in Israeli Jews is associated with DRB1 locus alleles of the DR4 group.
Treatment of primary fibrositis/fibromyalgia syndrome with ibuprofen and alprazolam. A double‐blind, placebo‐controlled study
Authors: Russell I. Jon , Fletcher Ellen M. , Michalek Joel E. , McBroom Patrick C. , Hester G. Gene
Published: February 2007

A multidimensional evaluation of 78 patients with primary fibrositis/fibromyalgia syndrome (PFS) revealed no significant relationship between clinical measures of physical discomfort and psychological measures. This observation provided evidence against the notion that the pain of PFS has a psychological etiology. The same patients were randomized into 4 groups for treatment with ibuprofen and/or alprazolam in a randomized, double‐blind, double‐dummy, placebo‐controlled pilot trial. Clinical improvement in patient rating of disease severity and in the severity of tenderness upon palpation was most apparent in the subgroup of patients who were receiving both ibuprofen and alprazolam. An 8‐week, open‐label study in which 52 patients received both drugs further documented improvement in outcome measures. These data indicate that treatment with a combination of ibuprofen and alprazolam can be beneficial for some patients with PFS.
Synovial T lymphocyte–specific immune response to Chlamydia trachomatis in Reiter's disease
Authors: Sieper Joachim , Kingsley Gabrielle , Palacios‐Boix Alberto , Pitzalis Costantino , Panayi Gabriel S. , Treharne John , Hughes Rod , Keat Andrew
Published: February 2007

We studied the lymphocyte proliferative response to Chlamydia trachomatis in Reiter's syndrome (RS) compared with that in other rheumatic diseases. RS patients showed significantly increased C trachomatis–specific synovial fluid (SF) T cell proliferation. Proliferating cells were found in both CD4+ and CD8+ T cell subsets. The SF lymphocyte proliferative response to C trachomatis in RS was inhibited by anti–class I and class II major histocompatibility complex monoclonal antibodies, while the response to tuberculin purified protein derivative was inhibited only by anti–class II monoclonal antibodies. T cell receptor γ/δ–bearing T cells were not consistently increased in RS SF compared with peripheral blood, nor did such cells consistently expand upon in vitro culture with C trachomatis. Finally, there was no correlation between the cellular immune response and levels of antibody to C trachomatis antigens. Our results indicate that a specific T cell response to C trachomatis within the joint plays a role in the pathogenesis of RS.
Collagen‐induced arthritis in an outbred group of rhesus monkeys comprising responder and nonresponder animals. Relationship between the course of arthritis and collagen‐specific immunity
Authors: Bakker Nicolaas P. M. , van Erck Monique G. M. , Botman Caroline A. D. , Jonker Margreet , Hart Bert A. 'T
Published: February 2007

It is speculated that the autoimmune response to type II collagen (CII) is a driving force in the pathogenesis of human rheumatoid arthritis (RA). In this report, we describe the relationship between the induction of collagen arthritis and the CII‐specific humoral, as well as cellular, immune response in rhesus monkeys. Ten of 14 monkeys immunized with bovine type II collagen (B‐CII) developed polyarthritis. Susceptible animals showed a T cell response to B‐CII; resistant animals did not. After the primary immunization, the humoral response to B‐CII, as well as to rhesus monkey type II collagen, was dominated by antibodies of the IgM isotype in the susceptible animals and by antibodies of the IgG isotype in the resistant animals. Because of the close phylogenic relationship between the rhesus monkey and humans, these data contribute valuable information about the role of CII‐specific immunity in the pathogenesis of human RA.