bluuebunny/crossref_metadata_2025_split huggingface dataset:
High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome
Authors: Mikecz Anna Von , Konstantinov Konstantin , Buchwald Dedra S. , Gerace Larry , Tan Eng M. 
Published: February 2007

AbstractObjective. To elucidate the humoral immune response in patients with chronic fatigue syndrome (CFS), by identification and characterization of autoantibodies.Methods. Initial immunofluorescence histochemistry studies of sera using human HEp‐2 cell substrate were followed by antibody class subtyping and colocalization studies with reference antibodies. Association of CFS autoantigens with insoluble cellular components was determined by in situ extraction of soluble components and subsequent immunofluorescence histochemistry studies on the extracted cell substrate.Results. Of 60 CFS patients, 41 (68%) were positive for antinuclear antibodies. Localization of nuclear staining was found at the nuclear envelope (52%), in reticulated speckles (25%), in nucleoli (13%), and in dense fine speckles (5%). Twenty‐eight CFS sera (47%) also had antibodies to cytoplasmic antigens. The major cytoplasmic staining pattern was of the intermediate filament type (35%). The observed nuclear envelope pattern of staining co‐localized with lamina‐associated polypeptide 2 (an integral nuclear membrane protein), the reticulated speckle pattern co‐localized with nonsmall nuclear RNP splicing factor SC‐35, and the intermediate filament pattern co‐localized with vimentin. The intermediate filament antigen was shown to be vimentin in immunoblotting experiments using recombinant human vimentin, and one of the nuclear envelope antigens was shown previously to be lamin B1. Fifty of the 60 CFS patients (83%) had antibodies to one or another of these antigens, all of which are relatively insoluble cellular antigens, whereas a control group of patients without chronic fatigue had a significantly lower frequency of such antibodies (17%).Conclusion. The high frequency of autoantibodies to insoluble cellular antigens in CFS represents a unique feature which might help to distinguish CFS from other rheumatic autoimmune diseases.
In vitro apoptosis and expression of apoptosis‐related molecules in lymphocytes from patients with systemic lupus erythematosus and other autoimmune diseases
Authors: Lorenz Hanns‐Martin , Grünke Mathias , Hieronymus Thomas , Herrmann Martin , Kühnel Almuth , Manger Bernhard , Kalden Joachim R. 
Published: February 2007

AbstractObjective. To analyze factors related to apoptosis in systemic lupus erythematosus (SLE) peripheral blood mononuclear cells (PBMC) and to compare the findings in SLE PBMC with those in normal donor PBMC or PBMC from patients with other autoimmune diseases.Methods. PBMC from normal healthy donors or patients with SLE, mixed connective tissue disease (MCTD), rheumatoid arthritis (RA), or various vasculitides were isolated. The percentage of apoptosis after activation through different signaling pathways was quantified using propidium iodide staining. Protein expression of Fas/APO‐1 or bcl‐2, and messenger RNA (mRNA) expression of bcl‐2, bcl‐xL, bax, bak, Fas/APO‐1, Fas ligand (Fas‐L), c‐myc, mad, or max were determined.Results. We confirmed previous findings of increased numbers of apoptotic cells in SLE PBMC compared with normal donor cells after in vitro incubation. After activation of PBMC with CD28 monoclonal antibody plus phorbol myristate acetate (CD28 MAb/PMA), staphylococcal enterotoxin B (SEB), or phytohemagglutinin (PHA), the percentage of apoptotic cells was unchanged (SEB) or diminished (CD28 MAb/PMA, PHA) in SLE cells, and the difference between normal donor and SLE cells was less pronounced. On the mRNA level, expression of apoptosis‐related gene products did not differ between SLE cells and normal donor cells. Expression of Fas/APO‐1 protein was increased in freshly isolated SLE T lymphocytes compared with normal donor T lymphocytes, whereas bcl‐2 protein was up‐regulated after a 3‐day culture period. Cellular activation further increased bcl‐2 protein levels, eliminating differences between normal donors and SLE patients. In RA cells, the percentage of apoptosis was similar to that in normal donor PBMC, whereas results using cells from patients with other autoimmune diseases (MCTD, Wegener's granulomatosis, Takayasu arteritis, polyarteritis nodosa) were comparable with those found using SLE PBMC. Addition of growth factors such as interleukin‐2 (IL‐2), IL‐4, or IL‐15 to culture medium decreased the percentage of in vitro apoptosis in both normal donor and SLE cells.Conclusion. Based on these data, we conclude that accelerated in vitro apoptosis and increased Fas/APO‐1 and bcl‐2 protein expression in SLE are nonspecific for the disease, and might be explained at least in part by the increased in vivo activation levels of PBMC from patients with SLE, MCTD, or autoimmune vasculitides combined with in vitro incubation under “noninflammatory” conditions and growth factor withdrawal.
Oral L‐arginine supplementation and cutaneous vascular responses in patients with primary Raynaud's phenomenon
Authors: Khan Faisel , Litchfield Stuart J. , McLaren Margaret , Veale Douglas J. , Littleford Roberta C. , Belch Jill J. F. 
Published: February 2007

AbstractObjective. To assess the effects of oral L‐arginine supplementation on cutaneous vascular responses in patients with primary Raynaud's phenomenon (RP).Methods. Double‐blind, crossover comparison of placebo versus L‐arginine (8 gm/day for 28 days). Cutaneous vascular responses in the fingers were assessed during iontophoresis of acetylcholine and sodium nitroprusside, which are endothelium‐dependent and endothelium‐independent vasodilators.Results. In comparison with control subjects, patients with primary RP had diminished endothelium‐dependent and ‐independent vasodilatation (P < 0.05, and P < 0.005, respectively, by analysis of variance). At the 3 doses used, vascular responses to acetylcholine were reduced by 71%, 64%, and 63%, respectively, and responses to sodium nitroprusside were reduced by 67%, 73%, and 66%, respectively. L‐arginine had no significant effect on cutaneous vascular responses to acetylcholine or sodium nitroprusside in control subjects or patients with primary RP.Conclusion. Reduced vasodilator ability in primary RP is unlikely to be due to an impairment in the L‐arginine/nitric oxide pathway.
Development and initial validation of the vasculitis damage index for the standardized clinical assessment of damage in the systemic vasculitides
Authors: Exley A. R. , Bacon P. A. , Luqmani R. A. , Kitas G. D. , Gordon C. , Savage C. O. S. , Adu D. 
Published: February 2007

AbstractObjective. To develop and validate the Vasculitis Damage Index (VDI) for the standardized clinical assessment of damage in the systemic vasculitides.Methods. Using a nominal group consensus approach, the Birmingham Vasculitis Group generated guiding principles for assessment of damage in all systemic vasculitides. Damage was defined as irreversible change resulting from scars. Consensus principles were developed into the VDI, including guidelines for use, a list of items of damage, and a glossary.Results. For 100 surviving patients with systemic vasculitis, the median VDI score at last observation was 3 (range 0–8). Within the Wegener's granulomatosis subgroup, the median VDI score for 12 non‐survivors was higher than for 47 survivors (non‐survivors median score 7, interquartile range 5–8 versus survivors median score 4, interquartile range 2–5; P = 0.003). VDI scores for 100 patients with systemic vasculitis increased from initial presentation to last observation by a median score of 3 (range 1–4; P < 0.001). The VDI assesses more items and is more sensitive to change than other indices of damage (P < 0.001). Using the VDI, trained observers can produce moderately consistent damage scores.Conclusion. The VDI is a sensitive, reproducible, comprehensive, and credible clinical tool for quantifying damage. The data presented herein should enable further validation and testing of the VDI in specific vasculitic syndromes, and should facilitate the comparison of different therapies.
Monozygotic twins discordant for congenital complete heart block
Authors: Cooley Helen M. , Keech Catherine L. , Melny B. Joy , Menahem Samuel , Morahan Grant , Kay Thomas W. H. 
Published: February 2007

AbstractObjective. Isolated congenital complete heart block (CCHB) occurs in 1/20,000 live births. More than 85% of mothers giving birth to affected infants are anti–Ro antibody positive, but only ˜ 1% of babies with anti–Ro‐positive mothers develop CCHB. We studied 2 sets of monozygotic twins discordant for CCHB.Methods. Monozygosity was determined using placental examination and DNA microsatellite analysis. HLA typing was performed. Autoantibody studies were performed using counterimmunoelectrophoresis, immunoblotting, Ro 52 and Ro 60 enzyme‐linked immunosorbent assay (ELISA), and indirect immuno‐fluorescence (IIF) on Ro 60− and Ro 52−transfected HEp‐2 cells.Results. Both sets of twins were monozygotic. They had similar birth weights. Twin 2 in the second set required a pacemaker at age 2 months. Both mothers were positive for anti–Ro 52 and anti–Ro 60 antibody, and neither had anti–La antibody on immunoblot. One set of twins was studied at birth. Similar titers of anti–Ro 52 and anti–Ro 60 antibody were found by IIF and ELISA.Conclusion. There are no previous well‐documented reports of monozygotic twins discordant for CCHB. These cases demonstrate that there is still discordance in the development of CCHB despite identical genetics and environmental exposure to anti–Ro antibody.
Juvenile rheumatoid arthritis‐like polyarthritis in chromosome 22q11.2 deletion syndrome (digeorge anomalad/velocardiofacial syndrome/conotruncal anomaly face syndrome)
Authors: Sullivan Kathleen E. , McDonald‐McGinn Donna M. , Driscoll Deborah A. , Zmijewski Chester M. , Ellabban Abdou S. , Reed Lori , Emanuel Beverly S. , Zackai Elaine H. , Athreya Balu H. , Keenan Gregory 
Published: February 2007

AbstractObjective. To investigate the association of polyarthritis and chromosome 22q11.2 deletions.Methods. Eighty patients with chromosome 22q11.2 deletion syndrome followed up at The Children's Hospital of Philadelphia were examined for evidence of arthropathy or arthritis. Patients with chromosome 22q11.2 deletion syndrome and polyarthritis underwent laboratory evaluations of immunologic function to determine the relationship of their immunodeficiency to the polyarthritis.Results. The prevalence of polyarthritis in patients with chromosome 22q11.2 deletion syndrome was markedly increased over the prevalence of polyarticular juvenile rheumatoid arthritis (JRA) in the general population. All 3 patients with polyarthritis had evidence of impaired T cell function. Two of the patients with polyarthritis also had IgA deficiency.Conclusion. The chromosome 22q11.2 deletion syndrome represents a primary T cell disorder which can be associated with a JRA‐like polyarthritis. All 3 patients with polyarthritis had evidence of more extensive immunoregulatory derangements than those typically seen in patients with chromosome 22q11.2 deletion, and these derangements may have predisposed to the development of polyarthritis.
Incidence OF systemic sclerosis in allegheny county, Pennsylvania. A twenty‐year study of hospital‐diagnosed cases, 1963–1982
Authors: Steen Virginia D. , Oddis Chester V. , Conte Claudia G. , Janoski Janine , Casterline Gayle Ziegler , Medsger Thomas A. 
Published: February 2007

AbstractObjective. To determine the incidence of hospital‐diagnosed systemic sclerosis (SSc) among residents of Pittsburgh and Allegheny County, PA, from 1963 through 1982.Methods. Medical records from all Allegheny County hospitals were searched using International Classification of Diseases codes for patients diagnosed with SSc. Each case was reviewed and verified by a physician, according to specified criteria. Age‐adjusted incidence rates were computed for race and sex, and results were expressed as new cases per million population per year, with the 1970 Allegheny County population serving as the standard.Results. Four hundred forty‐four cases of SSc were identified during this 20‐year survey, for a total annual incidence of 13.9 per million population. Overall, the incidence rate doubled during 1973–1982 compared with the first time interval of the study, with the greatest increase occurring in women. Among the younger population (ages 15–24), black women had the highest incidence of SSc (21.2 per million population). Overall, the female‐to‐male incidence ratio was 3:1, and was slightly higher (3.4:1) during the childbearing years (ages 15–44). Men under age 35 and children infrequently developed SSc.Conclusion. The incidence of SSc reported in this study increased with time. Although this trend was most likely due to improved detection and medical record techniques, the incidence rate stability in men compared with women suggests that there may have been a true increase in the incidence of SSc in this population, particularly in women.
Increased rates of fibromyalgia following cervical spine injury. A Controlled study of 161 cases of traumatic injury
Authors: Buskila Dan , Neumann Lily , Vaisberg Genady , Alkalay Daphna , Wolfe Frederick 
Published: February 2007

AbstractObjective. To study the relationship between cervical spine injury and the development of fibromyalgia syndrome (FMS).Methods. One hundred two patients with neck injury and 59 patients with leg fractures (control group) were assessed for nonarticular tenderness and the presence of FMS. A count of 18 tender points was conducted by thumb palpation, and tenderness thresholds were assessed by dolorimetry at 9 tender sites. All patients were interviewed about the presence and severity of neck and FMS‐related symptoms. FMS was diagnosed using the American College of Rheumatology 1990 criteria. Additional questions assessed measures of physical functioning and quality of life (QOL).Results. Although no patient had a chronic pain syndrome prior to the trauma, FMS was diagnosed following injury in 21.6% of those with neck injury versus 1.7% of the control patients with lower extremity fractures (P = 0.001). Almost all symptoms were more common and severe in the group with neck injury. FMS was noted at a mean of 3.2 months (SD 1.1) after the trauma. Neck injury patients with FMS (n = 22) had more tenderness, had more severe and prevalent FMS‐related symptoms, and reported lower QOL and more impaired physical functioning than did those without FMS (n = 80). In spite of the injury or the presence of FMS, all patients were employed at the time of examination. Twenty percent of patients with neck injury and 24% of patients with leg fractures filed an insurance claim. Claims were not associated with the presence of FMS, increased FMS symptoms, pain, or impaired functioning.Conclusion. FMS was 13 times more frequent following neck injury than following lower extremity injury. All patients continued to be employed, and insurance claims were not increased in patients with FMS.
Human synovial mast cells. II. Heterogeneity of the pharmacologic effects of antiinflammatory and immunosuppressive drugs
Authors: de Paulis Amato , Ciccarelli Anna , Marinò Isabella , de Crescenzo Gennaro , Marinò Domenico , Marone Gianni 
Published: February 2007

AbstractObjective. To evaluate the in vitro effects of 4 antiinflammatory and 5 immunosuppressive agents on the release of preformed and de novo‐synthesized mediators from human synovial mast cells (HSyMC) activated by immunologic and nonimmunologic stimuli.Methods. The effects of antiinflammatory and immunosuppressive agents were evaluated on the in vitro release of histamine and tryptase and the de novo synthesis of prostaglandin D2 (PGD2) and leukotriene C4 (LTC4) by HSyMC challenged with anti‐IgE and substance P.Results. Nimesulide, a sulfonanilide nonsteroidal antiinflammatory drug (NSAID) chemically unrelated to other acidic NSAIDs (such as acetylsalicylic acid [ASA], diclofenac, and piroxicam) inhibited in a concentration‐dependent manner the release of preformed (histamine and tryptase) mediators from HSyMC challenged with anti‐IgE. In contrast, diclofenac and piroxicam had little or no effect on HSyMC activated by anti‐IgE. ASA, diclofenac, piroxicam, and nimesulide caused a concentration‐dependent inhibition of IgE‐mediated PGD2 release from HSyMC. Nimesulide, but not diclofenac or piroxicam, also inhibited the de novo synthesis of LTC4 by HSyMC challenged with anti‐IgE. Nimesulide, diclofenac, and piroxicam had no effect on HSyMC activated by substance P. Cyclosporin A (CSA) inhibited histamine release from HSyMC challenged with anti‐IgE, whereas cyclosporin H (CSH) had no effect. FK‐506 also inhibited histamine release from HSyMC activated by anti‐IgE, whereas rapamycin had no effect. Neither CSA, CSH, FK‐506, nor rapamycin inhibited the release of histamine from HSyMC induced by substance P. Methotrexate had no effect on the release of mediators from these cells, whereas adenosine (R‐phenylisopropyl adenosine and 5‐N‐ethylcarboxamide adenosine) enhanced histamine release from immunologically activated HSyMC in a concentration‐dependent manner.Conclusion. Mast cells isolated from human synovia display 4 levels of pharmacologic heterogeneity with regard to 1) the inhibitory effects of 4 antiinflammatory drugs; 2) the capacity of different immunosuppressive drugs to exert antiinflammatory activity; 3) the inhibition of the release of different mediators; and 4) the capacity of antiinflammatory and immunosuppressive drugs to modulate HSyMC activated by different stimuli. This complexity of pharmacologic modulation of HSyMC in vitro might help explain the different activity of the compounds used to treat various pathophysiologic aspects of the inflammatory arthritides.
Mast cell responses in rheumatoid synovium. Association of the MCTC subset with matrix turnover and clinical progression
Authors: Gotis‐Graham Ian , McNeil H. Patrick 
Published: February 2007

AbstractObjective. To determine the distribution of mast cell subsets and their density in synovium from normal subjects and from patients with osteoarthritis (OA) and rheumatoid arthritis (RA).Methods. A sequential double‐immunohisto‐chemical staining technique was used to distinguish mast cells as positive for tryptase only (MCT) or for tryptase plus chymase (MCTC). Synovial tissue was obtained from RA patients (n = 16), OA patients (n = 18), and normal subjects (n = 15). Sections were analyzed to a depth of 1 mm from the synoviocyte lining layer by quantitative histomorphometry. Immunohisto‐chemical data were correlated with histologic findings and clinical indices of disease activity.Results. In normal synovium, the majority of mast cells belonged to the MCTC subset, outnumbering MCT cells by 5:1. The mean density of mast cells was significantly increased in RA synovia (60.9 cells/mm2) compared with OA (21.7 cells/mm2) and with normal (9.4 cells/mm2) synovia. Selective expansion of the MCT subset accounted for the increased mast cell density in OA. In RA, both subsets expanded and were associated with infiltrating inflammatory cells or with regions of highly cellular fibrous tissue (mainly MCTC). An association was noted between clinical parameters of activity or progression of rheumatoid disease and the density of MCTC cells, especially the density in the superficial layer of synovium. In RA synovia, we found no evidence of the chymase only, or MCC, immunophenotype.Conclusion. MCTC mast cells expand in RA but not OA, associate with regions of “active” fibrosis, and correlate with parameters of disease activity or progression of RA. These findings implicate the MCTC subset of mast cells in the pathologic mechanisms that mediate tissue damage in RA.
Adjuvant arthritis as a model of inflammatory cachexia
Authors: Roubenoff Ronenn , Freeman Lisa M. , Smith Donald E. , Abad Leslie W. , Dinarello Charles A. , Kehayias Joseph J. 
Published: February 2007

AbstractObjective. To determine whether adjuvant arthritis (AA) leads to changes in body composition and cytokine production similar to those seen in patients with rheumatoid arthritis.Methods. AA was induced in Lewis rats using Freund's complete adjuvant. Body cell mass was measured by determining the concentration of total exchangeable potassium using 42K gavage. Splenocyte production of interleukin‐1 (IL‐1) and tumor necrosis factor α (TNFα) was measured by bioassay. Weight and food intake were also measured.Results. Animals that developed AA lost 6% of their body weight by the onset of clinically evident arthritis (day 14; P < 0.01) and lost 20% by the end of the inflammatory phase of AA (day 28; P < 0.0001). Body cell mass fell 24.7 ± 8.6% (mean ± SEM) in animals with AA, but did not change significantly in controls (increase of 6.3 ± 7.9%) (P < 0.03). Pair‐fed animals lost one‐fourth of the weight lost by the animals with AA (P < 0.01), indicating that anorexia alone does not explain inflammatory cachexia. Weight loss was correlated with TNFα production by spleen mononuclear cells (r = 0.68, P < 0.007), and a weaker correlation was seen with IL‐1 production (r = 0.45, P < 0.04).Conclusion. AA in rats is a useful model of inflammatory cachexia that mimics the human pathophysiology in important ways, and is consistent with cytokine‐driven cachexia in chronic inflammatory arthritis.
Up‐regulation of class II major histocompatibility complex and intercellular adhesion molecule 1 expression on scleroderma fibroblasts and endothelial cells by interferon‐γ and tumor necrosis factor α in the early disease stage
Authors: Gruschwitz Matthias S. , Vieth Gisela 
Published: February 2007

AbstractObjective. To investigate the expression patterns of interferon‐γ (IFNγ) and tumor necrosis factor α (TNFα), both of which are potent inducers of class II major histocompatibility complex (MHC) and intercellular adhesion molecule 1 (ICAM‐1) expression, and their codistribution with HLA—DR and ICAM‐1 in skin lesions, cultured fibroblasts, and peripheral blood mononuclear cells (PBMC) of systemic sclerosis (SSc) patients in different stages of disease.Methods. Investigations were carried out using immunohistochemistry studies, reverse transcriptasepolymerase chain reaction, dot‐blot hybridization, and cytometric analysis. Serum levels of TNFα were determined by enzyme‐linked immunosorbent assay.Results. In the early inflammatory stage of SSc, class II MHC and ICAM‐1 expression could be detected on most endothelial cells and on fibroblasts located especially in perivascular areas surrounded by infiltrating lymphocytes, which belong to the T helper 1 phenotype expressing IFNγ and TNFα. In this early disease stage, an enhanced expression of TNFα on cultured dermal fibroblasts and PBMC, as well as elevated serum titers of soluble TNFα, could be found.Conclusion. These data suggest that class II MHC antigens and ICAM‐1 on fibroblasts and endothelial cells are induced by IFNγ and TNFα in an early stage of SSc after the influx of mononuclear cells, and may be important in the putative autoimmune response and in the perpetuation of fibrotic processes in SSc.