bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg‐Strauss syndrome
Authors: Sinico Renato A. , Di Toma Lucafrancesco , Maggiore Umberto , Bottero Paolo , Radice Antonella , Tosoni Cinzia , Grasselli Chiara , Pavone Laura , Gregorini Gina , Monti Stefano , Frassi Micol , Vecchio Filomena , Corace Caterina , Venegoni Emanuela , Buzio Carlo 
Published: September 2005

AbstractObjectiveChurg‐Strauss syndrome (CSS) is classified among the so‐called antineutrophil cytoplasmic antibody–associated systemic vasculitides (AASVs) because of its clinicopathologic features that overlap with the other AASVs. However, while antineutrophil cytoplasmic antibodies (ANCAs) are consistently found in 75–95% of patients with Wegener's granulomatosis or microscopic polyangiitis, their prevalence in CSS varies widely and their clinical significance remains uncertain. We undertook this study to examine the prevalence and antigen specificity of ANCAs in a large cohort of patients with CSS. Moreover, we evaluated the relationship between ANCA positivity and clinicopathologic features.MethodsImmunofluorescence and enzyme‐linked immunosorbent assay were used to determine the presence or absence of ANCAs in 93 consecutive patients at the time of diagnosis. The main clinical and pathologic data, obtained by retrospective analysis, were correlated with ANCA status.ResultsANCAs were present by immunofluorescence in 35 of 93 patients (37.6%). A perinuclear ANCA (pANCA) pattern was found in 26 of 35 patients (74.3%), with specificity for myeloperoxidase (MPO) in 24 patients, while a cytoplasmic ANCA pattern, with specificity for proteinase 3, was found in 3 of 35 patients (8.6%). Atypical patterns were found in 6 of 30 patients with anti‐MPO antibodies (20.0%). ANCA positivity was associated with higher prevalences of renal disease (51.4% versus 12.1%; P < 0.001) and pulmonary hemorrhage (20.0% versus 0.0%; P = 0.001) and, to a lesser extent, with other organ system manifestations (purpura and mononeuritis multiplex), but with lower frequencies of lung disease (34.3% versus 60.3%; P = 0.019) and heart disease (5.7% versus 22.4%; P = 0.042).ConclusionANCAs are present in ∼40% of patients with CSS. A pANCA pattern with specificity for MPO is found in most ANCA‐positive patients. ANCA positivity is mainly associated with glomerular and alveolar capillaritis.
Serum pulmonary and activation‐regulated chemokine/CCL18 levels in patients with systemic sclerosis: A sensitive indicator of active pulmonary fibrosis
Authors: Kodera Masanari , Hasegawa Minoru , Komura Kazuhiro , Yanaba Koichi , Takehara Kazuhiko , Sato Shinichi 
Published: September 2005

AbstractObjectiveTo clarify the clinical significance of serum levels of pulmonary and activation‐regulated chemokine (PARC) in the diagnosis and monitoring of pulmonary fibrosis (PF) in patients with systemic sclerosis (SSc) and to compare PARC levels with KL‐6 antigen or surfactant protein D (SP‐D) levels.MethodsSerum PARC levels were determined by enzyme‐linked immunosorbent assay in 123 SSc patients. In a retrospective longitudinal study, correlation of serum PARC levels with the activity of PF was assessed in 21 SSc patients with active PF.ResultsPARC levels at the first visit were higher in patients with SSc than in patients with systemic lupus erythematosus (SLE) or healthy controls. Increased serum PARC levels were associated with involvement of PF, decreased diffusing capacity for carbon monoxide, and decreased vital capacity in SSc patients. In the longitudinal study, serum PARC levels were significantly decreased in SSc patients with inactive PF compared with those with active PF.ConclusionElevated serum PARC levels correlated with PF and more sensitively reflected the PF activity than did serum KL‐6 or SP‐D levels in SSc. Serum PARC levels may be a useful new serum marker for active PF in SSc.
Use of a gonadotropin‐releasing hormone analog for protection against premature ovarian failure during cyclophosphamide therapy in women with severe lupus
Authors: Somers Emily C. , Marder Wendy , Christman Gregory M. , Ognenovski Vladimir , McCune W. Joseph 
Published: September 2005

AbstractObjectiveCyclophosphamide (CYC) therapy for systemic lupus erythematosus (SLE), a disease predominantly affecting women of childbearing age, causes an unacceptably high incidence of irreversible premature ovarian failure (POF). This study was performed to evaluate the effectiveness of depot leuprolide acetate, a synthetic gonadotropin‐releasing hormone analog (GnRH‐a), for protection against POF during CYC therapy.MethodsYoung women with severe SLE treated in a standardized protocol of monthly intravenous bolus CYC were offered treatment with GnRH‐a (depot leuprolide acetate; a 3.75‐mg monthly injection during the standard CYC regimen). Patients treated with GnRH‐a were compared with controls individually matched by age (±5 years) and by cumulative CYC dose (±5 gm). Reproductive status was determined after a minimum followup of 3 years after CYC therapy. The primary outcome was time to POF. Paired summary statistical analyses, Kaplan‐Meier survival estimates, and Cox regression analyses were performed to assess differences in outcome between groups.ResultsPOF developed in 1 of 20 women treated with GnRH‐a (5%) compared with 6 of 20 controls (30%) matched by age and cumulative CYC dose (matched odds ratio 0.09, P < 0.05). Kaplan‐Meier estimates demonstrated improved cumulative ovarian protection over time in the GnRH‐a–treated group (P = 0.04).ConclusionTreatment with GnRH‐a during CYC therapy was associated with a significant reduction of POF in young women with severe SLE.
Localized scleroderma in childhood is not just a skin disease
Authors: Zulian Francesco , Vallongo Cristina , Woo Patricia , Russo Ricardo , Ruperto Nicolino , Harper John , Espada Graciela , Corona Fabrizia , Mukamel Masha , Vesely Richard , Musiej‐Nowakowska Elzbieta , Chaitow Jeff , Ros Joan , Apaz Maria T. , Gerloni Valeria , Mazur‐Zielinska Henryka , Nielsen Susan , Ullman Susanne , Horneff Gerd , Wouters Carine , Martini Giorgia , Cimaz Rolando , Laxer Ronald , Athreya Balu H. 
Published: September 2005

AbstractObjectiveJuvenile localized scleroderma is usually considered a disease that is confined to the skin and subcutaneous tissue. We studied the prevalence and clinical features of extracutaneous manifestations in a large cohort of children with juvenile localized scleroderma.MethodsData from a multinational study on juvenile scleroderma was used for this in‐depth study. Clinical features of patients with extracutaneous manifestations were compared with those of patients who had exclusively skin involvement.ResultsSeven hundred fifty patients entered the study. One hundred sixty‐eight patients (22.4%) presented with a total of 193 extracutaneous manifestations, as follows: articular (47.2%), neurologic (17.1%), vascular (9.3%), ocular (8.3%), gastrointestinal (6.2%), respiratory (2.6%), cardiac (1%), and renal (1%). Other autoimmune conditions were present in 7.3% of patients. Neurologic involvement consisted of epilepsy, central nervous system vasculitis, peripheral neuropathy, vascular malformations, headache, and neuroimaging abnormalities. Ocular manifestations were episcleritis, uveitis, xerophthalmia, glaucoma, and papilledema. In more than one‐fourth of these children, articular, neurologic, and ocular involvements were unrelated to the site of skin lesions. Raynaud's phenomenon was reported in 16 patients. Respiratory involvement consisted essentially of restrictive lung disease. Gastrointestinal involvement was reported in 12 patients and consisted exclusively of gastroesophageal reflux. Thirty patients (4%) had multiple extracutaneous features, but systemic sclerosis (SSc) developed in only 1 patient. In patients with extracutaneous involvement, the prevalence of antinuclear antibodies and rheumatoid factor was significantly higher than that among patients with only skin involvement. However, Scl‐70 and anticentromere, markers of SSc, were not significantly increased.ConclusionExtracutaneous manifestations of juvenile localized scleroderma developed in almost one‐fourth of the children in this study. These extracutaneous manifestations often were unrelated to the site of the skin lesions and sometimes were associated with multiple organ involvement. The risk of developing SSc was very low. This subgroup of patients with juvenile localized scleroderma should be evaluated extensively, treated more aggressively, and monitored carefully.
Increased acinar damage of salivary glands of patients with Sjögren's syndrome is paralleled by simultaneous imbalance of matrix metalloproteinase 3/tissue inhibitor of metalloproteinases 1 and matrix metalloproteinase 9/tissue inhibitor of metalloproteinases 1 ratios
Authors: Pérez Paola , Kwon Yoon‐Jeoung , Alliende Cecilia , Leyton Lisette , Aguilera Sergio , Molina Claudio , Labra Cecilia , Julio Marcela , Leyton Cecilia , González María‐Julieta 
Published: September 2005

AbstractObjectivePrevious findings in labial salivary glands (LSGs) from patients with Sjögren's syndrome (SS) suggest that increased activity and expression of matrix metalloproteinase 9 (MMP‐9) and MMP‐3 trigger the destruction of acinar structures in these glands. Tissue inhibitors of matrix metalloproteinases (TIMPs) tightly control MMP activity, and TIMP expression is an important modulator of effects attributed to MMPs. This study was undertaken to investigate the correlation between the balance of MMPs/TIMPs in the LSGs of SS patients and the degree of inflammatory infiltration and acinar structure integrity.MethodsThree groups of SS patients classified according to focus score and residual tissue were studied. The expression of MMP‐2, MMP‐3, MMP‐9, TIMP‐1, and TIMP‐2 was examined at the messenger RNA and protein levels. The ratio of MMP/TIMP expression (R value) was calculated. Focus score and acinar structure were evaluated by histologic analysis.ResultsIn SS patients the MMP‐3/TIMP‐1 ratio was higher than 1 and the MMP‐9/TIMP‐1 ratio was much higher than 1 whereas the MMP‐2/TIMP‐2 ratio nearly equaled 1, suggesting elevated proteolytic activity due mainly to MMP‐9. R values were independent of the focus score of inflammatory cells, but correlated well with the dramatic changes observed in morphologic integrity of acini, as revealed mainly by the lack of nuclear polarity. Acinar changes were more evident when R values for both MMP‐9/TIMP‐1 and MMP‐3/TIMP‐1 were higher.ConclusionThis study provides evidence that an altered balance between MMPs and their inhibitors is associated with acinar damage. Since salivary gland acinar cells express both MMPs and TIMPs, these cells may play an important role in extracellular matrix destruction and in the LSG pathophysiology in SS.
Antigen microarray profiling of autoantibodies in rheumatoid arthritis
Authors: Hueber Wolfgang , Kidd Brian A. , Tomooka Beren H. , Lee Byung J. , Bruce Bonnie , Fries James F. , Sønderstrup Grete , Monach Paul , Drijfhout Jan W. , van Venrooij Walther J. , Utz Paul J. , Genovese Mark C. , Robinson William H. 
Published: September 2005

AbstractObjectiveBecause rheumatoid arthritis (RA) is a heterogeneous autoimmune disease in terms of disease manifestations, clinical outcomes, and therapeutic responses, we developed and applied a novel antigen microarray technology to identify distinct serum antibody profiles in patients with RA.MethodsSynovial proteome microarrays, containing 225 peptides and proteins that represent candidate and control antigens, were developed. These arrays were used to profile autoantibodies in randomly selected sera from 2 different cohorts of patients: the Stanford Arthritis Center inception cohort, comprising 18 patients with established RA and 38 controls, and the Arthritis, Rheumatism, and Aging Medical Information System cohort, comprising 58 patients with a clinical diagnosis of RA of <6 months duration. Data were analyzed using the significance analysis of microarrays algorithm, the prediction analysis of microarrays algorithm, and Cluster software.ResultsAntigen microarrays demonstrated that autoreactive B cell responses targeting citrullinated epitopes were present in a subset of patients with early RA with features predictive of the development of severe RA. In contrast, autoimmune targeting of the native epitopes contained on synovial arrays, including several human cartilage gp39 peptides and type II collagen, were associated with features predictive of less severe RA.ConclusionProteomic analysis of autoantibody reactivities provides diagnostic information and allows stratification of patients with early RA into clinically relevant disease subsets.
Bone marrow lesions in the knee are associated with increased local bone density
Authors: Lo Grace H. , Hunter David J. , Zhang Yuqing , McLennan Christine E. , LaValley Michael P. , Kiel Douglas P. , McLean Robert R. , Genant Harry K. , Guermazi Ali , Felson David T. 
Published: September 2005

AbstractObjectiveBone marrow lesions are associated with pain and compartment‐specific progression of joint space narrowing in patients with knee osteoarthritis (OA). Bone marrow lesions occur in regions under increased loading, and excess loading produces increased bone mineral density (BMD). The ratio of BMD in the medial tibial plateau compared with that in the lateral tibial plateau (M:L BMD ratio) reflects loading in the knee. Therefore, we hypothesized that a higher M:L BMD ratio would be associated with medial bone marrow lesions, and that lower ratios would be associated with lateral bone marrow lesions.MethodsParticipants in the Framingham Osteoarthritis Study underwent magnetic resonance imaging (MRI), measurement of bone mineral density (BMD), and knee radiography between 2002 and 2004. MRI was used to define medial and lateral bone marrow lesions in the medial and lateral tibiofemoral compartments, respectively. We performed a logistic regression analysis with medial bone marrow lesions as the outcome, testing M:L BMD ratio groups as predictor variables. We adjusted for age, sex, body mass index, and systemic BMD, using generalized estimating equations to adjust for correlations between knees. An identical analysis evaluating lateral bone marrow lesions was performed.ResultsMedial bone marrow lesions were strongly associated with a high M:L BMD ratio. The odds ratios (ORs) for prevalent medial bone marrow lesions, for the lowest to the highest quartile of M:L BMD ratios, were 1.0 (referent), 1.3, 5.0, and infinity (P for trend < 0.0001). Lateral bone marrow lesions were strongly associated with low M:L BMD ratios (the ORs for prevalent lateral bone marrow lesions, for the highest to the lowest quartile, were 1.0 [referent], 3.0, 26.8, and 54.0 [P for trend < 0.0001]).ConclusionMedial bone marrow lesions occur in knees with relatively higher local medial tibial bone density, and lateral bone marrow lesions occur in knees with relatively higher lateral tibial bone density, supporting the hypothesis that local BMD reflects loading within the knee. Our findings emphasize the importance of loading in the pathophysiology of OA.
Protein structural changes in keratin fibers induced by chemical modification using 2‐iminothiolane hydrochloride: A Raman spectroscopic investigation
Authors: Kuzuhara Akio 
Published: September 2005

AbstractFor the purpose of investigating in detail the influence of chemical modification using 2‐iminothiolane hydrochloride (2‐IT) on keratin fibers, the structure of cross‐sections at various depths of white human hair, treated with 2‐IT and then oxidized, was directly analyzed without isolating the cuticle and cortex, using Raman spectroscopy. In particular, the β‐sheet and/or random coil content (β/R) and the α‐helix (α) content in human hair fibers were estimated by amide I band analysis. The SS band intensity, amide III (unordered) band intensity, and β/R content existing from the cuticle region to the center of cortex region of virgin white human hair remarkably increased by performing the chemical modification using 2‐IT. On the other hand, not only the SS band intensity, but also SO band intensity existing throughout the cortex region of the bleached (damaged) white human hair increased by performing chemical modification using 2‐IT. In particular, β/R content existing throughout the cortex region of the bleached white human hair decreased, while the skeletal CC stretch (α) band intensity at 935 cm−1 and the α content remarkably increased. This indicates a secondary structural change from the random coil form to the α‐helix form in the proteins existing throughout the cortex region. From these experiments, we concluded that the formation of new disulfide (SS) groups resulting from chemical modification using 2‐IT induced the secondary structural changes of proteins existing throughout the cortex region. © 2005 Wiley Periodicals, Inc. Biopolymers 79: 173–184, 2005This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Effect of spatial architecture on cellular colonization
Authors: Huang Yan , Siewe Mbonda , Madihally Sundararajan V. 
Published: September 2005

AbstractThe spatial cell‐material interaction remains vital issue in forming biodegradable scaffolds in Tissue Engineering. In this study, to understand the influence of spatial architecture on cellular behavior, 2D and 3D chitosan scaffolds of 50–190 kD and >310 kD MW were synthesized through air drying and controlled rate freezing/lypohilization technique, respectively. In addition, chitosan was emulsified with 19, 76, and 160 kD 50:50 poly lactide‐co‐glycolide (PLGA) using 1,2‐Dimyristoyl‐sn‐Glycero‐3‐Phosphocholine (DMPC) as stabilizer. 2D and 3D scaffolds were formed by air drying and lyophilization as before. Tensile and compressive properties of films and scaffolds were analyzed in wet conditions at 37°C. Alterations in the cell spreading, proliferation, and cytoskeletal organization of human umbilical vein endothelial cells (HUVECs) and mouse embryonic fibroblasts (MEFs) were studied. These results showed that the formed 3D chitosan scaffolds had interconnected open pore architecture (50–200 µm size). HUVECs and MEFs had reduced spreading areas and circular morphology on 2D chitosan membranes compared with 3D chitosan scaffolds. The fluorescence photomicrographs for actin (using Alexa Fluor 488 phalloidin) and cytoplasm staining (using carboxyfluorescein diacetate‐succinimidyl ester) demonstrated that the cells spread within 3D chitosan matrix. 2D and 3D emulsified chitosan and chitosan/PLGA scaffolds reduced the spreading of HUVECs and MEFs even further. Proliferation results, analyzed via MTT‐Formazan assay and BrdU uptake assay, correlated with the spreading characteristics. The reductions in cell spreading area on emulsified surfaces were not detrimental to the viability and endocytic activity but to proliferation. The observed alterations in cellular colonization are in part due to the substrate stiffness and surface topography. In summary, these results suggest a significant influence of spatial architecture on cellular colonization. © 2005 Wiley Periodicals, Inc.
Simultaneous determination of mycophenolic acid and valproic acid based on derivatization by high‐performance liquid chromatography with fluorescence detection
Authors: Zhong Yan , Jiao Zheng , Yu Yunqiu 
Published: September 2005

AbstractA reliable and validated reversed‐phase high‐performance liquid chromatography (HPLC) method using fluorescence detection is reported for the simultaneous quantitation of mycophenolic acid (MPA) and valproic acid (VPA) in human plasma. The method is based on the pre‐column derivatization of valproic acid with 4‐bromomethyl‐6, 7‐dimethoxycoumarin (BrMMC) and online solvatochromism of MPA by pH adjustment. The linear calibration range was 0.50–30 µg/mL for MPA and 5.00–150 µg/mL for VPA. The relative standard deviations of the method of intra‐ and inter‐day analyses (n = 6) were below 6.5 and 6.7% for MPA, and 5.8 and 6.3% for VPA, respectively. Dichloromethane was used for the simultaneous extraction of MPA and VPA from acidified plasma. This reliable method can be applied in the analysis of MPA and VPA in human plasma using only a small volume (100 µL). Copyright © 2005 John Wiley & Sons, Ltd.
Effects of patulin on thymus capillary of rats
Authors: Gül Nursel , Özsoy Nesrin , Osmanagaoglu Özlem , Selmanoğlu Güldeniz , Koçkaya E. Arzu 
Published: September 2005

AbstractPatulin is a mycotoxin that is produced by species of Penicillum, Aspergillus, and Byssochylamys molds that may grow on a variety of foods including fruit, grains and cheese. Patulin, at a dose of 0.1 mg kg−1 bw day−1 was administered orally to growing male rats aged 5–6 weeks for a period of 60 or 90 days. The dose of patulin used in the present study was based on estimated human exposure levels. At the end of these periods, the thymus glands of patulin‐treated and control Wistar rats were removed and ultrastructural changes in capillary cells of the thymus of patulin‐treated Wistar rats were determined by electron microscopy. The walls of thymus capillaries of the 60‐day patulin‐treated rat groups (P‐60) exhibited degeneration observable in electron microscopic sections. For example, loss of cytoplasm and mitochondrial cristae of cells, swollen endothelial cells, increased thickness of the basement membrane, closed lumen of capillaries, accumulation of fibrous material at the periphery of the capillaries and nuclear anomalies were seen in these sections. Such degeneration and changes were also observed in sections of capillaries of the 90‐day patulin‐treated rat groups (P‐90). The levels of degeneration of endothelial cell nucleus of P‐90 were greater than those of P‐60. This study demonstrated the ultrastructural degeneration of thymus capillary cells of patulin‐treated rats. The results obtained from this study may provide a guide to research dealing with the toxic effects of patulin on tissue and organ ultrastructure. Copyright © 2005 John Wiley & Sons, Ltd.