bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salivary proteomic and genomic biomarkers for primary Sjögren's syndrome
Authors: Hu Shen , Wang Jianghua , Meijer Jiska , Ieong Sonya , Xie Yongming , Yu Tianwei , Zhou Hui , Henry Sharon , Vissink Arjan , Pijpe Justin , Kallenberg Cees , Elashoff David , Loo Joseph A. , Wong David T. 
Published: October 2007

AbstractObjectiveTo identify a panel of protein and messenger RNA (mRNA) biomarkers in human whole saliva (WS) that may be used in the detection of primary Sjögren's syndrome (SS).MethodsMass spectrometry and expression microarray profiling were used to identify candidate protein and mRNA biomarkers of primary SS in WS samples. Validation of the discovered mRNA and protein biomarkers was also demonstrated using real‐time quantitative polymerase chain reaction and immunoblotting techniques.ResultsSixteen WS proteins were found to be down‐regulated and 25 WS proteins were found to be up‐regulated in primary SS patients compared with matched healthy control subjects. These proteins reflected the damage of glandular cells and inflammation of the oral cavity system in patients with primary SS. In addition, 16 WS peptides (10 up‐regulated and 6 down‐regulated in primary SS) were found at significantly different levels (P < 0.05) in primary SS patients and controls. Using stringent criteria (3‐fold change; P < 0.0005), 27 mRNA in saliva samples were found to be significantly up‐regulated in the primary SS patients. Strikingly, 19 of 27 genes that were found to be overexpressed were interferon‐inducible or were related to lymphocyte filtration and antigen presentation known to be involved in the pathogenesis of primary SS.ConclusionOur preliminary study has indicated that WS from patients with primary SS contains molecular signatures that reflect damaged glandular cells and an activated immune response in this autoimmune disease. These candidate proteomic and genomic biomarkers may improve the clinical detection of primary SS once they have been further validated. We also found that WS contains more informative proteins, peptides, and mRNA, as compared with gland‐specific saliva, that can be used in generating candidate biomarkers for the detection of primary SS.
Association of reactive oxygen and nitrogen intermediate and complement levels with apoptosis of peripheral blood mononuclear cells in lupus patients
Authors: Oates James C. , Farrelly Libby W. , Hofbauer Ann F. , Wang Wei , Gilkeson Gary S. 
Published: October 2007

AbstractObjectiveBoth increased production of reactive oxygen and nitrogen intermediates (RONI) and reduced levels of complement may play a role in the increased apoptosis and reduced clearance of apoptotic cells in systemic lupus erythematosus (SLE). The objective of this study was to evaluate both processes in a parallel, prospective, longitudinal manner.MethodsSixty‐seven SLE patients were evaluated during multiple visits, and 31 healthy control subjects were evaluated once or twice. Clinical and laboratory features of SLE disease activity were determined, and blood was collected for measurement of serum nitrate plus nitrite (NOx) levels and for isolation of peripheral blood mononuclear cells (PBMCs). PBMCs were cultured with a nitric oxide (NO) donor and SLE or control plasma, with or without heat inactivation, cobra venom factor (CVF), or lipopolysaccharide plus interferon‐γ treatment. Cells were analyzed for apoptotic index (AI), cellular subsets, and RONI production.ResultsThe PBMC AI was associated with SLE and was inversely associated with complement levels over time. Changes in the AI with addition of a NO donor was longitudinally associated with serum NOx levels, and stimulation of SLE PBMCs led to parallel increases in RONI production and apoptosis. Addition of SLE plasma resulted in a greater PBMC AI, an effect that was increased with heat inactivation and was corrected with CVF treatment.ConclusionThese data suggest that the greater AI observed in SLE PBMCs relates to increased PBMC RONI production and reduced complement levels. The longitudinal nature of these parallel associations within individuals suggests that these processes are dynamic and additive.
Carpal tunnel syndrome and keyboard use at work: A population‐based study
Authors: Atroshi Isam , Gummesson Christina , Ornstein Ewald , Johnsson Ragnar , Ranstam Jonas 
Published: October 2007

AbstractObjectiveTo investigate the relationship between carpal tunnel syndrome (CTS) and keyboard use at work in a general population.MethodsA health status questionnaire was mailed to 2,465 persons of working age (25–65 years) who were randomly selected from the general population of a representative region of Sweden. The questionnaire required the subjects to provide information about the presence and severity of pain, numbness and tingling in each body region, employment history, and work activities, including average time spent using a keyboard during a usual working day. Those reporting recurrent hand numbness or tingling in the median nerve distribution were asked to undergo a physical examination and nerve conduction testing. The prevalence of CTS, defined as symptoms plus abnormal results on nerve conduction tests, was compared between groups of subjects that differed in their intensity of keyboard use, adjusting for age, sex, body mass index, and smoking status.ResultsEighty‐two percent responded to the questionnaire, and 80% of all symptomatic persons attended the examinations. Persons who had reported intensive keyboard use on the questionnaire were significantly less likely to be diagnosed as having CTS than were those who had reported little keyboard use, with a prevalence that increased from 2.6% in the highest keyboard use group (≥4 hours/day), to 2.9% in the moderate use group (1 to <4 hours/day), 4.9% in the low use group (<1 hour/day), and 5.2% in the no keyboard use at work group (Pfor trend = 0.032). Using ≥1 hour/day to designate high keyboard use and <1 hour/day to designate low keyboard use, the prevalence ratio of CTS in the groups with high to low keyboard use was 0.55 (95% confidence interval 0.32, 0.96).ConclusionIntensive keyboard use appears to be associated with a lower risk of CTS.
Pattern and distribution of myocardial fibrosis in systemic sclerosis: A delayed enhanced magnetic resonance imaging study
Authors: Tzelepis George E. , Kelekis Nikolaos L. , Plastiras Sotiris C. , Mitseas Panayiotis , Economopoulos Nikolaos , Kampolis Christos , Gialafos Elias J. , Moyssakis Ioannis , Moutsopoulos Haralampos M. 
Published: October 2007

AbstractObjectiveTo assess the prevalence and pattern of myocardial fibrosis as detected by delayed enhanced magnetic resonance imaging (DE‐MRI) in patients with systemic sclerosis (SSc), and to evaluate a possible association between myocardial fibrosis and cardiac arrhythmias.MethodsForty‐one patients with SSc underwent 24‐hour Holter monitoring, Doppler echocardiography, and DE‐MRI following gadolinium administration.ResultsTechnically acceptable DE‐MRIs were obtained in 36 patients with SSc. Enhancement on DE‐MRI, consistent with myocardial fibrosis, was observed in 24 of these patients (66%), and it was invariably midwall with a linear pattern, mostly involving basal and midcavity segments of the left ventricle. The volume of enhancement (total volume percentage index [TVPI]) did not differ between patients with diffuse SSc and those with limited SSc (mean ± SD 1.46 ± 1.73% versus 1.44 ± 1.77%; P = 0.98). Patients with a long duration (≥15 years) of Raynaud's phenomenon had a greater number of enhancing segments (mean ± SD 6.55 ± 4.93 versus 2.96 ± 3.46; P = 0.017) and a greater TVPI (mean ± SD 2.44 ± 1.97% versus 1.02 ± 1.43%; P = 0.02) than those with a duration of Raynaud's phenomenon <15 years. Nineteen patients with SSc (53%) had abnormal Holter study results. Compared with patients with normal Holter study results, those with abnormal results had a greater number of enhancing segments (mean ± SD 5.4 ± 4.8 versus 2.5 ± 2.9; P < 0.05) and a greater TVPI (mean ± SD 2.1 ± 1.9% versus 0.8 ± 1.2%; P < 0.05).ConclusionDE‐MRI can identify myocardial fibrosis in a significant percentage of patients with SSc and may be a useful noninvasive tool for determining cardiac involvement.
The aminobisphosphonate risedronate preserves localized mineral and material properties of bone in the presence of glucocorticoids
Authors: Balooch Guive , Yao Wei , Ager Joel W. , Balooch Mehdi , Nalla Ravi K. , Porter Alexandra E. , Ritchie Robert O. , Lane Nancy E. 
Published: October 2007

AbstractObjectiveGlucocorticoids (GCs) alter bone strength such that patients receiving these medications have a high rate of fragility‐related fractures. The purpose of this study was to assess whether concurrent treatment with GCs (prednisolone) and risedronate (an aminobisphosphonate) would prevent the reduction in bone strength induced by GCs, in a mouse model of GC‐induced bone loss and in patients enrolled in a clinical study.MethodsWe evaluated mice treated with prednisolone pellets alone, GCs plus risedronate, or placebo alone and iliac crest biopsy specimens obtained from patients who were treated with GCs plus placebo or GCs plus risedronate for 1 year. We measured the mass, architecture, and physical and material properties of bone (subject to therapeutic treatments) at nanoscale to macroscopic dimensions, using synchrotron x‐ray tomography, elastic modulus mapping, transmission electron microscopy, and small‐angle x‐ray scattering techniques.ResultsGC treatment reduced trabecular bone mass, microarchitecture, and the degree of bone mineralization and elastic modulus within the trabeculae. Concurrent treatment with GCs and risedronate prevented the deterioration of trabecular bone architecture, reduced the degree of mineralization, and preserved elastic modulus within the trabeculae, in both mouse and human bone. In addition, treatment with risedronate plus GCs in mice appeared to preserve bone crystal orientation, compared with treatment with GCs alone.ConclusionRisedronate prevented the localized changes in mineral and material properties of bone induced by GCs, which may ultimately improve bone strength.
Overexpression of human decoy receptor 3 in mice results in a systemic lupus erythematosus–like syndrome
Authors: Han Bing , Moore Paul A. , Wu Jiangping , Luo Hongyu 
Published: October 2007

AbstractObjectiveDecoy receptor 3 (DcR3), a tumor necrosis factor receptor family member, is a secreted protein that can enhance cell survival by interfering with multiple apoptosis pathways. This study was undertaken to investigate the role of DcR3 in the pathogenesis of autoimmune disease.MethodsWe generated transgenic mice with actin promoter–driven expression of human DcR3 and investigated the development of autoimmune disease in these mice.ResultsT cell immune responses were compromised in young DcR3‐transgenic mice. Beyond 5–6 months of age, transgenic mice developed a systemic lupus erythematosus (SLE)–like syndrome, with numerous features of the disease. They produced autoantibodies against double‐stranded DNA. Their kidneys showed pathologic changes indicative of glomerular nephritis and IgG and C3 deposition, and proteinuria, leukocyturia, and hematuria, were evident. Aged transgenic mice also developed skin lesions and lymphocyte infiltration in the liver, and exhibited leukopenia, anemia, and thrombocytopenia. The SLE‐like syndrome penetrance in DcR3‐transgenic mice was sex associated, occurring in ∼60% of females versus 20% of males. Exogenous recombinant DcR3 or endogenous DcR3 produced by transgenic T cells effectively protected T cells against activation‐induced apoptosis in vitro. Probably as a consequence of this, CD4 cells with a phenotype of previous activation were increased in the peripheral blood of transgenic mice beyond 6 months of age.ConclusionThese results show that DcR3 overexpression could lead to an SLE‐like syndrome in mice.
Early identification of radiographic osteoarthritis of the hip using an active shape model to quantify changes in bone morphometric features: Can hip shape tell us anything about the progression of osteoarthritis?
Authors: Gregory Jennifer S. , Waarsing Jan H. , Day Judd , Pols Huibert A. , Reijman Max , Weinans Harrie , Aspden Richard M. 
Published: October 2007

AbstractObjectiveFew methods exist to measure the progression of osteoarthritis (OA) or to identify people at high risk of developing OA. Striking radiographic changes include deformation of the femoral head and osteophyte growth, which are usually measured semiquantitatively following visual assessment. In this study, an active shape model (ASM) of the proximal femur was used to determine whether morphologic changes to the bone could be quantified and used as a marker of hip OA.MethodsOne hundred ten subjects who had no signs of radiographic hip OA at baseline (Kellgren/Lawrence [K/L] scores 0–1) were selected from the Rotterdam Study cohort of subjects ages ≥55 years. To measure the progression of OA, subjects were followed up with radiographic assessment after 6 years. At the 6‐year followup, 55 subjects had established OA (K/L score 3), and in 12 of these OA subjects, the progression of the disease required a total hip replacement (THR). Age‐ and sex‐matched control subjects had a K/L score of 0 at followup. Using the ASM, subjects were assessed for shape changes in the femoral head and neck before, during, and after the development of radiographic OA. Scores of shape variance, or mode scores, were assigned for 10 modes of variation in each subject, and differences in mode scores were determined.ResultsDuring followup, significant changes in shape of the proximal femur occurred within the OA group from baseline to followup (P < 0.0001 for mode 1 and P = 0.002 for mode 6) but not within the control group. At baseline (all subjects having K/L scores 0–1), there were significant differences in mode 6 between the OA group and the control group (P = 0.020), and in modes 3 and 6 between the OA subjects who underwent THR and the remaining OA subjects (P = 0.012 and P = 0.019, respectively).ConclusionCompared with traditional scoring methods, the ASM can be used more precisely to quantify the deforming effect of OA on the proximal femur and to identify, at an earlier stage of disease, those subjects at highest risk of developing radiographic OA or needing a THR. The ASM may therefore be useful as an imaging biomarker in the assessment of patients with hip OA.
Mechanotransduction of bovine articular cartilage superficial zone protein by transforming growth factor β signaling
Authors: Neu Corey P. , Khalafi Afshin , Komvopoulos Kyriakos , Schmid Thomas M. , Reddi A. Hari 
Published: October 2007

AbstractObjectiveMechanical signals are key determinants in tissue morphogenesis, maintenance, and restoration strategies in regenerative medicine, although molecular mechanisms of mechanotransduction remain to be elucidated. This study was undertaken to investigate the mechanotransduction process of expression of superficial zone protein (SZP), a critical joint lubricant.MethodsRegional expression of SZP was first quantified in cartilage obtained from the femoral condyles of immature bovines, using immunoblotting, and visualized by immunohistochemistry. Contact pressure mapping in whole joints was accomplished using pressure‐sensitive film and a load application system for joint testing. Friction measurements on cartilage plugs were acquired under boundary lubrication conditions using a pin‐on‐disk tribometer modified for reciprocating sliding. Direct mechanical stimulation by shear loading of articular cartilage explants was performed with and without inhibition of transforming growth factor β (TGFβ) signaling, and SZP content in media was quantified by enzyme‐linked immunosorbent assay.ResultsAn unexpected pattern of SZP localization in knee cartilage was initially identified, with anterior regions exhibiting high levels of SZP expression. Regional SZP patterns were regulated by mechanical signals and correlated with tribological behavior. Direct relationships were demonstrated between high levels of SZP expression, maximum contact pressures, and low friction coefficients. Levels of SZP expression and accumulation were increased by applying shear stress, depending on location within the knee, and were decreased to control levels with the use of a specific inhibitor of TGFβ receptor type I kinase and subsequent phospho‐Smad2/3 activity.ConclusionThese findings indicate a new role for TGFβ signaling in the mechanism of cellular mechanotransduction that is especially significant for joint lubrication.
Vascular endothelial damage and repair in antineutrophil cytoplasmic antibody–associated vasculitis
Authors: de Groot K. , Goldberg C. , Bahlmann F. H. , Woywodt A. , Haller H. , Fliser D. , Haubitz M. 
Published: October 2007

AbstractObjectiveAntineutrophil cytoplasmic antibody–associated vasculitis (AAV) is characterized by necrotizing vessel wall inflammation, paralleled by the detachment of endothelial cells. The repair of such endothelial defects is crucial for the maintenance of regular structure and function of the injured vessels. Bone marrow–derived endothelial progenitor cells (EPCs) are thought to play a pivotal role in the regeneration of damaged endothelium. The aim of this study was to investigate whether EPCs are involved in vascular repair in AAV.MethodsWe assessed disease activity, CD34+ hematopoietic progenitor cells (HPCs) using flow cytometry, EPCs using an in vitro assay, and circulating endothelial cells (CECs) by immunomagnetic isolation from the peripheral blood of 31 patients with active AAV at 1, 3, and 6 months after the initiation of immunosuppressive therapy.ResultsIn patients with untreated active disease, HPC and EPC numbers were comparable with those in healthy control subjects (n = 64). With the induction of remission, the number of HPCs and EPCs increased significantly, from a median of 1.5 cells/μl (range 0.0–7.0) to a median of 3.2 cells/μl (range 0.76–9.2) (P < 0.001) and from a median of 261 cells/high‐power field (range 171–643) to a median of 470 cells/high‐power field (range 168–996) (P < 0.021), respectively. In contrast, the initially elevated number of CECs decreased significantly (P < 0.001). We observed no correlation between the number of HPCs or EPCs and the leukocyte count, the thrombocyte count, or kidney function.ConclusionIn patients with AAV, the numbers of circulating CD34+ HPCs and EPCs increased significantly after the institution of immunosuppressive therapy and disease remission. This finding points to a role of circulating CD34+ HPCs and EPCs in endothelial repair in vasculitis. Targeted stimulation of these cells might represent a new possibility of improving vascular healing in AAV.
Fetal thermal dose considerations during the obstetrician's watch: Implications for the pediatrician's observations
Authors: Miller Morton W. , Church Charles C. , Miller Richard K. , Edwards Marsh J. 
Published: October 2007

AbstractThere are a number of seemingly “usual” thermal episodes during pregnancy for which it is relatively easy to determine a rudimentary aspect of thermal dose; these episodes include fever, labor, labor plus epidural, and the normally‐occurring 0.5°C temperature elevation above maternal core temperature of the fetus during the entirety of the third trimester. Complications can involve, for instance, fever during the third trimester. We consider the thermal doses of five different but “usual” or “normal” hyperthermic episodes during human pregnancy and compare those doses with the thermal doses involved with both single and cohort exposures of pregnant guinea pigs throughout their gestational period. The end‐point studied in the guinea pigs was microencephaly. In nine of the 10 comparisons (human fetal thermal dose vs. guinea pig fetal thermal dose) the human dose is substantially larger than that of the guinea pig thermal dose, which was substantially teratogenic. This situation is essentially the inverse of the type of information contained in the Physician's Desk Reference (PDR) on drugs, in which it is not unusual to discern that at high drug levels there may be teratogenic effects in laboratory animals, but such effects were not observed at “clinical” drug levels in animals or subsequent clinical trials. With hyperthermic events, however, it appears that the teratogenically‐effective thermal dose levels associated with animal testing are quite low relative to those thermal doses associated with relatively “normal” obstetric observations during a pregnancy. Birth Defects Research (Part C) 81:135‐143, 2007. © 2007 Wiley‐Liss, Inc.
Air pollutant effects on fetal and early postnatal development
Authors: Wang Lei , Pinkerton Kent E. 
Published: October 2007

AbstractNumerical research on the health effects of air pollution has been published in the last decade. Epidemiological studies have shown that children's exposure to air pollutants during fetal development and early postnatal life is associated with many types of health problems including abnormal development (low birth weight [LBW], very low birth weight [VLBW], preterm birth [PTB], intrauterine growth restriction [IUGR], congenital defects, and intrauterine and infant mortality), decreased lung growth, increased rates of respiratory tract infections, childhood asthma, behavioral problems, and neurocognitive decrements. This review focuses on the health effects of major outdoor air pollutants including particulates, carbon monoxide (CO), sulfur and nitrogen oxides (SO2, NOx), ozone, and one common indoor air pollutant, environmental tobacco smoke (ETS). Animal data is presented that demonstrate perinatal windows of susceptibility to sidestream smoke, a surrogate for ETS, resulting in altered airway sensitivity and cell type frequency. A study of neonatal monkeys exposed to sidestream smoke during the perinatal period and/or early postnatal period that resulted in an altered balance of Th1‐/Th2‐cytokine secretion, skewing the immune response toward the allergy‐associated Th2 cytokine phenotype, is also discussed. Birth Defects Research (Part C) 81:144–154, 2007. © 2007 Wiley‐Liss, Inc.
Radiation effects on development
Authors: De Santis Marco , Cesari Elena , Nobili E. , Straface Gianluca , Cavaliere Anna Franca , Caruso Alessandro 
Published: October 2007

AbstractIt has been widely reported that prenatal exposure to ionizing radiation can interfere with embryonic and fetal development, depending on dose and gestational age in which exposure occurs. According to several studies on animal models, different well‐defined stages during prenatal life can be distinguished in relation to teratogenic effects. During the preimplantation stage, elevated doses of radiation can result in abortion, while lower doses may produce genomic damage that is usually repaired. On the other hand, during the organogenesis stage in mice (embryonic day 6.5 [E6.5] to E13.5), irradiation is associated with increased incidence of malformation and intrauterine growth restriction (IUGR). Later exposure is linked to brain damage. Doses used in animal studies are generally higher than those used for diagnostic procedures in humans. Usually, radiation exposure to diagnostic range (<0.05 Gy = 5 rads) is not associated with an increased risk of congenital anomalies. In human studies, elevated doses produce adverse outcomes, depending on stage of development, as in animal studies. Blastogenesis (up to two weeks) is associated with failure to implant or no significant health effects. An increased risk of malformation and growth retardation can be observed for two to seven weeks exposure (organogenesis stage), while exposure at later stages (fetogenesis) is mainly associated with brain damage. In this review we focus on the relevance of estimating the cumulative dose of radiation to the fetus and the gestational age in which exposure occurs, to provide appropriate counseling to pregnant women. Birth Defects Research (Part C) 81:177–182, 2007. © 2007 Wiley‐Liss, Inc.