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Find video protocols related to scientific articles indexed in Pubmed.
Myositis registries and biorepositories: powerful tools to advance clinical, epidemiologic and pathogenic research.
Curr Opin Rheumatol
PUBLISHED: 09-17-2014
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Clinical registries and biorepositories have proven extremely useful in many studies of diseases, especially rare diseases. Given their rarity and diversity, the idiopathic inflammatory myopathies, or myositis syndromes, have benefited from individual researchers' collections of cohorts of patients. Major efforts are being made to establish large registries and biorepositories that will allow many additional studies to be performed that were not possible before. Here, we describe the registries developed by investigators and patient support groups that are currently available for collaborative research purposes.
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Reproductive and Hormonal Risk Factors for Antinuclear Antibodies (ANA) in a Representative Sample of U.S. Women.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 08-01-2014
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Autoantibodies are of growing interest in cancer research as potential biomarkers; yet, the determinants of autoimmunity are not well understood. Antinuclear antibodies (ANA) are common in the general population and are more prevalent in women and older adults. Here, we examined the relationship of ANA with reproductive and hormonal factors in a representative sample of U.S. women.
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Respiratory tract lung geometry and dosimetry model for male Sprague-Dawley rats.
Inhal Toxicol
PUBLISHED: 07-25-2014
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While inhalation toxicological studies of various compounds have been conducted using a number of different strains of rats, mechanistic dosimetry models have only had tracheobronchial (TB) structural data for Long-Evans rats, detailed morphometric data on the alveolar region of Sprague-Dawley rats and limited alveolar data on other strains. Based upon CT imaging data for two male Sprague-Dawley rats, a 15-generation, symmetric typical path model was developed for the TB region. Literature data for the alveolar region of Sprague-Dawley rats were analyzed to develop an eight-generation model, and the two regions were joined to provide a complete lower respiratory tract model for Sprague-Dawley rats. The resulting lung model was used to examine particle deposition in Sprague-Dawley rats and to compare these results with predicted deposition in Long-Evans rats. Relationships of various physiologic variables and lung volumes were either developed in this study or extracted from the literature to provide the necessary input data for examining particle deposition. While the lengths, diameters and branching angles of the TB airways differed between the two Sprague-Dawley rats, the predicted deposition patterns in the three major respiratory tract regions were very similar. Between Sprague-Dawley and Long-Evans rats, significant differences in TB and alveolar predicted deposition fractions were observed over a wide range of particle sizes, with TB deposition fractions being up to 3- to 4-fold greater in Sprague-Dawley rats and alveolar deposition being significantly greater in Long-Evans rats. Thus, strain-specific lung geometry models should be used for particle deposition calculations and interspecies dose comparisons.
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Expert panel workshop consensus statement on the role of the environment in the development of autoimmune disease.
Int J Mol Sci
PUBLISHED: 06-09-2014
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Autoimmune diseases include 80 or more complex disorders characterized by self-reactive, pathologic immune responses in which genetic susceptibility is largely insufficient to determine disease onset. In September 2010, the National Institute of Environmental Health Sciences (NIEHS) organized an expert panel workshop to evaluate the role of environmental factors in autoimmune diseases, and the state of the science regarding relevant mechanisms, animal models, and human studies. The objective of the workshop was to analyze the existing data to identify conclusions that could be drawn regarding environmental exposures and autoimmunity and to identify critical knowledge gaps and areas of uncertainty for future study. This consensus document summarizes key findings from published workshop monographs on areas in which "confident" and "likely" assessments were made, with recommendations for further research. Transcribed notes and slides were reviewed to synthesize an overview on exposure assessment and questions addressed by interdisciplinary panels. Critical advances in the field of autoimmune disease research have been made in the past decade. Collaborative translational and interdisciplinary research is needed to elucidate the role of environmental factors in autoimmune diseases. A focus on exposure assessment methodology is needed to improve the effectiveness of human studies, and more experimental studies are needed to focus on causal mechanisms underlying observed associations of environmental factors with autoimmune disease in humans.
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Novel assessment tools to evaluate clinical and laboratory responses in a subset of patients enrolled in the Rituximab in Myositis trial.
Clin. Exp. Rheumatol.
PUBLISHED: 03-20-2014
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We aimed to assess changes in myositis core set measures and ancillary clinical and laboratory data from the National Institutes of Health's subset of patients enrolled in the Rituximab in Myositis trial.
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Accommodating measurements below a limit of detection: a novel application of Cox regression.
Am. J. Epidemiol.
PUBLISHED: 03-04-2014
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In environmental epidemiology, measurements of exposure biomarkers often fall below the assay's limit of detection. Existing methods for handling this problem, including deletion, substitution, parametric regression, and multiple imputation, can perform poorly if the proportion of "nondetects" is high or parametric models are mis-specified. We propose an approach that treats the measured analyte as the modeled outcome, implying a role reversal when the analyte is a putative cause of a health outcome. Following a scale reversal as well, our approach uses Cox regression to model the analyte, with confounder adjustment. The method makes full use of quantifiable analyte measures, while appropriately treating nondetects as censored. Under the proportional hazards assumption, the hazard ratio for a binary health outcome is interpretable as an adjusted odds ratio: the odds for the outcome at any particular analyte concentration divided by the odds given a lower concentration. Our approach is broadly applicable to cohort studies, case-control studies (frequency matched or not), and cross-sectional studies conducted to identify determinants of exposure. We illustrate the method with cross-sectional survey data to assess sex as a determinant of 2,3,7,8-tetrachlorodibenzo-p-dioxin concentration and with prospective cohort data to assess the association between 2,4,4'-trichlorobiphenyl exposure and psychomotor development.
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Idiopathic inflammatory myopathies and the anti-synthetase syndrome: a comprehensive review.
Autoimmun Rev
PUBLISHED: 01-11-2014
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Autoantibodies are a hallmark in the diagnosis of many systemic autoimmune rheumatic diseases (SARD) including idiopathic inflammatory myopathies (IIM). Based on their specificity, autoantibodies in IIM are grouped into myositis specific (MSA) and myositis associated autoantibodies (MAA). Among the MSA, autoantibodies against aminoacyl-tRNA synthetases (ARS) represent the most common antibodies and can be detected in 25-35% of patients. The presence of ARS and other autoantibodies has become a key feature for classification and diagnosis of IIM and is increasingly used to define clinically distinguishable IIM subsets. For example, anti-ARS autoantibodies are the key features of what has become known as anti-synthetase syndrome (aSS), characterized by multiple organ involvement, primarily interstitial lung disease, often accompanied by myositis, non-erosive arthritis, Raynaud's phenomenon, fever, and "mechanic's hands". Autoantibodies directed to eight different ARS have been described: Jo-1 (histidyl), PL-7 (threonyl), PL-12 (alanyl), OJ (isoleucyl), EJ (glycyl), KS (asparaginyl), Zo (phenylalanyl) and Ha (tyrosyl). Each anti-ARS antibody seems to define a distinctive clinical phenotype. Although several research methods and commercial tests are available, routine testing for anti-ARS autoantibodies (other than anti-Jo-1/histidyl-tRNA synthetase) is not widely available, sometimes leading to delays in diagnosis and poor disease outcomes.
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Twins discordant for myositis and systemic lupus erythematosus show markedly enriched autoantibodies in the affected twin supporting environmental influences in pathogenesis.
BMC Musculoskelet Disord
PUBLISHED: 01-06-2014
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Studies of twin pairs discordant for autoimmune conditions provide a unique opportunity to explore contributing factors triggered by complex gene-environment interactions.
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Estimating lung burdens based on individual particle density estimated from scanning electron microscopy and cascade impactor samples.
Inhal Toxicol
PUBLISHED: 12-06-2013
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Abstract Workplace air is monitored for overall dust levels and for specific components of the dust to determine compliance with occupational and workplace standards established by regulatory bodies for worker health protection. Exposure monitoring studies were conducted by the International Copper Association (ICA) at various industrial facilities around the world working with copper. Individual cascade impactor stages were weighed to determine the total amount of dust collected on the stage, and then the amounts of soluble and insoluble copper and other metals on each stage were determined; speciation was not determined. Filter samples were also collected for scanning electron microscope analysis. Retrospectively, there was an interest in obtaining estimates of alveolar lung burdens of copper in workers engaged in tasks requiring different levels of exertion as reflected by their minute ventilation. However, mechanistic lung dosimetry models estimate alveolar lung burdens based on particle Stokes diameter. In order to use these dosimetry models the mass-based, aerodynamic diameter distribution (which was measured) had to be transformed into a distribution of Stokes diameters, requiring an estimation be made of individual particle density. This density value was estimated by using cascade impactor data together with scanning electron microscopy data from filter samples. The developed method was applied to ICA monitoring data sets and then the multiple path particle dosimetry (MPPD) model was used to determine the copper alveolar lung burdens for workers with different functional residual capacities engaged in activities requiring a range of minute ventilation levels.
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Consensus statement on screening, diagnosis, classification and treatment of endemic (Balkan) nephropathy.
Nephrol. Dial. Transplant.
PUBLISHED: 10-28-2013
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Currently used diagnostic criteria in different endemic (Balkan) nephropathy (EN) centers involve different combinations of parameters, various cut-off values and many of them are not in agreement with proposed international guidelines. Leaders of EN centers began to address these problems at scientific meetings, and this paper is the outgrowth of those discussions. The main aim is to provide recommendations for clinical work on current knowledge and expertise. This document is developed for use by general physicians, nephrologists, urologist, public health experts and epidemiologist, and it is hoped that it will be adopted by responsible institutions in countries harboring EN. National medical providers should cover costs of screening and diagnostic procedures and treatment of EN patients with or without upper urothelial cancers.
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The myositis autoantibody phenotypes of the juvenile idiopathic inflammatory myopathies.
Medicine (Baltimore)
PUBLISHED: 07-24-2013
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The juvenile idiopathic inflammatory myopathies (JIIM) are systemic autoimmune diseases characterized by skeletal muscle weakness, characteristic rashes, and other systemic features. In follow-up to our study defining the major clinical subgroup phenotypes of JIIM, we compared demographics, clinical features, laboratory measures, and outcomes among myositis-specific autoantibody (MSA) subgroups, as well as with published data on adult idiopathic inflammatory myopathy patients enrolled in a separate natural history study. In the present study, of 430 patients enrolled in a nationwide registry study who had serum tested for myositis autoantibodies, 374 had either a single specific MSA (n = 253) or no identified MSA (n = 121) and were the subject of the present report. Following univariate analysis, we used random forest classification and exact logistic regression modeling to compare autoantibody subgroups. Anti-p155/140 autoantibodies were the most frequent subgroup, present in 32% of patients with juvenile dermatomyositis (JDM) or overlap myositis with JDM, followed by anti-MJ autoantibodies, which were seen in 20% of JIIM patients, primarily in JDM. Other MSAs, including anti-synthetase, anti-signal recognition particle (SRP), and anti-Mi-2, were present in only 10% of JIIM patients. Features that characterized the anti-p155/140 autoantibody subgroup included Gottron papules, malar rash, "shawl-sign" rash, photosensitivity, cuticular overgrowth, lowest creatine kinase (CK) levels, and a predominantly chronic illness course. The features that differed for patients with anti-MJ antibodies included muscle cramps, dysphonia, intermediate CK levels, a high frequency of hospitalization, and a monocyclic disease course. Patients with anti-synthetase antibodies had higher frequencies of interstitial lung disease, arthralgia, and "mechanics hands," and had an older age at diagnosis. The anti-SRP group, which had exclusively juvenile polymyositis, was characterized by high frequencies of black race, severe onset, distal weakness, falling episodes, Raynaud phenomenon, cardiac involvement, high CK levels, chronic disease course, frequent hospitalization, and wheelchair use. Characteristic features of the anti-Mi-2 subgroup included Hispanic ethnicity, classic dermatomyositis and malar rashes, high CK levels, and very low mortality. Finally, the most common features of patients without any currently defined MSA or myositis-associated autoantibodies included linear extensor erythema, arthralgia, and a monocyclic disease course. Several demographic and clinical features were shared between juvenile and adult idiopathic inflammatory myopathy subgroups, but with several important differences. We conclude that juvenile myositis is a heterogeneous group of illnesses with distinct autoantibody phenotypes defined by varying clinical and demographic characteristics, laboratory features, and outcomes.
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Reproducibility of the effects of theta burst stimulation on motor cortical plasticity in healthy participants.
Clin Neurophysiol
PUBLISHED: 07-04-2013
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Theta-burst stimulation (TBS) is a repetitive transcranial magnetic stimulation (TMS) protocol, capable of enhancing or suppressing the amplitude of contralateral motor-evoked potentials (MEP) for several minutes after stimulation over the primary motor cortex. Continuous TBS (cTBS) produces a long-term depression (LTD)-like reduction of cortical excitability. The purpose of this study was to assess the test-retest reproducibility of the effects of cTBS and to investigate which neurophysiologic markers of cTBS-induced plasticity are most reproducible.
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Brief report: ultraviolet radiation exposure is associated with clinical and autoantibody phenotypes in juvenile myositis.
Arthritis Rheum.
PUBLISHED: 04-16-2013
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Genetic and environmental factors may contribute to the etiology of the juvenile idiopathic inflammatory myopathies (IIMs), which are systemic autoimmune diseases that are characterized by muscle and skin inflammation. We undertook this study to investigate the association between ultraviolet radiation (UVR) exposure and the clinical and autoantibody expression of juvenile IIM.
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The clinical phenotypes of the juvenile idiopathic inflammatory myopathies.
Medicine (Baltimore)
PUBLISHED: 03-13-2013
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The juvenile idiopathic inflammatory myopathies (JIIM) are systemic autoimmune diseases characterized by skeletal muscle weakness, characteristic rashes, and other systemic features. Although juvenile dermatomyositis (JDM), the most common form of JIIM, has been well studied, the other major clinical subgroups of JIIM, including juvenile polymyositis (JPM) and juvenile myositis overlapping with another autoimmune or connective tissue disease (JCTM), have not been well characterized, and their similarity to the adult clinical subgroups is unknown. We enrolled 436 patients with JIIM, including 354 classified as JDM, 33 as JPM, and 49 as JCTM, in a nationwide registry study. The aim of the study was to compare demographics; clinical features; laboratory measures, including myositis autoantibodies; and outcomes among these clinical subgroups, as well as with published data on adult patients with idiopathic inflammatory myopathies (IIM) enrolled in a separate natural history study. We used random forest classification and logistic regression modeling to compare clinical subgroups, following univariate analysis. JDM was characterized by typical rashes, including Gottron papules, heliotrope rash, malar rash, periungual capillary changes, and other photosensitive and vasculopathic skin rashes. JPM was characterized by more severe weakness, higher creatine kinase levels, falling episodes, and more frequent cardiac disease. JCTM had more frequent interstitial lung disease, Raynaud phenomenon, arthralgia, and malar rash. Differences in autoantibody frequency were also evident, with anti-p155/140, anti-MJ, and anti-Mi-2 seen more frequently in patients with JDM, anti-signal recognition particle and anti-Jo-1 in JPM, and anti-U1-RNP, PM-Scl, and other myositis-associated autoantibodies more commonly present in JCTM. Mortality was highest in patients with JCTM, whereas hospitalizations and wheelchair use were highest in JPM patients. Several demographic and clinical features were shared between juvenile and adult IIM subgroups. However, JDM and JPM patients had a lower frequency of interstitial lung disease, Raynaud phenomenon, "mechanics hands" and carpal tunnel syndrome, and lower mortality than their adult counterparts. We conclude that juvenile myositis is a heterogeneous group of illnesses with distinct clinical subgroups, defined by varying clinical and demographic characteristics, laboratory features, and outcomes.
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Variation in presentation and presence of DNA adducts and p53 mutations in patients with endemic nephropathy--an environmental form of the aristolochic acid nephropathy.
Kidney Blood Press. Res.
PUBLISHED: 02-26-2013
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Endemic nephropathy (EN) and associated urothelial cell cancers (UUC) are an environmental form of aristolochic acid nephropathy where the most probable rout of ingestion of aristolochic acid (AA) was made by bread contaminated with AA, leading to chronic dietary intoxication. Clinical courses of three members of the same family, similarly exposed to toxin, who exhibited different clinical courses of the disease are presented.
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Clinical and laboratory features distinguishing juvenile polymyositis and muscular dystrophy.
Arthritis Care Res (Hoboken)
PUBLISHED: 02-23-2013
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To differentiate juvenile polymyositis (PM) and muscular dystrophy, both of which may present with chronic muscle weakness and inflammation.
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Post-zygotic and inter-individual structural genetic variation in a presumptive enhancer element of the locus between the IL10R? and IFNAR1 genes.
PLoS ONE
PUBLISHED: 01-01-2013
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Although historically considered as junk-DNA, tandemly repeated sequence motifs can affect human phenotype. For example, variable number tandem repeats (VNTR) with embedded enhancers have been shown to regulate gene transcription. The post-zygotic variation is the presence of genetically distinct populations of cells in an individual derived from a single zygote, and this is an understudied aspect of genome biology. We report somatically variable VNTR with sequence properties of an enhancer, located upstream of IFNAR1. Initially, SNP genotyping of 63 monozygotic twin pairs and multiple tissues from 21 breast cancer patients suggested a frequent post-zygotic mosaicism. The VNTR displayed a repeated 32 bp core motif in the center of the repeat, which was flanked by similar variable motifs. A total of 14 alleles were characterized based on combinations of segments, which showed post-zygotic and inter-individual variation, with up to 6 alleles in a single subject. Somatic variation occurred in ?24% of cases. In this hypervariable region, we found a clustering of transcription factor binding sites with strongest sequence similarity to mouse Foxg1 transcription factor binding motif. This study describes a VNTR with sequence properties of an enhancer that displays post-zygotic and inter-individual genetic variation. This element is within a locus containing four related cytokine receptors: IFNAR2, IL10R?, IFNAR1 and IFNGR2, and we hypothesize that it might function in transcriptional regulation of several genes in this cluster. Our findings add another level of complexity to the variation among VNTR-based enhancers. Further work may unveil the normal function of this VNTR in transcriptional control and its possible involvement in diseases connected with these receptors, such as autoimmune conditions and cancer.
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Aristolactam-DNA adducts are a biomarker of environmental exposure to aristolochic acid.
Kidney Int.
PUBLISHED: 11-09-2011
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Endemic (Balkan) nephropathy is a chronic tubulointerstitial disease frequently accompanied by urothelial cell carcinomas of the upper urinary tract. This disorder has recently been linked to exposure to aristolochic acid, a powerful nephrotoxin and human carcinogen. Following metabolic activation, aristolochic acid reacts with genomic DNA to form aristolactam-DNA adducts that generate a unique TP53 mutational spectrum in the urothelium. The aristolactam-DNA adducts are concentrated in the renal cortex, thus serving as biomarkers of internal exposure to aristolochic acid. Here, we present molecular epidemiologic evidence relating carcinomas of the upper urinary tract to dietary exposure to aristolochic acid. DNA was extracted from the renal cortex and urothelial tumor tissue of 67 patients that underwent nephroureterectomy for carcinomas of the upper urinary tract and resided in regions of known endemic nephropathy. Ten patients from nonendemic regions with carcinomas of the upper urinary tract served as controls. Aristolactam-DNA adducts were quantified by (32)P-postlabeling, the adduct was confirmed by mass spectrometry, and TP53 mutations in tumor tissues were identified by chip sequencing. Adducts were present in 70% of the endemic cohort and in 94% of patients with specific A:T to T:A mutations in TP53. In contrast, neither aristolactam-DNA adducts nor specific mutations were detected in tissues of patients residing in nonendemic regions. Thus, in genetically susceptible individuals, dietary exposure to aristolochic acid is causally related to endemic nephropathy and carcinomas of the upper urinary tract.
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Coincident light and clock regulation of pseudoresponse regulator protein 37 (PRR37) controls photoperiodic flowering in sorghum.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-19-2011
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Optimal flowering time is critical to the success of modern agriculture. Sorghum is a short-day tropical species that exhibits substantial photoperiod sensitivity and delayed flowering in long days. Genotypes with reduced photoperiod sensitivity enabled sorghums utilization as a grain crop in temperate zones worldwide. In the present study, Ma(1), the major repressor of sorghum flowering in long days, was identified as the pseudoresponse regulator protein 37 (PRR37) through positional cloning and analysis of SbPRR37 alleles that modulate flowering time in grain and energy sorghum. Several allelic variants of SbPRR37 were identified in early flowering grain sorghum germplasm that contain unique loss-of-function mutations. We show that in long days SbPRR37 activates expression of the floral inhibitor CONSTANS and represses expression of the floral activators Early Heading Date 1, FLOWERING LOCUS T, Zea mays CENTRORADIALIS 8, and floral induction. Expression of SbPRR37 is light dependent and regulated by the circadian clock, with peaks of RNA abundance in the morning and evening in long days. In short days, the evening-phase expression of SbPRR37 does not occur due to darkness, allowing sorghum to flower in this photoperiod. This study provides insight into an external coincidence mechanism of photoperiodic regulation of flowering time mediated by PRR37 in the short-day grass sorghum and identifies important alleles of SbPRR37 that are critical for the utilization of this tropical grass in temperate zone grain and bioenergy production.
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State of the art: what we know about infectious agents and myositis.
Curr Opin Rheumatol
PUBLISHED: 09-03-2011
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Increasing evidence suggests that the idiopathic inflammatory myopathies (IIMs) result from certain environmental exposures in genetically susceptible individuals. Investigations have demonstrated that a variety of infections not only cause infectious myopathies but also could be possible triggers for IIM. This review summarizes published studies on the possible roles of infections in inflammatory muscle disease.
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The fractions of respiratory tract cells at risk in formaldehyde carcinogenesis.
Inhal Toxicol
PUBLISHED: 09-02-2011
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Clonal growth modeling of carcinogenesis requires data on the number of cells at risk of becoming cancerous. We synthesized literature data to estimate the fraction of respiratory tract epithelial cells that are progenitor cells, and therefore at risk, in formaldehyde carcinogenesis for specific respiratory tract regions. We concluded that the progenitor cells for the transitional and respiratory epithelia of the nose are basal and nonciliated cells and Type II cells in the alveolar region. In the conducting airways, our evaluation indicated that ciliated and basal cells are not in the progenitor pool. Respiratory tract epithelial cell fractions of 0.819 in rats and 0.668 in humans were estimated from the data. The total numbers of epithelial cells in the lower respiratory tract of humans and rats were allocated to individual generations. Cell cycle times were also estimated from literature data, since the reciprocal of cell cycle time is an important variable in clonal growth modeling. Sensitivity analyses of a previously published risk model for formaldehyde carcinogenesis showed that specification of the fraction of cells at risk markedly affects estimates of some parameters of the clonal growth model. When all epithelial cells are considered part of the progenitor pool, additional risks for the non-smoking population was typically over predicted by about 35% for high exposure levels. These results demonstrate the importance of accurately identifying cell populations at risk when applying quantitative models in risk assessments.
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Xenotropic murine leukemia virus-related virus is not associated with chronic fatigue syndrome in patients from different areas of the us in the 1990s.
Virol. J.
PUBLISHED: 08-29-2011
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In 2009, xenotropic murine leukemia virus-related virus (XMRV) was reported in 67% of patients with chronic fatigue syndrome (CFS) compared to 4% of controls. Since then numerous reports failed to detect XMRV in other cohorts of CFS patients, and some studies suggested that XMRV sequences in human samples might be due to contamination of these samples with mouse DNA.
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Post-epidemic eosinophilia-myalgia syndrome associated with L-tryptophan.
Arthritis Rheum.
PUBLISHED: 06-25-2011
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Eosinophilia-myalgia syndrome (EMS) is characterized by subacute onset of myalgias and peripheral eosinophilia, followed by chronic neuropathy and skin induration. An epidemic of EMS in 1989 was linked to consumption of L-tryptophan that had originated from a single source. Following the ban by the Food and Drug Administration (FDA) on the sale of L-tryptophan, the incidence of EMS declined rapidly. Moreover, no new cases have been described since the FDA ban was lifted in 2005. We report the clinical, histopathologic, and immunogenetic features of a new case of L-tryptophan-associated EMS, along with evidence of activated transforming growth factor ? and interleukin-4 signaling in the lesional skin.
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Adolescent transition: Ordinary People (1980), Fly Away Home (1996), and (500) Days Of Summer (2009).
Am J Psychoanal
PUBLISHED: 06-16-2011
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Five important transitional tasks of adolescent development are (i) taming the upsurge of desires and impulses, both sexual and aggressive, into constructive and creative directions; (ii) establishing independence from infantile family ties (while maintaining some involvement with the family of origin); (iii) reconciling self-preoccupations with social attachments; (iv) reworking identifications, especially sexual; and (v) establishing romantic attachments and solidifying ongoing stable love relationships. These tasks are illustrated with the help of three movies, namely Ordinary People, Fly Away Home, and (500) Days of Summer.
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Mass spectrometric determination of IgG subclass-specific glycosylation profiles in siblings discordant for myositis syndromes.
J. Proteome Res.
PUBLISHED: 06-08-2011
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Many autoimmune conditions are believed to result from chronic inflammation as a consequence of the interaction of genetic and environmental factors in susceptible individuals. One common feature in some autoimmune diseases is the decrease in terminal galactosylation of the constant region N-glycan of the total plasma immunoglobulin. To determine whether a similar pattern is characteristic for the autoimmune disorder myositis, we analyzed the antibody subclass specific glycosylation in patients with myositis, their asymptomatic siblings, and healthy unrelated age- and sex-matched controls. The antibody subclass specific glycosylation was determined from the LC-MS analyses of the IgG glycopeptides generated by trypsin digestion of the antibody heavy chain. The glycosylation profiles of the IgG subclasses were determined relative to the total abundance of all glycoforms. We found elevated amounts of glycoforms lacking terminal galactose in myositis patients. Pairwise statistical analyses reveals that galactosylation is statistically different between the myositis patients and control groups. Furthermore, the trend analysis for glycosylation indicates a pattern of decreasing galactosylation in the order controls ? siblings ? myositis patients, suggesting the existence of a genetic, immune-related predisposition in the group of asymptomatic siblings that can be detected before the onset of clinical symptoms at the level of plasma proteins.
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Environmental agents and autoimmune diseases.
Adv. Exp. Med. Biol.
PUBLISHED: 06-02-2011
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Autoimmune diseases, which comprise over 80 clinically distinct conditions, are characterized by the presence of autoantibodies or autoreactive T cells directed against self structures (autoantigens). While these often incurable disorders appear to be rapidly increasing in recognition throughout the world, their rarity, heterogeneity and complex etiologies have limited our understanding of their pathogeneses. The precise mechanisms for the development of autoimmune diseases are not known, however, evidence from many complementary lines of investigation suggests that autoimmune diseases result from the interactions of both environmental and genetic risk factors. While considerable progress has been made in understanding multiple genetic risk factors for many autoimmune diseases, relatively little information is now available regarding the role of the environment in the development of these illnesses. This chapter examines the limited but growing evidence for the role of the environment in the development and progression of autoimmune diseases, the specific exposures that have been suspected of being involved, the possible mechanisms by which these agents may induce and sustain autoimmune processes and the approaches needed to better understand these issues in the future. Identifying the necessary and sufficient genetic and environmental risk factors for disease holds the promise of allowing for the prevention of some illnesses through avoidance of environmental risk factors by genetically susceptible individuals or via gene or other therapies to correct the effects of deleterious genetic risk factors in the case of unavoidable environmental agents.
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Gene expression profiles from discordant monozygotic twins suggest that molecular pathways are shared among multiple systemic autoimmune diseases.
Arthritis Res. Ther.
PUBLISHED: 02-28-2011
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The objective of this study is to determine if multiple systemic autoimmune diseases (SAID) share gene expression pathways that could provide insights into pathogenic mechanisms common to these disorders.
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[Documental review of community health promotion experiences in primary health care].
Aten Primaria
PUBLISHED: 02-20-2011
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Describe the community activities (CA) published or registered in health promotion networks in which Primary Health Care (PHC) has taken part.
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Deciphering the clinical presentations, pathogenesis, and treatment of the idiopathic inflammatory myopathies.
JAMA
PUBLISHED: 01-13-2011
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The idiopathic inflammatory myopathies or myositis syndromes (the most common forms are polymyositis, dermatomyositis, and inclusion body myositis) are systemic autoimmune diseases defined by chronic muscle weakness and inflammation of unknown etiology and result in significant morbidity and mortality. Research suggests that categorizing heterogeneous myositis syndromes into mutually exclusive and stable phenotypes by using clinical and immune response features is useful for predicting clinical signs and symptoms, associated genetic and environmental risk factors, and responses to therapy and prognosis. Knowledge of myositis phenotypes should enhance clinicians ability to recognize and manage these rare disorders.
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Plasma proteomic profiles from disease-discordant monozygotic twins suggest that molecular pathways are shared in multiple systemic autoimmune diseases.
Arthritis Res. Ther.
PUBLISHED: 01-05-2011
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Although systemic autoimmune diseases (SAID) share many clinical and laboratory features, whether they also share some common features of pathogenesis remains unclear. We assessed plasma proteomic profiles among different SAID for evidence of common molecular pathways that could provide insights into pathogenic mechanisms shared by these diseases.
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Environmental factors preceding illness onset differ in phenotypes of the juvenile idiopathic inflammatory myopathies.
Rheumatology (Oxford)
PUBLISHED: 08-27-2010
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To assess whether certain environmental factors temporally associated with the onset of juvenile idiopathic inflammatory myopathies (JIIMs) differ between phenotypes.
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Inhibitor of NF-kappa B kinases alpha and beta are both essential for high mobility group box 1-mediated chemotaxis [corrected].
J. Immunol.
PUBLISHED: 03-15-2010
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Inhibitor of NF-kappaB kinases beta (IKKbeta) and alpha (IKKalpha) activate distinct NF-kappaB signaling modules. The IKKbeta/canonical NF-kappaB pathway rapidly responds to stress-like conditions, whereas the IKKalpha/noncanonical pathway controls adaptive immunity. Moreover, IKKalpha can attenuate IKKbeta-initiated inflammatory responses. High mobility group box 1 (HMGB1), a chromatin protein, is an extracellular signal of tissue damage-attracting cells in inflammation, tissue regeneration, and scar formation. We show that IKKalpha and IKKbeta are each critically important for HMGB1-elicited chemotaxis of fibroblasts, macrophages, and neutrophils in vitro and neutrophils in vivo. By time-lapse microscopy we dissected different parameters of the HMGB1 migration response and found that IKKalpha and IKKbeta are each essential to polarize cells toward HMGB1 and that each kinase also differentially affects cellular velocity in a time-dependent manner. In addition, HMGB1 modestly induces noncanonical IKKalpha-dependent p52 nuclear translocation and p52/RelB target gene expression. Akin to IKKalpha and IKKbeta, p52 and RelB are also required for HMGB1 chemotaxis, and p52 is essential for cellular orientation toward an HMGB1 gradient. RAGE, a ubiquitously expressed HMGB1 receptor, is required for HMGB1 chemotaxis. Moreover, IKKbeta, but not IKKalpha, is required for HMGB1 to induce RAGE mRNA, suggesting that RAGE is at least one IKKbeta target involved in HMGB1 migration responses, and in accord with these results enforced RAGE expression rescues the HMGB1 migration defect of IKKbeta, but not IKKalpha, null cells. Thus, proinflammatory HMGB1 chemotactic responses mechanistically require the differential collaboration of both IKK-dependent NF-kappaB signaling pathways.
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[Factors involved in the development of the community projects. Observational study of the Catalonian primary care centers AUPA network].
Aten Primaria
PUBLISHED: 02-04-2010
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To describe the characteristics of the AUPA Health Centres network, identify the favourable elements and the obstacles when carrying out community projects (CP), the impact of belonging to the AUPA network, and the types of support members expect from the AUPA Network.
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Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus.
Genome Res.
PUBLISHED: 12-22-2009
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Monozygotic (MZ) twins are partially concordant for most complex diseases, including autoimmune disorders. Whereas phenotypic concordance can be used to study heritability, discordance suggests the role of non-genetic factors. In autoimmune diseases, environmentally driven epigenetic changes are thought to contribute to their etiology. Here we report the first high-throughput and candidate sequence analyses of DNA methylation to investigate discordance for autoimmune disease in twins. We used a cohort of MZ twins discordant for three diseases whose clinical signs often overlap: systemic lupus erythematosus (SLE), rheumatoid arthritis, and dermatomyositis. Only MZ twins discordant for SLE featured widespread changes in the DNA methylation status of a significant number of genes. Gene ontology analysis revealed enrichment in categories associated with immune function. Individual analysis confirmed the existence of DNA methylation and expression changes in genes relevant to SLE pathogenesis. These changes occurred in parallel with a global decrease in the 5-methylcytosine content that was concomitantly accompanied with changes in DNA methylation and expression levels of ribosomal RNA genes, although no changes in repetitive sequences were found. Our findings not only identify potentially relevant DNA methylation markers for the clinical characterization of SLE patients but also support the notion that epigenetic changes may be critical in the clinical manifestations of autoimmune disease.
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Damage extent and predictors in adult and juvenile dermatomyositis and polymyositis as determined with the myositis damage index.
Arthritis Rheum.
PUBLISHED: 10-31-2009
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We undertook this study to validate the Myositis Damage Index (MDI) in juvenile and adult myositis, to describe the degree and types of damage and to develop predictors of damage.
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Immunogenetic risk and protective factors for the development of L-tryptophan-associated eosinophilia-myalgia syndrome and associated symptoms.
Arthritis Rheum.
PUBLISHED: 10-01-2009
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To assess L-tryptophan (LT) dose, age, sex, and immunogenetic markers as possible risk or protective factors for the development of LT-associated eosinophilia-myalgia syndrome (EMS) and related clinical findings.
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Genetic risk and protective factors for the idiopathic inflammatory myopathies.
Curr Rheumatol Rep
PUBLISHED: 08-21-2009
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The idiopathic inflammatory myopathies, or myositis syndromes, are heterogeneous autoimmune diseases defined by chronic muscle inflammation of unknown cause. They likely develop after the interaction of genetic and environmental risk factors in the absence of protective factors. The known genetic risk and protective factors are common alleles at polymorphic immune response loci and vary depending on phenotype. Furthermore, genetic associations are stronger with phenotypes defined by clinical features and autoantibodies than with myositis patients as a whole. Genetic factors for myositis also vary by age of onset, ethnicity, and environmental exposure group. Of interest, risk genes for one phenotype are often protective for another, possibly explaining the mutual exclusivity of many myositis subgroups. International collaborations using genome-wide association studies are needed to identify additional genes, gene-gene, and gene-environment interactions, all of which have pathogenic, therapeutic, and preventative implications for these increasingly recognized disorders.
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Ultraviolet radiation intensity predicts the relative distribution of dermatomyositis and anti-Mi-2 autoantibodies in women.
Arthritis Rheum.
PUBLISHED: 08-01-2009
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Because studies suggest that ultraviolet (UV) radiation modulates the myositis phenotype and Mi-2 autoantigen expression, we conducted a retrospective investigation to determine whether UV radiation may influence the relative prevalence of dermatomyositis and anti-Mi-2 autoantibodies in the US.
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Metabolic abnormalities and cardiovascular risk factors in children with myositis.
J. Pediatr.
PUBLISHED: 05-18-2009
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To characterize the metabolic abnormalities and risk factors for future cardiovascular disease in children with myositis.
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Review of the classification and assessment of the cutaneous manifestations of the idiopathic inflammatory myopathies.
Dermatol. Online J.
PUBLISHED: 04-02-2009
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Adult and juvenile dermatomyositis, polymyositis and myositis overlapping with another connective tissue disease are rare systemic autoimmune diseases with a primary feature of weakness and muscle inflammation. Cutaneous findings specific to the underlying condition are present in many patients with these disorders. Some lesions are highly characteristic of the idiopathic inflammatory myopathies (IIM), especially in dermatomyositis. Some cutaneous findings are common but not specific to the IIM and others are less frequently observed in patients with these illnesses. Many of these manifestations also have different grades of disease activity or damage. This photoessay reviews the classification and assessment of the cutaneous manifestations of the IIM and presents example photographs of many of the lesions of adult and juvenile IIM accumulated from the clinical experience of international experts in these conditions. The purpose of this work is to facilitate better recognition of the diverse cutaneous manifestations associated with these inflammatory myopathies.
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Photoessay of the cutaneous manifestations of the idiopathic inflammatory myopathies.
Dermatol. Online J.
PUBLISHED: 04-02-2009
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Adult and juvenile dermatomyositis, polymyositis and myositis overlapping with another connective tissue disease are rare systemic autoimmune diseases with a primary feature of weakness and muscle inflammation. Cutaneous findings specific to the underlying condition are present in many patients with these disorders. Some lesions are highly characteristic of the idiopathic inflammatory myopathies (IIM), especially in dermatomyositis. Some cutaneous findings are common but not specific to the IIM and others are less frequently observed in patients with these illnesses. Many of these manifestations also have different grades of disease activity or damage. This photoessay reviews the classification and assessment of the cutaneous manifestations of the IIM and presents example photographs of many of the lesions of adult and juvenile IIM accumulated from the clinical experience of international experts in these conditions. The purpose of this work is to facilitate better recognition of the diverse cutaneous manifestations associated with these inflammatory myopathies.
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HLA type and immune response to Borrelia burgdorferi outer surface protein a in people in whom arthritis developed after Lyme disease vaccination.
Arthritis Rheum.
PUBLISHED: 04-01-2009
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To investigate whether persons with treatment-resistant Lyme arthritis-associated HLA alleles might develop arthritis as a result of an autoimmune reaction triggered by Borrelia burgdorferi outer surface protein A (OspA), the Lyme disease vaccine antigen.
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Microstructure and mineral composition of dystrophic calcification associated with the idiopathic inflammatory myopathies.
Arthritis Res. Ther.
PUBLISHED: 02-24-2009
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Calcified deposits (CDs) in skin and muscles are common in juvenile dermatomyositis (DM), and less frequent in adult DM. Limited information exists about the microstructure and composition of these deposits, and no information is available on their elemental composition and contents, mineral density (MD) and stiffness. We determined the microstructure, chemical composition, MD and stiffness of CDs obtained from DM patients.
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On Determining the Effects of Therapy on Disease Damage in Non- randomized Studies with Multiple Treatments: A study of Juvenile Myositis.
Commun Stat Theory Methods
PUBLISHED: 01-01-2009
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This article discusses predicting damage in patients with juvenile myositis after treatment with various medications. These data were taken from medical records and not randomized. Investigators advocate using propensity scores for analysis of such non-randomized studies in order to reduce the effect of selection of treatment. Thus far, the studies have typically been comparing drug administration versus no drug after including a propensity score to compensate for potential bias in selecting patients for use of the agent. In this study, we use propensity scoring for multiple treatments given singly or in combination. We study two methods. We use a multiple logistic regression model with continuous propensity scores and a model that develops strata based on the dichotomous treatment assignment (received drug or not). We find the multiple logistic regression models predict damage better than the dichotomous model. In many cases, the propensity score also accounts for the effect of the treatment.
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Reversible left ventricular dysfunction and acute kidney injury in a patient with nonamyloid light chain deposition disease.
Clin. Nephrol.
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Non-amyloid light chain deposition disease (LCDD) is a rare entity that most commonly presents as proteinuria and/or renal dysfunction. We report on a patient who initially presented with acutely decompensated heart failure and subsequently developed nephrotic range proteinuria with attendant advanced renal dysfunction. The diagnosis of LCCD was made on renal biopsy.She was treated with five cycles of bortezomib and dexamethasone followed by cyclophosphamide priming for peripheral blood stem cell (PBSC) mobilization and auto logousstem cell transplant (ASCT). Four years later, she remains in very good partial response (VGPR) with a left ventricular ejection fraction (LVEF) of 58% and serum creatinine of 1.1 mg/dl. This observation supports the approach of aggressive management of patients with LCDD who have multiple organ failure.
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Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans.
Inhal Toxicol
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The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of the animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 µm in size were examined for endotracheal and and up to 5 µm for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model.
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Intestinal infarction and portal vein thrombosis in a patient with henoch schonlein purpura.
Case Rep Rheumatol
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Henoch Schonlein purpura is a systemic vasculitis that commonly affects children and teenagers but also affects adults of all ages. In most instances it has a benign course. Organ involvement, particularly in adults, and notably the kidneys and gastrointestinal tract may require therapeutic intervention and may have a less favorable outcome. We report a case of a 58-year-old man who presented with purpura and who rapidly developed catastrophic intestinal vasculitis, leading to his demise.
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Criteria for environmentally associated autoimmune diseases.
J. Autoimmun.
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Increasing evidence supports a role for the environment in the development of autoimmune diseases, as reviewed in the accompanying three papers from the National Institute of Environmental Health Sciences Expert Panel Workshop. An important unresolved issue, however, is the development of criteria for identifying autoimmune disease phenotypes for which the environment plays a causative role, herein referred to as environmentally associated autoimmune diseases. There are several different areas in which such criteria need to be developed, including: 1) identifying the necessary and sufficient data to define environmental risk factors for autoimmune diseases meeting current classification criteria; 2) establishing the existence of and criteria for new environmentally associated autoimmune disorders that do not meet current disease classification criteria; and 3) identifying in clinical practice specific environmental agents that induce autoimmune disease in individual patients. Here we discuss approaches that could be useful for developing criteria in these three areas, as well as factors that should be considered in evaluating the evidence for criteria that can distinguish individuals with such disorders from individuals without such disorders with high sensitivity and specificity. Current studies suggest that multiple lines of complementary evidence will be important and that in many cases there will be clinical, serologic, genetic, epigenetic, and/or other laboratory features that could be incorporated as criteria for environmentally associated autoimmune diseases to improve diagnosis and treatment and possibly allow for preventative strategies in the future.
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Epidemiology of environmental exposures and human autoimmune diseases: findings from a National Institute of Environmental Health Sciences Expert Panel Workshop.
J. Autoimmun.
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Autoimmune diseases (AID) are a collection of many complex disorders of unknown etiology resulting in immune responses to self-antigens and are thought to result from interactions between genetic and environmental factors. Here we review the epidemiologic evidence for the role of environmental factors in the development of human AID, the conclusions that can be drawn from the existing data, critical knowledge gaps, and research needed to fill these gaps and to resolve uncertainties. We specifically summarize the state of knowledge and our levels of confidence in the role of specific agents in the development of autoimmune diseases, and we define the areas of greatest impact for future investigations. Among our consensus findings we are confident that: 1) crystalline silica exposure can contribute to the development of several AID; 2) solvent exposure can contribute to the development of systemic sclerosis; 3) smoking can contribute to the development of seropositive rheumatoid arthritis; and 4) an inverse association exists between ultraviolet radiation exposure and the risk of development of multiple sclerosis. We suggest that more studies of phenotypes, genotypes, and multiple exposures are needed. Additional knowledge gaps needing investigation include: defining important windows in the timing of exposures and latencies relating to age, developmental state, and hormonal changes; understanding dose-response relationships; and elucidating mechanisms for disease development. Addressing these essential issues will require more resources to support research, particularly of rare AID, but knowledge of the risks conferred by environmental factors in specific genetic contexts could pave the way for prevention of AID in the future.
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Laboratory Test Abnormalities are Common in Polymyositis and Dermatomyositis and Differ Among Clinical and Demographic Groups.
Open Rheumatol J
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Given the difficulties regarding the interpretation of common laboratory test results in polymyositis (PM) and dermatomyositis (DM) in clinical practice, we assessed their range of abnormalities, differences among phenotypes and interrelationships in a large referral population.
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Childhood socioeconomic factors and perinatal characteristics influence development of rheumatoid arthritis in adulthood.
Ann. Rheum. Dis.
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Rheumatoid arthritis (RA) has been associated with lower socioeconomic status (SES), but the reasons for this are not known.
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New approaches to the assessment and treatment of the idiopathic inflammatory myopathies.
Ann. Rheum. Dis.
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The rarity and heterogeneity of the idiopathic inflammatory myopathies (IIM), and the few validated assessment tools available, have limited information to guide the management of patients with polymyositis, dermatomyositis or inclusion body myositis. In light of the need for such tools, the International Myositis Assessment and Clinical Studies Group (IMACS) was formed as a multidisciplinary consortium of rheumatologists, neurologists, dermatologists, physiatrists and other myositis experts to develop consensus and standards for the conduct and reporting of myositis studies, and to facilitate myositis research. IMACS has developed consensus core set measures of disease activity, disease damage and patient-reported outcomes, and compiled a preliminary definition of improvement. The IMACS tools assist in the evaluation of the extent of disease activity and damage, although other approaches--including key clinical features, laboratory tests, muscle T1 and short ? inversion recovery MRI and immunological markers--are also helpful. Clinical remission is a realistic objective for most patients and should be pursued aggressively to optimise outcomes. Physical therapy and rehabilitation should be applied early and consistently to achieve optimal strength and function. Treatments that have been developed for other immune-mediated diseases are also being used and tested in the IIM, and some have shown anecdotal evidence of benefit. Recent advances in understanding the pathogenesis of myositis, development of assessments and treatments for other diseases that can be applied to myositis, and international collaborations and consensus standards for evaluating the IIM, all promise improvements in the assessment and treatment of myositis in the future.
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Retroperitoneal mass in a patient with Wegeners granulomatosis.
Clin. Nephrol.
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Wegeners granulomatosis (WG) is a necrotizing vasculitis that classically involves the upper and lower respiratory tracts and kidneys. Uncommonly, other sites may also be involved. We report on a patient previously diagnosed with and treated for WG who presented with flank pain and on further imaging was found to have a retroperitoneal mass. A surgical specimen of the tissue revealed multiple foci of necrotizing vasculitis. Consideration should be given to the possibility that mass-like lesions in patients with WG may not be tumors since the management and outcome differ from that of an active vasculitis.
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Age-related somatic structural changes in the nuclear genome of human blood cells.
Am. J. Hum. Genet.
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Structural variations are among the most frequent interindividual genetic differences in the human genome. The frequency and distribution of de novo somatic structural variants in normal cells is, however, poorly explored. Using age-stratified cohorts of 318 monozygotic (MZ) twins and 296 single-born subjects, we describe age-related accumulation of copy-number variation in the nuclear genomes in vivo and frequency changes for both megabase- and kilobase-range variants. Megabase-range aberrations were found in 3.4% (9 of 264) of subjects ?60 years old; these subjects included 78 MZ twin pairs and 108 single-born individuals. No such findings were observed in 81 MZ pairs or 180 single-born subjects who were ?55 years old. Recurrent region- and gene-specific mutations, mostly deletions, were observed. Longitudinal analyses of 43 subjects whose data were collected 7-19 years apart suggest considerable variation in the rate of accumulation of clones carrying structural changes. Furthermore, the longitudinal analysis of individuals with structural aberrations suggests that there is a natural self-removal of aberrant cell clones from peripheral blood. In three healthy subjects, we detected somatic aberrations characteristic of patients with myelodysplastic syndrome. The recurrent rearrangements uncovered here are candidates for common age-related defects in human blood cells. We anticipate that extension of these results will allow determination of the genetic age of different somatic-cell lineages and estimation of possible individual differences between genetic and chronological age. Our work might also help to explain the cause of an age-related reduction in the number of cell clones in the blood; such a reduction is one of the hallmarks of immunosenescence.
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Partial nephrectomy for a large renal lymphatic malformation in a child presenting with hypertension.
J. Pediatr. Surg.
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A 9-year-old girl had hypertension (systolic blood pressure of 125 mm Hg) noted at an annual well child visit. An ultrasound study demonstrated a large right renal cystic mass. A partial nephrectomy was performed. The surgical specimen was 9.7 × 9.4 × 6.4 cm and weighed 413.2 g. The tumor stained diffusely positive for smooth muscle actin and focally positive for factor VIII. Final histologic diagnosis was primary intrarenal lymphatic malformation. The case is unusual because of the presentation, size of the mass, as well as the therapeutic approach of partial nephrectomy.
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Early Illness Features Associated with Mortality in the Juvenile Idiopathic Inflammatory Myopathies.
Arthritis Care Res (Hoboken)
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Objectives: Because juvenile idiopathic inflammatory myopathies (JIIM) are potentially life-threatening systemic autoimmune diseases, we examined risk factors for JIIM mortality. Methods: Mortality status was available for 405 patients (329 juvenile dermatomyositis [JDM], 30 juvenile polymyositis [JPM], 46 juvenile connective tissue disease-associated myositis [JCTM]) enrolled in nationwide protocols. Standardized mortality ratios (SMR) were calculated using United States population statistics. Cox regression was used to assess univariable associations with mortality, and random survival forest (RSF) classification and Cox regression for multivariable associations. Results: Of 17 deaths (4.2% overall mortality), 8 (2.4%) were in JDM patients. Death was related to the pulmonary system, primarily interstitial lung disease (ILD), in 7 patients, gastrointestinal in 3, multisystem in 3, and of unknown etiology in 4 patients. The SMR for JIIM overall was 14.4 [95% confidence interval (CI) 12.2, 16.5] and 8.3 [95% CI 6.4, 10.3] for JDM. The top mortality risk factors in the univariable analysis included clinical subgroup (JCTM, JPM), anti-synthetase autoantibodies, older age at diagnosis, ILD and Raynauds phenomenon at diagnosis. In multivariable analyses, clinical subgroup, illness severity at onset, age at diagnosis, weight loss and delay to diagnosis were the most important predictors from RSF; clinical subgroup and illness severity at onset were confirmed by multivariable Cox regression. Conclusions: Overall mortality was higher in JIIM patients, and several early illness features were identified as risk factors. Clinical subgroup, anti-synthetase autoantibodies, older age at diagnosis, and ILD are also recognized as mortality risk factors in adult myositis. © 2013 American College of Rheumatology.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.