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41.
Pinto D Kasteleijn-Nolst Trenité DG Cordell HJ Mattheisen M Strauch K Lindhout D Koeleman BP 《Genetic epidemiology》2007,31(1):42-50
In traits suspected to be governed by at least two loci, linkage analysis incorporating the joint action of both loci may improve the power to detect linkage, increase the precision of estimating locus positions and provide insight into the underlying etiological mechanism. Recently, we mapped two susceptibility loci for epilepsy-related photosensitivity (or photoparoxysmal response, PPR) at regions 7q32 (PPR1) and 16p13 (PPR2) in PPR families with prominent myoclonic seizures background (MS-related PPR). To follow-up these results and evaluate interaction effects between these regions, we conducted two-locus (2L) linkage analyses using parametric and non-parametric methods. The 2L linkage was calculated under a multiplicative (MULT) epistasis model, encompassing models where each locus is necessary but not sufficient for MS-related PPR and a heterogeneity (HET) model, encompassing models in which each locus is by itself sufficient but not necessary for MS-related PPR expression. We found maximal 2L linkage under the (MULT) model, which was significantly better than the 2L linkage under the (HET) model (P = 0.001). The 2L analyses gave no increase in power to detect linkage over the single-locus analyses nor did they improve location estimates at PPR1 and PPR2, as expected under a best-fit 2L (MULT) model in an affecteds-only analysis. Our findings suggest that the genes underlying the PPR1 and PPR2 susceptibility loci may have similar functions or act in the same biochemical pathway. 相似文献
42.
Treatment of experimental asthma by decoy-mediated local inhibition of activator protein-1 总被引:4,自引:0,他引:4
43.
Increased endogenous antigen presentation in the periphery enhances susceptibility to inflammation‐induced gastric autoimmunity in mice
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Sarah A. Overall Dorothée Bourges Ian R. van Driel Paul A. Gleeson 《European journal of immunology》2017,47(1):155-167
How the immune system maintains peripheral tolerance under inflammatory conditions is poorly understood. Here we assessed the fate of gastritogenic T cells following inflammatory activation in vivo. Self‐reactive T cells (A23 T cells) specific for the gastric H+/K+ ATPase α subunit (HKα) were transferred into immunosufficient recipient mice and immunised at a site distant to the stomach with adjuvant containing the cognate HKα peptide antigen. Activation of A23 T cells by immunisation did not impact on either immune tolerance or protection from gastric autoimmunity in wild‐type BALB/c mice. However, increased presentation of endogenously derived HKα epitopes by dendritic cells (DCs) in the gastric lymph node of IE‐H+/K+β transgenic mice (IEβ) reduces A23 T‐cell tolerance to gastric antigens after inflammatory activation, with subsequent development of gastritis. While HKα‐specific A23 T cells from immunised wild‐type mice were poorly responsive to in vitro antigen specific activation, A23 T cells from immunised IEβ transgenic mice were readily re‐activated, indicating loss of T‐cell anergy. These findings show that DCs of gastric lymph nodes can maintain tolerance of pathogenic T cells following inflammatory stimulation and that the density of endogenous antigen presented to self‐reactive T cells is critical in the balance between tolerance and autoimmunity. 相似文献
44.
45.
Christiane Margue Susanne Reinsbach Demetra Philippidou Nicolas Beaume Casandra Walters Jochen G. Schneider Dorothée Nashan Iris Behrmann Stephanie Kreis 《Oncotarget》2015,6(14):12110-12127
MiRNAs are increasingly recognized as biomarkers for the diagnosis of cancers where they are profiled from tumor tissue (intracellular miRNAs) or serum/plasma samples (extracellular miRNAs). To improve detection of reliable biomarkers from blood samples, we first compiled a healthy reference miRNome and established a well-controlled analysis pipeline allowing for standardized quantification of circulating miRNAs. Using whole miRNome and custom qPCR arrays, miRNA expression profiles were analyzed in 126 serum, whole blood and tissue samples of healthy volunteers and melanoma patients and in primary melanocyte and keratinocyte cell lines. We found characteristic signatures with excellent prognostic scores only in late stage but not in early stage melanoma patients. Upon comparison of melanoma tissue miRNomes with matching serum samples, several miRNAs were identified to be exclusively tissue-derived (miR-30b-5p, miR-374a-5p and others) while others had higher expression levels in serum (miR-3201 and miR-122-5p). Here we have compiled a healthy and widely applicable miRNome from serum samples and we provide strong evidence that levels of cell-free miRNAs only change significantly at later stages of melanoma progression, which has serious implications for miRNA biomarker studies in cancer. 相似文献
46.
Krummel T Bazin D Faller AL Hannedouche T 《Presse medicale (Paris, France : 1983)》2012,41(2):116-124
Hypertensive nephrosclerosis is the leading cause of end stage renal disease (ESRD) in France, however, in prospective clinical trials of hypertension, ESRD accounts only for a small fraction of all events (incidence rate 0.2 to 0.4% by year). Hypertensive nephrosclerosis is characterized histologically by a series of vascular injury, none of which is truly specific and that can be observed also in obesity or normal aging. Hypertensive nephrosclerosis is mildly symptomatic, but the prognosis is never benign, due to cardiovascular and renal burden. This unspecific presentation may explain why the diagnosis of hypertensive nephrosclerosis is easily carried by excess, the main differential diagnoses are atherosclerotic ischemic renal disease, poorly symptomatic primitive nephropathies or the sequelae of unnoticed malignant hypertensive nephrosclerosis. The very high prevalence of hypertensive nephrosclerosis in populations from African ancestry has suggested a genetic predisposition. MYH9/APOL1 gene variants have recently been identified and are strongly associated with hypertensive nephrosclerosis, however the pathophysiological link between these variants and renal disease is still unclear. The treatment is mainly based on blocking the renin angiotensin system, especially when proteinuria is present. The target blood pressure is less firmly established, the latest data from the AASK study, however, do suggest a benefit on progression of lower values < 135/80 or even < 130/80 mmHg, especially in patients with proteinuria. 相似文献
47.
Jan Kassubek Alexander Unrath Hans-Jürgen Huppertz Dorothée Lulé Thomas Ethofer Anne-Dorte Sperfeld Albert C Ludolph 《Amyotrophic lateral sclerosis and other motor neuron disorders》2005,6(4):213-220
In ALS, advanced magnetic resonance imaging (MRI) techniques are increasingly used to investigate the underlying pathology. In this study, the technique of voxel-based morphometry (VBM) was applied to 3-D MRI data in ALS patients to localize regional grey and white matter changes. Twenty-two ALS patients (mean age 58+/-9 years) with clinically definite ALS by revised El Escorial criteria were studied. None of the patients had any signs of associated frontotemporal dementia. High-resolution 3-D MRI data sets of the whole brain, collected on a 1.5 T scanner, were analysed by statistical parametric mapping (SPM) and VBM in comparison to an age-matched normal data base consisting of 22 healthy volunteers (mean age 59+/-11 years), for grey matter and white matter segments separately. Global brain atrophy was assessed by calculation of brain parenchymal fractions (BPF). In ALS patients, BPF were significantly reduced compared to controls (p = 0.0003), indicating global brain atrophy. Regional decreases of grey matter density were found in the ALS patients at corrected p<0.01 in the right-hemispheric primary motor cortex (area of the highest Z-score) and in the left medial frontal gyrus. Furthermore, regional white matter alterations were observed along the corticospinal tracts bilaterally and in multiple smaller areas including corpus callosum, cerebellum, frontal and occipital subcortical regions. Besides considerable global atrophy in ALS, the topography of ALS-associated cerebral morphological changes could be mapped using VBM, in particular white matter signal changes along the bilateral corticospinal tracts, but also in extra-motor areas. VBM might be a potential tool to visualize disease progression in future longitudinal studies. 相似文献
48.
Pieper S Out D Bakermans-Kranenburg MJ van Ijzendoorn MH 《Journal of traumatic stress》2011,24(4):373-380
We evaluated the role of the serotonin transporter gene promoter polymorphism (5-HTTLPR) in the etiology of dissociation. Adult twin pairs (N = 184 pairs; mean age 33.0 years, SD = 10.8) completed measures for dissociation and trauma. The DNA samples were genotyped for 5-HTTLPR adjusted for rs25531 alleles. Behavioral genetic analyses showed that genetic factors explained 45% of the variance in dissociative symptoms, while 55% of the variance was explained by unique environment and measurement error. Participants with the SS genotype of 5-HTTLPR reported more dissociative symptoms compared to participants with the other genotypes (p = .02), and they showed more pathological dissociative symptoms than the other participants (p = .04) when they reported more depressive symptoms and when they had experienced trauma. 相似文献
49.
50.
Nashan D Müller ML Braun-Falco M Reichenberger S Szeimies RM Bruckner-Tuderman L 《Journal of cancer research and clinical oncology》2009,135(1):1-14
Background Up to 10% of all visceral malignancies develop cutaneous metastases. As cutaneous metastases are underestimated and underdiagnosed
they can be a clinical challenge. The clinical appearance and patterns of distribution of cutaneous metastases, the characterisation
of clinical outcomes and available therapeutic options are compiled.
Patients and methods Literature (over the last 6 years) MESH in terms of cutaneous metastases was comprehensively evaluated. Characteristics from
92 available cases are elaborated and adjusted with terms (time unlimited) of published epidemiological reviews to single
organs.
Results The broad clinical spectrum with differential diagnoses is displayed. An allocation of cutaneous metastases and a particular
organ is not reliable. In 22% of all cases cutaneous metastases can lead to the diagnosis of an internal malignoma. The majority
of cases reveal cutaneous metastases to emerge in a tumour-free interval in about 36 months, after a successful treatment
of the primary tumour, most commonly along with other organ metastases. Probable survival turned out to be less than 12 months.
Consistently with this end-stage condition, treatment aligns with rules of palliation. Local treatment of choice is excision.
Only a minority of investigators attempted to come up with tumour-specific treatment strategies, and almost no randomised
therapy studies can be presented.
Conclusion A reference guide of cutaneous metastases is given; the clinical spectrum is adjusted to an actual status; state of the art
of the treatment is accomplished. An epidemiological, improved registration and diagnostic work-up for targeted therapies
in conjunction with dermatologists are favoured. 相似文献