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Katja Kobow Christopher A. Reid Erwin A. van Vliet Albert J. Becker Gemma L. Carvill Alica M. Goldman Shinichi Hirose Iscia Lopes-Cendes Hela Mrabet Khiari Annapurna Poduri Michael R. Johnson David C. Henshall 《Epileptic Disord》2020,22(2):127-141
Epigenetics refers broadly to processes that influence medium to long‐term gene expression by changing the readability and accessibility of the genetic code. The Neurobiology Commission of the International League Against Epilepsy (ILAE) recently convened a Task Force to explore and disseminate advances in epigenetics to better understand their role and intersection with genetics and the neurobiology of epilepsies and their co‐morbidities, and to accelerate translation of these findings into the development of better therapies. Here, we provide a topic primer on epigenetics, explaining the key processes and findings to date in experimental and human epilepsy. We review the growing list of genes with epigenetic functions that have been linked with epilepsy in humans. We consider potential practical applications, including using epigenetic signals as biomarkers for tissue‐ and biofluid‐based diagnostics and the prospects for developing epigenetic‐based treatments for epilepsy. We include a glossary of terms, FAQs and other supports to facilitate a broad understanding of the topic for the non‐expert. Last, we review the limitations, research gaps and the next challenges. In summary, epigenetic processes represent important mechanisms controlling the activity of genes, providing opportunities for insight into disease mechanisms, biomarkers and novel therapies for epilepsy. 相似文献
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PJ Commerford 《Cardiovascular journal of Africa》2015,26(4):151-Aug;26(4):151
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Vincent Laville Sigrid Le Clerc Khaled Ezzedine Randa Jdid Lieng Taing Toufik Labib Cdric Coulonges Damien Ulveling Pilar Galan Christiane Guinot Leopold Fezeu Frdrique Morizot Julie Latreille Denis Malvy Erwin Tschachler Jean‐Franois Zagury 《Experimental dermatology》2019,28(8):892-898
Sagging eyelid is considered as an outward of skin ageing and may cause medical issues. However, little is known about the factors involved in sagging eyelid. The study, which aims at determining genetic risk factors for eyelid sagging, was conducted in a cohort of 502 unrelated Caucasian women living in the Paris region. All included participants were aged between 44 and 70 years old (mean age, 57.6 years old). The severity of sagging eyelid was graded in 6 categories by a dermatologist using standardized photographs of the face. A genome wide association study adjusted on potential risk factors (including age and smoking habits) was conducted to identify genetic associations. Two single nucleotide polymorphisms in total linkage disequilibrium on chromosome 10, rs16927253 (P = 7.07 × 10‐10) and rs4746957 (P = 1.06 × 10‐8), were significantly associated with eyelid sagging severity. The rs16927253‐T and rs4746957‐A alleles showed a dominant protective effect towards eyelid sagging. These polymorphisms are located in intronic parts of the H2AFY2 gene which encodes a member of the H2A histone family and very close to the AIFM2 gene that induces apoptosis. Additionally, single nucleotide polymorphisms with a false discovery rate below 0.25 were located nearby the type XIII collagen COL13A1 gene on chromosome 10 and in the ADAMTS18 gene on chromosome 16. Several relevant genes were identified by the genome wide association study for their potential role in the sagging eyelid severity. 相似文献
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Petra Schwingenschuh Karoline Wenzel Petra Katschnig Ronald Saurugg Erwin Ott 《Movement disorders》2007,22(5):742-745
We describe a case of a palatal tic resembling palatal tremor (PT) in a young female patient with a previously unrecognized mild Tourette syndrome. At the time of her visit, the patient complained about ear clicks that were audible to others. We discuss the differential diagnoses of hyperkinetic palatal movements emphasizing the ongoing discussion about essential PT representing a more heterogeneous disorder than previously thought. 相似文献
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Hazel B Breitz Richard E Wendt Michael S Stabin Sui Shen William D Erwin Joseph G Rajendran Janet F Eary Lawrence Durack Ebrahim Delpassand William Martin Ruby F Meredith 《Journal of nuclear medicine》2006,47(3):534-542
166Ho-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate (DOTMP) is a tetraphosphonate molecule radiolabeled with 166Ho that localizes to bone surfaces. This study evaluated pharmacokinetics and radiation-absorbed dose to all organs from this beta-emitting radiopharmaceutical. METHODS: After two 1.1-GBq administrations of 166Ho-DOTMP, data from whole-body counting using a gamma-camera or uptake probe were assessed for reproducibility of whole-body retention in 12 patients with multiple myeloma. The radiation-absorbed dose to normal organs was estimated using MIRD methodology, applying residence times and S values for 166Ho. Marrow dose was estimated from measured activity retained after 18 h. The activity to deliver a therapeutic dose of 25 Gy to the marrow was determined. Methods based on region-of-interest (ROI) and whole-body clearance were evaluated to estimate kidney activity, because the radiotracer is rapidly excreted in the urine. The dose to the surface of the bladder wall was estimated using a dynamic bladder model. RESULTS: In clinical practice, gamma-camera methods were more reliable than uptake probe-based methods for whole-body counting. The intrapatient variability of dose calculations was less than 10% between the 2 tracer studies. Skeletal uptake of 166Ho-DOTMP varied from 19% to 39% (mean, 28%). The activity of 166Ho prescribed for therapy ranged from 38 to 67 GBq (1,030-1,810 mCi). After high-dose therapy, the estimates of absorbed dose to the kidney varied from 1.6 to 4 Gy using the whole-body clearance-based method and from 8.3 to 17.3 Gy using the ROI-based method. Bladder dose ranged from 10 to 20 Gy, bone surface dose ranged from 39 to 57 Gy, and doses to other organs were less than 2 Gy for all patients. Repetitive administration had no impact on tracer biodistribution, pharmacokinetics, or organ dose. CONCLUSION: Pharmacokinetics analysis validated gamma-camera whole-body counting of 166Ho as an appropriate approach to assess clearance and to estimate radiation-absorbed dose to normal organs except the kidneys. Quantitative gamma-camera imaging is difficult and requires scatter subtraction because of the multiple energy emissions of 166Ho. Kidney dose estimates were approximately 5-fold higher when the ROI-based method was used rather than the clearance-based model, and neither appeared reliable. In future clinical trials with 166Ho-DOTMP, we recommend that dose estimation based on the methods described here be used for all organs except the kidneys. Assumptions for the kidney dose require further evaluation. 相似文献
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The hypothesis that some of ethanol's acute effects are mediated via neurotensinergic systems was investigated by characterizing neurotensin (NT) receptors in mice (LS and SS) selectively bred for differences in sensitivity to ethanol. [3H]Neurotensin binding in brain membranes from both mouse lines was specific, saturable, reversible, and linear with protein concentrations. Subcellular localization studies showed specific NT binding to be concentrated in the microsomal/synaptosomal fractions. Scatchard analyses of [3H]NT binding indicated similar KD values for membranes from various brain regions of LS and SS mice. However, Bmax values in frontal cortex, cerebellum, and striatum were greater in SS than in LS mice. In competitive binding studies IC50 values were lower for NT8-13 than for NT1-13, and IC50 values for NT1-8, NT1-11, D-Trp11-NT, and D-Tyr11-NT were greater than 1000 nM. Association and dissociation rate constants for [3H]NT and resulting KD values (0.8 nM) were similar for LS and SS brain membranes. Ethanol, in vitro, had no effect on NT binding characteristics, but as expected various cations markedly increased KD values. 相似文献
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Shlomo Matalon Hagay Slutzky Erwin I Weiss 《American journal of orthodontics and dentofacial orthopedics》2005,127(1):56-63
BACKGROUND: White spot lesions are observed in nearly 50% of patients undergoing orthodontic treatment. Long-lasting antibacterial properties of orthodontic cements can reduce this phenomenon. METHODS: The antibacterial properties of 4 orthodontic cements were evaluated by direct contact test (DCT) and agar diffusion test (ADT). With the DCT technique, octet specimens of glass ionomer (CX-Plus; Shofu, Kyoto, Japan), reinforced glass ionomer (GC Fuji ORTHO LC; GC Corporation, Tokyo, Japan), and 2 composite (Transbond XT and Transbond Plus; 3M Unitek, Monrovia, Calif) orthodontic cements were placed on the sidewalls of wells of a 96-microtiter plate. Streptococcus mutans cells (ca. 1 x 10(6) ) were placed on the surface of each specimen for 1 hour at 37 degrees C. Then, fresh media was added to each well, and bacterial growth was monitored for 16 hours with a temperature-controlled spectrophotometer. This was repeated on specimens aged in phosphate-buffered saline for 1 day, 1 week, and 1 month. The ADT was performed by placing specimens in wells punched in agar plates. RESULTS: Measurement of the halo in bacterial lawn after 48 hours showed that only the glass ionomer cement (CX-Plus) produced an inhibition zone (1.2 mm around the sample). Results at the DCT showed that only the reinforced glass ionomer cement (GC Fuji ORTHO LC) exhibited potent antibacterial activity, which lasted 1 week and diminished over the next 3 weeks. CONCLUSIONS: The reinforced glass ionomer cement possessed the most potent and long-lasting antibacterial activity. 相似文献