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101.
Zenker M Horn D Wieczorek D Allanson J Pauli S van der Burgt I Doerr HG Gaspar H Hofbeck M Gillessen-Kaesbach G Koch A Meinecke P Mundlos S Nowka A Rauch A Reif S von Schnakenburg C Seidel H Wehner LE Zweier C Bauhuber S Matejas V Kratz CP Thomas C Kutsche K 《Journal of medical genetics》2007,44(10):651-656
Background
Heterozygous gain‐of‐function mutations in various genes encoding proteins of the Ras‐MAPK signalling cascade have been identified as the genetic basis of Noonan syndrome (NS) and cardio‐facio‐cutaneous syndrome (CFCS). Mutations of SOS1, the gene encoding a guanine nucleotide exchange factor for Ras, have been the most recent discoveries in patients with NS, but this gene has not been studied in patients with CFCS.Methods and results
We investigated SOS1 in a large cohort of patients with disorders of the NS–CFCS spectrum, who had previously tested negative for mutations in PTPN11, KRAS, BRAF, MEK1 and MEK2. Missense mutations of SOS1 were discovered in 28% of patients with NS. In contrast, none of the patients classified as having CFCS was found to carry a pathogenic sequence change in this gene.Conclusion
We have confirmed SOS1 as the second major gene for NS. Patients carrying mutations in this gene have a distinctive phenotype with frequent ectodermal anomalies such as keratosis pilaris and curly hair. However, the clinical picture associated with SOS1 mutations is different from that of CFCS. These findings corroborate that, despite being caused by gain‐of‐function mutations in molecules belonging to the same pathway, NS and CFCS scarcely overlap genotypically. 相似文献102.
103.
104.
Andre C. Felicio MD PhD Katherine Dinelle MSc Pankaj A. Agarwal MD DNB DM Jessamyn McKenzie LPN Nicole Heffernan RN Jeremy D. Road MD Silke Appel‐Cresswell MD Zbigniew K. Wszolek MD Matthew J. Farrer PhD Michael Schulzer MD PhD Vesna Sossi PhD A. Jon Stoessl CM MD FRCPC 《Movement disorders》2014,29(9):1197-1201
105.
Malte A. Kluger Michael Luig Claudia Wegscheid Boeren Goerke Hans-Joachim Paust Silke R. Brix Isabell Yan Hans-Willi Mittrücker Beate Hagl Ellen D. Renner Gisa Tiegs Thorsten Wiech Rolf A.K. Stahl Ulf Panzer Oliver M. Steinmetz 《Journal of the American Society of Nephrology : JASN》2014,25(6):1291-1302
106.
Ursula G. Sauer Sandra Vogel Alexandra Aumann Annemarie Hess Susanne N. Kolle Lan Ma-Hock Wendel Wohlleben Martina Dammann Volker Strauss Silke Treumann Sibylle Gröters Karin Wiench Bennard van Ravenzwaay Robert Landsiedel 《Toxicology and applied pharmacology》2014
The applicability of rat precision-cut lung slices (PCLuS) in detecting nanomaterial (NM) toxicity to the respiratory tract was investigated evaluating sixteen OECD reference NMs (TiO2, ZnO, CeO2, SiO2, Ag, multi-walled carbon nanotubes (MWCNTs)). Upon 24-hour test substance exposure, the PCLuS system was able to detect early events of NM toxicity: total protein, reduction in mitochondrial activity, caspase-3/-7 activation, glutathione depletion/increase, cytokine induction, and histopathological evaluation. Ion shedding NMS (ZnO and Ag) induced severe tissue destruction detected by the loss of total protein. Two anatase TiO2 NMs, CeO2 NMs, and two MWCNT caused significant (determined by trend analysis) cytotoxicity in the WST-1 assay. At non-cytotoxic concentrations, different TiO2 NMs and one MWCNT increased GSH levels, presumably a defense response to reactive oxygen species, and these substances further induced a variety of cytokines. One of the SiO2 NMs increased caspase-3/-7 activities at non-cytotoxic levels, and one rutile TiO2 only induced cytokines. Investigating these effects is, however, not sufficient to predict apical effects found in vivo. Reproducibility of test substance measurements was not fully satisfactory, especially in the GSH and cytokine assays. Effects were frequently observed in negative controls pointing to tissue slice vulnerability even though prepared and handled with utmost care. Comparisons of the effects observed in the PCLuS to in vivo effects reveal some concordances for the metal oxide NMs, but less so for the MWCNT. The highest effective dosages, however, exceeded those reported for rat short-term inhalation studies. To become applicable for NM testing, the PCLuS system requires test protocol optimization. 相似文献
107.
Ester Lovsin Barle Gian Christian Winkler Peter Ulrich Christopher Perino Martin Kuster Alessandro Probst Silke Thielen Rudolf Bechter 《Regulatory toxicology and pharmacology : RTP》2014
During the chemical and pharmaceutical production of active pharmaceutical substances which are intended for immunosuppressive therapy, the employees may be exposed to these substances via inhalation. Immunosuppressants are linked to development of certain types of cancers e.g., lymphoma or skin cancer in transplant patients. The development of these cancers in patients is linked to the level of immunosuppression needed for transplantation in order to avoid organ rejection. Below these levels, with the immune system functioning uninhibited, cancer is unlikely to develop. 相似文献
108.
Dr. Silke Kuhn Dr. Jens Kalke Sven Buth Dr. Philipp Hiller Prof. Dr. Jens Reimer 《Pr?vention und Gesundheitsf?rderung》2014,9(2):104-110
Objective
Based on the initial survey of the project “Strengthen parents for dealing with the alcohol consumption of their children” parental style was quantified. The survey addressed the following issues: 1. The parents information of the alcohol consumption of their adolescents. 2. Adequate rules when dealing with the alcohol consumption of their children. 3. Parent?s reactions to a potential intoxication of their children.Method
2,793 parents of students in grades 8–10 were surveyed in Baden-Württemberg, Berlin, Saxony and Schleswig-Holstein. The questionnaires were passed back through the teachers. The questionnaires were collected by the teachers.Results
The results show that parents feel well informed about alcohol related education of children. 71?% use the internet as an information source. Approx. 95?% of the parents have talked with their children about alcohol consumption, particularly adviced them of health damages and development of dependence. Those rules of behavior guaranteeing a safe way home are favored by parents. In response to rule violations the parents talk with their children first. The comparison with current youth surveys shows that parents underestimate their children?s drinking.Conclusions
Alcohol and its consequences are a topic of conversation among parents and children. The parents need support to argue objectively and according to youth. The Internet should be used for drug prevention education activities. 相似文献109.
110.
The color complementation assay (CCA) is a method of allele-specific DNA amplification by which competitive priming and extension of fluorescently labeled oligonucleotide primers determine the color of DNA amplification product. This diagnostic method precludes the need for radioisotopes, electrophoresis, and multiple high-stringency reaction conditions. The multiplicity of mutant globin genes present in Southeast Asians complicates clinical diagnosis and underscores the importance of DNA-based diagnostic methods. We have applied CCA to distinguish beta A and beta E alleles. Competing 15mer primers were a fluorescein-labeled complement to beta A and a rhodamine-labeled complement to beta E, identical except for their central nucleotides. A common unlabeled primer was used to amplify DNA product, the color of which was determined by the perfectly complementary primer. Color photography and spectrofluorometry, as well as a method of black-white photography that we developed to distinguish fluorescein- and rhodamine- labeled DNA, were used to record results. We applied CCA to define the complex genotype of a Thai woman with thalassemia intermedia, 96% HbE, and 4% HbF whose possible genotypes included several permutations of alpha-thalassemia, beta-thalassemia, and beta E genes. zeta-Globin gene mapping of DNA doubly digested with Bg/II and Asp 718 showed the -alpha 3.7/--SEA genotype, and CCA confirmed homozygous beta E/beta E. The CCA is useful for diagnosing the compound hemoglobin genotypes of Southeast Asians and could be applied also to prenatal diagnosis in this population. 相似文献