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91.
Jockers-Scherübl MC Bauer A Kuhn S Reischies F Danker-Hopfe H Schmidt LG Rentzsch J Hellweg R 《Neuroscience letters》2007,419(1):78-82
Long-term alcohol abuse has deleterious effects on the peripheral and central nervous system. Nerve growth factor (NGF) is a pleiotropic neurotrophic protein involved in development, maintenance of function and regeneration of nerve cells. We examined patients in different stages of alcohol disease and measured their NGF serum concentrations based on the hypothesis that these reflect the state of disease. We examined 57 patients suffering from alcohol-dependence for more than 2 years (DSM IV) on day 8 of a qualified withdrawal, 18 patients with Korsakoff's syndrome and 40 healthy controls. In addition to clinical examination, careful history taking and a standard neuropsychological test battery, serum NGF concentrations were measured by a highly sensitive enzyme-immunoassay. Of the 57 patients 9 had suffered from severe withdrawal delirium in the past, other clinical parameters were alike. Cognitive test performance did not differ from the control group. Mean NGF levels of controls amounted to 42.1pg/ml (S.D. 68.0); mean levels of patients with alcohol dependence were raised significantly to 401.5pg/ml (S.D. 932.6) without delirium in the past and even further to 3292.5pg/ml (S.D. 4879.6) with former withdrawal delirium. By contrast, patients with persistent amnestic disorder (Korsakoff's syndrome) showed values identical to the controls. NGF serum levels were significantly elevated in alcohol-dependent patients, more so in those with prior delirium. Their cognitive tests being normal, this possibly reflects the activity of NGF as an endogenous repair mechanism for damaged neurons. In accordance with this hypothesis, NGF values are "normal" in patients with persistent alcohol-related cognitive decline. 相似文献
92.
Stertz S Reichelt M Spiegel M Kuri T Martínez-Sobrido L García-Sastre A Weber F Kochs G 《Virology》2007,361(2):304-315
In this study, we analyzed the replication and budding sites of severe acute respiratory syndrome coronavirus (SARS-CoV) at early time points of infection. We detected cytoplasmic accumulations containing the viral nucleocapsid protein, viral RNA and the non-structural protein nsp3. Using EM techniques, we found that these putative viral replication sites were associated with characteristic membrane tubules and double membrane vesicles that most probably originated from ER cisternae. In addition to its presence at the replication sites, N also accumulated in the Golgi region and colocalized with the viral spike protein. Immuno-EM revealed that budding occurred at membranes of the ERGIC (ER-Golgi intermediate compartment) and the Golgi region as early as 3 h post infection, demonstrating that SARS-CoV replicates surprisingly fast. Our data suggest that SARS-CoV establishes replication complexes at ER-derived membranes. Later on, viral nucleocapsids have to be transported to the budding sites in the Golgi region where the viral glycoproteins accumulate and particle formation occurs. 相似文献
93.
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94.
95.
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
96.
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
97.
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
98.
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
99.
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100.