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71.
72.
Wilson disease: novel mutations in the ATP7B gene and clinical correlation in Brazilian patients 总被引:1,自引:0,他引:1
Deguti MM Genschel J Cancado EL Barbosa ER Bochow B Mucenic M Porta G Lochs H Carrilho FJ Schmidt HH 《Human mutation》2004,23(4):398
Wilson disease (WD) is a rare inherited autosomal recessive disorder caused by a defect in a metal transporting P-type ATPase, resulting in copper overload in various tissues and cells. The aim was to assess both the phenotype in Brazilian WD patients and the corresponding ATP7B genotype. Sixty subjects belonging to 46 pedigrees diagnosed as WD were included in this study. Direct sequencing of all 21 exons within ATP7B and their flanking introns was performed. Demographic, clinical, laboratory and histopathological data at the time of diagnosis were obtained. We identified twenty-five mutations, twelve of them reported for the first time. The c.3402delC mutation had the highest allelic frequency (30.8%), followed by the c.2123T>C (p.L708P) (16.7%). Exons 8 and 15 were the site of 62.5% of the mutations. The common European mutation c.3207C>A (p.H1069Q) was not present at all. Phenotype varied greatly among individuals with the same ATP7B genotype. Our data confirm the heterogeneity of ATP7B genotype in Brazilian WD patients. The mutational spectrum is compatible with the Brazilian history of Mediterranean immigration; however, new mutations, and different frequencies and phenotype associated with the previously known mutations characterize this population. Exons 8 and 15 should be preferentially screened in WD cases from Brazil. Phenotype variation among subjects with the same ATP7B genotype suggests that modifying factors play an additional role in the pathogenesis of WD. 相似文献
73.
Chwieralski CE Schnurra I Thim L Hoffmann W 《American journal of respiratory cell and molecular biology》2004,31(5):528-537
Injured areas of the respiratory epithelium are subject to rapid repair by the migration of adjacent epithelial cells, a process termed "restitution". Rapid re-epithelialization is promoted by interactions between migrating cells and the extracellular matrix proteins. Furthermore, epidermal growth factor (EGF) as well as trefoil factor family (TFF) peptides are well known regulators of epithelial restitution due to their motogenic effects. Migration of the human bronchial epithelial cell line BEAS-2B in modified Boyden chambers was used as a model system for airway restitution. EGF or recombinant human TFF2 or TFF3 showed mainly chemotactic activity. The motogenic response was strictly dependent upon a haptotactic substrate, but to different degrees. EGF induced phosphorylation of extracellular signal-regulated kinases (ERK) 1/2, c-Jun-N-terminal kinase, p38, Akt, and p70S6K in BEAS-2B cells. Using specific inhibitors, the signaling cascades responsible for the motogenic response were shown to differ drastically when EGF was compared with TFF2. The motogenic effect of TFF2 was previously demonstrated to depend on ERK1/2 and protein kinase C activation; whereas the EGF-triggered motogenic response was completely independent of ERK1/2 activation but sensitive to the inhibition of phosphoinositide 3-kinase, p38, protein kinase C, or nuclear factor kappaB. However, the motogenic effects of EGF and TFF2 are additive. These data suggest that luminal EGF and TFF peptides can act synergistically in the human respiratory epithelium to enhance rapid repair processes in the course of diseases such as asthma. 相似文献
74.
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76.
A Serda Kantarcio?lu Teun Boekhout G Sybren De Hoog Bart Theelen Ayhan Yücel Tuba R Ekmekci Bettina C Fries Reiko Ikeda Adem Koslu Kemal Altas 《Medical mycology》2007,45(2):173-181
Environmental fungi, in particular primary pathogens and Cryptococcus spp. can be responsible for skin lesions mimicking sporotrichosis. In this paper, we report a case of subcutaneous cryptococcosis in an apparently healthy, young male patient due to a non-C. neoformans Cryptococcus species, C. diffluens. The isolate showed in vitro phenotypic switching that may affect virulence and host inflammatory and immune responses, and in vitro resistance to amphotericin B and 5-flucytosin. This species shares several phenotypic traits with C. neoformans, and, therefore, decisive diagnosis should be based on biopsy and culturing results followed by molecular identification. 相似文献
77.
S. Liendl C. J. Lauer R. M. Hoffmann 《Somnologie - Schlafforschung und Schlafmedizin》2004,8(3):67-70
Summary
Question of the study Sleep logs are common tools in sleep research and clinical routine. Usually sleep logs have to be completed during a 2-week
period, with the first week serving as an adaptation to the instrument itself. In the present study, we investigated whether
there is indeed such an adaptation bias or not.
Patients and methods A total of 236 chronically sleep-disordered outpatients completed the standardized sleep log ‘Abend-Morgen-Protokoll’ during
a 2-week pre-screening period prior to the first visit in our sleep ambulance. Two sets of items were established, the ‘instrumental’
and the ‘therapeutic’ set. The respective ratings of the first and second week (week A, B) were compared to evaluate clinically
relevant changes.
Results The ratings of several ‘instrumental’ items significantly differed between week A and B. However, these changes—on average—were
only marginal and therefore of little clinical importance. Regarding the ‘therapeutic’ set of items, no systematic variations
could be ascertained over the assessment period.
Conclusion The present investigation could not confirm the presence of adaptation biases (instrumental, therapeutic) in a large sample
of chronically sleep-disordered outpatients. Therefore, we consider a 1-week pre-screening period via sleep log as sufficient
for the diagnostic process in these patients.
相似文献
78.
Novel mouse model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis 下载免费PDF全文
Hoffmann N Rasmussen TB Jensen PØ Stub C Hentzer M Molin S Ciofu O Givskov M Johansen HK Høiby N 《Infection and immunity》2005,73(4):2504-2514
Pseudomonas aeruginosa causes a chronic infection in the lungs of cystic fibrosis (CF) patients by establishing an alginate-containing biofilm. The infection has been studied in several animal models; however, most of the models required artificial embedding of the bacteria. We present here a new pulmonary mouse model without artificial embedding. The model is based on a stable mucoid CF sputum isolate (NH57388A) with hyperproduction of alginate due to a deletion in mucA and functional N-acylhomoserine lactone (AHL)-based quorum-sensing systems. Chronic lung infection could be established in both CF mice (Cftr(tmlUnc-/-)) and BALB/c mice, as reflected by the detection of a high number of P. aeruginosa organisms in the lung homogenates at 7 days postinfection and alginate biofilms, surrounded by polymorphonuclear leukocytes in the alveoli. In comparison, both an AHL-producing nonmucoid revertant (NH57388C) from the mucoid isolate (NH57388A) and a nonmucoid isolate (NH57388B) deficient in AHL were almost cleared from the lungs of the mice. This model, in which P. aeruginosa is protected against the defense system of the lung by alginate, is similar to the clinical situation. Therefore, the mouse model provides an improved method for evaluating the interaction between mucoid P. aeruginosa, the host, and antibacterial therapy. 相似文献
79.
Site-independent prognostic value of chromosome 9q loss in primary gastrointestinal stromal tumours 总被引:5,自引:0,他引:5
Gunawan B Schulten HJ von Heydebreck A Schmidt B Enders C Höer J Langer C Schüler P Schindler CG Kuhlgatz J Füzesi L 《The Journal of pathology》2004,202(4):421-429
Although the significance of tumour site for estimating malignant potential in gastrointestinal stromal tumours (GISTs) has recently been recognized, site-specific genetic patterns have not to date been defined. This study examined 52 c-kit-positive primary GISTs (with a mean follow-up of 42.3 months in 51 cases) from three different locations (35 gastric, 12 small intestinal, and five colorectal) using comparative genomic hybridization (CGH). In general, tumour site correlated with key prognostic factors, including tumour size, mitotic rate, proliferative activity, and probable malignant potential. Furthermore, several DNA copy number changes showed a site-dependent pattern. These included losses at 14q (gastric 83%, intestinal 35%; p = 0.001), losses at 22q (gastric 46%, intestinal 82%; p = 0.02), losses at 1p (gastric 23%, intestinal 88%; p = 1 x 10(-5)), losses at 15q (gastric 14%, intestinal 59%; p = 0.002), losses at 9q (gastric 14%, intestinal 53%; p = 0.006), and gains at 5p (gastric 11%, intestinal 53%; p = 0.002). These data demonstrate strong site-dependent genetic heterogeneity in GISTs that may form a basis for subclassification. Prognostic evaluation of DNA copy number changes identified losses at 9q as a site-independent prognostic marker associated with shorter disease-free survival (p = 0.03) and overall survival (p = 0.002). Furthermore, 9q loss also appeared to carry prognostic value in predicting overall survival for patients with advanced or progressive GISTs (p = 0.003). 相似文献
80.
Update on Pneumocystis carinii f. sp. hominis Typing Based on Nucleotide Sequence Variations in Internal Transcribed Spacer Regions of rRNA Genes 总被引:6,自引:0,他引:6 下载免费PDF全文
Chao-Hung Lee Jannik Helweg-Larsen Xing Tang Shaoling Jin Baozheng Li Marilyn S. Bartlett Jang-Jih Lu Bettina Lundgren Jens D. Lundgren Mats Olsson Sebastian B. Lucas Patricia Roux Antonietta Cargnel Chiara Atzori Olga Matos James W. Smith 《Journal of clinical microbiology》1998,36(3):734-741
Pneumocystis carinii f. sp. hominis isolates from 207 clinical specimens from nine countries were typed based on nucleotide sequence variations in the internal transcribed spacer regions I and II (ITS1 and ITS2, respectively) of rRNA genes. The number of ITS1 nucleotides has been revised from the previously reported 157 bp to 161 bp. Likewise, the number of ITS2 nucleotides has been changed from 177 to 192 bp. The number of ITS1 sequence types has increased from 2 to 15, and that of ITS2 has increased from 3 to 14. The 15 ITS1 sequence types are designated types A through O, and the 14 ITS2 types are named types a through n. A total of 59 types of P. carinii f. sp. hominis were found in this study. 相似文献