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1.
Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of ganglion cells in the nerve plexuses of the lower digestive tract. Although mutations in eight different genes (EDNRB, EDN3, ECE1, SOX10, RET, GDNF, NTN, SIP1) have been identified in affected individuals, it is now clear that RET and EDNRB are the primary genes implicated in the etiology of HSCR. All eight genes are involved in the early development of the enteric nervous system, and most act through two distinct biochemical pathways mediated by RET and EDNRB. Mutations in RET and EDNRB account for up to 50% and 5% of HSCR cases in the general population, respectively. Interaction between these two signaling pathways could modify RET expression and, therefore, HSCR phenotype. Here, we report the case of a 1-year-old Taiwanese boy who presented with abdominal distension since birth and bilious vomiting after feeding. HSCR (short-segment type) was diagnosed based on X-ray, lower gastrointestinal series and biopsy findings. Mutation analysis revealed a heterozygous T>C missense mutation in exon 1 of the EDNRB gene, that substitutes the highly conserved cysteine-90 residue in the extracellular domain of the G protein-coupled receptor with an arginine residue (C90R). No RET gene mutation was detected in this patient. 相似文献
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I J Fox L L Perry M S Sy B Benacerraf M I Greene 《Clinical immunology and immunopathology》1980,17(1):141-155
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Begusova M Sy D Charlier M Spotheim-Maurizot M 《International journal of radiation biology》2000,76(8):1063-1073
PURPOSE: To calculate the expected pattern of frank strand breaks (FSB) induced in the DNA of a nucleosome core particle (NCP) by the attack of radiolytic OH* radicals and to compare this with the experimental pattern of FSB induced by the in vitro irradiation of chicken NCP. MATERIALS AND METHODS: The structure of NCP was obtained from the PDB databank. Using molecular modelling, the structure of a linear DNA fragment with the central 60 bp sequence of NCP-DNA was determined. The accessibility of the sugar attack sites to OH* radicals at each nucleotide of the linear fragment or of the NCP-DNA was calculated. The probability of reaction of OH* with each sugar reactive site was calculated using a Monte-Carlo method-based stochastic model. RESULTS: The accessibility of attack sites in the NCP-DNA and the calculated probabilities of sugar attack are mainly modulated through masking by histones, and only slightly through bending. The periodicity of the calculated FSB probabilities is identical to that of the experimental FSB probabilities in chicken NCP (period 10.4 +/- 0.1 bp). CONCLUSIONS: The good agreement between the calculated and experimental results recommends the presented modelling procedure as a tool in predicting the radiosensitivity of DNA in DNA-ligand complexes of known structure. 相似文献
6.
Barone F Begusova M La Nave E Matzeu M Mazzei F Sy D 《International journal of radiation biology》2000,76(6):731-740
PURPOSE: This study is aimed at comparing the radiosensitivity of a 21-mer DNA fragment in duplex and triplex form (Py x Pu duplex and Py x Pu:Py triplex) and to give insights into the fine structural features due to the different strandedness. MATERIALS AND METHODS: The triplex sample was characterized by means of electrophoretic mobility, circular dichroism spectra and UV melting experiments. Triplex and duplex, labelled on the homopyrimidine or homopurine strand, were irradiated with 60Co gamma-rays. The samples were analysed by sequencing gel electrophoresis and the patterns of relative probabilities of frank strand breakage (FSB) and alkali-revealed breakage (ARB) at each nucleotide site were determined. Relative probabilities of OH* radical attack to duplex and triplex DNA built up with a molecular modelling software were calculated using a previously reported simulation procedure (Sy et al. 1997). The experimental data were compared with the results of the theoretical simulations of OH* radical attack to DNA. RESULTS: Globally, the duplex is more attacked than the triplex, mainly in the Pu strand. Sequence-dependent variations of FSB and FSB+ARB probabilities in both duplex and triplex were revealed. No significant differences between the patterns of damage in the triplex and in the duplex were observed. CONCLUSIONS: The presence of the third Py strand located in the major groove of the DNA duplex modifies the total yields of radiation-induced DNA damage, but not the sequence-dependent patterns of relative probability of damage at each nucleotide site. 相似文献
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Smart pen technology has evolved over the past decade with new features such as Bluetooth connectivity, bolus dose calculators, and integration with mobile apps and continuous glucose monitors. While similar in appearance to a traditional insulin pen, smart pens have the ability to record and store data of insulin injections. These devices have the potential to transform diabetes management for clinicians, and patients with type 1 and type 2 diabetes on insulin therapy by improving adherence, glycemic control, and addressing barriers to diabetes management. Smart pens can also highlight the relationship between insulin, food, and physical activity, and provide insight into optimizing insulin regimens. Education of clinicians and patients, and more clinical studies showing the benefits of smart pens and cost-effectiveness, are needed. 相似文献
9.
Four new decarestrictine analogues (botryolides A-D; 1- 4), a biosynthetically related gamma-lactone (botryolide E; 5), and the known compounds decarestrictine D ( 6) and sterigmatocystin have been isolated from cultures of a fungicolous isolate of Botryotrichum sp. (NRRL 38180). The structures of these compounds were determined by analysis of 2D NMR and ESIMS data. The relative configurations of 1- 5 were established on the basis of NMR data and/or X-ray diffraction analysis, while the absolute configuration of 1 was assigned using the modified Mosher method. 相似文献
10.
Brosens IA Puttemans P Campo R Gordts S Gordts S 《Fertility and sterility》2007,88(2):534-534; author reply 535