排序方式: 共有70条查询结果,搜索用时 16 毫秒
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Coulbault L Herlicoviez D Chapon F Read MH Penniello MJ Reynier P Fayet G Lombès A Jauzac P Allouche S 《Biochemical and biophysical research communications》2005,329(3):1152-1154
We describe a lethal mitochondrial disease in a 10-month-old child who presented with encephalomyopathy. Histochemical and electron microscopy examinations of skeletal muscle biopsy revealed abnormal mitochondria associated with a combined deficiency of complexes I and IV. After excluding mitochondrial DNA deletions and depletion, direct sequencing was used to screen for mutation in all transfer RNA (tRNA) genes. A T-to-C substitution at position 5693 in the tRNA(Asn) gene was found in blood and muscle. Microdissection of muscle biopsy and its analysis revealed the highest level of this mutation in cytochrome c oxidase (COX)-negative fibres. We suggest that this novel mutation would affect the anticodon loop structure of the tRNA(Asn) and cause a fatal mitochondrial disease. 相似文献
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S. Zanssen M. Molnar J.M. Schröder G. Buse 《Molecular and cellular biochemistry》1997,174(1-2):231-236
We have identified a cluster of mitochondrial tRNALeu[UUR], mutations in a severe case of infantile myopathy. There were A to G transitions found at mtDNA positions 3259, 3261, 3266 and 3268. These point mutations change the anticodon arm and the anticodon UAA, normally found in tRNALeu[UUR], to UGA which is the one of the tRNAsSer[UCN]. This is the first anticodon alteration described in this tRNA. Another swap straight to the anticodon of tRNAPro alone was recently described in a less severe case [1]. Until now infantile myopathies have not been attributed to defined mtDNA alterations. This study reports for the first time mtDNA point mutations causing this early onset of a mitochondrial disorder. The apparent homoplasmy of these mutations and especially the location in the anticodon must be considered lethal, if the child would not have been respirated for 5 years from its birth. (Mol Cell Biochem 174: 231–236, 1997) 相似文献
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William J.J. Finlay James E. Coleman Jonathan S. Edwards Kevin S. Johnson 《MABS-AUSTIN》2019,11(1):26-44
Monoclonal anti-programmed cell death 1 (PD1) antibodies are successful cancer therapeutics, but it is not well understood why individual antibodies should have idiosyncratic side-effects. As the humanized antibody SHR-1210 causes capillary hemangioma in patients, a unique toxicity amongst anti-PD1 antibodies, we performed human receptor proteome screening to identify nonspecific interactions that might drive angiogenesis. This screen identified that SHR-1210 mediated aberrant, but highly selective, low affinity binding to human receptors such as vascular endothelial growth factor receptor 2 (VEGFR2), frizzled class receptor 5 and UL16 binding protein 2 (ULBP2). SHR-1210 was found to be a potent agonist of human VEGFR2, which may thereby drive hemangioma development via vascular endothelial cell activation. The v-domains of SHR-1210’s progenitor murine monoclonal antibody ‘Mab005? also exhibited off-target binding and agonism of VEGFR2, proving that the polyspecificity was mediated by the original mouse complementarity-determining regions (CDRs), and had survived the humanization process. Molecular remodelling of SHR-1210 by combinatorial CDR mutagenesis led to deimmunization, normalization of binding affinity to human and cynomolgus PD1, and increased potency in PD1/PD-L1 blockade. Importantly, CDR optimization also ablated all off-target binding, rendering the resulting antibodies fully PD1-specific. As the majority of changes to the paratope were found in the light chain CDRs, the germlining of this domain drove the ablation of off-target binding. The combination of receptor proteome screening and optimization of the antibody binding interface therefore succeeded in generating novel, higher-potency, specificity-enhanced therapeutic IgGs from a single, clinically sub-optimal progenitor. This study showed that highly-specific off-target binding events might be an under-appreciated phenomenon in therapeutic antibody development, but that these unwanted properties can be fully ameliorated by paratope refinement. 相似文献
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E. Sigamani, V. K. Iyer and S. Agarwala Fine needle aspiration cytology of infantile haemangioendothelioma of the liver: a report of two cases Background: Fine needle aspiration cytology (FNAC) of infantile haemangioendothelioma of the liver (IHL) has not previously been described because routine use of FNAC is contraindicated due to the risk of bleeding. Methods and materials: Two patients presented with progressively increasing right upper quadrant abdominal mass. The index case was a girl aged two and a half years with a large single mass in the right lobe of the liver. The second was a 3‐month‐old girl in whom ultrasonography revealed multiple hypoechoic lesions in the liver. Ultrasound‐guided fine needle aspiration had been performed on both patients. May‐Grünwald‐Giemsa stained smears from these two patients were reviewed and correlated with histopathology. Results: Both aspirates showed predominantly normal hepatocytes and bile ductules amongst which tumour cells were admixed. The latter were oval to spindle‐shaped with scant cytoplasm and wavy, kinked and indented nuclear outlines. The non‐epithelial character of the tumour cells was apparent and helped to rule out hepatoblastoma. One case showed extramedullary haemopoiesis. The diagnosis of IHL was established on subsequent excision in the first case and a wedge biopsy in the second case. CD34 and factor VIII R antigen were positive in the tumour cells. Conclusion: Radiological diagnosis of IHL is possible in a majority of cases, but sometimes features may overlap with hepatoblastoma and fine needle aspiration may be performed inadvertently. Characteristic kinked nuclei and intermixed normal liver tissue might suggest IHL in the differential diagnosis of a spindle cell vasoformative tumour. 相似文献
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从ALV-J中国地方分离株SCAU-HN06株(血管瘤病变型)、NX0101株和JS-nt株(骨髓瘤病变型)病毒的细胞培养物提取前病毒DNA,通过PCR扩增各毒株的LTR并克隆,随后进行测序分析。与国内外ALV-J参考毒株LTR序列比较发现:国内地方分离株与英国ALV-J原型株HPRS-103和美国ALV-J原型株ADOL-7501的LTR核苷酸序列相似性为88.0%~97.2%;LTR中的U5区及R区具有较高的保守性,而U3区内存在较大差异。将不同病变型ALV-J的LTR片段分别插入pCAT-basic载体CAT报告基因5'端。用所得的重组报告基因表达质粒转染DF-1细胞,48h后通过测定转染细胞中的CAT表达量来评价LTR启动子的活性。结果表明,SCAU-HN06株与骨髓瘤病变型ALV-J(JS-nt株,NX0101株)LTR启动子活性差异不显著。 相似文献
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