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van Duist MM Albrecht M Podswiadek M Giachino D Lengauer T Punzi L De Marchi M 《European journal of human genetics : EJHG》2005,13(6):742-747
The caspase recruitment domain gene CARD15/NOD2, encoding a cellular receptor involved in an NF-kappaB-mediated pathway of innate immunity, was first identified as a major susceptibility gene for Crohn's disease (CD), and more recently, as responsible for Blau syndrome (BS), a rare autosomal-dominant trait characterized by arthritis, uveitis, skin rash and granulomatous inflammation. While CARD15 variants associated with CD are located within or near the C-terminal leucine-rich repeat domain and cause decreased NF-kappaB activation, BS mutations affect the central nucleotide-binding NACHT domain and result in increased NF-kappaB activation. In an Italian family with BS, we detected a novel mutation E383K, whose pathogenicity is strongly supported by cosegregation with the disease in the family and absence in controls, and by the evolutionary conservation and structural role of the affected glutamate close to the Walker B motif of the nucleotide-binding site in the NACHT domain. Interestingly, substitutions at corresponding positions in another NACHT family member cause similar autoinflammatory phenotypes. 相似文献
73.
High-Throughput Generation of P. falciparum Functional Molecules by Recombinational Cloning 总被引:2,自引:0,他引:2
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Joo Carlos Aguiar Joshua LaBaer Peter L. Blair Victoria Y. Shamailova Malvika Koundinya Joshua A. Russell Fengying Huang Wenhong Mar Robert M. Anthony Adam Witney Sonia R. Caruana Leonardo Brizuela John B. Sacci Jr. Stephen L. Hoffman Daniel J. Carucci 《Genome research》2004,14(10B):2076-2082
Large-scale functional genomics studies for malaria vaccine and drug development will depend on the generation of molecular tools to study protein expression. We examined the feasibility of a high-throughput cloning approach using the Gateway system to create a large set of expression clones encoding Plasmodium falciparum single-exon genes. Master clones and their ORFs were transferred en masse to multiple expression vectors. Target genes (n = 303) were selected using specific sets of criteria, including stage expression and secondary structure. Upon screening four colonies per capture reaction, we achieved 84% cloning efficiency. The genes were subcloned in parallel into three expression vectors: a DNA vaccine vector and two protein expression vectors. These transfers yielded a 100% success rate without any observed recombination based on single colony screening. The functional expression of 95 genes was evaluated in mice with DNA vaccine constructs to generate antibody against various stages of the parasite. From these, 19 induced antibody titers against the erythrocytic stages and three against sporozoite stages. We have overcome the potential limitation of producing large P. falciparum clone sets in multiple expression vectors. This approach represents a powerful technique for the production of molecular reagents for genome-wide functional analysis of the P. falciparum genome and will provide for a resource for the malaria resource community distributed through public repositories. 相似文献
74.
Oncocytic adencarcinoma of the rectum with diffuse intra-luminal microcalcifications: the first reported case 总被引:1,自引:0,他引:1
Piscitelli D Ingravallo G Resta L Fiore MG Maiorano E 《Virchows Archiv : an international journal of pathology》2003,443(4):579-582
Several histological variants of colorectal carcinoma have been reported, some of them bearing prognostic significance, others only incidental findings showing unusual morphological features. The current report was aimed to describe the histological, immunohistochemical and ultrastructural features of an oncocytic adenocarcinoma of the rectum occurring in a 66-year-old woman. Histologically, it was a moderately differentiated adenocarcinoma composed by glandular structures lined by eosinophilic cells. The latter showed abundant granular cytoplasm and large nuclei with prominent nucleoli. Several glandular structures contained intraluminal, basophilic and non-birifrangent microcalcifications. The tumour cells displayed consistent anti-mitochondrial antigen, carcinoembryonic antigen, p53, CDX2 and cytokeratin 20 immunoreactivity. Ultrastructurally, more than 80% of the cytoplasmic area was occupied by abnormal mitochondria, while exocrine or endocrine granules were undetectable. The tumour infiltrated the intestinal wall through the subserosal tissue, but lymph node or distant metastases were absent. The patient is disease free 22 months after surgery. Based on the above features, this case could be appropriately named oncocytic adenocarcinoma with intraluminal microcalcifications. Like gastric neoplasms showing similar morphologic features, this tumour might have a better prognosis, and the presence of microcalcifcations could help its proper recognition at a pre-operative stage. 相似文献
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C Raphael 《Physics in medicine and biology》1992,37(6):1293-1311
We view radiation therapy treatment planning (RTTP) as a problem of constrained optimization. In this context, the 'optimal' treatment is one that maximizes some objective function subject to the inherent constraints of the problem. We discuss two objective functions which are motivated by biological considerations rather than mathematical expedience. One of these measures the 'goodness' of a treatment in terms of its probability of success. The other measures the degree to which a treatment succeeds in satisfying a system of constraints that are mutually contradictory. We describe how to actually perform the optimization of these objective functions in practice and show some numerical results which demonstrate advantages of these objective functions over their more conventional counterparts. 相似文献
79.
Age and sex influence on oxidative damage and functional status in human skeletal muscle 总被引:3,自引:0,他引:3
Fanò Giorgio Mecocci Patrizia Vecchiet Jacopo Belia Silvia Fulle Stefania Polidori M. Cristina Felzani Giorgio Senin Umberto Vecchiet Leonardo Beal M. Flint 《Journal of muscle research and cell motility》2001,22(4):345-351
A reduction in muscle mass, with consequent decrease in strength and resistance, is commonly observed with advancing age. In this study we measured markers of oxidative damage to DNA, lipids and proteins, some antioxidant enzyme activities as well Ca2+ transport in sarcoplasmic reticulum membranes in muscle biopsies from vastus lateralis of young and elderly healthy subjects of both sexes in order to evaluate the presence of age- and sex- related differences. We found a significant increase in oxidation of DNA and lipids in the elderly group, more evident in males, and a reduction in catalase and glutathione transferase activities. The experiments on Ca2+ transport showed an abnormal functional response of aged muscle after exposure to caffeine, which increases the opening of Ca2+ channels, as well a reduced activity of the Ca2+ pump in elderly males. From these results we conclude that oxidative stress play an important role in muscle aging and that oxidative damage is much more evident in elderly males, suggesting a gender difference maybe related to hormonal factors.This revised version was published online in September 2005 with corrections to the Cover Date. 相似文献
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