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31.
The bone marrow is patrolled by NK cells that are primed and expand in response to systemic viral activation 下载免费PDF全文
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Severe congenital neutropenia with neurological impairment due to a homozygous VPS45 p.E238K mutation: A case report suggesting a genotype–phenotype correlation 下载免费PDF全文
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Vasyutina E Stebler J Brand-Saberi B Schulz S Raz E Birchmeier C 《Genes & development》2005,19(18):2187-2198
Long-range migrating progenitor cells generate hypaxial muscle, for instance the muscle of the limbs, hypoglossal cord, and diaphragm. We show here that migrating muscle progenitors express the chemokine receptor CXCR4. The corresponding ligand, SDF1, is expressed in limb and branchial arch mesenchyme; i.e., along the routes and at the targets of the migratory cells. Ectopic application of SDF1 in the chick limb attracts muscle progenitor cells. In CXCR4 mutant mice, the number of muscle progenitors that colonize the anlage of the tongue and the dorsal limb was reduced. Changes in the distribution of the muscle progenitor cells were accompanied by increased apoptosis, indicating that CXCR4 signals provide not only attractive cues but also control survival. Gab1 encodes an adaptor protein that transduces signals elicited by tyrosine kinase receptors, for instance the c-Met receptor, and plays a role in the migration of muscle progenitor cells. We found that CXCR4 and Gab1 interact genetically. For instance, muscle progenitors do not reach the anlage of the tongue in CXCR4;Gab1 double mutants; this target is colonized in either of the single mutants. Our analysis reveals a role of SDF1/CXCR4 signaling in the development of migrating muscle progenitors and shows that a threshold number of progenitor cells is required to generate muscle of appropriate size. 相似文献
34.
Proteases, extracellular matrix, and cancer: a workshop of the path B study section 总被引:1,自引:0,他引:1 下载免费PDF全文
DeClerck YA Mercurio AM Stack MS Chapman HA Zutter MM Muschel RJ Raz A Matrisian LM Sloane BF Noel A Hendrix MJ Coussens L Padarathsingh M 《The American journal of pathology》2004,164(4):1131-1139
The role of the extracellular matrix (ECM) in the tumor microenvironment is not limited to being a barrier against tumor invasion. The ECM is a reservoir of cell binding proteins and growth factors that affect tumor cell behavior. It is also substantially modified by proteases produced by tumor cells or stroma cells. As a result of the activity of these proteases, cell-cell and cell-ECM interactions are altered, new biologically active ECM molecules are generated, and the bioavailability and activity of many growth factors, growth factor receptors, and cytokines are modified. ECM-degrading proteases also play a critical role in angiogenesis, where they can act as positive as well as negative regulators of endothelial cell proliferation and vascular morphogenesis. This review article summarizes some of the most relevant findings made over the recent years that were discussed at a workshop organized by the Path B Study Section of the National Institutes of Health in October 2002. 相似文献
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Patient organizations are increasingly involved in national and international bioethical debates and health policy deliberations. In order to examine how and to what extent cultural factors and organizational contexts influence the positions of patient organizations, this study compares the positions of German and Israeli patient organizations (POs) on issues related to end-of-life medical care. We draw on a qualitative pilot study of thirteen POs, using as a unit of analysis pairs comprised of one German PO and one Israeli PO that were matched on the basis of organizational category. Bioethical positions that emanated from the interviews concerned advance directives—general views, recent legal framework, and formalization; as well as active and passive euthanasia, withholding and withdrawing of treatment, and physician-assisted suicide. In addition to the unifying, within-country impact of cultural factors, we found that constituency-based organizations and partner organizations in both countries often share common views, whereas disease-based support organizations have very heterogeneous positions. We conclude by discussing how organizational contexts provide a source of uniformity as well as diversity in the positions of POs. 相似文献
38.
23S rRNA base pair 2057-2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A-->G 下载免费PDF全文
Pfister P Corti N Hobbie S Bruell C Zarivach R Yonath A Böttger EC 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(14):5180-5185
The 23S rRNA A2058G alteration mediates macrolide, lincosamide, and streptogramin B resistance in the bacterial domain and determines the selectivity of macrolide antibiotics for eubacterial ribosomes, as opposed to eukaryotic ribosomes. However, this mutation is associated with a disparate resistance phenotype: It confers high-level resistance to ketolides in mycobacteria but only marginally affects ketolide susceptibility in streptococci. We used site-directed mutagenesis of nucleotides within domain V of 23S rRNA to study the molecular basis for this disparity. We show that mutational alteration of the polymorphic 2057-2611 base pair from A-U to G-C in isogenic mutants of Mycobacterium smegmatis significantly affects susceptibility to ketolides but does not influence susceptibility to other macrolide antibiotics. In addition, we provide evidence that the 2057-2611 polymorphism determines the fitness cost of the 23S rRNA A2058G resistance mutation. Supported by structural analysis, our results indicate that polymorphic nucleotides mediate the disparate phenotype of genotypically identical resistance mutations and provide an explanation for the large species differences in the epidemiology of defined drug resistance mutations. 相似文献
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Chazan B Colodner R Teitler N Chen Y Raz R 《American journal of infection control》2008,36(6):436-438
Health care workers (HCWs) are susceptible to hospital acquired varicella zoster virus (VZV). We evaluated seroprevalence and predictive value of a history of varicella disease (VD) with VZV serology in HCWs in northern Israel. A total of 200 HCWs were enrolled. A high rate of seropositivity for VZV-IgG was found: 98.5% seropositive and only 1.5% seronegative. A positive history of VD was an excellent predictor for the presence of VZV-IgG; however, a negative history of VD does not rule out the presence of VZV-IgG. 相似文献