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The malignant cells of acute promyelocytic leukemia (APL) contain a reciprocal chromosomal translocation that fuses the promyelocytic leukemia gene (PML) with the retinoic acid receptor alpha gene (RAR alpha). To test the hypothesis that the chimera PMLRAR alpha plays a role in leukemogenesis, we expressed a PMLRAR alpha cDNA in myeloid cells of transgenic mice. PMLRAR alpha transgenic mice exhibited impaired neutrophil maturation early in life, which progressed at a low frequency over the course of several months to overt APL. Both the preleukemic state and the leukemia could be transplanted to nontransgenic mice, and the transplanted preleukemia could progress to APL. The APL recapitulated features of the human disease, including a response to retinoic acid. Retinoic acid caused the leukemic cells to differentiate in vitro and in vivo, eliciting remissions of both the preleukemic state and APL in mice. Our results demonstrate that PMLRAR alpha impairs neutrophil differentiation and initiates the development of APL. The transgenic mice described here provide an apparently accurate model for human APL that includes clear evidence of tumor progression. The model should be useful for exploring the molecular pathogenesis of APL and the mechanisms of the therapeutic response to retinoic acid, as well as for preclinical studies of therapeutic regimens.  相似文献   
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The transmembrane proteoglycan NG2 is able to interact both with components of the extracellular matrix and with the actin cytoskeleton. An examination of the distribution of NG2 during cell spreading suggests that NG2 can associate with two distinct types of actin-containing cytoskeletal structures, depending on the nature of the stimulus derived from the substratum. On fibronectin-coated dishes, cell surface NG2 associates exclusively with stress fibers developing within the cell. On poly-L-lysine-coated dishes, cell surface NG2 is associated with radial processes extending from the cell periphery. Spreading on fibronectin/poly-L-lysine mixtures, as well as on matrix components such as laminin, tenascin, and type VI collagen, produces cells with mosaic characteristics, i.e., NG2 is associated with both types of structures. NG2-positive radial processes are distinct from a second population of radial structures that contain fascin. NG2-positive extensions appear to be individual self-contained units (filopodia), whereas fascin is associated with actin ribs within sheets of membrane (lamellipodia). NG2- and fascin-positive structures are often localized to opposite poles of spreading cells, suggesting a possible role for the two classes of cellular extensions in the establishment of cell polarity during morphogenesis or migration. Time lapse imaging confirms the presence of lamellipodia on the leading edges of migrating cells, while numerous filopodia are present on trailing edges.  相似文献   
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BACKGROUND: In a series of 229 patients infected with mycobacterial organisms, we noted a specific female phenotype that involves isolated infections of the middle lobe and lingula. METHODS: Thirteen patients were found to have infections of the middle lobe, lingula, or both. All of them were infected with Mycobacterium other then Mycobacterium tuberculosis, all were women, 12 of the 13 were slender, and most had variable combinations of skeletal abnormalities. All underwent resection of the middle lobe, lingula, or both. RESULTS: There were no operative deaths. Only 2 patients have had reactivation requiring additional antibiotic therapy. All patients have had a decreased number of pulmonary infections in the postoperative period. Anatomic findings at operation included a complete major fissure and at least a partially complete minor fissure with middle lobe resections or an elongated lingula. CONCLUSIONS: Mycobacterial infection of the middle lobe and lingula is primarily a disease of asthenic women and is often associated with skeletal abnormalities and complete fissures or an elongated lingula. We recommend that surgical intervention be performed early once the condition is identified.  相似文献   
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Text search is a type of strategic reading that involves locating specific goal-relevant information. Previous research has indicated that college and high school students often exhibit inefficient or unsuccessful text-search performance. Consequently, the effects of 2 manipulations on text-search performance were investigated: (1) the presence of indexed terms in a text-search task and (2) the use of a planning prompt before beginning a task. 34 college students engaged in 6 text-search tasks. Half of these tasks contained terms that could be used in an index; half required that a search term be generated. Half of the subjects were randomly assigned to a prompt condition in which they were prompted to plan their search before beginning each task. The results indicated that a planning prompt raised the success level of search performance, as did the presence of terms that were searchable in the textbook's index. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
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This social research project investigated community receptivity to using rainwater and greywater as alternative domestic water sources. It was focused in the Ku-ring-gai local government area in northern Sydney, and involved a household questionnaire followed by community leader interviews and resident focus groups. Trends, such as a prolonged drought and increasing population, compound the current crisis and concern facing Sydney's available water supply. Substitution of domestic potable water has been promoted as part of the solution. The research results revealed that community receptivity was highest for external uses, such as watering gardens and flushing toilets, and progressively decreased with increasing personal contact. Receptivity to greywater reuse fell more rapidly with the community believing there was a higher health risk associated with its use. Gender and cultural background were revealed as significant variables and give insight into the design of strategies to target these demographic groups. This evidence provides a reliable stocktake of current receptivity revealing that the community has good awareness and positive association with water reuse for many household activities. This now needs to be harnessed through programs targeted at developing skills, resources and motivation for new water reuse practices and technologies across diverse social groupings.  相似文献   
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