No abstract

No abstract

Stimulation of lymphocytes through the Ag receptor can lead to cytokine responsiveness or unresponsiveness. We examined the importance of cyclin-dependent kinase (CDK)4 to establish and maintain IL-2 responsiveness in human T cells. Our results show that a herbimycin A- and staurosporine-sensitive phase of CDK4 expression and activity preceded the acquisition of IL-2-responsiveness in mitogen-stimulated peripheral blood T cells. Intriguingly, CDK4 expression and activity were demonstrable in purified unstimulated peripheral blood T cells from ∼30% (5/16) of healthy individuals examined for this study. These T cells proliferated in response to IL-2 without additional mitogens, and both the expression and activity of CDK4 and the ability to respond to cytokines were resistant to herbimycin A and staurosporine. The pattern of CDK4 expression and response to IL-2 in this subset of individuals resembled that seen in the human IL-2-dependent Kit-225 T cell line. However, in contrast to normal T cells, Kit-225 cells were rendered unresponsive to IL-2 by stimulation through the Ag receptor. In these cells, PHA, anti-CD3, or PMA induced marked reductions of CDK4 expression and activity that paralleled IL-2 unresponsiveness, and these effects were not reversible by IL-2. Furthermore, IL-2-dependent proliferation could be similarly inhibited in Kit-225 cells by overexpression of the CDK inhibitors p16/Ink4-a or p21/Waf-1a or by overexpression of a kinase-inactive CDK4 mutant. The data indicate that CDK4 expression and activity are necessary to induce and maintain cytokine responsiveness in T cells, suggesting that CDK4 is important to link T cell signaling pathways to the machinery that controls cell cycle progression.

Within an RtI problem-solving context, assessment and decision making generally center around the tasks of problem identification, problem analysis, progress monitoring, and program evaluation. We use this framework to discuss the current state of the literature regarding curriculum based measurement, its technical properties, and its utility for making instructional decisions. Cursory examination of emerging alternatives (e.g., computer adaptive tests) is included, where appropriate. We then offer recommendations for local decision making, with an emphasis on high-quality assessment, responsible decision making, bridging the research-practice gap, and capitalizing on the expertise of school psychologists. C

This article summarizes the current knowledge of response-to-intervention (RTI) models in preschool settings, with an emphasis on evaluating the strengths and weaknesses of our current research base. Particular attention is given to the unique challenges of high-risk preschool settings. Presently, sufficient empirical support exists to begin establishing tiered intervention systems and building teacher capacity. Lacking, however, are valid and reliable assessment tools and insufficiently trained personnel to support a data-based decision-model within high-risk preschools. We conclude that organizational development should focus on building teacher capacity, establishing high-quality classroom instruction, and planning for sustainable programs, with adoption of a full RTI service delivery model serving as a long-range aspirational goal. C 2011 Wiley Periodicals, Inc.Over the past decade, rapid changes have occurred in general educational practice to increase the focus on early identification of and intervention for students considered at risk. The aptly named response-to-intervention (RTI) model of service delivery is generally described as a multitiered model whereby students receive interventions of increasing intensity, with movement from one level to another based on demonstrated performance and rate of progress (Gresham, 2007). This sizable paradigm shift has been influenced in part by recent special education legislation, which permits the use of RTI as an alternative to the traditional "IQ-achievement discrepancy" model of learning disability identification and allows up to 15% of federal special education funding to be allocated toward early intervening services (Individuals with Disabilities Education Improvement Act, 2004). Moreover, RTI has gained favor in light of mounting evidence suggesting that intensive intervention during the primary grades is effective for remediating academic difficulties (e.g., Vellutino, Scanlon, Small, & Fanuele, 2006;. Practitioners may also intuitively gravitate toward an RTI model of practice, which has more ideological appeal than traditional models in the sense that it emphasizes identifying and solving problems as soon as possible rather than waiting for students to fall far behind their peers before providing additional services (e.g., Vaughn & Fuchs, 2006).Currently, much of the published literature on full-scale RTI implementation is focused on conceptual and logistical issues related to RTI. Furthermore, a majority of the empirical studies relevant to RTI is focused either on case studies of RTI implementation in particular schools or on intensive intervention with students in the early elementary grades. Dozens of studies have documented the effectiveness of specific interventions for remediating skill deficits in reading (e.g., Case et al

No abstract

We evaluated the utility of cytochemistry, immunophenotyping, flow cytometry, and in vitro culture with forced differentiation of leukemic cells as diagnostic aids to identify the malignant cell ontogeny in a dog with leukemia. A tentative diagnosis of monoblastic leukemia was established by microscopic examination of Romanowsky-stained blood smears and bone marrow aspirate smears. This diagnosis also was supported by the light scatter signature that identified the blast cells as large, non-granular monocytic cells using a CellDyn 3500 automated hematology analyzer; as well as by the detection of N-butyrate esterase and the lack of choloroacetate esterase or leukocyte peroxidase by cytochemical staining. Subsequently, leukemic cells were isolated from the dog's peripheral blood and placed into tissue culture or cryopreserved. The leukemic cells grew in suspension cultures and proliferated spontaneously for up to 4 days. By day 7, proliferation was negligible. Upon culture with conditioned supernatant using mitogen-stimulated human T cells as a source of cytokines, an increased proportion of cells entered S phase by day 2 of culture; however, proliferation declined markedly by day 4, at which time the cells had apparently differentiated to adherent, vacuolated macrophages. The cytokine-stimulated leukemic cells were positive for the monocyte/macrophage specific markers alpha-1-antitrypsin, alpha-1-antichymotrypsin, lysozyme, CD14, MHC class II, and calprotectin, an antigen found in differentiated macrophages and granulocytes. Despite the strong tendency of the leukemic cells towards monocytic differentiation, our results suggested that they retained some features of a myelomonocytic precursor. These data show that cytochemistry, immunophenotyping, flow cytometry, and in vitro differentiation of canine leukemia cells are useful tools for confirming the lineage of malignant hematopoietic cells.

This study examined the predictive validity and classification accuracy of two commonly used universal screening measures relative to a statewide achievement test. Results indicated that second-grade performance on oral reading fluency and the Measures of Academic Progress (MAP), together with special education status, explained 68% of the variance in third-grade standardized test performance (N = 399). Six methods of dichotomous risk classification were also explored to predict whether students would pass or fail the state test. A random sample of half of the participants was used to establish locally appropriate risk cut-scores, holding sensitivity constant at .95; the cut-scores were then cross-validated on the remaining participants. Cross-validation reflected sensitivity of above .90 for all methods, with MAP Language Usage and two multi-screener methods demonstrating the strongest overall technical adequacy for risk classification. The limitations and implications of these findings are discussed.