Search

Adolescents with high-functioning autism (HFA) possess core social and pragmatic deficits, which interfere with normal relationship development. At a time when friendships are increasingly important, many adolescents with HFA realize they are different from their peers. Initial research has indicated that adolescence is the time when symptoms of anxiety and depression are most likely to develop. The purpose of this study was to increase knowledge about anxiety and depression in HFA through focusing on the adolescent development period and obtaining assessment information from multiple sources. Results indicate that adolescents reported elevated levels of social anxiety, separation panic, and anhedonia compared with normative samples. Parents and teachers reported that adolescents experienced significant overall anxiety and depressive symptomatology compared with the normative samples. Manifestations of HFA were associated with higher levels of anxiety as reported by parents. Results bring into question the validity of self-report scales for adolescents with HFA in the ability to accurately self-report and in the measures' capacity to differentiate between internalizing symptoms and core HFA behaviors.

The Response to Intervention (RTI) framework, a preventive model of universal screening, tiered interventions, and ongoing progress monitoring, poses an interesting consideration for identification and service delivery for children with autism spectrum disorders (ASD). Upon examination of the existing literature, paucity exists regarding how RTI might guide identification and service delivery for students with ASD; however, the authors consider core tenets of RTI and how they are relevant for students with ASD given what is known about this unique population. Due to the importance of early identification and interventions for individuals with ASD, the RTI framework could be problematic if used to delay education eligibility. Thus, two routes of identification are outlined by the authors, one of which expedites evaluation based on pervasive symptomatology, while the other route uses a form of universal screening to assist in moving toward evaluation for those suspected of ASD. The use of tiered interventions for prevention or service delivery could cause potential complications given the need for early identification and individualized intensive programming. However, there is a clear match for several instructional RTI components and ASD, specifically for evidence-based interventions that are implemented with fidelity and monitored frequently, and other aspects such as family involvement, which could improve programming for students with ASD. (Contains 1 table and 1 figure.)

Hypoxia-inducible factor 1α (HIF-1α) and HIF-2α display unique and sometimes opposing activities in regulating cellular energy homeostasis, cell fate decisions, and oncogenesis. Macrophages exposed to hypoxia accumulate both HIF-1α and HIF-2α, and overexpression of HIF-2α in tumor-associated macrophages (TAMs) is specifically correlated with high-grade human tumors and poor prognosis. However, the precise role of HIF-2α during macrophage-mediated inflammatory responses remains unclear. To fully characterize cellular hypoxic adaptations, distinct functions of HIF-1α versus HIF-2α must be elucidated. We demonstrate here that mice lacking HIF-2α in myeloid cells ([Hif2a.sup.Δ/Δ] mice) are resistant to lipopolysaccharide-induced endotoxemia and display a marked inability to mount inflammatory responses to cutaneous and peritoneal irritants. Furthermore, HIF-2α directly regulated proinflammatory cytokine/chemokine expression in macrophages activated in vitro. [Hif2a.sup.Δ/Δ] mice displayed reduced TAM infiltration in independent murine hepatocellular and colitisassociated colon carcinoma models, and this was associated with reduced tumor cell proliferation and progression. Notably, HIF-2α modulated macrophage migration by regulating the expression of the cytokine receptor M-CSFR and the chemokine receptor CXCR4, without altering intracellular ATP levels. Collectively, our data identify HIF-2α as an important regulator of innate immunity, suggesting it may be a useful therapeutic target for treating inflammatory disorders and cancer., Introduction Macrophages are versatile hematopoietic cells that mediate a wide array of immune functions, e.g., initiating inflammatory responses, executing phagocytosis and bacterial killing, and facilitating adaptive immunity (1-3). The plasticity [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2007.01.032 Byline: Asa Abeliovich, Rachel Hammond Keywords: Dopamine neuron; Parkinson disease; Stem cell; Midbrain; Floor plate; Sonic hedgehog; nurr1; pitx3 Abstract: Dopaminergic neurons in the midbrain (mDNs) play a central role in the regulation of voluntary movement as well as other complex behaviors, and their loss is associated with Parkinson's disease (PD). The development of functional mDNs from multipotent progenitors is orchestrated by cell-intrinsic factors and cell-extrinsic environmental cues in a series of stages: early midbrain patterning, specification of mitotic precursors, postmitotic mDN development, and functional maturation. Of particular interest is how extracellular information is integrated with cell-intrinsic developmental programs. Cell fate mapping studies suggest that the stem-like progenitors for mDNs reside at the ventral midline floor plate, a region that also serves as a source of inductive signals for mDN specification such as Sonic Hedgehog (SHH). Cell replacement therapies, and in particular the use of embryonic or adult stem cell-derived dopaminergic neurons, offer potential novel treatment venues for PD, but such strategies require a detailed understanding of mDN development. Author Affiliation: Taub Institute for the Aging Brain, Departments of Pathology and Neurology, Center for Neurobiology and Behavior, Columbia University, P&S 15-403, 630 W. 168th Street, New York, NY 10032, USA Article History: Received 23 August 2006; Revised 26 December 2006; Accepted 20 January 2007

Abstract Background Liposomal doxorubicin (Doxil) is a cytotoxic chemotherapy drug with a favorable hematologic toxicity profile. Its active drug, doxorubicin, has interesting immunomodulatory properties. Here, the effects of Doxil on surviving tumor cell immunophenotype were investigated. Methods Using ID8 murine ovarian cancer cells, the immunomodulatory effects of Doxil were studied by measuring its impact on ovarian cancer cell expression of MHC class-I and Fas, and susceptibility to immune attack in vitro. To evaluate the ability of Doxil to cooperate with cancer immunotherapy, the interaction between Doxil and Interleukin 18 (IL-18), a pleiotropic immunostimulatory cytokine, was investigated in vivo in mice bearing ID8-Vegf tumors. Results While Doxil killed ID8 tumor cells in a dose-dependent manner, tumor cells escaping Doxil-induced apoptosis upregulated surface expression of MHC-I and Fas, and were sensitized to CTL killing and Fas-mediated death in vitro. We therefore tested the hypothesis that the combination of immunotherapy with Doxil provides positive interactions. Combination IL-18 and Doxil significantly suppressed tumor growth compared with either monotherapy in vivo and uniquely resulted in complete tumor regression and long term antitumor protection in a significant proportion of mice. Conclusion These data demonstrate that Doxil favorably changes the immunophenotype of a large fraction of the tumor that escapes direct killing thus creating an opportunity to expand tumor killing by immunotherapy, which can be capitalized through addition of IL-18 in vivo.