Phenylketonuria (PKU) is a metabolic disorder in which an inability to properly metabolize the amino acid phenylalanine (Phe) leads to a buildup of Phe in the blood, causing neurotoxicity and resulting in intellectual disability, delayed speech, seizures, and behavior abnormalities. Individuals with PKU are also susceptible to other adverse outcomes, including impaired executive function, reduced processing speed, attention problems, impaired fine motor skills, and mental health concerns (such as anxiety and depression symptoms). The most severe form of PKU, classic PKU, is typically characterized by blood Phe levels exceeding 1,200 umol/L while on a normal diet. PKU is typically diagnosed at birth following abnormal newborn screening results. With adherence to a Phe-restricted diet, poor outcomes can be mitigated.

关键词：苯丙酮酸尿;代谢疾病;氨基酸;血液;诊断(医学)

查看摘要 索取原文[16页]

During the past 12 months, we have received IRB approval from Mount Sinai School of Medicine, the James P. Peters VA Medical Center IRBs, and the Department of Defense. We have also held three focus groups with prostate cancer patients undergoing hormone therapy and multiple research team meetings were held to discuss focus group results, software development, and study protocol. We are currently integrating feedback from the final focus group into the vasomotor symptom intervention (VSI) and plan to run a final focus group to test the usability of the application. Our progress over the previous project period has led us to refine the methodology and software development, and this will allow us to begin the intervention phase during Y2 of the award.

关键词：前列腺癌激素;;计算机程序;医疗服务;症状和体征,治疗

查看摘要 索取原文[6页]

EGFR and HER2 are overexpressed in 20and 30of invasive breast cancer, respectively, and are associated with aggressive tumor subtypes and shortened patient survival. Both receptors are important targets of breast cancer therapy. However, despite the apparent promise of some of these therapies, EGFR- and HER2-based monotherapy and combination regimens have serious limitations and need improvement. The goal of this study is, thus, to gain insights into the biology of EGFR- and HER2-expressing invasive breast cancer in order to provide rationales for more effective EGFR- and HER2-based combination therapy for women with breast cancer. Our proposal is built on novel significant findings made from the initial Idea Award. We discovered that proapoptotic PUMA protein is highly expressed in the breast cancer cell lines and patient tumors that overexpress HER2 and/or EGFR. In addition to co- expression, we found HER2 and EGFR to interact with PUMA constitutively and under the treatment of apoptosis inducers. The HER2-PUMA and EGFR-PUMA interactions are not disrupted when breast cancer cells are treated with the EGFR kinase inhibitors, indicating a kinase-independent interaction. Despite the fact that PUMA has been reported to be primarily located on the mitochondrial membranes and initiate apoptosis upon appropriate stress, our results showed PUMA to be sequestered in the cytoplasm of EGFR-expressing breast cancer cells. Although, the BH3-only proapoptotic proteins can be functionally redundant, we observed PUMA to be essential for apoptotic induction in breast cancer cells. Interestingly, while no reports have investigated PUMA phosphorylation, our preliminary results show that PUMA undergoes tyrosine phosphorylation mediated by HER2 and EGFR.

关键词：凋亡;乳腺癌;表皮受体网站(生理学);细胞(生物学);细胞质;感应系统

查看摘要 索取原文[10页]

The Agency for Healthcare Research and Quality (AHRQ) has identified the need for clinical, administrative, and other kinds of health care information from very large populations to address topics central to its mission, and to the missions of other Federal agencies. A distributed health data network advances AHRQs Effective Health Care and Health Information Technology research goals by focusing on standardized and reusable information technology approaches for speeding the initiation and conduct of large-scale comparative effectiveness studies, including studies of treatments covered by Medicaid, Medicare, CHIP, and other Federal payers. The current team developed design specifications for a scalable, distributed, health data network, created a prototype for the network, performed a study using distributed principles assessing the comparative effectiveness of second line anti-hypertensive therapy, and created a blueprint for implementing a distributed health data network.

关键词：卫生保健;临床医疗信息;行政卫生信息;健康数据网络

查看摘要 索取原文[96页]

The NBL-Tag neuroblastoma mice were crossed with B-cell deficient mice in order to determine the effect of B-cell activity on tumor growth characteristics. Homozygous deficient B-Cell mice and heterozygous NBL-Tag mice were established. The NBL-Tag/B-cell deficient mice lacked B-cells as expected using flow cytometry analyses and immunohistochemistry. However, the lack of B- cells did not alter the growth patterns of NBL-Tag tumor formation as imaged by MRI. Studies using anti-B cell therapy were also conducted. The efficacy of the anti-mouse B-cell antibody was tested in wildtype C57B6 mice tissues (blood, spleen, and peritoneal cavity lymphocytes) and demonstrated superiority of the antibody to eliminate B-cells when given in the peritoneum. NBL-Tag mice given this antibody starting at 4 weeks of age did not show any difference in their growth characteristics. The anti-B cell antibody combination with chemotherapy in established tumors showed superiority compared with anti-Ragweed antibody control. Further studies are underway to elucidate the effect of macrophages on tumor formation and growth.

关键词：神经母细胞瘤;抗体;血压;龋齿;化疗;淋巴细胞,巨噬细胞;肿瘤;病理;腹膜

查看摘要 索取原文[8页]

The application of cellular therapies to treat battlefield injuries offers a novel and promising approach to address longstanding challenges in the repair of tissue damage with regard to both structural and functional improvement. The results of currently published investigations describing mesenchymal stem cell (MSC) efficacy in a variety of injury models demonstrate the unique qualities of this reparative cell population to adapt to the requirements of the damaged tissue in which the cells integrate. MSC therapy represents a single medical intervention that can simultaneously provide a broad range of therapeutic efficacy, with local activity, at multiple tissue and organ sites. The data presented in this report demonstrate that MSCs can be routinely isolated from adult bone marrow and expanded in cell culture to consistently and reliably produce pharmaceutical quantities of therapeutic product. Characterization of stem cell properties of culture-expanded MSCs is shown by in vitro differentiation to form mature cell types. The production methodology described will provide the means for producing test material for use in evaluating MSC therapy as a candidate treatment modality for injuries of concern to medical defense.

关键词：对策;干细胞;骨髓细胞(生物学);文化(生物学);损害;药物

查看摘要 索取原文[26页]

关键词：前列腺癌;放射学;放射性药物;放疗;化学;测定;药物

查看摘要 索取原文[9页]

Described herein is the final technical information pertaining to a multi-year effort to determine and characterize the use of adipose (fat)- derived stem cells in the treatment of epidermal (skin) wounds. Adipose tissue was successfully harvested from the nuchal fat pad of six Atlantic Bottlenose dolphins via liposuction; cells released during the digestion of the adipose tissue were analyzed for cytology, assayed for the total number of colony- forming cells, expanded in culture, differentiated into multiple cell lineages, analyzed for stem cell surface markers and stem cell related genes. Cultured cells were also cryogenically frozen for autologous and allogeneic cell therapy treatment of dolphin skin wounds. Stem cells were incubated with white blood cells from non-donor dolphins and were shown to be non-immunogenic. Injection of stem cells along the wound axis into skin wounds of dolphins display a more rapid healing than carrier solution alone.

关键词：海豚(哺乳动物);干细胞;脂肪组织,细胞(生物学);细胞学;脂肪;创伤和损伤

查看摘要 索取原文[26页]

Traumatic brain injury (TBI) is a worldwide problem with an estimated incidence of 200 cases per 100,000 people per year. Recent military conflicts have produced a spike in the incidence of combat related brain injury. Preclinical research has identified potential pharmacologic therapeutic agents; however, no single drug has consistently shown benefit in the clinical setting. In an effort to advance the therapeutic and molecular target realms of basic research, our team tested two hypotheses: (1) diazoxide (DZ) administered after brain injury will result in short and long-term improvement in memory, motor, and behavioral function; and (2) graded traumatic brain injury will produce early and sustained alternations of polysialylated neural cell adhesion molecular (PSA-NCAM) expression.

关键词：药物;脑;行为;病理学;临床医学

查看摘要 索取原文[73页]

Prostate cancers that recur after so-called androgen ablation therapy ( CR-CaP ) are typically more aggressive, more likely to spread to local lymph nodes and bones, and less likely to respond to second-tier treatments, and therefore, contribute to significantly decreased patient survival. We posit that enzymes called Src-family kinases (SFK) are required for the progression to CR-CaP, and thus, targeting these enzymes should prevent CR-CaP formation to suppress their growth. We will use animal models of human and mouse CR-CaP in conjunction with genetic and biochemical experiments to show that SFK are critical to the formation of CR-CaP, and thus, are therapeutically targetable using SFK-specific drugs. Our important pre-clinical studies on the critical role played by SFK in CR-CaP disease will serve as the foundation to establish immediate clinical trials in which CaP patients are treated with drugs such as KX2-391 at the commencement of androgen-deprivation therapy.

关键词：前列腺癌;雄激素;酶;基础(结构);基因;淋巴结;前列腺;治疗

查看摘要 索取原文[8页]