The metastasis-associated gene CD24 is regulated by Ral GTPase and is a mediator of cell proliferation and survival in human cancer.

Ral GTPases are important mediators of transformation, tumorigenesis, and cancer progression. We recently identified the metastasis-associated protein CD24, a glycosyl phosphatidyl inositol-linked surface protein, as a downstream target of Ral signaling by profiling the expression of RalA/B-depleted bladder carcinoma cells. Because CD24 is highly expressed in bladder and many other tumor types, we sought to determine if this protein plays an essential role in maintaining the malignant phenotype.

Interaction between AT1 and AT2 receptors during postinfarction left ventricular remodeling.

The relative contribution of the angiotensin II type 1 and 2 receptors (AT1-R and AT2-R) in postmyocardial infarction (MI) remodeling remains incompletely understood. We studied five groups of C57Bl/6 mice after 1 h of left anterior descending artery occlusion-reperfusion: 1) wild type, untreated (n = 12); 2) wild type, treated with the AT1-R blocker losartan (10-20 mg.kg(-1).

Endothelin axis is a target of the lung metastasis suppressor gene RhoGDI2.

Half of patients treated for locally advanced bladder cancer relapse with often fatal metastatic disease to the lung. We have recently shown that reduced expression of the GDP dissociation inhibitor, RhoGDI2, is associated with decreased survival of patients with advanced bladder cancer. However, the effectors by which RhoGDI2 affects metastasis are unknown.

A comparison of developmental versus functional assessment in the rehabilitation of young children.

Background: The purpose of this study was to explore the differences in and potential uses of information derived from developmental vs. functional assessment during the acute rehabilitation of very young children with acquired brain injury. Both methods of assessment are typically used during hospitalization in order to assist in developing individualized goals and outcome measures.

Efficacy and complications of covered Wallstents in malignant distal biliary obstruction.

Background: This study evaluated the efficacy and the complications associated with the use of the covered Wallstent in the setting of unresectable malignant biliary obstruction.

Methods: Between March 2001 and January 2003, all patients with distal malignant biliary obstruction that required drainage were treated with a covered Wallstent. Every 2 months, the patients were evaluated clinically and biochemical tests of liver function were obtained.

Safety-related knowledge and behavior changes in participants of farm safety day camps.

Significant resources are devoted to conducting farm safety day camps throughout North America, but the impact and effectiveness of these programs has not been systematically demonstrated. This project assessed changes in safety-related knowledge and behaviors among participants in the Progressive Farmer Farm Safety Day Camp program. A written pre-test and a three-month telephone post-test were administered to three samples of participants, ages 8 to 13, in camps held in 1999, 2000, and 2001.

Effect of exogenous surfactant (calfactant) in pediatric acute lung injury: a randomized controlled trial.

Context: Despite evidence that patients with acute lung injury (ALI) have pulmonary surfactant dysfunction, trials of several surfactant preparations to treat adults with ALI have not been successful. Preliminary studies in children with ALI have shown that instillation of a natural lung surfactant (calfactant) containing high levels of surfactant-specific protein B may be beneficial.

Objective: To determine if endotracheal instillation of calfactant in infants, children, and adolescents with ALI would shorten the course of respiratory failure.

Combination antiangiogenic and androgen deprivation therapy for prostate cancer: a promising therapeutic approach.

Purpose: Androgen ablation therapy leads to mild regression or stabilization of prostate cancer, followed by progression to the fatal androgen-independent state. Whereas androgen ablation diminishes tumor angiogenesis by suppressing vascular endothelial growth factor (VEGF) production, androgen-independent disease is marked by androgen-independent VEGF expression. We examined combined androgen ablation and inhibition of VEGF signaling in an androgen-sensitive human prostate cancer xenograft model (LNCaP) that is known to develop androgen-independent growth after androgen ablation.

Factors predictive of malignancy and endoscopic resectability in ampullary neoplasia.

Objective: Endoscopic treatment of ampullary lesions has been well described, though it remains uncertain if specific features predict malignancy, and whether identifiable factors are associated with successful endoscopic resection of benign lesions.

Methods: Fifty-six consecutive patients undergoing endoscopic evaluation of ampullary neoplasia between March 2000 and May 2004 were included in the study. Clinical presentation, underlying medical conditions, endoscopic treatment, endoscopic ultrasound (EUS) to define extent of local involvement, pathology results, and outcome were documented.

Profiling the evolution of human metastatic bladder cancer.

Pulmonary metastases frequently develop in patients with aggressive bladder cancer, yet investigation of this process at the molecular level suffers from the poor availability of human metastatic tumor tissue and the absence of suitable animal models. To address this, we developed progressively more metastatic human bladder cancer cell lines and an in vivo bladder-cancer lung-metastasis model, and we successfully used these to identify genes of which the expression levels change according to the degree of pulmonary metastatic potential. By initially intravenously injecting the poorly metastatic T24T human urothelial cancer cells into nude mice, and then serially reintroducing and reisolating the human tumor cells from the resultant mouse lung tumors, three derivative human lines with increasingly metastatic phenotypes, designated FL1, FL2, and FL3, were sequentially isolated.

Designs for single- or multiple-agent phase I trials.

Phase I trials of cytotoxic agents in oncology are usually dose-finding studies that involve a single cytotoxic agent. Many statistical methods have been proposed for these trials, all of which are based on the assumption of a monotonic dose-toxicity curve. For single-agent trials, this is a valid assumption.

Translating lifestyle intervention to practice in obese patients with type 2 diabetes: Improving Control with Activity and Nutrition (ICAN) study.

Objective: To assess the efficacy of a lifestyle intervention program that can be readily translated into clinical practice for obese patients with type 2 diabetes.

Research Design And Methods: The study consisted of a 12-month randomized controlled trial of 147 health plan members with type 2 diabetes and obesity (BMI >or=27 kg/m(2)). Participants were randomized to lifestyle case management or usual care.

Reduced expression of metastasis suppressor RhoGDI2 is associated with decreased survival for patients with bladder cancer.

Purpose: RhoGDI2 was recently shown to be a metastasis suppressor gene in models of bladder cancer. We sought to further understand its importance in human cancer by determining the level of its expression and the distribution of its encoded protein in normal human tissues and cell lines and to evaluate whether its protein expression is a determinant of human bladder cancer progression.

Experimental Design: RhoGDI2 mRNA and protein expression was evaluated in cell lines and human tissues using Affymetrix and tissue microarrays, respectively.

Bodily pain and health-related quality of life in children with cerebral palsy.

Pain frequency and its association with participation, function, and health-related quality of life were evaluated in a sample of 198 children (58% male; mean age 10 years 7 months, SD 3 years 11 months; range 5 to 18 years) with moderate to severe cerebral palsy (CP). Gross Motor Functional Classification System (GMFCS) levels were III to V (23% level III, 23% level IV, 31% level V without a gastrostomy tube, and 23% were level V with a gastrostomy tube). Assessment was carried out using the parent-report Child Health Questionnaire (CHQ) and questions assessing health, medical utilization, and medication use.

Long-term exposure to tamoxifen induces hypersensitivity to estradiol.

In women with hormone-dependent breast cancer, tamoxifen (TAM) frequently induces tumor regression, but regrowth occurs with continuation of antiestrogen therapy. Studies of breast xenografts in nude mice suggest that this secondary resistance to TAM may reflect the development of enhanced sensitivity to the estrogenic properties of TAM. In the current study, we examined the hypothesis that TAM could also induce a state of hypersensitivity to estradiol (E(2)) itself.

The novel Ras antagonist, farnesylthiosalicylate, suppresses growth of prostate cancer in vitro.

Background: The majority of men with advanced prostate cancer (PCa) respond to androgen deprivation therapy (ADT) with objective evidence of tumor regression. However, these tumors will regrow in the presence of low-androgen levels after 12-18 months. Regrowth after ADT is associated with upregulation of growth factor (GF) mediated pathways.

Effect of shortened length of stay on functional and educational outcome after pediatric rehabilitation.

Objective: The purpose of this study was to assess changes in the length of stay and its effect on effectiveness and return to school in an inpatient pediatric rehabilitation unit during a 5-yr period from fiscal year 1997 through 2001.

Design: We reviewed prospectively collected data for a cohort of 321 children during fiscal years 1997-2001.

Results: Length of stay was significantly shortened, with mean lengths of stay of 58.

Brain imaging as a predictor of early functional outcome following traumatic brain injury in children, adolescents, and young adults.

Objectives: A depth of lesion (DOL) model using brain imaging has been proposed to aid in medical decision-making and planning for rehabilitation resource needs. The purpose of this study was to determine the early prognostic value of a DOL classification system for children and young adults following severe traumatic brain injury.

Methods And Outcome Measures: CT/MRI brain imaging studies on 92 patients, aged 3 to 21, admitted to the Kluge Children's Rehabilitation Center, University of Virginia, were evaluated to determine DOL.

Transient, ligand-dependent arrest of the androgen receptor in subnuclear foci alters phosphorylation and coactivator interactions.

Here we report that mutations within the DNA-binding domain of AR, shown previously to inhibit nuclear export to the cytoplasm, cause an androgen-dependent defect in intranuclear trafficking of AR. Mutation of two conserved phenylalanines within the DNA recognition helix (F582, 583A) results in androgen-dependent arrest of AR in multiple subnuclear foci. A point mutation in one of the conserved phenylalanines (DeltaF582, F582Y) is known to cause androgen insensitivity syndrome (AIS).

Adaptive hypersensitivity following long-term estrogen deprivation: involvement of multiple signal pathways.

Long-term estrogen deprivation causes hypersensitivity of MCF-7 cells to the mitogenic effect of estradiol (E2) which is associated with activation of mitogen-activated protein kinase (MAPK). However, several lines of evidence indicate that MAPK activation is not the exclusive mechanism for E2 hypersensitivity and multiple signal pathways might be involved. The current study explores the possible role of the PI3 kinase (PI3K) pathway in development of E2 hypersensitivity.

The impact of tailored interventions on a community health center population.

We conducted a 4-year randomized study in a community health center that serves primarily low income Blacks in Durham, North Carolina. Patients (1318 at baseline) were assigned randomly to one of three study groups: provider prompting intervention alone, provider prompting and tailored print materials or the previous group and tailored telephone counseling. The purpose of the study was to determine whether increasingly intensive, tailored print and telephone interventions also were increasingly effective in promoting adherence to mammograms, Pap tests and overall cancer screening compliance.

Relationships among musculoskeletal impairments and functional health status in ambulatory cerebral palsy.

Orthopedic surgery for patients with cerebral palsy addresses motion impairments, assuming that this will improve motor function. This study evaluates the relationships among clinical impairment measures with standardized assessments of function and disability as an initial step in testing this assumption. A total of 129 ambulatory children and adolescents across six institutions participated in a prospective evaluation that consisted of passive motion and spasticity examination of the lower extremities, three-dimensional gait temporal-spatial and kinematic analysis, and administration of the Gross Motor Function Measure (GMFM) and the Pediatric Outcomes Data Collection Instrument (PODCI).

The use of dopamine enhancing medications with children in low response states following brain injury.

Primary Objective: The study examines the possible relationship between dopamine-enhancing medications and improvement of arousal and awareness in children during persistent low response states (Rancho Los Amigos Levels I, II and III).

Research Design: A retrospective review was conducted of 10 children enrolled in an existing clinical protocol. The Kluge Children's Rehabilitation Center (KCRC) low response protocol provides a double baseline serial measure (A, A, B, B, B) design.

Gene profiling and promoter reporter assays: novel tools for comparing the biological effects of botanical extracts on human prostate cancer cells and understanding their mechanisms of action.

The use of botanical mixtures is commonplace in patients with prostate cancer, yet the majority of these products have not been rigorously tested in clinical trials. Here we use PC-SPES, a combination of eight herbs that has been shown to be effective in clinical trials in patients with prostate cancer, as a model system to demonstrate 'proof of principle' as to how gene expression profiling coupled with promoter assays can evaluate the effect of herbal cocktails on human prostate cancer. In addition, we demonstrate how such approaches may be used for standardization of herbal extract activity by comparing the gene profile of PC-SPES with that of PC-CARE, a product with a similar herbal composition.