Localization of bicoid mRNA in late oocytes is maintained by continual active transport.

Localization of bicoid mRNA to the anterior of the Drosophila oocyte is essential to produce the Bicoid protein gradient that patterns the anterior-posterior axis of the embryo. Previous studies have characterized a microtubule-dependent pathway for bicoid mRNA localization during midoogenesis, when bicoid first accumulates at the anterior. We show that the majority of bicoid is actually localized later in oogenesis, when the only known mechanism for mRNA localization is based on passive trapping.

Renal lithiasis: addressing the risks of austere desert deployments.

Introduction: Renal lithiasis affects approximately 5% of the general population, with higher risks for men and increasing risks with increasing age. The forward deployment of the Air Force into austere desert environments with integration of the active duty, Reserves, and Guard presents increasing risks to mission accomplishment with the increased risk of developing renal lithiasis.

Methods: This paper describes seven cases of presumed renal lithiasis in a deployed desert setting in Air Force personnel on flying status.

Tubulin polymerization modulates interleukin-2 receptor signal transduction in human T cells.

Few data exist on the modulation of cytokine receptor signaling by the actin or tubulin cytoskeleton. Therefore, we studied interleukin-2 receptor (IL-2R) signaling in phytohemagglutinine (PHA)-pretreated human T cells in the context of alterations in the cytoskeletal system induced by cytochalasin D (CyD), jasplaklinolide (Jas), taxol (Tax), or colchicine (Col). We found that changes in cytoskeletal tubulin polymerization altered the strength of several IL-2-triggered signals.

Patterns and determinants of muscle strength change with aging in older men.

Decreased muscle strength with aging is associated with functional disability in older adults. However, few studies have longitudinally evaluated the rate of muscle strength loss and the risk factors for the loss in older men. This study examined the patterns and determinants of muscle strength change with aging in a healthy older male population.

Atorvastatin affects interleukin-2 signaling by altering the lipid raft enrichment of the interleukin-2 receptor beta chain.

Although the immunomodulatory properties of statins are in part independent of their lipid-lowering effects, cholesterol is a major component of lipid rafts. We therefore studied the effects of atorvastatin (AS) on the raft enrichment of the interleukin-2 receptor (IL-2R) beta chain previously described by us and on early IL-2R signaling events in activated human T cells. We found that concomitant AS exposure during a 3-day stimulation with phytohemagglutinin (PHA) attenuates activation-associated events, such as the enhanced surface expression of the raft marker GM-1 and the induced expression of the activation marker CD25 (the IL-2R alpha chain).

Daclizumab therapy in kidney transplantation-different mechanisms of action in- versus ex-vivo?

Stimulated human T cells from healthy volunteers demonstrate attenuated early interleukin (IL)-2 receptor (R) signaling in the presence of daclizumab (Dac). Aiming to confirm that this ex-vivo effect of Dac is also observed in-vivo, we studied T cells from 3 kidney transplant recipients before and 2-3 weeks and 4-6 months after transplantation. We found by flow cytometry that T cells obtained pre-transplant and stimulated ex-vivo with phytohemeagglutinine upregulated the IL-2R alpha-(CD25) and beta-(CD122) chains as expected.

Genetic professionals' reports of nondisclosure of genetic risk information within families.

Patients attending genetic clinics are often the main gatekeepers of information for other family members. There has been much debate about the circumstances under which professionals may have an obligation, or may be permitted, to pass on personal genetic information about their clients but without their consent to other family members. We report findings from the first prospective study investigating the frequency with which genetics professionals become concerned about the failure of clients to pass on such information to their relatives.

Separation of sperm and epithelial cells in a microfabricated device: potential application to forensic analysis of sexual assault evidence.

Forensic DNA analysis of sexual assault evidence requires separation of DNA from epithelial (victim) and sperm (perpetrator) cells. The conventional method used by crime laboratories, which is termed "differential extraction", is a time-consuming process. To supplant the conventional process, separation of sperm from a biological mixture containing epithelial cells has been demonstrated on a microfluidic device.

Systematic review: is ingestion of paracetamol or non-steroidal anti-inflammatory drugs associated with exacerbations of inflammatory bowel disease?

Aim: To examine the published evidence on the association between paracetamol or non-steroidal anti-inflammatory drugs and relapse in inflammatory bowel disease.

Methods: Medline searches were performed till June 2004 and Embase till April 2003. Abstracts published in Gut and Gastroenterology from 1999 to 2004 were hand-searched.

Temporal complexity within a translational control element in the nanos mRNA.

Translational control of gene expression plays a fundamental role in the early development of many organisms. In Drosophila, selective translation of nanos mRNA localized to the germ plasm at the posterior of the embryo, together with translational repression of nanos in the bulk cytoplasm, is essential for development of the anteroposterior body pattern. We show that both components to spatial control of nanos translation initiate during oogenesis and that translational repression is initially independent of Smaug, an embryonic repressor of nanos.

Family communication about genetic risk: the little that is known.

Although family communication is important in clinical genetics only a small number of studies have specifically explored the passing on of genetic knowledge to family members. In addition, many of these present exploratory or tentative findings based upon small sample sizes, or data collected only a short time after testing. Nevertheless, if health professionals are to develop effective strategies to help patients' deal with communication issues, we need to know more about what actually happens in families.

The measurement of nicotine in human plasma by high-performance liquid chromatography-electrospray-tandem mass spectrometry.

The authors describe a reverse-phase high-performance liquid chromatography-electrospray-tandem mass spectrometry method for the measurement of nicotine in human plasma. Samples (500 microL) with added deuterium-labeled d3-nicotine as an internal standard (IS) were treated with a 2-step process of ether extraction (6 mL) followed by back-extraction into 0.1% formic acid (50 microL).

Using FTE and RVU performance measures to assess financial viability of academic nurse-managed centers.

Financial performance measures are essential to improve the fiscal management of academic nurse-managed centers (ANMCs). Measures are compared among six ANMCs in a consortium and against an external, self-sustainable, profitable ANMC and national data for family practice physicians. Performance measures help identify a center's strengths and weaknesses facilitating the development of strategies aimed at a variety of targets (business practices related to revenue and costs) to improve financial viability.

Lipid rafts in cytokine signaling.

Lipid rafts are established as critical structures for a variety of cellular processes, including immune cell activation. Beyond their importance for initial immune cell activation at the immunological synapse, lipid rafts are now also being recognized as important sites for cytokine and growth factor signal transduction, both in immune cells as part of secondary regulatory processes, and in non-immune cells. This review summarizes current knowledge regarding the roles of rafts in cytokine signaling and emphasizes the need for measures to better standardize the study of rafts.

Eosinophils in a tri-cell multicellular tumor spheroid (MTS)/endothelium complex.

Eosinophils have been found in infiltrates of many different cancers. It is still unclear as to whether they are passive bystanders in the cellular milieu or active cellular agents in host responses. Thus their harmful or helpful nature remains equivocal.

Activated eosinophils upregulate the metastasis suppressor molecule E-cadherin on prostate tumor cells.

Cell adhesion molecules (CAMs) play an important role in cancer metastasis by facilitating attachment to vascular endothelia, invasion and spread into secondary tissue sites. We have shown that activated eosinophils (EosA) inhibited the growth of prostate cancer (Pca) cells in vitro. In the present study, we examined the ability of EosA 24 hr conditioned supernatants (EosAcs) to modulate the expression of ICAM-1, VCAM-1, ELAM-1, E-cadherin and N-cadherin expression on human Pca cell lines, Du-145 and PC-3 by flow cytometry.

To tell or not to tell: barriers and facilitators in family communication about genetic risk.

Communication about genetic risk in families is an important issue for genetic counsellors. The objective of this study was to explore the barriers and facilitators in family communication about genetic risk. Semi-structured interviews were undertaken with patients in the Northeast of Scotland who had attended genetic counselling for risk of hereditary breast and ovarian cancer and Huntington's disease, and with some spouses/partners.

Diagnostic criteria of developmental apraxia of speech used by clinical speech-language pathologists.

The diagnostic criteria used to identify developmental apraxia of speech (DAS) have been at the center of controversy for decades. Despite the difficulty in determining the characteristics that differentiate DAS from other speech acquisition disorders, many children are identified with this disorder. The current report presents the criteria used by 75 speech-language pathologists to establish a diagnosis of DAS.

Inhibition of prostate cancer cell growth by activated eosinophils.

Background: Host Immune response to prostate cancer primarily involves the CTL and NK effector cells. Recent immunotherapeutic strategies incorporating cytokine genes into the tumor cell and/or dendritic cells have had encouraging results. In this study, we describe the inhibitory activity of a third potential effector cell, the eosinophil, against DU 145 and PC-3 prostate tumor cells growth in vitro.

Live imaging of endogenous RNA reveals a diffusion and entrapment mechanism for nanos mRNA localization in Drosophila.

Background: Localization of nanos mRNA to the posterior pole of the Drosophila embryo directs local synthesis of Nanos protein that is essential for patterning of the anterior-posterior body axis and germ cell function. While nanos RNA is synthesized by the ovarian nurse cells and appears at the posterior pole of the ooctye late in oogenesis, the mechanism by which this RNA is translocated to and anchored at the oocyte posterior is unknown.

Results: By labeling endogenous nanos RNA with GFP, we have been able to follow the dynamic pathway of nanos localization in living oocytes.

Insulin resistance-related factors, but not glycemia, predict coronary artery disease in type 1 diabetes: 10-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications Study.

Objective: To determine the independent risk factors for coronary artery disease (CAD) in type 1 diabetes by type of CAD at first presentation.

Research Design And Methods: This is a historical prospective cohort study of 603 patients with type 1 diabetes diagnosed before 18 years of age between 1950 and 1980. The mean age and duration of diabetes at baseline were 28 (range 8-47) and 19 years (7-37), respectively, and patients were followed for 10 years.

Do plasminogen activator inhibitor (PAI-1) or tissue plasminogen activator PAI-1 complexes predict complications in Type 1 diabetes: the Pittsburgh Epidemiology of Diabetes Complications Study.

Aims: To examine the predictive power of plasminogen activator inhibitor-1 (PAI-1) and the complexes it forms with tissue plasminogen activator (tPA-PAI-1) for the two major Type 1 diabetes (T1D) complications (coronary artery disease (CAD) and overt nephropathy) in the context of standard risk factors.

Methods: Observational prospective study of 454 participants with childhood onset (< 17 years) T1D, aged 18+ years at baseline. PAI-1 and tPA-PAI-1 were determined using ELISA methodology.

Lipid rafts, major histocompatibility complex molecules, and immune regulation.

Glycolipid-enriched membrane microdomains ("rafts") are critical sites for signal transduction and other processes such as intracellular transport. While the participation of T-cell rafts in the formation of the immunological synapse is well established, the role of rafts on antigen-presenting cells (APCs) as well as the relationship between these domains and major histocompatibility complex (MHC) molecules is less clearly defined. We therefore investigated whether MHC class I or II molecules are found in rafts of the human macrophage-monocytic cell line U937.

Calpain II colocalizes with detergent-insoluble rafts on human and Jurkat T-cells.

Calpain, a calcium-dependent cysteine protease, is known to associate with the T-cell plasma membrane and subsequently cleave a number of cytoskeletal-associated proteins. In this study, we report the novel observation that calpain II, but not calpain I, associates with membrane lipid rafts on human peripheral blood T-cells and Jurkat cells. Raft-associated calpain activity is enhanced with exogenous calcium and inhibited with calpeptin, a specific inhibitor of calpain activity.