Burkholderia cenocepacia induces neutrophil necrosis in chronic granulomatous disease.

Burkholderia cepacia complex is a life-threatening group of pathogens for patients with chronic granulomatous disease (CGD), whose phagocytes are unable to produce reactive oxygen species (ROS). Unlike other CGD pathogens, B. cepacia complex is particularly virulent, characteristically causing septicemia, and is the bacterial species responsible for most fatalities in these patients.

Listening to the decision makers: sustainability of PBMA in Alberta.

Background: Decision makers within the Calgary Health Region adopted and applied programme budgeting and marginal analysis (PBMA) for priority-setting activity across major service portfolios within the Region.

Methods: Seventeen in-depth qualitative interviews were conducted with senior managers and clinicians to gain a user perspective and identify specific areas for process refinement. Data were thematically coded and categorised into relevant themes.

Increased expression of insulin-like growth factor-I (IGF-I) during embryonic development produces neocortical overgrowth with differentially greater effects on specific cytoarchitectonic areas and cortical layers.

The in vivo actions of insulin-like growth factor-I (IGF-I) on the growth and development of the cerebral cortex were investigated in transgenic (Tg) mice that overexpress IGF-I in the brain, beginning as early as embryonic day (E) 13. Compared to non-Tg littermate controls, Tg mice at postnatal day (P) 12 exhibited significant increases in total cortical volume (31%) and in total neuron number (27%). The numerical density of neurons did not differ significantly between Tg and control mice, except in layer I.

Role of IGF-1R in mediating breast cancer invasion and metastasis.

In this review we bring forward what is currently known about the role of type I insulin-like growth factor receptor (IGF-1R) in mediating breast cancer invasion and metastasis. We begin by addressing how activated IGF-1R could allow pre-cancerous cells to become invasive. To this effect, we discuss clinical reports suggesting that activation of IGF-1R could stimulate ductal carcinoma in situs to become invasive.

Neonatal procedural pain exposure predicts lower cortisol and behavioral reactivity in preterm infants in the NICU.

Data from animal models indicate that neonatal stress or pain can permanently alter subsequent behavioral and/or physiological reactivity to stressors. However, cumulative effects of pain related to acute procedures in the neonatal intensive care unit (NICU) on later stress and/or pain reactivity has received limited attention. The objective of this study is to examine relationships between prior neonatal pain exposure (number of skin breaking procedures), and subsequent stress and pain reactivity in preterm infants in the NICU.

Role of carboxypeptidase E in processing of pro-islet amyloid polypeptide in {beta}-cells.

Islet amyloid polypeptide (IAPP; amylin) is a peptide hormone that is cosecreted with insulin from beta-cells. Impaired processing of proIAPP, the IAPP precursor, has been implicated in islet amyloid formation in type 2 diabetes. We previously showed that proIAPP is processed to IAPP by the prohormone convertases PC1/3 and PC2 at its carboxyl (COOH) and amino (NH(2)) termini, respectively.

Repression of the human sex hormone-binding globulin gene in Sertoli cells by upstream stimulatory transcription factors.

Expression of the sex hormone-binding globulin gene (SHBG) in the liver produces SHBG, which transports sex steroids in the blood. In rodents, the SHBG gene is also expressed in Sertoli cells giving rise to the testicular androgen-binding protein, which is secreted into the seminiferous tubule where it presumably controls testosterone action. Evidence that the SHBG gene functions in this way in the human testis is lacking, and mice containing a human SHBG transgene (shbg4) under the control of its own promoter sequence are characterized by SHBG gene expression in the liver but not in the testis.

Overexpression of follicle-stimulating hormone receptor activates oncogenic pathways in preneoplastic ovarian surface epithelial cells.

It has been previously demonstrated that human ovarian cancer cells express FSH receptor (FSHR). However, whether FSHR plays a role in ovarian cancer development is still ambiguous. To investigate the role of FSHR in tumor progression, we overexpressed the receptor in SV40 Tag immortalized ovarian surface epithelium (OSE) cell lines (IOSE-80PC, a postcrisis line, and IOSE-398), which are preneoplastic and nontumorigenic.

Expression of leptin receptors and potential effects of leptin on the cell growth and activation of mitogen-activated protein kinases in ovarian cancer cells.

Leptin, a secreted protein of the ob gene by white adipose tissue, plays an important role in the regulation of food intake and energy consumption in the brain and acts as a potential growth stimulator in normal and neoplastic breast cancer cells. However, a potential role of leptin as an endocrine regulator is unknown in ovarian cancer. In the present study, we investigated the expression of leptin receptors in immortalized ovarian surface epithelium (IOSE) and ovarian cancer cell lines, and potential effect of leptin on the cell growth and activation of mitogen-activated protein kinases (MAPKs) in the BG-1 ovarian cancer cell line.

Polyunsaturated fatty acids in human milk: an essential role in infant development.

The n-6 and n-3 fatty acids are essential dietary nutrients required for optimal growth and development, particularly of the brain and retina. Large amounts of the n-3 fatty acid docosahexaenoic acid (DHA) is accumulated in the brain grey matter and the visual elements of the retina during development, and reduced DHA in these tissues can result in decreased visual and psychomotor development. Although the possible importance of differences in n-6 and n-3 fatty acids, particularly DHA, between human milk and infant formulas has been the subject of intense clinical research, the variability in the essential fatty acid content of milk within and among different populations of women and implications of this to infant growth and development have received much less attention.

n-6 Docosapentaenoic acid is not a predictor of low docosahexaenoic acid status in Canadian preschool children.

Background: The n-3 fatty acid docosahexaenoic acid (DHA; 22:6n-3) is important for neural and visual functional development. In animals, 22:6n-3 deficiency is accompanied by increased docosapentaenoic acid (DPA; 22:5n-6), which suggests that the ratio of 22:6n-3 to 22:5n-6 could be a useful biochemical marker of low n-3 fatty acid status. The n-3 fatty acid status of preschool children has not been described, and data are lacking on whether low 22:6n-3 is accompanied by high 22:5n-6 in humans.

Differential expression of a novel ankyrin containing E3 ubiquitin-protein ligase, Hace1, in sporadic Wilms' tumor versus normal kidney.

We have analyzed the chromosome 6q21 breakpoint of a non-constitutional t(6;15)(q21;q21) rearrangement in sporadic Wilms' tumor. This identified a novel gene encoding a protein with six N-terminal ankyrin repeats linked to a C-terminal HECT ubiquitin-protein ligase domain. We therefore designated this gene HACE1 (HECT domain and Ankyrin repeat Containing E3 ubiquitin-protein ligase 1).

Specific Newborn Individualized Developmental Care and Assessment Program movements are associated with acute pain in preterm infants in the neonatal intensive care unit.

Objective: The Newborn Individualized Developmental Care and Assessment Program (NIDCAP) is widely used in neonatal intensive care units and comprises 85 discrete infant behaviors, some of which may communicate infant distress. The objective of this study was to identify developmentally relevant movements indicative of pain in preterm infants.

Methods: Forty-four preterm infants were assessed at 32 weeks' gestational age (GA) during 3 phases (baseline, lance/squeeze, and recovery) of routine blood collection in the neonatal intensive care unit.

The depiction of car light beams in a child born completely blind.

A 12-year-old child (DI) who was completely blind from birth, made a series of tactual (raised-lines) drawings of cars. Among them, there was the depiction of a 'fast car at night' in which DI drew beams of light projecting out of the car. We analyse this drawing, and the preceding ones.

Differential post-transcriptional activation of human phagocytes by different Pseudomonas aeruginosa isolates.

Pseudomonas aeruginosa is a pulmonary pathogen in individuals with impaired mucociliary clearance such as cystic fibrosis or mechanical ventilation. Non-opsonic phagocytosis of P. aeruginosa can be mediated by either CR3 or CD14 and different strains appear to have a bias towards one or the other receptor.

In vitro culture studies of Sutherlandia frutescens on human tumor cell lines.

Sutherlandia frutescens is a South African herb used traditionally by the natives to treat cancer, and more recently to improve the overall health in HIV/AIDS patients. Gas chromatography/mass spectrometer profiling and liquid chromatographic/mass spectral investigation confirmed and quantified the presence of canavanine, GABA and arginine in the herbal preparation used in this study. In vitro study demonstrated a concentration dependent effect of Sutherlandia on several tumor cell lines, with 50% inhibition (IC50) of proliferation of MCF7, MDA-MB-468, Jurkat and HL60 cells at 1/250, 1/200, 1/150 and 1/200 dilutions, respectively.

Type II gonadotropin-releasing hormone stimulates p38 mitogen-activated protein kinase and apoptosis in ovarian cancer cells.

Recent results indicate that a novel second form of GnRH, GnRH-II, has an antiproliferative effect on ovarian and endometrial cancer cells and might be considered as a possible therapy for gynecological tumors. However, the mechanism of the GnRH-II-induced antiproliferative effect is not known. The p38 MAPK, one of the stress-activated protein kinases, is activated by diverse cellular stress and proinflammatory cytokines.

Foundations of knowledge about neonatal pain.

This review appraises trends in the neonatal pain research literature. We searched the literature produced from 1941 to 2001. Information about the model of pain, measures of pain, design, and sample characteristics is included for each citation.

Mutations in the SAM domain of the ETV6-NTRK3 chimeric tyrosine kinase block polymerization and transformation activity.

The 12p13 ETV6 (TEL) gene is frequently targeted by chromosomal translocations in human malignancies, resulting in the formation of oncogenic ETV6 gene fusions. Many of the known partner genes encode protein tyrosine kinases (PTKs), generating fusion proteins that function as chimeric PTKs. ETV6-NTRK3 (EN), comprised of the ETV6 SAM domain fused to the NTRK3 PTK, is unique among ETV6 chimeric oncoproteins, as it is expressed in cancers of multiple lineages.

Health care priority setting: principles, practice and challenges.

BACKGROUND: Health organizations the world over are required to set priorities and allocate resources within the constraint of limited funding. However, decision makers may not be well equipped to make explicit rationing decisions and as such often rely on historical or political resource allocation processes. One economic approach to priority setting which has gained momentum in practice over the last three decades is program budgeting and marginal analysis (PBMA).

Insulin signaling and glucose homeostasis in mice lacking protein tyrosine phosphatase alpha.

Studies in cultured cells have implicated protein tyrosine phosphatase alpha (PTPalpha) as a potential regulator of insulin signaling. The physiological role of PTPalpha in insulin action was investigated using gene-targeted mice deficient in PTPalpha. PTPalpha-null animals had normal body weights and circulating levels of glucose and insulin in random fed and fasted states.

Expression of the insulin-like growth factor I receptor and urokinase plasminogen activator in breast cancer is associated with poor survival: potential for intervention with 17-allylamino geldanamycin.

Urokinase plasminogen activator (uPA) expression in breast cancer is associated with relapse and a reduction in disease-specific survival. Thus, efforts are under way to identify uPA inhibitors. By screening a chemical library of >1000 compounds, 17-allyaminogeldanamycin (17AAG) was identified as a potent inhibitor of uPA by the National Cancer Institute and is now in Phase I clinical trials.