pH recovery from a proton load in rat cardiomyocytes: effects of chronic exercise.

The ability of cardiomyocytes to recover from a proton load was examined in the hearts of exercise-trained and sedentary control rats in CO/[Formula: see text]-free media. Acidosis was created by the NHCl prepulse technique, and intracellular pH (pH) was determined using fluorescence microscopy on carboxy-SNARF-1 AM-loaded isolated cardiomyocytes. CO-independent pH buffering capacity (β) was measured by incrementally reducing the extracellular NHCl concentration in steps of 50% from 20 to 1.

The role of developmental factors in predicting young children's use of a self-report scale for pain.

Accurate pain assessment is the foundation for effective pain management in children. At present, there is no clear consensus regarding the age at which young children are able to appropriately use self-report scales for pain. This study examined young children's ability to use the Faces Pain Scale-Revised; (FPS-R; [Hicks CL, von Baeyer CL, Spafford PA, van Korlaar I, Goodenough B.

Antioxidant and anti-inflammatory properties of ESSIAC and Flor-Essence.

Essiac (ES) and Flor-Essence (FE) are two herbal teas widely taken by North American cancer patients during chemo- and radiation-therapy. The antioxidant and anti-inflammatory properties of these two herbal teas were assessed in this study. Cell-free Trolox equivalent antioxidant capacity assay shows that at 1/5 dilution, ES and FE have hydroxyl radical scavenging activity equivalent to 10.

The association of skewed X chromosome inactivation with aneuploidy in humans.

Recently, we reported that skewed X chromosome inactivation (XCI) was more common in women who had experienced a trisomic pregnancy as compared to control women. Rather than an overall shift in the distribution of skewing there appears to only be an excess of extreme (= 95%) skewing. Further analysis of our data reveals that the increase in skewed XCI is dependent on which chromosome is involved in the trisomy and how many trisomies the woman has experienced, although sample sizes in each group are small.

The X-linked inhibitor of apoptosis protein enhances survival of murine islet allografts.

Allotransplantation of pancreatic islets represents a promising approach to treat type 1 diabetes. Destruction of beta-cells in islet allografts involves multiple immune mechanisms that lead to activation of caspases and apoptotic cell death. The X-linked inhibitor of apoptosis (XIAP) inhibits apoptosis induced by a variety of triggers, primarily by preventing the activation of caspases.

Priority-setting in health authorities: moving beyond the barriers. The Calgary experience.

The objective of this study was to identify key issues relevant to the development and implementation of a macro-level priority-setting framework (i.e., across broad service areas) within the Calgary Health Region.

ETV6-NTRK3: a chimeric protein tyrosine kinase with transformation activity in multiple cell lineages.

The ETV6-NTRK3 (TEL-TRKC) gene fusion was discovered by breakpoint analysis of the t(12;15)(p13;q25) translocation associated with congenital fibrosarcoma, a pediatric soft tissue malignancy. ETV6-NTRK3 (EN) encodes the sterile alpha motif oligomerization domain of the ETV6 (TEL) transcription factor linked to the protein tyrosine kinase domain of the neurotrophin-3 receptor NTRK3 (TRKC). The EN chimeric oncoprotein links to multiple signaling cascades including Ras-MAP kinase and PI3K-AKT through the IRS-1 adapter protein.

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.

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.

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.

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.

Comprehensive description of newborn distress behavior in response to acute pain (newborn male circumcision).

One of the most difficult challenges still facing researchers and clinicians is assessing pain in the newborn. Behaviors provide one of the most promising avenues for deepening our fundamental understanding of complex phenomenon like newborn pain, and are key to developing descriptive-level knowledge to further newborn pain assessment efforts. In this ethologically based research, we report on the duration and frequency of neonatal distress behavior to seven distinct noxious and non-noxious but distress-provoking events including baseline (diaper change, post-diaper change, application of arm and leg restraints, post-application of arm and leg restraints, circumcision, post-circumcision) associated with newborn surgical pain.

In vitro comparison of Essiac and Flor-Essence on human tumor cell lines.

Essiac (ES) and Flor-Essence (FE) are two herbal teas widely taken by North American cancer patients during chemo- and radiation therapy. In vitro studies on the antiproliferative and differentiation inducing activities of these teas were performed. ES and FE showed negligible antiproliferative activity on Jurkat leukemia cells.

Biofilm formation and acyl homoserine lactone production in the Burkholderia cepacia complex.

Acyl homoserine lactone (acyl-HSL)-mediated gene regulation has been shown to influence biofilm formation in one Burkholderia cepacia cystic fibrosis isolate, but it is not known whether this relationship is a consistent feature of the several genomic species that make up the B. cepacia complex (BCC). We screened strains belonging to genomovars I to V of the BCC for biofilm formation on an abiotic surface and for acyl-HSL synthesis.

ETV6-NTRK3 transformation requires insulin-like growth factor 1 receptor signaling and is associated with constitutive IRS-1 tyrosine phosphorylation.

Congenital fibrosarcoma (CFS) and cellular mesoblastic nephroma (CMN) are pediatric spindle cell malignancies that share two specific cytogenetic abnormalities: trisomy of chromosome 11 and a t(12;15)(p13;q25) translocation. The t(12;15) rearrangement creates a transcriptionally active fusion gene that encodes a chimeric oncoprotein, ETV6-NTRK3 (EN). EN transforms NIH3T3 fibroblasts through constitutive activation of both the Ras-mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol-3'kinase (PI3K)-Akt pathway.

Rescue of rubella virus replication-defective mutants using vaccinia virus recombinant expressing rubella virus nonstructural proteins.

The genome of rubella virus (RV) is translated into a polyprotein precusor, p200, of the nonstructural proteins (NSPs). This is proteolytically processed by a viral-encoded protease into two mature products, p150 and p90. p150 contains sequence corresponding to the predicted methyltransferase and protease activities, while p90 has sequence for the proposed helicase and RNA-dependent RNA polymerase activities.

Outcomes of planned home births versus planned hospital births after regulation of midwifery in British Columbia.

Background: The choice to give birth at home with a regulated midwife in attendance became available to expectant women in British Columbia in 1998. The purpose of this study was to evaluate the safety of home birth by comparing perinatal outcomes for planned home births attended by regulated midwives with those for planned hospital births.

Methods: We compared the outcomes of 862 planned home births attended by midwives with those of planned hospital births attended by either midwives (n = 571) or physicians (n = 743).

Genetic linkage and association studies of Type I diabetes: challenges and rewards.

Family and twin studies have shown clearly that Type I (insulin-dependent) diabetes mellitus has a genetic basis. However, only within the past decade has it been possible to systematically attempt to identify the genes that increase susceptibility to this disorder using linkage and association analysis of genetic markers distributed across the genome. More than 20 putative diabetes-predisposing genes have been localised in addition to HLA region susceptibility genes detected more than 25 years ago.

The chimeric protein tyrosine kinase ETV6-NTRK3 requires both Ras-Erk1/2 and PI3-kinase-Akt signaling for fibroblast transformation.

There is increasing interest in the potential role of the NTRK family of neurotrophin receptors in human neoplasia. These receptor protein tyrosine kinases (PTKs) are well-known mediators of neuronal cell survival and differentiation, but altered NTRK signaling has also been implicated in mesenchymal, hematopoietic, and epithelial malignancies. We recently identified a novel gene fusion involving one of the neurotrophin receptor genes, NTRK3, in the pediatric solid tumor, congenital fibrosarcoma.

Lymphocyte recognition of human parvovirus B19 non-structural (NS1) protein: associations with occurrence of acute and chronic arthropathy?

Immune recognition of recombinant parvovirus B19 non-structural (rNS1) protein was studied by immunoblot and lymphoproliferative assays in blood from the following B19 seropositive groups: B19 infected (n = 14), B19 exposed but non-infected (n = 16), other illness with rash (n = 3), chronic arthropathy of unknown aetiology (n = 4) and healthy controls (n = 7). Sera from 11 B19 seronegative subjects were also studied. Sera collected at initial diagnosis or at the time of accidental B19 exposure in pregnancy were tested for NS1 antibody and evidence of B19 DNA by nested PCR.

Nonopsonic phagocytosis of Pseudomonas aeruginoas: insights from an infant with leukocyte adhesion deficiency.

Children with leukocyte adhesion deficiency type I are at risk for overwhelming infection because their neutrophils lack surface beta 2 integrins (CD18/CD11) that normally interact with endothelial cell adhesion molecules and mediate migration to sites of bacterial invasion. In vitro studies of phagocytic cells from an infant with leukocyte adhesion deficiency type I demonstrated that complement receptor 3 (CD18/CD11b) mediates nonopsonic phagocytosis of some Pseudomonas aeruginosa strains and might play a control role in the control of Pseudomonas infections at sites where there are low levels of opsonins.

Melatonin treatment of non-epileptic myoclonus in children.

Oral melatonin (MLT) has been used by our Vancouver research group in the treatment of paediatric sleep disorders since 1991; slightly over 200 children, mainly with multiple disabilities, who frequently had seizures, have been treated. Three children with markedly delayed sleep onset due to recurring myoclonus were also referred for MLT treatment: two had non-epileptic, and one had epileptic and non-epileptic myoclonus. Low doses of oral MLT (3 to 5 mg) unexpectedly abolished their myoclonus and allowed them to sleep.