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.

Role of beta-cell prohormone convertase (PC)1/3 in processing of pro-islet amyloid polypeptide.

Islet amyloid polypeptide (IAPP) (amylin), the major component of islet amyloid, is produced by cleavage at the COOH- and NH(2)-termini of its precursor, proIAPP, likely by the beta-cell prohormone convertases (PC) 1/3 and PC2. Mice lacking PC2 can process proIAPP at its COOH- but not its NH(2)-terminal cleavage site, suggesting that PC1/3 is capable of initiating proIAPP cleavage at its COOH-terminus. To determine the precise role of PC1/3 in proIAPP processing, Western blot analysis was performed on islets isolated from mice lacking PC1/3 (PC1/3(-/-)).

A highly conserved NTRK3 C-terminal sequence in the ETV6-NTRK3 oncoprotein binds the phosphotyrosine binding domain of insulin receptor substrate-1: an essential interaction for transformation.

Receptor tyrosine kinases are integral components of cellular signaling pathways and are frequently deregulated in malignancies. The NTRK family of neurotrophin receptors mediate neuronal cell survival and differentiation, but altered NTRK signaling has also been implicated in oncogenesis. The ETV6-NTRK3 (EN) gene fusion occurs in human pediatric spindle cell sarcomas and secretory breast carcinoma, and encodes the oligomerization domain of the ETV6 transcription factor fused to the protein-tyrosine kinase domain of NTRK3.

Hospitals and academic health sciences centres: leaders or followers in health globalization?

The overall impact of globalization on health outcomes is contentious, but there is no doubt that knowledge transfer and the extension of specific health interventions to developing countries promise extraordinary benefits. It has been suggested that improved information/communications technology and the creation of distributed hospital systems leading a virtual healthcare web will permit realization of the promise of globalization. It is argued in this commentary that such evolution will require a new model of shared governance in the healthcare system.

Identification of a beta-cell-specific HLA class I restricted epitope in type 1 diabetes.

Type 1 diabetes is an autoimmune disease in which pancreatic beta-cells are destroyed by cytotoxic T-cells that recognize peptide epitopes presented by HLA class I molecules. The identification of human beta-cell epitopes may significantly improve the prospects for immunodiagnosis and immunotherapy in type 1 diabetes. Using algorithms to predict nonameric beta-cell peptides that would bind to the common HLA allele, HLA-A*0201, we identified a potential epitope from the leader sequence of islet amyloid polypeptide (human islet amyloid polypeptide [IAPP] precursor protein [preproIAPP] 5-13: KLQVFLIVL).

Lack of islet neogenesis plays a key role in beta-cell depletion in mice infected with a diabetogenic variant of coxsackievirus B4.

Group B coxsackieviruses (CVBs) have a well-established association with type 1 diabetes but the mechanism of depletion of beta-cell mass following infection has not yet been defined. In this report we show that the major difference in pathogenesis between the E2 diabetogenic strain of CVB4 and the prototypic JVB strain in SJL mice is not in tropism for islet cells but in the degree of damage inflicted on the exocrine pancreas and the resulting capacity for regeneration of both acinar and islet tissue by the host. Both strains replicated to a high titre in acinar tissue up to day 3 post-infection (p.

Retroposon compensatory mechanism hypothesis not supported: Zfa knockout mice are fertile.

It is hypothesized that autosomal retroposons compensate for the loss of their inactivated essential X-chromosome progenitors during spermatogenesis. Here we test this Retroposon Compensatory Mechanism (RCM) hypothesis using the Zfy gene family. The mouse autosomal retroposon Zfa is expressed in testes at the same developmental time points at which Zfx levels decline, which correspond to the time of male sex chromosome inactivation, suggesting that Zfa may compensate for the loss of Zfx during spermatogenesis.

Are there developmentally distinct motor indicators of pain in preterm infants?

The aims of this study were to examine preterm infant reactions to pain in detail over prolonged time periods using multiple measures, and to assess the value of including specific body movements of the Neonatal Individualized Developmental Care and Assessment Program (NIDCAP) system to evaluate pain. Ten preterm infants born at 31 weeks mean gestational age (GA) and mean birth weight 1676 g were studied during a routine blood collection in a Level III neonatal intensive care unit (NICU). At 32-week post-conceptional age, computerized physiologic and video recordings were obtained continuously for 60 min (prior to, during and after lance).

Clinical aspects, prenatal diagnosis, and pathogenesis of trisomy 16 mosaicism.

Introduction: Analysis of data from cases of trisomy mosaicism can provide insight for genetic counselling after prenatal diagnosis and for the elucidation of the pathogenesis of trisomy during pregnancy.

Methods: Statistical analysis was carried out on data from 162 cases of pregnancies with prenatal diagnosis of trisomy 16 mosaicism.

Results: The majority of cases resulted in live birth (66%) with an average gestational age of 35.

Loss of a single allele of SHIP exacerbates the immunopathology of Pten heterozygous mice.

Phosphatidylinositol 3-kinase (PI3K) has emerged as a critical component of multiple immune system intracellular signalling pathways. The levels and relative ratios of PI3K products, phosphatidylinositol (3,4) bisphosphate (PI(3,4)P(2)) and phosphatidylinositol (3,4,5) trisphosphate (PIP(3)), are regulated by inositol phosphatases such as Pten and SHIP. Interestingly, mice heterozygous for Pten, a 3'-inositol phosphatase, develop a progressive lymphoproliferative syndrome with autoimmune features.

Early pain in preterm infants. A model of long-term effects.

There are multiple lines of evidence suggesting that in vulnerable prematurely born infants, repeated and prolonged pain exposure may affect the subsequent development of pain systems, as well as potentially contribute to alterations in long-term development and behavior. Multiple factors cumulatively contribute to altered developmental trajectories in such infants. These include characteristics of the developing organism (low tactile threshold, sensitization, rapid brain development), characteristics intrinsic to the infant (gestation, illness severity), characteristics of the experience in the neonatal intensive care unit (pain exposure and cumulative stress), and characteristics of the caregivers within their family and social context.

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.

Does parenchymal brain injury affect biobehavioral pain responses in very low birth weight infants at 32 weeks' postconceptional age?

Objective: Children with neurologic impairments have shown diminished pain response compared with control subjects; however, it remains unclear what mechanisms underlie this response or when it develops. If this were also true with premature infants who undergo neonatal intensive care, then infants with parenchymal brain injury (PBI) would be at increased risk of underrecognition and undertreatment of procedural pain. The purpose of this study was to determine whether infants with PBI display altered responses to acute procedural pain at 32 weeks' postconceptional age (PCA), compared with control subjects.

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.

Novel Sxr(a) ES cell line offers hope for Y chromosome gene-targeted mice.

A mouse targeted for a Y Chromosome gene has not been reported. Because the Y Chromosome is present in only one copy, and most of its genes are critical for germ cell development, such a mouse would likely be infertile. Thus, we describe a new reproductive strategy to enable transmission of targeted Y Chromosome genes to subsequent generations.

Novel vertebrate genes and putative regulatory elements identified at kidney disease and NR2E1/fierce loci.

Fierce (frc) mice are deleted for nuclear receptor 2e1 (Nr2e1), and exhibit cerebral hypoplasia, blindness, and extreme aggression. To characterize the Nr2e1 locus, which may also contain the mouse kidney disease (kd) allele, we compared sequence from human, mouse, and the puffer fish Fugu rubripes. We identified a novel gene, c222389, containing conserved elements in noncoding regions.

Disruption of a single Pten allele augments the chemotactic response of B lymphocytes to stromal cell-derived factor-1.

The tumor suppressor, Pten, has emerged as a critical negative regulator of phosphatidylinositol-3-kinase-dependent intracellular signaling pathways responsible for phenomena such as cellular adhesion, proliferation, and apoptosis. Herein, we present evidence that Pten regulates chemokine-dependent events in B lymphocytes. Primary B cells isolated from Pten(+/-) mice demonstrated increased responsiveness to stromal cell-derived factor-1-induced chemotaxis.

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.

Pattern of learning disabilities in children with extremely low birth weight and broadly average intelligence.

Objectives: To examine the prevalence and pattern of specific areas of learning disability (LD) in neurologically normal children with extremely low birth weight (ELBW) (< or = 800 g) who have broadly average intelligence compared with full-term children with normal birth weight of comparable sociodemographic background, and to explore concurrent cognitive correlates of the specific LDs.

Design: Longitudinal follow-up; geographically defined region.

Setting: Regional follow-up program.

Meningococcal disease and vaccination in North America.

In North America, meningococcal disease occurs at a rate of I case per 100000 population per year, producing 2725 cases notified in the US in 1998 and 155 laboratory confirmed cases in Canada in the same year. A majority of these cases occur in the winter season and in early childhood, with a case fatality rate of approximately 10%. There has been an increase in the proportion of cases due to serogroup Y meningococci over the past decade: in 1995-98 in the US, 33% of cases were due to serogroup B, 28% were due to serogroup C and 34% were due to serogroup Y; in Canada in 1995-96, 47% of cases were due to serogroup B, 40% were due to serogroup C and 10% were due to serogroup Y.

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.

Relations between behavioral and cardiac autonomic reactivity to acute pain in preterm neonates.

Objective: The purpose of this study was to assess relations and concordance between behavioral and physiologic reactivity to pain in preterm neonates at 32 weeks postconceptional age as a function of gestational age at birth.

Setting: Level III neonatal intensive care unit.

Design/patients: The study group comprised 136 preterm neonates (mean [range] birthweight, 1,020 g [445-1,500 g]: gestational age at birth, 28 weeks [23-32 weeks]) separated into three groups according to gestational age at birth as follows: 23 to 26 weeks (n = 48), 27 to 29 weeks (n = 52), and 30 to 32 weeks (n = 36).

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.

Infection with Burkholderia cepacia complex genomovars in patients with cystic fibrosis: virulent transmissible strains of genomovar III can replace Burkholderia multivorans.

Infection with Burkholderia cepacia complex in patients with cystic fibrosis (CF) results in highly variable clinical outcomes. The purpose of this study was to determine if there are genomovar-specific disparities in transmission and disease severity. B.