A new way of targeting to treat nerve injury.

Although neurons within the peripheral nervous system have a remarkable ability to repair themselves after injury, neurons within the central nervous system do not spontaneously regenerate. This problem has remained recalcitrant despite a century of research on the reaction of axons to injury. The balance between inhibitory cues present in the environment and the intrinsic growth capacity of the injured neuron determines the extent of axonal regeneration following injury.

A new way of targeting to treat coronary artery disease.

Atherosclerosis is a complex disease process in which genetic, lipid, cellular and immunological factors combine to determine the location, severity and timing of lesion development and clinical events. It has been demonstrated, however, that inflammation governs atherosclerosis during the course of development of atherosclerosis. It has also been demonstrated that regulation of the inflammatory reaction (e.

Cancer therapy using tumor-associated antigens to reduce side effects.

Tumor-associated antigens recently have become very popular in cancer therapy. They can be targeted to reduce side effects of traditional cancer therapy. In this review, ten promising tumor-associated antigens are being discussed in detail.

Akt-mediated YB-1 phosphorylation activates translation of silent mRNA species.

YB-1 is a broad-specificity RNA-binding protein that is involved in regulation of mRNA transcription, splicing, translation, and stability. In both germinal and somatic cells, YB-1 and related proteins are major components of translationally inactive messenger ribonucleoprotein particles (mRNPs) and are mainly responsible for storage of mRNAs in a silent state. However, mechanisms regulating the repressor activity of YB-1 are not well understood.

Selective degeneration and nuclear localization of mutant huntingtin in the YAC128 mouse model of Huntington disease.

Huntington disease (HD) is an adult onset neurodegenerative disorder that predominantly affects the striatum and cortex despite ubiquitous expression of mutant huntingtin (htt). Here we demonstrate that this pattern of selective degeneration is present in the YAC128 mouse model of HD. At 12 months, YAC128 mice show significant atrophy in the striatum, globus pallidus and cortex with relative sparing of the hippocampus and cerebellum (striatum: -10.

Body movements: an important additional factor in discriminating pain from stress in preterm infants.

Objectives: To describe developmentally appropriate, specific body movements and other biobehavioral responses of preterm infants to a group of routine care giving tasks (Clustered Care), and to compare responses to acute pain with those of Clustered Care.

Methods: In a randomized design, 54 preterm infants were assessed at 32 weeks gestational age during 3 phases of blood collection (Baseline, Lance/squeeze, Recovery) and of diaper changing, measuring abdominal girth and axillary temperature, and mouth care (Baseline, Clustered Care, Recovery) in a neonatal intensive care unit. The Newborn Individualized Developmental Care and Assessment Program and 1 facial action from the Neonatal Facial Coding System, Brow Bulge, were coded from separate continuous bedside video recordings.

Celecoxib analogues disrupt Akt signaling, which is commonly activated in primary breast tumours.

Introduction: Phosphorylated Akt (P-Akt) is an attractive molecular target because it contributes to the development of breast cancer and confers resistance to conventional therapies. Akt also serves as a signalling intermediate for receptors such as human epidermal growth factor receptor (HER)-2, which is overexpressed in 30% of breast cancers; therefore, inhibitors to this pathway are being sought. New celecoxib analogues reportedly inhibit P-Akt in prostate cancer cells.

Ethyl-EPA treatment improves motor dysfunction, but not neurodegeneration in the YAC128 mouse model of Huntington disease.

Huntington disease (HD) is an adult-onset neurodegenerative disorder that is characterized by selective degeneration in the striatum. There are currently no treatments that can prevent the progressive decline of motor and cognitive function in HD. In parallel with a human clinical trial, we examined the efficacy of ethyl-EPA treatment in the YAC128 mouse model of HD.

Pseudomonas aeruginosa: role in the pathogenesis of the CF lung lesion.

Lung disease is the leading cause of morbidity and mortality in individuals with cystic fibrosis (CF), with P. aeruginosa the main pulmonary infectious agent. Although CF patients can become infected with other microorganisms (such as Burkholderia cepacia complex, Staphylococcus aureus, Haemophilus influenzae, and atypical mycobacteria), P.

Therapy with both magnesium sulfate and nifedipine does not increase the risk of serious magnesium-related maternal side effects in women with preeclampsia.

Objective: Does the use of nifedipine and magnesium sulfate together increase serious magnesium-related effects?

Study Design: This was a retrospective chart review of women who were admitted to BC Women's Hospital and Health Centre (1997-2001) and were given intravenous magnesium sulfate for preeclampsia. Serious magnesium-related effects were compared among 162 cases who received magnesium sulfate and contemporaneous nifedipine and 215 control subjects who received magnesium sulfate and either another antihypertensive (n=32 women) or no antihypertensive (n=183 women) medication. Chi-squared test, Fisher's exact test, or the Student t test was used for data comparison between cases and each control group.

Pathological aggression in "fierce" mice corrected by human nuclear receptor 2E1.

"Fierce" mice, homozygous for the deletion of nuclear receptor 2E1 (NR2E1), show abnormal brain-eye development and pathological aggression. To evaluate functional equivalency between mouse and human NR2E1, we generated mice transgenic for a genomic clone spanning the human NR2E1 locus and bred these animals to fierce mice deleted for the corresponding mouse gene. In fierce mutants carrying human NR2E1, structural brain defects were eliminated and eye abnormalities ameliorated.

Gonadotropins upregulate the epidermal growth factor receptor through activation of mitogen-activated protein kinases and phosphatidyl-inositol-3-kinase in human ovarian surface epithelial cells.

Gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) have been implicated as probable risk factors in epithelial ovarian carcinomas, most of which are derived from ovarian surface epithelium (OSE). Since epidermal growth factor (EGF) increases the growth of ovarian surface epithelial cells, we determined the effect of gonadotropins on the expression of epidermal growth factor receptor (EGFR). We investigated the basal levels of EGFR mRNA and protein, and the mechanisms involved in the regulation of EGFR at the transcriptional and translational levels by FSH and LH.

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.

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.

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.

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.

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.

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.