Selection on cis-regulatory variation at B4galnt2 and its influence on von Willebrand factor in house mice.

The RIIIS/J inbred mouse strain is a model for type 1 von Willebrand disease (VWD), a common human bleeding disorder. Low von Willebrand factor (VWF) levels in RIIIS/J are due to a regulatory mutation, Mvwf1, which directs a tissue-specific switch in expression of a glycosyltransferase, B4GALNT2, from intestine to blood vessel. We recently found that Mvwf1 lies on a founder allele common among laboratory mouse strains.

Metronomic scheduling of imatinib abrogates clonogenicity of neuroblastoma cells and enhances their susceptibility to selected chemotherapeutic drugs in vitro and in vivo.

Imatinib is currently in early clinical trials as targeted therapy for relapsed neuroblastomas and other childhood solid tumors expressing platelet-derived growth factor receptors (PDGFR) or c-Kit. Short-term treatment with imatinib in clinically achievable concentrations is ineffective in neuroblastoma in vitro. However, clinically, imatinib is administered daily over long time periods.

Substance use disorders among psychotic patients admitted to inpatient psychiatric care.

Previous epidemiological and clinical studies have shown high rates of substance use disorders in patients with psychotic disorders. There are few studies from the Scandinavian countries. The aim of this study was to investigate the rate of substance use disorders in a group of Norwegian psychotic inpatients from a specific catchment area.

Tumor-growth-promoting cyclooxygenase-2 prostaglandin E2 pathway provides medulloblastoma therapeutic targets.

Prostaglandin E(2) (PGE(2)) has been shown to play important roles in several aspects of tumor development and progression. PGE(2) is synthesized from arachidonic acid by cyclooxygenases (COX) and prostaglandin E synthases (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP(1) through EP(4). In this study, we show for the first time that medulloblastoma (MB), the most common malignant childhood brain tumor, expresses high levels of COX-2, microsomal prostaglandin E synthase-1, and EP(1) through EP(4) and secretes PGE(2).

Expression of enzymes and receptors of the leukotriene pathway in human neuroblastoma promotes tumor survival and provides a target for therapy.

The metabolism of arachidonic acid by the cyclooxygenase (COX) or lipoxygenase (LO) pathways generates eicosanoids that have been implicated in the pathogenesis of a variety of human diseases, including cancer. In this study, we examined the expression and significance of components within the 5-LO pathway in human neuroblastoma, an embryonal tumor of the sympathetic nervous system. High expression of 5-LO, 5-LO-activating protein (FLAP), leukotriene A(4) hydrolase, leukotriene C(4) synthase, and leukotriene receptors was detected in a majority of primary neuroblastoma tumors and all cell lines investigated.

The endothelial-specific regulatory mutation, Mvwf1, is a common mouse founder allele.

Mvwf1 is a cis-regulatory mutation previously identified in the RIIIS/J mouse strain that causes a unique tissue-specific switch in the expression of an N-acetylgalactosaminyltransferase, B4GALNT2, from intestinal epithelium to vascular endothelium. Vascular B4galnt2 expression results in aberrant glycosylation of von Willebrand Factor (VWF) and accelerated VWF clearance from plasma. We now report that 13 inbred mouse strains share the Mvwf1 tissue-specific switch and low VWF phenotype, including five wild-derived strains.

Adherence in Internet-based interventions.

Background: The Internet is a promising channel for delivering health-promoting interventions. A common problem for Internet-based interventions is low adherence. The current paper reports adherence rates from three different Internet-based trials with potential covariates.

Inhibitors of mammalian target of rapamycin downregulate MYCN protein expression and inhibit neuroblastoma growth in vitro and in vivo.

Mammalian target of rapamycin (mTOR) has been shown to play an important function in cell proliferation, metabolism and tumorigenesis, and proteins that regulate signaling through mTOR are frequently altered in human cancers. In this study we investigated the phosphorylation status of key proteins in the PI3K/AKT/mTOR pathway and the effects of the mTOR inhibitors rapamycin and CCI-779 on neuroblastoma tumorigenesis. Significant expression of activated AKT and mTOR were detected in all primary neuroblastoma tissue samples investigated, but not in non-malignant adrenal medullas.

Physiology of the motor cortex in polio survivors.

We hypothesized that the corticospinal system undergoes functional changes in long-term polio survivors. Central motor conduction times (CMCTs) to the four limbs were measured in 24 polio survivors using transcranial magnetic stimulation (TMS). Resting motor thresholds and CMCTs were normal.

The novel melphalan prodrug J1 inhibits neuroblastoma growth in vitro and in vivo.

Neuroblastoma is the most common extracranial solid tumor of childhood. The activity of J1 (l-melphalanyl-p-l-fluorophenylalanine ethyl ester), an enzymatically activated melphalan prodrug, was evaluated in neuroblastoma models in vitro and in vivo. Seven neuroblastoma cell lines with various levels of drug resistance were screened for cytotoxicity of J1 alone or in combination with standard cytotoxic drugs, using a fluorometric cytotoxicity assay.

Comparison of hamstring and quadriceps femoris electromyographic activity between men and women during a single-limb squat on both a stable and labile surface.

The purpose of this study was to determine if women are quadriceps dominant and men are hamstring dominant during the performance of a partial single-leg squat (SLS) on both a stable and labile ground surface against body weight resistance. Thirty healthy participants (15 men and 15 women) performed an SLS on both a stable surface and a 6.4-cm-thick vinyl pad.

Celecoxib prevents neuroblastoma tumor development and potentiates the effect of chemotherapeutic drugs in vitro and in vivo.

Purpose: Neuroblastoma is the most common and deadly solid tumor of childhood. Cyclooxygenase-2 is expressed in clinical neuroblastoma tumors and cell lines and inhibitors of this enzyme induce apoptosis in human neuroblastoma cells in vitro and in neuroblastoma xenografts in vivo. We hypothesized that the cyclooxygenase-2-specific inhibitor celecoxib could enhance the cytotoxic effect of chemotherapeutic drugs currently used in neuroblastoma treatment.

The antimicrobial peptide, lactoferricin B, is cytotoxic to neuroblastoma cells in vitro and inhibits xenograft growth in vivo.

Antimicrobial peptides have been shown to exert cytotoxic activity towards cancer cells through their ability to interact with negatively charged cell membranes. In this study the cytotoxic effect of the antimicrobial peptide, LfcinB was tested in a panel of human neuroblastoma cell lines. LfcinB displayed a selective cytotoxic activity against both MYCN-amplified and non-MYCN-amplified cell lines.

Neuroblastoma cell death in response to docosahexaenoic acid: sensitization to chemotherapy and arsenic-induced oxidative stress.

Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid vital for the developing nervous system and significantly decreased in neuroblastoma cells compared to nontransformed nervous tissue. We investigated whether supplementation of DHA affects the susceptibility of neuroblastoma cells to oxidative stress generated endogenously and in response to cytotoxic therapy. DHA, but not the monounsaturated oleic acid (OA), induced dose- and time-dependent neuroblastoma cell death.

Predictors of psychiatric hospitalization for adults with co-occurring substance and mental disorders as compared to adults with mental illness only.

Predictors of psychiatric hospitalization, predisposing, enabling and need, of adults with co-occurring mental and substance disorders were compared to predictors for adults with a mental illness only. Research participants were 1613 users of crisis intervention services. Findings using Cox regression show that dually-diagnosed individuals were more likely to be hospitalized.

NSAIDs in neuroblastoma therapy.

Cyclooxygenases (COX) catalyse the conversion of arachidonic acid to prostaglandins. COX-2 is upregulated in several adult epithelial cancers. In neuroblastoma it has been shown that the majority of primary tumours and cell lines express high levels of COX-2, whereas normal adrenal medullas from children do not express COX-2.

Proton magnetic resonance spectroscopy in neuroblastoma: current status, prospects and limitations.

Non-invasive biological information about residual neuroblastoma tumour tissue could allow treatment monitoring without the need for repeated biopsies. Magnetic resonance spectroscopy (MRS) can be performed with standard MR-scanners, providing specific biochemical information from selected tumour regions. By proton 1H-MRS, lipids, certain amino acids and lactate can be detected and their relative concentrations estimated in vivo.

[Drug screening among patients aged 17-40 admitted with psychosis].

Background: High frequency of co-occurring substance use disorders and psychiatric disorders is reported in several studies. An important issue is whether we can rely on patient reports only. The purpose of this investigation was to find the prevalence of substance use among younger psychotic inpatients in Norway and to compare patients' self reports with the results of screening for drugs.

Synergistic induction of apoptosis in neuroblastoma cells using a combination of cytostatic drugs with interferon-gamma and TRAIL.

The majority of high-risk neuroblastomas lack the expression of caspase-8 due to gene silencing which suggest a mechanism for the selection of tumour cells that are refractory to multiple cytotoxic drugs including tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). Inhibitors of DNA methyltransferases and IFN-gamma induce expression of caspase-8, and sensitise some neuroblastoma cells to TRAIL-mediated apoptosis. Here we demonstrate that a combination of cytostatic drugs with IFN-gamma and TRAIL synergistically induces neuroblastoma cell death, which may have implications for future therapy of children with neuroblastoma.

Cyclooxygenase-2 is expressed in neuroblastoma, and nonsteroidal anti-inflammatory drugs induce apoptosis and inhibit tumor growth in vivo.

Neuroblastoma is the single most common and deadly tumor of childhood and is often associated with therapy resistance. Cyclooxygenases (COXs) catalyze the conversion of arachidonic acid to prostaglandins. COX-2 is up-regulated in several adult epithelial cancers and is linked to proliferation and resistance to apoptosis.

Facilitators and barriers to support group participation for family caregivers of adults with mental illness.

Objective: Few low-income and minority caregivers of persons with serious mental illness participate in support groups. This study examined the facilitators and barriers to participation in support groups for families of persons with serious mental illness among lower socioeconomic African-American and Caucasian family caregivers. Three hypotheses were tested in a multivariate model which included need, enabling and predisposing variables utilizing a revised version of the Andersen model.

Status of pretreatment evaluation, treatment and follow-up regimens for renal cell carcinoma in the Nordic countries.

Objective: One prerequisite for performing multicentre studies is that the clinical handling of the patients must be uniform. We therefore evaluated possible differences in pretreatment evaluation, surgical treatment and follow-up regimes between the Nordic countries and between the different departments that performed nephrectomy due to renal cell carcinoma.

Material And Methods: A questionnaire comprising 21 different questions was sent to all hospitals in the five Nordic countries performing nephrectomy.