Proteolytic processing of the ovine prion protein in cell cultures.

The cellular compartment and purpose of the proteolytic processing of the prion protein (PrP) are still under debate. We have studied ovine PrP constructs expressed in four cell lines; murine neuroblastoma cells (N2a), human neuroblastoma cells (SH-SY5Y), dog kidney epithelial cells (MDCK), and human furin-deficient colon cancer cells (LoVo). Cleavage of PrP in LoVo cells indicates that the processing is furin independent.

Morphological changes in the Royal College of Surgeons rat retina during photoreceptor degeneration and after cell-based therapy.

There are concomitant morphological and functional changes in the inner retina during the course of photoreceptor degeneration in a range of animal models of retina degeneration and in humans with eye disease. One concern that has been raised is that the changes occurring in the inner retina might compromise attempts to rescue or restore visual input by various interventional approaches. It is known that cell-based therapy can preserve significant visual capability for many months.

The crystal structure of recombinant proDer p 1, a major house dust mite proteolytic allergen.

Allergy to house dust mite is among the most prevalent allergic diseases worldwide. Most house dust mite allergic patients react to Der p 1 from Dermatophagoides pteronyssinus, which is a cysteine protease. To avoid heterogeneity in the sample used for crystallization, a modified recombinant molecule was produced.

Hip dysplasia and osteoarthrosis: a survey of 4151 subjects from the Osteoarthrosis Substudy of the Copenhagen City Heart Study.

Introduction: Hip dysplasia (HD) is assumed to be an etiological factor in the development of premature hip osteoarthrosis (OA). We established the prevalences of HD and OA in adults according to qualified radiographic discriminators, and investigated the relationship between HD and OA.

Methods: Wiberg's CE angle (CE), Sharp's angle, the femoral head extrusion index, the acetabular depth ratio (ADR), the radiographic OA discriminators of Croft, and of Kellgren and Lawrence, and also minimum joint space width (JSW) < or = 2 mm were applied to the standing, standardized pelvic radiographs of 1429 men (22-93 years), and 2430 women (22-92 years).

Grafting of ARPE-19 and Schwann cells to the subretinal space in RCS rats.

Purpose: To study the distribution of the human retinal pigment epithelium (hRPE) cell line ARPE-19 and human Schwann (hSC) cells grafted to the subretinal space of the Royal College of Surgeon (RCS) rat and the relation of graft cell distribution to photoreceptor rescue.

Methods: Cell suspensions of both donor types were injected into the subretinal space of 3-week-old dystrophic RCS rats through a transscleral approach, human fibroblast and medium were used as control grafts. All animals were maintained on oral cyclosporine.

Intracellular collagen degradation mediated by uPARAP/Endo180 is a major pathway of extracellular matrix turnover during malignancy.

We recently reported that uPARAP/Endo180 can mediate the cellular uptake and lysosomal degradation of collagen by cultured fibroblasts. Here, we show that uPARAP/Endo180 has a key role in the degradation of collagen during mammary carcinoma progression. In the normal murine mammary gland, uPARAP/Endo180 is widely expressed in periductal fibroblast-like mesenchymal cells that line mammary epithelial cells.

CEP-11004, an inhibitor of the SAPK/JNK pathway, reduces TNF-alpha release from lipopolysaccharide-treated cells and mice.

CEP-11004, a mixed lineage kinase (MLK) inhibitor, was examined for its effects on tumor necrosis factor-alpha (TNF-alpha) production in human THP-1 monocytes, mouse BV-2 microglia, and C57Bl/6 mice. CEP-11004 inhibited TNF-alpha secretion up to 90% in THP-1 cells incubated with 3 mug/ml lipopolysaccharide, with an IC50 of 137+/-14 nM. CEP-11004 also inhibited TNF-alpha production in lipopolysaccharide-stimulated microglial cells, but did not inhibit the initial increase in TNF-alpha mRNA expression as measured by real-time polymerase chain reaction (PCR).

Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase.

X inactivation involves the stable silencing of one of the two X chromosomes in XX female mammals. Initiation of this process occurs during early development and involves Xist (X-inactive-specific transcript) RNA coating and the recruitment of Polycomb repressive complex (PRC) 2 and PRC1 proteins. This recruitment results in an inactive state that is initially labile but is further locked in by epigenetic marks such as DNA methylation, histone hypoacetylation, and MACROH2A deposition.

Augmenting tumor sensitivity to topotecan by transient hypoxia.

We examined how the effect of topotecan is modulated by transient hypoxia in three different tumor lines, Lewis lung carcinoma (LLC), U87 human glioblastoma and DMS273 human small cell lung cancer. Four groups of tumor bearing mice were treated with saline or a single dose of topotecan, immediately followed by 6-h or 72-h exposure to a hypoxic environment (10% O(2)) or normal air. Topotecan + hypoxia resulted in significantly greater suppression of tumor growth than normoxic topotecan or hypoxia alone.

Diacylglycerol kinase iota regulates Ras guanyl-releasing protein 3 and inhibits Rap1 signaling.

To study the physiological function of diacylglycerol (DAG) kinase iota (DGKiota), which converts DAG to phosphatidic acid, we deleted this gene in mice. In contrast to previous studies showing that DGK isoforms decrease Ras activity, signaling downstream of Ras in embryonic fibroblasts was significantly reduced in cells lacking DGKiota. DGKs regulate Ras signaling by attenuating the function of the DAG-dependent Ras guanyl nucleotide-releasing proteins (RasGRPs).

Assessing health-related quality of life in adolescents: some psychometric properties of the first Norwegian version of KINDL.

The study presented in this paper is part of a larger Norwegian investigation among adolescents, where the overall aim is to develop methods to promote their quality of life (QoL), to discover risk factors or threats to adolescents' well-being, and finally to prevent the negative effects of such factors. An adequate generic health-related quality of life (HR-QoL) measure is therefore needed. However, only a limited number of well validated instruments that measure HR-QoL in adolescents exist, and to date only a few has been translated into Norwegian.

In vitro culture of skin-homing T lymphocytes from inflammatory skin diseases.

We, in this study, describe how T lymphocytes in a skin biopsy can proliferate in vitro for up to 3 months by using T-cell growth factors - interleukin-2 (IL-2) and IL-4 yielding approximately 100-160 million T lymphocytes within 1 month. We established cell lines from three tuberculin skin tests, four positive patch tests, 15 of 16 biopsies from atopic dermatitis (AD), 15 of 19 biopsies from mycosis fungoides (MF), 12 of 24 biopsies from psoriasis vulgaris, which was significantly less than AD (P < 0.05), and with a reduced cumulative number of lymphocytes (P < 0.

Garlic arrests MDA-MB-435 cancer cells in mitosis, phosphorylates the proapoptotic BH3-only protein BimEL and induces apoptosis.

Components of garlic (Allium sativum) can cause disruption of microtubules, cell cycle arrest, and apoptosis in cancer cells. We show here that a water-soluble extract of garlic arrested MDA-MB-435 cancer cells in mitosis and caused apoptosis. The proapoptotic BH3-only, bcl-2 family protein BimEL, which in healthy cells can be tightly sequestered to the microtubule-associated dynein motor complex, was modified after garlic treatment.

Mechanism of protein tyrosine phosphatase 1B-mediated inhibition of leptin signalling.

Upon leptin binding, the leptin receptor is activated, leading to stimulation of the JAK/STAT signal transduction cascade. The transient character of the tyrosine phosphorylation of JAK2 and STAT3 suggests the involvement of protein tyrosine phosphatases (PTPs) as negative regulators of this signalling pathway. Specifically, recent evidence has suggested that PTP1B might be a key regulator of leptin signalling, based on the resistance to diet-induced obesity and increased leptin signalling observed in PTP1B-deficient mice.

Ca2+-induced permeability transition in human lymphoblastoid cell mitochondria from normal and Huntington's disease individuals.

Huntington's disease (HD) is associated with expansion of polyglutamine tract in a protein named huntingtin (htt) that is expressed in virtually all body tissues. Thus mutated htt (HD-htt) might affect all organs, although clinical manifestations of HD are associated with selective loss of corticostriatal neurons of the brain. In this work we studied how HD-htt affects mitochondria in human peripheral blood cells.

An 18-month follow-up study after randomized treatment of phimosis in boys with topical steroid versus placebo.

Objective: To evaluate the treatment of phimosis using topical steroid.

Material And Methods: This was a follow-up study after a prospective, randomized, double-blind study. A total of 137 boys with phimosis were randomly assigned to either betamethasone treatment or placebo for 4 weeks, with application of the cream twice daily.

Xenobiotics and the glucocorticoid receptor: additive antagonistic effects on tyrosine aminotransferase activity in rat hepatoma cells.

Methylsulfonyl-PCBs (MeSO2-PCBs) and some fungicides were studied for their functional effects on the glucocorticoid signal transduction in the Reuber rat hepatoma H-II-E-C3 cell line. 4-Substituted MeSO2-PCBs, tolylfluanid and ketoconazole displayed antagonistic effects on dexamethasone-induced tyrosine aminotransferase specific activity (IC50 ranging from 0.7-5.

Inhibition of microglial inflammation by the MLK inhibitor CEP-1347.

CEP-1347 is a potent inhibitor of the mixed lineage kinases (MLKs), a distinct family of mitogen-activated protein kinase kinase kinases (MAPKKK). It blocks the activation of the c-Jun/JNK apoptotic pathway in neurons exposed to various stressors and attenuates neurodegeneration in animal models of Parkinson's disease (PD). Microglial activation may involve kinase pathways controlled by MLKs and might contribute to the pathology of neurodegenerative diseases.

Accumulation of miR-155 and BIC RNA in human B cell lymphomas.

We show that the microRNA miR-155 can be processed from sequences present in BIC RNA, a spliced and polyadenylated but non-protein-coding RNA that accumulates in lymphoma cells. The precursor of miR-155 is likely a transient spliced or unspliced nuclear BIC transcript rather than accumulated BIC RNA, which is primarily cytoplasmic. By using a sensitive and quantitative assay, we find that clinical isolates of several types of B cell lymphomas, including diffuse large B cell lymphoma (DLBCL), have 10- to 30-fold higher copy numbers of miR-155 than do normal circulating B cells.

Ryanodine receptor-operated activation of TRP-like channels can trigger critical Ca2+ signaling events in pancreatic beta-cells.

There is little information available concerning the link between the ryanodine (RY) receptors and the downstream Ca(2+) signaling events in beta-cells. In fura-2 loaded INS-1E cells, activation of RY receptors by 9-methyl 5,7-dibromoeudistomin D (MBED) caused a rapid rise of [Ca(2+)]i followed by a plateau and repetitive [Ca(2+)]i spikes on the plateau. The [Ca(2+)]i plateau was abolished by omission of extracellular Ca(2+) and by SKF 96365.

The androgen metabolite, 5alpha-androstane-3beta, 17beta-diol, is a potent modulator of estrogen receptor-beta1-mediated gene transcription in neuronal cells.

5alpha-Androstane-3beta, 17beta-diol (3betaAdiol) is a metabolite of the potent androgen, 5alpha-dihydrotestosterone. Recent studies showed that 3betaAdiol binds to estrogen receptor (ER)-beta and regulates growth of the prostate gland through an estrogen, and not androgen, receptor-mediated pathway. These data raise the possibility that 3betaAdiol could regulate important physiological processes in other tissues that produce 3betaAdiol, such as the brain.

Factors related to abstinence in a telephone helpline for smoking cessation.

Background: Studies indicate that shortage of cessation counsellors may be a major barrier for tobacco prevention among physicians. Telephone helplines (quitlines) may be an option. The effectiveness of the Swedish quitline and factors related to abstinence from smoking 12 months after the first contact were assessed.

Preservation of vision following cell-based therapies in a model of retinal degenerative disease.

This study examines whether subretinal transplantation of a human retinal pigment epithelial cell line (ARPE19) or human Schwann cells early in the course of degeneration can limit the loss of visual acuity that normally occurs in dystrophic Royal College of Surgeons (RCS) rats as they age. The acuity of both transplanted groups was significantly better than controls at all ages tested, though the rescue profile of each cell type was unique. These data indicate that the transplantation of cells with very different phenotypes can be used to limit the deterioration of spatial vision in an animal model of retinal degenerative disease.

Improved treatment of pelvis and inguinal nodes using modified segmental boost technique: dosimetric evaluation.

Purpose: To describe a novel, yet simple, modified segmental boost technique (MSBT) and to compare the dosimetry of our method with that of other traditional methods of treatment for the pelvis and inguinal nodes.

Methods And Materials: We developed a radiotherapy technique that uses linear accelerators with multileaf collimators to treat the pelvis and sequentially boost the inguinal regions, while minimizing "hot spots" across the match-line. This was achieved by angling the gantry for the inguinal fields so that their medial borders aligned with the divergence of the posterior pelvic field.