Effect of repeated intracoronary injection of bone marrow cells in patients with ischaemic heart failure the Danish stem cell study--congestive heart failure trial (DanCell-CHF).

Background: It has been suggested that myocardial regeneration may be achieved by a single intracoronary bone marrow derived stem cell infusion in selected patients with ischaemic heart disease. The effect is uncertain in patients with chronic ischaemic heart failure and it is not known whether repeated infusions would have additional positive effects.

Aims: To assess whether two treatments of intracoronary infusion of bone marrow stem cells, administered 4 months apart, could improve left ventricular (LV) systolic function in patients with chronic ischaemic heart failure.

Analysis of potential transcriptomic biomarkers for Huntington's disease in peripheral blood.

Highly quantitative biomarkers of neurodegenerative disease remain an important need in the urgent quest for disease-modifying therapies. For Huntington's disease (HD), a genetic test is available (trait marker), but necessary state markers are still in development. In this report, we describe a large battery of transcriptomic tests explored as state biomarker candidates.

Proteomic profiling of plasma in Huntington's disease reveals neuroinflammatory activation and biomarker candidates.

Huntington's disease (HD) causes widespread CNS changes and systemic abnormalities including endocrine and immune dysfunction. HD biomarkers are needed to power clinical trials of potential treatments. We used multiplatform proteomic profiling to reveal plasma changes with HD progression.

Disease-associated prion protein oligomers inhibit the 26S proteasome.

The mechanism of cell death in prion disease is unknown but is associated with the production of a misfolded conformer of the prion protein. We report that disease-associated prion protein specifically inhibits the proteolytic beta subunits of the 26S proteasome. Using reporter substrates, fluorogenic peptides, and an activity probe for the beta subunits, this inhibitory effect was demonstrated in pure 26S proteasome and three different cell lines.

Hsp27 overexpression in the R6/2 mouse model of Huntington's disease: chronic neurodegeneration does not induce Hsp27 activation.

Huntington's disease (HD) is caused by an expanded polyglutamine tract in the huntingtin protein. Mitochondrial dysfunction and free radical damage occur in both R6/2 mice and HD patient brains and might play a role in disease pathogenesis. In cell culture systems, heat-shock protein 27 (Hsp27), a small molecular chaperone, suppresses mutant huntingtin-induced reactive oxygen species formation and cell death.

Health effects of migration.

The proportion of citizens with an ethnic minority background in Denmark is rising and considerations about how to adapt health care services to the needs of this part of the population are becoming increasingly relevant. To do this, knowledge is needed about the factors influencing the health of these population groups. Migration is one of these factors.

[Health effects of migration].

Migration may have a negative impact on the health status of migrants due to the multiple physical and psychosocial strains affecting them during the entire process of migration. Being exposed to these strains and suffering different kinds of losses might lead to stress and increase in risk behaviour among migrants, thereby impacting negatively on their somatic and mental health. The negative health effects of migration are mediated by the individual's resources e.

Iminosugars as potential inhibitors of glycogenolysis: structural insights into the molecular basis of glycogen phosphorylase inhibition.

Iminosugars DAB (5), isofagomine (9), and several N-substituted derivatives have been identified as potent inhibitors of liver glycogen phosphorylase a (IC(50) = 0.4-1.2 microM) and of basal and glucagon-stimulated glycogenolysis (IC(50) = 1-3 microM).

Thioridazine reduces resistance of methicillin-resistant staphylococcus aureus by inhibiting a reserpine-sensitive efflux pump.

Previous studies suggested that the phenothiazine chlorpromazine (CPZ) could reverse or reduce the antibiotic resistance of bacteria. In some areas of the world, the majority of Staphylococcus aureus isolates are now resistant to methicillin, prompting this study to see whether such resistance can be altered by phenothiazine thioridazine (TZ), an agent with equal antibacterial activity, which is free of the severe side-effects associated with chronic administration of CPZ. The results indicated that, whereas methicillin-sensitive strains of Staphylococcus aureus (MSSA) were not rendered more susceptible to oxacillin, resistance to oxacillin by highly-resistant strains (MRSA) could be significantly reduced by sub-inhibitory concentrations of TZ.

[Stem cell therapy in ischemic heart disease].

Stem cell therapy is a treatment of great potential, including in cardiology. In the past few years, it has been shown that the heart has the potential for regeneration. Clinical studies have shown that intracoronary or intracardiac transplantation of bone marrow stem cells to patients with chronic or acute ischemic heart diseases improves the function and regional myocardial perfusion of the left ventricle.

"Test, score and scope": a selection strategy for safe reduction of upper gastrointestinal endoscopies in young dyspeptic patients referred from primary care.

Objective: To test the ability of pre-endoscopic clinical evaluation to predict clinically relevant findings of upper gastrointestinal endoscopy.

Material And Methods: Patients (341) who had been referred to upper gastrointestinal endoscopy for further evaluation of dyspeptic symptoms were included in this prospective, single-blinded study. Prior to endoscopy, the patients underwent a standardized clinical evaluation consisting of 1) a symptom questionnaire, 2) serological testing for Helicobacter pylori antibody and 3) determination of blood hemoglobin.

Novel splicing mutation in the NEMO (IKK-gamma) gene with severe immunodeficiency and heterogeneity of X-chromosome inactivation.

We report on a family with three stillborn males, three affected males who were small for gestational age and died within 8 months, and one male who died at age 5 years. This boy had cone-shaped teeth and oligoodontia. He had serious bacterial infections and inflammatory bowel disease.

Disease-related prion protein forms aggresomes in neuronal cells leading to caspase activation and apoptosis.

The molecular basis for neuronal death in prion disease is not established, but putative pathogenic roles for both disease-related prion protein (PrP(Sc)) and accumulated cytosolic PrP(C) have been proposed. Here we report that only prion-infected neuronal cells become apoptotic after mild inhibition of the proteasome, and this is strictly dependent upon sustained propagation of PrP(Sc). Whereas cells overexpressing PrP(C) developed cytosolic PrP(C) aggregates, this did not cause cell death.

High frequency of skewed X-chromosome inactivation in females with autoimmune thyroid disease: a possible explanation for the female predisposition to thyroid autoimmunity.

Context: Autoimmune thyroid diseases (AITD) comprise Graves' disease (GD) and Hashimoto's thyroiditis (HT). They are characterized by loss of immunological self-tolerance and female preponderance. Theoretically, X chromosome inactivation (XCI) and resultant tissue chimerism could offer an explanation for the female predisposition to AITD.

Dietary supplement use by varsity athletes at a Canadian university.

The purpose of this study was to assess reasons for and prevalence of supplement use among varsity athletes and nonvarsity athlete students (controls) at a Canadian university. A questionnaire, distributed to 247 varsity athletes and 204 controls, included variables regarding sports participation, supplements used, reasons for usage, perceived effects, and areas of interest about supplements. Response rates were 85.

High incidence of skewed X chromosome inactivation in young patients with familial non-BRCA1/BRCA2 breast cancer.

Background: A higher frequency of skewed X chromosome inactivation has been reported in a consecutive series of young patients with breast cancer compared with controls of a similar age.

Objective: To investigate the X inactivation pattern in patients with familial non-BRCA1/BRCA2 breast cancer (n = 272), BRCA1/BRCA2 germline mutations (n = 35), and sporadic breast cancer (n = 292).

Methods: X inactivation pattern was determined by polymerase chain reaction analysis of the highly polymorphic CAG repeat in the androgen receptor (AR) gene.

Twin study of genetic and aging effects on X chromosome inactivation.

To investigate the genetic influence on X chromosome inactivation and on age-related skewing of X inactivation, in particular, we analysed the X inactivation pattern (XIP) in peripheral blood cells from 118 young monozygotic (MZ) twin pairs (18-53 years), 82 elderly MZ twin pairs (55-94 years), 146 young dizygotic (DZ) twin pairs (20-54 years) and 112 elderly DZ twin pairs (64-95 years). Elderly twins had a higher frequency of skewed X inactivation (34%) than young twins (15%) (P<0.001).

Inhibition of the Carpobrotus edulis methanol extract on the growth of phagocytosed multidrug-resistant Mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus.

The Carpobrotus edulis methanol extract, inactive against the methicillin-resistant Staphylococcus aureus or the multidrug-resistant Mycobacterium tuberculosis, does inhibit the growth of these two bacteria once they are phagocytosed by monocyte derived human macrophages.

Mesenchymal stem cells: cell biology and potential use in therapy.

Mesenchymal stem cells are clonogenic, non-haematopoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages e.g. osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages e.

Expression of leptin receptor isoforms and effects of leptin on the proliferation and hormonal secretion in human pituitary adenomas.

Objective: To pursue whether leptin regulates anterior pituitary cells, we studied the ex vivo expression of several isoforms of the leptin receptor (OB-R) as well as the in vitro effects of leptin administration in human pituitary adenomas.

Methods: OB-R mRNA expression and in vitro response to leptin were studied in 39 pituitary macroadenomas.

Results: All 4 OB-R subtypes were expressed in most adenomas.

Identification, synthesis, and characterization of new glycogen phosphorylase inhibitors binding to the allosteric AMP site.

Inhibition of glycogen phosphorylase (GP) has attracted considerable attention during the last five to 10 years as a means of treating the elevated hepatic glucose production seen in patients with type 2 diabetes. Several different GP inhibitors binding to various binding sites of the GP enzyme have been reported in the literature. In this paper we report on a novel class of compounds that have been identified as potent GP inhibitors.

Growth hormone receptor expression and function in pituitary adenomas.

Objective And Design: Hypopituitarism, in particular GH deficiency, is prevalent in patients with clinically nonfunctioning pituitary adenomas (NFPAs) both before and after surgery. The factors regulating the growth of pituitary adenomas in general and residual tumour tissue in particular are not fully characterized, and the effect of GH and IGF-I on human pituitary cell proliferation has not previously been reported. In NFPA tissue from 14 patients we evaluated GH receptor (GHR) expression and signal transduction, and the effect of GH and IGF-I exposure on cell proliferation and hormone secretion in vitro.

ABC transporter activities of murine hematopoietic stem cells vary according to their developmental and activation status.

Primitive hematopoietic cells from several species are known to efflux both Hoechst 33342 and Rhodamine-123. We now show that murine hematopoietic stem cells (HSCs) defined by long-term multilineage repopulation assays efflux both dyes variably according to their developmental or activation status. In day 14.

Hydrolytic and enzymatic degradation of liquid-crystalline aromatic/aliphatic copolyesters.

Aromatic/aliphatic copolyesters containing hydrophilic moieties in the main chain or side chain were synthesized by bulk polycondensation of aromatic monomers without or with solubilizing substituents and aliphatic monomers. Hydrolytic and enzymatic degradation studies were carried out in vitro at 37 degrees C in pH 7.4 phosphate buffer and in Tris-HCl buffer containing proteinase K.

X chromosome inactivation in cervical cancer patients.

Development of cervical carcinomas is strongly associated with presence of human papilloma virus (HPV). Recently we found that young patients with breast cancer had a higher frequency of skewed X inactivation in peripheral blood cells, indicating an effect of X-linked genes on breast cancer development. In this study, we investigated the frequency of skewed X-inactivation pattern in blood and tumor biopsies from patients with cervical cancer.