Telomere attrition and dysfunction: a potential trigger of the progeroid phenotype in nijmegen breakage syndrome.

Background: Nibrin, as part of the NBN/MRE11/RAD50 complex, is mutated in Nijmegen breakage syndrome (NBS), which leads to impaired DNA damage response and lymphoid malignancy.

Results: Telomere length (TL) was markedly reduced in homozygous patients (and comparably so in all chromosomes) by ~40% (qPCR) and was slightly reduced in NBS heterozygotes older than 30 years (~25% in qPCR), in accordance with the respective cancer rates. Humanized cancer-free NBS mice had normal TL.

Ectopic expression of Snord115 in choroid plexus interferes with editing but not splicing of 5-Ht2c receptor pre-mRNA in mice.

Serotonin 5-HT2C receptor is a G-protein coupled excitatory receptor that regulates several biochemical pathways and has been implicated in obesity, mental state, sleep cycles, autism, neuropsychiatric disorders and neurodegenerative diseases. The activity of 5-HT2CR is regulated via alternative splicing and A to I editing of exon Vb of its pre-mRNA. Snord115 is a small nucleolar RNA that is expressed in mouse neurons and displays an 18-nucleotide base complementary to exon Vb of 5-HT2CR pre-mRNA.

Genome sequence of the basal haplorrhine primate Tarsius syrichta reveals unusual insertions.

Tarsiers are phylogenetically located between the most basal strepsirrhines and the most derived anthropoid primates. While they share morphological features with both groups, they also possess uncommon primate characteristics, rendering their evolutionary history somewhat obscure. To investigate the molecular basis of such attributes, we present here a new genome assembly of the Philippine tarsier (Tarsius syrichta), and provide extended analyses of the genome and detailed history of transposable element insertion events.

Exploring prostate cancer genome reveals simultaneous losses of PTEN, FAS and PAPSS2 in patients with PSA recurrence after radical prostatectomy.

The multifocal nature of prostate cancer (PCa) creates a challenge to patients' outcome prediction and their clinical management. An approach that scrutinizes every cancer focus is needed in order to generate a comprehensive evaluation of the disease, and by correlating to patients' clinico-pathological information, specific prognostic biomarker can be identified. Our study utilized the Affymetrix SNP 6.

Prognostic impact of Bcl-2 depends on tumor histology and expression of MALAT-1 lncRNA in non-small-cell lung cancer.

Introduction: Apoptosis is a crucial pathway in tumor growth and metastatic development. Apoptotic proteins regulate the underlying molecular cascades and are thought to modulate the tumor response to chemotherapy and radiation. However, the prognostic value of the expression of apoptosis regulators in localized non-small-cell lung cancer (NSCLC) is still unclear.

Genome-wide investigation of multifocal and unifocal prostate cancer-are they genetically different?

Prostate cancer is widely observed to be biologically heterogeneous. Its heterogeneity is manifested histologically as multifocal prostate cancer, which is observed more frequently than unifocal prostate cancer. The clinical and prognostic significance of either focal cancer type is not fully established.

Opposing effects of ATP and adenosine on barrier function of rat coronary microvasculature.

ATP can differentially affect the micro- and macrovascular endothelial barrier. It has been shown that it can both increase and/or decrease macromolecule permeability of microvascular endothelial cells and microvessels, in vivo. We hypothesised that the barrier stabilising effect is mediated by ATP itself via P2 receptors, while barrier-disrupting effect is mediated by its metabolite adenosine via adenosine receptors.

Transgenic model of smooth muscle cell cycle reentry: expression pattern of the collageneous matrix.

Background: We have previously shown that genetically induced smooth muscle cell (SMC) cycle reentry in transgenic mouse models expressing the SV40 T antigen (TAg) resulted in adaptive arterial remodeling. The present investigation targeted the in vitro expression pattern of the collageneous matrix associated with TAg-induced SMC cycle modulation.

Methods: SMC cultures were established from the transgenic model expressing temperature-sensitive TAg.

Pharmacodynamics of two different dosing regimens of tirofiban in citrate or PPACK anticoagulated blood.

The primary objective of this study was to compare the inhibitory activity of tirofiban measured with the rapid platelet function assay (RPFA) and with light transmission aggregometry using two different anticoagulants (citrate versus PPACK). Twenty patients treated with tirofiban for percutaneous coronary intervention were studied at six time points during tirofiban treatment. Tirofiban was given with a bolus dose of 10 microg/kg and an infusion of 0.

Gender differences in the outcome of cardiac interventions.

I. The actual data base on the decision-making process of indication for revascularization reveals that angiographic severity of coronary artery disease (CAD) is the primary determinant of referral to coronary interventional procedures. Several recent studies demonstrated that after an acute myocardial infarction, women undergo cardiac catheterization to a lesser extent than men.

NF{kappa}B-dependent down-regulation of tumor necrosis factor receptor-associated proteins contributes to interleukin-1-mediated enhancement of ultraviolet B-induced apoptosis.

Activation of the transcription factor nuclear factor-kappaB (NFkappaB) by inflammatory cytokines like tumor necrosis (TNF) factor and interleukin-1 (IL-1) is generally associated with the induction of antiapoptotic pathways. Therefore, NFkappaB inhibits both intrinsically and extrinsically induced apoptosis and thus is regarded to act universally in an antiapoptotic fashion. Accordingly, activation of NFkappaB by IL-1 was shown to result in reduction of death ligand-induced apoptosis via up-regulation of antiapoptotic inhibitor of apoptosis proteins (IAPs).

Use of gadobutrol in coronary angiography.

Gadobutrol was used in coronary angiography in three patients. All three patients had a substantially increased risk of developing renal complications with iodinated contrast agents. Gadobutrol was well tolerated in all three patients without any complications.

Expression profiling of t(12;22) positive clear cell sarcoma of soft tissue cell lines reveals characteristic up-regulation of potential new marker genes including ERBB3.

Clear cell sarcoma of soft tissue (CCSST), also known as malignant melanoma of soft parts, represents a rare lesion of the musculoskeletal system usually affecting adolescents and young adults. CCSST is typified by a chromosomal t(12;22)(q13;q12) translocation resulting in a fusion between the Ewing sarcoma gene (EWSR1) and activating transcription factor 1 (ATF1), of which the activity in nontransformed cells is regulated by cyclic AMP. Our aim was to identify critical differentially expressed genes in CCSST tumor cells in comparison with other solid tumors affecting children and young adults to better understand signaling pathways regulating specific features of the development and progression of this tumor entity.

Prediction of risk of coronary events in middle-aged men in the Prospective Cardiovascular Münster Study (PROCAM) using neural networks.

Background: Logistic regression (LR) is commonly used to estimate risk of coronary heart disease. We investigated if neural networks improved on the risk estimate of LR by analysing data from the Prospective Cardiovascular Münster Study (PROCAM), a large prospective epidemiological study of risk factors for coronary heart disease among men and women at work in northern Germany.

Methods: We used a multi-layer perceptron (MLP) and probabilistic neural networks (PNN) to estimate the risk of myocardial infarction or acute coronary death (coronary events) during 10 years' follow-up among 5159 men aged 35-65 years at recruitment into PROCAM.

Cytogenetic alterations and cytokeratin expression patterns in breast cancer: integrating a new model of breast differentiation into cytogenetic pathways of breast carcinogenesis.

The introduction of a concept proposing multiple cellular subgroups in the normal female breast, including cytokeratin 5/6 (Ck 5/6)-positive progenitor cells, offers a new explanation for the existence of highly aggressive breast cancers with and without Ck 5/6 expression. Using the tissue microarray technique, 166 breast cancer cases, all characterized by comparative genomic hybridization, were evaluated by immunohistochemistry, using 15 different antibodies (estrogen receptor, progesterone receptor, p53, Ki-67, c-erbB2, epidermal growth factor receptor, cyclins A, D1, and E, bcl-2, p21, p27, Ck 5/6, Ck 8/18, and smooth muscle actin) and chromogenic in situ hybridization for c-erbB2. Biomathematical cluster analysis was applied to confirm the conventional interpretation of the results by an independent approach.

Inhibition of platelet adhesion and aggregation by a defined region (Gly-486-Lys-502) of high molecular weight kininogen.

Proteolytic cleavage of single chain high molecular weight kininogen (HK) by kallikrein releases the short-lived vasodilator bradykinin and leaves behind two-chain high molecular weight kininogen (HKa). HKa and particularly its His-Gly-Lys-rich domain 5 have been previously reported to exert anti-adhesive properties by binding to the extracellular matrix protein vitronectin (VN). In this study the ability of HKa and domain 5 to interfere with platelet adhesion and aggregation was investigated.