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Shobini Jayaraman, Christian Haupt, Olga Gursky
Oxidative stress and inflammation, which involves a dramatic increase in serum amyloid A (SAA) levels, are critical in the development of atherosclerosis. Most SAA circulates on plasma HDL particles, altering their cardioprotective properties. SAA-enriched HDL have diminished anti-oxidant effects on LDL, which may contribute to atherogenesis. We determined combined effects of SAA enrichment and oxidation on biochemical changes in HDL. Normal human HDL were incubated with SAA, oxidized by various factors (Cu2+, myeloperoxidase, H2O2, OCl-), and analyzed for lipid and protein modifications and biophysical remodeling...
October 15, 2016: Journal of Lipid Research
S J Jacober, M J Prince, J M Beals, M L Hartman, Y Qu, H Linnebjerg, P Garhyan, A Haupt
Basal insulin peglispro (BIL) is a novel basal insulin with a flat, prolonged activity profile. BIL has been demonstrated in a dog model, in healthy men and in patients with type 1 diabetes (T1D) to have significant hepato-preferential action resulting from reduced peripheral activity. In the IMAGINE-Phase 3 clinical trial program, more than 6000 patients were included, of whom ~3900 received BIL. Of the 7 pivotal IMAGINE trials, 3 studies were double-blinded and 3 were in T1D patients. BIL consistently demonstrated a greater HbA1c reduction, less glycaemic variability and a clinically relevant reduction in the rates of nocturnal hypoglycaemia across comparator [glargine and isophane insulin (NPH)] studies...
October 2016: Diabetes, Obesity & Metabolism
K Cusi, A J Sanyal, S Zhang, B J Hoogwerf, A M Chang, S J Jacober, J M Bue-Valleskey, A N Higdon, E J Bastyr, A Haupt, M L Hartman
AIMS: To compare effects of basal insulin peglispro (BIL), a hepatopreferential insulin, to insulin glargine (glargine) on aminotransferases and liver fat content (LFC) in patients with type 1 and type 2 diabetes (T1D, T2D). MATERIALS AND METHODS: Data from two Phase 2 and five Phase 3 randomized trials comparing BIL and glargine in 1709 T1D and 3662 T2D patients were integrated for analysis of liver laboratory tests. LFC, measured by magnetic resonance imaging (MRI) at baseline, 26 and 52 weeks, was analyzed in 182 T1D patients, 176 insulin-naïve T2D patients and 163 T2D patients previously treated with basal insulin...
October 2016: Diabetes, Obesity & Metabolism
Julia Neitzel, Marion Ortner, Marleen Haupt, Petra Redel, Timo Grimmer, Igor Yakushev, Alexander Drzezga, Peter Bublak, Christoph Preul, Christian Sorg, Kathrin Finke
Posterior cortical atrophy is dominated by progressive degradation of parieto-occipital grey and white matter, and represents in most cases a variant of Alzheimer's disease. Patients with posterior cortical atrophy are characterized by increasing higher visual and visuo-spatial impairments. In particular, a key symptom of posterior cortical atrophy is simultanagnosia i.e. the inability to perceive multiple visual objects at the same time. Two neuro-cognitive mechanisms have been suggested to underlie simultanagnosia, either reduced visual short-term memory capacity or decreased visual processing speed possibly resulting from white matter impairments over and above damage to cortical brain areas...
October 3, 2016: Brain: a Journal of Neurology
A Lindsay, E Haupt, C Chan, A Spiguel, M T Scarborough, C P Gibbs, R A Zlotecki
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Glyn N Stacey, Sandra Coecke, Anna-Bal Price, Lyn Healy, Paul Jennings, Anja Wilmes, Christian Pinset, Magnus Ingelman-Sundberg, Jochem Louisse, Simone Haupt, Darren Kidd, Andrea Robitski, Heinz-Georg Jahnke, Gilles Lemaitre, Glenn Myatt
Quality control of cell cultures used in new in vitro toxicology assays is crucial to the provision of reliable, reproducible and accurate toxicity data on new drugs or constituents of new consumer products. This chapter explores the key scientific and ethical criteria that must be addressed at the earliest stages of developing toxicology assays based on human pluripotent stem cell (hPSC) lines. It also identifies key considerations for such assays to be acceptable for regulatory, laboratory safety and commercial purposes...
2016: Advances in Experimental Medicine and Biology
Sara Haupt, Itay Lazar, Hana Weitman, Yaron Shav-Tal, Benjamin Ehrenberg
Photodynamic therapy (PDT) is well established as a clinical treatment modality for various diseases, including cancer and especially for the treatment of superficial tumors. However, one of the disadvantages of the photoactivatable molecules is their low absorbance in the optical window for photosensitizer excitation. The use of nanoparticles in photodynamic therapy can address this deficiency and improve treatment efficiency. Pdots are nano-sized particles, composed of conjugated chromophoric polymers. By mixing them with PEGylated phospholipids they can become soluble and stable colloids...
September 14, 2016: Journal of Photochemistry and Photobiology. B, Biology
Michael Dobosz, Ute Haupt, Werner Scheuer
Preclinical efficacy studies of antibodies targeting a tumor-associated antigen are only justified when the expression of the relevant antigen has been demonstrated. Conventionally, antigen expression level is examined by immunohistochemistry of formalin-fixed paraffin-embedded tumor tissue section. This method represents the diagnostic "gold standard" for tumor target evaluation, but is affected by a number of factors, such as epitope masking and insufficient antigen retrieval. As a consequence, variances and discrepancies in histological staining results can occur, which may influence decision-making and therapeutic outcome...
September 23, 2016: MAbs
Elizabeth A M Feijen, Anna Font-Gonzalez, Elvira C van Dalen, Helena J H van der Pal, Raoul C Reulen, David L Winter, Claudia E Kuehni, Riccardo Haupt, Daniela Alessi, Julianne Byrne, Edit Bardi, Zsuzsanna Jakab, Desiree Grabow, Stanislaw Garwicz, Momcilo Jankovic, Gill A Levitt, Roderick Skinner, Lorna Zadravec Zaletel, Lars Hjorth, Wim J E Tissing, Florent de Vathaire, Mike M Hawkins, Leontien C M Kremer
BACKGROUND AND AIM: Childhood cancer survivors are at high risk of long-term adverse effects of cancer and its treatment, including cardiac events. The pan-European PanCareSurFup study determined the incidence and risk factors for cardiac events among childhood cancer survivors. The aim of this article is to describe the methodology of the cardiac cohort and nested case-control study within PanCareSurFup. METHODS: Eight data providers in Europe participating in PanCareSurFup identified and validated symptomatic cardiac events in their cohorts of childhood cancer survivors...
2016: PloS One
Julie C Antvorskov, Knud Josefsen, Martin Haupt-Jorgensen, Petra Fundova, David P Funda, Karsten Buschard
Studies have documented that the pathogenesis of autoimmune diabetes is influenced by the intake of gluten. Aims. To investigate the importance of gluten exposure during pregnancy and the subsequent development of autoimmune diabetes in offspring. Methods. Nonobese diabetic mice were divided into 7 groups to receive combinations of gluten-free and standard diet before, during, or after pregnancy. Diabetes incidence in offspring was followed in each group (n = 16-27) for 310 days. Insulitis score and intestinal expression of T-cell transcription factors (RT-QPCR) were evaluated in animals from the different diet groups...
2016: Journal of Diabetes Research
P J Paul, D Raghu, A-L Chan, T Gulati, L Lambeth, E Takano, M J Herold, J Hagekyriakou, R L Vessella, C Fedele, M Shackleton, E D Williams, S Fox, S Williams, S Haupt, C Gamell, Y Haupt
Restoration of tumor suppression is an attractive onco-therapeutic approach. It is particularly relevant when a tumor suppressor is excessively degraded by an overactive oncogenic E3 ligase. We previously discovered that the E6-associated protein (E6AP; as classified in the human papilloma virus context) is an E3 ligase that has an important role in the cellular stress response, and it directly targets the tumor-suppressor promyelocytic leukemia protein (PML) for proteasomal degradation. In this study, we have examined the role of the E6AP-PML axis in prostate cancer (PC)...
September 19, 2016: Oncogene
M Raithel, H Albrecht, W Scheppach, M Farnbacher, W Haupt, A F Hagel, V Schellerer, F Vitali, M F Neurath, H T Schneider
BACKGROUND: Acute gastrointestinal (GI) wall defects contain a high risk of morbidity and mortality and may be closed endoscopically by a full-thickness over-the-scope clip (OTSC). METHODS: Unselected consecutive patients presenting with acute non-surgical perforations or postoperative anastomotic leaks or perforations underwent attempted OTSC placement as primary closure method after interdisciplinary consensus in three tertiary referral centres. Their clinical data and intervention characteristics were evaluated in an intention to treat analysis during a 24-month period to assess closure rates, 30-day mortality, hospitalization and comorbidity...
September 15, 2016: Surgical Endoscopy
Jörg C Heinrich, Sainitin Donakonda, V Joachim Haupt, Petra Lennig, Yixin Zhang, Michael Schroeder
Drug resistance is an important open problem in cancer treatment. In recent years, the heat shock protein HSP27 (HSPB1) was identified as a key player driving resistance development. HSP27 is overexpressed in many cancer types and influences cellular processes such as apoptosis, DNA repair, recombination, and formation of metastases. As a result cancer cells are able to suppress apoptosis and develop resistance to cytostatic drugs. To identify HSP27 inhibitors we follow a novel computational drug repositioning approach...
September 8, 2016: Oncotarget
Benjamin M Schwenk, Hannelore Hartmann, Alperen Serdaroglu, Martin H Schludi, Daniel Hornburg, Felix Meissner, Denise Orozco, Alessio Colombo, Sabina Tahirovic, Meike Michaelsen, Franziska Schreiber, Simone Haupt, Michael Peitz, Oliver Brüstle, Clemens Küpper, Thomas Klopstock, Markus Otto, Albert C Ludolph, Thomas Arzberger, Peer-Hendrik Kuhn, Dieter Edbauer
Nuclear clearance of TDP-43 into cytoplasmic aggregates is a key driver of neurodegeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), but the mechanisms are unclear. Here, we show that TDP-43 knockdown specifically reduces the number and motility of RAB11-positive recycling endosomes in dendrites, while TDP-43 overexpression has the opposite effect. This is associated with delayed transferrin recycling in TDP-43-knockdown neurons and decreased β2-transferrin levels in patient CSF Whole proteome quantification identified the upregulation of the ESCRT component VPS4B upon TDP-43 knockdown in neurons...
September 12, 2016: EMBO Journal
Christian Schütz, Juan Carlos Varela, Karlo Perica, Carl Haupt, Mathias Oelke, Jonathan P Schneck
Redirection of T cells to target and destroy tumors has become an important clinical tool and major area of research in tumor immunology. Here we present a novel, nanoparticle-based approach to selectively bind antigen-specific cytotoxic T cells (CTL) and redirect them to kill tumors, termed ATR (Antigen-specific T cell Redirectors). ATR were generated by decorating nanoparticles with both an antigen-specific T cell binding moiety, either peptide loaded MHC-Ig dimer or clonotypic anti-TCR antibody, and a model tumor cell binding moiety, anti-CD19 antibody to engage CD19+ tumor cells...
September 1, 2016: Oncotarget
Sofia Nestora, Franck Merlier, Elise Prost, Karsten Haupt, Claire Rossi, Bernadette Tse Sum Bui
Betanin is a natural pigment with significant antioxidant and biological activities currently used as food colorant. The isolation of betanin is problematic due to its instability. In this work, we developed a fast and economic procedure based on molecularly imprinted solid-phase extraction (MISPE) for the selective clean-up of betanin and its stereoisomer isobetanin from beetroot extracts. Dipicolinic acid was used as template for the MIP preparation because of its structural similarity with the chromophore group of betanin...
September 23, 2016: Journal of Chromatography. A
Line Jee Hartmann Rasmussen, Steen Ladelund, Thomas Huneck Haupt, Gertrude Ellekilde, Jørgen Hjelm Poulsen, Kasper Iversen, Jesper Eugen-Olsen, Ove Andersen
OBJECTIVE: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker associated with presence and progression of disease and with increased risk of mortality. We aimed to evaluate the unspecific biomarker suPAR as a prognostic marker in patients admitted to acute care. METHODS: This registry-based retrospective cohort study included 4343 consecutively admitted patients from the Acute Medical Unit at a large Danish university hospital...
September 2, 2016: Emergency Medicine Journal: EMJ
Anette-G Ziegler, Florian Haupt, Marlon Scholz, Katharina Weininger, Susanne Wittich, Stephanie Löbner, Claudia Matzke, Cigdem Gezginci, Stephanie Riethausen, Andreas Beyerlein, Stephanie Zillmer, Marie Amoroso, Rebecca Coles, Michael Powell, Jadwiga Furmaniak, Bernard Rees Smith, Christiane Winkler, Ezio Bonifacio, Peter Achenbach
BACKGROUND: Testing for beta cell autoantibodies is used for wide-scale identification of early stages of type 1 diabetes. This requires suitable screening assays. We aimed to establish screening that utilized a first step assay (3 Screen) able to detect autoantibodies to the target antigens glutamic acid decarboxylase-65 (GAD), insulinoma-associated antigen 2 (IA-2), and zinc transporter 8 (ZnT8) to identify children positive for multiple beta cell autoantibodies. METHODS: An ELISA format was used where plates were coated with a mixture of recombinant GAD, IA-2, and ZnT8325W/R-dimer molecules...
August 23, 2016: Diabetes Technology & Therapeutics
Paul Haupt-Renaud, Liuwei Jiang, Richard Kenneth Marcus
Functionalized lipid tethered ligands use physical adsorption to anchor reactive head groups to hydrophobic supports. We previously demonstrated the use of these species adsorbed onto polypropylene capillary-channeled polymer fibers. The general use of lipid tethered ligands on other hydrophobic chromatographic supports is demonstrated here for polystyrene-divinylbenzene. Evaluation of ligand adsorption conditions was performed using a fluorescein isocyanate head group to quantify the extent of loading by UV-Vis absorbance and by fluorescence microscopy...
October 2016: Journal of Separation Science
C Hutterer, S Hamilton, M Steingruber, I Zeitträger, H Bahsi, N Thuma, Z Naing, Z Örfi, L Örfi, E Socher, H Sticht, W Rawlinson, S Chou, V J Haupt, M Marschall
HCMV is a member of the family Herpesviridae and represents a worldwide distributed pathogen with seropositivity rates in the adult population ranging between 40% and 90%. Notably, HCMV infection is a serious, sometimes life-threatening medical problem for newborns and immunosuppressed individuals, including transplant recipients and patients under antitumoral chemotherapy. Current standard therapy with valganciclovir has the disadvantage of inducing drug-resistant virus mutants and toxicity-related side effects...
October 2016: Antiviral Research
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