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https://www.readbyqxmd.com/read/28728084/purification-of-monoclonal-antibodies-entirely-in-flow-through-mode
#1
Tsuyoshi Yamada, Koichi Yamamoto, Takashi Ishihara, Shigeru Ohta
A depth filter is widely used in biopharmaceutical manufacturing process. In this study, we found that buffer exchange to reduce conductivity dramatically improved the removal of impurities in depth filtration. The host cell protein clearance was comparable to that of protein A affinity chromatography, which is generally used as a first capture step in monoclonal antibody purification. In addition, a combination of different depth filters showed enhanced purification. Additional flow-through purification is possible without any sample preparation, and a biopharmaceutical-quality purity level (<100ppm for host cell protein and <5% for high molecular weight species) can be attained...
July 3, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28727946/confounding-by-single-nucleotide-polymorphism-rs117648444-p70s-affects-the-association-of-interferon-lambda-locus-variants-with-response-to-interferon-%C3%AE-ribavirin-therapy-in-patients-with-chronic-genotype-3-hepatitis-c-virus-infection
#2
Anand Bhushan, Sumona Ghosh, Samsiddhi Bhattacharjee, Sreedhar Chinnaswamy
Genome-wide association studies discovered interferon lambda (IFNL or IFN-λ) locus on chromosome 19 to be involved in clearance of chronic hepatitis C virus (HCV) infection in patients following interferon-α-ribavirin (IFN-RBV) therapy. Subsequent studies established a dinucleotide polymorphism rs368234815, as the prime causal variant behind this association. The ΔG allele of this variant gives rise to a new IFNL gene, IFNL4, coding for IFN-λ4 whose activity paradoxically associates with lesser viral clearance rates...
July 20, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28727781/escherichia-coli-mastitis-strains-in-vitro-phenotypes-and-severity-of-infection-in-vivo
#3
Perrine Roussel, Adeline Porcherie, Maryline Répérant-Ferter, Patricia Cunha, Christophe Gitton, Pascal Rainard, Pierre Germon
Mastitis remains a major infection of dairy cows and an important issue for dairy farmers and the dairy industry, in particular infections due to Escherichia coli strains. So far, properties specific to E. coli causing mastitis remain ill defined. In an attempt to better understand the properties required for E. coli to trigger mastitis, we used a range of in vitro assays to phenotypically characterize four E. coli strains, including the prototypical E. coli mastitis strain P4, possessing different relative abilities to cause mastitis in a mouse model...
2017: PloS One
https://www.readbyqxmd.com/read/28727655/preterm-infants-with-biliary-atresia-a-nationwide-cohort-analysis-from-the-netherlands
#4
Daan B E van Wessel, Thomas Boere, Christian V Hulzebos, Ruben H J de Kleine, Henkjan J Verkade, Jan B F Hulscher
OBJECTIVES: atresia (BA) occurs in 0.54/10.000 of overall live births in The Netherlands. BA has an unfavorable prognosis: less than 40% of patients are cleared of jaundice after Kasai portoenterostomy (KPE), 4-year transplant-free survival rate is 46% and the 4-year survival rate is ∼75%. Little is known on difficulties in diagnosis and the outcome of BA in preterm infants. We aimed to analyze the incidence and outcome of BA in preterm infants in The Netherlands. METHODS: Retrospective study including Dutch preterm infants treated for BA...
July 19, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28727430/renal-clearable-peptide-functionalized-nagdf4-nanodots-for-high-efficiency-tracking-orthotopic-colorectal-tumor-in-mouse
#5
Hongda Chen, Xiaodong Li, Fuyao Liu, Huimao Zhang, Zhenxin Wang
The effective delivery of bioimaging probes to a selected cancerous tissue has extensive significance for biological studies and clinical investigations. Herein, the peptide functionalized NaGdF4 nanodots (termed as, pPeptide-NaGdF4 nanodots) have been prepared for highly efficient magnetic resonance imaging (MRI) of tumor by formation of Gd-phosphonate coordinate bonds among hydrophobic NaGdF4 nanodots (4.2 nm in diameter) with mixed phosphorylated peptide ligands including a tumor targeting phosphopeptide and a cell penetrating phosphopeptide...
July 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28726129/immunological-aspects-of-rabies-a-literature-review
#6
REVIEW
Iana Suly Santos Katz, Fernanda Guedes, Elaine Raniero Fernandes, Sandriana Dos Ramos Silva
Rabies is a lethal disease caused by the neurotropic virus rabies virus (RABV), and it remains an important public health problem globally. It is known that the host immune response is important for control of viral infection and promoting viral clearance. In this context, it is well documented that, in addition to RABV neutralizing antibody, interferons and cell-mediated immunity also have an important role in preventing the establishment of disease. On the other hand, RABV suppresses host immunity through different mechanisms, for example, direct inhibition of host gene expression, sequestration of pathogen-associated molecular patterns, or modification of cytokine signalling pathways, which hinder the protective host immune responses to RABV infection...
July 19, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28725637/opportunistic-pathogen-porphyromonas-gingivalis-modulates-danger-signal-atp-mediated-antibacterial-nox2-pathways-in-primary-epithelial-cells
#7
JoAnn S Roberts, Kalina R Atanasova, Jungnam Lee, Gill Diamond, Jeff Deguzman, Chul Hee Choi, Özlem Yilmaz
Porphyromonas gingivalis, a major opportunistic pathogen in the etiology of chronic periodontitis, successfully survives in human gingival epithelial cells (GECs). P. gingivalis abrogates the effects of a host danger molecule, extracellular ATP (eATP)/P2X7 signaling, such as the generation of reactive oxygen species (ROS) via the mitochondria and NADPH oxidases (NOX) from primary GECs. However, antimicrobial functions of ROS production are thoroughly investigated in myeloid-lineage immune cells and have not been well-understood in epithelial cells...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28725223/gas-exchange-disturbances-regulate-alveolar-fluid-clearance-during-acute-lung-injury
#8
REVIEW
István Vadász, Jacob I Sznajder
Disruption of the alveolar-capillary barrier and accumulation of pulmonary edema, if not resolved, result in poor alveolar gas exchange leading to hypoxia and hypercapnia, which are hallmarks of acute lung injury and the acute respiratory distress syndrome (ARDS). Alveolar fluid clearance (AFC) is a major function of the alveolar epithelium and is mediated by the concerted action of apically-located Na(+) channels [epithelial Na(+) channel (ENaC)] and the basolateral Na,K-ATPase driving vectorial Na(+) transport...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28724773/nkp46-recognizes-the-sigma1-protein-of-reovirus-implications-for-reovirus-based-cancer-therapy
#9
Yotam Bar-On, Yoav Charpak-Amikam, Ariella Glasner, Batya Isaacson, Alexandra Duev-Cohen, Pinchas Tsukerman, Alexander Varvak, Michal Mandelboim, Ofer Mandelboim
The recent approval of onclolytic virus for therapy of melanoma patients has increased the need for precise evaluation of the mechanisms by which oncolytic viruses affect tumor growth. Here we show that the human NK activating receptor, NKp46, and its mouse orthologous protein, NCR1, recognize the reovirus sigma1 protein in a sialic-acid-dependent manner. We identify NKp46/NCR1 binding sites to sigma1 and show that sigma1 binding by NKp46/NCR1 leads to NK cell activation in vitro Finally, we demonstrate that NCR1 activation is essential for reovirus-based therapy in vivo Collectively, we identified sigma1 as a novel ligand for NKp46/NCR1 and demonstrated that NKp46/NCR1 is needed for both clearance of reovirus infections and reovirus-based tumor therapy...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724607/renal-hemodynamic-effects-of-glucagon-like-peptide-1-agonist-are-mediated-by-nitric-oxide-but-not-prostaglandin
#10
Scott Culver Thomson, Ali Kashkouli, Zhi Zhao Liu, Prabhleen Singh
The incretin hormone, glucagon like peptide-1 (GLP-1), is known for responding to dietary fat and carbohydrate. It elicits effects on pancreas, gut, and brain to stabilize blood glucose levels. We have previously reported that the GLP-1 agonist, exenatide, vasodilates the kidney and suppresses proximal reabsorption. The present study was undertaken to determine whether the renal effects of exenatide are mediated by nitric oxide (NO) and/or prostaglandins. Inulin clearance (GFR) and urine flow rate (UV) were measured in anesthetized rats before and during exenatide infusion (1 nmol/h iv)...
July 19, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28724233/examining-the-impact-of-active-clearance-of-chest-drainage-catheters-on-postoperative-atrial-fibrillation
#11
Samuel St-Onge, Walid Ben Ali, Ismail Bouhout, Denis Bouchard, Yoan Lamarche, Louis P Perrault, Philippe Demers
OBJECTIVE: Postoperative atrial fibrillation (POAF) is one of the most frequent complications encountered after heart surgery, and significantly increases complications and mortality. An obstructed chest tube, leaving unevacuated blood around the heart and lungs, can lead to atrial inflammation, which can trigger POAF. The aim of this study was to assess the effectiveness of chest drainage incorporating an active tube clearance (ATC) system in reducing the rate of POAF. METHODS: This retrospective analysis based on 300 consecutive patients undergoing heart surgery compared 142 patients allocated to an ATC drainage protocol with 158 controls managed with standard chest drainage...
August 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28724202/population-pharmacokinetics-of-lenalidomide-in-healthy-volunteers-and-patients-with-hematologic-malignancies
#12
Jamie N Connarn, Renfang Hwang, Yue Gao, Maria Palmisano, Nianhang Chen
A population pharmacokinetic (PopPK) model of lenalidomide was developed using data pooled from 13 clinical studies (dose range, 5-400 mg) in participants who were considered to have adequate capability for renal excretion of lenalidomide (creatinine clearance [CrCl] > 50 mL/min). The analysis population included 305 healthy volunteers and 83 patients with multiple myeloma or myelodysplastic syndromes. A 1-compartment model with linear absorption and elimination described well the observed data for both healthy volunteers and patients...
July 19, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28723886/prolonged-viral-replication-and-longitudinal-viral-dynamic-differences-among-respiratory-syncytial-virus-rsv-infected-infants
#13
Monica E Brint, Joshua M Hughes, Aditya Shah, Chelsea R Miller, Lisa G Harrison, Elizabeth A Meals, Jacqueline Blanch, Charlotte R Thompson, Stephania A Cormier, John P DeVincenzo
BACKGROUND: Longitudinal RSV dynamics have not been well-studied despite existence of factors favoring prolonged RSV replication including: high mutation rates allowing rapid evolution and potential escape from immune control. We therefore measured viral load in previously RSV-naïve infants over prolonged time-spans. METHODS: During 2014-2015, quantitative nasal aspirates were collected from 51 RSV-PCR+ infants. Multiple parallel assessments of viral loads were quantified at each collected time point using a well-validated real-time qRT-PCR assay...
July 19, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28723840/cervical-spine-evaluation-and-clearance-in-the-intoxicated-patient-a-prospective-western-trauma-association-multi-institutional-trial-and-survey
#14
Matthew J Martin, Lisa D Bush, Kenji Inaba, Saskya Byerly, Martin Schreiber, Kimberly A Peck, Galinos Barmparas, Jay Menaker, Joshua P Hazelton, Raul Coimbra, Martin D Zielinski, Carlos V R Brown, Chad G Ball, Jill R Cherry-Bukowiec, Clay Cothren Burlew, Julie Dunn, C Todd Minshall, Matthew M Carrick, Gina M Berg, Demetrios Demetriades, William Long
INTRODUCTION: Intoxication often prevents clinical clearance of the cervical spine (Csp) after trauma leading to prolonged immobilization even with a normal CT scan. We evaluated the accuracy of CT at detecting clinically significant Csp injury, and surveyed participants on related opinions and practice. METHODS: A prospective multicenter study (2013-2015) at 17 centers. All adult blunt trauma patients underwent structured clinical examination and imaging including a Csp CT, with follow-up thru discharge...
July 19, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28723548/the-fc-domain-of-immunoglobulin-is-sufficient-to-bridge-nk-cells-with-virally-infected-cells
#15
Hong-Sheng Dai, Nathaniel Griffin, Chelsea Bolyard, Hsiaoyin Charlene Mao, Jianying Zhang, Timothy P Cripe, Tadahiro Suenaga, Hisashi Arase, Ichiro Nakano, E A Chiocca, Balveen Kaur, Jianhua Yu, Michael A Caligiuri
Clearance of pathogens or tumor cells by antibodies traditionally requires both Fab and Fc domains of IgG. Here, we show the Fc domain of IgG alone mediates recognition and clearance of herpes simplex virus (HSV1)-infected cells. The human natural killer (NK) cell surface is naturally coated with IgG bound by its Fc domain to the Fcγ receptor CD16a. NK cells utilize the Fc domain of bound IgG to recognize gE, an HSV1-encoded glycoprotein that also binds the Fc domain of IgG but at a site distinct from CD16a...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723387/sigma-1-receptor-activation-modifies-intracellular-calcium-exchange-in-the-g93a-hsod1-als-model
#16
Vedrana Tadić, Ayse Malci, Nadine Goldhammer, Beatrice Stubendorff, Saikata Sengupta, Tino Prell, Silke Keiner, Jingyu Liu, Madlen Guenther, Christiane Frahm, Otto W Witte, Julian Grosskreutz
Aberrations in intracellular calcium (Ca(2+)) have been well established within amyotrophic lateral sclerosis (ALS), a severe motor neuron disease. Intracellular Ca(2+) concentration is controlled in part through the endoplasmic reticulum (ER) mitochondria Ca(2+) cycle (ERMCC). The ER supplies Ca(2+) to the mitochondria at close contacts between the two organelles, i.e. the mitochondria-associated ER membranes (MAMs). The Sigma 1 receptor (Sig1R) is enriched at MAMs, where it acts as an inter-organelle signalling modulator...
July 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28723101/virus-derived-peptides-for-clinical-applications
#17
Mingying Yang, Kegan Sunderland, Chuanbin Mao
Novel affinity agents with high specificity are needed to make progress in disease diagnosis and therapy. Over the last several years, peptides have been considered to have fundamental benefits over other affinity agents, such as antibodies, due to their fast blood clearance, low immunogenicity, rapid tissue penetration, and reproducible chemical synthesis. These features make peptides ideal affinity agents for applications in disease diagnostics and therapeutics for a wide variety of afflictions. Virus-derived peptide techniques provide a rapid, robust, and high-throughput way to identify organism-targeting peptides with high affinity and selectivity...
July 19, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28722618/clinical-evidence-of-acute-mesoamerican-nephropathy
#18
Rebecca S B Fischer, Sreedhar Mandayam, Denis Chavarria, Chandan Vangala, Melissa N Garcia, Linda L Garcia, Lesbia Palma, Felix Garcia, Ramón García-Trabanino, Kristy O Murray
Mesoamerican nephropathy (MeN), an epidemic of unexplained kidney disease in Central America, affects mostly young, healthy individuals. Its etiology is a mystery that requires urgent investigation. Largely described as a chronic kidney disease (CKD), no acute clinical scenario has been characterized. An understanding of the early disease process could elucidate an etiology and guide treatment and prevention efforts. We sought to document the earliest clinical signs in patients with suspected MeN in a high-risk population in Nicaragua...
July 17, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28722611/phase-2a-open-label-4-escalating-dose-randomized-multicenter-study-evaluating-the-safety-and-activity-of-ferroquine-ssr97193-plus-artesunate-versus-amodiaquine-plus-artesunate-in-african-adult-men-with-uncomplicated-plasmodium-falciparum-malaria
#19
Christian Supan, Ghyslain Mombo-Ngoma, Maryvonne Kombila, Carmen L Ospina Salazar, Jana Held, Bertrand Lell, Cathy Cantalloube, Elhadj Djeriou, Bernhards Ogutu, John Waitumbi, Nekoye Otsula, Duncan Apollo, Mark E Polhemus, Peter G Kremsner, Douglas S Walsh
Artemisinin-based combination therapies are recommended as first-line agents for treating uncomplicated Plasmodium falciparum malaria. Ferroquine, a 4-aminoquinolone, is a novel long-acting combination partner for fast-acting drugs like artesunate (AS). We did a small phase 2a, multicenter, open-label, safety-focused dose-ranging randomized study of ferroquine at three African hospitals: two Gabonese and one Kenyan. We recruited adult men with symptomatic uncomplicated P. falciparum monoinfection. Four escalating doses of ferroquine (100, 200, 400, and 600 mg) were assessed in sequence, versus an amodiaquine comparator...
May 30, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28722515/construction-of-a-plga-based-targeted-sirna-delivery-system-for-treatment-of-osteoporosis
#20
Deniz Sezlev Bilecen, Jose Carlos Rodriguez-Cabello, Hasan Uludag, Vasif Hasirci
Osteoporosis is a systemic skeletal disorder which occurs when the bone turnover balance is disrupted. With the identification of the genes involved in the pathogenesis of the disease, studies on development of new osteoporosis treatments has intensified. RNA interference (RNAi) mechanism uses short interfering RNA (siRNA) to knockdown disease related gene expression as a treatment approach. Targeting while protecting siRNA against hydrolysis by nucleases in vivo is, however, challenging. The maintenance of therapeutic plasma level is also hampered by the clearance of siRNA from the body...
July 19, 2017: Journal of Biomaterials Science. Polymer Edition
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