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Downing Heather J HJ Department of Women's and Children's Health, Institute of Translational Medicine, The University of Liverpool, Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool L12 2AP, - - 2013
A number of medications do not have a licence, or label, for use in the paediatric age group nor for the specific indication for which they are being used in children. Over recent years, mycophenolate mofetil has increasingly been used off-label (i.e. off-licence) in adults for a number of indications, ...
DeSilva Tara M - - 2012
The major regulators of synaptic glutamate in the cerebral cortex are the excitatory amino acid transporters 1-3 (EAAT1-3). In this study, we determined the cellular and temporal expression of EAAT1-3 in the developing human cerebral cortex. We applied single- and double-label immunocytochemistry to normative frontal or parietal (associative) cortex samples ...
Qin Wen-Jie WJ Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, - - 2012
This study aimed to investigate the effect of metamizole on bupropion hydroxylation related to different CYP2B6 genotype groups in healthy volunteers. Sixteen healthy male volunteers (6 CYP2B6*1/*1, 6 CYP2B6*1/*6 and 4 CYP2B6*6/*6) received orally administered bupropion alone and during daily treatment with metamizole 1500 mg day(-1) (500 mg tablet taken three times ...
Peluso Carolyn E CE Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts 02111, - - 2012
Position within a tissue often correlates with cellular phenotype, for example, differential expression of odorant receptors and cell adhesion molecules across the olfactory mucosa (OM). The association between position and phenotype is often paralleled by gradations in the concentration of retinoic acid (RA), caused by differential expression of the RA ...
Akins Michael R MR Department of Neuroscience, Brown University, Providence, Rhode Island 02912, - - 2012
Loss of Fragile X mental retardation protein (FMRP) leads to Fragile X syndrome (FXS), the most common form of inherited intellectual disability and autism. Although the functions of FMRP and its homologs FXR1P and FXR2P are well studied in the somatodendritic domain, recent evidence suggests that this family of RNA ...
Asteriti S - - 2012
Recently, a small molecule (Q94) was reported to selectively block PAR(1) /Gα(q) interaction and signalling. Here, we describe the pharmacological properties of Q94 and two analogues that share its benzimidazole scaffold (Q109, Q89). Q109 presents a modest variation from Q94 in the substituent group at the 2-position, while Q89 has ...
Bröer Stefan - - 2012
The solute carrier 6 (SLC6) family of the human genome comprises transporters for neurotransmitters, amino acids, osmolytes and energy metabolites. Members of this family play critical roles in neurotransmission, cellular and whole body homeostasis. Malfunction or altered expression of these transporters is associated with a variety of diseases. Pharmacological inhibition ...
Jun D W - - 2012
Recently, the DNA damage response (DDR) has emerged as a promising target for anticancer drug development. In our previous study, we identified several DDR-inhibiting compounds via high-content screening of a small molecule library using γH2AX foci as a biomarker. Here, we studied the effects of the DNA damage response inhibitor ...
Iyer Rohin K - - 2012
We previously showed that the sequential, but not simultaneous, culture of endothelial cells (ECs), fibroblasts (FBs), and cardiomyocytes (CMs) resulted in elongated, beating cardiac organoids. We hypothesized that the expression of Cx43 and contractile function are mediated by vascular endothelial growth factor (VEGF) released by nonmyocytes during the preculture period. ...
Gallyas Ferenc - - 2012
Recently, cystathionine-γ-lyase (CSE) was found to provide the major physiological pathway for H(2) S, the third member of the gasotransmitter family. In various pathophysiological conditions, H(2) S exerted protective effects based on its antioxidant, anti-inflammatory, anti-hypertensive and other regulatory functions. Interestingly, CSE expression had been only poorly studied and only ...
Rengo G G Cardiology Division, Fondazione Salvatore Maugeri, IRCCS, Telese Terme (BN), Italy. - - 2012
Sympathetic nervous system (SNS) hyperactivity is characteristic of chronic heart failure (HF) and significantly worsens prognosis. The success of β-adrenoceptor antagonist (β-blockers) therapy in HF is primarily attributed to protection of the heart from the noxious effects of augmented catecholamine levels. β-Blockers have been shown to reduce SNS hyperactivity in ...
Murthy Shubha - - 2012
Rac1, a small GTPase, regulates macrophage MMP (matrix metalloproteinase)-9 in an ERK (extracellular-signal-regulated kinase)- and SP (specificity protein)-1-dependent manner. SP-1 contains a PEST (Pro-Glu-Ser-Thr) domain that may modulate protein stability. We hypothesize that Thr578, Ser586 and/or Ser587 in the PEST domain are required for SP-1 stability and MMP-9 expression secondary ...
Liu Xinrong - - 2012
A three-component nanoparticle consisting of biotinylated Trastuzumab antiHer2 antibody, tat transferring peptide and radiolabeled antisense oligomer, linked together through streptavidin, have shown promise in the delivery to Her2+ tumor in mice following intravenous administration and with evidence of radiotherapeutic efficacy. These results have encouraged us to consider the nanoparticle as ...
Gros Frédéric - - 2012
Macroautophagy was recently shown to regulate both lymphocyte biology and innate immunity. In this study we sought to determine whether a deregulation of autophagy was linked to the development of autoimmunity. Genome-wide association studies have pointed out nucleotide polymorphisms that can be associated with systemic lupus erythematosus, but the potential ...
Pande Chandana - - 2012
Spontaneous bacterial peritonitis (SBP) may occur despite antibiotic prophylaxis. We investigated whether the addition of probiotics to norfloxacin enhances its efficacy in the prevention of SBP. A double-blind, randomized-controlled trial was conducted among consecutive cirrhotic patients who had either recovered from SBP (secondary prophylaxis) or who were at a high ...
Chakrabarti Rumela - - 2012
The transcription factor E74-like factor 5 (Elf5) functions downstream of the prolactin receptor signaling pathway and plays an important role in mammary gland development. Using conditional mouse knockouts, we have previously shown that Elf5-null mammary glands exhibit a complete failure of alveologenesis during pregnancy. The Elf5-null developmental phenotype is mediated ...
Salcedo Isidro - - 2012
Like type-2 diabetes mellitus (T2DM), neurodegenerative disorders and stroke are an ever increasing, health, social and economic burden for developed Westernized countries. Age is an important risk factor in all of these; due to the rapidly increasing rise in the elderly population T2DM and neurodegenerative disorders, both represent a looming ...
Reny J-L - - 2012
A poor biological response to clopidogrel is associated with an increased risk of major cardiovascular ischemic events (MACE). Paraoxonase 1 (PON1) enzyme activity is modulated by the PON1-Q192R variant (rs662) and was recently suggested to be strongly involved in clopidogrel bioactivation, but the influence of the PON1-Q192R variant on the ...
Rea Matthew - - 2012
Imprinting, i.e. parent-of-origin expression of alleles, plays an important role in regulating development in mammals and plants. DNA methylation catalyzed by DNA methyltransferases plays a pivotal role in regulating imprinting by silencing parental alleles. DEMETER (DME), a DNA glycosylase functioning in the base-excision DNA repair pathway, can excise 5-methylcytosine from ...
Lipsky Michael J - - 2012
The da Vinci Surgical System (dVSS) has been reported to eliminate innate hand dominance of the surgeon. There are no studies to date, however, that specifically address whether the dVSS has its own inherent "handedness" resulting from the fixed left-right preference of specific instrument docking and assistant positioning. We identified ...
Munoz-Pinto Dany J - - 2012
Growth factors have been shown to be potent mediators of osteogenesis. However, their use in tissue-engineered scaffolds not only can be costly but also can induce undesired responses in surrounding tissues. Thus, the ability to specifically induce osteogenic differentiation in the absence of exogenous growth factors through manipulation of scaffold ...
van den Bogaard Ellen H - - 2012
The use of tissue-engineered human skin equivalents (HSE) for fundamental research and industrial application requires the expansion of keratinocytes from a limited number of skin biopsies donated by adult healthy volunteers or patients. A pharmacological inhibitor of Rho-associated protein kinases, Y-27632, was recently reported to immortalize neonatal human foreskin keratinocytes. ...
Alghamdi Hamdan S - - 2012
Osteoporosis is a frequent human metabolic bone disorder. Prospectively, global ageing of populations will lead to a major increase of subjects being diagnosed with osteoporosis and in need for dental rehabilitation. However, as local osteoporosis of the jaws affects bone quantity and quality of edentulous regions, osseointegration of dental implants ...
Olmer Ruth - - 2012
Therapeutic and industrial applications of pluripotent stem cells and their derivatives require large cell quantities generated in defined conditions. To this end, we have translated single cell-inoculated suspension cultures of human pluripotent stem cells (hPSCs; including human induced pluripotent stem cells [hiPS] and human embryonic stem cells [hESC]) to stirred ...
Moukharskaya Julia - - 2012
Topoisomerase 1 inhibitors cure human cancer xenografts in animal models, more so than most other chemotherapy agents. However, their activity in patients with cancer is modest. Ongoing research is studying the optimal analogues that could reproduce animal data in the cancer population. This article analyzes the clinical research with topoisomerase ...
Cohen Deirdre J - - 2012
The Hedgehog (Hh) pathway is a signaling cascade that is evolutionally highly conserved and plays an important role in embryonic pattern formation and stem cell response to tissue damage. Given the pivotal role the Hh pathway plays in embryonic development in terms of proliferation and differentiation, it is not surprising ...
Balantic Mateja - - 2012
Asthma is a common chronic disease characterized by airway inflammation and structural remodeling. Vascular endothelial growth factor (VEGF), a major regulator of angiogenesis, is elevated in asthma patients. VEGF contributes to airway responsiveness and remodeling. It has been shown that treatment of asthma patients decreases VEGF levels, and inhibition of ...
Teles Liz M B - - 2012
Neutrophils have an impressive array of microbicidal weapons, and in the presence of a pathogen, progress from a quiescent state in the bloodstream to a completely activated state. Failure to regulate this activation, for example, when the blood is flooded with cytokines after severe trauma, causes inappropriate neutrophil activation that ...
Lee Youngsoo - - 2012
The rapid proliferation of progenitors during neurogenesis requires a stringent genomic maintenance program to ensure transmission of genetic fidelity. However the essential factors that govern neural progenitor genome integrity are unknown. Here we report that conditional inactivation of mouse TopBP1, a protein linked to DNA replication, and a key activator ...
Wang Deli - - 2012
Prenatal development and early childhood are critical periods for establishing the tissue-specific epigenome, and may have a profound impact on health and disease in later life. However, epigenomic profiles at birth and in early childhood remain largely unexplored. The focus of this report is to examine the individual variation and ...
Li Qian - - 2012
Colorectal cancer (CRC) is the third most common cancer in the United States. Approximately 90% of colon cancer deaths arise from the metastasis of primary tumors. Aberrant expression of Wnt5a, one of the WNT signaling factors, has been reported during colon cancer development and progression. We found that both mRNA ...
Balog Judit - - 2012
The aim of our study was to identify relationships between epigenetic parameters correlating with a relaxed chromatin state of the DUX4 promoter region and clinical severity as measured by a clinical severity score or muscle pathologic changes in D4Z4 contraction-dependent (FSHD1) and -independent (FSHD2) facioscapulohumeral muscular dystrophy patients. Twenty primary ...
Shimoda S - - 2012
One of the major obstacles in dissecting the mechanism of pathology in human primary biliary cirrhosis (PBC) has been the absence of animal models. Our laboratory has focused on a model in which mice, following immunization with a xenobiotic chemical mimic of the immunodominant autoepitope of the E2 component of ...
Yang C-Y - - 2012
Although the hallmark of primary biliary cirrhosis (PBC) is the presence of anti-mitochondrial antibodies (AMA), a significant number of patients have anti-nuclear antibodies (ANA) directed primarily against two nuclear proteins, gp210 and sp100. In PBC, there are considerable data on the specificity of these anti-nuclear antibodies as well as suggestive ...
Nagayama Y - - 2012
Major histocompatibility complex (MHC) class I-restricted T cell epitopes are generated mainly by the immunoproteasome in antigen-presenting cells. Therefore, inhibition of activity of this proteolytic complex molecule is thought to be a potential treatment for cell-mediated autoimmune diseases. We therefore studied the efficacy of an immunoproteasome inhibitor, ONX 0914 (formerly ...
Adler K - - 2012
The impact of gestation and fetal-maternal interactions on pre-existent autoimmune beta cell destruction is widely unknown. The aim of this study was to investigate the influence of gestation per se and fetal mismatching on the onset of autoimmune diabetes in female non-obese diabetic (NOD) mice. We examined cumulative diabetes frequencies ...
De Bortoli Teixeira Larissa - - 2012
Hev b 13 is an allergenic esterase obtained from the rubber tree Hevea brasiliensis, which has been shown recently to induce human monocytes to release interleukin (IL)-10 in vitro, and to exert a potent anti-inflammatory effect in vivo. Moreover, Hev b 13 has been shown to reduce clinical signs of ...
Boccon-Gibod I - - 2012
We evaluated the efficacy and safety of icatibant self-administration in 15 patients with hereditary angioedema (HAE) types I or III, for 55 acute attacks (mostly severe or very severe). Icatibant self-administration was generally effective: first symptom improvement occurred in 5 min-2 h (HAE type I; n = 17) and 8 min-1 h (HAE type III; n = 9) ...
Behrendt A-K - - 2012
The co-stimulatory molecule CD137 (4-1BB) plays a crucial role in the development and persistence of asthma, characterized by eosinophilic airway inflammation, mucus hypersecretion, airway hyperreactivity, increased T helper type 2 (Th2) cytokine production and serum immunoglobulin (Ig)E levels. We have shown previously that application of an agonistic CD137 monoclonal antibody ...
Kotani H - - 2012
LIGHT [the name of which is derived from 'homologous to lymphotoxins, exhibits inducible expression, competes with herpes simplex virus glycoprotein D for herpes simplex virus entry mediator (HVEM), and expressed by T lymphocytes'], is a member of the tumour necrosis factor superfamily that is involved in various inflammatory diseases. We ...
Adler Mark J - - 2012
Antibody-based therapeutics against cancer are highly successful and currently enjoy unprecedented recognition of their potential; 13 monoclonal antibodies (mAbs) have been approved for clinical use in the European Union and in the United States. Bevacizumab, rituximab, and trastuzumab had sales in 2010 of more than $5 billion each. Hundreds of ...
Park Sook Ryun - - 2012
Recently, the development of poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors as a synthetic lethality approach has brought a major breakthrough in the treatment of breast cancer susceptibility gene (BRCA)-mutant cancers. Because sporadic cancers have also been found to commonly have other defects in DNA repair, PARP inhibitors are under active clinical ...
de Oliveira G L V - - 2012
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by T cell-mediated destruction of pancreatic β cells, resulting in insulin deficiency and hyperglycaemia. Recent studies have described that apoptosis impairment during central and peripheral tolerance is involved in T1D pathogenesis. In this study, the apoptosis-related gene expression in T1D ...
Mitchell David - - 2012
Ultraviolet radiation (UVR) exposure to internal tissues for diagnostic, therapeutic and cosmetic procedures has increased dramatically over the past decade. The greatest increase in UVR exposure of internal tissues occurs in the cosmetic industry where it is combined with oxidizing agents for teeth whitening, often in conjunction with indoor tanning. ...
Lee Jaymi F - - 2012
Healthcare providers use recombinant biologics such as monoclonal antibodies to treat a variety of serious illnesses. Manufacturing of approved biotechnology products is complex, and the quality of the resulting biologic is dependent on careful control of process inputs and operating conditions. Biosimilars, which are similar but not identical to innovator ...
Nelson Heather H - - 2012
Epigenetic alterations are a common event in lung cancer and their identification can serve to inform on the carcinogenic process and provide clinically relevant biomarkers. Using paired tumor and non-tumor lung tissues from 146 individuals from three independent populations we sought to identify common changes in DNA methylation associated with ...
Quinn Roswell R Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, - - 2012
Human papillomavirus (HPV) infection among men who have sex with men (MSM) is the primary risk factor for anal cancer. Of 105 Peruvian MSM examined, 77.1% were infected with HPV; of these 79.0% were coinfected with two or more types and 47.3% were infected by a carcinogenic type. HPV types ...
Visentin Michele M Department of Medicine and the Albert Einstein Cancer Center, The Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, - - 2012
This article focuses on the cellular, biochemical, and molecular pharmacology of antifolates and how a basic understanding of the mechanism of action of methotrexate, its cytotoxic determinants, mechanisms of resistance, and transport into and out of cells has led to the development of a new generation of antifolates, a process ...
Anquetil Delphine D UMR 5234 CNRS and Laboratoire de Virologie (WHO accredited), University Hospital of Bordeaux, Bordeaux, - - 2012
Abstract We analyzed subtype C HIV-1 isolates from patients at failure of a regimen including nevirapine or efavirenz for their susceptibility or resistance to etravirine according to the ANRS and STANFORD algorithms. Statistical analysis showed a consensus that more than 45% of these viral strains are potentially resistant to etravirine.
Chamberlain Sophie E L SE School of Physiology and Pharmacology, Medical Research Council Centre for Synaptic Plasticity, University of Bristol, Bristol, - - 2012
Phosphorylation or SUMOylation of the kainate receptor (KAR) subunit GluK2 have both individually been shown to regulate KAR surface expression. However, it is unknown whether phosphorylation and SUMOylation of GluK2 are important for activity-dependent KAR synaptic plasticity. We found that protein kinase C–mediated phosphorylation of GluK2 at serine 868 promotes ...
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