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Plant Ashley S - - 2013
Undifferentiated embryonal liver sarcoma (UELS) makes up 9% to 15% of all malignant liver tumors in children. UELS is characteristically diagnosed between the ages of 6 and 10 years and presents with abdominal pain, vomiting, and an abdominal mass. There is currently no standardized treatment for UELS except attempt at ...
Kimura Yukiko - - 2013
Systemic juvenile idiopathic arthritis (JIA) is characterized by fevers, rash, and arthritis, for which interleukin-1 (IL-1) and IL-6 inhibitors appear to be effective treatments. Pulmonary arterial hypertension (PAH), interstitial lung disease (ILD), and alveolar proteinosis (AP) have recently been reported with increased frequency in systemic JIA patients. Our aim was ...
Gao K K Department of Plastic and Reconstructive Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, - - 2013
Pulsed-dye laser (PDL)-mediated photothermolysis is the current standard treatment for port-wine stain (PWS) birthmarks. Vascular-targeted photodynamic therapy (PDT) might be an alternative for the treatment of PWS. To compare clinical outcomes of PDT and PDL treatment of PWS. Two adjacent flat areas of PWS lesions were selected from each of ...
Marder Wendy W University of Michigan, Ann Arbor, MI 48105, - - 2013
Azathioprine (AZA) is recognized among immunosuppressive medications as relatively safe during pregnancy for women with systemic lupus erythematosus (SLE) requiring aggressive treatment. This pilot study aimed to determine whether SLE therapy during pregnancy was associated with developmental delays in offspring. This cohort study included SLE patients with at least one ...
Oyomopito Rebecca A RA Faculty of Medicine, The Kirby Institute, UNSW, Sydney, Australia. - - 2013
HIV-1 group M viruses diverge 25%-35% in envelope, important for viral attachment during infection, and 10%-15% in the pol region, under selection pressure from common antiretrovirals. In Asia, subtypes B and CRF01_AE are common genotypes. Our objectives were to determine whether clinical, immunological, or virological treatment responses differed by genotype ...
Chen Yu - - 2013
Amygdalin, a naturally occurring substance, has been suggested to be efficacious as an anticancer substance. The effect of amygdalin on cervical cancer cells has never been studied. In this study, we found that the viability of human cervical cancer HeLa cell line was significantly inhibited by amygdalin. 4,6-Diamino-2-phenyl indole (DAPI) ...
Castelli Roberto - - 2013
Deficiencies in the inhibitor of the first component of human complement (C1-INH) are clinically associated with both hereditary angioedema (HAE) and acquired angioedema (AAE). The reduction in C1-INH function leads to the activation of the classical complement pathway and consequent complement consumption, as well as to the activation of the ...
Singh Kumud K - - 2013
Apolipoprotein B mRNA editing catalytic polypeptide 3G (APOBEC3G) protein is incorporated into nascent virus particles and mediates cytidine deamination (C-to-U) of first-strand reverse transcripts of HIV-1 in target cells resulting in G-to-A hypermutation of the coding strand and premature degradation. We investigated the effects of APOBEC3G genetic variants on HIV-1-related ...
Topete-Reyes Jorge F - - 2013
The angiotensin (Ang)-converting enzyme (ACE) insertion/deletion (I/D) polymorphism determines Ang II levels, but its relationship with lupus nephritis (LN) in different populations is controversial. To describe the allelic and genotypic distribution of the I/D polymorphism in Mexican mestizos with LN and assess an association with histological classes. We included 24 ...
Haddow James E JE Division of Medical Screening and Special Testing, Women and Infants Hospital, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA. - - 2013
Among euthyroid pregnant women in a large clinical trial, free thyroxine (FT4) measurements below the 2.5th centile were associated with a 17 lb higher weight (2.9 kg/m(2)) than in the overall study population. We explore this relationship further. Among 9351 women with second trimester thyrotropin (TSH) measurements between 1st and 98th centiles, ...
Jaja Blessing N R BN St. Michael's Hospital, University of Toronto, Toronto, ON, - - 2013
Clinical prediction models can enhance clinical decision-making and research. However, available prediction models in aneurysmal subarachnoid hemorrhage (aSAH) are rarely used. We evaluated the methodological validity of SAH prediction models and the relevance of the main predictors to identify potentially reliable models and to guide future attempts at model development. ...
Gavriilidis Christos C Newcastle University, Newcastle upon Tyne, - - 2013
Superoxide dismutase 2 (SOD2) is down- regulated in osteoarthritis (OA). This study was undertaken to investigate the functional effects of this down-regulation in the context of oxidative damage and mitochondrial dysfunction. Lipid peroxidation in articular cartilage from OA patients and from lesion-free control subjects with femoral neck fracture was assessed ...
Nicholls Samantha B SB Department of Chemistry, University of Massachusetts Amherst, Amherst, Massachusetts 01003, - - 2013
Apoptosis is critical for organismal homeostasis and a wide variety of diseases. Caspases are the ultimate executors of the apoptotic programmed cell death pathway. As caspases play such a central role in apoptosis, there is significant demand for technologies to monitor caspase function. We recently developed a caspase activatable-GFP (CA-GFP) ...
Alagaratnam Sharmini S Department of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital, Oslo, - - 2013
To circumvent difficulties of isolating pure populations of cancer stem cells (CSCs) for the purpose of identifying malignancy-specific gene expression, we have compared exon-resolution transcriptomic profiles of 5 embryonal carcinoma (EC) cell lines, a histological subtype of germ cell tumor (GCT), to their nonmalignant caricature, specifically 6 human embryonic stem ...
Marsden Edward - - 2013
The rat is the routine species of choice as the rodent model for regulatory safety testing of xenobiotics such as medicinal products, food additives, and other chemicals. However, the rat is not always suitable for pharmacological, toxicological, immunogenic, pharmacokinetic, or even practical reasons. Under such circumstances, the mouse offers an ...
Holt Janet E - - 2013
The first meiotic division of mammalian oocytes physiologically occurs in the ovary in the hours preceding ovulation. Fortunately, oocytes removed from their follicular environment will readily undergo this process in culture. Their large size, optical transparency, and efficiency in translating exogenous cRNA make mouse oocytes very amenable to study this ...
Reynaud Lucie - - 2013
A skeletal examination of fetuses is required in regulatory embryo-fetal development studies. This chapter describes a method of skeletal examination using alizarin staining. All fetuses are removed from the mother by caesarean section before birth. The fetuses are first examined externally. For larger species (rabbit and minipig), an internal examination ...
Schulpen Sjors H W - - 2013
The embryonic stem cell test is an animal-free alternative test method for developmental toxicity. Mouse embryonic stem cells are cultured in a hanging drop method to form embryoid bodies. These embryoid bodies, when plated on tissue culture dishes, differentiate to form contracting myocardial cell foci within 10 days. Inhibition of ...
Reynaud Lucie - - 2013
Under normal circumstances, fertility and embryotoxicity studies are run separately according to the ICH S5(R2) guideline for the detection of toxicity to reproduction of medicinal products (1). However, the flexible approach of the S5(R2) guideline also allows the reproduction stages covered in the fertility and embryo-fetal development studies (stages A ...
Dumont Julien - - 2013
Oocytes are extremely large cells that have to coordinate accurate chromosome segregation, asymmetric cytoplasm partitioning together with their own development as fertilizable gametes. For this, they undergo both global (cell cycle progression related) and local changes. It is therefore essential to be able to monitor local changes as they take ...
Leconte Isabelle - - 2013
Frog embryo teratogenesis assay on Xenopus (FETAX) has been routinely used in our laboratory for the last 12 years as a routine developmental toxicity screening test for pharmaceutical candidate compounds. To date, out of more than 400 candidates tested in FETAX, around 60 have also been evaluated in mammalian embryotoxicity ...
French Julian M - - 2013
The use of magnetic resonance imaging of the fetal rat and rabbit head, as an alternative to the traditional methods of fixation and preparation of serial sections, is described. Labeled magnetic resonance images of normal head anatomy have been provided as a reference for use when evaluating the internal structures ...
Ridings James E - - 2013
It is close to 60 years since thalidomide was created by the German company, Chemie-Grünenthal, and launched as "Contergan." This was soon to be followed in England by the launch of "Distaval." Of all the drugs developed in the intervening years, thalidomide has undoubtedly had the greatest influence on shaping ...
Chambon Jean-Philippe - - 2013
This chapter describes a technique for performing chromosome spreads from mouse oocytes. It is based on a previously described protocol (Hodges and Hunt, Chromosoma 111: 165-169, 2002), which we have modified. Chromosomes are stained with either Propidium Iodide or Hoechst. This spreading technique allows for simultaneous immunostaining of proteins associated ...
Ulbrich Beate - - 2013
Human health risk assessment for pesticides is based mainly on animal studies submitted by the applicant and aims to determine safe exposure levels for operators (farmers and agricultural workers) and consumers of all age groups. Critical effects, including those resulting from reproductive toxicity, are identified during hazard assessment from an ...
Fuchs Antje - - 2013
Embryo fetal development (EFD) studies in nonhuman primates are frequently conducted in macaques with Macaca fascicularis (cynomolgus monkey, long-tailed macaque, crab-eating macaque) being the most accepted model. EFD studies are also feasible in the marmoset. Due to recent guideline changes (ICH M3(R2) and S6(R1)), EFD studies are largely confined to ...
Hill Patrick L - - 2013
The current study examined whether dispositional gratitude predicts physical health among adults, and if so, whether this relationship occurs because grateful individuals lead healthier lives, either psychologically or physically. Specifically, we examined whether psychological health, healthy activities, and willingness to seek help for health concerns mediated the link between gratitude ...
Spézia François - - 2013
In Europe, the developmental toxicity testing (including teratogenicity) of new cosmetic ingredients is performed according to the Cosmetics Directive 76/768/EEC: only alternatives leading to full replacement of animal experiments should be used. This chapter presents the three scientifically validated animal alternative methods for the assessment of embryotoxicity: the embryonic stem ...
Weinbauer Gerhard F - - 2013
The enhanced pre- and postnatal (ePPND) study design has been developed in response to new scientific knowledge and subsequent guideline changes [ICH M3(R2) and ICH S6(R1)]. The changes in study design were basically driven by the experiences obtained during preclinical development of biopharmaceuticals. The standard ePPND concept does not apply ...
Barrow Paul C - - 2013
Preventative and therapeutic vaccines are increasingly used during pregnancy and present special considerations for developmental toxicity testing. The various components of the vaccine formulation (i.e., protein or polysaccharide antigen, adjuvants, and excipients) need to be assessed for direct effects on the developing conceptus. In addition, possible adverse influences of the ...
Danielsson Bengt R - - 2013
Although demonstration of some degree of maternal toxicity is required in regulatory developmental toxicology studies, marked maternal toxicity may be a confounding factor in data interpretation. Reduction in maternal body weight gain is the far most frequently used endpoint of toxicity, but alternative endpoints, like organ toxicity or exaggerated pharmacological ...
Barrow Paul C - - 2013
The regulatory toxicology report is an unusual document that requires a particular skill to write. The report must be clear, accurate, concise, and focused. A clear and direct writing style is required. The end-users of the report will hope to find the information they seek with as little effort as ...
Davidson Elizabeth - - 2013
This chapter outlines a regulator's personal approach to the assessment of reproductive toxicology data in the context of the assessment of the overall nonclinical data package for pharmaceutical agents. Using as a framework the International Conference on Harmonisation Common Technical Document headings, guidance is provided on the expectations of regulators ...
Yang Kuo-Tai - - 2013
We previously isolated Aurora-C (Aurkc/Aie1) in a screen for kinases expressed in mouse sperm and eggs. Aurora-C kinase was reported to be a chromosomal passenger protein that plays critical roles in chromosome alignment, segregation, kinetochore-microtubule attachment, and cytokinesis in female mouse meiosis. This chapter describes experimental approaches for examining the ...
Levasseur Mark - - 2013
Fluorescently tagged proteins have become a crucial weapon in the armory of a successful cell biology laboratory. This chapter describes how to produce cRNA coding for a fluorescently tagged protein of choice, such that it is suitable for microinjection and subsequent expression studies in live oocytes.
Buschmann Jochen - - 2013
In many countries the process of toxicity testing of environmental chemicals is ruled by a framework of OECD guidelines. The present paper will give an overview over the relevant OECD guidelines and guidance documents and mainly focus on methodological issues related to the prenatal toxicity testing guideline. Relevant guideline text ...
Polanski Zbigniew - - 2013
Mouse oocytes and zygotes are semitransparent and large cells approximately 80 μm in diameter. Bisection is one of the easiest ways for performing micromanipulations on such cells. It allows living sister halves or smaller fragments to be obtained, which can be cultured and observed for long periods of time. Bisection ...
Critchell Karon - - 2013
This chapter describes the method used for serial sectioning and soft tissue examination of the Bouin's fixed fetus (mainly whole rat and or mouse fetuses or rabbit fetal heads) for the assessment of developmental and structural abnormalities. Fetuses are examined externally, together with the internal structures of the head as ...
Kubiak Jacek Z - - 2013
Protein phosphorylation plays a pivotal role in cell cycle regulation. MPF (M-phase Promoting Factor) and MAPK (Mitogen-activated protein kinase) are two major kinases driving oocyte maturation and early embryonic divisions. Their activities can be measured experimentally with kinase assays that use specific exogenous substrates. The activities of MPF and MAPK ...
Mylchreest Eve - - 2013
Reproductive and developmental toxicity studies in laboratory animals are conducted as part of the process of evaluating the risk of pharmaceuticals and chemicals to human reproduction and development. In these studies, comparison of data from groups dosed with the test article to a concurrent control group is considered the most ...
Robinson Joshua F - - 2013
The emergence of toxicogenomic applications provides new tools to characterize, classify, and potentially predict teratogens. However, due to the vast number of experimental and statistical procedural steps, toxicogenomic studies are challenging. Here, we guide researchers through the basic framework of conducting toxicogenomic investigations in the field of developmental toxicology, providing ...
Knudsen Thomas - - 2013
Understanding the potential health risks posed by environmental chemicals is a significant challenge elevated by the large number of diverse chemicals with generally uncharacterized exposures, mechanisms, and toxicities. The ToxCast computational toxicology research program was launched by EPA in 2007 and is part of the federal Tox21 consortium to develop ...
McAnulty Peter A - - 2013
The minipig is a suitable species for regulatory teratology testing and may be regarded as an alternative to the rabbit, dog, and primate. The first successful regulatory teratology studies in the minipig were performed in the 1990s. It became clear that minipigs have several benefits over the other non-rodents, as ...
Barton Steve - - 2013
REACH guidelines may require teratology testing for new and existing chemicals. This chapter discusses procedures to assess the need for teratology testing and the conduct and interpretation of teratology tests where required.
Jaroudi Souraya - - 2013
The cytogenetic analysis of single cells, such as oocytes and polar bodies, is extremely challenging. The main problem is low probability of obtaining a metaphase preparation in which all of the chromosomes are sufficiently well spread to permit accurate analysis (no overlapping chromosomes, no chromosomes lost). As a result, a ...
Wise L David - - 2013
Relying on previous regulatory guidelines from multiple countries, the ICH S5(R2) guideline outlines the preclinical safety studies needed for registration of new medicinal products in the member countries (European Union, Japan, and the United States). The primary purpose of the guideline is to provide a testing strategy to detect and ...
Anguish Lynne - - 2013
The visualization of subcellular organelles and structures is a valuable tool for understanding cellular changes that occur in oocytes and early embryos as a result of genetic alterations, incubation conditions, drug treatments, and many other manipulations. Preparing oocytes for transmission electron microscopic analysis can be challenging as these cells cannot ...
Vasquez Sergio X - - 2013
Micro-computed tomography imaging technology allows for the whole-mount investigation of skeletal structures in preclinical specimens at both fetal and postnatal time points. The imaging process is nondestructive to the specimen and can be performed at various resolutions to derive the region of interest information most relevant to individual researchers. In ...
Brannen Kimberly C - - 2013
As a model for teratogenicity research, zebrafish are gaining popularity and creditability. Zebrafish embryos have been proven to be a highly valuable tool in genetics and developmental biology research and have advanced our understanding of a number of known developmental toxicants. It has yet to be determined conclusively how reliably ...
Leroy Mariline - - 2013
This chapter describes methods for the examination of fetal abdominal and thoracic soft tissues by microdissection on either fresh (non-rodent) or fixed (rodent) specimens in order to detect structural abnormalities. With hundreds of fetuses examined for each species (rodent and non-rodent) in regulatory reproductive toxicity assessments (ICH, http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Multidisciplinary/M3_R2/Step4/M3_R2__Guideline.pdf, 2009; ICH, ...
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