Publications

TitleAbstractYear
Filter
PMID(sorted descending)
Filter
haplotype diversity generated by ancient recombination-like events in the mhc of indian rhesus macaques.the mamu-a, mamu-b, and mamu-drb genes of the rhesus macaque show several levels of complexity such as allelic heterogeneity (polymorphism), copy number variation, differential segregation of genes/alleles present on a haplotype (diversity) and transcription level differences. a combination of techniques was implemented to screen a large panel of pedigreed indian rhesus macaques (1,384 individuals representing the offspring of 137 founding animals) for haplotype diversity in an efficient and ine ...201323715823
oral immunotherapy for allergic diseases using transgenic rice seeds: current state and future prospects.allergen-specific immunotherapy (it) has been shown to provide clinical benefit for patients with allergic diseases. at present, subcutaneous and sublingual its are mainly authorized for clinical treatment. oral administration of allergens seems to be the easiest way to achieve it, though it has yet to be translated to the clinical setting, mainly due to the requirement of a large amount of allergens. plants, especially rice seeds, have recently been recognized as superior allergen carriers for ...201323711869
pharmacokinetics and safety in cynomolgus monkeys of a monoclonal antibody targeting human scavenger receptor class b type-1 for hepatitis c treatment.scavenger receptor class b type-1 (sr-b1) is one of the many receptors used by hcv to infect hepatocytes. it is used by the virus not only to directly infect cells but also to facilitate cell-to-cell transmission of the virus. agents such as anti-human sr-b1 (anti-hsr-b1) antibodies represent potential therapeutics for the treatment of hcv infections. the purpose of this study was to evaluate the safety and pharmacokinetics of an anti-hsr-b1 antibody (seq2) in cynomolgus monkeys.201323702590
major histocompatibility complex class i haplotype diversity in chinese rhesus macaques.the use of chinese-origin rhesus macaques (macaca mulatta) for infectious disease immunity research is increasing despite the relative lack of major histocompatibility complex (mhc) class i immunogenetics information available for this population. we determined transcript-based mhc class i haplotypes for 385 chinese rhesus macaques from five different experimental cohorts, providing a concise representation of the full complement of mhc class i major alleles expressed by each animal. in total, 1 ...201323696100
preclinical evaluation of the toxicological effects of a novel constrained ethyl modified antisense compound targeting signal transducer and activator of transcription 3 in mice and cynomolgus monkeys.isis 481464 is a constrained ethyl (cet) modified phosphorothioate antisense oligonucleotide (aso) targeting signal transducer and activator of transcription 3 (stat3) studied in mice and monkey to support oncology clinical trials. six-week toxicology studies were performed in mice and cynomolgus monkey (up to 70 and 30 mg/kg/week respectively). reduction in stat3 protein up to 90% of control was observed in monkey. cynomolgus monkey was considered the most relevant species to human with respect ...201323692080
monocyte-derived il-5 reduces tnf production by mycobacterium tuberculosis-specific cd4 t cells during siv/m. tuberculosis coinfection.hiv-infected individuals are significantly more susceptible to tuberculosis (tb) than uninfected individuals. although it is established that hiv reduces mycobacterium tuberculosis-specific t cell responses, the causes of this dysfunction are not known. we used the cynomolgus macaque model of tb to demonstrate that ex vivo siv reduces the frequency of m. tuberculosis-specific tnf and ifn-γ-producing t cells within 24 h after infection. in vivo, t cell ifn-γ responses in granulomas from animals w ...201323690470
preclinical qt safety assessment: cross-species comparisons and human translation from an industry consortium.in vivo models have been required to demonstrate relative cardiac safety, but model sensitivity has not been systematically investigated. cross-species and human translation of repolarization delay, assessed as qt/qtc prolongation, has not been compared employing common methodologies across multiple species and sites. therefore, the accurate translation of repolarization results within and between preclinical species, and to man, remains problematic.201423689033
assessment of menstrual cycle length in cynomolgus monkeys as a female fertility endpoint of a biopharmaceutical in a 6 month toxicity study.according to ich s6(r1), mating studies are not practical for assessing effects on female fertility of biopharmaceuticals that are pharmacologically active only in non-human primates (nhps). instead, fertility should be assessed by evaluating histopathology and organ weights of the reproductive tract in studies of at least 3 months dosing duration using sexually mature nhps. an assessment of the menstrual cycle in females can be included if there is cause for concern based on pharmacological mod ...201323680404
effects of bazedoxifene, conjugated equine estrogens, and a tissue-selective estrogen complex containing both bazedoxifene and conjugated equine estrogens on cerebral artery atherosclerosis in postmenopausal monkeys.this study aims to evaluate the effects of a new selective estrogen receptor modulator (bazedoxifene acetate [bza]) and a tissue-specific estrogen complex (bza combined with conjugated equine estrogens [cee]) on the extent and severity of cerebral artery atherosclerosis.201423676638
high hematocrit resulting from administration of erythropoiesis-stimulating agents is not fully predictive of mortality or toxicities in preclinical species.we conducted a retrospective analysis of publicly available preclinical toxicology studies with erythropoiesis-stimulating agents (esas) to examine common adverse events in rats, beagle dogs, and cynomolgus monkeys. mortality and/or thrombotic events were reported sporadically in a subset of studies and attributed to the high hematocrit (hct) achieved in the animals. however, similarly high hct was achieved in both high-dose and low-dose groups, but there were no reported adverse events in the l ...201423674390
long-tailed macaques (macaca fascicularis) understand what conspecifics can see in a competitive situation.visual perspective taking (vpt), an understanding of what others can see, is a prerequisite for theory of mind (tom). while vpt in apes is proven, its presence in monkeys is much-debated. several different paradigms have been developed to test its existence, but all face interpretational problems since results can be explained by simpler cognitive mechanisms than vpt. therefore, we adjusted one method where two individuals compete for access to food, visible or invisible for the dominant competi ...201423666397
behavioural profiles in captive-bred cynomolgus macaques: towards monkey models of mental disorders?to date, experimental and preclinical studies on neuropsychiatric conditions have almost exclusively been performed in experimentally-induced animal models and have only rarely relied upon an ethological approach where animals have been observed in more naturalistic settings. the laboratory species of choice has been the rodent while the potential of more closely-related non-human primates have remained largely underexplored.201323658620
reach-to-grasp movements in macaca fascicularis monkeys: the isochrony principle at work.humans show a spontaneous tendency to increase the velocity of their movements depending on the linear extent of their trajectory in order to keep execution time approximately constant. termed the isochrony principle, this compensatory mechanism refers to the observation that the velocity of voluntary movements increases proportionally with their linear extension. although there is a wealth of psychophysical data regarding isochrony in humans, there is none regarding non-human primates. the pres ...201323658547
assessment of the protective effect of imvamune and acam2000 vaccines against aerosolized monkeypox virus in cynomolgus macaques.to support the licensure of a new and safer vaccine to protect people against smallpox, a monkeypox model of infection in cynomolgus macaques, which simulates smallpox in humans, was used to evaluate two vaccines, acam2000 and imvamune, for protection against disease. animals vaccinated with a single immunization of imvamune were not protected completely from severe and/or lethal infection, whereas those receiving either a prime and boost of imvamune or a single immunization with acam2000 were p ...201323658452
cytochrome p450 metabolic activities in the small intestine of cynomolgus macaques bred in cambodia, china, and indonesia.cynomolgus macaques, used in drug metabolism studies due to their evolutionary closeness to humans, are mainly bred in asian countries, including cambodia, china, and indonesia. cytochromes p450 (p450s) are important drug-metabolizing enzymes, present in the liver and small intestine, major drug metabolizing organs. previously, our investigation did not find statistically significant differences in hepatic p450 metabolic activities measured in cynomolgus macaques bred in cambodia (macfacam) and ...201323648676
foodborne transmission of bovine spongiform encephalopathy to nonhuman primates.risk for human exposure to bovine spongiform encephalopathy (bse)-inducing agent was estimated in a nonhuman primate model. to determine attack rates, incubation times, and molecular signatures, we orally exposed 18 macaques to 1 high dose of brain material from cattle with bse. several macaques were euthanized at regular intervals starting at 1 year postinoculation, and others were observed until clinical signs developed. among those who received ≥5 g bse-inducing agent, attack rates were 100% ...201323647575
highly specific and sensitive measurements of human and monkey interleukin 21 using sequential protein and tryptic peptide immunoaffinity lc-ms/ms.a highly specific and sensitive immunoaffinity lc-ms/ms assay for quantification of human and cynomolgus monkey interleukin 21 (il-21) was developed, qualified, and implemented. the workflow includes offline enrichment of il-21 using an anti-il-21 capture antibody, followed by isolation using magnetic beads, trypsin digestion, online enrichment of il-21 derived tryptic peptides using antipeptide antibodies, and quantification using nanoflow lc-ms/ms. this assay was developed and qualified in hum ...201323638938
ex vivo-expanded cynomolgus macaque regulatory t cells are resistant to alemtuzumab-mediated cytotoxicity.alemtuzumab (campath-1h) is a humanized monoclonal antibody (ab) directed against cd52 that depletes lymphocytes and other leukocytes, mainly by complement-dependent mechanisms. we investigated the influence of alemtuzumab (i) on ex vivo-expanded cynomolgus monkey regulatory t cells (treg) generated for prospective use in adoptive cell therapy and (ii) on naturally occurring treg following alemtuzumab infusion. treg were isolated from pbmc and lymph nodes and expanded for two rounds. cd52 expres ...201323635093
novel humanized anti-cd20 antibody bm-ca binds to a unique epitope and exerts stronger cellular activity than others.cellular activity of bm-ca, a novel humanized anti-cd20 antibody, was quantitatively compared with that of two other anti-cd20 antibodies used for clinical practice, rituximab and ofatumumab. the results of a complement-dependent cytotoxicity (cdc) assay revealed that the strongest antibody was ofatumumab, followed by bm-ca, with rituximab being the weakest. ofatumumab and bm-ca were effective not only against rituximab-sensitive su-dhl-4 cells but also against rituximab-resistant rc-k8 cells. i ...201323634281
characterization of recombinantly expressed rat and monkey intestinal alkaline phosphatases: in vitro studies and in vivo correlations.intestinal alkaline phosphatases (ialps) are widely expressed in the brush border of epithelial cells of the intestinal mucosa. although their physiologic role is unclear, they are very significant when it comes to the release of bioactive parent from orally dosed phosphate prodrugs. such prodrugs can be resistant to cleavage by ialp, or alternatively undergo rapid cleavage leading to the release and precipitation of the less soluble parent. because purified ialps from preclinical species are no ...201323633529
fgf21 can be mimicked in vitro and in vivo by a novel anti-fgfr1c/β-klotho bispecific protein.the endocrine hormone fgf21 has attracted considerable interest as a potential therapeutic for treating diabetes and obesity. as an alternative to the native cytokine, we generated bispecific avimer polypeptides that bind with high affinity and specificity to one of the receptor and coreceptor pairs used by fgf21, fgfr1c and β-klotho. these avimers exhibit fgf21-like activity in in vitro assays with potency greater than fgf21. in a study conducted in obese male cynomolgus monkeys, animals treate ...201323630589
transmission of hepatitis e virus from rabbits to cynomolgus macaques.the recent discovery of hepatitis e virus (hev) strains in rabbits in the people's republic of china and the united states revealed that rabbits are another noteworthy reservoir of hev. however, whether hev from rabbits can infect humans is unclear. to study the zoonotic potential for and pathogenesis of rabbit hev, we infected 2 cynomolgus macaques and 2 rabbits with an hev strain from rabbits in china. typical hepatitis developed in both monkeys; they exhibited elevated liver enzymes, viremia, ...201323628346
molecular and functional characterization of flavin-containing monooxygenases in cynomolgus macaque.flavin-containing monooxygenases (fmos), drug-metabolizing enzymes essential for the metabolism of endogenous biochemicals and foreign compounds, have been characterized in human (including fmo1-5 and fmo6p), but remain to be investigated in cynomolgus macaque. in this study, cdnas of cynomolgus fmo1-5 and fmo6 were isolated and characterized. amino acid sequences of cynomolgus fmo1-5, respectively, shared high sequence identities (94-98%) and were closely clustered in a phylogenetic tree, with ...201323623750
abruptio placentae in cynomolgus macaques (macaca fascicularis): male bias.abruptio placentae is a serious problem with a high rate of maternal and fetal mortality and documented sexual dimorphism in reoccurrence. macaca fascicularis is a well-described reproductive model; however, there are no data available regarding sexual dimorphism in abruptio placentae in these species.201323621893
structural and functional effects of hemiretinal endodiathermy axotomy in cynomolgus macaques.outer retinal injury has been well described in glaucoma. to better understand the source of this injury, we wanted to develop a reliable model of partial retinal ganglion cell (rgc) axotomy.201323620427
long-term structural and functional effects of autologous muscle precursor cell therapy in a nonhuman primate model of urinary sphincter deficiency.we measured the long-term efficacy of autologous muscle precursor cell therapy in premenopausal female nonhuman primates with sustained urinary sphincter deficiency.201323618586
adoptive transfer of lymphocytes isolated from simian immunodeficiency virus sivmac239δnef-vaccinated macaques does not affect acute-phase viral loads but may reduce chronic-phase viral loads in major histocompatibility complex-matched recipients.the live attenuated simian immunodeficiency virus (siv) sivmac239δnef is the most effective siv/human immunodeficiency virus (hiv) vaccine in preclinical testing. an understanding of the mechanisms responsible for protection may provide important insights for the development of hiv vaccines. leveraging the uniquely restricted genetic diversity of mauritian cynomolgus macaques, we performed adoptive transfers between major histocompatibility complex (mhc)-matched animals to assess the role of cel ...201323616658
differential effects of estradiol on carotid artery inflammation when administered early versus late after surgical menopause.the aim of this study was to determine the effects of estrogen therapy (et) on carotid artery inflammation when initiated early and late relative to surgical menopause.201323615645
selection of new appropriate reference genes for rt-qpcr analysis via transcriptome sequencing of cynomolgus monkeys (macaca fascicularis).in the investigation of the expression levels of target genes, reverse transcription quantitative real-time polymerase chain reaction (rt-qpcr) is the most accurate and widely used method. however, a normalization step is a prerequisite to obtain accurate quantification results from rt-qpcr data. therefore, many studies regarding the selection of reference genes have been carried out. recently, these studies have involved large-scale gene analysis methods such as microarray and next generation s ...201323613744
nonhuman primate retroviruses from cambodia: high simian foamy virus prevalence, identification of divergent stlv-1 strains and no evidence of siv infection.nonhuman primates (nhps) carry retroviruses such as simian immunodeficiency viruses (siv), simian t-cell lymphotropic viruses (stlv) and simian foamy viruses (sfv). here, we revisited nhps from cambodia to assess the prevalence and diversity of these retroviruses using updated viral detection tools. we screened blood from 118 nhps consisting of six species (macaca fascicularis (n=91), macaca leonine (n=8), presbytis cristata (n=3), nycticebus coucang (n=1), hylobates pileatus (n=14), and pongo p ...201323612320
comparison of the in vitro and in vivo stability of a succinimide intermediate observed on a therapeutic igg1 molecule.deamidation of asparagine residues, a post-translational modification observed in proteins, is a common degradation pathway in monoclonal antibodies (mabs). the kinetics of deamidation is influenced by primary sequence as well as secondary and tertiary folding. analytical hydrophobic interaction chromatography (hic) is used to evaluate hydrophobicity of candidate mabs and uncover post-translational modifications. using hic, we discovered atypical heterogeneity in a highly hydrophobic molecule (m ...201523608772
cell number and neuropil alterations in subregions of the anterior hippocampus in a female monkey model of depression.the anterior hippocampus is associated with emotional functioning and hippocampal volume is reduced in depression. more women are clinically depressed than men, yet the depressed female brain is little studied. we reported reduced anterior hippocampal volume in behaviorally depressed adult female cynomolgus macaques; the mechanisms contributing to that reduction are unknown. the present study represents the first systematic morphological investigation of the entire hippocampus in depressed femal ...201323607969
effects of age on noninvasive assessments of vascular function in nonhuman primates: implications for translational drug discovery.endothelium-dependent flow mediated dilation (fmd) and pulse-wave velocity (pwv), are used as measures of vascular health and predictors of cardiovascular risk in clinical studies, and both are age-dependent. numbers of circulating endothelial microparticles (emps) and endothelial progenitor cells (epcs) are also associated with cardiovascular risk, but independent of age in humans. the use of these measurements for pre-clinical assessment of drug cardiovascular safety and efficacy in non-human ...201323607770
minipig and beagle animal model genomes aid species selection in pharmaceutical discovery and development.improving drug attrition remains a challenge in pharmaceutical discovery and development. a major cause of early attrition is the demonstration of safety signals which can negate any therapeutic index previously established. safety attrition needs to be put in context of clinical translation (i.e. human relevance) and is negatively impacted by differences between animal models and human. in order to minimize such an impact, an earlier assessment of pharmacological target homology across animal m ...201323602889
dcdt2980s, an anti-cd22-monomethyl auristatin e antibody-drug conjugate, is a potential treatment for non-hodgkin lymphoma.antibody-drug conjugates (adc), potent cytotoxic drugs linked to antibodies via chemical linkers, allow specific targeting of drugs to neoplastic cells. we have used this technology to develop the adc dcdt2980s that targets cd22, an antigen with expression limited to b cells and the vast majority of non-hodgkin lymphomas (nhl). dcdt2980s consists of a humanized anti-cd22 monoclonal igg1 antibody with a potent microtubule-disrupting agent, monomethyl auristatin e (mmae), linked to the reduced cys ...201323598530
lead optimization of 5-amino-6-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)-4-hydroxyhexanamides to reduce a cardiac safety issue: discovery of ds-8108b, an orally active renin inhibitor.with the aim to address an undesired cardiac issue observed with our related compound in the recently disclosed novel series of renin inhibitors, further chemical modifications of this series were performed. extensive structure-activity relationships studies as well as in vivo cardiac studies using the electrophysiology rat model led to the discovery of clinical candidate trans-adamantan-1-ol analogue 56 (ds-8108b) as a potent renin inhibitor with reduced potential cardiac risk. oral administrat ...201323598247
species differences in hepatic and intestinal metabolic activities for 43 human cytochrome p450 substrates between humans and rats or dogs.1. prediction of human pharmacokinetics might be made more precise by using species with similar metabolic activities to humans. we had previously reported the species differences in intestinal and hepatic metabolic activities of 43 cytochrome p450 (cyp) substrates between cynomolgus monkeys and humans. however, the species differences between humans and rats or dogs had not yet been determined using comparable data sets with sufficient number of compounds. 2. here, we investigated metabolic sta ...201323593983
decreased hippocampal mineralocorticoid:glucocorticoid receptor ratio is associated with low birth weight in female cynomolgus macaque neonates.during pregnancy, glucocorticoids transfer environmental signals to the growing brain and its associated neuroendocrine system to modulate their maturation and function during adolescence and adulthood. increased in utero exposure to glucocorticoids is associated with impaired fetal growth resulting in low birth weight (lbw) and compromised neural development. the underlying molecular changes affecting brain development, however, are largely unknown. here, we compared the relative mrna expressio ...201323592886
toward reduction in animal sacrifice for drugs: molecular modeling of macaca fascicularis p450 2c20 for virtual screening of homo sapiens p450 2c8 substrates.macaca fascicularis p450 2c20 shares 92% identity with human cytochrome p450 2c8, which is involved in the metabolism of more than 8% of all prescribed drugs. to date, only paclitaxel and amodiaquine, two substrate markers of the human p450 2c8, have been experimentally confirmed as m. fascicularis p450 2c20 drugs. to bridge the lack of information on the ligands recognized by m. fascicularis p450 2c20, in this study, a three-dimensional homology model of this enzyme was generated on the basis o ...201223586958
exploring of primate models of tick-borne flaviviruses infection for evaluation of vaccines and drugs efficacy.tick-borne encephalitis virus (tbev) is one of the most prevalent and medically important tick-borne arboviruses in eurasia. there are overlapping foci of two flaviviruses: tbev and omsk hemorrhagic fever virus (ohfv) in russia. inactivated vaccines exist only against tbe. there are no antiviral drugs for treatment of both diseases. optimal animal models are necessary to study efficacy of novel vaccines and treatment preparations against tbe and relative flaviviruses. the models for tbe and ohf ...201323585873
mechanistic pharmacokinetic-pharmacodynamic modeling of bace1 inhibition in monkeys: development of a predictive model for amyloid precursor protein processing.this study was conducted to determine the pharmacokinetics (pk) and pharmacodynamics (pd) of two novel inhibitors of β-site amyloid precursor protein (app)-cleaving enzyme (bace1), gne-629 [(4s,4a's,10a's)-2-amino-8'-(2-fluoropyridin-3-yl)-1-methyl-3',4',4a',10a'-tetrahydro-1'h-spiro[imidazole-4,10'-pyrano[4,3-b]chromen]-5(1h)-one] and gne-892 [(r)-2-amino-1,3',3'-trimethyl-7'-(pyrimidin-5-yl)-3',4'-dihydro-2'h-spiro[imidazole-4,1'-naphthalen]-5(1h)-one], and to develop a pk-pd model to predict ...201323584887
poxvirus antigen staining of immune cells as a biomarker to predict disease outcome in monkeypox and cowpox virus infection in non-human primates.infection of non-human primates (nhps) such as rhesus and cynomolgus macaques with monkeypox virus (mpxv) or cowpox virus (cpxv) serve as models to study poxvirus pathogenesis and to evaluate vaccines and anti-orthopox therapeutics. intravenous inoculation of macaques with high dose of mpxv (>1-2×10(7) pfu) or cpxv (>10(2) pfu) results in 80% to 100% mortality and 66 to 100% mortality respectively. here we report that nhps with positive detection of poxvirus antigens in immune cells by flow cyto ...201323577120
high throughput transcriptome analysis of lipid metabolism in syrian hamster liver in absence of an annotated genome.whole transcriptome analyses are an essential tool for understanding disease mechanisms. approaches based on next-generation sequencing provide fast and affordable data but rely on the availability of annotated genomes. however, there are many areas in biomedical research that require non-standard animal models for which genome information is not available. this includes the syrian hamster mesocricetus auratus as an important model for dyslipidaemia because it mirrors many aspects of human disea ...201323575280
visuospatial properties of caudal area 7b in macaca fascicularis.to proceed from sensation to movement, integration and transformation of information from different senses and reference frames are required. several brain areas are involved in this transformation process, but previous neuroanatomical and neurophysiological studies have implicated the caudal area 7b as one particular component of this transformation system. in this study, we present the first quantitative report on the spatial coding properties of caudal area 7b. the results showed that neurons ...201323572367
[trimcyp frequency of the cynomolgus macaque (macaca fascicularis) in captivity in china].in most old world monkey species, trim5α plays a role in combating retroviruses and restricting hiv-1. alongside trim5α, the trimcyp fusion gene formed by the retrotransposition of a cypa pseudogene cdna to 3' terminal or 3'-utr of trim5 gene in these monkeys has become a key research area in anti hiv-1 factors. the regional differences, gene frequencies, genotypes, and retrovirus restrictive activities of trimcyp vary among different primate species. while the frequencies of cynomolgus trimcyp ...201323572358
a safety study of inactivated enterovirus 71 vaccine.enterovirus 71 (ev71) is one of the major causative agents for hand, foot and mouth disease (hfmd) in childhood. nowadays, hfmd or ev71 infections have already become an important public health issue throughout the world. vaccination may be the most effective measure to control the transmission of the virus. therefore, to pave ev71 vaccine into human clinical trial, in the present study a comprehensive preclinical safety assessment of inactivated ev71 vaccine including single- and repeat-dose to ...201323571172
effects of acute psychosocial stress in a nonhuman primate model of allergic asthma.current husbandry and care guidelines for laboratory animals recommend social housing for nonhuman primates and all other social species. however, not all individuals of a social species are compatible, which can lead to psychosocial stress on certain members. because stress affects immune responses, we undertook the present study to determine whether psychosocial stress associated with changes in the group housing of nonhuman primates affected allergic responses in a nonhuman primate model of a ...201323562098
pharmacokinetics of 2 formulations of buprenorphine in macaques (macaca mulatta and macaca fascicularis).buprenorphine is the cornerstone of pain management in nonhuman primates, but the pharmacokinetics of this widely used drug are unknown. the purpose of this study was to evaluate the pharmacokinetic profiles of buprenorphine (0.01 and 0.03 mg/kg im) and sustained-release buprenorphine (0.2 mg/kg sc) in 2 macaque species (m. mulatta and m. fascicularis) by using mass spectrometry. the pharmacokinetics did not differ significantly between species, and buprenorphine was dose-proportional at the tes ...201323562033
immune suppression in cynomolgus monkeys by xpro9523: an improved ctla4-ig fusion with enhanced binding to cd80, cd86 and neonatal fc receptor fcrn.the ctla4-ig fusion proteins abatacept and belatacept are clinically proven immunosuppressants used for rheumatoid arthritis and renal transplant, respectively. given that both biologics are typically administered chronically by infusion, a need exists for a next-generation ctla4-ig with more convenient dosing. we used structure-based protein engineering to optimize the affinity of existing ctla4-ig therapeutics for the ligands cd80 and cd86, and for the neonatal fc receptor, fcrn. from a ration ...201323549103
the placenta in toxicology. part i: animal models in toxicology: placental morphology and tolerance molecules in the cynomolgus monkey (macaca fascicularis).the immune system represents a key defense mechanism against potential pathogens and adverse non-self materials. during pregnancy, the placenta is the point of contact between the maternal organism and non-self proteins of the fetal allograft and hence undoubtedly fulfils immune functions. in the placenta bacteria, foreign (non-self) proteins and proteins that might be introduced in toxicological studies or by medication are barred from reaching the progeny, and the maternal immune system is pri ...201423548606
palladium mediated ¹¹c-cyanation and characterization in the non-human primate brain of the novel mglur5 radioligand [¹¹c]azd9272.the aims of the present positron emission tomography (pet) study were to set up a system for (11)c-cyanation labeling of the selective mglur5-antagonist [(11)c]azd9272 and to perform the first in vivo characterization of [(11)c]azd9272 binding in cynomolgus monkeys.201323541825
biomarkers for non-human primate type-i hypersensitivity: antigen-specific immunoglobulin e assays.immunoglobulin e (ige) is the least abundant immunoglobulin in serum. however, development of an ige immune response can induce ige receptor-expressing cells to carry out potent effector functions. a reliable antigen-specific ige biomarker method for use in non-human primate studies would facilitate (i) confirmation of type-i hypersensitivity reactions during safety toxicology testing, and (ii) a better understanding of non-human primate models of allergic disease. we cloned and expressed a reco ...201323541488
a multi-atlas based method for automated anatomical macaca fascicularis brain mri segmentation and pet kinetic extraction.mri templates and digital atlases are needed for automated and reproducible quantitative analysis of non-human primate pet studies. segmenting brain images via multiple atlases outperforms single-atlas labelling in humans. we present a set of atlases manually delineated on brain mri scans of the monkey macaca fascicularis. we use this multi-atlas dataset to evaluate two automated methods in terms of accuracy, robustness and reliability in segmenting brain structures on mri and extracting regiona ...201323537938
discovery of naturally occurring transmissible chronic hepatitis b virus infection among macaca fascicularis from mauritius island.despite a high prevalence of hepatitis b virus (hbv) infection in endangered apes, no hbv infection has been reported in small, old-world monkeys. in search for a small, nonhuman primate model, we investigated the prevalence of hbv infection in 260 macaque (cercopithecidae) sera of various geographical origins (i.e., morocco, mauritius island, and asia). hbv-positive markers were detected in cynomolgus macaques (macaca fascicularis) from mauritius island only, and, remarkably, hbv dna was positi ...201323536484
characterization of cells expressing lymphatic marker lyve-1 in macaque large intestine during simian immunodeficiency virus infection identifies a large population of nonvascular lyve-1(+)/dc-sign(+) cells.abstract lyve-1 is a marker expressed by lymphatic endothelial cells (lecs) that line the lymphatic endothelium. through studies designed to examine potential changes in expression of lyve-1 in cynomolgus macaque colon tissues during the course of simian immunodeficiency virus (siv) infection, we discovered that lyve-1 was expressed by heterogenous populations of cells. as revealed by in situ hybridization (ish), lyve-1 mrna levels in colon were decreased in macaques with aids compared with acut ...201323531182
working group consultation: alloimmunity as a vaccine approach against hiv/aids: national institutes of health meeting report, may 24, 2012.alloimmunization vaccine strategies propose to avoid the problem of the extreme antigenic variability of human immunodeficiency virus (hiv) by instead focusing on the cellular antigens incorporated into hiv virions as they bud from infected cells. this report summarizes a consultation meeting convened by the national institute of allergy and infectious diseases, national institutes of health on may 24, 2012. the objectives of the meeting were to (1) reach a consensus on the essential questions s ...201323530996
correlations between serum levels of beta amyloid, cerebrospinal levels of tau and phospho tau, and delayed response tasks in young and aged cynomolgus monkeys (macaca fascicularis).in an attempt to explore cynomolgus monkeys as an animal model for alzheimer's disease, the present study focused on the alzheimer's biomarkers beta amyloid 1-42 (aβ42 ) in serum, and total tau (t-tau) and phosphorylated tau (p-tau) levels in cerebrospinal fluid.201323530983
pharmacological control of platelet-leukocyte interactions by the human anti-p-selectin antibody inclacumab--preclinical and clinical studies.elevated levels of platelet-leukocyte aggregates (plas) have been reported in several cardiovascular diseases and suggested to contribute to disease pathology. our aim was to characterize the effects of inclacumab, a novel human anti-p-selectin antibody, on the interactions between leukocytes and platelets in preclinical and clinical studies.201323522853
genetic diversity of bartonella quintana in macaques suggests zoonotic origin of trench fever.bartonella quintana is a bacterium that causes a broad spectrum of diseases in humans including trench fever. humans were previously considered to be the primary, if not the only, reservoir hosts for b. quintana. to identify the animal reservoir and extend our understanding of the ecological and evolutionary history of b. quintana, we examined blood samples from macaques and performed multilocus sequence typing (mlst) analysis. we demonstrated the prevalence of b. quintana infection was common i ...201323517327
evaluation of the effectiveness and safety of chitosan derivatives as adjuvants for intranasal vaccines.intranasal immunization is currently used to deliver live virus vaccines such as influenza. however, to develop an intranasal vaccine to deliver inactivated virus, a safe and effective adjuvant is necessary to enhance the mucosal immune response. here, we demonstrate the effectiveness of a chitosan microparticle (1-20 μm, 50 kda, degree of deacetylation=85%) and a cationized chitosan (1000 kda, degree of deacetylation=85%) derived from natural crab shells as adjuvants for an intranasal vaccine c ...201323509985
diurnal pituitary-adrenal activity during schedule-induced polydipsia of water and ethanol in cynomolgus monkeys (macaca fascicularis).intermittent delivery of an important commodity (e.g., food pellets) generates excessive behaviors as an adjunct to the schedule of reinforcement (adjunctive behaviors) that are hypothesized to be due to conflict between engaging and escaping a situation where reinforcement is delivered, but at suboptimal rates.201323508555
note on the formulation of thermosensitive and mucoadhesive vaginal hydrogels containing the minicd4 m48u1 as anti-hiv-1 microbicide.the minicd4 m48u1 was formulated into thermosensitive and mucoadhesive pluronic(®) hydrogels as anti-hiv-1 microbicide. the release kinetics of m48u1 from f127/hpmc (20/1 wt%) and f127/f68/hpmc (22.5/2.5/1 wt%) studied during 24h by using franz diffusion cells showed that hec hydrogel (1.5 wt%) used as control released 93% of the peptide, while about 25% of m48u1 remained in pluronic(®) hydrogels. the formulation of m48u1 in pluronic(®) hydrogels ensures a local delivery because no diffusion of ...201323500765
reconstruction of cartilage with clonal mesenchymal stem cell-acellular dermal matrix in cartilage defect model in nonhuman primates.articular cartilage defects are commonly associated with trauma, inflammation and osteoarthritis. mesenchymal stem cell (msc)-based therapy is a promising novel approach for repairing articular cartilage. direct intra-articular injection of uncommitted mscs does not regenerate high-quality cartilage. this study explored utilization of a new three-dimensional, selected chondrogenic clonal msc-loaded monkey acellular dermal matrix (msc-adm) scaffold to repair damaged cartilage in an experimental m ...201323499511
the mutation rate of mycobacterial repetitive unit loci in strains of m. tuberculosis from cynomolgus macaque infection.mycobacterial interspersed repetitive units (mirus) are minisatellites within the mycobacterium tuberculosis (mtb) genome. copy number variation (cnv) in miru loci is used for epidemiological typing, making the rate of variation important for tracking the transmission of mtb strains. in this study, we developed and assessed a whole-genome sequencing (wgs) approach to detect miru cnv in mtb. we applied this methodology to a panel of mtb strains isolated from the macaque model of tuberculosis (tb) ...201323496945
the organization of prefrontal-subthalamic inputs in primates provides an anatomical substrate for both functional specificity and integration: implications for basal ganglia models and deep brain stimulation.the identification of a hyperdirect cortico-subthalamic nucleus connection highlighted the important role of the subthalamic nucleus (stn) in regulating behavior. however, this pathway was shown primarily from motor areas. hyperdirect pathways associated with cognitive and motivational cortical regions are particularly relevant given recent data from deep brain stimulation, both for neurologic and psychiatric disorders. our experiments were designed to demonstrate the existence and organization ...201323486951
trim5 genotypes in cynomolgus monkeys primarily influence inter-individual diversity in susceptibility to monkey-tropic human immunodeficiency virus type 1.trim5α restricts human immunodeficiency virus type 1 (hiv-1) infection in cynomolgus monkey (cm) cells. we previously reported that a trimcyp allele expressing trim5-cyclophilin a fusion protein was frequently found in cms. here, we examined the influence of trim5 gene variation on the susceptibility of cms to a monkey-tropic hiv-1 derivative (hiv-1mt) and found that trimcyp homozygotes were highly susceptible to hiv-1mt not only in vitro but also in vivo. these results provide important insight ...201323486671
blood glucose levels in rhesus monkeys (macaca mulatta) and cynomolgus macaques (macaca fascicularis) under moderate stress and after recovery.we evaluated normal blood glucose levels in two species of monkeys, namely rhesus monkeys (macaca mulatta) and cynomolgus macaques (macaca fascicularis) kept in the breeding center of the institute of medical primatology. the animals were either under moderate stress due to catching or after recovery of defensive and orienting reactions by habituation to the blood sampling. based on these data, seasonal, gender- and age-dependent variations in glucose levels were found. glucose levels in rhesus ...201323486590
the genetic composition of populations of cynomolgus macaques (macaca fascicularis) used in biomedical research.the genetic composition of cynomolgus macaques used in biomedical research is not as well-characterized as that of rhesus macaques.201323480663
object discrimination and reversal learning in infant and juvenile non-human primates in a non-clinical laboratory.biopharmaceutical development necessitates use of non-human primates in toxicology, leading to adoption of non-traditional methods including cognitive function assessment.201323480632
control of communicable disease; foreign--requirements for importers of nonhuman primates (nhp). final rule.the centers for disease control and prevention (cdc), located within the department of health and human services (hhs), is amending regulations for the importation of live nonhuman primates (nhps) by extending existing requirements for the importation of macaca fascicularis (cynomolgus), chlorocebus aethiops (african green), and macaca mulatta (rhesus) monkeys to all nhps with the exception of the filovirus testing requirement. filovirus testing will only be required for old world nhps in quaran ...201323476983
unexpected thrombocytopenia and anemia in cynomolgus monkeys induced by a therapeutic human monoclonal antibody.cynomolgus monkeys dosed with a therapeutic monoclonal antibody (maby.1) at ≥ 50 mg/kg had unexpected acute thrombocytopenia (nadir ~3,000 platelets/µl), sometimes with decreases in red cell mass. increased activated macrophages, mitotic figures, and erythrophagocytosis were observed in the spleen. binding of maby.1 to cynomolgus peripheral blood cells could not be detected in vitro. maby.1 induced phagocytosis of platelets by peripheral blood monocytes from cynomolgus monkeys, but not from huma ...201323475561
a 39-week oral toxicity study of ulipristal acetate in cynomolgus monkeys.ulipristal acetate (upa) is a novel progesterone receptor modulator (prm) and registered for the pre-operative treatment of symptomatic uterine fibroids during 3months. in a study which assessed the potential toxicity of upa in female cynomolgus monkeys following daily oral administration of 1, 5, or 25mg/kg for 39weeks, upa was well tolerated with dose-dependent macroscopic and microscopic observations limited to the uterus and oviducts. these findings were considered to be related to the pharm ...201323474274
[the establishment of environmental endocrine disruptors induced precocious puberty macaca fascicularis model and the intervention of yin nourishing fire purging chinese materia medica].to establish the environmental endocrine disruptors (eeds) induced precocious puberty macaca fascicularis model, thus verifying the antagonism of yin nourishing fire purging chinese materia medica (ynfpcmm) against the estrogenic effects.201223469612
identification and multidimensional optimization of an asymmetric bispecific igg antibody mimicking the function of factor viii cofactor activity.in hemophilia a, routine prophylaxis with exogenous factor viii (fviii) requires frequent intravenous injections and can lead to the development of anti-fviii alloantibodies (fviii inhibitors). to overcome these drawbacks, we screened asymmetric bispecific igg antibodies to factor ixa (fixa) and factor x (fx), mimicking the fviii cofactor function. since the therapeutic potential of the lead bispecific antibody was marginal, fviii-mimetic activity was improved by modifying its binding properties ...201323468998
the rock inhibitor eye drop accelerates corneal endothelium wound healing.to evaluate the effect of rho kinase (rock)-inhibitor eye drops on a corneal endothelial dysfunction primate model and human clinical case series of corneal endothelial dysfunction.201323462749
measuring t-cell responses against lcv and cmv in cynomolgus macaques using elispot: potential application to non-clinical testing of immunomodulatory therapeutics.a number of immunomodulatory therapeutics increase the risk of disease associated with latent herpesviruses such as cytomegalovirus (cmv) and epstein-barr virus (ebv), a member of the lymphocryptovirus (lcv) family that infects humans. the diseases associated with loss of immunity to these viruses can have major impacts on patients as well as on the commercial viability of the immunomodulatory therapeutics. in an effort to develop non-clinical methods for measuring effects on anti-viral immunity ...201323461640
selection of appropriate reference genes for rt-qpcr analysis in a streptozotocin-induced alzheimer's disease model of cynomolgus monkeys (macaca fascicularis).reverse transcription quantitative real-time polymerase chain reaction (rt-qpcr) has been widely used to quantify relative gene expression because of the specificity, sensitivity, and accuracy of this technique. in order to obtain reliable gene expression data from rt-qpcr experiments, it is important to utilize optimal reference genes for the normalization of target gene expression under varied experimental conditions. previously, we developed and validated a novel icv-stz cynomolgus monkey mod ...201323457495
[18f]fdg-pet as an imaging biomarker to nmda receptor antagonist-induced neurotoxicity.positron emission tomography (pet) is an effective tool for noninvasive examination of the body and provides a range of functional information. pet imaging with [(18)f]fluoro-2-deoxy-d-glucose ([(18)f]fdg) has been used to image alterations in glucose metabolism in brain or cancer tissue in the field of clinical diagnosis but not in the field of toxicology. a single dose of n-methyl-d-aspartate (nmda) receptor antagonist induces neuronal cell degeneration/death in the rat retrosplenial/posterior ...201323457119
antagonism of chemokine receptor ccr8 is ineffective in a primate model of asthma.expression of the t-cell-associated chemokine receptor ccr8 and its ligand ccl1 have been demonstrated to be elevated in patients with asthma. ccr8 deficiency or inhibition in models of allergic airway disease in mice resulted in conflicting data.201323457038
primate b-1 cells generate antigen-specific b cell responses to t cell-independent type 2 antigens.ab responses to t cell-independent type 2 (ti-2) ags, such as bacterial capsular polysaccharides, are critical for host defense. in mice, b-1b cells expressing a cd11b(+)fsc(hi)cd21(lo/-)cd19(hi) phenotype play a key role in producing abs against ti-2 ags. in primates, a distinct igm(+)cd27(+) "memory" b cell population is thought to generate ti-2 ab responses, and evidence for a b-1b-like cell population participating in these responses is lacking. in this article, we demonstrate that nonhuman ...201323455507
diet, activity, habitat use, and ranging of two neighboring groups of food-enhanced long-tailed macaques (macaca fascicularis).we conducted observations of two neighboring groups of food-enhanced long-tailed macaques (macaca fascicularis) over a period of one year. we examined their diet, behavior, habitat use, and ranging and how within-population variability reflected differential utilization of anthropogenic food resources. the group that consumed more anthropogenic food spent less time feeding on wild fruits and flowers, less time resting, and more time locomoting. they used forest habitats less often, and had a lar ...201323447101
monkeys perform as well as apes and humans in a size discrimination task.whether the cognitive competences of monkeys and apes are rather similar or whether the larger-brained apes outperform monkeys in cognitive experiments is a highly debated topic. direct comparative analyses are therefore essential to examine similarities and differences among species. we here compared six primate species, including humans, chimpanzees, bonobos, gorillas (great apes), olive baboons, and long-tailed macaques (old world monkeys) in a task on fine-grained size discrimination. except ...201323443407
power spectral analysis of heart rate variability in cynomolgus monkeys in safety pharmacology studies: comparative study with beagle dogs.power spectral analysis of heart rate variability is a tool known to provide information of interest on the autonomic control of heart rate in human. however, its use and its conditions of application and interpretation for safety purposes are not well defined for cardiovascular safety pharmacology studies. likewise, data of power spectral analysis of heart rate variability in cynomolgus monkeys, a species often appropriate for use as second non rodent species in preclinical safety programmes, a ...201323435316
dehydroepiandrosterone sulfate levels reflect endogenous luteinizing hormone production and response to human chorionic gonadotropin challenge in older female macaque (macaca fascicularis).we propose that the adrenal gland of an older higher primate female animal model will respond to human chorionic gonadotropin (hcg) hormone challenge by secreting additional dehydroepiandrosterone sulfate (dheas). such a response in surgically and chemically castrated animals will provide proof of concept and a validated animal model for future studies to explore the rise in dheas during the menopausal transition of women.201323435031
effects of bazedoxifene alone and with conjugated equine estrogens on coronary and peripheral artery atherosclerosis in postmenopausal monkeys.the objectives of this study were to evaluate the effects of bazedoxifene acetate (bza), a new selective estrogen receptor modulator, on coronary and peripheral artery atheroscleroses and to determine if it would antagonize the atheroprotective effects of conjugated equine estrogens (cee) on a monkey model.201323435024
reciprocal interaction between intestinal microbiota and mucosal lymphocyte in cynomolgus monkeys after alemtuzumab treatment.it has been known that the gut microbiota plays a central role in shaping normal mucosal immunity, however, little information is available whether the variability of mucosal lymphocytes impacts the commensal flora. here, we applied a cynomolgus monkey model to characterize the structure and composition of the gut microbiota in response to lymphocyte depletion and to determine their potential association. molecular profiling of 16s rdna showed that the intestinal microbiota composition was pertu ...201323433407
simian immunodeficiency virus infection potently modulates chemokine networks and immune environments in hilar lymph nodes of cynomolgus macaques.chemokines provide critical immune cell homing and activation signals that if altered could affect the inflammatory milieu and cellular composition of lymphoid tissues. during hiv-1 and simian immunodeficiency virus (siv)-infection, the virus triggers an increase in inflammation or activation, leading to immunodeficiency and development of opportunistic infections, such as in the lungs-a massive interface between the host and the environment.201323429503
pharmacology of amg 181, a human anti-α4 β7 antibody that specifically alters trafficking of gut-homing t cells.amg 181 is a human anti-α4 β7 antibody currently in phase 1 and 2 trials in subjects with inflammatory bowel diseases. amg 181 specifically targets the α4 β7 integrin heterodimer, blocking its interaction with mucosal addressin cell adhesion molecule-1 (madcam-1), the principal ligand that mediates α4 β7 t cell gut-homing.201323425116
block/homo polyplex micelle-based gm-csf gene therapy via intraperitoneal administration elicits antitumor immunity against peritoneal dissemination and exhibits safety potentials in mice and cynomolgus monkeys.a block/homo-mixed polyplex micelle, comprising of cationic homo polymer: poly{n'-[n-(2-aminoethyl)-2-aminoethyl]aspartamide} p[asp(det)] and block copolymer: polyethylene glycol (peg)-b-p[asp(det)], has been reported to exhibit the efficient transgene expression in vivo by intratracheal and systemic administration. in the present study, we investigated the potential of immunogene therapy by intraperitoneal (i.p.) administration of block/homo polyplex micelles for peritoneal dissemination. for e ...201323422727
axonal and glial responses to a mid-thoracic spinal cord hemisection in the macaca fascicularis monkey.a comprehensive understanding of the pathology of spinal cord injury (sci) in non-human primates may facilitate greatly the development of new strategies to promote recovery in humans with sci. relatively few studies, however, have been conducted to systemically examine pathological changes in the monkey, a non-human primate, after sci. we report axonal, glial, and fibrotic responses in the spinal cord of monkey macaca fascicularis after a thoracic (t) 8-9 lateral hemisection. we examined these ...201323421822
understanding of and reasoning about object-object relationships in long-tailed macaques?diagnostic reasoning, defined as the ability to infer unobserved causes based on the observation of their effects, is a central cognitive competency of humans. yet, little is known about diagnostic reasoning in non-human primates, and what we know is largely restricted to the great apes. to track the evolutionary history of these skills within primates, we investigated long-tailed macaques' understanding of the significance of inclinations of covers of hidden food as diagnostic indicators for th ...201323417558
oestradiol modulation of serotonin reuptake transporter and serotonin metabolism in the brain of monkeys.serotonin (5-hydroxytryptamine; 5-ht) is an important brain neurotransmitter that is implicated in mental and neurodegenerative diseases and is modulated by ovarian hormones. nevertheless, the effect of oestrogens on 5-ht neurotransmission in the primate caudate nucleus, putamen and nucleus accumbens, which are major components of the basal ganglia, and the anterior cerebral cortex, mainly the frontal and cingulate gyrus, is not well documented. the present study evaluated 5-ht reuptake transpor ...201323414342
isolation of antibodies from non-human primates for clinical use.antibodies intended for clinical use have been isolated from non-human primates (nhp), chimpanzees (pan troglodytes) and macaques (macaca fascicularis and macaca mulatta), essentially with the use of the phage-display technology. all studies presenting such isolations have been reviewed and presented here, following the main steps of this technology, and advantages and disadvantages of nhp species were analyzed. optimization of the tolerance of chimeric nhp-human antibodies by germline humanizat ...201423410051
genome sequence of moraxella macacae 0408225, a novel bacterial species isolated from a cynomolgus macaque with epistaxis.moraxella macacae is a recently described bacterial species that has been associated with at least two outbreaks of epistaxis in macaques. here we present the first genome sequence of this novel species, isolated from a symptomatic cynomolgus macaque at the u.s. army medical research institute of infectious diseases.201323409273
"candidatus mycoplasma haemomacaque" and bartonella quintana bacteremia in cynomolgus monkeys.here, we report latent infections with bartonella quintana and a hemotropic mycoplasma sp. in a research colony of cynomolgus monkeys (macaca fascicularis). sequence alignments, evolutionary analysis, and signature nucleotide sequence motifs of the hemotropic mycoplasma 16s rrna and rnase p genes indicate the presence of a novel organism.201323408694
venezuelan equine encephalitis virus replicon particle vaccine protects nonhuman primates from intramuscular and aerosol challenge with ebolavirus.there are no vaccines or therapeutics currently approved for the prevention or treatment of ebolavirus infection. previously, a replicon vaccine based on venezuelan equine encephalitis virus (veev) demonstrated protective efficacy against marburg virus in nonhuman primates. here, we report the protective efficacy of sudan virus (sudv)- and ebola virus (ebov)-specific veev replicon particle (vrp) vaccines in nonhuman primates. vrp vaccines were developed to express the glycoprotein (gp) of either ...201323408633
recurrent abruptio placentae in a cynomolgus monkey (macaca fascicularis).abruptio placentae, defined as premature separation of a normally implanted placenta, is a life threatening pregnancy complication with unknown pathophysiology. a history of abruptio placentae is the major risk factor for this pregnancy complication in humans. we describe the first case of recurrent abruptio placentae in a macaca fascicularis.201323398915
characterization of marmoset cyp2b6: cdna cloning, protein expression and enzymatic functions.the common marmoset is a promising species for evaluating the safety of drug candidates. to further understand the capacity for drug metabolism in marmosets, a cdna encoding a cyp2b enzyme was cloned from the total rna fraction of marmoset liver by 3'- and 5'-race methods. nucleotide and deduced amino acid sequences showed 90.8 and 86.2% identity, respectively, with human cyp2b6. the marmoset cyp2b6 (marcyp2b6) protein was expressed in insect cells, and its enzymatic properties were compared wit ...201323395694
endometrial profile of bazedoxifene acetate alone and in combination with conjugated equine estrogens in a primate model.objective: concerns of breast cancer risk in postmenopausal women taking combined estrogen + progestin therapy have generated interest in the use of selective estrogen receptor modulators (serms) as potential progestin alternatives. endometrial proliferation and cancer risk are major concerns, however, for estrogens and certain types of serms when given alone. the primary aim of this study was to evaluate the endometrial profile of bazedoxifene acetate (bza), a third-generation serm, alone and i ...201323385717
an inter-laboratory retrospective analysis of immunotoxicological endpoints in non-human primates: flow cytometry immunophenotyping.non-human primates may be the only relevant species for pharmacology or toxicology studies of certain biologics, due to lack of activity in other species. flow cytometry immunophenotyping is often included as a minimally invasive adjunct to standard toxicity testing. a retrospective inter-laboratory analysis was conducted to assess counts and variability of the main cell types monitored in toxicity studies, and to provide guidance for conduct and interpretation of immunophenotyping assessments i ...201323384295
Refresh
firstprev
...21222324252627282930...
nextlast
Displaying items 2801 - 2900 of 11313