Publications
| Title | Abstract | Year Filter | PMID(sorted descending) Filter |
|---|
| live attenuated francisella novicida vaccine protects against francisella tularensis pulmonary challenge in rats and non-human primates. | francisella tularensis causes the disease tularemia. human pulmonary exposure to the most virulent form, f. tularensis subsp. tularensis (ftt), leads to high morbidity and mortality, resulting in this bacterium being classified as a potential biothreat agent. however, a closely-related species, f. novicida, is avirulent in healthy humans. no tularemia vaccine is currently approved for human use. we demonstrate that a single dose vaccine of a live attenuated f. novicida strain (fn igld) protects ... | 2014 | 25340543 |
| the impact of simplifications on the performance of a finite element model of a macaca fascicularis cranium. | in recent years finite element analysis (fea) has emerged as a useful tool for the analysis of skeletal form-function relationships. while this approach has obvious appeal for the study of fossil specimens, such material is often fragmentary with disrupted internal architecture and can contain matrix that leads to errors in accurate segmentation. here we examine the effects of varying the detail of segmentation and material properties of teeth on the performance of a finite element model of a ma ... | 2015 | 25339306 |
| metabolism by conjugation appears to confer resistance to paracetamol (acetaminophen) hepatotoxicity in the cynomolgus monkey. | 1. paracetamol overdose remains the leading cause of acute liver failure in humans. this study was undertaken in cynomolgus monkeys to study the pharmacokinetics, metabolism and the potential for hepatotoxic insult from paracetamol administration as a possible model for human toxicity. 2. no adverse effects were observed for doses of up to 900 mg/kg/d for 14 d. only minor sporadic increases in alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase in a number of animals ... | 2015 | 25335570 |
| congenital foot deformation alters the topographic organization in the primate somatosensory system. | limbs may fail to grow properly during fetal development, but the extent to which such growth alters the nervous system has not been extensively explored. here we describe the organization of the somatosensory system in a 6-year-old monkey (macaca radiata) born with a deformed left foot in comparison to the results from a normal monkey (macaca fascicularis). toes 1, 3, and 5 were missing, but the proximal parts of toes 2 and 4 were present. we used anatomical tracers to characterize the patterns ... | 2016 | 25326245 |
| morphologic, stereologic, and morphometric evaluation of the nervous system in young cynomolgus monkeys (macaca fascicularis) following maternal administration of tanezumab, a monoclonal antibody to nerve growth factor. | tanezumab, an antibody to nerve growth factor, was administered to pregnant cynomolgus monkeys at 0, 0.5, 4, and 30 mg/kg weekly, beginning gestation day (gd) 20 through parturition (∼gd165). maternal tanezumab administration appeared to increase stillbirths and infant mortality, but no consistent pattern of gross and/or microscopic change was detected to explain the mortality. offspring exposed in utero were evaluated at 12 months of age using light microscopy (all tissues), stereology (basal f ... | 2014 | 25326242 |
| identification of adult stem cells in schwalbe's line region of the primate eye. | to identify stem cells in the chamber angle of the monkey eye by detection of 5-bromo-2'-deoxyuridine (brdu) long-term retention. | 2014 | 25324280 |
| streptozotocin-associated lymphopenia in cynomolgus monkeys. | streptozotocin (stz) is used to induce diabetes in experimental animals. it has a variety of adverse effects, ranging from nausea, emesis, and weight loss to liver damage, renal failure, and metabolic acidosis. stz also has effects on the immune system, being associated with lymphopenia in rodents, the mechanism of which is not fully understood. we present data on a significant stz-associated reduction in lymphocyte count in nonhuman primates. we report a significant reduction in absolute lympho ... | 2014 | 25322828 |
| evaluation of 89 compounds for identification of substrates for cynomolgus monkey cyp2c76, a new bupropion/nifedipine oxidase. | cynomolgus monkeys are widely used in preclinical studies during drug development because of their evolutionary closeness to humans, including their cytochrome p450s (p450s). most cynomolgus monkey p450s are almost identical (≥90%) to human p450s; however, cyp2c76 has low sequence identity (approximately 80%) to any human cyp2cs. although cyp2c76 has no ortholog in humans and is partly responsible for species differences in drug metabolism between cynomolgus monkeys and humans, a broad evaluatio ... | 2015 | 25318994 |
| contrasting infection susceptibility of the japanese macaques and cynomolgus macaques to closely related malaria parasites, plasmodium vivax and plasmodium cynomolgi. | although the human malaria parasite plasmodium vivax is closely related to asian old world monkey malaria parasites, there are no reports of p. vivax infections in macaques. in this study, we compared the infectivity of p. vivax and plasmodium cynomolgi in japanese macaques (macaca fuscata) and in cynomolgus macaques (macaca fascicularis). the japanese macaques were highly susceptible to p. cynomolgi but not to p. vivax, whereas cynomolgus macaques showed mild/limited p. cynomolgi infection and ... | 2015 | 25316604 |
| cytogenesis in the adult monkey motor cortex: perivascular ng2 cells are the major adult born cell type. | we used confocal microscopy and immunohistochemistry (ihc) to look for new cells in the motor cortex of adult macaque monkeys that might form the cellular bases of improved brain function from exercise. twenty-four female macaca fascicularis monkeys divided into groups by age (10-12 years, 15-17 years), postexercise survival periods, and controls, received 10 weekly injections of the thymidine analog, bromodeoxyuridine (brdu) to mark new cells. sixteen monkeys survived 15 weeks (5 weeks postexer ... | 2015 | 25308320 |
| preclinical pharmacology, ocular tolerability and ocular hypotensive efficacy of a novel non-peptide bradykinin mimetic small molecule. | we sought to characterize the ocular pharmacology, tolerability and intraocular pressure (iop)-lowering efficacy of fr-190997, a non-peptidic bradykinin (bk) b2-receptor agonist. fr-190997 possessed a relatively high receptor binding affinity (ki = 27 nm) and a high in vitro potency (ec50 = 18.3 ± 4.4 nm) for inositol-1-phosphate generation via human cloned b2-receptors expressed in host cells with mimimal activity at b1-receptors. it also mobilized intracellular ca2+ in isolated human trabecula ... | 2014 | 25307520 |
| the extracellular domain of myelin oligodendrocyte glycoprotein elicits atypical experimental autoimmune encephalomyelitis in rat and macaque species. | atypical models of experimental autoimmune encephalomyelitis (eae) are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (ms). conversely, models of classical eae feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of ms. the study of atypical eae however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient ... | 2014 | 25303101 |
| alzheimer's disease-like pathology induced by amyloid-β oligomers in nonhuman primates. | alzheimer's disease (ad) is a devastating neurodegenerative disorder and a major medical problem. here, we have investigated the impact of amyloid-β (aβ) oligomers, ad-related neurotoxins, in the brains of rats and adult nonhuman primates (cynomolgus macaques). soluble aβ oligomers are known to accumulate in the brains of ad patients and correlate with disease-associated cognitive dysfunction. when injected into the lateral ventricle of rats and macaques, aβ oligomers diffused into the brain and ... | 2014 | 25297091 |
| lethal factor, but not edema factor, is required to cause fatal anthrax in cynomolgus macaques after pulmonary spore challenge. | inhalational anthrax is caused by inhalation of bacillus anthracis spores. the ability of b. anthracis to cause anthrax is attributed to the plasmid-encoded a/b-type toxins, edema toxin (edema factor and protective antigen) and lethal toxin (lethal factor and protective antigen), and a poly-d-glutamic acid capsule. to better understand the contribution of these toxins to the disease pathophysiology in vivo, we used b. anthracis ames strain and isogenic toxin deletion mutants derived from the ame ... | 2014 | 25285720 |
| [marburg and ebola hemorrhagic fevers--pathogens, epidemiology and therapy]. | marburg and ebola hemorrhagic fevers are severe, systemic viral diseases affecting humans and non-human primates. they are characterized by multiple symptoms such as hemorrhages, fever, headache, muscle and abdominal pain, chills, sore throat, nausea, vomiting and diarrhea. elevated liver-associated enzyme levels and coagulopathy are also associated with these diseases. marburg and ebola hemorrhagic fevers are caused by (lake victoria) marburg virus and different species of ebola viruses, respec ... | 2014 | 25282746 |
| development of lc-ms methods for quantitation of hepcidin and demonstration of sirna-mediated hepcidin suppression in serum. | a requisite step in developing a therapeutic to modulate the levels of hepcidin is the development of a quantitative method for measuring the concentration of serum hepcidin. | 2015 | 25281793 |
| transcriptome reconstruction and annotation of cynomolgus and african green monkey. | non-human primates (nhps) and humans share major biological mechanisms, functions, and responses due to their close evolutionary relationship and, as such, provide ideal animal models to study human diseases. rna expression in nhps provides specific signatures that are informative of disease mechanisms and therapeutic modes of action. unlike the human transcriptome, the transcriptomes of major nhp animal models are yet to be comprehensively annotated. | 2014 | 25277458 |
| potent cholesteryl ester transfer protein inhibitors of reduced lipophilicity: 1,1'-spiro-substituted hexahydrofuroquinoline derivatives. | a series of 1,1'-spiro-substituted hexahydrofuroquinoline derivatives exhibiting potent cholesteryl ester transfer protein (cetp) inhibition at reduced lipophilicity was identified. a focused structure-activity relationship (sar) exploration led to the potent and comparatively polar cetp inhibitor 26 showing robust high density lipoprotein-cholesterol (hdl-c) elevation and low density lipoprotein-cholesterol (ldl-c) reduction in transgenic hcetp/hapob-100 mice. compound 26 was also shown to posi ... | 2014 | 25265559 |
| effects of the inhibition of intestinal p-glycoprotein on aliskiren pharmacokinetics in cynomolgus monkeys. | aliskiren is a substrate for p-glycoprotein (p-gp) and is metabolized via cytochrome p450 3a4 (cyp3a4). the aim of the present study was to assess whether p-gp influenced the pharmacokinetics of aliskiren and also if drug-drug interactions (ddis) mediated through p-gp could be reproduced in cynomolgus monkeys. the study investigated the pharmacokinetics of aliskiren in mdr1a/1b gene-deficient (p-gp ko) and wild-type (wt) mice. the area under the plasma concentration-time curve (auc) following th ... | 2015 | 25264342 |
| experimental fetal endoscopic tracheal occlusion in rhesus and cynomolgus monkeys: nonhuman primate models. | the monkey model is the best model to investigate some physiological response to the fetal transitory tracheal occlusion but it has never been described in macaca monkeys. the aim of this study was to evaluate the feasibility of fetal endoscopic tracheal occlusion (feto) in a non-human primate model. | 2015 | 25260124 |
| generation and characterization of tabalumab, a human monoclonal antibody that neutralizes both soluble and membrane-bound b-cell activating factor. | b-cell activating factor (baff) is a b-cell survival factor with a key role in b-cell homeostasis and tolerance. dysregulated baff expression may contribute to autoimmune diseases or b-cell malignancies via effects on abnormal b-lymphocyte activation, proliferation, survival, and immunoglobulin secretion. monoclonal antibodies were generated against human baff, characterized for species specificity and affinity, and screened for the ability to neutralize both membrane-bound and soluble baff. in ... | 2014 | 25258549 |
| intravenously injected newcastle disease virus in non-human primates is safe to use for oncolytic virotherapy. | newcastle disease virus (ndv) is an avian paramyxovirus with oncolytic potential. detailed preclinical information regarding the safety of oncolytic ndv is scarce. in this study, we evaluated the toxicity, biodistribution and shedding of intravenously injected oncolytic ndvs in non-human primates (macaca fascicularis). two animals were injected with escalating doses of a non-recombinant vaccine strain, a recombinant lentogenic strain or a recombinant mesogenic strain. to study transmission, naiv ... | 2014 | 25257305 |
| systematic identification and characterization of carboxylesterases in cynomolgus macaques. | carboxylesterase (ces) is important for detoxification of a wide range of drugs and xenobiotics and catalyzes cholesterol and fatty acid metabolism. cynomolgus macaques are widely used in drug metabolism studies; however, cynomolgus ces has not been fully investigated at molecular levels, partly due to the lack of gene information. in this study, we isolated and characterized cdnas for ces homologous to human ces1, ces2, and ces5a in cynomolgus macaques. by genome analysis, in the cynomolgus mac ... | 2014 | 25256558 |
| pharmacokinetics of 3 formulations of meloxicam in cynomolgus macaques (macaca fascicularis). | meloxicam is a commonly used cox2-preferential nsaid in both human and veterinary patients. minimal information has been published regarding appropriate dosing in nonhuman primates. here we investigated the pharmacokinetic parameters of 3 formulations of meloxicam in cynomolgus macaques. a single dose of meloxicam sr, an extended-release formulation purported to provide therapeutic levels for as long as 72 h, was compared with the intramuscular and oral formulations dosed for 3 consecutive days ... | 2014 | 25255073 |
| comparative community-level associations of helminth infections and microparasite shedding in wild long-tailed macaques in bali, indonesia. | helminthes have the capacity to modulate host immunity, leading to positive interactions with coinfecting microparasites. this phenomenon has been primarily studied during coinfections with a narrow range of geo-helminthes and intracellular microparasites in human populations or under laboratory conditions. far less is known regarding differences in coinfection dynamics between helminth types, the range of microparasites that might be affected or the overall community-level effects of helminth i ... | 2015 | 25249163 |
| results of life-supporting galactosyltransferase knockout kidneys in cynomolgus monkeys using two different sources of galactosyltransferase knockout swine. | various durations of survival have been observed in the xenotransplantation of life-supporting α-1,3-galactosyltransferase knockout (galt-ko) porcine kidneys into nonhuman primates. although others have demonstrated loss of galt-ko-transplanted kidneys within 2 weeks, we have reported an average survival of 51 days with the cotransplantation of the kidney and vascularized thymus and an average of 29 days with the kidney alone. to determine the factors responsible for this difference in survival ... | 2014 | 25243512 |
| costs of mate-guarding in wild male long-tailed macaques (macaca fascicularis): physiological stress and aggression. | mate-guarding is an important determinant of male reproductive success in a number of species. however, it is known to potentially incur costs. the aim of the present study was to assess the effect of mate-guarding on male physiological stress and aggression in long-tailed macaques, a species in which males mate-guard females to a lesser extent than predicted by the priority of access model (poa). the study was carried out during two mating periods on three groups of wild long-tailed macaques in ... | 2014 | 25236888 |
| complement inhibition in cynomolgus monkeys by anti-factor d antigen-binding fragment for the treatment of an advanced form of dry age-related macular degeneration. | anti-factor d (afd; fcfd4514s, lampalizumab) is a humanized igg fab fragment directed against factor d (fd), a rate-limiting serine protease in the alternative complement pathway (ap). evaluation of afd as a potential intravitreal (ivt) therapeutic for dry age-related macular degeneration patients with geographic atrophy (ga) is ongoing. however, it is unclear whether ivt administration of afd can affect systemic ap activation and potentially compromise host-immune responses. we characterized th ... | 2014 | 25232192 |
| glycoprotein ibα clustering induces macrophage-mediated platelet clearance in the liver. | many immune thrombocytopenia (itp) patients, particularly patients with anti-glycoprotein (gp) ib-ix autoantibodies, do not respond to the conventional treatments such as splenectomy. however, the underlying mechanism remains unclear. here we found that anti-gpibα n-terminus antibody an51, but not other anti-gpibα antibodies (ak2, hip1, vm16d, or wm23), induced gpibα clustering that led to integrin αiibβ3-dependent platelet aggregation. after intravenous injection, an51 dose-dependently induced ... | 2015 | 25231551 |
| brain-derived neurotrofic factor and its receptor trkb are present, but segregated, within mature cutaneous pacinian corpuscles of macaca fascicularis. | some mechanoreceptors in mammals depend totally or in part on the neurotrophins brain-derived neurotrophic factor (bdnf) and neurotrophin-4 (nt-4), and their receptor trkb, for development and maintenance. these actions are presumably exerced regulating the survival of discrete sensory neurons in the dorsal root ganglia which form mechanoreceptors at the periphery. in addition, the cells forming the mechanoreceptors also express both neurotrophins and their receptors although large differences h ... | 2015 | 25230956 |
| a technique for orthotopic liver transplantation in cynomolgus monkeys. | 2014 | 25221902 | |
| a new bispecific antibody targeting non-overlapping epitopes on igf2: design, in vitro characterization and pharmacokinetics in macaques. | the insulin-like growth factor 2 (igf2) is an important target for cancer therapy. we have previously proposed an approach for fast and irreversible removal of igf2 from the circulation by using monoclonal antibodies (mabs) that bind to two or more non-overlapping epitopes on the same molecule. we provided initial evidence for the formation of oligomeric antibody-ligand complexes that can bind to cells expressing fc gamma receptors (fcγrs) with high avidity using an antibody domain with relative ... | 2014 | 25220345 |
| pig-to-monkey islet xenotransplantation using multi-transgenic pigs. | the generation of pigs with genetic modifications has significantly advanced the field of xenotransplantation. new genetically engineered pigs were produced on an α1,3-galactosyltransferase gene-knockout background with ubiquitous expression of human cd46, with islet beta cell-specific expression of human tissue factor pathway inhibitor and/or human cd39 and/or porcine ctla4-lg. isolated islets from pigs with 3, 4 or 5 genetic modifications were transplanted intraportally into streptozotocin-dia ... | 2014 | 25220221 |
| measurement of hyper- and hypotension during repeated dose toxicity studies in either freely moving or physically restrained cynomolgus monkeys. | the measurement of cardiovascular endpoints in standard toxicology studies remains a challenge as the routinely used non-invasive methods require physical restraint, causing an increase of sympathetic neural activity, leading to excitement and potentially hypertension in the experimental animals. in this study, a miniature telemetry blood pressure transmitter was used to evaluate if the acute hyper- and hypotension could be detected in free moving cynomolgus monkeys as well as physically restrai ... | 2014 | 25219539 |
| non-clinical safety evaluation of single and repeated intramuscular administrations of mage-a3 cancer immunotherapeutic in rabbits and cynomolgus monkeys. | the mage-a3 recombinant protein combined with as15 immunostimulant (mage-a3 cancer immunotherapeutic) is under development by glaxosmithkline for the treatment of lung cancer and melanoma. we performed non-clinical safety studies evaluating potential local and systemic toxic effects induced by mage-a3 cancer immunotherapeutic in rabbits (study 1) and cynomolgus monkeys (study 2). animals were allocated to two groups to receive a single (rabbits) or 25 repeated (every 2 weeks) injections (monkeys ... | 2015 | 25219328 |
| the dual peroxisome proliferator-activated receptor alpha/delta agonist gft505 exerts anti-diabetic effects in db/db mice without peroxisome proliferator-activated receptor gamma-associated adverse cardiac effects. | we report here the efficacy and safety of gft505, a novel liver-targeted peroxisome proliferator-activated receptor alpha/delta (pparα/δ) agonist, in the db/db mouse model of diabetes. mice were treated with vehicle, gft505, pparγ agonist rosiglitazone or dual-pparα/γ agonist aleglitazar for up to 8 weeks. all compounds comparably reduced fasting glycaemia and hba1c and improved insulin sensitivity. the glucose-lowering effect of gft505 was associated with decreased hepatic gluconeogenesis, corr ... | 2014 | 25212694 |
| modified vaccinia virus ankara encoding influenza virus hemagglutinin induces heterosubtypic immunity in macaques. | current influenza virus vaccines primarily aim to induce neutralizing antibodies (nabs). modified vaccinia virus ankara (mva) is a safe and well-characterized vector for inducing both antibody and cellular immunity. we evaluated the immunogenicity and protective efficacy of mva encoding influenza virus hemagglutinin (ha) and/or nucleoprotein (np) in cynomolgus macaques. animals were given 2 doses of mva-based vaccines 4 weeks apart and were challenged with a 2009 pandemic h1n1 isolate (h1n1pdm) ... | 2014 | 25210172 |
| preclinical development of amg 139, a human antibody specifically targeting il-23. | amg 139 is a human anti-il-23 antibody currently in a phase ii trial for treating crohn's disease. to support its clinical development in humans, in vitro assays and in vivo studies were conducted in cynomolgus monkeys to determine the pharmacology, preclinical characteristics and safety of this monoclonal antibody. | 2015 | 25205227 |
| regioselective glucuronidation of andrographolide and its major derivatives: metabolite identification, isozyme contribution, and species differences. | andrographolide (and) and two of its derivatives, deoxyandrographolide (deo) and dehydroandrographolide (deh), are widely used in clinical practice as anti-inflammatory agents. however, udp-glucuronosyltransferase (ugt)-mediated phase ii metabolism of these compounds is not fully understood. in this study, glucuronidation of and, deo, and deh was characterized using liver microsomes and recombinant ugt enzymes. we isolated six glucuronides and identified them using 1d and 2d nuclear magnetic res ... | 2015 | 25204783 |
| a fully integrated wireless system for intracranial direct cortical stimulation, real-time electrocorticography data transmission, and smart cage for wireless battery recharge. | wireless transmission of cortical signals is an essential step to improve the safety of epilepsy procedures requiring seizure focus localization and to provide chronic recording of brain activity for brain computer interface (bci) applications. our group developed a fully implantable and externally rechargeable device, able to provide wireless electrocorticographic (ecog) recording and cortical stimulation (cs). the first prototype of a wireless multi-channel very low power ecog system was custo ... | 2014 | 25202300 |
| species-associated differences in the inhibition of propofol glucuronidation by magnolol. | magnolol, a major active constituent in herbal medicine, potently inhibits propofol glucuronidation in human liver microsomes, with inhibition constants in the nanomolar range. this study was conducted to investigate magnolol-induced inhibition of propofol glucuronidation in liver microsomes from swiss-hauschka mice, sprague-dawley rats, chinese bama pigs, and cynomolgus macaques. results indicated that magnolol (10 μm) inhibited propofol glucuronidation in liver microsomes from bama pigs and cy ... | 2014 | 25199099 |
| humoral and lung immune responses to mycobacterium tuberculosis infection in a primate model of protection (.) | recently we reported (mehra et al., 2013), that lung granulomas from mycobacterium bovis bacille calmette-guérin (bcg)-vaccinated cynomolgus macaques exhibit upon challenge with m. tuberculosis a more balanced expression of α- and β-chemokines, relative to comparable samples from sham-vaccinated animals by comparative transcriptomics. here, we studied the recruitment of immune cells to blood and lungs in m. tuberculosis-infected macaques as a function of prior bcg-vaccination. vaccination initia ... | 2014 | 25197327 |
| artifactual prolongation of activated partial thromboplastin time with pegylated compounds in silica-based assays. | conjugation of polyethylene glycol (peg) to another molecule prolongs its half-life in the body, but has a potential to artifactually increase the activated partial thromboplastin time (aptt) as measured with certain assays. studies conducted in-house at bristol-myers squibb using the sta-ptt automate 5 assay, the routine assay used to measure aptt, demonstrated prolongation of aptt in plasma samples spiked in vitro with 40-kda branched peg (peg40) conjugated compounds or peg40 alone, but not in ... | 2014 | 25192241 |
| the success rate in a complicated spatial memory test is determined by age, sex, life history and search strategies in cynomolgus monkeys. | in a retrospective analysis of data from three studies using a delayed response task in cynomolgus monkeys, we examined the subjects' search patterns and success rates. twenty-seven monkeys of both sexes, divided into three age groups, were tasked with retrieving two food items hidden in an array of six identical opaque cups. although the task was challenging for all subjects, generating a high level of guesswork, evidence of common behaviors when approaching the spatial memory test were found. ... | 2014 | 25189885 |
| preclinical profile of the her2-targeting adc syd983/syd985: introduction of a new duocarmycin-based linker-drug platform. | a linker-drug platform was built on the basis of a cleavable linker-duocarmycin payload for the development of new-generation antibody-drug conjugates (adc). a leading adc originating from that platform is syd983, a her2-targeting adc based on trastuzumab. her2-binding, antibody-dependent cell-mediated cytotoxicity and her2-mediated internalization are similar for syd983 as compared with trastuzumab. her2-expressing cells in vitro are very potently killed by syd983, but syd983 is inactive in cel ... | 2014 | 25189543 |
| improved quality of cartilage repair by bone marrow mesenchymal stem cells for treatment of an osteochondral defect in a cynomolgus macaque model. | integration of repaired cartilage with surrounding native cartilage is a major challenge for successful tissue-engineering strategies of cartilage repair. we investigated whether incorporation of mesenchymal stem cells (mscs) into the collagen scaffold improves integration and repair of cartilage defects in a cynomolgus macaque model. | 2015 | 25175660 |
| genetic substructure in cynomolgus macaques (macaca fascicularis) on the island of mauritius. | nonhuman primates are commonly used in biomedical research as animal models of human disease and behavior. compared to common rodent models, nonhuman primates are genetically, physiologically, behaviorally and neurologically more similar to humans owing to more recent shared ancestry and therefore provide the advantage of greater translational validity in preclinical studies. the cynomolgus macaque (macaca fascicularis) is one of the most commonly used nonhuman primates in academic and industry ... | 2014 | 25174998 |
| the induction of prolonged myelopoietic effects in monkeys by gw003, a recombinant human granulocyte colony-stimulating factor genetically fused to recombinant human albumin. | gw003, a genetic fusion protein of human serum albumin and granulocyte colony-stimulating factor (g-csf), was developed based on a novel strategy for producing long-acting proteins. the purpose of this study was to evaluate the hematologic, pharmacokinetic, and toxicokinetic effects of gw003 on cynomolgus monkeys. we show that following a single subcutaneous administration of gw003, the absolute neutrophil count increased significantly compared with monkeys that received only the vehicle, and th ... | 2015 | 25174614 |
| aqw051, a novel and selective nicotinic acetylcholine receptor α7 partial agonist, reduces l-dopa-induced dyskinesias and extends the duration of l-dopa effects in parkinsonian monkeys. | nicotinic acetylcholine receptor (nachr)-mediated signaling has been implicated in levodopa (l-dopa)-induced dyskinesias (lid). this study investigated the novel selective α7 nachr partial agonist (r)-3-(6-ρ-tolyl-pyridin-3-yloxy)-1-aza-bicyclo(2.2.2)octane (aqw051) for its antidyskinetic activity in l-dopa-treated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (mptp)-lesioned cynomolgus monkeys. six mptp monkeys were repeatedly treated with l-dopa to develop reproducible dyskinesias. aqw051 (2, 8 ... | 2014 | 25172125 |
| early biodistribution and persistence of a protective live attenuated siv vaccine elicits localised innate responses in multiple lymphoid tissues. | vaccination of mauritian cynomolgus macaques with the attenuated nef-truncated c8 variant of sivmac251/32h (sivmacc8) induces early, potent protection against pathogenic, heterologous challenge before the maturation of cognate immunity. to identify processes that contribute to early protection in this model the pathogenesis, anatomical distribution and viral vaccine kinetics were determined in relation to localised innate responses triggered by vaccination. the early biodistribution of sivmacc8 ... | 2014 | 25162725 |
| blood reference materials from macaques infected with variant creutzfeldt-jakob disease agent. | variant creutzfeldt-jakob disease (vcjd) is a fatal neurodegenerative infection that can be transmitted by blood and blood products from donors in the latent phase of the disease. currently, there is no validated antemortem vcjd blood screening test. several blood tests are under development. any useful test must be validated with disease-relevant blood reference panels. | 2015 | 25154296 |
| costs of and investment in mate-guarding in wild long-tailed macaques (macaca fascicularis): influences of female characteristics and male-female social bonds. | male primates living in multimale groups tend to direct mate and mate-guarding choices toward females of high reproductive value, i.e., high-ranking, parous females, or females with which they share strong bonds. little is known, however, about the constraints that may limit male mate-guarding choices (the costs of this behavior) and the influence of the females' quality on male investment in mate-guarding. we aimed to study the effects of female rank, parity status, and male-female social bond ... | 2014 | 25152554 |
| multilocus typing of cryptosporidium spp. and giardia duodenalis from non-human primates in china. | non-human primates (nhps) are commonly infected with cryptosporidium spp. and giardia duodenalis. however, molecular characterisation of these pathogens from nhps remains scarce. in this study, 2,660 specimens from 26 nhp species in china were examined and characterised by pcr amplification of 18s rrna, 70kda heat shock protein (hsp70) and 60kda glycoprotein (gp60) gene loci for cryptosporidium; and 1,386 of the specimens by ssrrna, triosephosphate isomerase (tpi) and glutamate dehydrogenase (gd ... | 2014 | 25148945 |
| intra- and interspecific variation in macaque molar enamel thickness. | enamel thickness has played an important role in studies of primate taxonomy, phylogeny, and functional morphology, although its variation among hominins is poorly understood. macaques parallel hominins in their widespread geographic distribution, relative range of body sizes, and radiation during the last five million years. to explore enamel thickness variation, we quantified average and relative enamel thickness (aet and ret) in macaca arctoides, macaca fascicularis, macaca fuscata, macaca mu ... | 2014 | 25146639 |
| continental monophyly and molecular divergence of peninsular malaysia's macaca fascicularis fascicularis. | the phylogenetic relationships of long-tailed macaque (macaca fascicularis fascicularis) populations distributed in peninsular malaysia in relation to other regions remain unknown. the aim of this study was to reveal the phylogeography and population genetics of peninsular malaysia's m. f. fascicularis based on the d-loop region of mitochondrial dna. sixty-five haplotypes were detected in all populations, with only vietnam and cambodia sharing four haplotypes. the minimum-spanning network projec ... | 2014 | 25143948 |
| immunochemical quantification of cynomolgus cyp2j2, cyp4a and cyp4f enzymes in liver and small intestine. | 1. an increasing number of studies have indicated the roles of cyp4 proteins in drug metabolism; however, cyp4 expression has not been measured in cynomolgus monkeys, an important animal species for drug metabolism studies. 2. in this study, cynomolgus cyp4a11, cyp4f2/3, cyp4f11 and cyp4f12, along with cyp2j2, were immunoquantified using selective antibodies in 28 livers and 35 small intestines, and their content was compared with cyp1a, cyp2a, cyp2b6, cyp2c9/19, cyp2d, cyp2e1, cyp3a4 and cyp3a5 ... | 2015 | 25138712 |
| lymphocyte depletion after alemtuzumab induction disrupts intestinal fungal microbiota in cynomolgus monkeys. | the interactions of specific fungal phylotypes with immune cells have been recently documented; however, little is known whether gut fungal microbiota is influenced by aberrant immune response in immunosuppressive state. this study aimed to define the biologic impact of lymphocyte depletion on gut fungal microbiota and their relationship. | 2014 | 25136848 |
| preclinical safety evaluation of human mesenchymal stem cell transplantation in cerebrum of nonhuman primates. | the efficacy of stem cell transplantation for promoting recovery of patients with neurological diseases, such as stroke, has been reported in several studies. however, the safety of the intracerebral transplantation of human mesenchymal stem cells (hmscs) remains unclear. the aim of the study was to evaluate the safety of hmscs transplanted in cerebrum of macaca fascicularis and to provide evidence for clinical application. a total of 24 m fascicularis were assigned to 3 groups randomly: low dos ... | 2014 | 25136035 |
| suggestion of suitable animal models for in vivo studies of protein tyrosine phosphatase 1b (ptp1b) inhibitors using computational approaches. | ptp1b is a prototypic enzyme of the superfamily protein tyrosine phosphatases (ptps) which are critical regulators of tyrosine phosphorylation-dependent signaling events. it is a highly plausible candidate for designing therapeutic inhibitors of obesity and type 2 diabetes (t2d). in this study, a detailed comparative analysis to reveal the evolutionary relationship of human ptp1b among related vertebrates has been addressed. the phylogenetic trees were constructed with maximum likelihood algorit ... | 2014 | 25133088 |
| postsacral vertebral morphology in relation to tail length among primates and other mammals. | tail reduction/loss independently evolved in a number of mammalian lineages, including hominoid primates. one prerequisite to appropriately contextualizing its occurrence and understanding its significance is the ability to track evolutionary changes in tail length throughout the fossil record. however, to date, the bony correlates of tail length variation among living taxa have not been comprehensively examined. this study quantifies postsacral vertebral morphology among living primates and oth ... | 2015 | 25132483 |
| rapid, repeated, low-dose challenges with sivmac239 infect animals in a condensed challenge window. | simian immunodeficiency virus (siv) infection of nonhuman primates is the predominant model for preclinical evaluation of human immunodeficiency virus (hiv) vaccines. these studies frequently utilize high-doses of siv that ensure infection after a single challenge but do not recapitulate critical facets of sexual hiv transmission. investigators are increasingly using low-dose challenges in which animals are challenged once every week or every two weeks in order to better replicate sexual hiv tra ... | 2014 | 25125288 |
| combined alphavirus replicon particle vaccine induces durable and cross-protective immune responses against equine encephalitis viruses. | alphavirus replicons were evaluated as potential vaccine candidates for venezuelan equine encephalitis virus (veev), western equine encephalitis virus (weev), or eastern equine encephalitis virus (eeev) when given individually or in combination (v/w/e) to mice or cynomolgus macaques. individual replicon vaccines or the combination v/w/e replicon vaccine elicited strong neutralizing antibodies in mice to their respective alphavirus. protection from either subcutaneous or aerosol challenge with ve ... | 2014 | 25122801 |
| pathogenesis of fulminant monkeypox with bacterial sepsis after experimental infection with west african monkeypox virus in a cynomolgus monkey. | the pathogenesis of severe human monkeypox, which causes systemic and fulminant infections, is not clear. this study presents a case repot of fulminant monkeypox with bacterial sepsis after experimental infection with monkeypox virus in a cynomolgus monkey (macaca fascicularis). in our previous study (saijo et al., 2009, j gen virol), two cynomolgus monkeys became moribund after experimental infection with monkeypox virus liberia strain, west african strain. one exhibited typical monkeypox-relat ... | 2014 | 25120821 |
| influenza virus a/anhui/1/2013 (h7n9) replicates efficiently in the upper and lower respiratory tracts of cynomolgus macaques. | in march 2013, three fatal human cases of infection with influenza a virus (h7n9) were reported in china. since then, human cases have been accumulating. given the public health importance of this virus, we performed a pathogenicity study of the h7n9 virus in the cynomolgus macaque model, focusing on clinical aspects of disease, radiographic, histological, and gene expression profile changes in the upper and lower respiratory tracts, and changes in systemic cytokine and chemokine profiles during ... | 2014 | 25118237 |
| new method for sperm evaluation by 3-dimensional laser scanning microscopy in different laboratory animal species. | sperm analysis is one of the end points in reproductive toxicology studies. different methods for quantitative sperm analysis have been described. for qualitative morphological sperm analysis, either such techniques or smears of sperm and histological sperm staging are in use. any of these methods provides morphological results on a light microscopy level. laser scanning microscopy is a technique using a focused laser for scanning an object. the olympus 3d laser scanning microscope lext ols4000 ... | 2014 | 25116922 |
| protection from pulmonary tissue damage associated with infection of cynomolgus macaques by highly pathogenic avian influenza virus (h5n1) by low dose natural human ifn-α administered to the buccal mucosa. | using an established nonhuman primate model for h5n1 highly pathogenic influenza virus infection in humans, we have been able to demonstrate the prophylactic mitigation of the pulmonary damage characteristic of human fatal cases from primary influenza virus pneumonia with a low dose oral formulation of a commercially available parenteral natural human interferon alpha (alferon n injection®). at the highest oral dose (62.5iu/kg body weight) used there was a marked reduction in the alveolar inflam ... | 2014 | 25111905 |
| sleep electroencephalographic characteristics of the cynomolgus monkey measured by telemetry. | cynomolgus monkeys are widely used as models of diseases and in pre-clinical studies to assess the impact of new pharmacotherapies on brain function and behaviour. however, the time course of electroencephalographic delta activity during sleep, which represents the main marker of sleep intensity associated with recovery during sleep, has never been described in this non-human primate. in this study, telemetry implants were used to record one spontaneous 24-h sleep-wake cycle in four freely-movin ... | 2014 | 25109588 |
| alterations to dna methylation and expression of cxcl14 are associated with suboptimal birth outcomes. | cxcl14 is a chemokine that has previously been implicated in insulin resistance in mice. in humans, the role of cxcl14 in metabolic processes is not well established, and we sought to determine whether cxcl14 is a risk susceptibility gene important in fetal programming of metabolic disease. for this purpose, we investigated whether cxcl14 is differentially regulated in human umbilical cords of infants with varying birth weights. we found an elevated expression of cxcl14 in human low birth weight ... | 2014 | 25102097 |
| identification of a derived dental trait in the papionini relative to other old world monkeys. | variation in the shape of teeth provides an immense amount of information about the evolutionary history and adaptive strategy of a mammalian lineage. here, we explore variation in the expression of a purported molar lingual remnant (the interconulus) across the old world monkeys (primates: cercopithecidae) with the aim of elucidating a component of the adaptive radiation of this family. this radiation is characterized by a wide geographic range (asia and africa) as well as diverse dietary niche ... | 2014 | 25100299 |
| efficacy of primate humoral passive transfer in a murine model of pneumonic plague is mouse strain-dependent. | new vaccines against biodefense-related and emerging pathogens are being prepared for licensure using the us federal drug administration's "animal rule." this allows licensure of drugs and vaccines using protection data generated in animal models. a new acellular plague vaccine composed of two separate recombinant proteins (rf1 and rv) has been developed and assessed for immunogenicity in humans. using serum obtained from human volunteers immunised with various doses of this vaccine and from imm ... | 2014 | 25097863 |
| foodborne transmission of bovine spongiform encephalopathy to non-human primates results in preclinical rapid-onset obesity. | obesity has become one of the largest public health challenges worldwide. recently, certain bacterial and viral pathogens have been implicated in the pathogenesis of obesity. in the present study, we retrospectively analyzed clinical data, plasma samples and post-mortem tissue specimens derived from a risk assessment study in bovine spongiform encephalopathy (bse)-infected female cynomolgus monkeys (macaca fascicularis). the original study design aimed to determine minimal infectious doses after ... | 2014 | 25090610 |
| ind-directed safety and biodistribution study of intravenously injected cetuximab-irdye800 in cynomolgus macaques. | the use of receptor-targeted antibodies conjugated to fluorophores is actively being explored for real-time imaging of disease states; however, the toxicity of the bioconjugate has not been assessed in non-human primates. | 2015 | 25080323 |
| plasma proteome analysis on cynomolgus monkey (macaca fascicularis) pedigrees with early onset drusen formation. | the central region of the primate retina is called macula. the fovea is located at the center of the macula, where the photoreceptors are concentrated to create neural network adapted for high visual acuity. damage to the fovea by macular dystrophies and age-related macular degeneration (amd) can reduce the central visual acuity. the molecular mechanisms leading to these diseases are most likely dependent on the proteins in macula differ from that in peripheral retina in expression level. previo ... | 2014 | 25077760 |
| high diversity of mic genes in non-human primates. | the human mhc class i (mhc-i) chain-related genes a and b (mica and micb) encode stress-induced glycoproteins, ligands for the activating receptor nkg2d. they display an unusually high degree of polymorphism, next only to that of classical mhc-i. the functional relevance and selective pressure behind this peculiar polymorphism, which is quite distinct from that of classical mhc-i, remain largely unknown. this study increases the repertoire of allelic sequences determined for the mic genes of non ... | 2014 | 25073428 |
| retinal pathology detected by optical coherence tomography in an animal model of parkinson's disease. | optical coherence tomography (oct) is a noninvasive procedure for analysis of retinal morphology. significant changes in the thickness of the peripapillary retinal nerve fiber layer (rnfl) in parkinson's disease (pd) have been reported, and the current study was performed to examine whether such changes can also be detected in an animal model of pd. | 2014 | 25070726 |
| hepatitis e virus infection in farmed rabbits and swine in the eastern chinese city lianyungang: showing no potential interspecies transmission. | rabbit hev isolated recently from farmed rabbits in china has been shown experimentally to be able to infect both cynomolgus macaques and pigs. the purpose of the present study was to investigate the extent to which cross-species transmission of rabbit hev in farm settings is a significant factor in the spread of this zoonotic infection. rabbit and swine feces were collected from the same area in eastern china (lianyungang city) and analyzed by rt-pcr. partial genome sequencing of a 365 bp regio ... | 2014 | 25069969 |
| telemetry video-electroencephalography (eeg) in rats, dogs and non-human primates: methods in follow-up safety pharmacology seizure liability assessments. | non-clinical seizure liability studies typically aim to: 1) confirm the nature of eeg activity during abnormal clinical signs, 2) identify premonitory clinical signs, 3) measure plasma levels at seizure onset, 4) demonstrate that drug-induced seizures are self-limiting, 5) confirm that conventional drugs (e.g. diazepam) can treat drug-induced seizures and 6) confirm the no observed adverse effect level (noael) at eeg. our aim was to originally characterize several of these items in a three speci ... | 2014 | 25065541 |
| quantitative pcr assays reveal high prevalence of lymphocryptovirus as well as lytic phase gene expression in peripheral blood cells of cynomolgus macaques. | lymphocryptoviruses such as epstein-barr virus (ebv) are important pathogens in both human and non-human primates, particularly during immunosuppression. immunomodulatory molecules that may suppress antiviral immunity are commonly tested in the cynomolgus macaque. to enable the study of lymphocryptovirus (lcv) in this non-clinical model, pcr-based assays were developed to measure lcv viral load, as well as transcripts for the lytic phase lcv gene, balf-2. results from studies employing these ass ... | 2014 | 25064358 |
| transmission and control of plasmodium knowlesi: a mathematical modelling study. | plasmodium knowlesi is now recognised as a leading cause of malaria in malaysia. as humans come into increasing contact with the reservoir host (long-tailed macaques) as a consequence of deforestation, assessing the potential for a shift from zoonotic to sustained p. knowlesi transmission between humans is critical. | 2014 | 25058400 |
| frontal cortical and subcortical projections provide a basis for segmenting the cingulum bundle: implications for neuroimaging and psychiatric disorders. | the cingulum bundle (cb) is one of the brain's major white matter pathways, linking regions associated with executive function, decision-making, and emotion. neuroimaging has revealed that abnormalities in particular locations within the cb are associated with specific psychiatric disorders, including depression and bipolar disorder. however, the fibers using each portion of the cb remain unknown. in this study, we used anatomical tract-tracing in nonhuman primates (macaca nemestrina, macaca fas ... | 2014 | 25057206 |
| macrophage- and neutrophil-derived tnf-α instructs skin langerhans cells to prime antiviral immune responses. | dendritic cells are major apcs that can efficiently prime immune responses. however, the roles of skin-resident langerhans cells (lcs) in eliciting immune responses have not been fully understood. in this study, we demonstrate for the first time, to our knowledge, that lcs in cynomolgus macaque skin are capable of inducing antiviral-specific immune responses in vivo. targeting hiv-gag or influenza hemagglutinin ags to skin lcs using recombinant fusion proteins of anti-langerin ab and ags resulte ... | 2014 | 25057007 |
| integrative "omic" analysis of experimental bacteremia identifies a metabolic signature that distinguishes human sepsis from systemic inflammatory response syndromes. | sepsis is a leading cause of morbidity and mortality. currently, early diagnosis and the progression of the disease are difficult to make. the integration of metabolomic and transcriptomic data in a primate model of sepsis may provide a novel molecular signature of clinical sepsis. | 2014 | 25054455 |
| spontaneous unilateral renal dysplasia in a clinically healthy cynomolgus monkey (macaca fascicularis). | renal dysplasia is a congenital renal malformation characterized by disruption of normal renal development with asynchronous differentiation of nephrons, collecting ducts, and parenchyma and abnormal patterning of cortical and medullary tissues. the present article describes unilateral renal dysplasia discovered in a cynomolgus monkey from a routine toxicology study. the affected kidney was small and characterized by extensive interstitial fibrosis with the formation of fibromuscular collars aro ... | 2014 | 25053241 |
| repeated intravenous injections in non-human primates demonstrate preclinical safety of an anti-inflammatory phosphorus-based dendrimer. | dendrimers are nanosized hyperbranched polymers synthesized through an iterative step-by-step process; their size and structure are perfectly controlled, and they are widely used for biomedical purposes. previously, we showed that a phosphorous-based dendrimer capped with anionic azabisphosphonate groups (so-called abp dendrimer) has immunomodulatory and anti-inflammatory properties toward the human immune system. it dramatically inhibits the onset and development of experimental arthritis in a ... | 2015 | 25051330 |
| efficacy of selective pde4d negative allosteric modulators in the object retrieval task in female cynomolgus monkeys (macaca fascicularis). | cyclic adenosine monophosphate (camp) signalling plays an important role in synaptic plasticity and information processing in the hippocampal and basal ganglia systems. the augmentation of camp signalling through the selective inhibition of phosphodiesterases represents a viable strategy to treat disorders associated with dysfunction of these circuits. the phosphodiesterase (pde) type 4 inhibitor rolipram has shown significant pro-cognitive effects in neurological disease models, both in rodents ... | 2014 | 25050979 |
| the distribution of transplanted human mesenchymal stem cells in the cns of young macaca fascicularis. | mesenchymal stem cell (msc)-based therapies have generated much hope and promise as a potential source of cells for cell-based therapeutic strategies in pediatric degenerative diseases. however, the distribution and migratory routes of mscs are unknown. here, real-time pcr and microscopy were used to observe the migration and distribution of labeled human mscs (hmscs) transplanted into the striatum of young macaca fascicularis. moreover, the differentiation of hmscs was also detected using immun ... | 2014 | 25050543 |
| a review of piscine islet xenotransplantation using wild-type tilapia donors and the production of transgenic tilapia expressing a "humanized" tilapia insulin. | most islet xenotransplantation laboratories have focused on porcine islets, which are both costly and difficult to isolate. teleost (bony) fish, such as tilapia, possess macroscopically visible distinct islet organs called brockmann bodies which can be inexpensively harvested. when transplanted into diabetic nude mice, tilapia islets maintain long-term normoglycemia and provide human-like glucose tolerance profiles. like porcine islets, when transplanted into euthymic mice, they are rejected in ... | 2016 | 25040337 |
| cyp2c19 polymorphisms account for inter-individual variability of drug metabolism in cynomolgus macaques. | cyp2c19 (formerly known as cyp2c75), highly homologous to human cyp2c19, has been identified in cynomolgus and rhesus macaques, non-human primate species widely used in drug metabolism studies. cyp2c19 is predominantly expressed in liver and encodes a functional drug-metabolizing enzyme. genetic variants in human cyp2c genes account for the inter-individual variability in drug metabolism; however, genetic variants have not been investigated in macaque cyp2c19. in the present study, re-sequencing ... | 2014 | 25036290 |
| cynomolgus monkey as a surrogate for human aldehyde oxidase metabolism of the egfr inhibitor bibx1382. | bibx1382 was an epidermal growth factor receptor inhibitor under clinical investigation for treatment of cancer. this candidate possessed an attractive preclinical absorption, distribution, metabolism, and excretion profile, yet failed in clinical studies due in part to poor oral exposure, resulting from extensive metabolism by aldehyde oxidase (ao). in vitro metabolism studies were performed in liver cytosol and cryopreserved hepatocytes from multiple species. in addition, a pharmacokinetic stu ... | 2014 | 25035284 |
| ultrasensitive detection of prp(sc) in the cerebrospinal fluid and blood of macaques infected with bovine spongiform encephalopathy prion. | prion diseases are characterized by the prominent accumulation of the misfolded form of a normal cellular protein (prp(sc)) in the central nervous system. the pathological features and biochemical properties of prp(sc) in macaque monkeys infected with the bovine spongiform encephalopathy (bse) prion have been found to be similar to those of human subjects with variant creutzfeldt-jakob disease (vcjd). non-human primate models are thus ideally suited for performing valid diagnostic tests and dete ... | 2014 | 25024281 |
| acute hantavirus infection induces galectin-3-binding protein. | hantaviruses are zoonotic viruses that cause life-threatening diseases when transmitted to humans. severe hantavirus infection is manifested by impairment of renal function, pulmonary oedema and capillary leakage. both innate and adaptive immune responses contribute to the pathogenesis, but the underlying mechanisms are not fully understood. here, we showed that galectin-3-binding protein (gal-3bp) was upregulated as a result of hantavirus infection both in vitro and in vivo. gal-3bp is a secret ... | 2014 | 25013204 |
| fibronectin expression in the intervertebral disc of monkey. | fibronectin, a large dimeric plasma glycoprotein found only in vertebrates, is a core component of several extracellular matrices. integrin receptors regulate different cell activities. fibronectin expression patterns in intervertebral disc have not been extensively studied. the aim of this study was to evaluate the distribution of fibronectin in the different regions of the intervertebral disc, and in intervertebral discs of different levels of monkeys. | 2015 | 25012735 |
| generic automated method for liquid chromatography-multiple reaction monitoring mass spectrometry based monoclonal antibody quantitation for preclinical pharmacokinetic studies. | quantitation of therapeutic monoclonal antibodies (mab) using liquid chromatography-tandem mass spectrometry (lc-ms/ms) for pharmacokinetic (pk) studies is becoming an essential complement to traditional antibody-based ligand binding assays (lba). here we show an automated method to perform lc-ms/ms-based quantitation, with igg1 conserved peptides, a heavy isotope labeled mab internal standard, and anti-human fc enrichment. all reagents in the method are commercially available with no requiremen ... | 2014 | 25010922 |
| adequacy of a compartment model for cmro₂ quantitation using ¹⁵o-labeled oxygen and pet: a clearance measurement of ¹⁵o-radioactivity following intracarotid bolus injection of ¹⁵o-labeled oxyhemoglobin on macaca fascicularis. | we aimed at evaluating the adequacy of the commonly employed compartmental model for quantitation of cerebral metabolic rate of oxygen (cmro2) using (15)o-labeled oxygen ((15)o2) and positron emission tomography (pet). sequential pet imaging was carried out on monkeys following slow bolus injection of blood samples containing (15)o2-oxyhemoglobin ((15)o2-hb), (15)o-labeled water (h2(15)o), and c(15)o-labeled hemoglobin (c(15)o-hb) into the internal carotid artery (ica). clearance slopes were ass ... | 2014 | 25005879 |
| no expression of porcine endogenous retrovirus after pig to monkey xenotransplantation. | this study was performed to investigate the expression of two porcine endogenous retrovirus (perv) elements, perv gag and full-length conserved perv, in blood cells collected periodically from organ-recipient monkeys that underwent pig to non-human primate xenotransplantation. the heart and kidney-respectively acquired from α-1,3-galactosyltransferase knockout (gt-ko) pigs that survived for24 and 25 days-were xenografted into cynomolgus monkeys. the two perv elements expressed in the xenografted ... | 2014 | 24999364 |
| estimation of glomerular filtration rate in cynomolgus monkeys (macaca fascicularis). | to estimate the glomerular filtration rate (gfr) in cynomolgus monkeys (macaca fascicularis), a three-blood-sample method using iodixanol was assessed in comparison with the conventional multisample strategy using inulin. iodixanol and inulin were coadministered intravenously 40 mg i/kg and 50 mg/kg, respectively, to male monkeys, followed by blood collection 60, 90 and 120 min later. a close correlation (r=0.96) was noted between the gfr values estimated by both methods. in clinically healthy m ... | 2014 | 24998395 |
| discovery and development of 11c-lu ae92686 as a radioligand for pet imaging of phosphodiesterase10a in the brain. | phosphodiesterase 10a (pde10a) plays a key role in the regulation of brain striatal signaling, and several pharmaceutical companies currently investigate pde10a inhibitors in clinical trials for various central nervous system diseases. a pde10a pet ligand may provide evidence that a clinical drug candidate reaches and binds to the target. here we describe the successful discovery and initial validation of the novel radiolabeled pde10a ligand 5,8-dimethyl-2-[2-((1-(11)c-methyl)-4-phenyl-1h-imidaz ... | 2014 | 24994928 |
| hepatic, intestinal, renal, and plasma hydrolysis of prodrugs in human, cynomolgus monkey, dog, and rat: implications for in vitro-in vivo extrapolation of clearance of prodrugs. | hydrolysis plays an important role in metabolic activation of prodrugs. in the current study, species and in vitro system differences in hepatic and extrahepatic hydrolysis were investigated for 11 prodrugs. ten prodrugs in the data set are predominantly hydrolyzed by carboxylesterases (ces), whereas olmesartan medoxomil is also metabolized by carboxymethylenebutenolidase (cmbl) and paraoxonase. metabolic stabilities were assessed in cryopreserved hepatocytes, liver s9 (ls9), intestinal s9 (is9) ... | 2014 | 24994071 |
| effects of askp1240 combined with tacrolimus or mycophenolate mofetil on renal allograft survival in cynomolgus monkeys. | blocking the cd40-cd154 signal pathway has previously shown promise as a strategy to prevent allograft rejection. in this study, the efficacy of a novel fully human anti-cd40 monoclonal antibody-askp1240, administered as a monotherapy or combination therapy (subtherapeutic dose of tacrolimus or mycophenolate mofetil), on the prevention of renal allograft rejection was evaluated in cynomolgus monkeys. | 2014 | 24992357 |
| pathology of experimental machupo virus infection, chicava strain, in cynomolgus macaques (macaca fascicularis) by intramuscular and aerosol exposure. | machupo virus, the causative agent of bolivian hemorrhagic fever (bhf), is a highly lethal viral hemorrhagic fever of which little is known and for which no food and drug administration-approved vaccines or therapeutics are available. this study evaluated the cynomolgus macaque as an animal model using the machupo virus, chicava strain, via intramuscular and aerosol challenge. the incubation period was 6 to 10 days with initial signs of depression, anorexia, diarrhea, mild fever, and a petechial ... | 2015 | 24990481 |