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levodopa induces long-lasting modification in the functional activity of the nigrostriatal pathway.much controversy exists concerning the effect of levodopa on striatal dopaminergic markers in parkinson's disease (pd) and its influence on functional neuroimaging. to deal with this issue we studied the impact of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (mptp) and chronic levodopa administration on striatal (18)f-dopa uptake (ki) in an animal model of pd. the levels of several striatal dopaminergic markers and the number of surviving dopaminergic neurons in the substantia nigra ( ...201424076099
human and non-human primate intestinal fcrn expression and immunoglobulin g transcytosis.to evaluate transcytosis of immunoglobulin g (igg) by the neonatal fc receptor (fcrn) in adult primate intestine to determine whether this is a means for oral delivery of monoclonal antibodies (mabs).201424072267
autologous transplantation of gdnf-expressing mesenchymal stem cells protects against mptp-induced damage in cynomolgus monkeys.glial cell-derived neurotrophic factor (gdnf) has shown beneficial effects in models of parkinson's disease. the mild results observed in the double-blind clinical trial by intraputamenal infusion of recombinant gdnf proteins warrant a search for alternative delivery methods. in this study, we investigated the function of autologous mesenchymal stem cells (mscs) expressing gdnf (gdnf-mscs) for protection against mptp-induced injury in cynomolgus monkeys. mscs were obtained from the bone marrow o ...201324071770
adeno-associated virus type 6 is retrogradely transported in the non-human primate brain.we recently demonstrated that axonal transport of adeno-associated virus (aav) is serotype-dependent. thus, aav serotype 2 (aav2) is anterogradely transported (e.g., from cell bodies to nerve terminals) in both rat and non-human primate (nhp) brain. in contrast, aav serotype 6 (aav6) is retrogradely transported from terminals to neuronal cell bodies in the rat brain. however, the directionality of axonal transport of aav6 in the nhp brain has not been determined. in this study, two cynomolgus ma ...201324067867
a test of agent-based models as a tool for predicting patterns of pathogen transmission in complex landscapes.landscape complexity can mitigate or facilitate host dispersal, influencing patterns of pathogen transmission. spatial transmission of pathogens through landscapes, therefore, presents an important but not fully elucidated aspect of transmission dynamics. using an agent-based model (link) that incorporates gis data, we examined the effects of landscape information on the spatial patterns of host movement and pathogen transmission in a system of long-tailed macaques and their gut parasites. we fi ...201324063811
compositionality in neural control: an interdisciplinary study of scribbling movements in primates.this article discusses the compositional structure of hand movements by analyzing and modeling neural and behavioral data obtained from experiments where a monkey (macaca fascicularis) performed scribbling movements induced by a search task. using geometrically based approaches to movement segmentation, it is shown that the hand trajectories are composed of elementary segments that are primarily parabolic in shape. the segments could be categorized into a small number of classes on the basis of ...201324062679
progressive loss of striatal dopamine terminals in mptp-induced acute parkinsonism in cynomolgus monkeys using vesicular monoamine transporter type 2 pet imaging ([(18)f]av-133).the 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (mptp)-induced parkinsonism model, particularly in non-human primates, remains the gold-standard for studying the pathogenesis and assessing novel therapies for parkinson's disease. however, whether the loss of dopaminergic neurons in this model is progressive remains controversial, mostly due to the lack of objective in vivo assessment of changes in the integrity of these neurons. in the present study, parkinsonism was induced in cynomolgus monke ...201424061965
animal models for ebola and marburg virus infections.ebola and marburg hemorrhagic fevers (ehf and mhf) are caused by the filoviridae family, ebolavirus and marburgvirus (ebolavirus and marburgvirus), respectively. these severe diseases have high mortality rates in humans. although ehf and mhf are endemic to sub-saharan africa. a novel filovirus, lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in spain where filoviral hemorrhagic fever had never been reported. the virulence of this virus has no ...201324046765
identification of mamu-dpa1, mamu-dqa1, and mamu-dra alleles in a cohort of chinese rhesus macaques.rhesus macaques have long been used as animal models for various human diseases; the susceptibility and/or resistance to some of these diseases are related to the major histocompatibility complex (mhc). to gain insight into the mhc background and to facilitate the experimental use of chinese rhesus macaques, mamu-dpa1, mamu-dqa1, and mamu-dra alleles were investigated in 30 chinese rhesus macaques by gene cloning and sequencing. a total of 14 mamu-dpa1, 17 mamu-dqa1, and 9 mamu-dra alleles were ...201324042461
the whole mitochondrial genome of the cynomolgus macaque (macaca fascicularis).macaca fascicularis, known as the long-tailed macaque, is widely distributed in southern of east asia and southeast asia. it was one of the most commonly used non-human primates in biomedical research. thus, to illustrate the maternal phylogenetic status of m. fascicularis in primates based on the whole mitochondrial dna (mtdna) genome and determine a reference sequence for future population genetic studies by taking mtdna as molecular marker, in this study, the high quality whole mtdna genome o ...201524041448
immunopathologic characterization of naturally acquired trypanosoma cruzi infection and cardiac sequalae in cynomolgus macaques (macaca fascicularis).trypanosoma cruzi, the causative agent of chagas disease, is endemic in south texas due to the abundant vector and wild small mammalian reservoir populations. this situation predisposes nonhuman primate colonies exposed to outdoor housing to infection from ingestion or bite of triatomid insects. using a t. cruzi-specific real-time pcr and trypanosome spp.-specific elisa, we revealed a prevalence rate of 8.5% in a colony of outdoor-housed cynomolgus macaques. by using a discriminating kinetoplast ...201324041209
myocarditis, disseminated infection, and early viral persistence following experimental coxsackievirus b infection of cynomolgus monkeys.coxsackievirus b (cvb) infection is a common cause of acute viral myocarditis. the clinical presentation of myocarditis caused by this enterovirus is highly variable, ranging from mildly symptoms to complete hemodynamic collapse. these variations in initial symptoms and in the immediate and long term outcomes of this disease have impeded development of effective treatment strategies. nine cynomolgus monkeys were inoculated with myocarditic strains of cvb. virological studies performed up to 28 d ...201324040287
finding the factors of reduced genetic diversity on x chromosomes of macaca fascicularis: male-driven evolution, demography, and natural selection.the ratio of genetic diversity on x chromosomes relative to autosomes in organisms with xx/xy sex chromosomes could provide fundamental insight into the process of genome evolution. here we report this ratio for 24 cynomolgus monkeys (macaca fascicularis) originating in indonesia, malaysia, and the philippines. the average x/a diversity ratios in these samples was 0.34 and 0.20 in the indonesian-malaysian and philippine populations, respectively, considerably lower than the null expectation of 0 ...201324026095
fully validated lc-ms/ms assay for the simultaneous quantitation of coadministered therapeutic antibodies in cynomolgus monkey serum.an lc-ms/ms assay was developed and fully validated for the simultaneous quantitation of two coadministered human monoclonal antibodies (mabs), mab-a and mab-b of igg4 subclass, in monkey serum. the total serum proteins were digested with trypsin at 50 °c for 30 min after methanol denaturation and precipitation, dithiothreitol reduction, and iodoacetamide alkylation. the tryptic peptides were chromatographically separated with a c18 column (2.1 × 100 mm, 1.7 μm) with mobile phases of 0.1% formic ...201324024648
target-directed development and preclinical characterization of the proposed biosimilar rituximab gp2013.biosimilar development involves a target-directed iterative process to ensure a similar product to the originator. here we report the preclinical development of the proposed biosimilar rituximab (gp2013). post-translational modifications and bioactivities of gp2013 versus originator rituximab were engineered and monitored to ensure similar pharmacological profiles. antibody-dependent cellular cytotoxicity (adcc) was used to illustrate how different glycosylation patterns and structure-function r ...201424024472
expression of the memory marker cd45ro on helper t cells in macaques.in humans it has been reported that a major site of the latent reservoir of hiv is within cd4+ t cells expressing the memory marker cd45ro, defined by the mab uchl1. there are conflicting reports regarding the expression of this antigen in macaques, the most relevant animal species for studying hiv pathogenesis and testing new therapies. there is now a major effort to eradicate hiv reservoirs and cure the infection. one approach is to eliminate subsets of cells housing the latent reservoir, usin ...201324023920
depression-like behavioral phenotypes by social and social plus visual isolation in the adult female macaca fascicularis.major depressive disorder (mdd) is a debilitating psychiatric mood disorder that affects millions of individuals globally. our understanding of the biological basis of mdd is poor, and current treatments are ineffective in a significant proportion of cases. this current situation may relate to the dominant rodent animal models of depression, which possess translational limitations due to limited homologies with humans. therefore, a more homologous primate model of depression is needed to advance ...201324023857
immunohistochemical localization of oxytocin receptors in human brain.the neuropeptide oxytocin (ot) regulates rodent, primate and human social behaviors and stress responses. ot binding studies employing (125)i-d(ch2)5-[tyr(me)2,thr4,tyr-nh2(9)] ornithine vasotocin ((125)i-ota), has been used to locate and quantify ot receptors (otrs) in numerous areas of the rat brain. this ligand has also been applied to locating otrs in the human brain. the results of the latter studies, however, have been brought into question because of subsequent evidence that (125)i-ota is ...201324012742
development of a novel fluorine-18 labeled deuterated fluororasagiline ([(18)f]fluororasagiline-d2) radioligand for pet studies of monoamino oxidase b (mao-b).the objective of this study was to synthesize and evaluate a novel fluorine-18 labeled deuterium substituted analogue of rasagiline (9, [(18)f]fluororasagiline-d2) as a potential pet radioligand for studies of monoamine oxidase b (mao-b). the precursor compound (6) and reference standard (7) were synthesized in multi-step syntheses. radiolabeling of 9 was accomplished by a two-step synthesis, compromising a nucleophilic substitution followed by hydrolysis of the sulfamidate group. the incorporat ...201324012376
synthesis, radiolabeling, and in vivo pharmacokinetic evaluation of the amyloid beta radioligand [11c]azd4694 in nonhuman primates.[(18)f]azd4694 (2-(2-(18)f-fluoro-6-(methylamino)-3-pyridyl)benzofuran-5-ol) is a radioligand suitable for imaging of amyloid beta deposits in the living human brain using positron emission tomography (pet). here, we report the preparation and pharmacokinetic profile of its carbon-11 (t1/2 = 20.4 min) labeled isotopolog [(11)c]azd4694 and compare [(11)c]azd4694 with the hitherto most widely applied amyloid pet radioligand [(11)c]pittsburgh compound b (pib).201424002613
modeling approach to investigate the effect of neonatal fc receptor binding affinity and anti-therapeutic antibody on the pharmacokinetic of humanized monoclonal anti-tumor necrosis factor-α igg antibody in cynomolgus monkey.several neonatal fc receptor (fcrn) variants of an anti-tumor necrosis factor (tnf)-α humanized monoclonal igg antibodies (mabs) were developed but the effect of their differential fcrn binding affinities on pharmacokinetic (pk) behavior were difficult to be definitively measured in vivo due to formation of anti-therapeutic antibody (ata). a semi-mechanistic model was developed to investigate the quantitative relationship between the fcrn binding affinity and pk of mabs in cynomolgus monkey with ...201423999033
molecular demonstration of hemotropic mycoplasmas in wild japanese monkeys (macaca fuscata).the prevalence of hemotropic mycoplasmas in wild monkeys is largely unknown. here, we report the presence of hemoplasmas in blood specimens collected from wild japanese monkeys (macaca fuscata) tentatively captured for ecological survey in mie prefecture, japan. we examined 9 monkeys using hemoplasma-specific real-time pcr and found all of them positive for a hemoplasma infection. the 16s rrna gene and 16s to 23s rrna intergenic spacer region of the hemoplasma detected in wild monkeys were ampli ...201423978941
investigation of an f-18 oxytocin receptor selective ligand via pet imaging.the compound 1-(1-(2-(2-(2-fluoroethoxy)-4-(piperidin-4-yloxy)phenyl)acetyl)piperidin-4-yl)-3,4-dihydroquinolin-2(1h)-one (1) was synthesized and positively evaluated in vitro for high potency and selectivity with human oxytocin receptors. the positron emitting analogue, [f-18]1, was synthesized and investigated in vivo via pet imaging using rat and cynomolgus monkey models. pet imaging studies in female sprague-dawley rats suggested [f-18]1 reached the brain and accumulated in various regions o ...201323978650
use-wear patterns on wild macaque stone tools reveal their behavioural history.burmese long-tailed macaques (macaca fascicularis aurea) are one of a limited number of wild animal species to use stone tools, with their tool use focused on pounding shelled marine invertebrates foraged from intertidal habitats. these monkeys exhibit two main styles of tool use: axe hammering of oysters, and pound hammering of unattached encased foods. in this study, we examined macroscopic use-wear patterns on a sample of 60 wild macaque stone tools from piak nam yai island, thailand, that ha ...201323977365
prospective comparison of the detection rates of human enterovirus and parechovirus rt-qpcr and viral culture in different pediatric specimens.reverse-transcriptase quantitative real-time polymerase chain reaction (rt-qpcr) has become the gold standard for the diagnosis of human enterovirus (ev) and parechovirus (hpev) infections. the detection rate of rt-qpcr in different pediatric body specimens has not been compared prospectively in a multicentre study.201323973350
insulin/igf signaling-related gene expression in the brain of a sporadic alzheimer's disease monkey model induced by intracerebroventricular injection of streptozotocin.we reported previously that the intracerebroventricular streptozotocin (icv-stz)-treated cynomolgus monkey showed regionally specific glucose hypometabolism in fdg-pet imaging, similar to that observed in the early stages of sporadic alzheimer's disease (sad). however, further pathological analyses of this model at the molecular level are needed to validate it as a feasible model for sad. two cynomolgus monkeys were injected with 2 mg/kg stz into the cerebellomedullary cistern at day 1, 7 and 14 ...201423948941
a fully human anti-hepcidin antibody modulates iron metabolism in both mice and nonhuman primates.iron maldistribution has been implicated in the etiology of many diseases including the anemia of inflammation (ai), atherosclerosis, diabetes, and neurodegenerative disorders. iron metabolism is controlled by hepcidin, a 25-amino-acid peptide. hepcidin is induced by inflammation and causes iron to be sequestered within cells of the reticuloendothelial system, suppressing erythropoiesis and blunting the activity of erythropoiesis stimulating agents (esas). for this reason, neutralization of hepc ...201323945155
current challenges and opportunities in nonclinical safety testing of biologics.nonclinical safety testing of new biotherapeutic entities represents its own challenges and opportunities in drug development. hot topics in this field have been discussed recently at the 2nd annual biosafe european general membership meeting. in this feature article, discussions on the challenges surrounding the use of pegylated therapeutic proteins, selection of cynomolgus monkey as preclinical species, unexpected pharmacokinetics of biologics and the safety implications thereof are summarized ...201323942260
progestin effects on cell proliferation pathways in the postmenopausal mammary gland.menopausal hormone therapies vary widely in their effects on breast cancer risk, and the mechanisms underlying these differences are unclear. the primary goals of this study were to characterize the mammary gland transcriptional profile of estrogen + progestin therapy in comparison with estrogen-alone or tibolone and investigate pathways of cell proliferation in a postmenopausal primate model.201323938070
measurement of in vivo therapeutic mab concentrations: comparison of conventional serum/plasma collection and analysis to dried blood spot sampling.development of an alternative sampling method that uses small amounts of whole blood, such as dried blood spots (dbs), would be an advance in the quantitative assay field. previously, we assessed the ability to quantitate therapeutic monoclonal antibodies present in dbs compared with a typical serum sample-based method, and concluded that measurements in dbs were reproducible and yielded methods that met requirements for precision, accuracy and sensitivity. the goal herein was to assess the meas ...201323937133
fatal atypical o:3 yersinia pseudotuberculosis infection in cynomolgus macaques.fatal yersinia pseudotuberculosis infection in cynomolgus macaques was diagnosed based upon pathology, microbiology and pcr for this study. pathological findings included acute, erosive to ulcerative, necrohemorrhagic enterocolitis. genotyping by pcr showed an o:3 pattern (gmd-fcl(+), ddhc-prt(+), manb(+), ddha-b(+)), but an additional gene, wbyk, was detected. this is the second report to identify wbyk+ o:3 genotype as the cause of fatal yersiniosis. the first case was reported in 2008, and inv ...201323932075
pitavastatin as an in vivo probe for studying hepatic organic anion transporting polypeptide-mediated drug-drug interactions in cynomolgus monkeys.drug-drug interactions (ddis) caused by the inhibition of hepatic uptake transporters such as organic anion transporting polypeptide (oatp) can affect therapeutic efficacy and cause adverse reactions. we investigated the potential utility of pitavastatin as an in vivo probe substrate for preclinically studying oatp-mediated ddis using cynomolgus monkeys. cyclosporine a (csa) and rifampicin (rif), typical oatp inhibitors, inhibited active uptake of pitavastatin into monkey hepatocytes with half-m ...201323929936
influence of shape and gradient refractive index in the accommodative changes of spherical aberration in nonhuman primate crystalline lenses.to estimate changes in surface shape and gradient refractive index (grin) profile in primate lenses as a function of accommodation. to quantify the contribution of surface shape and grin to spherical aberration changes with accommodation.201323927893
non-invasive ultrasonic surgery of the brain in non-human primates.high-intensity focused ultrasound causes selective tissue necrosis efficiently and safely, namely, in the prostate, liver, and uterine fibroid. nevertheless, ablation of brain tissue using focused ultrasound remains limited due to strong aberrations induced by the skull. to achieve ultrasonic transcranial brain ablation, such aberrations have to be compensated. in this study, non-invasive therapy was performed on monkeys using adaptive correction of the therapeutic beam and 3d simulations of tra ...201323927203
target-mediated drug disposition and prolonged liver accumulation of a novel humanized anti-cd81 monoclonal antibody in cynomolgus monkeys.cd81 is an essential receptor for hepatitis c virus (hcv). k21 is a novel high affinity anti-cd81 antibody with potent broad spectrum anti-hcv activity in vitro. the pharmacokinetics (pk), pharmacodynamics and liver distribution of k21 were characterized in cynomolgus monkeys after intravenous (i.v.) administration of k21. characteristic target-mediated drug disposition (tmdd) was shown based on the pk profile of k21 and a semi-mechanistic tmdd model was used to analyze the data. from the tmdd m ...201323924796
proceedings of the 2013 joint jstp/ntp satellite symposium.the first joint japanese society of toxicologic pathology (jstp) and national toxicology program (ntp) satellite symposium, entitled "pathology potpourri," was held on january 29(th) at okura frontier hotel in tsukuba, ibaraki, japan, in advance of the jstp's 29(th) annual meeting. the goal of this symposium was to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. this article presents summaries of the speakers' presentations, including diagnosti ...201323914068
subchronic safety evaluation of epo-018b, a pegylated peptidic erythropoiesis stimulating agent, after 5-week subcutaneous injection in cynomolgus monkeys and sprague-dawley rats.epo-018b, a synthetic peptide-based erythropoiesis stimulating agent (esa), is coupled to polyethylene glycol (peg) and designed to specifically bind and activate the erythropoietin (epo) receptor to result in production of red blood cells. this study was designed to evaluate the potential subchronic toxicity of epo-018b for cynomolgus monkeys and sprague-dawley rats both at 0, 0.5, 5 and 50 mg/kg every week for 5 weeks, followed by 6-week recovery for rats and 12-week recovery for monkeys. the ...201323911802
comparison of antiplatelet effects of prasugrel and ticagrelor in cynomolgus monkeys by an elisa-based vasp phosphorylation assay and platelet aggregation.prasugrel is the third generation thienopyridine prodrug, and ticagrelor is a non-competitive direct acting p2y12 antagonist. in phase 3 studies, both agents reduced ischaemic event rates compared to clopidogrel. the present in vitro human and monkey studies showed that ticagrelor's active metabolite (am) was more potent than ticagrelor and prasugrel's am on inhibition of adp-induced platelet aggregation by light transmission aggregometry and elisa-based vasodilator-stimulated phosphoprotein (va ...201323903326
onartuzumab (metmab): using nonclinical pharmacokinetic and concentration-effect data to support clinical development.we characterized the pharmacokinetics of onartuzumab (metmab) in animals and determined a concentration-effect relationship in tumor-bearing mice to enable estimation of clinical pharmacokinetics and target doses.201323894056
development of a validated liquid chromatography tandem mass spectrometry assay for a pegylated adnectin in cynomolgus monkey plasma using protein precipitation and trypsin digestion.a liquid chromatography tandem mass spectrometry (lc-ms/ms) method has been developed and validated for a pegylated adnectin therapeutic protein in cynomolgus monkey plasma. the validated method was performed using protein precipitation coupled with trypsin digestion, followed by lc-ms/ms detection of a surrogate peptide generated from the pegylated adnectin protein. a tryptic peptide generated from a pegylated adnectin protein analog was used as the internal standard to standardize the digestio ...201323891912
inhibition of spleen tyrosine kinase attenuates allergen-mediated airway constriction.spleen tyrosine kinase (syk) is a key activator of signaling pathways downstream of multiple surface receptors implicated in asthma. syk function has been extensively studied in mast cells downstream of the high-affinity ige receptor, fcεr1. preclinical studies have demonstrated a role for syk in models of allergic inflammation, but a role in airway constriction has not been demonstrated. here, we have used a potent and selective pharmacological inhibitor of syk to determine the role of syk in a ...201323889698
reproductive toxicity of denosumab in cynomolgus monkeys.denosumab is a monoclonal antibody that inhibits bone resorption by targeting rankl, an essential mediator of osteoclast formation, function, and survival. reproductive toxicity of denosumab was assessed in cynomolgus monkeys in an embryofetal development study (dosing gd20-50) and a pre-postnatal toxicity study (dosing gd20-parturition). in the embryofetal toxicity study, denosumab did not elicit maternal toxicity, fetal harm or teratogenicity. in the pre-postnatal toxicity study, there were in ...201323886817
synthesis and optimization of novel (3s,5r)-5-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)piperidine-3-carboxamides as orally active renin inhibitors.we report synthesis and optimization of a series of (3s,5r)-5-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)piperidine-3-carboxamides as renin inhibitors. chemical modification of p1', p2' and p3 portions led to a promising 3,5-disubstituted piperidine 32o showing high renin inhibitory activity and favorable oral exposure in both rats and cynomolgus monkeys with acceptable cyp and herg current inhibition. compound 32o exhibited a significant blood pressure lowering effect by oral administration in ...201323886807
quantification of β-cell insulin secretory function using a graded glucose infusion with c-peptide deconvolution in dysmetabolic, and diabetic cynomolgus monkeys.quantitation of β-cell function is critical in better understanding of the dynamic interactions of insulin secretion, clearance and action at different phases in the progression of diabetes. the present study aimed to quantify β-cell secretory function independently of insulin sensitivity in the context of differential metabolic clearance rates of insulin (mcri) in nonhuman primates (nhps).201323886319
differential expression of dipeptidyl peptidase iv in human versus cynomolgus monkey skin eccrine sweat glands.dipeptidyl peptidase iv (dpp4) is a peptidase whose inhibition is beneficial in type ii diabetes treatment. several evidences suggest potential implication of dpp4 in skin disorders such as psoriasis, keloids and fibrotic skin diseases where its inhibition could also be beneficial. dpp4 expression in human skin was described mainly in dermal fibroblasts and a subset of keratinocytes in the basal layer. of importance in the perspective of preclinical experimentation, dpp4 distribution in skin of ...201323880984
metabolism of fenofibrate in beagle dogs: new metabolites identified and metabolic pathways revealed.fenofibrate is a prototypical agonist of peroxisome proliferator-activated receptor alpha (pparalpha) which is well known to be associated with species related carcinogenesis. important species differences have been reported in its metabolism and elimination pattern. its new metabolites have been revealed in cynomolgus monkeys and sprague-dawley rats. however in beagle dogs, several polar metabolites of fenofibrate have not been identified yet. in this study, beagle dogs were orally dosed with f ...201323875247
birth origin differentially affects depressive-like behaviours: are captive-born cynomolgus monkeys more vulnerable to depression than their wild-born counterparts?adverse early-life experience might lead to the expression of abnormal behaviours in animals and the predisposition to psychiatric disorder (e.g. major depressive disorder) in humans. common breeding processes employ weaning and housing conditions different from what happens in the wild.201323861787
generation of haploid embryonic stem cells from macaca fascicularis monkey parthenotes.recent success in the derivation of haploid embryonic stem cells (haescs) from mouse via parthenogenesis and androgenesis has enabled genetic screening in mammalian cells and generation of gene-modified animals. however, whether haescs can be derived from primates remains unknown. here, we report the derivation of haescs from parthenogenetic blastocysts of macaca fascicularis monkeys. these cells, termed as pg-haescs, are pluripotent and can differentiate to cells of three embryonic germ layers ...201323856644
effect of an investigational cyp17a1 inhibitor, orteronel (tak-700), on estrogen- and corticoid-synthesis pathways in hypophysectomized female rats and on the serum estradiol levels in female cynomolgus monkeys.orteronel (tak-700) is an investigational, non-steroidal inhibitor of cyp17a1 with preferential inhibition of 17,20-lyase in nci-h295 cells. estrogen is synthesized from androgen by aromatase activity, and the effect of orteronel on estrogen synthesis was therefore evaluated. first, it was confirmed that orteronel does not directly inhibit aromatase activity. second, the specific decline of serum estradiol and androgen levels in hypophysectomized female rats by orteronel in comparison with aroma ...201323856460
body-centered, mixed, but not hand-centered coding of visual targets in the medial posterior parietal cortex during reaches in 3d space.the frames of reference used by neurons in posterior parietal cortex (ppc) to encode spatial locations during arm reaching movements is a debated topic in modern neurophysiology. traditionally, target location, encoded in retinocentric reference frame (rf) in caudal ppc, was assumed to be serially transformed to body-centered and then hand-centered coordinates rostrally. however, recent studies suggest that these transformations occur within a single area. the caudal ppc area v6a has been shown ...201423853212
topographically organized projection to posterior insular cortex from the posterior portion of the ventral medial nucleus in the long-tailed macaque monkey.prior anterograde tracing work identified somatotopically organized lamina i trigemino- and spinothalamic terminations in a cytoarchitectonically distinct portion of posterolateral thalamus of the macaque monkey, named the posterior part of the ventral medial nucleus (vmpo; craig [2004] j. comp. neurol. 477:119-148). microelectrode recordings from clusters of selectively thermoreceptive or nociceptive neurons were used to guide precise microinjections of various tracers in vmpo. a prior report ( ...201423853108
natural infection of cynomolgus monkeys with dengue virus occurs in epidemic cycles in the philippines.to investigate the potential role of non-human primates (nhps) in a dengue virus (denv) epidemic, we conducted serological and genomic studies using plasma samples collected from 100 cynomolgus monkeys (macaca fascicularis) in an animal breeding facility in the philippines. an elisa revealed 21 monkeys with a positive igm reaction and 19 positive for igg. five of the monkeys were positive for both igm and igg. of the 21 igm-positive samples, a neutralization assay identified seven containing den ...201323851439
dpp8 and dpp9 expression in cynomolgus monkey and sprague dawley rat tissues.dipeptidyl peptidases (dpps) are proteolytic enzymes that regulate many physiological systems by degrading signaling peptides. dpp8 and dpp9 are distinct from dpp4 in sequence, cellular localization and expression levels, thus implying distinct functions. however, dpp8 and dpp9 expression needs further delineation. we evaluated dpp4, dpp8 and dpp9 expression using three independent methods at the mrna, protein, and functional levels to better understand the local physiological contribution of ea ...201323850796
the effect of short moderate stress on the midbrain corticotropin-releasing factor system in a macaque model of functional hypothalamic amenorrhea.to study the effect of moderate stress on corticotropin-releasing factor (crf) components in the serotonergic midbrain region in a monkey model of functional hypothalamic amenorrhea.201323849846
askp1240, a fully human anti-cd40 monoclonal antibody, prolongs pancreatic islet allograft survival in nonhuman primates.a strategy for inhibiting cd40 has been considered as an alternative approach for immunosuppression because of undesirable effects of anti-cd154 monoclonal antibodies (mabs). previously, we demonstrated that askp1240, which is a fully human anti-cd40 mab, significantly prolonged kidney and liver allograft survival in cynomolgus monkeys without causing thromboembolic complications. herein, we evaluated the effect of askp1240 on pancreatic islet transplantation (pitx) in cynomolgus monkeys. diabet ...201323841873
meeting report: emerging respiratory viral infections and nonhuman primate case reports.a workshop on emerging respiratory viral infections and spontaneous diseases in nonhuman primates was sponsored by the concurrent annual meetings of the american college of veterinary pathologists and the american society for veterinary clinical pathology, held december 1-5, 2012, in seattle, washington. the session had platform presentations from drs karen terio, thijs kuiken, guy boivin, and robert palermo that focused on naturally occurring influenza, human respiratory syncytial virus, and me ...201323839235
muscle wasting associated with pathologic change is a risk factor for the exacerbation of joint swelling in collagen-induced arthritis in cynomolgus monkeys.not only joint destruction but also muscle wasting due to rheumatoid cachexia has been problem in terms of quality of life of patients with rheumatoid arthritis (ra). in the present study, we performed histopathological examination and assessed relationships between characteristic parameters relating to muscle and joint swelling in a collagen-induced arthritis (cia) model using cynomolgus monkeys (cms).201323834772
pharmacological profile of the selective β3-adrenoceptor agonist mirabegron in cynomolgus monkeys.mirabegron is a novel β3-adrenoceptor agonist developed for the treatment of overactive bladder. to clarify the relationship between the pharmacological effects of mirabegron in monkeys and the clinical efficacy in patients with overactive bladder, the effect of mirabegron on bladder function was evaluated using cynomolgus monkeys. quantitative pcr revealed that mrna expression of β3-adrenoceptors was most abundant (98 %) among β-adrenoceptor subtypes in the bladder of cynomolgus monkeys. mirabe ...201323832377
optimizing the transduction efficiency of capsid-modified aav6 serotype vectors in primary human hematopoietic stem cells in vitro and in a xenograft mouse model in vivo.although recombinant adeno-associated virus serotype 2 (aav2) vectors have gained attention because of their safety and efficacy in numerous phase i/ii clinical trials, their transduction efficiency in hematopoietic stem cells (hscs) has been reported to be low. only a few additional aav serotype vectors have been evaluated, and comparative analyses of their transduction efficiency in hscs from different species have not been performed.201323830234
effect of repeated apoa-imilano/popc infusion on lipids, (apo)lipoproteins, and serum cholesterol efflux capacity in cynomolgus monkeys.mdco-216, a complex of dimeric recombinant apoa-imilano (apoa-im) and palmitoyl-oleoyl-phosphatidylcholine (popc), was administered to cynomolgus monkeys at 30, 100, and 300 mg/kg every other day for a total of 21 infusions, and effects on lipids, (apo)lipoproteins, and ex-vivo cholesterol efflux capacity were monitored. after 7 or 20 infusions, free cholesterol (fc) and phospholipids (pl) were strongly increased, and hdl-cholesterol (hdl-c), apoa-i, and apoa-ii were strongly decreased. we then ...201323828780
systematic identification and characterization of glutathione s-transferases in cynomolgus macaque.glutathione s-transferases (gsts) are essential drug-metabolizing enzymes, involved in conjugation of various endogenous and exogenous substrates. cynomolgus macaque is an important primate species in drug metabolism studies; however, cynomolgus gsts have not been fully characterized. in this study the cdnas of 12 gsts (gsta3-a5, gstk1, gstm2-m4, gsto2, gstp1, gsts1, and gstt1/2) were isolated from cynomolgus macaque and rhesus macaque liver. cynomolgus gstm1 cdna was not amplified and only an a ...201323827461
interleukin-21 enhances rituximab activity in a cynomolgus monkey model of b cell depletion and in mouse b cell lymphoma models.rituximab, a monoclonal antibody targeting cd20 on b cells, is currently used to treat many subtypes of b cell lymphomas. however, treatment is not curative and response rates are variable. recombinant interleukin-21 (ril-21) is a cytokine that enhances immune effector function and affects both primary and transformed b cell differentiation. we hypothesized that the combination of ril-21 plus rituximab would be a more efficacious treatment for b cell malignancies than rituximab alone. we culture ...201323825648
sox-2 positive neural progenitors in the primate striatum undergo dynamic changes after dopamine denervation.the existence of endogenous neural progenitors in the nigrostriatal system could represent a powerful tool for restorative therapies in parkinson's disease. sox-2 is a transcription factor expressed in pluripotent and adult stem cells, including neural progenitors. in the adult brain sox-2 is expressed in the neurogenic niches. there is also widespread expression of sox-2 in other brain regions, although the neurogenic potential outside the niches is uncertain. here, we analyzed the presence of ...201323824751
induction of experimental autoimmune encephalomyelitis with recombinant human myelin oligodendrocyte glycoprotein in incomplete freund's adjuvant in three non-human primate species.the experimental autoimmune encephalitis (eae) model is used for preclinical research into the pathogenesis of multiple sclerosis (ms), mostly in inbred, specific pathogen free (spf)-raised laboratory mice. however, the naive state of the laboratory mouse immune system is considered a major hurdle in the translation of principles from the eae model to the ms patient. non-human primates (nhp) have an immune system harboring t- and b-cell memory against environmental antigens, similar as in humans ...201323821341
comparison of high-definition oscillometry -- a non-invasive technology for arterial blood pressure measurement -- with a direct invasive method using radio-telemetry in awake healthy cats.this study compared indirect blood pressure measurements using a non-invasive method, high-definition oscillometry (hdo), with direct measurements using a radio-telemetry device in awake cats. paired measurements partitioned to five sub-ranges were collected in six cats using both methods. the results were analysed for assessment of correlation and agreement between the two methods, taking into account all pressure ranges, and with data separated in three sub-groups, low, normal and high ranges ...201323813147
development and preclinical characterization of a humanized antibody targeting cxcl12.our goal was to develop a potent humanized antibody against mouse/human cxcl12. this report summarized its in vitro and in vivo activities.201323812669
radiosynthesis and evaluation of new α1-adrenoceptor antagonists as pet radioligands for brain imaging.evaluation of the α1-adrenoceptors in relation to brain pathophysiology and drug treatment has been hindered by lack of α1-adrenoceptor specific radioligands with sufficient brain exposure. our aim was to develop an α1-adrenoceptor specific pet radioligand for brain imaging.201323810488
thymic stromal lymphopoietin receptor blockade reduces allergic inflammation in a cynomolgus monkey model of asthma.thymic stromal lymphopoietin (tslp) pathway blockade is a potential strategy for asthma treatment because the main activities of tslp are activation of myeloid dendritic cells (mdcs) and modulation of cytokine production by mast cells. tslp-activated mdcs prime the differentiation of naive t cells into inflammatory th2 cells.201323810153
protein expression, biochemical pharmacology of signal transduction, and relation to intraocular pressure modulation by bradykinin b₂ receptors in ciliary muscle.to examine the bradykinin (bk) b₂-receptor system in human and monkey ciliary muscle (cm) using immunohistochemical techniques, and to pharmacologically characterize the associated biochemical signal transduction systems in human cm (h-cm) cells. bk-induced modulation of intraocular pressure (iop) in pigmented dutch-belt rabbits and cynomolgus monkeys was also studied.201323805043
macaque paneth cells express lymphoid chemokine cxcl13 and other antimicrobial peptides not previously described as expressed in intestinal crypts.cxcl13 is a constitutively expressed chemokine that controls migration of immune cells to lymphoid follicles. previously, we found cxcl13 mrna levels increased in rhesus macaque spleen tissues during aids. this led us to examine the levels and locations of cxcl13 by detailed in situ methods in cynomolgus macaque lymphoid and intestinal tissues. our results revealed that there were distinct localization patterns of cxcl13 mrna compared to protein in germinal centers. these patterns shifted during ...201323803902
effect of physical restraint on glucose tolerance in cynomolgus monkeys.physiologic stress has been demonstrated to impair glucose tolerance.201323802316
expression levels of 10 candidate genes in lung tissue of vaccinated and tb-infected cynomolgus macaques.the expression of ten tuberculosis candidate genes in lung and lymph nodes of cynomolgus macaques vaccinated and experimentally infected with mycobacterium tuberculosis (mtb) was quantified. the expression of tnfα, il10, il1β, tlr4, il17, il6, il12, and inos in the lungs of vaccinated animals was higher than that of non-vaccinated animals.201323802315
radiologic responses in cynomolgus macaques for assessing tuberculosis chemotherapy regimens.trials to test new drugs currently in development against tuberculosis in humans are impractical. all animal models to prioritize new regimens are imperfect, but nonhuman primates (nhps) infected with mycobacterium tuberculosis develop active tuberculosis (tb) disease with a full spectrum of lesion types seen in humans. serial 2-deoxy-2-[(18)f]-fluoro-d-glucose (fdg) positron emission tomography (pet) with computed tomography (ct) imaging was performed on cynomolgus macaques during infection and ...201323796926
endometrial profile of bazedoxifene acetate alone and in combination with conjugated equine estrogens in a primate model.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 in combinati ...201323793168
comprehensive identification of high-frequency and co-occurring mafa-dpa1, mafa-dqa1, mafa-dra, and mafa-doa alleles in vietnamese cynomolgus macaques.high-frequency alleles and/or co-occurring human leukocyte antigen alleles across loci appear to be more important than individual alleles as markers of disease risk and have clinical value as biomarkers for targeted screening or the development of new disease therapies. to better elucidate the major histocompatibility complex (mhc) background and to facilitate the experimental use of cynomolgus macaques, mafa-dpa1, mafa-dqa1, mafa-dra, and mafa-doa alleles were characterized, and their combinat ...201323793105
cynomolgus monkey induced pluripotent stem cells established by using exogenous genes derived from the same monkey species.induced pluripotent stem (ips) cells established by introduction of the transgenes pou5f1 (also known as oct3/4), sox2, klf4 and c-myc have competence similar to embryonic stem (es) cells. ips cells generated from cynomolgus monkey somatic cells by using genes taken from the same species would be a particularly important resource, since various biomedical investigations, including studies on the safety and efficacy of drugs, medical technology development, and research resource development, have ...201323792767
acute-phase cd8 t cell responses that select for escape variants are needed to control live attenuated simian immunodeficiency virus.the overall cd8 t cell response to human/simian immunodeficiency virus (hiv/siv) targets a collection of discrete epitope specificities. some of these epitope-specific cd8 t cells emerge in the weeks and months following infection and rapidly select for sequence variants, whereas other cd8 t cell responses develop during the chronic infection phase and rarely select for sequence variants. in this study, we tested the hypothesis that acute-phase cd8 t cell responses that do not rapidly select for ...201323785211
characterization of microsomal glutathione s-transferases mgst1, mgst2, and mgst3 in cynomolgus macaque.the glutathione s-transferase (gst) family comprises cytosolic, mitochondrial, and microsomal gsts, all essential enzymes that metabolize a wide range of endogenous and exogenous substrates. among the microsomal gsts (mgsts) in humans, mgst1, mgst2, and mgst3 are involved in detoxification; however, mgsts have not been fully investigated in cynomolgus macaque, an important primate species widely used in drug metabolism and toxicity studies. in the present study, cynomolgus mgst2 and mgst3 cdnas ...201323785063
a novel truncated glucagon-like peptide 2 (glp-2) as a tool for analyzing glp-2 receptor agonists.glucagon-like peptide 2 (glp-2) is an intestinotropic peptide that binds to glp-2 receptor (glp-2r), a class-b g protein-coupled receptor. the glp-2r antagonist glp-2(3-33) has relatively high partial agonistic activity, and there are as yet no ideal known potent glp-2r antagonists. we therefore prepared several truncated forms of human glp-2 and characterized them by binding and reporter assays to find antagonists more potent than glp-2(3-33). we found that glp-2(11-33) was the most potent orth ...201323782746
a strategy for risk mitigation of antibodies with fast clearance.a majority of human therapeutic antibody candidates show pharmacokinetic properties suitable for clinical use, but an unexpectedly fast antibody clearance is sometimes observed that may limit the clinical utility. pharmacokinetic data in cynomolgus monkeys collected for a panel of 52 antibodies showed broad distribution of target-independent clearance values (2.4-61.3 ml/day/kg), with 15 (29%) having clearance > 10 ml/day/kg. alteration in the interaction with the recycling fcrn receptor did not ...201223778268
trim5α polymorphism identification in cynomolgus macaques of vietnamese origin and chinese rhesus macaques.trim5α is a retroviral restriction factor, in which the b30.2 (spry) and coiled-coil domains cooperate to determine the specificity of trim5α-mediated capture of retroviral capsids. here, all exons of trim5α were analyzed in 39 vietnamese cynomolgus macaques (vce) and 29 chinese rhesus macaques (cr). our results revealed the presence of 22 alleles using the phase 2.0 software package (phylogenetics and sequence evolution), including two novel species-specific alleles with a low frequency in vce ...201323775985
persistent human hepatitis b virus infection in cynomolgus monkeys: a novel animal model in the search for a cure? 201323775673
eldecalcitol, a vitamin d analog, reduces bone turnover and increases trabecular and cortical bone mass, density, and strength in ovariectomized cynomolgus monkeys.vitamin d insufficiency is common in elderly people worldwide, and intake of supplementary calcium and vitamin d is recommended to those with a high risk of fracture. several clinical studies and meta-analyses have shown that calcium and vitamin d supplementation reduces osteoporotic fractures, and a strong correlation exists between vitamin d status and fracture risk. vitamin d supplementations improve calcium balance in the body; however, it remains unclear whether vitamin d directly affects b ...201323774444
a method for conducting functional mri studies in alert nonhuman primates: initial results with opioid agonists in male cynomolgus monkeys.functional mri (fmri) has emerged as a powerful technique for assessing neural effects of psychoactive drugs and other stimuli. several experimental approaches have been developed to use fmri in anesthetized and awake animal subjects, each of which has its advantages and complexities. we sought to assess whether one particular method to scan alert postanesthetized animals can be used to assess fmri effects of opioid agonists. to date, the use of fmri as a method to compare pharmacological effect ...201323773004
dietary soy effects on mammary gland development during the pubertal transition in nonhuman primates.while epidemiologic studies suggest that soy intake early in life may reduce breast cancer risk, there are also concerns that exposure to soy isoflavones during childhood may alter pubertal development and hormonal profiles. here, we assessed the effect of a high-soy diet on pubertal breast development, sex hormones, and growth in a nonhuman primate model. pubertal female cynomolgus monkeys were randomized to receive a diet modeled on a typical north american diet with one of two protein sources ...201323771522
death receptor 5 agonistic antibody pro95780: preclinical pharmacokinetics and concentration-effect relationship support clinical dose and regimen selection.pro95780, a human monoclonal antibody (mab) against death receptor 5 (dr5/trail-r2/tnfrsf10b), was developed for the treatment for cancer. our objective was to characterize pharmacokinetics (pk) in mice, rats, and cynomolgus monkeys and concentration-effect relationships of pro95780 in xenograft mouse models of human cancers; this would guide the selection of dose and regimen for clinical trials.201323771513
asynchronous onset of clinical disease in bse-infected macaques.to estimate the effect of the variability of prion disease onset on primary bovine spongiform encephalopathy transmission to humans, we studied 6 cynomolgus macaques. the preclinical incubation period was significantly prolonged in 2 animals, implying that onset of variant creutzfeldt-jacob disease in humans could be more diverse than previously expected.201323764183
age- and sex-based hematological and biochemical parameters for macaca fascicularis.the cynomolgus monkey (macaca fascicularis) has been increasingly used in biomedical research, making knowledge of its blood-based parameters essential to support the selection of healthy subjects and its use in preclinical research. as age and sex affect these blood-based parameters, it is important to establish baseline indices for these parameters on an age and sex basis and determine the effects of age and sex on these indices.201323762263
in vivo imaging of the glucagonlike peptide 1 receptor in the pancreas with 68ga-labeled do3a-exendin-4.the glucagonlike peptide 1 receptor (glp-1r) is mainly expressed on β-cells in the islets of langerhans and is therefore an attractive target for imaging of the β-cell mass. in the present study, (68)ga-labeled exendin-4 was evaluated for pet imaging and quantification of glp-1r in the pancreas.201323761918
effects of estradiol on transcriptional profiles in atherosclerotic iliac arteries in ovariectomized cynomolgus macaques.this study aimed to assess the in vivo effects of estradiol treatment on arterial gene expression in atherosclerotic postmenopausal female monkeys.201423760433
isolation and characterization of toxigenic corynebacterium ulcerans from 2 closed colonies of cynomolgus macaques (macaca fascicularis) in japan.the aim of the present study was to determine the prevalence of infection by toxigenic corynebacterium ulcerans in cynomolgus macaques (macaca fascicularis) housed in an animal facility in japan. samples from the pharynges of animals from 2 closed colonies (colony a, n = 47; colony b, n = 21) were cultured. c. ulcerans grew from 43% and 47% of the samples from colonies a and b, respectively. the toxigenicity of these isolates was assessed by using pcr analysis for the diphtheria toxin gene and t ...201323759530
differential response of the cynomolgus macaque gut microbiota to shigella infection.little is known about the role of gut microbiota in response to live oral vaccines against enteric pathogens. we examined the effect of immunization with an oral live-attenuated shigella dysenteriae 1 vaccine and challenge with wild-type s. dysenteriae 1 on the fecal microbiota of cynomolgus macaques using 16 s rrna analysis of fecal samples. multi-dimensional cluster analysis identified different bacterial community types within macaques from geographically distinct locations. the fecal microbi ...201323755118
the use of a polycaprolactone-tricalcium phosphate scaffold for bone regeneration of tooth socket facial wall defects and simultaneous immediate dental implant placement in macaca fascicularis.bone regeneration and aesthetic outcomes may be compromised when immediate implants are placed at extraction sites with dehiscence defects. the aim of this study was to compare, in a monkey model, peri-implant bone regeneration and implant stability after immediate implant placement into tooth sockets with facial wall defects in two treatment groups. in eight control monkeys, the bony defect was reconstructed with autogenous particulate bone, whereas in 10 test monkeys a polycaprolactone-tricalc ...201423733534
a novel assay to measure b cell responses to keyhole limpet haemocyanin vaccination in healthy volunteers and subjects with systemic lupus erythematosus.the aim of the study was to characterize performance of a complementary set of assays to measure antigen-specific immune responses in subjects immunized with a neoantigen. healthy volunteers (hv) (n = 8) and patients with systemic lupus erythematosus (sle) (n = 6) were immunized with keyhole limpet haemocyanin (klh) on days 1 and 29. serum antibodies were detected using a flow cytometric bead array (cba) that multiplexed the klh response alongside pre-existing anti-tetanus antibodies. peripheral ...201323731388
cynomolgus monkey gallbladder bile contains high concentrations of fibroblast growth factor 19. 201423729389
variation in hair δ(13)c and δ (15)n values in long-tailed macaques (macaca fascicularis) from singapore.much of the primatology literature on stable isotope ratios of carbon (δ(13)c) and nitrogen (δ(15)n) has focused on african and new world species, with comparatively little research published on asian primates. here we present hair δ(13)c and δ(15)n isotope values for a sample of 33 long-tailed macaques from singapore. we evaluate the suggestion by a previous researcher that forest degradation and biodiversity loss in singapore have led to a decline in macaque trophic level. the results of our a ...201423729223
indocyanine green fluorescence imaging in the pregnant cynomolgus macaque: childbearing is supported by a unilateral uterine artery and vein alone?uterine blood flow is required for the maintenance of uterine viability in pregnancy and delivery, but it is unknown how many vessels are necessary for maintenance of uterine viability. the objective of this study was to examine whether unilateral uterine vessels provide sufficient nutrition in pregnancy in a cynomolgus macaque and to evaluate hemodynamics of pregnant uterus by indocyanine green (icg) fluorescence imaging.201323722286
immunoreactivity for choline acetyltransferase of peripheral-type (pchat) in the trigeminal ganglion neurons of the non-human primate macaca fascicularis.transcripts of the choline acetyltransferase (chat) gene reveal a number of different splice variants including chat of a peripheral type (pchat). immunohistochemical staining of the brain using an antibody against pchat clearly revealed peripheral cholinergic neurons, but failed to detect cholinergic neurons in the central nervous system. in rodents, pchat-immunoreactivity has been detected in cholinergic parasympathetic postganglionic and enteric ganglion neurons. in addition, pchat has been o ...201323720604
estradiol and brain serotonin reuptake transporter in long-term ovariectomized parkinsonian monkeys.this study evaluated the effect of a one month 17β-estradiol treatment on brain serotonin (5-ht) reuptake transporter (sert) in long-term ovariectomized (ovx) female monkeys (macaca fascicularis) bearing a unilateral lesion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (mptp) injected directly into the left substantia nigra modeling parkinson disease (pd). ovariectomy and mptp lesion were performed four years before the estrogen treatment to model postmenopausal pd patients. sert was measure ...201323719069
expression patterns of killer cell immunoglobulin-like receptors (kir) of nk-cell and t-cell subsets in old world monkeys.the expression of killer cell immunoglobulin-like receptors (kir) on lymphocytes of rhesus macaques and other old world monkeys was unknown so far. we used our recently established monoclonal anti-rhesus macaque kir antibodies in multicolour flow cytometry for phenotypic characterization of kir protein expression on natural killer (nk) cells and t cell subsets of rhesus macaques, cynomolgus macaques, hamadryas baboons, and african green monkeys. similar to human kir, we found clonal expression p ...201323717676
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