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massive mobilization of dendritic cells during influenza a virus subtype h5n1 infection of nonhuman primates.highly pathogenic avian influenza virus infection is characterized by a marked inflammatory response, but the impact of infection on dendritic cells (dcs) is unknown. we show that influenza a virus subtype h5n1 infection rapidly and profoundly impacts dcs in cynomolgus macaques, increasing the number of blood myeloid and plasmacytoid dcs by 16- and 60-fold, respectively. infection was associated with recruitment, activation, and apoptosis of dcs in lung-draining lymph nodes; granulocyte and macr ...201424403559
chikungunya vaccine candidate is highly attenuated and protects nonhuman primates against telemetrically monitored disease following a single dose.chikungunya virus (chikv) is a mosquito-borne alphavirus that causes major epidemics of rash, fever, and debilitating arthritis. currently, there are no vaccines or antivirals available for prevention or treatment. we therefore generated 2 live-attenuated vaccine candidates based on the insertion of a picornavirus internal ribosome entry site (ires) sequence into the genome of chikv. vaccination of cynomolgus macaques with a single dose of either vaccine produced no signs of disease but was high ...201424403555
the immunogenicity and protection effect of the bpl-inactivated ca16 vaccine in different animal systems.we evaluated the effect of a β-propiolactone (bpl)-inactivated coxsackievirus a16 (ca16) vaccine, using three immunogenicity evaluation and two animal challenge systems. a ca16 virus strain, named 419, was used as the production strain. another ca16 strain, named 1131, was isolated and used as the challenge strain in intracerebral inoculation of neonatal mice for the calculation of median lethal dose (ld 50). in the passive and maternal antibody-protection challenge systems, all results indicate ...201424401488
outbreak of pathogenic escherichia coli in an outdoor-housed non-human primate colony.pathogenic escherichia coli has been identified as an etiologic agent in humans causing acute diarrhea or even death but has been rarely reported in non-human primates (nhp). an outbreak of diarrhea occurred in an outdoor-housed nhp colony over a period of 2 months with an attack rate of 29%.201424400996
occurrence of multinucleated hepatocytes in cynomolgus monkeys (macaca fascicularis) from different geographical regions.multinucleated hepatocytes (mnhs) have been occasionally reported in macaques, as well as chimpanzees and gorillas, as an incidental finding. however, information is sparse on variations in incidence in the cynomolgus macaque (macaca fascicularis). a survey was conducted to assess the occurrence of mnhs in the liver of stock (nonstudy) animals from snbl src (alice, tx) and snbl usa (everett, wa) submitted for diagnostic purposes. a total of 215 cynomolgus monkeys originally from cambodia (61), c ...201424395914
distinction between hand dominance and hand preference in primates: a behavioral investigation of manual dexterity in nonhuman primates (macaques) and human subjects.background the present study aimed to determine and confront hand preference (hand chosen in priority to perform a manual dexterity task) and hand dominance (hand with best motor performance) in eight macaques (macaca fascicularis) and in 20 human subjects (10 left-handers and 10 right-handers). methods four manual dexterity tests have been executed by the monkeys, over several weeks during learning and stable performance phases (in controlled body position): the modified brinkman board, the rea ...201324392278
placental transfer of fc-containing biopharmaceuticals across species, an industry survey analysis.understanding species differences in placental transfer of fc-containing biopharmaceuticals (particularly monoclonal antibodies) will improve human risk extrapolation from nonclinical embryo-fetal development toxicity data.201324391099
pharmacokinetics and pharmacodynamics of askp1240, a fully human anti-cd40 antibody, in normal and renal transplanted cynomolgus monkeys.the purpose of this study was to evaluate the serum concentration of askp1240 (pharmacokinetics [pk]) and the cd40 occupancy of askp1240 (pharmacodynamics [pd]) in normal and renal transplanted cynomolgus monkeys to clarify the pk/pd relationship.201424389907
protection against h5n1 highly pathogenic avian and pandemic (h1n1) 2009 influenza virus infection in cynomolgus monkeys by an inactivated h5n1 whole particle vaccine.h5n1 highly pathogenic avian influenza virus (hpaiv) infection has been reported in poultry and humans with expanding clade designations. therefore, a vaccine that induces immunity against a broad spectrum of h5n1 viruses is preferable for pandemic preparedness. we established a second h5n1 vaccine candidate, a/duck/hokkaido/vac-3/2007 (vac-3), in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of h5n1 hpaiv strains that caused severe ...201324376571
deleterious impact of feto-maternal mhc compatibility on the success of pregnancy in a macaque model.the impact of feto-maternal histocompatibility on reproduction has inspired long-lasting debates. however, after the review of numerous articles, the impact of hla allele sharing within couples on fecundity remains questionable. we decided to explore the impact of major histocompatibility complex (mhc) feto-maternal compatibility on reproduction in a cynomolgus macaque facility composed of animals of mauritian descent. the mauritian-derived macaque population presents a very restricted mhc polym ...201424374979
pharmacological characterization of the novel γ-secretase modulator as2715348, a potential therapy for alzheimer's disease, in rodents and nonhuman primates.γ-secretase is the enzyme responsible for the intramembranous proteolysis of various substrates, such as amyloid precursor protein (app) and notch. amyloid-β peptide 42 (aβ42) is produced through the sequential proteolytic cleavage of app by β- and γ-secretase and causes the synaptic dysfunction associated with memory impairment in alzheimer's disease. here, we identified a novel cyclohexylamine-derived γ-secretase modulator, {(1r*,2s*,3r*)-3-[(cyclohexylmethyl)(3,3-dimethylbutyl)amino]-2-[4-(tr ...201424373902
detection of qtc interval prolongation using jacket telemetry in conscious non-human primates: comparison with implanted telemetry.during repeat-dose toxicity studies, ecgs are collected from chemically or physically-restrained animals over a short timeframe. this is problematic due to cardiovascular changes caused by manual restraint stress and anesthesia, and limited ecg sampling. these factors confound data interpretation, but may be overcome by using a non-invasive jacket-based ecg collection (jet). the current study investigated whether a jacketed external telemetry system could detect changes in cardiac intervals and ...201424372552
use of contrast-enhanced sonography to investigate intraneural vascularity in a cohort of macaca fascicularis with suspected median mononeuropathy.the purpose of this study was to provide clinical evidence of the use of contrast-enhanced sonography in detecting and quantifying changes in intraneural vascularity due to median mononeuropathy.201424371104
the metabolism of trifluoperazine (tfp) exhibits atypical kinetic behavior in both human liver microsomes (hlms) and monkey liver microsomes (mylm).glucuronidation reaction of trifluoperazine (tfp) is a typical probe reaction to phenotype the activity of udp-glucuronosyltransferase 1a4. the present study aims to compare the metabolic behavior of tfp in the liver microsomes from human and cynomolgus monkey, including the kinetic type and parameters. in vitro human liver microsome incubation system was used. the eadie-hofstee plot was used to determine the kinetic type. the results showed that the data for human liver microsomes (hlms) and mo ...201424370939
cardiopulmonary bypass induces recruitment of bone marrow-derived leukocytes to the lungs in monkeys.a bone marrow (bm) response induced by cardiopulmonary bypass (cpb) as a systemic inflammatory reaction has previously been postulated but not clarified. newly released polymorphonuclear leukocytes (pmns) and monocytes from the bm are known to be immature, indicating their greater potential to damage tissue. the present study aimed to examine the kinetics of bm-derived leukocytes associated with cpb in a nonhuman primate model.201424370199
vesicular stomatitis virus-based vaccines protect nonhuman primates against bundibugyo ebolavirus.ebola virus (ebov) causes severe and often fatal hemorrhagic fever in humans and nonhuman primates (nhps). currently, there are no licensed vaccines or therapeutics for human use. recombinant vesicular stomatitis virus (rvsv)-based vaccine vectors, which encode an ebov glycoprotein in place of the vsv glycoprotein, have shown 100% efficacy against homologous sudan ebolavirus (sebov) or zaire ebolavirus (zebov) challenge in nhps. in addition, a single injection of a blend of three rvsv vectors co ...201324367715
experimental infection of macaques with a wild water bird-derived highly pathogenic avian influenza virus (h5n1).highly pathogenic avian influenza virus (hpaiv) continues to threaten human health. non-human primate infection models of human influenza are desired. to establish an animal infection model with more natural transmission and to determine the pathogenicity of hpaiv isolated from a wild water bird in primates, we administered a japanese isolate of hpaiv (a/whooper swan/hokkaido/1/2008, h5n1 clade 2.3.2.1) to rhesus and cynomolgus monkeys, in droplet form, via the intratracheal route. infection of ...201324367600
a new phenylpyrazoleanilide, y-320, inhibits interleukin 17 production and ameliorates collagen-induced arthritis in mice and cynomolgus monkeys.interleukin (il)-15 and il-17 are thought to play an important role in the pathogenesis of rheumatoid arthritis (ra) because both pro-inflammatory cytokines are found in synovial fluid of ra patients. in this study, we examined the pharmacological profiles of y-320, a new phenylpyrazoleanilide immunomodulator. y-320 inhibited il-17 production by cd4 t cells stimulated with il-15 with ic50 values of 20 to 60 nm. oral administration of y-320 (0.3 to 3 mg/kg) significantly inhibited the development ...201324366113
eye movements reveal planning in humans: a comparison with scarf and colombo's (2009) monkeys.on sequential response tasks, a long pause preceding the first response is thought to reflect participants taking time to plan a sequence of responses. by tracking the eye movements of two monkeys (macaca fascicularis), scarf and colombo (2009, eye movements during list execution reveal no planning in monkeys [macaca fascicularis], journal of experimental psychology: animal behavior processes, vol. 35, pp. 587-592) demonstrated that, at least with respect to monkeys, the long pause preceding the ...201424364670
effects of a farnesoid x receptor antagonist on hepatic lipid metabolism in primates.we aimed to elucidate the mechanism underlying the anti-dyslipidemic effect of compound-t3, a farnesoid x receptor antagonist, by investigating its effects on hepatic lipid metabolism in non-human primates. we administered lipid-lowering drugs for 7 days to cynomolgus monkeys receiving a high-fat diet, and subsequently measured the levels of lipid parameters in plasma, feces, and hepatic tissue fluids. compound-t3 (0.3 and 3mg/kg p.o.) significantly decreased the plasma levels of non-high-densit ...201424361308
identification and characterization of micrornas in the crab-eating macaque (macaca fascicularis) using transcriptome analysis.micrornas (mirnas), with an average length between 16 nt and 26 nt, are small non-coding rnas that can repress gene expression on the post-transcriptional level. macaca fascicularis (m. fascicularis), one of the most important nonhuman primate animal models, is widely used in basic and applied preclinical research, especially in studies that involve neuroscience and disease. however, due to the lack of a complete genome sequence, the mirnas in m. fascicularis have not been completely characteriz ...201424355555
preclinical and clinical development of a yfv 17 d-based chimeric vaccine against west nile virus.substantial success has been achieved in the development and implementation of west nile (wn) vaccines for horses; however, no human wn vaccines are approved. this review focuses on the construction, pre-clinical and clinical characterization of chimerivax-wn02 for humans, a live chimeric vaccine composed of a yellow fever (yf) 17d virus in which the prm-e envelope protein genes are replaced with the corresponding genes of the wn ny99 virus. pre-clinical studies demonstrated that chimerivax-wn02 ...201324351795
postnatal change in sulcal length asymmetry in cerebrum of cynomolgus monkeys (macaca fascicularis).the purpose of this study was to determine the timing of the onset of adult-type sulcal length asymmetry during postnatal development of the male cynomolgus monkey cerebrum. the monkey brain has already reached adult size by 3 months of age, although the body weight only represents 1/8 of the adult body weight by that time. the fronto-occipital length and the cerebral width also reached adult levels by that postnatal age with no left/right bias. consistently, lengths of the major primary sulci r ...201424347432
dynamic hyperpolarized carbon-13 mr metabolic imaging of nonhuman primate brain.to investigate hyperpolarized (13) c metabolic imaging methods in the primate brain that can be translated into future clinical trials for patients with brain cancer.201424346964
polymorphisms and interspecies differences of the activating and inhibitory fcγrii of macaca nemestrina influence the binding of human igg subclasses.little is known of the impact of fc receptor (fcr) polymorphism in macaques on the binding of human (hu)igg, and nothing is known of this interaction in the pig-tailed macaque (macaca nemestrina), which is used in preclinical evaluation of vaccines and therapeutic abs. we defined the sequence and huigg binding characteristics of the m. nemestrina activating fcγriia (mnfcγriia) and inhibitory fcγriib (mnfcγriib) and predicted their structures using the huiggfc/hufcγriia crystal structure. large d ...201424342805
sterilization of granulomas is common in active and latent tuberculosis despite within-host variability in bacterial killing.over 30% of the world's population is infected with mycobacterium tuberculosis (mtb), yet only ∼5-10% will develop clinical disease. despite considerable effort, researchers understand little about what distinguishes individuals whose infection progresses to active tuberculosis (tb) from those whose infection remains latent for decades. the variable course of disease is recapitulated in cynomolgus macaques infected with mtb. active disease occurs in ∼45% of infected macaques and is defined by cl ...201424336248
expression and characterization of cynomolgus monkey cytochrome cyp3a4 in a novel human embryonic kidney cell-based mammalian system.cynomolgus monkeys are a commonly used species in preclinical drug discovery, and have high genetic similarity to humans, especially for the drug-metabolizing cytochrome p450s. however, species differences are frequently observed in the metabolism of drugs between cynomolgus monkeys and humans, and delineating these differences requires expressed cyps. toward this end, cynomolgus monkey cyp3a4 (c3a4) was cloned and expressed in a novel human embryonic kidney 293-6e cell suspension system. follow ...201424335510
primate cerebellar granule cells exhibit a tonic gabaar conductance that is not affected by alcohol: a possible cellular substrate of the low level of response phenotype.in many rodent brain regions, alcohol increases vesicular release of gaba, resulting in an increase in the frequency of spontaneous inhibitory postsynaptic currents (sipscs) and the magnitude of tonic gabaa receptor (gabaar) currents. a neglected issue in translating the rodent literature to humans is the possibility that phylogenetic differences alter the actions of alcohol. to address this issue we made voltage-clamp recordings from granule cells (gcs) in cerebellar slices from the non-human p ...201324324408
a nonhuman primate model of human radiation-induced venocclusive liver disease and hepatocyte injury.human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease.201424315566
bovine alpha-2-hs-glycoprotein functions as a booster antigen for efficiently stimulating humoral immune responses to ccr5 and sivmac239 envelope glycoprotein.the presence of anti-ccr5 and anti-hiv-1 envelope glycoprotein (env) gp41 antibodies (abs) at sites of hiv-1 exposure was effective in preventing its transmission to hiv-1-exposed seronegative (esn) subjects. here, we design an immunogen that can induce abs against ccr5 and sivmac239 env simultaneously and show that bovine alpha-2-hs-glycoprotein (bahsg) functions as a booster antigen for efficiently stimulating humoral immune responses to ccr5 and env. initially, we generated a rhesus ccr5-deri ...201424309114
home cage locomotor changes in non-human primates after prolonged welding-fume exposure.to define the relationship between the brain concentration of manganese and neurological signs, such as locomotion, after prolonged welding-fume exposure, cynomolgus monkeys were acclimated for 1 month and then divided into three concentration groups: unexposed, low concentration (31 mg/m(3) total suspended particulate (tsp), 0.9 mg/m(3) of mn), and high concentration (62 mg/m(3) tsp, 1.95 mg/m(3) of mn) of tsp. the monkeys were exposed to manual metal-arc stainless steel (mma-ss) welding fumes ...201324304306
low brain cb1 receptor occupancy by a second generation cb1 receptor antagonist tm38837 in comparison with rimonabant in nonhuman primates: a pet study.both central and peripheral cannabinoid receptor type 1 (cb1r) have been considered to be among the key targets for obesity treatment. first generation cb1r antagonists/inverse agonists such as rimonabant and taranabant exhibited severe cns side effects such as anxiety and depression, which are considered to be related to the compounds' ability to access central cb1r. recently, several compounds have been developed as second generation antagonists with a profile of restriction to peripheral cb1r ...201424293119
epithelial mesenchymal transition-like phenomenon in trabecular meshwork cells.the trabecular meshwork (tm) is a major component of the conventional outflow pathway and the excess extracellular matrix (ecm), and fibrosis in the tm causes increased outflow resistance. in this study, we first investigated the effects of several ecm components in the induction of an epithelial mesenchymal transition (emt)-like phenomenon in tm cells. tm cells were isolated from cynomolgus monkeys (macaca fascicularis). the cells were cultured in ecm-coated dishes and then subjected to both we ...201424291802
mechanistic pharmacokinetic/target engagement/pharmacodynamic (pk/te/pd) modeling in deciphering interplay between a monoclonal antibody and its soluble target in cynomolgus monkeys.for therapeutic monoclonal antibodies (mabs) against soluble ligands, the free ligand level can, theoretically, be used as a surrogate for efficacy. however, it can be extremely challenging technically to measure free ligand level in the presence of an excessive amount of antibody-ligand complex. the interplay among such mabs, ligands, and the downstream pharmacodynamic (pd) effects has not been well defined. using siltuximab and interleukin-6 (il-6) as model compounds, a pharmacokinetic (pk)/ta ...201424287601
ontogeny of material stiffness heterogeneity in the macaque mandibular corpus.evidence is accumulating that bone material stiffness increases during ontogeny, and the role of elastic modulus in conditioning attributes of strength and toughness is therefore a focus of ongoing investigation. developmental changes in structural properties of the primate mandible have been documented, but comparatively little is known about changes in material heterogeneity and their impact on biomechanical behavior. we examine a cross-sectional sample of macaca fascicularis (n = 14) to inves ...201424282152
a novel approach to evaluate the pharmacokinetic biocomparability of a monoclonal antibody derived from two different cell lines using simultaneous crossover design.a parallel study design with a large number of subjects has been a typical path for pharmacokinetic (pk) biocomparability assessment of biotherapeutics with long half-lives and immunogenic propensity, for example, monoclonal antibodies (mab). a recently published innovative bioanalytical method that can quantify mab produced from two different cell lines in the same sample opened an avenue to exploring a simultaneous crossover study design for pk biocomparability assessment of biotherapeutics. s ...201424281691
milk transfer and toxicokinetics of valproic acid in lactating cynomolgus monkeys.studies on milk transfer of drugs in non-human primates (nhps) are among the crucial components in the assessment of peri- and postnatal toxicity because of the similarity between nhps and humans. to evaluate the milk transfer of valproic acid (vpa) in nhps, the toxicokinetics of vpa, an antiepileptic drug, were studied in pregnant cynomolgus monkeys. vpa was administered once daily to pregnant cynomolgus monkeys at doses of 0, 30, 90, and 270 mg/kg by oral gavage from day 100 of gestation (gd 1 ...201324278629
placenta transfer and toxicokinetics of valproic acid in pregnant cynomolgus monkeys.placenta transfer study in non-human primate (nhp) is one of the crucial components in the assessment of developmental toxicity because of the similarity between nhp and humans. to establish the method to determine placenta transfer in non-human primate, toxicokinetics of valproic acid (vpa) , a drug used to treat epilepsy in pregnant women, were determined in pregnant cynomolgus monkeys. after mating, pregnancy-proven females were daily administered with vpa at dose levels of 0, 20, 60 and 180 ...201024278535
tumor necrosis therapy antibody interleukin-2 fusion protein elicits prolonged and targeted antitumor effects in vivo.interleukin-2 (il-2) is one of the most successful cytokines applied in tumor immunotherapy because of its ability to stimulate potent cellular immune response. the life-threatening toxicity of vascular leak syndrome (vls) associated with the high-dose il-2 treatment regimen has limited its use in tumor immunotherapy. to reverse this situation, a tumor-targeted fusion protein, recombinant human tnt-il2 (rhtnt-il2), was generated with both the cytokine activity of il-2 and the tumor-targeting abi ...201424276620
attenuation of responses to endotoxin by the triggering receptor expressed on myeloid cells-1 inhibitor lr12 in nonhuman primate.the triggering receptor expressed on myeloid cells-1 is an immunoreceptor that amplifies the inflammatory response mediated by toll-like receptors engagement. triggering receptor expressed on myeloid cells-1 inhibitory peptides such lr12 have been shown to prevent hyperresponsiveness and death in several experimental models of septic shock.201424270127
subcutaneous versus intravenous administration of rituximab: pharmacokinetics, cd20 target coverage and b-cell depletion in cynomolgus monkeys.the cd20-specific monoclonal antibody rituximab (mabthera(®), rituxan(®)) is widely used as the backbone of treatment for patients with hematologic disorders. intravenous administration of rituximab is associated with infusion times of 4-6 hours, and can be associated with infusion-related reactions. subcutaneous administration of rituximab may reduce this and facilitate administration without infusion-related reactions. we sought to determine the feasibility of achieving equivalent efficacy (me ...201324265828
effects of telemetric epicardial leads and ventricular catheters on arrhythmia incidence in cynomolgus monkeys.utilization of implantable bio-telemetry devices represents a common approach to contemporary cardiovascular safety assessment. depending on the specific needs of the study design, and corresponding surgical methodologies employed, application of telemetry devices may have more or less liability to interact with ongoing physiology. the potential for intrathoracic procedures (epicardial/intracardiac ecg lead arrangements, left ventricular catheterization) to influence baseline cardiovascular func ...201424262389
segmental mandibular bone reconstruction with a carbonate-substituted hydroxyapatite-coated modular endoprosthetic poly(ɛ-caprolactone) scaffold in macaca fascicularis.a bio-degradable scaffold incorporating osteoinductive factors is one of the alternative methods for achieving the regeneration of a mandibular bone defect. the current pilot study addressed such a bone reconstruction in a non-human primate model, macaca fascicularis monkeys, with an engineered poly(ɛ-caprolactone) (pcl) scaffold, provided with a carbonate-substituted hydroxyapatite coating. the scaffolds were implanted into unilaterally created mandibular segmental defects in 24 monkeys. three ...201424259321
nonclinical evaluation of the serum pharmacodynamic biomarkers hgf and shed met following dosing with the anti-met monovalent monoclonal antibody onartuzumab.onartuzumab, a humanized, monovalent monoclonal anti-met antibody, antagonizes met signaling by inhibiting binding of its ligand, hepatocyte growth factor (hgf). we investigated the effects of onartuzumab on cell-associated and circulating (shed) met (smet) and circulating hgf in vitro and nonclinically to determine their utility as pharmacodynamic biomarkers for onartuzumab. effects of onartuzumab on cell-associated met were assessed by flow cytometry and immunofluorescence. smet and hgf were m ...201424258345
an antibody against the c-terminal domain of pcsk9 lowers ldl cholesterol levels in vivo.proprotein convertase subtilisin/kexin type 9 (pcsk9) is associated with autosomal dominant hypercholesterolemia, a state of elevated levels of ldl (low-density lipoprotein) cholesterol. autosomal dominant hypercholesterolemia can result in severe implications such as stroke and coronary heart disease. the inhibition of pcsk9 function by therapeutic antibodies that block interaction of pcsk9 with the epidermal growth factor-like repeat a domain of ldl receptor (ldlr) was shown to successfully lo ...201424252255
delayed response task performance as a function of age in cynomolgus monkeys (macaca fascicularis).we compared delayed response task performance in young, middle-aged, and old cynomolgus monkeys using three memory tests that have been used with non-human primates. eighteen cynomolgus monkeys--6 young (4-9 years), 6 middle-aged (10-19 years), and 6 old (above 20 years)--were tested. in general, the old monkeys scored significantly worse than did the animals in the two other age groups. longer delays between stimulus presentation and response increased the performance differences between the ol ...201424248474
alopecia in three macaque species housed in a laboratory environment.alopecia is a persistent problem in captive macaque populations and despite recent interest, no factors have been identified that can unequivocally explain the presence of alopecia in a majority of cases. seasonal, demographic, and environmental factors have been identified as affecting alopecia presentation in rhesus macaques, the most widely studied macaque species. however, few studies have investigated alopecia rates in other macaque species. we report alopecia scores over a period of 12 mon ...201424243351
isolation and characterization of faecal bifidobacteria and lactobacilli isolated from dogs and primates.although bifidobacteria and lactobacilli have been suggested beneficial for the host and are components of many probiotics and competitive exclusion mixtures, the knowledge on abundance, metabolic and probiotic characteristics in isolates from dogs and monkeys is still limited. the present study was aimed to isolate bifidobacterium and lactobacillus strains (faeces of 22 dogs and of 5 primates: cebus apella, eulemur fulvus, erythrocebus patas, macaca fascicularis, papio hamadryas) with the maldi ...201424239978
post-injection sciatic neuropathy in a cynomolgus macaque (macaca fascicularis).intramuscular injection is a common route parenteral used in primates.201424236754
establishing an imaging protocol for detection of vascularity within the median nerve using contrast-enhanced ultrasound.this preclinical study was conducted to develop discrete sonographic instrumentation settings and also safe contrast dosing that would consistently demonstrate perineural vascularity along the median nerve. this set of imaging studies was conducted with a convenience cohort of young adult female monkeys (macaca fascicularis). sonographic equipment settings and dosing were refined throughout the imaging series to ensure consistent contrast-enhanced ultrasound imaging. a mechanical index of 0.13 w ...201324236299
l-dopa-treatment in primates disrupts the expression of a(2a) adenosine-cb(1) cannabinoid-d(2) dopamine receptor heteromers in the caudate nucleus.the molecular basis of priming for l-dopa-induced dyskinesias in parkinson's disease (pd), which depends on the indirect pathway of motor control, is not known. in rodents, the indirect pathway contains striatopallidal gabaergic neurons that express heterotrimers composed of a(2a) adenosine, cb(1) cannabinoid and d(2) dopamine receptors that regulate dopaminergic neurotransmission. the present study was designed to investigate the expression of these heteromers in the striatum of a primate model ...201424230991
mechanistic investigations of test article-induced pancreatic toxicity at the endocrine-exocrine interface in the rat.pancreatic toxicity commonly affects the endocrine or exocrine pancreas. however, it can also occur at the endocrine-exocrine interface (eei), where the capillary network of the islet merges with the capillaries of the surrounding acinar tissue, that is, the insulo-acinar portal system. the goal of this article is to describe a novel, test article-induced pancreatic toxicity that originated at the eei and to summarize investigations into the mechanistic basis of the injury. this injury was initi ...201424226507
coding potential of ul/b' from the initial source of rhesus cytomegalovirus strain 68-1.rhesus cytomegalovirus (rhcmv) 68-1 is the prototypic strain of rhcmv that has been used for pathogenesis and vaccine development. we determined the complete sequence of the rhcmv 68-1 ul/b' region directly from the original urine from which rhcmv 68-1 was isolated in 1968, and compared it to other rhcmvs. the laboratory passaged rhcmv 68-1 has inversions, deletions, and stop codons in ul/b' that are absent in the original isolate and other low passage rhcmv isolates. fourteen of the 17 open rea ...201324210116
sertraline effects on cerebrospinal fluid monoamines and species-typical socioemotional behavior of female cynomolgus monkeys.although widely prescribed, little is known about the effects of selective serotonin reuptake inhibitors (ssris) on social behavior and cerebrospinal fluid (csf) monoamines in female primates.201424193371
assessment of the performance of three multiplex array panels for the detection of circulating cytokines and chemokines in naive, lps, and seb-treated cynomolgus macaques.to assess relative sensitivity for detection of cytokines and chemokines in cynomolgus serum samples, we tested three commercially available multiplex array kits using the luminex® platform with sera from animals exposed by intravenous injection to 150 μg/kg staphylococcal enterotoxin b (seb) or 20 μg/kg lipopolysaccharide (lps). each of these kits detected similar patterns of changes in circulating cytokines/chemokines in response to seb or lps stimulation, especially the induction of high amou ...201424190913
adult carrion arthropod community in a tropical rainforest of malaysia: analysis on three common forensic entomology animal models.decomposing carrion provides a temporary microhabitat and food source for a distinct community of organisms. arthropods constitute a major part of this community and can be utilized to estimate the postmortem interval (pmi) of cadavers during criminal investigations. however, in malaysia, knowledge of carrion arthropod assemblages and their succession is superficial. therefore, a study on three types of forensic entomology animal model was conducted from 27 september 2010 to 28 october 2010 in a ...201324189678
development and application of next generation se36 malaria vaccine formulated with a novel adjuvant: approach to travelers' vaccine.the se36 antigen, derived from serine repeat antigen 5 (sera5) of plasmodium falciparum, is a promising blood stage malaria vaccine candidate. previous clinical trials indicated the protective efficacy of bk-se36 malaria vaccine that is constituted of se36 recombinant protein and aluminum hydroxide gel. in this study, we assessed the safety, immunogenicity and protective efficacy of se36/ahg formulated with tlr9 ligand adjuvants k3 cpg oligodeoxyribonucleotides (cpg odns) (k3 odn), d3 odn or syn ...201324189556
color vision test for dichromatic and trichromatic macaque monkeys.dichromacy is a color vision defect in which one of the three cone photoreceptors is absent. individuals with dichromacy are called dichromats (or sometimes "color-blind"), and their color discrimination performance has contributed significantly to our understanding of color vision. macaque monkeys, which normally have trichromatic color vision that is nearly identical to humans, have been used extensively in neurophysiological studies of color vision. in the present study we employed two tests, ...201324187056
the effect of ketamine-contaminated control plasma on small-molecule plasma protein binding.due to macroeconomic factors, the pharmaceutical industry has progressively outsourced larger amounts of its internal research efforts. one such example is the purchase of large volumes of control nonhuman primate (nhp) plasma from external vendors. during the bioanalysis of plasma samples collected during a cynomolgus monkey pk study with racemic (±) ketamine, it was discovered that the vendor control nhp plasma used for standard curve samples contained ketamine (32 µm). this ketamine concentra ...201324180502
horizontal acquisition and a broad biodistribution typify simian foamy virus infection in a cohort of macaca fascicularis.foamy viruses are non-pathogenic in vivo and naturally infect all species of non-human primates (nhp). simian foamy viruses (sfv) are highly prevalent in both free ranging and captive nhp but few longitudinal studies have been performed to assess the prevalence and biodistribution of sfv within captive nhp.201324180225
species- and dose-specific pancreatic responses and progression in single- and repeat-dose studies with gi181771x: a novel cholecystokinin 1 receptor agonist in mice, rats, and monkeys.compound-induced pancreatic injury is a serious liability in preclinical toxicity studies. however, its relevance to humans should be cautiously evaluated because of interspecies variations. to highlight such variations, we evaluated the species- and dose-specific pancreatic responses and progression caused by gi181771x, a novel cholecystokinin 1 receptor agonist investigated by glaxosmithkline for the treatment of obesity. acute (up to 2,000 mg/kg gi181771x, as single dose) and repeat-dose stud ...201424178573
haplessly hoping: macaque major histocompatibility complex made easy.major histocompatibility complex (mhc) gene products control the repertoire of t cell responses that an individual may create against pathogens and foreign tissues. this text will review the current understanding of mhc genetics in nonhuman primates, with a focus on mauritian-origin cynomolgus macaques (macaca fascicularis) and indian-origin rhesus macaques (macaca mulatta). these closely related macaque species provide important experimental models for studies of infectious disease pathogenesis ...201324174442
old world monkeys and new age science: the evolution of nonhuman primate systems virology.nonhuman primate (nhp) biomedical models are critical to our understanding of human health and disease, yet we are still in the early stages of developing sufficient tools to support primate genomic research that allow us to better understand the basis of phenotypic traits in nhp models of disease. a mere 7 years ago, the limited nhp transcriptome profiling that was being performed was done using complementary dna arrays based on human genome sequences, and the lack of nhp genomic information an ...201324174440
unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans.we report the discovery and translational therapeutic efficacy of a peptide with potent, balanced co-agonism at both of the receptors for the incretin hormones glucagon-like peptide-1 (glp-1) and glucose-dependent insulinotropic polypeptide (gip). this unimolecular dual incretin is derived from an intermixed sequence of glp-1 and gip, and demonstrated enhanced antihyperglycemic and insulinotropic efficacy relative to selective glp-1 agonists. notably, this superior efficacy translated across rod ...201324174327
chronic cadmium treatment induces tubular nephropathy and osteomalacic osteopenia in ovariectomized cynomolgus monkeys.in an attempt to establish a primate model of chronic cadmium toxicosis, we ovariectomized cynomolgus monkeys and treated them with cdcl2 by repeated intravenous injections for 13 to 15 months. the animals showed normocytic-normochromic anemia. the cadmium treatment resulted in increases of urinary enzyme activity indicative of renal tubular degeneration. histopathology of the kidney revealed renal proximal tubular atrophy accompanied by interstitial fibrosis. decreased bone mineral density was ...201424165203
occurrence of human-pathogenic enterocytozoon bieneusi, giardia duodenalis and cryptosporidium genotypes in laboratory macaques in guangxi, china.captive nonhuman primates have been identified as common hosts of enterocytozoon bieneusi, giardia duodenalis, cryptosporidium hominis, and cyclospora spp., thus are potential reservoirs of some enteric parasites in humans. however, few studies have examined the source and human-infective potential of enteric parasites in laboratory nonhuman primates. in the present work, 205 fecal specimens were collected from three groups of captive macaca fascicularis kept in different densities in a laborato ...201424157444
outcomes of alpha 1,3-gt-knockout porcine heart transplants into a preclinical nonhuman primate model.solid organ xenotransplantation is a potential solution to current organ shortages in allotransplantation. we performed four heart transplantations from alpha1, 3-galactosyltransferase gene-knockout (gt-ko) pigs to cynomolgus monkeys and monitored immunological parameters before and after transplantation.201324157041
t cell response specificity and magnitude against sivmac239 are not concordant in major histocompatibility complex-matched animals.cd8+ t cell responses, restricted by major histocompatibility complex (mhc) class i molecules, are critical to controlling human immunodeficiency virus type 1 (hiv-1) and simian immunodeficiency virus (siv) replication. previous studies have used mhc-matched siblings and monozygotic twins to evaluate genetic and stochastic influences on hiv-specific t cell responses and viral evolution. here we used a genetically restricted population of mauritian cynomolgus macaques (mcm) to characterize t cell ...201324156675
towards the non-invasive assessment of mhc genotype in wild primates: analysis of wild assamese macaque mhc-drb from fecal samples.the major histocompatibility complex (mhc) plays an important role in the immune response and may thus crucially affect an individual's fitness, relevant also for studies on evolutionary ecology and wildlife conservation. detailed knowledge on the genomic organization, polymorphism and diversity of the mhc has a narrow taxonomic focus though and among macaques is only available for rhesus and long-tailed macaques-the species most commonly kept for biomedical research. the lack of data on wild po ...201424151109
brain and peripheral pharmacokinetics of levodopa in the cynomolgus monkey following administration of opicapone, a third generation nitrocatechol comt inhibitor.the present study aimed at evaluating the effect of opicapone, a third generation nitrocatechol catechol-o-methyltransferase (comt) inhibitor, on the systemic and central bioavailability of 3,4-dihydroxy-l-phenylalanine (levodopa) and related metabolites in the cynomolgus monkey.201424148813
infection by brazilian and dutch swine hepatitis e virus strains induces haematological changes in macaca fascicularis.hepatitis e virus (hev) has been described as an emerging pathogen in brazil and seems to be widely disseminated among swine herds. an autochthonous human case of acute hepatitis e was recently reported. to obtain a better understanding of the phenotypic profiles of both human and swine hev strains, a experimental study was conducted using the animal model, macaca fascicularis.201324148233
longitudinal design for sonographic measurement of median nerve swelling with controlled exposure to physical work using an animal model.in the study described here, we examined the feasibility of a longitudinal design to measure sonographically swelling of the median nerve caused by controlled exposure to a work task and to evaluate the relationship of changes in morphology to diagnostic standards. fifteen macaques, macaca fascicularis, pinched a lever in various wrist positions at a self-regulated pace (8 h/d, 5 d/wk, 18-20 wk). nerve conduction velocity (ncv) and cross-sectional area (csa) were measured every 2 wk from baselin ...201324139197
the origin of projections from the posterior cingulate and retrosplenial cortices to the anterior, medial dorsal and laterodorsal thalamic nuclei of macaque monkeys.interactions between the posterior cingulate cortex (areas 23 and 31) and the retrosplenial cortex (areas 29 and 30) with the anterior, laterodorsal and dorsal medial thalamic nuclei are thought to support various aspects of cognition, including memory and spatial processing. to detail these interactions better, the present study used retrograde tracers to reveal the origins of the corticothalamic projections in two closely related monkey species (macaca mulatta, macaca fascicularis). the medial ...201424134130
pharmacokinetic and pharmacodynamic properties of gs-9620, a novel toll-like receptor 7 agonist, demonstrate interferon-stimulated gene induction without detectable serum interferon at low oral doses.gs-9620 [8-(3-(pyrrolidin-1-ylmethyl)benzyl)-4-amino-2-butoxy-7,8-dihydropteridin-6(5h)-one] is a potent, orally bioavailable small-molecule agonist of toll-like receptor 7 (tlr7) developed for finite treatment of chronic hepatitis b viral (hbv) infection, with the goal of inducing a liver-targeted antiviral effect without inducing the adverse effects associated with current systemic interferon-α (ifn-α) therapies. we characterized the pharmacodynamic response of gs-9620 in cd-1 mice and cynomol ...201424133297
mabs and ad-vectored ifn-α therapy rescue ebola-infected nonhuman primates when administered after the detection of viremia and symptoms.zmab is a promising treatment against ebola virus (ebov) disease that has been shown to protect 50% (two of four) of nonhuman primates (nhps) when administered 2 days post-infection (dpi). to extend the treatment window and improve protection, we combined zmab with adenovirus-vectored interferon-α (ad-ifn) and evaluated efficacy in ebov-infected nhps. seventy-five percent (three of four) and 100% (four of four) of cynomolgus and rhesus macaques survived, respectively, when treatment was initiate ...201324132638
infectivity of cryptosporidium andersoni and cryptosporidium muris to normal and immunosuppressive cynomolgus monkeys.cryptosporidium andersoni and cryptosporidium muris infections have been found in the mice and/or cattle. the oocysts of c. andersoni and c. muris have been sporadically detected in human feces, but the infectious capacity and features have been unknown, because of the scarcity of reports involving human infections. to assess the infectivity and the clinical and pathological features of c. andersoni and c. muris in primates, an experimental infectious study was conducted using cynomolgus monkeys ...201424132296
leptin and its receptor expression in dental and periodontal tissues of primates.leptin and its receptor (obr) have attracted much attention since their discovery. they have been reported to play central roles in energy balance, the immune-inflammatory response and bone metabolism. evidence indicates that leptin and obr are associated with inflammatory diseases of dental and periodontal tissues. the first step for establishing this is to determine the expression of leptin and obr in these tissues. our study is the first to examine systematically the expression of leptin and ...201424126952
inverse relationship between ldl cholesterol and pcsk9 plasma levels in dyslipidemic cynomolgus monkeys: effects of ldl lowering by ezetimibe in the absence of statins.to assess the lipid-lowering efficacy of ezetimibe in dyslipidemic cynomolgus monkeys comparing two dosing methods, and to evaluate pcsk9 plasma levels during dyslipidemia induction by feeding a high-fat/high-cholesterol diet (hfd), ezetimibe (zetia(®), ezetrol(®)) treatment, ezetimibe washout, and hfd washout.201324125416
hormone suppression with gnrh antagonist promotes spermatogenic recovery from transplanted spermatogonial stem cells in irradiated cynomolgus monkeys.hormone suppression given before or after cytotoxic treatment stimulates the recovery of spermatogenesis from endogenous and transplanted spermatogonial stem cells (ssc) and restores fertility in rodents. to test whether the combination of hormone suppression and transplantation could enhance the recovery of spermatogenesis in primates, we irradiated (7 gy) the testes of 12 adult cynomolgus monkeys and treated six of them with gonadotropin-releasing hormone antagonist (gnrh-ant) for 8 weeks. at ...201324124124
human behavior and opportunities for parasite transmission in communities surrounding long-tailed macaque populations in bali, indonesia.spatial overlap and shared resources between humans and wildlife can exacerbate parasite transmission dynamics. in bali, indonesia, an agricultural-religious temple system provides sanctuaries for long-tailed macaques (macaca fascicularis), concentrating them in areas in close proximity to humans. in this study, we interviewed individuals in communities surrounding 13 macaque populations about their willingness to participate in behaviors that would put them at risk of exposure to gastrointestin ...201424123083
trimethoprim-sulfamethoxazole treatment does not reverse obstructive pulmonary changes in pneumocystis-colonized nonhuman primates with shiv infection.despite antiretroviral therapy and trimethoprim-sulfamethoxazole (tmp-smx) prophylaxis, pneumocystis pneumonia remains an important serious opportunistic infection in hiv-infected persons. pneumocystis (pc) colonization in hiv-infected individuals and in hiv-uninfected smokers is associated with chronic obstructive pulmonary disease (copd). we previously developed a nonhuman primate model of hiv infection and pc colonization and demonstrated that pc colonization correlated with copd development. ...201424121760
post-transplant repopulation of naïve and memory t cells in blood and lymphoid tissue after alemtuzumab-mediated depletion in heart-transplanted cynomolgus monkeys.repopulation of memory t cells (tmem) in allograft recipients after lymphodepletion is a major barrier to transplant tolerance induction. ineffective depletion of naïve t cells (tn) and tmem may predispose to repopulation of tmem after transplantation. cynomolgus macaque monkeys given heart allografts were lymphodepleted using alemtuzumab (campath-1h; anti-cd52). peripheral blood (pb) and lymph nodes (ln) were analyzed for cd95(-) (tn) and cd95(+) cells (tmem), one day, one month and up to three ...201324120957
the cox-2 inhibitor meloxicam prevents pregnancy when administered as an emergency contraceptive to nonhuman primates.cyclooxygenase-2 (cox-2) inhibitors reduce prostaglandin synthesis and disrupt essential reproductive processes. ultrasound studies in women demonstrated that oral cox-2 inhibitors can delay or prevent follicle collapse associated with ovulation. the goal of this study was to determine if oral administration of a cox-2 inhibitor can inhibit reproductive function with sufficient efficacy to prevent pregnancy in primates.201324120248
large-scale polymorphism discovery in macaque g-protein coupled receptors.g-protein coupled receptors (gpcrs) play an inordinately large role in human health. variation in the genes that encode these receptors is associated with numerous disorders across the entire spectrum of disease. gpcrs also represent the single largest class of drug targets and associated pharmacogenetic effects are modulated, in part, by polymorphisms. recently, non-human primate models have been developed focusing on naturally-occurring, functionally-parallel polymorphisms in candidate genes. ...201324119066
establishment of depression behavioral criteria in cynomolgus monkeys. 201324118874
histologic and histomorphometric evaluation of peri-implant bone of immediate or delayed occlusal-loaded non-splinted implants in the posterior mandible--an experimental study in monkeys.the primary aim of this study was to compare the bone reaction around immediate-loaded non-splinted single implants vs. delayed loaded non-splinted single implants placed in healed ridges in the posterior mandible.201424118392
clinicopathological findings in non-human primate recipients of porcine renal xenografts: quantitative and qualitative evaluation of proteinuria.immunological and histopathological features in pig-to-primate renal xenotransplantation are widely studied. only limited data have been reported about clinicopathological findings in primate recipients of life-supporting renal xenografts. in human medicine, proteinuria represents a common complication in kidney transplantation and is associated with impaired graft survival. the detection of low molecular weight proteins of tubular origin is considered an early method for predicting potential gr ...201624112104
anatomical evidence that the superior colliculus controls saccades through central mesencephalic reticular formation gating of omnipause neuron activity.omnipause neurons (opns) within the nucleus raphe interpositus (rip) help gate the transition between fixation and saccadic eye movements by monosynaptically suppressing activity in premotor burst neurons during fixation, and releasing them during saccades. premotor neuron activity is initiated by excitatory input from the superior colliculus (sc), but how the tectum's saccade-related activity turns off opns is not known. since the central mesencephalic reticular formation (cmrf) is a major sc t ...201324107960
differential responses to jnj-37822681, a specific and fast dissociating dopamine d2 receptor antagonist, in cynomolgus monkey and sprague-dawley rat general toxicology studies: clinical observations, prolactin levels, mammary histopathology findings and toxicokinetics.jnj-37822681 is a potent, specific and fast dissociating dopamine d2 receptor antagonist intended for the treatment of schizophrenia. its nonclinical toxicological profile was investigated in a series of general repeat dose toxicity studies in cynomolgus monkeys and sprague-dawley rats. the maximum duration of treatment was 9 and 6 months, respectively. interspecies differences were noted in the response to jnj-37822681 in terms of extrapyramidal (eps)-like clinical signs and prolactin-mediated ...201424105799
seasonal h3n2 influenza a virus fails to enhance staphylococcus aureus co-infection in a non-human primate respiratory tract infection model.staphylococcus aureus community-acquired pneumonia is often associated with influenza or an influenza-like syndrome. morbidity and mortality due to methicillin-resistant s. aureus (mrsa) or influenza and pneumonia, which includes bacterial co-infection, are among the top causes of death by infectious diseases in the united states. we developed a non-lethal influenza a virus (iav) (h3n2)/s. aureus co-infection model in cynomolgus macaques (macaca fascicularis) to test the hypothesis that seasonal ...201324104465
hematologic reference intervals in cynomolgus (macaca fascicularis) monkeys.reference intervals are important aids for interpreting clinical pathology laboratory data especially in cynomolgus monkey (macaca fascicularis), the non-human primate species most widely used in biomedical research. the purpose of this study was to establish hematologic reference intervals for cynomolgus according to the international federation of clinical chemistry and clinical and laboratory standards institute guidelines using the databank at a primatology center.201424102586
long-tailed macaques select mass of stone tools according to food type.tool selection can affect the success of a tool-based feeding task, and thus tool-using animals should select appropriate tools when processing foods. we performed a field experiment on piak nam yai island in laem son national park, thailand, to test whether burmese long-tailed macaques (macaca fascicularis aurea) selected stone tools according to food type. we baited the island's shores with stone sets ('tool tests') in an effort to attract macaques to use stones presented in a quasi-experiment ...201324101623
dnmt1 and aim1 imprinting in human placenta revealed through a genome-wide screen for allele-specific dna methylation.genomic imprinting is an epigenetically regulated process wherein genes are expressed in a parent-of-origin specific manner. many imprinted genes were initially identified in mice; some of these were subsequently shown not to be imprinted in humans. such discrepancy reflects developmental, morphological and physiological differences between mouse and human tissues. this is particularly relevant for the placenta. study of genomic imprinting thus needs to be carried out in a species and developmen ...201324094292
co-expression of the human cannabinoid receptor coding region splice variants (hcb₁) affects the function of hcb₁ receptor complexes.the human type 1 cannabinoid (hcb1) receptor is expressed at high levels in the central nervous system. mrna variants of the coding region of this receptor, human cannabinoid hcb1a and hcb1b receptors, have been identified, their biological function remains unclear. the present study demonstrated that the three human cannabinoid hcb1 coding region variants are expressed in the human and monkey (macaca fascicularis) brain. western blot analyses of homogenates from different regions of the monkey ...201324091169
a humanized monoclonal antibody specific for invariant natural killer t (inkt) cells for in vivo depletion.invariant natural killer t (inkt) cells are a subset of t cells recognizing glycolipid antigens presented by cd1d. human inkt cells express a conserved t cell receptor (tcr)-α chain (vα24-jα18) paired with a specific beta chain, vβ11. the cells are both innate-like, with rapid cytokine release, and adaptive-like, including thymic positive selection. over activation of inkt cells can mediate tissue injury and inflammation in multiple organ systems and play a role in mediating the pathology associ ...201324086759
pathogenicity of pandemic h1n1 influenza a virus in immunocompromised cynomolgus macaques.pandemic (h1n1) 2009 influenza virus spread throughout the world since most people did not have immunity against the virus. in the post pandemic phase when many humans might possess immunity against the pandemic virus, one of the concerns is infection in immunocompromised people. therefore, we used an immunosuppressed macaque model to examine pathogenicity of the pandemic (h1n1) 2009 virus under an immunocompromised condition. the virus in nasal samples of immunosuppressed macaques infected with ...201324086663
a human hair keratin hydrogel scaffold enhances median nerve regeneration in nonhuman primates: an electrophysiological and histological study.a human hair keratin biomaterial hydrogel scaffold was evaluated as a nerve conduit luminal filler following median nerve transection injury in 10 macaca fascicularis nonhuman primates (nhp). a 1 cm nerve gap was grafted with a neuragen® collagen conduit filled with either saline or keratin hydrogel and nerve regeneration was evaluated by electrophysiology for a period of 12 months. the keratin hydrogel-grafted nerves showed significant improvement in return of compound motor action potential (c ...201424083825
a monovalent anti-human cd28 domain antibody antagonist: preclinical efficacy and safety.targeting the cd28-cd80/86 pathway with an anti-cd28 antagonist is a promising alternative to current therapies for autoimmunity. however, attempts at generating conventional anti-cd28 mabs lacking stimulatory activity has been challenging. in this study, we describe anti-human cd28 receptor antagonist domain abs (dabs) that are specific for human cd28. these dabs are potent inhibitors of t cell activation, with an ec50 of 35 ± 14 ng/ml for inhibition of proliferation. the ec50 of 53 ± 11 ng/ml ...201324081989
effects of repeated treatment with the dopamine d2/d3 receptor partial agonist aripiprazole on striatal d2/d3 receptor availability in monkeys.chronic treatment with dopamine (da) receptor agonists and antagonists can differentially affect measures of da d2/d3 receptor number and function, but the effects of chronic treatment with a partial d2/d3 receptor agonist are not clear.201324077804
crystal structure of rat intestinal alkaline phosphatase--role of crown domain in mammalian alkaline phosphatases.intestinal alkaline phosphatases (iaps) are involved in the cleavage of phosphate prodrugs to liberate the drug for absorption in the intestine. to facilitate in vitro characterization of phosphate prodrugs, we have cloned, expressed, purified and characterized iaps from rat and cynomolgus monkey (riap and ciap respectively) which are important pre-clinical species for drug metabolism studies. the recombinant rat and monkey enzymes expressed in sf9 insect cells (iap-ic) were found to be glycosyl ...201324076154
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