Publications
| Title | Abstract | Year Filter | PMID(sorted descending) Filter |
|---|
| application of bmp-bone cement and fgf-gel on periodontal tissue regeneration in nonhuman primates. | the ultimate challenge of tissue engineering research is the translation of experimental knowledge into clinical application. in the preclinical testing phase of any new therapy, animal models remain the gold standard. therefore, the methodological choice of a suitable model is critical to meet the requirements for a safe clinical application of the developed treatment. for instance, we have shown in rats that the application of calcium phosphate cement (cpc)/propylene glycol alginate (pga) with ... | 2019 | 31701811 |
| immunoaffinity lc-ms/ms to quantify a pegylated anti-factor d fab biotherapeutic in cynomolgus monkey serum. | aim: to develop a sensitive hybrid immunoaffinity lc-ms/ms monkey serum assay to quantify multiple components of anti-factor d; a complex pegylated fab biotherapeutic explored as a therapy for age-related macular degeneration. materials & methods: immunoaffinity enrichment of pegylated anti-factor d fab, including fully conjugated, partially conjugated and unconjugated (i.e., free) fab species, using a capture reagent coupled to magnetic beads was performed. the surrogate peptides derived from t ... | 2019 | 31701759 |
| expression levels of micrornas that are potential cytochrome p450 regulators in cynomolgus macaques. | 1. although the cynomolgus macaque is an important non-human primate species used in drug metabolism studies, cynomolgus macaque microrna expressions have not been fully investigated.2. the expressions of 11 cynomolgus micrornas, all orthologues of p450 regulators in humans, were measured by quantitative polymerase chain reaction in adrenal gland, brain, heart, jejunum, kidney, liver, ovary, testis and uterus. mfa-mir-122 and mfa-mir-192, potentially important biomarkers for liver toxicity, were ... | 2020 | 31682544 |
| role of p-glycoprotein in the brain disposition of seletalisib: evaluation of the potential for drug-drug interactions. | seletalisib is an orally bioavailable selective inhibitor of phosphoinositide 3-kinase delta (pi3kδ) in clinical development for the treatment of immune-mediated inflammatory diseases. the present study investigated the role of p-gp in seletalisib disposition, especially brain distribution, and the associated risks of interactions. seletalisib was found to be actively transported by rodent and human p-gp in vitro (transfected llc-pk1 cells; km of ca. 20 µm), with minimal or no affinity for the o ... | 2020 | 31678424 |
| in vitro culture of cynomolgus monkey embryos beyond early gastrulation. | gastrulation is a key event in embryonic development when the germ layers are specified and the basic animal body plan is established. the complexities of primate gastrulation remain a mystery because of the difficulties in accessing primate embryos at this stage. here, we report the establishment of an in vitro culture (ivc) system that supports the continuous development of cynomolgus monkey blastocysts beyond early gastrulation up to 20 days after fertilization. the ivc embryos highly recapit ... | 2019 | 31672918 |
| dissecting primate early post-implantation development using long-term in vitro embryo culture. | the transition from peri-implantation to gastrulation in mammals entails the specification and organization of the lineage progenitors into a body plan. technical and ethical challenges have limited understanding of the cellular and molecular mechanisms that underlie this transition. we established a culture system that enabled the development of cynomolgus monkey embryos in vitro for up to 20 days. cultured embryos underwent key primate developmental stages, including lineage segregation, bilam ... | 2019 | 31672917 |
| interspecies variation of clopidogrel hydrolysis in liver microsomes from various mammals. | clopidogrel, a clinically used antiplatelet agent, can be readily hydrolyzed by human carboxylesterase 1a (ces1a) to release an inactive metabolite clopidogrel carboxylic acid (cca). in this study, clopidogrel was used as a tool substrate to investigate the interspecies variation of clopidogrel hydrolysis in hepatic microsomes from various mammals including human and six laboratory animals (such as mouse, rat, rabbit, beagle dog, minipig and cynomolgus monkey). the results demonstrated that clop ... | 2020 | 31669218 |
| transgenic mouse models expressing human and macaque prion protein exhibit similar prion susceptibility on a strain-dependent manner. | cynomolgus macaque has been used for the evaluation of the zoonotic potential of prion diseases, especially for classical-bovine spongiform encephalopathy (classical-bse) infectious agent. prp amino acid sequence is considered to play a key role in the susceptibility to prion strains and only one amino acid change may alter this susceptibility. macaque and human-prp sequences have only nine amino acid differences, but the effect of these amino acid changes in the susceptibility to dissimilar pri ... | 2019 | 31666632 |
| palmoplantar depigmentation in macaca fascicularis following blaschko linear pattern. | hypomelanosis of ito is a rare neurocutaneous syndrome, characterized by streaks and swirls of hypopigmentation arranged in a blaschkoid pattern. other associated anomalies are observed. we report a case of a male cynomolgus monkey (macaca fascicularis) who presented the characteristic of hypomelanosis of ito with palmoplantar involvement and polythelia. | 2020 | 31657466 |
| novel highly potent oxe receptor antagonists with prolonged plasma lifetimes that are converted to active metabolites in vivo in monkeys. | the 5-lipoxygenase product 5-oxo-6e,8z,11z,14z-eicosatetraenoic acid (5-oxo-ete), acting through the oxe receptor, is a potent eosinophil chemoattractant that may be an important proinflammatory mediator in eosinophilic diseases such as asthma. we previously identified a series of indole-based oxe receptor antagonists that rapidly appear in the blood following oral administration but have limited lifetimes. the objective of this study was to increase the potency and plasma half-lives of these co ... | 2020 | 31655025 |
| inhibition of allergen-induced dermal eosinophilia by an oxoeicosanoid receptor antagonist in non-human primates. | 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ete), acting via the oxe receptor, is unique among 5-lipoxygenase products in its ability to directly induce human eosinophil migration, suggesting its involvement in eosinophilic diseases. to address this hypothesis, we synthesized selective indole-based oxe receptor antagonists. because rodents lack an oxe receptor orthologue, we sought to determine whether these antagonists could attenuate allergen-induced skin eosinophilia in sensitized monkeys. | 2020 | 31655023 |
| high diversity and novel enteric viruses in fecal viromes of healthy wild and captive thai cynomolgus macaques (macaca fascicularis). | cynomolgus macaques are common across south east asian countries including thailand. the national primate research center of thailand, chulalongkorn university (nprct-cu) captures wild-borne cynomolgus macaque for research use. limited information is available on the enteric viruses and possible zoonotic infections into or from cynomolgus macaques. we characterized and compare the fecal virome of two populations; healthy wild-originated captive cynomolgus macaques (n = 43) reared in nprct-cu and ... | 2019 | 31652508 |
| comparative genomics analysis reveals high levels of differential retrotransposition among primates from the hominidae and the cercopithecidae families. | mobile elements (mes), making ∼50% of primate genomes, are known to be responsible for generating inter- and intra-species genomic variations and play important roles in genome evolution and gene function. using a bioinformatics comparative genomics approach, we performed analyses of species-specific mes (ss-mes) in eight primate genomes from the families of hominidae and cercopithecidae, focusing on retrotransposons. we identified a total of 230,855 ss-mes, with which we performed normalization ... | 2019 | 31651947 |
| in vitro induction of human embryonic stem cells into the midbrain dopaminergic neurons and transplantation in cynomolgus monkey. | a simple, rapid, efficient, and specialized culture system was successfully developed in this study to induce human embryonic stem cells into dopaminergic neurons in vitro. it only took 5 days to generate quickly and directly a large number of homogeneous neural stem cell (nsc) spheres by the introduction of small molecules ldn (inhibitor of bmp [bone morphogenetic protein] pathway that inhibits bmp type i receptors alk2 and alk3), sb431542 (inhibitor of tgf-β/activin/dodal pathway that inhibits ... | 2019 | 31651190 |
| the enhanced immunopharmacology of vib4920, a novel tn3 fusion protein and cd40l antagonist, and assessment of its safety profile in cynomolgus monkeys. | inhibition of the t- and b-cell interaction through the cd40/cd40 ligand (l) axis is a favourable approach for inflammatory disease treatment. clinical studies of anti-cd40l molecules in autoimmune diseases have met challenges because of thromboembolic events and adverse haemostasis. vib4920 (formerly medi4920) is a novel cd40l antagonist and tn3 fusion protein designed to prevent adverse haemostasis and immunopharmacology. we evaluated the pharmacokinetics, activity and toxicity of vib4920 in m ... | 2020 | 31648370 |
| ultrasonographic measurement of the renal resistive index in the cynomolgus monkey (macaca fascicularis) under conscious and ketamine-immobilized conditions. | measurement of the renal resistive index (rri) is one of the standard diagnostic procedures for assessing kidney disability clinically. this method is expected to be used for the same purpose in many kinds of animals, including monkeys utilized in conventional toxicology studies. to establish a practical rri measurement procedure in cynomolgus monkeys (macaca fascicularis), rri was measured by ultrasonography in the spine position in conscious and ketamine-immobilized monkeys. the rri of conscio ... | 2020 | 31645524 |
| a green tea-triggered genetic control system for treating diabetes in mice and monkeys. | cell-based therapies are recognized as the next frontier in medicine, but the translation of many promising technologies into the clinic is currently limited by a lack of remote-control inducers that are safe and can be tightly regulated. here, we developed therapeutically active engineered cells regulated by a control system that is responsive to protocatechuic acid (pca), a metabolite found in green tea. we constructed multiple genetic control technologies that could toggle a pca-responsive on ... | 2019 | 31645456 |
| idiopathic chronic diarrhea associated with dysbiosis in a captive cynomolgus macaque (macaca fascicularis). | chronic inflammatory enteric diseases occur commonly in humans and animals, especially in captive bred macaques. however, information about the etiology of idiopathic chronic inflammatory diarrhea in cynomolgus monkeys is limited. in this paper, we reported the unusual case of idiopathic chronic diarrhea in a captive cynomolgus monkey based on microbial, imaging, and microbiome examinations. | 2020 | 31642533 |
| improvement of sperm cryo-survival of cynomolgus macaque (macaca fascicularis) by commercial egg-yolk-free freezing medium with type iii antifreeze protein. | when nonhuman primate sperm undergoes cryopreservation in an egg yolk medium there is an increased risk that the egg yolk might adversely affect the sperm due to containing of avian pathogens. although commercial egg-yolk-free medium for human sperm cryopreservation has been used for macaque sperm, the cryo-survival remains less than optimal. the present study, therefore, was conducted to determine the optimal concentration of antifreeze protein (afp) iii supplemented in a commercial egg-yolk-fr ... | 2019 | 31635783 |
| group-specific archaeological signatures of stone tool use in wild macaques. | stone tools in the prehistoric record are the most abundant source of evidence for understanding early hominin technological and cultural variation. the field of primate archaeology is well placed to improve our scientific knowledge by using the tool behaviours of living primates as models to test hypotheses related to the adoption of tools by early stone-age hominins. previously we have shown that diversity in stone tool behaviour between neighbouring groups of long-tailed macaques (macaca-fasc ... | 2019 | 31635691 |
| visualising reactive oxygen species in live mammals and revealing of ros-related system. | of all the aerobic respiration by-products, cytotoxic superoxide derived from mitochondrial-leaked electrons, is the only one known to be disposed of intracellularly. is this fate the only destiny for mitochondrial-leaked electrons? when cynomolgus monkeys were injected intravenously with reactive oxygen species (ros) indicators, the connective tissues of dura mater, facial fascia, pericardium, linea alba, dorsa fascia and other body parts, emitted specific and intense fluorescent signals. moreo ... | 2019 | 31631710 |
| single low-dose vsv-ebov vaccination protects cynomolgus macaques from lethal ebola challenge. | ebola virus (ebov), variant makona, was the causative agent of the 2013-2016 west african epidemic responsible for almost 30,000 human infections and over 11,000 fatalities. during the epidemic, the development of several experimental vaccines was accelerated through human clinical trials. one of them, the vesicular stomatitis virus (vsv)-based vaccine vsv-ebov, showed promising efficacy in a phase 3 clinical trial in guinea and is currently used in the ongoing ebov outbreak in the northeastern ... | 2019 | 31631035 |
| paracrine-endocrine fgf chimeras as potent therapeutics for metabolic diseases. | the development of a clinically useful fibroblast growth factor 21 (fgf21) hormone has been impeded by its inherent instability and weak fgf receptor (fgfr) binding affinity. there is an urgent need for innovative approaches to overcome these limitations. | 2019 | 31631034 |
| pharmacokinetics and intraocular pressure-lowering activity of tak-639, a novel c-type natriuretic peptide analog, in rabbit, dog, and monkey. | tak-639 is a topical, 9-amino acid, synthetic, c-type natriuretic peptide analog in development for the treatment of primary open-angle glaucoma and ocular hypertension. this study investigated the impact of tak-639 on intraocular pressure (iop), the levels of tak-639 in aqueous humor, and the pharmacokinetic/pharmacodynamic relationship of tak-639 following topical ocular administration to normotensive female dutch belted rabbits, beagle dogs, and cynomolgus monkeys. in the iop studies, rabbits ... | 2019 | 31626797 |
| sky59, a novel recycling antibody for complement-mediated diseases. | the complement system usually helps protect against microbial infection, but it could also be involved in the onset of various diseases. inhibition of complement component 5 (c5) with eculizumab has resulted in a significant reduction of hemolysis, reduction of thromboembolic events, and increased survival in patients with paroxysmal nocturnal hemoglobinuria (pnh). however, eculizumab requires frequent intravenous infusions due to the abundance of c5 in plasma and some patients may still experie ... | 2020 | 31622197 |
| short-term reciprocity in macaque's social decision-making. | primates live in complex social environments, where individuals create meaningful networks by adapting their behavior according to past experiences with others. although free-ranging primates do show signs of reciprocity, experiments in more controlled environments have mainly failed to reproduce such social dynamics. hence, the cognitive and neural processes allowing monkeys to reciprocate during social exchanges remains elusive. here, pairs of long-tailed macaques (macaca fascicularis) took tu ... | 2019 | 31616262 |
| therapy with 2'-o-me phosphorothioate antisense oligonucleotides causes reversible proteinuria by inhibiting renal protein reabsorption. | antisense oligonucleotide therapy has been reported to be associated with renal injury. here, the mechanism of reversible proteinuria was investigated by combining clinical, pre-clinical, and in vitro data. urine samples were obtained from duchenne muscular dystrophy (dmd) patients treated with drisapersen, a modified 2'o-methyl phosphorothioate antisense oligonucleotide (6 mg/kg). urine and kidney tissue samples were collected from cynomolgus monkeys (macaca fascicularis) dosed with drisapersen ... | 2019 | 31610379 |
| effects of transportation and relocation on immunologic measures in cynomolgus macaques (macaca fascicularis). | nhp are a small, but critical, portion of the animals studied in research laboratories. many nhp are imported or raised at one facility and subsequently moved to another facility for research purposes. to improve our understanding of the effects of transportation and relocation on the nhp immune system, to minimize potential confounds associated with relocation, and to maximize study validity, we examined the phenotype and function of pbmc in cynomolgus macaques (macaca fascicularis) that were t ... | 2019 | 31604484 |
| high susceptibility, viral dynamics and persistence of south american zika virus in new world monkey species. | south american zika virus (zikv) recently emerged as a novel human pathogen, linked with neurological disorders. however, comparative zikv infectivity studies in new world primates are lacking. two members of the callitrichidae family, common marmosets (callithrix jacchus) and red-bellied tamarins (saguinus labiatus), were highly susceptible to sub-cutaneous challenge with the puerto rico-origin zikvprvabc59 strain. both exhibited rapid, high, acute viraemia with early neuroinvasion (3 days) in ... | 2019 | 31601848 |
| comparison of vascular parameters between normal cynomolgus macaques and healthy humans by optical coherence tomography angiography. | the metabolic activity of retina is higher than other human tissues and is crucial to the vision. cynomolgus macaques is widely used in ophthalmic disease research. the evaluation and comparison of macular and optic disc vascular circulation parameters between normal adult cynomolgus macaques and healthy adult humans using oct-a can promote better use of nonhuman primate models in studies of ophthalmic vascular disease. | 2019 | 31601186 |
| nonpyramidal neurons in the primate basolateral amygdala: a golgi study in the baboon (papio cynocephalus) and long-tailed macaque (macaca fascicularis). | nonpyramidal gabaergic interneurons in the basolateral nuclear complex (bnc) of the amygdala are critical for the regulation of emotion. remarkably, there have been no golgi studies of these neurons in nonhuman primates. therefore, in the present study we investigated the morphology of nonpyramidal neurons (npns) in the bnc of the baboon and monkey using the golgi technique. npns were scattered throughout all nuclei of the bnc and had aspiny or spine-sparse dendrites. npns were morphologically h ... | 2020 | 31600841 |
| genotyping of enterocytozoon bieneusi among captive long-tailed macaques (macaca fascicularis) in hainan province: high genetic diversity and zoonotic potential. | enterocytozoon bieneusi is a potentially important zoonotic pathogen. however, there is no information on e. bieneusi infection of captive long-tailed macaques (macaca fascicularis) in hainan province, china. here 193 fecal specimens of m. fascicularis were collected from a breeding base in hainan province, china, housing non-human primates for experimental use. e. bieneusi was identified and genotyped by nested pcr analysis of the internal transcribed spacer (its) region of the rrna gene. a tot ... | 2020 | 31600522 |
| in vivo characterization of rc28-e, a fusion protein targeting vegf and bfgf: pharmacokinetics and ocular distribution in primates. | administration of rc28-e, a vegf/bfgf dual decoy receptor (igg1 fc-fusion protein), have shown relative therapeutic value in ocular in vivo models, including laser-induced choroidal neovascularization (cnv) in monkeys and streptozotocin (stz)-induced diabetic retinopathy (dr) in rats. in the present study, we have elucidated the pharmacokinetics profiles of rc28-e at the systemic, vitreous and aqueous humor after administration in a primate model (macaca fascicularis). moreover, here we tease ou ... | 2020 | 31600485 |
| target-mediated drug disposition pharmacokinetic/pharmacodynamic model-informed dose selection for the first-in-human study of avb-s6-500. | avb-s6-500 neutralized growth arrest-specific 6 (gas6) protein and effectively inhibited axl signaling in preclinical cancer models. a target-mediated drug disposition (tmdd) pharmacokinetic/pharmacodynamic (pk/pd) model was used to select first-in-human (fih) doses for avb-s6-500 based on predicted target (gas6) suppression in the clinic. the effect of tmdd on avb-s6-500 clearance was incorporated into a standard two-compartment model, providing parallel linear and nonlinear clearance. observed ... | 2020 | 31599479 |
| macular thickness measurements of healthy, naïve cynomolgus monkeys assessed with spectral-domain optical coherence tomography (sd-oct). | the purpose of this study was to measure central macular thickness in an unprecedented number of cynomolgus monkeys. macular thickness was measured with heidelberg spectral-domain oct in 320 eyes of healthy and treatment-naïve cynomolgus monkeys (80 males and 80 females). the macula was successfully measured in all 320 eyes. macular thickness was not significantly different between the sexes. the mean central macular thickness was 244 μm (+/- 21 μm). macular thicknesses in the quadrants were 327 ... | 2019 | 31589624 |
| evaluation of preclinical safety profile of sph3127, a direct renin inhibitor, after 28-day repeated oral administration in sprague-dawley rats and cynomolgus monkeys. | sph3127, a newly developed oral nonpeptide direct renin inhibitor with good tolerance and favorable adme (absorption distribution metabolism excretion) properties in preclinical species, is now being evaluated in phase ι clinical trial. in this work, the subchronic toxicity of sph3127 in sprague-dawley rats and cynomolgus monkeys has been characterized. rats and monkeys received sph3127 orally (30, 300, 900 and 20, 100, 450 mg/kg/day, respectively) on a consecutive daily dosing schedule for 28 d ... | 2019 | 31585137 |
| an allosteric anti-tryptase antibody for the treatment of mast cell-mediated severe asthma. | severe asthma patients with low type 2 inflammation derive less clinical benefit from therapies targeting type 2 cytokines and represent an unmet need. we show that mast cell tryptase is elevated in severe asthma patients independent of type 2 biomarker status. active β-tryptase allele count correlates with blood tryptase levels, and asthma patients carrying more active alleles benefit less from anti-ige treatment. we generated a noncompetitive inhibitory antibody against human β-tryptase, which ... | 2019 | 31585081 |
| organic anion-transporting polypeptide genes are not induced by the pregnane x receptor activator rifampin: studies in hepatocytes in vitro and in monkeys in vivo. | induction potentials of the pregnane x receptor (pxr) activator rifampin (rif) on transporter genes [e.g., organic anion-transporting polypeptides (oatps)] are still in its infancy or remain controversial in the field. the present investigations characterized changes in transporter gene expression by rif in sandwich-cultured hepatocytes from multiple donors of human and cynomolgus monkey using real-time quantitative reverse transcription polymerase chain reaction method. three-day treatment of r ... | 2019 | 31582395 |
| long-term outcome and rejection after allogeneic uterus transplantation in cynomolgus macaques. | uterus transplantation (utx) is an option for women with uterine factor infertility to have a child, but is still in the experimental stage. therefore, allogeneic animal models of utx are required for resolution of clinical issues. in this study, long-term outcomes were evaluated in four recipients (cases 1-4) after allogeneic utx in cynomolgus macaques. immunosuppression with antithymocyte globulin induction and a triple maintenance regimen was used. postoperative ultrasonography and biopsy of ... | 2019 | 31581534 |
| adverse vacuolation in multiple tissues in cynomolgus monkeys following repeat-dose administration of a pegylated protein. | pegylation is considered a safe mechanism to enhance the pharmacokinetics (pk) and pharmacodynamics (pd) of biotherapeutics. previous studies using pegylation as a pk enhancement tool have reported benign peg-related vacuolation in multiple tissues. this paper establishes a threshold for peg burden beyond which there are alterations in tissue architecture that could potentially lead to dysfunction. as part of the nonclinical safety assessment of compound a, a 12 kda protein conjugated to a 40 kd ... | 2019 | 31580884 |
| intrastriatal alpha-synuclein fibrils in monkeys: spreading, imaging and neuropathological changes. | several studies have demonstrated that intrastriatal injections of fibrillar α-synuclein in rodent brain induced a parkinson's disease-like propagation of lewy body pathology with significant nigrostriatal neurodegeneration. this study evaluated the pathological features when exogenous α-synuclein preformed fibrils were injected into the putamen of non-human primates. eight cynomolgus monkeys received unilateral intraputamen injections of α-synuclein preformed fibrils and four monkeys received s ... | 2019 | 31580415 |
| vaccines inducing immunity to lassa virus glycoprotein and nucleoprotein protect macaques after a single shot. | lassa fever is a major threat in western africa. the large number of people living at risk for this disease calls for the development of a vaccine against lassa virus (lasv). we generated live-attenuated lasv vaccines based on measles virus and mopeia virus platforms and expressing different lasv antigens, with the aim to develop a vaccine able to protect after a single shot. we compared the efficacy of these vaccines against lasv in cynomolgus monkeys. the vaccines were well tolerated and prote ... | 2019 | 31578242 |
| controlled-release mitochondrial protonophore (crmp) reverses dyslipidemia and hepatic steatosis in dysmetabolic nonhuman primates. | nonalcoholic fatty liver disease (nafld) is estimated to affect up to one-third of the general population, and new therapies are urgently required. our laboratory previously developed a controlled-release mitochondrial protonophore (crmp) that is functionally liver-targeted and promotes oxidation of hepatic triglycerides. although we previously demonstrated that crmp safely reverses hypertriglyceridemia, fatty liver, hepatic inflammation, and fibrosis in diet-induced rodent models of obesity, th ... | 2019 | 31578240 |
| sequelae of fetal infection in a non-human primate model of listeriosis. | listeria monocytogenes (lm) is a common environmental bacterium that thrives on vegetation and soil matter, but can infect humans if contaminated food products are ingested, resulting in severe disease in immunosuppressed populations, including pregnant women and newborns. to better understand how the unique immunological milieu of pregnancy increases susceptibility to infection, we study listeriosis in cynomolgus macaques, a non-human primate that closely resembles humans in placentation and in ... | 2019 | 31572310 |
| persistent crimean-congo hemorrhagic fever virus infection in the testes and within granulomas of non-human primates with latent tuberculosis. | crimean-congo hemorrhagic fever (cchf) is the most medically important tick-borne viral disease of humans and tuberculosis is the leading cause of death worldwide by a bacterial pathogen. these two diseases overlap geographically, however, concurrent infection of cchf virus (cchfv) with mycobacterial infection has not been assessed nor has the ability of virus to persist and cause long-term sequela in a primate model. in this study, we compared the disease progression of two diverse strains of c ... | 2019 | 31557262 |
| non-human primate papillomaviruses share similar evolutionary histories and niche adaptation as the human counterparts. | given high genetic diversity of papillomaviruses (pv) and complex scenario of virus-host interaction, the genetic basis underlying the mechanisms of hpv carcinogenicity is not well understood. in an effort to evaluate the origin and evolution of pv pathogenicity, we collected paired oral, perianal, and genital swabs from a wild macaque population. of the 117 surveyed macaques, 88 (75.2%) were positive for pv dna in one or more sites, mostly common from genital swabs, followed by oral and periana ... | 2019 | 31552003 |
| functional, biophysical, and structural characterization of human igg1 and igg4 fc variants with ablated immune functionality. | engineering of fragment crystallizable (fc) domains of therapeutic immunoglobulin (igg) antibodies to eliminate their immune effector functions while retaining other fc characteristics has numerous applications, including blocking antigens on fc gamma (fcγ) receptor-expressing immune cells. we previously reported on a human igg2 variant termed igg2σ with barely detectable activity in antibody-dependent cellular cytotoxicity, phagocytosis, complement activity, and fcγ receptor binding assays. her ... | 2017 | 31548527 |
| nonclinical safety of tildrakizumab, a humanized anti-il-23p19 monoclonal antibody, in nonhuman primates. | tildrakizumab (also known as mk-3222), is a high-affinity, humanized, immunoglobin g1κ monoclonal antibody targeting the p19 subunit of interleukin-23 recently approved for the treatment of moderate to severe plaque psoriasis in the us, europe, and australia. the safety profile of tildrakizumab was characterized in nonclinical studies using a pharmacologically relevant cynomolgus monkey model. in repeat-dose toxicity studies, cynomolgus monkeys were chronically treated with subcutaneous (sc) inj ... | 2019 | 31536773 |
| a vp35 mutant ebola virus lacks virulence but can elicit protective immunity to wild-type virus challenge. | zaire ebolavirus (ebov) vp35 protein is a suppressor of type i interferon (ifn) production, an inhibitor of dendritic cell maturation, and a putative virulence determinant. here, a recombinant ebov encoding a mutant vp35 virus (vp35m) is demonstrated to activate rig-i-like receptor signaling and innate antiviral pathways. when inoculated into cynomolgus macaques, vp35m exhibits dramatic attenuation as compared to wild-type ebov (wtebov), with 20 or 300 times the standard 100% lethal challenge do ... | 2019 | 31533029 |
| safety and pharmacodynamics of anti-cd2 monoclonal antibody treatment in cynomolgus macaques - an experimental study. | anti-cd2 treatment provides targeted immunomodulatory properties that have demonstrated clinical usefulness to condition the immune system and to treat transplant rejection. the treatment is species-specific due to structural cd2 antigen differences between nonhuman primates and humans. herein, we report the safety profile and efficacy of two modifications of the same anti-cd2 monoclonal antibody in cynomolgus macaques. twelve subjects received one i.v. anti-cd2 (of rat or rhesus type) dose each ... | 2020 | 31523849 |
| elucidation of n1-methyladenosine as a potential surrogate biomarker for drug interaction studies involving renal organic cation transporters. | endogenous substrates are emerging biomarkers for drug transporters, which serve as surrogate probes in drug-drug interaction (ddi) studies. in this study, the results of metabolome analysis using wild-type and oct1/2 double knockout mice suggested that n1-methyladenosine (m1a) was a novel organic cation transporter (oct) 2 substrate. an in vitro transport study revealed that m1a is a substrate of mouse oct1, oct2, mate1, human oct1, oct2, and multidrug and toxin exclusion protein (mate) 2-k, bu ... | 2019 | 31511257 |
| ferritin expression in the periodontal tissues of primates. | ferritin, an iron-binding protein, is composed of two subunits, a heavy chain and a light chain. it regulates many biological functions, such as proliferation, angiogenesis, and immunosuppression. the objective of this study was to determine the expression and distribution of ferritin in the periodontal tissuesof primates.first, we assessed the expression of ferritin in primary cultured cells isolated from human periodontal tissues using the polymerase chain reaction and immunofluorescent staini ... | 2019 | 31505926 |
| the nonclinical pharmacokinetics and prediction of human pharmacokinetics of sph3127, a novel direct renin inhibitor. | sph3127 is a novel direct renin inhibitor designed as an oral drug for the regulation of blood pressure and body fluid homeostasis via the renin-angiotensin-aldosterone system (raas). this candidate is now being evaluated in a phase i clinical trial in china. | 2020 | 31494843 |
| intradermal vaccination prevents anti-mog autoimmune encephalomyelitis in macaques. | autoimmune demyelinating diseases (add) are a major cause of neurological disability due to autoreactive cellular and humoral immune responses against brain antigens. a cure for chronic add could be obtained by appropriate immunomodulation. | 2019 | 31492559 |
| both diet and helicobacter pylori infection contribute to atherosclerosis in pre- and postmenopausal cynomolgus monkeys. | a number of viruses and bacterial species have been implicated as contributors to atherosclerosis, potentially providing novel pathways for prevention. epidemiological studies examining the association between helicobacter pylori and cardiovascular disease have yielded variable results and no studies have been conducted in nonhuman primates. in this investigation, we examined the relationship between h. pylori infection and atherosclerosis development in socially housed, pre- and postmenopausal ... | 2019 | 31490998 |
| jak3 inhibitor-based immunosuppression in allogeneic islet transplantation in cynomolgus monkeys. | islet transplantation is efficacious to prevent severe hypoglycemia and glycemic liability of selected patients of type 1 diabetes. however, since calcineurin inhibitor (cni) causes β-cell and nephrotoxicity, alternative drug(s) with similar potency and safety profile to cni will be highly desirable. here we tested whether jak3 inhibitor, tofacitinib could be used instead of tacrolimus in cit07 immunosuppression regimen in cynomolgus nonhuman primate (nhp) model. five independent streptozotocin ... | 2019 | 31483188 |
| physiological and drug-induced changes in blood levels of adrenal steroids and their precursors in cynomolgus monkeys: an application of steroid profiling by lc-ms/ms for evaluation of the adrenal toxicity. | the adrenal gland is the most common toxicological target of drugs within the endocrine system, and inhibition of adrenal steroidogenesis can be fatal in humans. however, methods to evaluate the adrenal toxicity are limited. the aim of the present study was to verify the usefulness of simultaneous measurement of blood levels of multiple adrenal steroids, including precursors, as a method to evaluate drug effects on adrenal steroidogenesis in cynomolgus monkeys. with this aim, physiological and d ... | 2019 | 31474739 |
| utilization of lipopolysaccharide challenge in cynomolgus macaques to assess il-10 receptor antagonism. | the current era of drug discovery has been marked by a significant increase in the development of immune modulating agents to address a range of diseases such as cancer, chronic inflammation, and other conditions of dysregulated immunity. non-clinical evaluation of these agents in animal models can be challenging, as the presence of an active immune state is often required in order to detect the effects of the test agent. modulation of interleukin (il)-10 signaling represents this type of situat ... | 2019 | 31464151 |
| the cynomolgus macaque mhc polymorphism in experimental medicine. | among the non-human primates used in experimental medicine, cynomolgus macaques (macaca fascicularis hereafter referred to as mafa) are increasingly selected for the ease with which they are maintained and bred in captivity. macaques belong to old world monkeys and are phylogenetically much closer to humans than rodents, which are still the most frequently used animal model. our understanding of the mafa genome has progressed rapidly in recent years and has greatly benefited from the latest tech ... | 2019 | 31455025 |
| partial sequence analyses of exon 7 of the abo locus of cynomolgus (macaca fascicularis) and rhesus (m. mulatta) macaques: indeterminate phenotypes show the presence of the o blood group. | compatibility tests to identify a, b, and o alleles are critical for establishing suitable donor-recipient matches among experimental animals. using a qpcr-based snp probe assay, we have identified a, b, ab, and indeterminate blood group phenotypes in cynomolgus and rhesus macaques. we have hypothesized, albeit without molecular confirmation, that the indeterminate phenotype represents homozygosity for the null o allele at the macaque abo locus. the indeterminate phenotype represents the unsucce ... | 2019 | 31448567 |
| preclinical development of a high affinity α-synuclein antibody, medi1341, that can enter the brain, sequester extracellular α-synuclein and attenuate α-synuclein spreading in vivo. | there are no approved drug therapies that can prevent or slow the progression of parkinson's disease (pd). accumulation and aggregation of α-synuclein protein is observed throughout the nervous system in pd. α-synuclein is a core component of lewy bodies and neurites that neuropathologically define pd, suggesting that α-synuclein may be a key causative agent in pd. recent experimental data suggest that pd progression may arise due to spreading of pathological forms of extracellular α-synuclein t ... | 2019 | 31445162 |
| deposition of aerosolized lucinactant in nonhuman primates. | background: lucinactant for inhalation is an investigational noninvasive, aerosolized surfactant replacement therapy for treatment of preterm neonates with respiratory distress syndrome. lucinactant for inhalation consists of lyophilized lucinactant and the aerosurf® delivery system (ads). the objective of this study was to characterize the total and regional pulmonary deposition of lucinactant delivered by the ads in nonhuman primates (nhps). methods: lucinactant was radiolabeled by the additio ... | 2020 | 31436493 |
| neutrophils express pro- and anti-inflammatory cytokines in granulomas from mycobacterium tuberculosis-infected cynomolgus macaques. | neutrophils are implicated in the pathogenesis of tuberculosis (tb), a disease caused by mycobacterium tuberculosis infection, but the mechanisms by which they promote disease are not fully understood. neutrophils can express cytokines that influence tb progression, and so we compared neutrophil and t-cell expression of the th1 cytokines ifnγ and tnf, the th2 cytokine il-4, and regulatory cytokine il-10 in m. tuberculosis-infected macaques to determine if neutrophil cytokine expression contribut ... | 2019 | 31434990 |
| preclinical efficacy and safety comparison of cd3 bispecific and adc modalities targeting bcma for the treatment of multiple myeloma. | the restricted expression pattern of b-cell maturation antigen (bcma) makes it an ideal tumor-associated antigen (taa) for the treatment of myeloma. bcma has been targeted by both cd3 bispecific antibody and antibody-drug conjugate (adc) modalities, but a true comparison of modalities has yet to be performed. here we utilized a single bcma antibody to develop and characterize both a cd3 bispecific and 2 adc formats (cleavable and noncleavable) and compared activity both in vitro and in vivo with ... | 2019 | 31434693 |
| long-tailed macaques extract statistical information from repeated types of events to make rational decisions under uncertainty. | human children and apes seem to be intuitive statisticians when making predictions from populations of objects to randomly drawn samples, whereas monkeys seem not to be. statistical reasoning can also be investigated in tasks in which the probabilities of different possibilities must be inferred from relative frequencies of events, but little is known about the performance of nonhuman primates in such tasks. in the current study, we investigated whether long-tailed macaques extract statistical i ... | 2019 | 31431638 |
| investigation of gene expression and dna methylation from seven different brain regions of a crab-eating monkey as determined by rna-seq and whole-genome bisulfite sequencing. | the crab-eating monkey is widely used in biomedical research for pharmacological experiments. epigenetic regulation in the brain regions of primates involves complex patterns of dna methylation. previous studies of methylated cpg-binding domains using microarray technology or peak identification of sequence reads mostly focused on developmental stages or disease, rather than normal brains. to identify correlations between gene expression and dna methylation levels that may be related to transcri ... | 2019 | 31428131 |
| from cell culture to cynomolgus macaque: infection models show lineage-specific virulence potential of coxiella burnetii. | coxiella burnetii is an obligate intracellular pathogen that causes the zoonotic disease q fever in humans, which can occur in either an acute or a chronic form with serious complications. the bacterium has a wide host range, including unicellular organisms, invertebrates, birds and mammals, with livestock representing the most significant reservoir for human infections. cell culture models have been used to decipher the intracellular lifestyle of c. burnetii, and several infection models, inclu ... | 2019 | 31424378 |
| indel-informed bayesian analysis suggests cryptic population structure between plasmodium knowlesi of humans and long-tailed macaques (macaca fascicularis) in malaysian borneo. | plasmodium knowlesi is an important causative agent of malaria in humans of southeast asia. macaques are natural hosts for this parasite, but little is conclusively known about its patterns of transmission within and between these hosts. here, we apply a comprehensive phylogenetic approach to test for patterns of cryptic population genetic structure between p. knowlesi isolated from humans and long-tailed macaques from the state of sarawak in malaysian borneo. our approach differs from previous ... | 2019 | 31421245 |
| efficacy of clarithromycin against h5n1 and h7n9 avian influenza a virus infection in cynomolgus monkeys. | clarithromycin (cam), a 14-membered ring macrolide, has anti-inflammatory and immunomodulatory actions and antiviral effects in seasonal influenza virus infection. we examined the prophylactic and therapeutic efficacy of cam against h5n1 highly pathogenic and h7n9 low pathogenic avian influenza virus infections in cynomolgus monkeys. cam suppressed h5n1 virus-induced severe signs of disease in the treated monkeys and inhibited virus propagation in tracheal samples and the production of inflammat ... | 2019 | 31421167 |
| vaccination of macaques with dna followed by adenoviral vectors encoding simian immunodeficiency virus (siv) gag alone delays infection by repeated mucosal challenge with siv. | vaccines aimed at inducing t cell responses to protect against human immunodeficiency virus (hiv) infection have been under development for more than 15 years. replication-defective adenovirus (rad) vaccine vectors are at the forefront of this work and have been tested extensively in the simian immunodeficiency virus (siv) challenge macaque model. vaccination with rad vectors coding for siv gag or other nonenvelope proteins induces t cell responses that control virus load but disappointingly is ... | 2019 | 31413132 |
| a novel anti-dr5 antibody-drug conjugate possesses a high-potential therapeutic efficacy for leukemia and solid tumors. | it is well known that tumor necrosis factor-related apoptosis inducing ligand receptor 1 or 2 (dr4/dr5) is specifically expressed in various tumor cells, but less or no expression in most normal cells. many first generations of trail agonists including recombinant preparations of trail, agonistic antibodies against dr4/dr5 have been developed in phase i/ii clinical trials for cancer therapy. however, the outcomes of clinical trials by using dr4/dr5 agonist mono-therapy were disappointed even tho ... | 2019 | 31410224 |
| normal anatomy, histology, and spontaneous pathology of the kidney, and selected renal biomarker reference ranges in the cynomolgus monkey. | to further our understanding of the nonhuman primate kidney anatomy, histology, and incidences of spontaneous pathology, we retrospectively examined kidneys from a total of 505 control cynomolgus monkeys (macaca fascicularis; 264 male and 241 females) aged 2 to 6 years, from toxicity studies. kidney weights, urinalysis, and kidney-related clinical biochemistry parameters were also evaluated. although the functional anatomy of the monkey kidney is relatively similar to that of other laboratory an ... | 2019 | 31409264 |
| antibody therapy for lassa fever. | serum from convalescent lassa fever patients was previously shown to be ineffective as a source of protective antibodies in some early studies. subsequently, monoclonal antibodies (mabs) to the lassa virus (lasv) glycoprotein produced by memory b cells of west african patients who survived lassa fever were identified. development of mabs as potential lassa immunotherapeutics was facilitated by structural studies and mutational analyses that identified protective epitopes on the prefusion form of ... | 2019 | 31401518 |
| receptor density pattern confirms and enhances the anatomic-functional features of the macaque superior parietal lobule areas. | the macaque monkey superior parietal lobule (spl) is part of a neuronal network involved in the integration of information from visual and somatosensory cortical areas for execution of reaching and grasping movements. we applied quantitative in vitro receptor autoradiography to analyse the distribution patterns of 15 different receptors for glutamate, gaba, acetylcholine, serotonin, dopamine, and adenosine in the spl of three adult male macaca fascicularis monkeys. for each area, mean (averaged ... | 2019 | 31392403 |
| social-valence-related increased attention in rett syndrome cynomolgus monkeys: an eye-tracking study. | the cognitive phenotypes of rett syndrome (rtt) remain unclarified compared with the well-defined genetic etiology. recent clinical studies suggest the eye-tracking method as a promising avenue to quantify the visual phenotypes of the syndrome. the present study explored various aspects of visual attention of the methyl-cpg-binding protein 2 gene mutant rtt monkeys with the eye-tracking procedure. comprehensive testing paradigms, including social valence comparison (svc), visual paired compariso ... | 2019 | 31389199 |
| impact of cmv reactivation, treatment approaches, and immune reconstitution in a nonmyeloablative tolerance induction protocol in cynomolgus macaques. | cytomegalovirus (cmv) infection is a serious complication in immunosuppressed patients, specifically transplant recipients. here, we describe the development and use of an assay to monitor the incidence and treatment of cmv viremia in a cynomolgus macaque model of bone marrow transplantation (bmt) for tolerance induction. we address the correlation between the course of viremia and immune reconstitution. | 2020 | 31385931 |
| analysis of macaque btn3a genes and transcripts in the extended mhc: conserved orthologs of human γδ t cell modulators. | butyrophilins (btn), specifically btn3a, play a central role in the modulation of γδ t cells, which are mainly present in gut and mucosal tissues. btn3a1 is known, for example, to activate vγ9vδ2 t cells by means of a phosphoantigen interaction. in the extended hla region, three genes are located, designated btn3a1, btn3a2 and btn3a3, which were also defined in rhesus macaques. in contrast to humans, rhesus monkeys have an additional gene, btn3a3like, which has the features of a pseudogene. cdna ... | 2019 | 31384962 |
| rvsvδg-zebov-gp (also designated v920) recombinant vesicular stomatitis virus pseudotyped with ebola zaire glycoprotein: standardized template with key considerations for a risk/benefit assessment. | the brighton collaboration viral vector vaccines safety working group (v3swg) was formed to evaluate the safety and characteristics of live, recombinant viral vector vaccines. a recent publication by the v3swg described live, attenuated, recombinant vesicular stomatitis virus (rvsv) as a chimeric virus vaccine for hiv-1 (clarke et al., 2016). the rvsv vector system is being explored as a platform for development of multiple vaccines. this paper reviews the molecular and biological features of th ... | 2019 | 31384731 |
| two validated liquid chromatography-mass spectrometry methods with different pretreatments for the quantification of an anti-cd47 monoclonal antibody in rat and cynomolgus monkey serum compared with an electrochemiluminescence method. | establishing reliable bioanalytical methods is essential to support pharmacokinetic (pk) studies in the preclinical and clinical evaluation of monoclonal antibody (mab) drugs. ligand binding assay (lba) has always been the gold standard for protein quantification, whereas lc-ms has gradually become a promising alternative method for the study of pharmacokinetics of biotherapeutics with its advantages of accuracy and rapid method development. here, we described for the first time two liquid chrom ... | 2019 | 31377653 |
| a divalent sirna chemical scaffold for potent and sustained modulation of gene expression throughout the central nervous system. | sustained silencing of gene expression throughout the brain using small interfering rnas (sirnas) has not been achieved. here we describe an sirna architecture, divalent sirna (di-sirna), that supports potent, sustained gene silencing in the central nervous system (cns) of mice and nonhuman primates following a single injection into the cerebrospinal fluid. di-sirnas are composed of two fully chemically modified, phosphorothioate-containing sirnas connected by a linker. in mice, di-sirnas induce ... | 2019 | 31375812 |
| carriage of methicillin-resistant staphylococcus aureus in a colony of rhesus (macaca mulatta) and cynomolgus (macaca fascicularis) macaques. | methicillin-resistant staphylococcus aureus (mrsa) carriage and infection are well documented in the human and veterinary literature; however only limited information is available regarding mrsa carriage and infection in laboratory nhp populations. the objective of this study was to characterize mrsa carriage in a representative research colony of rhesus and cynomolgus macaques through a cross-sectional analysis of 300 animals. mrsa carriage was determined by using nasal culture. demographic cha ... | 2019 | 31375150 |
| primary infection with dengue or zika virus does not affect the severity of heterologous secondary infection in macaques. | zika virus (zikv) and dengue virus (denv) are genetically and antigenically related flaviviruses that now co-circulate in much of the tropical and subtropical world. the rapid emergence of zikv in the americas in 2015 and 2016, and its recent associations with guillain-barré syndrome, birth defects, and fetal loss have led to the hypothesis that denv infection induces cross-reactive antibodies that influence the severity of secondary zikv infections. it has also been proposed that pre-existing z ... | 2019 | 31369649 |
| high prevalence of hepatitis e virus infection in imported cynomolgus monkeys in japan. | cynomolgus monkeys are important experimental animals for hepatitis e virus (hev) infection. in japan, cynomolgus monkeys are mainly imported from asian countries for use at animal facilities and institutions. however, the status of hev infection in cynomolgus monkeys remains unclear. overall, 187 pairs of serum and fecal samples were collected from cynomolgus monkeys (macaca fascicularis) imported from china and cambodia to detect anti-hev immunoglobulin (ig) g and igm antibodies, as well as he ... | 2019 | 31366861 |
| evaluation of factor viii polysialylation: identification of a longer-acting experimental therapy in mice and monkeys. | extended half-life (ehl) factor therapies are needed to reduce the burden of prophylaxis and improve treatment adherence in patients with hemophilia. bax 826 is a novel polysialylated full-length recombinant factor viii [polysialyic acid (psa) rfviii] with improved pharmacokinetics (pk), prolonged pharmacology, and maintained safety attributes to enable longer-acting rfviii therapy. in factor viii (fviii)-deficient hemophilic mice, psarfviii showed a substantially higher mean residence time (>2- ... | 2019 | 31366602 |
| interspecies variation in ncmn-o-demethylation in liver microsomes from various species. | ncmn (n-(3-carboxy propyl)-4-methoxy-1,8-naphthalimide), a newly developed ratiometric two-photon fluorescent probe for human cytochrome p450 1a (cyp1a), shows the best combination of specificity and reactivity for real-time detection of the enzymatic activities of cyp1a in complex biological systems. this study aimed to investigate the interspecies variation in ncmn-o-demethylation in commercially available liver microsomes from human, mouse, rat, beagle dog, minipig and cynomolgus monkey. meta ... | 2019 | 31366067 |
| evaluation of the developmental toxicity of vedolizumab, an α4β7 receptor antagonist, in rabbit and nonhuman primate. | vedolizumab, a humanized monoclonal antibody approved for the treatment of adults with moderately to severely active ulcerative colitis or crohn disease, targets α4β7 integrin and selectively blocks gut-specific lymphocyte trafficking. the potential effects of vedolizumab on development were assessed by standard preclinical toxicity studies in rabbits and cynomolgus monkeys. a single infusion of vedolizumab (0, 10, 30, or 100 mg/kg) was administered intravenously to pregnant rabbits on gestation ... | 2020 | 31364424 |
| systems approach reveals photosensitivity and per2 level as determinants of clock-modulator efficacy. | in mammals, the master circadian clock synchronizes daily rhythms of physiology and behavior with the day-night cycle. failure of synchrony, which increases the risk for numerous chronic diseases, can be treated by phase adjustment of the circadian clock pharmacologically, for example, with melatonin, or a ck1δ/ε inhibitor. here, using in silico experiments with a systems pharmacology model describing molecular interactions, and pharmacokinetic and behavioral experiments in cynomolgus monkeys, w ... | 2019 | 31353796 |
| in vivo intrathecal tracer dispersion in cynomolgus monkey validates wide biodistribution along neuraxis. | it is commonly believed that in intrathecal (it) drug delivery, agent distribution is confined to a narrow region close to the injection site, thereby undermining the efficacy of the method. | 2020 | 31352328 |
| haversian remodeling corresponds to load frequency but not strain magnitude in the macaque (macaca fascicularis) skeleton. | one way bone adapts to its mechanical environment is by haversian remodeling, a repair process in which existing bone is resorbed and replaced by new bone. haversian remodeling forms interconnected, cylindrical structures called secondary osteons. the amount of remodeling that occurs is related to the nature of mechanical loading and accrual of microdamage, but it is uncertain whether habitual loads of high magnitude versus high frequency result in more remodeling. the answer to this question is ... | 2019 | 31352155 |
| pkpd assessment of the anti-cd20 antibody obinutuzumab in cynomolgus monkey is feasible despite marked anti-drug antibody response in this species. | the pharmacokinetics (pk) of the anti-cd20 monoclonal antibody obinutuzumab was assessed after single intravenous dosing to cynomolgus monkeys. in addition, the pharmacokinetic-pharmacodynamic (pkpd) relationship for b-cell depletion was characterized. the pkpd model was used to estimate the b-cell repopulation during the recovery phase of chronic toxicology studies, thereby supporting the study design, in particular planning the recovery phase duration. marked immunogenicity against obinutuzuma ... | 2019 | 31351865 |
| preclinical development of u3-1784, a novel fgfr4 antibody against cancer, and avoidance of its on-target toxicity. | the fgfr4/fgf19 signaling axis is overactivated in 20% of liver tumors and currently represents a promising targetable signaling mechanism in this cancer type. however, blocking fgfr4 or fgf19 has proven challenging due to its physiological role in suppressing bile acid synthesis which leads to increased toxic bile acid plasma levels upon fgfr4 inhibition. an fgfr4-targeting antibody, u3-1784, was generated in order to investigate its suitability as a cancer treatment without major side effects. ... | 2019 | 31350344 |
| a sensitive and selective immunoassay for the quantitation of serum latent myostatin after in vivo administration of srk-015, a selective inhibitor of myostatin activation. | myostatin, a member of the transforming growth factor β (tgfβ) superfamily, is a key regulator of skeletal muscle mass and a therapeutic target for muscle wasting diseases. we developed a human monoclonal antibody, srk-015, that selectively binds to and inhibits proteolytic processing of myostatin precursors, thereby preventing growth factor release from the latent complex. as a consequence of antibody binding, latent myostatin accumulates in the circulation of animals treated with srk-015 or cl ... | 2020 | 31347449 |
| the pi3kδ selective inhibitor as2541019 suppresses donor-specific antibody production in rat cardiac and non-human primate renal allotransplant models. | long-term graft survival after organ transplantation is difficult to achieve because of the development of chronic rejection. one cause of chronic rejection arises from antibody-mediated rejection (amr), which is dependent on the production of donor-specific antibodies (dsa). current immunosuppression in organ transplantation is effective in preventing acute t cell-mediated rejection, but the risk of dsa production and graft loss due to amr remains unchanged. phosphatidylinositol-3-kinase p110δ ... | 2019 | 31344556 |
| refinement of the primate corticospinal pathway during prenatal development. | perturbation of the developmental refinement of the corticospinal (cs) pathway leads to motor disorders. while non-primate developmental refinement is well documented, in primates invasive investigations of the developing cs pathway have been confined to neonatal and postnatal stages when refinement is relatively modest. here, we investigated the developmental changes in the distribution of cs projection neurons in cynomolgus monkey (macaca fascicularis). injections of retrograde tracer at cervi ... | 2020 | 31343065 |
| unveil the transcriptional landscape at the cryptococcus-host axis in mice and nonhuman primates. | pathogens and hosts require rapid modulation of virulence and defense mechanisms at the infection axis, but monitoring such modulations is challenging. in studying the human fungal pathogen cryptococcus neoformans, mouse and rabbit infection models are often employed to shed light on the disease mechanisms but that may not be clinically relevant. in this study, we developed an animal infection model using the non-human primate cynomolgus monkey macaca fascicularis. in addition, we systematically ... | 2019 | 31329596 |
| the neglected medial part of macaque area pe: segregated processing of reach depth and direction. | area pe (brodmann's area 5), located in the posterior parietal cortex (ppc), is involved in the control of arm movements. many monkey studies showed pe's involvement in reach directions, while only a few revealed signals coding the depth of reaches. notably, all these studies focused on the lateral part of pe, leaving its medial part functionally largely unexplored. we here recorded neuronal activity in the medial part of pe in three male macaca fascicularis while they performed coordinated eye ... | 2019 | 31327073 |
| daily ascending dosing in cynomolgus monkeys to mitigate cytokine release syndrome induced by ery22, surrogate for t-cell redirecting bispecific antibody ery974 for cancer immunotherapy. | cd3 bispecific constructs show promising therapeutic potential as anti-tumor antibodies, but it has concurrently been difficult to manage cytokine release syndrome (crs) in clinical use. currently, the most effective measure for reducing crs is considered a combination of intra-patient/animal dose escalation and corticosteroid premedication. to examine how effectively an intra-animal ascending dose regimen without premedication would mitigate crs, we compared plasma cytokine levels in two groups ... | 2019 | 31326447 |
| human plasmodium knowlesi infections in south-east asian countries. | plasmodium knowlesi is now regarded as the fifth malaria parasite causing human malaria as it is widely distributed in south-east asian countries especially east malaysia where two malaysian states namely sabah and sarawak are situated. in 2004, polymerase chain reaction (pcr) was applied for diagnosing knowlesi malaria in the kapit division of sarawak, malaysia, so that human p. knowlesi infections could be detected correctly while blood film microscopy diagnosed incorrectly as plasmodium malar ... | 2019 | 31320238 |
| persistence of gut microbiota dysbiosis and chronic systemic inflammation after cerebral infarction in cynomolgus monkeys. | background: the bidirectional interaction between the gut and brain after stroke through the immune-mediated pathway has been studied. however, the long-term effects of gut microbiota and systemic immune homeostasis after cerebral ischemia remain unclear. we examined long-term changes in the gut microbiota and systemic inflammatory cytokines after cerebral infarction in cynomolgus monkeys. methods: twelve monkeys underwent successful distal m1 segment of the left middle cerebral artery occlusion ... | 2019 | 31316450 |
| a macaque connectome for large-scale network simulations in thevirtualbrain. | models of large-scale brain networks that are informed by the underlying anatomical connectivity contribute to our understanding of the mapping between the structure of the brain and its dynamical function. connectome-based modelling is a promising approach to a more comprehensive understanding of brain function across spatial and temporal scales, but it must be constrained by multi-scale empirical data from animal models. here we describe the construction of a macaque (macaca mulatta and macaca ... | 2019 | 31316116 |