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prima subretinal wireless photovoltaic microchip implantation in non-human primate and feline models.to evaluate the surgical technique for subretinal implantation of two sizes of prima photovoltaic wireless microchip in two animal models, and refine these surgical procedures for human trials.202032267845
transient mixed chimerism with nonmyeloablative conditioning does not induce liver allograft tolerance in nonhuman primates.although short-term outcomes for liver transplantation have improved, patient and graft survivals are limited by infection, cancer and other complications of immunosuppression. rapid induction of tolerance after liver transplantation would decrease these complications, improving survival and quality of life. tolerance to kidneys, but not thoracic organs or islets, has been achieved in nonhuman primates and humans through the induction of transient donor chimerism. since the liver is considered t ...202032265416
islet transplantation to the anterior chamber of the eye-a future treatment option for insulin-deficient type-2 diabetics? a case report from a nonhuman type-2 diabetic primate.replacement of the insulin-secreting beta cells through transplantation of pancreatic islets to the liver is a promising treatment for type-1 diabetes. however, low oxygen tension, shear stress, and the induction of inflammation lead to significant islet dysfunction and loss. the anterior chamber of the eye (ace) has gained considerable interest and represents an alternative therapeutic islet transplantation site because of its accessibility, high oxygen tension, and immune-privileged milieu. we ...202032264703
reference values of hematological and biochemical parameters in young-adult cynomolgus monkey (macaca fascicularis) and rhesus monkey (macaca mulatta) anesthetized with ketamine hydrochloride.nonhuman primate models are valuable in biomedical research. however, reference data for clinical pathology parameters in cynomolgus and rhesus monkeys are limited. in the present study, we established hematologic and biochemical reference intervals for healthy cynomolgus and rhesus monkeys anesthetized with ketamine hydrochloride. a total of 142 cynomolgus monkeys (28 males and 114 females) and 42 rhesus monkeys (22 males and 20 females) were selected and analyzed in order to examine reference ...201932257895
preclinical studies on the toxicology, pharmacokinetics and safety of k1-70tm a human monoclonal autoantibody to the tsh receptor with tsh antagonist activity.the human monoclonal autoantibody k1-70™ binds to the tsh receptor (tshr) with high affinity and blocks tshr cyclic amp stimulation by tsh and thyroid stimulating autoantibodies.201932257067
interleukin-1β and tumor necrosis factor-α affect cytochrome p450 expression in cynomolgus macaque hepatocytes.the cynomolgus macaque, partly due to its evolutionary closeness to humans, is an important nonhuman primate species used in drug metabolism studies. in humans, expressions of cytochromes p450 (p450s), including the important drug-metabolizing enzyme p450 3a4, are affected by various cytokines. however, this phenomenon has not been fully investigated in cynomolgus macaques. in this study, the effects of cytokines on p450 expression were investigated using the quantitative polymerase chain reacti ...202032253084
generation of transgenic cynomolgus monkeys overexpressing the gene for amyloid-β precursor protein.alzheimer's disease (ad) is the most common cause of dementia and understanding its pathogenesis should lead to improved therapeutic and diagnostic methods. although several groups have developed transgenic mouse models overexpressing the human amyloid-β precursor protein (app) gene with ad mutations, with and without presenilin mutations, as well as app gene knock-in mouse models, these animals display amyloid pathology but do not show neurofibrillary tangles or neuronal loss. this presumably i ...202032250299
group size experiences with enhanced pre- and postnatal development studies in the long-tailed macaque (macaca fascicularis).enhanced pre- and postnatal development (eppnd) studies have become the default developmental toxicity test for biopharmaceuticals if nonhuman primates represent the relevant species. spontaneous pregnancy losses and infant deaths can be significant in macaques such as long-tailed macaques. the international council for harmonisation of technical requirements for pharmaceuticals for human use (ich) guideline s6(r1) states that pregnancy outcome can be judged also by the normogram-based variabili ...202032232119
melengestrol acetate (veterinary medicinal products).food safety commission of japan (fscj) conducted a risk assessment of melengestrol acetate (mga, cas no. 2919-66-6), a synthetic hormone, based on results from various studies. mga was recognized to have no genotoxicity relevant to human health, and it enabled fscj to specify an acceptable daily intake (adi) in the assessment. in vitro studies using various human hormone-receptors showed that mga exerts biological action primarily as progestogens and secondarily as glucocorticoids. major adverse ...201732231940
modeling variant creutzfeldt-jakob disease and its pathogenesis in non-human primates.in the early 90s', europe was shaken by the fear that the prions from "mad cow disease" (bovine spongiform encephalopathy) would transmit the disease to humans via beef products. in 1996, the first variant creutzfeldt-jakob (vcjd) patients were described, and the same year our bovine spongiform encephalopathy (bse) transmission studies to cynomolgus macaques demonstrated that the bse prion was highly infectious for primates, inducing brain lesions identical to those observed in vcjd patients. th ...201732231924
non-human primate models of dengue virus infection: a comparison of viremia levels and antibody responses during primary and secondary infection among old world and new world monkeys.due to the global burden of dengue disease, a vaccine is urgently needed. one of the key points in vaccine development is the development of a robust and reliable animal model of dengue virus infection. characteristics including the ability to sustain viral replication, demonstration of clinical signs, and immune response that resemble those of human dengue virus infection are vital in animal models. preclinical studies in vaccine development usually include parameters such as safety evaluation, ...202032230836
excretion of the polymyxin derivative nab739 in murine urine.extremely multiresistant strains of enterobacteriaceae are emerging and spreading at a worrisome pace. polymyxins are used as the last-resort therapy against such strains, in spite of their nephrotoxicity. we have previously shown that novel polymyxin derivatives nab739 and nab815 are less nephrotoxic in cynomolgus monkeys than polymyxin b and are therapeutic in murine escherichia coli pyelonephritis at doses only one-tenth of that needed for polymyxin b. here we evaluated whether the increased ...202032230751
biophysical and immunological characterization and in vivo pharmacokinetics and toxicology in nonhuman primates of the anti-pd-1 antibody pembrolizumab.the programmed cell death 1 (pd-1) pathway represents a major immune checkpoint, which may be engaged by cells in the tumor microenvironment to overcome active t-cell immune surveillance. pembrolizumab (keytruda®, mk-3475) is a potent and highly selective humanized mab of the igg4/kappa isotype designed to directly block the interaction between pd-1 and its ligands, pd-l1 and pd-l2. this blockade enhances the functional activity of t cells to facilitate tumor regression and ultimately immune rej ...202032229606
prolonged intraocular residence and retinal tissue distribution of a fourth-generation compstatin-based c3 inhibitor in non-human primates.age-related macular degeneration (amd) is a leading cause of irreversible vision loss among the elderly population. genetic studies in susceptible individuals have linked this ocular disease to deregulated complement activity that culminates in increased c3 turnover, retinal inflammation and photoreceptor loss. therapeutic targeting of c3 has therefore emerged as a promising strategy for broadly intercepting the detrimental proinflammatory consequences of complement activation in the retinal tis ...202032229292
toward development of the delayed tolerance induction protocol for vascularized composite allografts in nonhuman primates.transplantation of vascularized composite allografts is limited mainly by the need for life-long immunosuppression. the consequent side effects and looming specter of chronic rejection portend eventual allograft loss. development of tolerogenic protocols is thus of utmost importance to the field of vascularized composite allograft transplantation.202032221215
rhesus macaques are most likely the ancestral source of helicobacter suis infection in pigs and not cynomolgus macaques. 202032219893
innate and secondary humoral responses are improved by increasing the time between mva vaccine immunizations.comprehending the mechanisms behind the impact of vaccine regimens on immunity is critical for improving vaccines. indeed, the time-interval between immunizations may influence b and t cells, as well as innate responses. we compared two vaccine schedules using cynomolgus macaques immunized with an attenuated vaccinia virus. two subcutaneous injections 2 weeks apart led to an impaired secondary antibody response and similar innate myeloid responses to both immunizations. in contrast, a delayed bo ...202032218996
development and validation of a multiplex immunoassay for the simultaneous quantification of type-specific igg antibodies to e6/e7 oncoproteins of hpv16 and hpv18.more than 170 types of human papilloma viruses (hpv) exist with many causing proliferative diseases linked to malignancy in indications such as cervical cancer and head and neck squamous cell carcinoma. characterization of antibody levels toward hpv serology is challenging due to complex biology of oncoproteins, pre-existing titers to multiple hpv types, cross-reactivity, and low affinity, polyclonal responses. using multiplex technology from msd, we have developed an assay that simultaneously c ...202032214362
early transcriptional changes within liver, adrenal gland, and lymphoid tissues significantly contribute to ebola virus pathogenesis in cynomolgus macaques.ebola virus (ebov) continues to pose a significant threat to human health, as evidenced by the 2013-2016 epidemic in west africa and the ongoing outbreak in the democratic republic of the congo. ebov causes hemorrhagic fever, organ damage, and shock culminating in death, with case fatality rates as high as 90%. this high lethality combined with the paucity of licensed medical countermeasures makes ebov a critical human pathogen. although ebov infection results in significant damage to the liver ...202032213610
an optimized purified inactivated zika vaccine provides sustained immunogenicity and protection in cynomolgus macaques.the recent spread of zika virus (zikv) through the americas and caribbean and its devastating consequences for pregnant women and their babies have driven the search for a safe and efficacious zikv vaccine. among the vaccine candidates, a first-generation zikv purified inactivated vaccine (zpiv), adjuvanted with aluminum hydroxide, developed by the walter reed army institute of research (wrair), has elicited high seroconversion rates in participants in three phase-i clinical trials. in collabora ...202032194996
a pathology review of the lower gastrointestinal tract in relation to ulcerative colitis in rats and cynomolgus macaques treated with ammonium perfluorooctanoate.among many short-term, subchronic, and chronic toxicology studies with ammonium perfluorooctanoate (pfoa), the gastrointestinal tract has not been identified as a target organ for pfoa-related toxicity in laboratory animals where the corresponding serum pfoa concentrations typically approach several orders of magnitude higher than the general human population. these lack of gastrointestinal tract-related findings were in direct contrast to an epidemiological observation where a positive trend wa ...202032186254
association of antimicrobial resistance and gut microbiota composition in human and non-human primates at an urban ecotourism site.the rise of nature-based ecotourism in the past decade has introduced unprecedented challenges in managing the increasing interaction between humans and animals. the potential transmission of antibiotic resistant microbes between humans and non-human primate populations is a concern due to their genetic similarity. malaysia is well known for hotspots of wildlife diversity where non-human primates like monkeys and orangutans have become popular tourist attractions. in this study, we assessed the ...202032175011
a cervical spinal cord hemi-contusion injury model based on displacement control in non-human primates (macaca fascicularis).non-human primate (nhp) spinal cord injury (sci) models can be informative in the evaluation of treatments that show promise in rodent models prior to translation to humans. in the present study, we aimed to establish a cervical spinal hemi-contusion model with controlled displacement and evaluate the abnormalities in behavior, electrophysiology, histology, and magnetic resonance imaging. twelve adult nhps were divided into an sci group (n = 8, 24 and 48 weeks) and a control group (n = 4). an im ...202032174266
echocardiographic evaluation of cardiac function in cynomolgus monkeys over a wide age range.various cardiovascular diseases can be detected and diagnosed using echocardiography. the demand for cardiovascular system research using nonhuman primates is increasing, but echocardiographic references for nonhuman primates are limited. this report describes the first comparison of echocardiographic reference values in 247 normal cynomolgus monkeys (135 females, 112 males) over a wide age range. echocardiography, electrocardiography, blood pressure and chest x-ray images were acquired under im ...202032173671
synthesis, biodistribution, and radiation dosimetry of a novel mglur5 radioligand: 18f-azd9272.the metabotropic glutamate receptor subtype mglur5 has been proposed as a potential drug target for cns disorders such as anxiety, depression, parkinson's disease, and epilepsy. the astrazeneca compound azd9272 has previously been labeled with carbon-11 and used as a pet radioligand for mglur5 receptor binding. the molecular structure of azd9272 allows one to label the molecule with fluorine-18 without altering the structure. the aim of this study was to develop a fluorine-18 analogue of azd9272 ...202032167745
[markers of hepatitis a in the monkeys of the adlers primate center.]hepatitis a is a widespread viral infection. the hav strains of "human" and "monkey" origin are similar in their morphological and antigenic properties, but differ genotypically.201932167690
local field potentials for bci control.the gold standard in brain-computer interface (bci) modalities is multi single-unit recordings in the primary motor cortex. it yields the fastest and most elegant control (i.e., most degrees of freedom and bitrate). unfortunately, single-unit electrodes are prone to encapsulation, which limit their single-unit recording life. however, encapsulation does not significantly affect intracortical local field potentials (lfps). lfps and single-unit activity were recorded from the motor cortices of thr ...202032164859
retinal features in cynomolgus macaques (macaca fascicularis) assessed by using scanning laser ophthalmoscopy and spectral domain optical coherence tomography.cynomolgus macaques are an important and commonly used species in preclinical toxicology studies, but structural reports of in vivo retinal findings are rare in this species. the purpose of this study was to diminish this gap and document optical coherence tomography and scanning laser ophthalmoscopy imaging data in the healthy posterior pole of cynomolgus monkeys' eyes at predose examinations. the current study is a retrospective assessment of baseline spectral domain oct data obtained from the ...202032164796
pharmacokinetics of polyethylene glycol-modified canine uricase following single and multiple intravenous injections in cynomolgus monkeys.polyethylene glycol-modified canine uricase (peg-uhc) prepared with a lower-molecular-weight (5 kda) peg is used to treat gout. this study investigated the comparative pharmacokinetics of single and multiple doses of peg-uhc administered intravenously and a single dose of uricase (uhc) administered intravenously in cynomolgus monkeys.202032162270
differentiated agonistic antibody targeting cd137 eradicates large tumors without hepatotoxicity.cd137 (4-1bb) is a member of the tnfr superfamily that represents a promising target for cancer immunotherapy. recent insights into the function of tnfr agonist antibodies implicate epitope, affinity, and igg subclass as critical features, and these observations help explain the limited activity and toxicity seen with clinically tested cd137 agonists. here, we describe the preclinical characterization of ctx-471, a fully human igg4 agonist of cd137 that engages a unique epitope that is shared by ...202032161196
simplified drug efficacy screening system for sleep-disorder drugs using non-human primates.the most widely used animal models to develop sleep-disorder drugs are rodents, particularly rats and mice. however, unlike humans, these rodents are nocturnal. thus, diurnal non-human primates represent a valuable and more translational animal model to study sleep. although sleep-disorder drugs have been screened in non-human primates, the use of a telemetry system is not a desirable method for a rapid drug efficacy assessment system because of the need for expensive equipment, complicated surg ...202032154428
a novel c2 domain binding cd33xcd3 bispecific antibody with potent t-cell redirection activity against acute myeloid leukemia.cd33 is expressed in 90% of patients with acute myeloid leukemia (aml), and its extracellular portion consists of a v domain and a c2 domain. a recent study showed that a single nucleotide polymorphism (snp), rs12459419 (c > t), results in the reduced expression of v domain-containing cd33 and limited efficacy of v domain-binding anti-cd33 antibodies. we developed jnj-67571244, a novel human bispecific antibody capable of binding to the c2 domain of cd33 and to cd3, to induce t-cell recruitment ...202032150609
preclinical testing of aav9-php.b for transgene expression in the non-human primate cochlea.in a number of mouse models of hereditary deafness, therapeutic transgene delivery to the cochlea and vestibular organs using adeno-associated viral vectors (aavs) has shown striking rescue of hearing and balance. however, only a subset of aav capsids have shown efficacy in transducing both inner hair cells and outer hair cells, and it is also not clear which of these can be translated to treatment of human inner ear. we recently reported efficient transgene expression of a gfp reporter in a non ...202032145977
ribavirin does not potentiate favipiravir antiviral activity against ebola virus in non-human primates.in spite of recurrent and dramatic outbreaks, there are no therapeutics approved against ebola virus disease. favipiravir, a rna polymerase inhibitor active against several rna viruses, recently demonstrated significant but not complete protection in a non-human primate model of ebola virus disease. in this study, we assessed the benefit of the combination of favipiravir and ribavirin, another broad spectrum antiviral agent, in the same model.202032135218
autologous fibroblasts induce fibrosis of the nucleus pulposus to maintain the stability of degenerative intervertebral discs.lumbar degenerative disc diseases cause low back pain (lbp). the maintenance of the height and stability of the intervertebral disc (ivd) space is an effective treatment for lbp. the following study evaluated the effects of fibroblast injection on intervertebral disc degeneration (idd) in a preclinical setting. compared with the idd group, the fibroblast treatment group demonstrated effective maintenance of ivd height, reduced endplate degeneration, and improved nuclear magnetic resonance signal ...202032128275
cynomolgus monkeys with spontaneous type-2-diabetes-mellitus-like pathology develop alpha-synuclein alterations reminiscent of prodromal parkinson's disease and related diseases.available evidence suggests that diabetes mellitus (dm) is a non-genetic risk factor for parkinson's disease (pd). pd and dm have shared similarities in pathogenetic mechanisms, including age, environmental factors, inflammatory reaction, and protein aggregation, etc. α-synuclein is the primary protein component in the protein inclusions in pd, while islet amyloid polypeptide (iapp) aggregates to form amyloid structures in β cells in type 2 diabetes mellitus (t2dm). pancreatic and cerebral funct ...202032116510
characterization of 100 extended major histocompatibility complex haplotypes in indonesian cynomolgus macaques.many medical advancements-including improvements to anti-rejection therapies in transplantation and vaccine development-rely on preclinical studies conducted in cynomolgus macaques (macaca fascicularis). major histocompatibility complex (mhc) class i and class ii genes of cynomolgus macaques are orthologous to human leukocyte antigen complex (hla) class i and class ii genes, respectively. both encode cell-surface proteins involved in cell recognition and rejection of non-host tissues. mhc class ...202032112172
unparalleled rapid evolution of kir genes in rhesus and cynomolgus macaque populations.the killer cell ig-like receptors (kir) modulate immune responses through interactions with mhc class i molecules. the kir region in large cohorts of rhesus and cynomolgus macaque populations were characterized, and the experimental design enabled the definition of a considerable number of alleles (n = 576) and haplotypes, which are highly variable with regard to architecture. although high levels of polymorphism were recorded, only a few alleles are shared between species and populations. the r ...202032111732
seroprevalence of viral infections in captive rhesus and cynomolgus macaques.macaques serve as important animal models for biomedical research. viral infection of macaques can compromise animal health as well as the results of biomedical research, and infected animals constitute an occupational health risk. therefore, monitoring macaque colonies for viral infection is an important task. we used a commercial chip-based assay to analyze sera of 231 macaques for the presence of antibody responses against nine animal and human viruses. we report high seroprevalence of cytome ...201932110713
feasibility of intravitreal injections and ophthalmic safety assessment in marmoset (callithrix jacchus) monkeys.to safeguard patients, regulatory authorities require that new drugs that are to be given by the intravitreal (ivt) route are assessed for their safety in a laboratory species using the same route of administration. due to the high similarity of ocular morphology and physiology between humans and nonhuman primates (nhps) and due to the species specificity of many biotherapeutics, the monkey is often the only appropriate model. to this end, intravitreal administration and assessment of ocular tox ...201732110696
identification and preclinical development of an anti-proteolytic upa antibody for rheumatoid arthritis.blocking the proteolytic capacity of urokinase-type plasminogen activator (upa) with a monoclonal antibody (mab) reduces arthritis progression in the collagen-induced mouse arthritis model to an extent that is on par with the effect of blocking tumor necrosis factor-alpha by etanercept. seeking to develop a novel therapy for rheumatoid arthritis, a humanized mab, nnc0266-0043, was selected for its dual inhibition of both the zymogen activation and the proteolytic capacity of human upa. the antib ...202032108909
does rank rule? rank-related grooming patterns in nicobar long-tailed macaques macaca fascicularis umbrosus.primates maintain social bonds with specific individuals in the group by directing grooming toward them. social grooming is often targeted toward individuals with whom the most benefits can be exchanged, which are usually the high-ranking individuals. we used the seyfarth model to investigate whether dominance rank alters the distribution of grooming in a group of macaca fascicularis umbrosus at great nicobar island. we investigated whether dominance rank predicted grooming rate in both males an ...202032108904
unusual sequence characteristics of human chromosome 19 are conserved across 11 nonhuman primates.human chromosome 19 has many unique characteristics including gene density more than double the genome-wide average and 20 large tandemly clustered gene families. it also has the highest gc content of any chromosome, especially outside gene clusters. the high gc content and concomitant high content of hypermutable cpg sites raises the possibility chromosome 19 exhibits higher levels of nucleotide diversity both within and between species, and may possess greater variation in dna methylation that ...202032106815
hx008: a humanized pd-1 blocking antibody with potent antitumor activity and superior pharmacologic properties.through reactivating tumor-infiltrating lymphocytes, therapeutics targeting programmed cell death protein 1 (pd-1) demonstrate impressive clinical efficacy in the treatment of multiple cancers. in this report, we characterize hx008, a humanized igg4s228p anti-pd-1 monoclonal antibody with an engineered fc domain, in a series of in vitro assays and in vivo studies. in vitro, hx008 binds to human pd-1 with high affinity and potently suppresses the interaction of pd-1 with pd-l1 and pd-l2. the lack ...202032106752
social status and reproductive success of male macaca fascicularis.dominant males of nonseasonally breeding species should have more opportunity than seasonal breeders to monopolize access to estrous females and thus enhance their reproductive success. they may also use other strategies for maximizing reproductive success such as producing offspring by relatively high ranking females. to test these hypotheses, the paternity of 35 (80%) of 44 macaca fascicularis offspring, born over a 28-month period, was established using electrophoretically and serologically d ...198532102492
summary of a workshop on preclinical and translational safety assessment of cd3 bispecifics.currently, there is a multitude of cd3 bispecifics with different molecular designs and binding properties in preclinical and clinical development for the treatment of liquid or solid tumors. the key safety concerns with cd3 bispecifics are excessive release of cytokines, which may translate to potentially life-threating cytokine release syndrome (crs), target organ toxicity due to redirection of t-cells to normal tissues expressing the tumor-associated antigen (taa) (off-tumor/on-target cytotox ...202032100588
leucine-rich alpha 2 glycoprotein is a new marker for active disease of tuberculosis.tuberculosis (tb) caused by mycobacterium tuberculosis (mtb) is a global health problem. at present, prior exposure to mtb can be determined by blood-based interferon-gamma release assay (igra), but active tb is not always detectable by blood tests such as crp and esr. this study was undertaken to investigate whether leucine-rich alpha-2 glycoprotein (lrg), a new inflammatory biomarker, could be used to assess active disease of tb. cynomolgus macaques pretreated with or without bacille calmette- ...202032099022
habitat suitability analysis reveals high ecological flexibility in a "strict" forest primate.research of many mammal species tends to focus on single habitats, reducing knowledge of ecological flexibility. the javan lutung (trachypithecus auratus) is considered a strict forest primate, and little is known about populations living in savannah. in 2017-2018, we investigated the density and distribution of javan lutung in baluran national park, indonesia. we conducted ad libitum follows and line transect distance sampling with habitat suitability analysis of javan lutung.202032095154
enzootic hepatitis a infection in cynomolgus monkeys (macaca fascicularis).during a toxicology study in cynomolgus (long-tailed or crab-eating) monkeys (macaca fascicularis), a randomly distributed incidence of significantly increased hepatic enzyme activity was observed. premedication hepatic enzyme activity in all monkeys of this study was normal, but increased alanine aminotransferase (alt) activity was found in 4 of the 24 animals 2 weeks after initiation of the study and in 10 of 24 at 4 weeks. a drug-related effect was considered unlikely initially because the in ...198832093430
an akr1c3-specific prodrug with potent anti-tumor activities against t-all.akr1c3 overexpression has been reported in various types of cancers, including t-all. ast-006 (th-3424), an akr1c3-specific prodrug, was reported recently to have potent cytotoxicity against liver cancer cells overexpressing akr1c3 and t-all. in this study, ast-006 demonstrated potent anti-tumor activity against different t-all cell lines in vitro and in vivo, including patient-derived xenograft (pdx) model. ast-006 also exhibited minimal cytotoxicity against primary human t-cells in vitro and l ...202032091283
venezuelan equine encephalitis vaccine with rearranged genome resists reversion and protects non-human primates from viremia after aerosol challenge.live-attenuated v4020 vaccine for venezuelan equine encephalitis virus (veev) containing attenuating rearrangement of the virus structural genes was evaluated in a non-human primate model for immunogenicity and protective efficacy against aerosol challenge with wild-type veev. the genomic rna of v4020 vaccine virus was encoded in the pmg4020 plasmid under control of the cmv promoter and contained the capsid gene downstream from the glycoprotein genes. it also included attenuating mutations from ...202032085953
proteome array of antibody responses to chlamydia trachomatis infection in nonhuman primates.nonhuman primates have been used to investigate pathogenic mechanisms and evaluate immune responses following chlamydia trachomatis inoculation. this study aimed to systemically profile antibody responses to c. trachomatis infection in nonhuman primates.202032084433
validation of a de-immunization strategy for monoclonal antibodies using cynomolgus macaque as a surrogate for human.the immunogenicity of biotherapeutics presents a major challenge during the clinical development of new protein drugs including monoclonal antibodies. to address this, multiple humanization and de-immunization techniques that employ in silico algorithms and in vitro test systems have been proposed and implemented. however, the success of these approaches has been variable and to date, the ability of these techniques to predict immunogenicity has not been systematically tested in humans or other ...202032080869
thalamic afferents emphasize the different functions of macaque precuneate areas.we studied the thalamic afferents to cortical areas in the precuneus using injections of retrograde fluorescent neuronal tracers in four male macaques (macaca fascicularis). six injections were within the limits of cytoarchitectural area pgm, one in area 31 and one in area peci. precuneate areas shared strong input from the posterior thalamus (lateral posterior nucleus and pulvinar complex) and moderate input from the medial, lateral, and intralaminar thalamic regions. area pgm received strong c ...202032078035
a potent pan-tgfβ neutralizing monoclonal antibody elicits cardiovascular toxicity in mice and cynomolgus monkeys.transforming growth factor β (tgfβ) signaling has been recently shown to reduce antitumor response to pd-l1 blockade, leading to a renewed enthusiasm in developing anti-tgfβ therapies for potential combination with cancer immunotherapy agents. inhibition of tgfβ signaling in nonclinical toxicology species is associated with serious adverse toxicities including cardiac valvulopathies and anemia. previously, cardiovascular toxicities have been thought to be limited to small molecule inhibitors of ...202032077954
survey of the long-tailed macaques introduced onto tinjil island, indonesia.from february 1988 though june 1990, 475 adult long-tailed macaques (macaca fascicularis) were released on tinjil island to establish a breeding program that will provide monkeys for biomedical research while contributing to indonesia's primate conservation efforts. a survey was conducted during the summer of 1990 to assess the status of the island's population. basic demographic data were consistent with those from other field studies of long-tailed macaques, and estimates of reproductivity sug ...199332070079
cerebrospinal fluid characterization in cynomolgus monkeys, beagle dogs, and göttingen minipigs.intrathecal administration is an important route for drug delivery, and in pharmacology and toxicology studies, cerebrospinal fluid (csf) collection and analysis is required for evaluating blood-brain barrier penetration and central nervous system exposure. the characteristics of csf in commonly used nonrodent models are lacking. the purpose of this study is to evaluate and provide some insights into normal cellular and biochemical composition of csf as well as diffusion potential following intr ...202032066300
novel abs targeting the n-terminus of fibroblast growth factor 19 inhibit hepatocellular carcinoma growth without bile-acid-related side-effects.hepatocellular carcinoma (hcc) is a common and particularly fatal form of cancer for which very few drugs are effective. the fibroblast growth factor 19 (fgf19) has been viewed as a driver of hcc development and a potential ab target for developing novel hcc therapy. however, a previously developed anti-fgf19 ab disrupted fgf19's normal regulatory function and caused severe bile-acid-related side-effects despite of having potent antitumor effects in preclinical models. here, we developed novel h ...202032061104
novel liver fibrosis model in macaca fascicularis induced by thioacetamide.although transplantation is the only definitive treatment for liver cirrhosis, there remains a shortage of donors, necessitating that novel treatments be developed. we aimed to establish a liver fibrosis model in macaca fascicularis that can help accelerate preclinical research. liver fibrosis was induced by administering thioacetamide (taa) and carbon tetrachloride (ccl4). analysis of residual liver function and fibrosis progression was based on clinical indices, such as the child-pugh score or ...202032051422
functional clusters of neurons in layer 6 of macaque v1.layer 6 appears to perform a very important role in the function of macaque primary visual cortex, v1, but not enough is understood about the functional characteristics of neurons in the layer 6 population. it is unclear to what extent the population is homogeneous with respect to their visual properties or if one can identify distinct subpopulations. here we performed a cluster analysis based on measurements of the responses of single neurons in layer 6 of primary visual cortex in male macaque ...202032041896
assessment of general and cardiac toxicities of astemizole in male cynomolgus monkeys: serum biochemistry and action potential duration.toxicology screening following treatment with astemizole, a histamine receptor antagonist, at oral doses of 0, 10, 30 and 60 mg/kg was carried out in male cynomolgus monkeys (macaca fascicularis). no dose-related changes in mortality, clinical signs, body weight changes, food consumption, or urine analysis occurred in any animal compared to the vehicle control. however, the high-dose group showed a decrease in bun and alp compared to vehicle control group. in addition, the levels of tg, ast, alp ...200832038807
toxicity screening of single dose of inorganic and organic arsenics on hematological and serum biochemical parameters in male cynomolgus monkeys.a screening study of the acute toxicity of organic arsenics such as arsenobetaine and arsenocholine, a product of arsenic methylation metabolite, and inorganic arsenic was carried out to examine hematological and serum biochemical parameters in cynomolgus monkeys (macaca fascicularis). we found soft and liquid feces, and vomiting in all treated groups with inorganic and organic arsenics. the monkeys in inorganic arsenic-treated group showed a significant increase in vomiting frequency compared w ...200832038799
a selective androgen receptor modulator sarm-2f activates androgen receptor, increases lean body mass, and suppresses blood lipid levels in cynomolgus monkeys.sarm-2f a selective androgen receptor (ar) modulator, increases skeletal muscle mass and locomotor activity in rats. this study aimed to clarify its pharmacological effects in monkeys. in reporter assays, the ec50 values of sarm-2f for rat, monkey, and human ar were 2.5, 3, and 3.6 nmol/l, respectively; those of testosterone were 12, 3.2, and 11 nmol/l, respectively. a single oral administration (10 mg/kg sarm-2f) produced a maximal plasma concentration of 3011 ng/ml, with an area under the 24 h ...202032030892
4-week toxicity study of biosimilar natalizumab in comparison to tysabri® by repeated intravenous infusion to cynomolgus monkeys.the objective of the study was to obtain information on the toxicity of biosimilar natalizumab (pb006) in comparison to the reference product tysabri®. cynomolgus monkeys (15 males and 15 females), three animals per sex and group were treated with either pb006 or the reference product tysabri® at dose levels of 3 or 30 mg/kg body weight or placebo by intravenous infusion every other day for a period of 4 weeks. the study is also meant to facilitate ethics committee approval in specific countries ...202032024395
resistance of cynomolgus monkeys to nipah and hendra virus disease is associated with cell-mediated and humoral immunity.the henipaviruses, hendra virus (hev) and nipah virus (niv), are capable of causing severe and often lethal respiratory and/or neurologic disease in animals and humans. given the sporadic nature of henipavirus outbreaks, licensure of vaccines and therapeutics for human use will likely require demonstration of efficacy in animal models that faithfully reproduce the human condition. currently, the african green monkey (agm) best mimics human henipavirus-induced disease.202032022850
do males bond? a study of male-male relationships in nicobar long-tailed macaques macaca fascicularis umbrosus.in primates, males compete for a mate, which is a non-sharable resource. this makes the conditions less conducive for males to have stable relationships. one such special kind of relationship is a bond where the interactions are reciprocated, equitable and differentiated. bonds in macaque societies are based on the degree of within-group contest competition for mates which is dependent on the synchronization of female fertile phase and reliability of fertility signals. species of the fasciculari ...202032020904
kmrc011, an agonist of toll-like receptor 5, mitigates irradiation-induced tissue damage and mortality in cynomolgus monkeys.in the study here, the potential applicability of kmrc011 - an agonist of toll-like receptor-5 - as a countermeasure for radiation toxicities was evaluated. following a single 5.5 gy total body irradiation (tbi, surface absorbed dose = 7 gy) of co60 γ-rays, mortality rates and degrees of pathological lesions that developed over 80 days were compared in monkeys that received tbi only and a group that was injected once with kmrc011 (10 μg/kg) after tbi. compared to the tbi-only hosts (80%), the de ...202032013650
the development and characterization of a long acting anti-thrombotic von willebrand factor (vwf) aptamer.thrombus formation involves coagulation proteins and platelets. the latter, referred to as platelet-mediated thrombogenesis, is predominant in arterial circulation. platelet thrombogenesis follows vascular injury when extracellular von willebrand factor (vwf) binds via its a3 domain to exposed collagen, and the free vwf a1 domain binds to platelet glycoprotein ib (gpib).202032011054
atypical presentation and pathogenesis of a macaque lymphocryptoviral-associated b-cell lymphoma in a cynomolgus monkey.we report the unique pathogenesis and presentation of a rapidly progressive b-cell lymphoma in a 3-year-old female cynomolgus monkey on day 50 of a 13-week toxicity study. clinical pathology evaluation revealed a marked leukocytosis with bicytopenia. a serum protein electrophoresis was consistent with monoclonal gammopathy. the architecture of the lymph node, spleen, and thymus were variably effaced by neoplastic cells, which also infiltrated other tissues. immunohistochemistry of the affected t ...202032009251
comparative nonclinical assessments of the biosimilar pf-06410293 and originator adalimumab.adalimumab, a recombinant fully human monoclonal antibody targeting tumor necrosis factor (tnf), is approved in the united states and europe to treat various inflammatory and autoimmune indications. biosimilars are approved biologics highly similar, but not identical, to approved biotherapeutics. to support clinical development of pf-06410293, an adalimumab biosimilar, nonclinical studies evaluated the structural, functional, toxicologic, and toxicokinetic similarity to originator adalimumab sou ...202032006671
fluoroquinolones suppress gluconeogenesis by inhibiting fructose 1,6-bisphosphatase in primary monkey hepatocytes.dysglycemia is one of the most serious adverse events associated with the clinical use of certain fluoroquinolones. the purpose of this study was to investigate the effects of the representative fluoroquinolones moxifloxacin and gatifloxacin on hepatic gluconeogenesis using primary monkey hepatocytes. glucose production was induced after the cells were incubated for 4 h with 10 mm sodium lactate and 1 mm sodium pyruvate as gluconeogenic substrates. under these conditions, moxifloxacin and gatifl ...202032004540
improved translation of stability for conjugated antibodies using an in vitro whole blood assay.for antibody-drug conjugates to be efficacious and safe, they must be stable in circulation to carry the payload to the site of the targeted cell. several components of a drug-conjugated antibody are known to influence stability: 1) the site of drug attachment on the antibody, 2) the linker used to attach the payload to the antibody, and 3) the payload itself. in order to support the design and optimization of a high volume of drug conjugates and avoid unstable conjugates prior to testing in ani ...202031997712
a novel gucy2c-cd3 t-cell engaging bispecific construct (pf-07062119) for the treatment of gastrointestinal cancers.gastrointestinal cancers remain areas of high unmet need despite advances in targeted and immunotherapies. here, we demonstrate potent, tumor-selective efficacy with pf-07062119, a t-cell engaging cd3 bispecific targeting tumors expressing guanylyl cyclase c (gucy2c), which is expressed widely across colorectal cancer and other gastrointestinal malignancies. in addition, to address immune evasion mechanisms, we explore combinations with immune checkpoint blockade agents and with antiangiogenesis ...202031996389
primates: their use in research on vasectomy.studies based on experimental vasectomies clearly reveal marked species differences in response to vasectomy. in rats, vasectomy invariably results in granuloma formation at the surgical site. in rabbits, immune-complex orchitis develops. allergic orchitis may also develop in guinea pigs, and the morphological lesions can be adoptively transferred. my co-workers and i have been able to study systematically, biochemically, hormonally, pathologically, and immunologically, primates vasectomized up ...198131995929
on the anatomical organization of the vagal nuclei.the neurons of origin of the right vagus and its components in both the monkey (macaca fascicularis) and albino rats were localized by the retrograde transport of horseradish peroxidase (hrp) applied to the stomach wall, the vagal trunk and its recurrent laryngeal branch. an attempt was also made to localize the neurons forming the superior laryngeal nerve and those supplying the thoracic organs by a combination of operative procedures. the results showed that the stomach was innervated by neuro ...198131995920
hematological and serum biochemical values in free-ranging macaca fascicularis of mauritius: possible diabetes mellitus and correlation with nutrition.obtained values are presented from a study of blood biochemistry and hematology of free-ranging crab-eating macaques (macaca fascicularis) in mauritius. normal values are generally comparable to those previously obtained from laboratory populations of this species. abnormal values included elevated serum glucose and triglycerides in certain individuals that suggested glucose intolerance and diabetes mellitus. a high-carbohydrate diet consisting of large proportions of sugar cane and molasses may ...198131995913
a description of the upper thoracic autonomic nervous system in the rhesus monkey (macaca mulatta).the purpose of this study was to describe the autonomic innervation of the carotid sinus and heart in the rhesus monkey. nine male rhesus monkeys (macaca mulatta) and one male crab-eating macaque (m. fascicularis) were carefully dissected from the origin of the vagus nerves and superior cervical ganglia to the level of the fourth thoracic ganglion. the specimens were either freshly killed or obtained no later than 24 hours post mortem. the macaque monkeys were found to possess an innervation pat ...198231995903
blastogenic response of peripheral blood lymphocytes to mitogens in cynomolgus monkeys (macaca fascicularis).optimal conditions for mitogen-induced transformation of cynomolgus monkey peripheral blood lymphocytes were determined. maximal stimulation estimated by the incorporation of tritiated thymidine (3h-tdr) occurred at the concentrations between 25 and 50 μg/ml with phytohemagglutinin (pha) and concanavalin a (con a), and between 50 and 100 μg/ml with poke weed mitogen (pwm) in a culture volume of 120 μl containing 2 × 105 mononuclear cells supplemented with 10% fresh autologous serum. lipopolysacc ...198231991994
identification of cynomolgus t lymphocytes by acid alpha-naphthyl acetate esterase staining and spontaneous erythrocyte rosette formation.cell surface markers and cytochemical characteristics of cynomolgus lymphocytes were studied. the proportion of lymphocytes with spot-like distribution of acid alpha-naphthyl acetate esterase (anae) activity was similar to that of lymphocytes which form spontaneous rosette with sheep erythrocytes (e rosette) in individual monkeys. fractionation by e rosette formation or passage through nylon wool column selectively enriched anae-spot-positive (anae+) lymphocytes and resulted in twofold increase ...198231991985
a comparison of the behavior of macaca fascicularis and macaca mulatta in relation to the menstrual cycle.observations on oppositely sexed pairs of m. fascicularis and m. mulatta revealed certain differences. m. fascicularis showed single-mount copulations, higher potency, less grooming activity, and milder but more frequent aggressive exchanges than the rhesus monkey. these differences might be due to the lower dominance gradient between the sexes and less sexual dimorphism in m. fascicularis than in m. mulatta. there were changes in the sexual, grooming, and aggressive interaction in relation to t ...198331991973
use of a radioreceptorassay (rra) for human luteinizing hormone/chorionic gonadotropin (hlh/cg) for detection of early pregnancy and estimation of time of ovulation in macaques.a radioreceptorassay (rra) for macaque luteinizing hormone (lh)/chorionic gonadotropin (cg) was adapted from the clinical rra for human lh/cg, biocept-g™, for the purposes of detection of pregnancy prior to day 20 of gestation and for estimation of the time of ovulation in macaques. the 90-min assay procedure was simple, accurate, and reliable. seventy-five rhesus monkeys (macaca mulatta) and 20 crab-eating monkeys (macaca fascicularis) were tested for the presence of cg in the serum on estimate ...198331991966
brief report: crocodile predation on a crab-eating macaque in borneo.an immature crab-eating macaque (macaca fascicularis), which was sitting on the river bank near the orangutan research and conservation project base camp in the tanjung puting reserve, kalimantan tengah, indonesia, was seized by a crocodile which rapidly emerged from the water and then resubmerged with the monkey in its jaws. as crocodile populations are in a decline throughout borneo, crocodile predation on crab-eating macaques was probably more frequent in the past. this predation may have inf ...198431986847
male endocrine responses to females: effects of social cues in cynomolgus macaques.this study tested the hypothesis that the hormonal responses of male macaques to sexually receptive females are mediated by specific socioenvironmental cues. twelve, socially living male macaca fascicularis were exposed to two-ovariectomized, estrogen-primed females under pair test, peer group, and peer group without dominant male conditions. preexposure to postexposure changes in serum cortisol levels and testosterone levels were examined in relation to male dominance rank, age, and conditions ...198431986832
effects of ovarian hormones on the behavior of captive macaca fascicularis.to examine the effects of ovarian hormones on the behavior of female macaca fascicularis and their male partners, daily 1-hr behavior tests were conducted while ovariectomized females were (1) untreated, (2) given estradiol benzoate (eb) (5 μg subcutaneously [s.c.]/day), (3) given estradiol benzoate together with increasing doses of progesterone (p) (5 mg, 10 mg, and 20 mg. s.c./day), and (4) given testosterone propionate (tp) (0.25 mg s.c./day) (six pairs, 540 tests). weekly blood samples were ...198531986815
luteinizing hormone-releasing hormone in olfactory bulbs of primates.this immunohistochemical study of luteinizing hormone-releasing hormone (lhrh) in the olfactory bulbs in primates was undertaken in order to see whether there was an lhrh innervation in these species similar to that found in rodents. one old world (macaca fascicularis) and two new world (saimiri sciureus and aotus trivirgatus) monkeys were studied. aotus trivirgatus was of particular interest as it is noctural and so presumably more dependent upon olfactory cues. animals were perfused with fixat ...198531986801
morphological and karyological studies on in vitro sertoli cells of adult crab-eating macaques (macaca fascicularis).sertoli cell cultures were obtained from isolated seminiferous tubules of adult crab-eating macaques (macaca fascicularis). cells were identified by their morphological characteristics and their capacity to produce and release in the culture medium 17β-estradiol and androgen-binding protein (abp). several cells were undergoing mitosis. karyological analysis showed both diploid and tetraploid metaphases. patterns of nuclear scission were also observed.198531986790
changed pga and postn levels in choroid plexus are associated with depressive-like behaviors in mice.major depressive disorder (mdd) has become a potential cause of death and disability among young people worldwide. numerous studies have indicated that the different cerebrospinal fluid (csf) proteins may be used as mediums for mdd. given the emergent interest of csf proteins in mdd, we validated proteins expression in the choroid plexus (cp), the brain region that produces csf in the lateral ventricle, the third ventricle, and the fourth ventricle of the central nervous system (cns). the csf co ...202031983432
utilization of the chronic atrioventricular block cynomolgus monkey as an in vivo model to evaluate drug interaction-associated torsade de pointes.it has been difficult to experimentally reproduce synergistic effects of ketoconazole on terfenadine-induced torsade de pointes. we assessed proarrhythmic effects of terfenadine (30 mg/kg, p.o.) with/without ketoconazole (100 mg/kg, p.o.) pretreatment using the chronic atrioventricular block cynomolgus monkeys with repeated-measured design (n = 4). terfenadine with ketoconazole pretreatment repeatedly induced non-sustained torsade de pointes in each animal, although terfenadine alone did not ind ...202031982331
duobody-cd3xcd20 induces potent t-cell-mediated killing of malignant b cells in preclinical models and provides opportunities for subcutaneous dosing.duobody®-cd3xcd20 (gen3013) is a full-length human igg1 bispecific antibody (bsab) recognizing cd3 and cd20, generated by controlled fab-arm exchange. its fc domain was silenced by introduction of mutations l234f l235e d265a.202031981978
an optimized full-length flt3/cd3 bispecific antibody demonstrates potent anti-leukemia activity and reversible hematological toxicity.flt3 (fms-like tyrosine kinase 3), expressed on the surface of acute myeloid leukemia (aml) blasts, is a promising aml target, given its role in the development and progression of leukemia, and its limited expression in tissues outside the hematopoietic system. small molecule flt3 kinase inhibitors have been developed, but despite having clinical efficacy, they are effective only on a subset of patients and associated with high risk of relapse. a durable therapy that can target a wider populatio ...202031981494
adoption success under single-cage conditions by cynomolgus macaque mothers (macaca fascicularis).retrospective data were studied to determine the success of experimental adoption by 122 cynomolgus macaques kept in individual cages at the tsukuba primate center. the four types of adoption procedures included (1) singletons adopted after weaning (saw)-21 cases; (2) singletons adopted after stillbirth (sas)-20 cases; (3) singletons adopted after forced separation of the biological infant during the nursing period (saf)-4 cases; and (4) adoption of a second "twin" while still nursing a biologic ...198631979486
adrenal responsiveness and social status in intact and ovariectomized macaca fascicularis.plasma cortisol (f) response to intravenous adrenocorticotropin (acth) infusion (following dexamethasone suppression) was examined in adult female macaca fascicularis that had been living for 22 months in social groups consisting of four to six females and one male. a portion of these females were ovariectomized (n = 21), while the rest were reproductively intact (n = 23). the social behavior of all animals was monitored with a focal sampling procedure, and dominance ranks were determined on the ...198631979461
the inheritance mode of simian-type e, f, and gh blood groups in cynomolgus monkeys.the mode of inheritance of four different red cell antigens (ecy, fcy, gcy, and hcy), detected by alloimmune reagents prepared by us for the cynomolgus monkey, was studied. the results of the segregation analysis suggest that each antigen is inherited in an autosomal dominant manner. both the random sample analysis and family study revealed that two of these red cell antigens (ecy and fcy) probably represent the products of two independent genes while the expression of the other two antigens (gc ...198631979444
comparative pharmacokinetics and pharmacodynamics of the advanced retinol-binding protein 4 antagonist in dog and cynomolgus monkey.accumulation of lipofuscin bisretinoids in the retina contributes to pathogenesis of macular degeneration. retinol-binding protein 4 (rbp4) antagonists reduce serum retinol concentrations thus partially reducing retinol delivery to the retina which decreases bisretinoid synthesis. bpn-14136 is a novel rbp4 antagonist with good in vitro potency and selectivity and optimal rodent pharmacokinetic (pk) and pharmacodynamic (pd) characteristics. to select a non-rodent species for regulatory toxicology ...202031978148
quantification of regional myocardial mean intracellular water lifetime: a nonhuman primate study in myocardial stress.heart failure with preserved ejection fraction (hfpef) is typically associated with early metabolic remodeling. noninvasive imaging biomarkers that reflect these changes will be crucial in determining responses to early drug interventions in these patients. mean intracellular water lifetime (τi ) has been shown to be partially inversely related to na, k-atpase transporter activity and may thus provide insight into the metabolic status in hfpef patients. here, we aim to perform regional quantific ...202031977123
epitope and fc-mediated cross-linking, but not high affinity, are critical for antitumor activity of cd137 agonist antibody with reduced liver toxicity.cd137 (tnfrsf9, 4-1bb) agonist antibodies (mab) have demonstrated potent antitumor activity with memory response while causing hepatotoxicity in mouse models. in clinical trials, the degrees of liver toxicity of anti-cd137 vary from grade 4 transaminitis (urelumab) to nonexistent (utomilumab). to exploit the antitumor potential of cd137 signaling, we identified a new class of cd137 agonist mabs with strong antitumor potency without significant transaminitis in vivo compared with cd137 agonists p ...202031974274
serum chorionic gonadotropin levels determined by radioreceptorassay and early diagnosis of pregnancy in the cynomolgus monkey (macaca fascicularis).the radioreceptorassay developed to determine serum luteinizing hormone level in the cynomolgus monkey was evaluated for its usefulness in early pregnancy diagnosis by the detection of serum chorionic gonadotropin (cg). blood samples were collected at weekly intervals from the 1st to the 5th week after conception to determine changes in circulating levels of cg. in the pregnancy cases, serum cg levels increased to above 50 μg/ml in almost all animals. by the determination of cg 3 weeks after con ...198731973513
sensory, motor, and postganglionic sympathetic neurons forming the ulnar and radial nerves of two macaque species: macaca nemestrina and macaca fascicularis.the motor, sensory, and postganglionic sympathetic neurons forming the left ulnar and right radial nerves of long-tailed macaques (macaca fascicularis) and pigtailed macaques (macaca nemestrina) were localized by the horseradish peroxidase method of tracing neuronal connections. the ulnar and radial motoneurons formed a longitudinal column of variable extent in the lateral part of the ventral horn. in most animals, the ulnar motoneurons extended between the caudal ends of the c7 and t1 segments; ...198731973505
prevalence of glucose intolerance in free-ranging macaca fascicularis of mauritius.oral glucose tolerance tests (ogtts) were carried out on 30 free-ranging long-tailed macaques (macaca fascicularis) on the island of mauritius, following the suggestion that severe glucose intolerance and diabetes mellitus might be prevalent in this macaque population. ogtts revealed no evidence of frank diabetes mellitus in the sample. however, 13% of individuals showed impaired glucose tolerance, with preserved insulin secretion, suggesting the presence of the target tissue resistance to insul ...198731973458
luteinizing hormone receptors in ovaries of the cynomolgus monkey (macaca fascicularis) during the menstrual cycle.ovarian luteinizing hormone (lh) receptors were characterized using ovarian tissues from 17 cynomolgus monkeys at different phases of the menstrual cycle. low binding affinity receptors for 125i-lh were observed throughout the menstrual cycle. the binding affinity of these receptors for lh (< 12 × 1010 m-1) was approximately the same as that of ovarian lh receptors previously reported in human and nonhuman primates. in addition, high-affinity receptors (17-85 × 1010 m-1) were also detected at th ...198731973456
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