• Proceedings of the Korean Society of Toxicology Conference
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• 2005.11a
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• pp.154-163
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• 2005

• IMMUNE NETWORK
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• v.22 no.6
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• pp.48.1-48.13
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• 2022

With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, which are randomly mutated, the dominant strains in regions are changing globally. The development of preclinical animal models is imperative to validate vaccines and therapeutics against SARS-CoV-2 variants. The objective of this study was to develop a non-human primate (NHP) model for SARS-CoV-2 Delta variant infection. Cynomolgus macaques infected with Delta variants showed infectious viruses and viral RNA in the upper (nasal and throat) and lower respiratory (lung) tracts during the acute phase of infection. After 3 days of infection, lesions consistent with diffuse alveolar damage were observed in the lungs. For cellular immune responses, all macaques displayed transient lymphopenia and neutrophilia in the early stages of infection. SARS-CoV-2 Delta variant spike protein-specific IgM, IgG, and IgA levels were significantly increased in the plasma of these animals 14 days after infection. This new NHP Delta variant infection model can be used for comparative analysis of the difference in severity between SARS-CoV-2 variants of concern and may be useful in the efficacy evaluation of vaccines and universal therapeutic drugs for mutations.

• Journal of the korean veterinary medical association
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• v.15 no.5
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• pp.277-280
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• 1979

• Toxicological Research
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• v.26 no.4
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• pp.275-283
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• 2010

Placenta transfer study in non-human primate (NHP) is one of the crucial components in the assessment of developmental toxicity because of the similarity between NHP and humans. To establish the method to determine placenta transfer in non-human primate, toxicokinetics of valproic acid (VPA), a drug used to treat epilepsy in pregnant women, were determined in pregnant cynomolgus monkeys. After mating, pregnancy-proven females were daily administered with VPA at dose levels of 0, 20, 60 and 180 mg/kg by oral route during the organogenesis period from gestation day (GD) 20 to 50. Concentrations of VPA and its metabolite, 4-ene-VPA, in maternal plasma on GDs 20 and 50, and concentrations of VPA and 4-ene-VPA in placenta, amniotic fluid and fetus on GD 50 were analyzed using LC/MS/MS. Following single oral administration of VPA to pregnant monkeys, concentrations of VPA and 4-ene-VPA were generally quantifiable in the plasma from all treatment groups up to 4-24 hours post-dose, demonstrating that VPA was absorbed and the monkeys were systemically exposed to VPA and 4-ene-VPA. After repeated administration of VPA to the monkeys, VPA was detected in amniotic fluid, placenta and fetus from all treatment groups, demonstrating that VPA was transferred via placenta and the fetus was exposed to VPA, and the exposures were increased with increasing dose. Concentrations of 4-ene-VPA in amniotic fluid and fetus were below the limit of quantification, but small amount of 4-ene-VPA was detected in placenta. In conclusion, pregnant monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at dose levels of 20, 60 and 180 mg/kg during the organogenesis period. VPA was transferred via placenta and the fetus was exposed to VPA with dose-dependent exposure. The metabolite, 4-ene VPA, was not detected in both amniotic fluid and fetus, but small amount of 4-ene-VPA was detected in placenta. These results demonstrated that proper procedures to investigate placenta transfer in NHP, such as mating and diagnosis of pregnancy via examining gestational sac with ultrasonography, collection of amniotic fluid, placenta and fetus after Caesarean section followed by adequate bioanalysis and toxicokinetic analysis, were established in this study using cynomolugus monkeys.

• Journal of Life Science
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• v.21 no.3
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• pp.459-463
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• 2011

The genome of the rhesus monkey has diverged as an average sequence identity of ~93%. The rhesus monkey has been widely used as a non-human primate in the field of biomedical and evolutional research. Insertion of transposable elements (TEs) induced several events such as transcriptional diversity and different expression in host genes. In this study, 112 transcripts were identified from a full-length cDNA library of brain tissues of the rhesus monkey. One transcript (R54) showed a different expression pattern between human and rhesus monkey tissues. This phenomenon can be an explanation that R54 transcript was acquired by splicing a donor site derived from exonization of the L2A element. Therefore, integration of TEs during primate radiation could contribute to transcriptional diversity and gene regulation.

• Journal of Veterinary Clinics
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• v.18 no.4
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• pp.380-389
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• 2001

Non-human primates have been increasing in demand as important experimental animals and companion animals, domestically and internationally. The number of non-human primates for these purposes will be much enhanced in the near future. Despite this trend, basic physiological data are scarcely available in these animal species, leading to the difficulty to diagnose diseases when necessary, due to the absence of reference values. Particularly, there is not any report on the total activity of LDH of non-human primates, let alone LDH isoenzyme patterns, in Korea. LDH isoenzymes have a high level of efficaciousness as diagnostic and prognostic aids in various diseases. In this study, total activities and isoenzyme patterns of LDH were measured to obtain their reference values in domestically reared common marmosets, crab-eating macaques and Japanese macaques. There were widespread different values of serum total LDH among the non-human primate species experimented in this study. Serum LDH values of common marmosets and crab-eating macaques were 597.5$\pm$243.1 IU/l and 605.3$\pm$312.6 IU/l, respectively, whereas those of Japanese macaque showed 1,209$\pm$473.8 IU/l. Five isoenzyme fractions of LDH were observed in all experimented non-human primates but their ranks and proportions represented different patterns one another. In common marmosets, the percent of fraction for serum LDH1, LDH$_2$, LDH$_3$, LDH$_4$, and LDH$_{5}$ was 13.7$\pm$6.4%, 23.3$\pm$3.6%, 29.2$\pm$5.0%, 9.4$\pm$1.4% and 24.4$\pm$7.5%, respectively. The rank of LDH isoenzymes was LDH$_3$>LDH$_{5}$>LDH$_2$>LDH$_1$>LDH$_4$, in the descending order. For crab-eating macaques, the fraction of serum LDH$_1$, LDH$_2$, LDH$_3$, LDH$_4$, and LDH$_{5}$ occupied 19.5$\pm$12.7%, 25.3$\pm$9.3%, 23.8$\pm$8.1%, 10.2$\pm$2.8% and 21.3$\pm$14.2%, respectively. The order of LDH isoenzymes was LDH$_2$>LDH$_3$>LDH$_{5}$>LDH$_1$>LDH$_4$, from top to down. On the while, in Japanese macaques, the fraction of serum LDH$_1$ to LDH$_{5}$ showed 23.4$\pm$11.8%, 30.5$\pm$4.1%, 17.4$\pm$3.9%, 11.3$\pm$3.7% and 13.8$\pm$5.6%, respectively. The decreasing order indicated LDH$_2$>LDH$_1$>LDH$_3$>LDH$_{5}$>LDH$_4$. In conclusion, values such as LDH and LDH isoenzyme patterns of investigated for the first time from non-human primates reaared in Korea, could be reference values for the optimal diagnosis and therapy of diseases of the corresponding animal species. Other parameters of hematology and blood biochemistry are urgently needed to study for the benefit of our intimate non-human primates.an primates.

• Clinical and Experimental Vaccine Research
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• v.12 no.4
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• pp.291-297
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• 2023

Enterovirus infections induce infectious diseases in young children, such as hand, foot, and mouth disease which is characterized by highly contagious rashes or blisters around the hands, feet, buttocks, and mouth. This predominantly arises from enterovirus A71 or coxsackievirus A16 infections and in severe cases, they can lead to encephalitis, paralysis, pulmonary edema, or even fatality, representing a global health threat. Due to the absence of effective therapeutic strategies for these infections, various experimental animal models are being investigated for the development of vaccines. During the early stages of research on enterovirus infections, non-human primate infections exhibited symptoms like those in humans, leading to their utilization as model animals. However, due to economic and ethical considerations, their current usage is limited. While enterovirus infections do not readily occur in mice, an infection model with mouse-adapted strain in neonatal mice has been employed. Cellular receptors have been identified in human cells, and genetically modified mice expressing these receptors have been used. Most recently, the utilization of Mongolian gerbil model is actively being considered and should be pursued for further animal model development. So, herein, we provide a summarized overview of the current portfolio of available enterovirus infection models, emphasizing their respective advantages and limitations.

• Proceedings of the Korean Environmental Health Society Conference
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• 2005.06a
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• pp.105-139
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• 2005

Increased signal in T1-weighted images was observed in the experimental manganese (Mn) poisoning of the non-human primate and a patient with Mn neurointoxication. However, our study showed that the increased signals in magnetic resonance images (MRI) were highly prevalent (41.6%) in Mn-exposed workers. Blood Mn concentration correlated with pallidal index. These changes in MRI tend to disappear following the withdrawal from the source of Mn accumulation, despite permanent neurological damage. Thus increased signal intensities on a T1-weighted image reflect exposure to Mn, but not necessarily manganism. Our study also showed that the concentration of Mn required to produce increased signal intensities on MRI is much lower than the threshold necessary to result in overt clinical signs of manganism. Increased signal intensities in the globus pallidus were determined by manganese accumulation in the animal experiment. Reanalysis of the previous data with the structural equation model revealed that pallidal index (Pl) on MRI reflects target organ dose of occupational Mn exposure

• Molecules and Cells
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• v.43 no.4
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• pp.331-339
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• 2020

Genetic modifications in noncoding regulatory regions are likely critical to human evolution. Human-accelerated noncoding elements are highly conserved noncoding regions among vertebrates but have large differences across humans, which implies human-specific regulatory potential. In this study, we found that human-accelerated noncoding elements were frequently coupled with DNase I hypersensitive sites (DHSs), together with monomethylated and trimethylated histone H3 lysine 4, which are active regulatory markers. This coupling was particularly pronounced in fetal brains relative to adult brains, non-brain fetal tissues, and embryonic stem cells. However, fetal brain DHSs were also specifically enriched in deeply conserved sequences, implying coexistence of universal maintenance and human-specific fitness in human brain development. We assessed whether this coexisting pattern was a general one by quantitatively measuring evolutionary rates of DHSs. As a result, fetal brain DHSs showed a mixed but distinct signature of regional conservation and outlier point acceleration as compared to other DHSs. This finding suggests that brain developmental sequences are selectively constrained in general, whereas specific nucleotides are under positive selection or constraint relaxation simultaneously. Hence, we hypothesize that human- or primate-specific changes to universally conserved regulatory codes of brain development may drive the accelerated, and most likely adaptive, evolution of the regulatory network of the human brain.

• Journal of Microbiology and Biotechnology
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• v.28 no.9
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• pp.1413-1425
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• 2018

Shiga toxins (Stxs) are the main virulence factors expressed by the pathogenic Stx-producing bacteria, namely, Shigella dysenteriae serotype 1 and certain Escherichia coli strains. These bacteria cause widespread outbreaks of bloody diarrhea (hemorrhagic colitis) that in severe cases can progress to life-threatening systemic complications, including hemolytic uremic syndrome (HUS) characterized by the acute onset of microangiopathic hemolytic anemia and kidney dysfunction. Shiga toxicosis has a distinct pathogenesis and animal models of Stx-associated HUS have allowed us to investigate this. Since these models will also be useful for developing effective countermeasures to Stx-associated HUS, it is important to have clinically relevant animal models of this disease. Multiple studies over the last few decades have shown that mice injected with purified Stxs develop some of the pathophysiological features seen in HUS patients infected with the Stx-producing bacteria. These features are also efficiently recapitulated in a non-human primate model (baboons). In addition, rats, calves, chicks, piglets, and rabbits have been used as models to study symptoms of HUS that are characteristic of each animal. These models have been very useful for testing hypotheses about how Stx induces HUS and its neurological sequelae. In this review, we describe in detail the current knowledge about the most well-studied in vivo models of Stx-induced HUS; namely, those in mice, piglets, non-human primates, and rabbits. The aim of this review is to show how each human clinical outcome-mimicking animal model can serve as an experimental tool to promote our understanding of Stx-induced pathogenesis.