Database : MEDLINE
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[PMID]: 29522521
[Au] Autor:Sunyakumthorn P; Somponpun SJ; Im-Erbsin R; Anantatat T; Jenjaroen K; Dunachie SJ; Lombardini ED; Burke RL; Blacksell SD; Jones JW; Mason CJ; Richards AL; Day NPJ; Paris DH
[Ad] Address:Department of Veterinary Medicine, United States Army Medical Directorate, Armed Forces Research Institute of Medical Sciences (USAMD-AFRIMS), Bangkok, Thailand.
[Ti] Title:Characterization of the rhesus macaque (Macaca mulatta) scrub typhus model: Susceptibility to intradermal challenge with the human pathogen Orientia tsutsugamushi Karp.
[So] Source:PLoS Negl Trop Dis;12(3):e0006305, 2018 Mar 09.
[Is] ISSN:1935-2735
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Scrub typhus is an important endemic disease in tropical Asia caused by Orientia tsutsugamushi for which no effective broadly protective vaccine is available. The successful evaluation of vaccine candidates requires well-characterized animal models and a better understanding of the immune response against O. tsutsugamushi. While many animal species have been used to study host immunity and vaccine responses in scrub typhus, only limited data exists in non-human primate (NHP) models. METHODOLOGY/PRINCIPLE FINDINGS: In this study we evaluated a NHP scrub typhus disease model based on intradermal inoculation of O. tsutsugamushi Karp strain in rhesus macaques (n = 7). After an intradermal inoculation with 106 murine LD50 of O. tsutsugamushi at the anterior thigh (n = 4) or mock inoculum (n = 3), a series of time course investigations involving hematological, biochemical, molecular and immunological assays were performed, until day 28, when tissues were collected for pathology and immunohistochemistry. In all NHPs with O. tsutsugamushi inoculation, but not with mock inoculation, the development of a classic eschar with central necrosis, regional lymphadenopathy, and elevation of body temperature was observed on days 7-21 post inoculation (pi); bacteremia was detected by qPCR on days 6-18 pi; and alteration of liver enzyme function and increase of white blood cells on day 14 pi. Immune assays demonstrated raised serum levels of soluble cell adhesion molecules, anti-O. tsutsugamushi-specific antibody responses (IgM and IgG) and pathogen-specific cell-mediated immune responses in inoculated macaques. The qPCR assays detected O. tsutsugamushi in eschar, spleen, draining and non-draining lymph nodes, and immuno-double staining demonstrated intracellular O. tsutsugamushi in antigen presenting cells of eschars and lymph nodes. CONCLUSIONS/SIGNIFICANCE: These data show the potential of using rhesus macaques as a scrub typhus model, for evaluation of correlates of protection in both natural and vaccine induced immunity, and support the evaluation of future vaccine candidates against scrub typhus.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.1371/journal.pntd.0006305

  2 / 4745 MEDLINE  
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[PMID]: 29367457
[Au] Autor:Khabou H; Garita-Hernandez M; Chaffiol A; Reichman S; Jaillard C; Brazhnikova E; Bertin S; Forster V; Desrosiers M; Winckler C; Goureau O; Picaud S; Duebel J; Sahel JA; Dalkara D
[Ad] Address:Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, France.
[Ti] Title:Noninvasive gene delivery to foveal cones for vision restoration.
[So] Source:JCI Insight;3(2), 2018 Jan 25.
[Is] ISSN:2379-3708
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Intraocular injection of adeno-associated viral (AAV) vectors has been an evident route for delivering gene drugs into the retina. However, gaps in our understanding of AAV transduction patterns within the anatomically unique environments of the subretinal and intravitreal space of the primate eye impeded the establishment of noninvasive and efficient gene delivery to foveal cones in the clinic. Here, we establish new vector-promoter combinations to overcome the limitations associated with AAV-mediated cone transduction in the fovea with supporting studies in mouse models, human induced pluripotent stem cell-derived organoids, postmortem human retinal explants, and living macaques. We show that an AAV9 variant provides efficient foveal cone transduction when injected into the subretinal space several millimeters away from the fovea, without detaching this delicate region. An engineered AAV2 variant provides gene delivery to foveal cones with a well-tolerated dose administered intravitreally. Both delivery modalities rely on a cone-specific promoter and result in high-level transgene expression compatible with optogenetic vision restoration. The model systems described here provide insight into the behavior of AAV vectors across species to obtain safety and efficacy needed for gene therapy in neurodegenerative disorders.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher

  3 / 4745 MEDLINE  
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[PMID]: 29517447
[Au] Autor:Gall AJ; Olds JE; Wünschmann A; Selmic LE; Rasmussen J; Lewis AD
[Ti] Title:LESIONS OF THE FEMALE REPRODUCTIVE TRACT IN JAPANESE MACAQUE ( MACACA FUSCATA) FROM TWO CAPTIVE COLONIES.
[So] Source:J Zoo Wildl Med;49(1):79-85, 2018 Mar.
[Is] ISSN:1042-7260
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Reproductive lesions have been described in various nonhuman primate species, including rhesus macaques ( Macaca mulatta), cynomolgus macaques ( Macaca fascicularis), baboons ( Papio spp.), squirrel monkeys ( Saimiri sciureus), and chimpanzees ( Pan spp.); however, there are few publications describing reproductive disease and pathology in Japanese macaques ( Macaca fuscata). A retrospective evaluation of postmortem reports for two captive M. fuscata populations housed within zoos from 1982 through 2015 was completed, comparing reproductive diseases diagnosed by gross pathology and histopathology. Disease prevalence, organs affected, and median age at death between the two institutions was also compared. Fifteen female captive M. fuscata, ranging in age from 15 to 29 yr were identified with reproductive tract lesions, including endometriosis, endometritis, leiomyoma, leiomyosarcoma, and adenomyosis. No significant differences were identified in disease prevalence, organs affected, and median age of death between the two institutions. Endometriosis was the most common disease process identified and was found in 10 of the 15 cases (66.7%), followed by leiomyoma (4 of 15; 26.7%). In four cases (26.7%), severe endometriosis and secondary hemorrhage was indicated as the cause of death or the primary reason for humane euthanasia. These findings were compared with a separate population of Japanese macaques managed within a research facility in the United States, with a prevalence of endometriosis of 7.6%. This study discusses possible risk factors and potential treatment options for the management of endometriosis in captive M. fuscata.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:In-Data-Review
[do] DOI:10.1638/2016-0171R1.1

  4 / 4745 MEDLINE  
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[PMID]: 29442501
[Au] Autor:Guarino C; Gruba N; Grzywa R; Dyguda-Kazimierowicz E; Hamon Y; LÈ©gowska M; Skorenski M; Dallet-Choisy S; Marchand-Adam S; Kellenberger C; Jenne DE; Sienczyk M; Lesner A; Gauthier F; Korkmaz B
[Ad] Address:INSERM UMR1100, "Centre d'Etude des Pathologies Respiratoires" , Université de Tours , 37032 Tours , France.
[Ti] Title:Exploiting the S4-S5 Specificity of Human Neutrophil Proteinase 3 to Improve the Potency of Peptidyl Di(chlorophenyl)-phosphonate Ester Inhibitors: A Kinetic and Molecular Modeling Analysis.
[So] Source:J Med Chem;61(5):1858-1870, 2018 Mar 08.
[Is] ISSN:1520-4804
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The neutrophilic serine protease proteinase 3 (PR3) is involved in inflammation and immune response and thus appears as a therapeutic target for a variety of infectious and inflammatory diseases. Here we combined kinetic and molecular docking studies to increase the potency of peptidyl-diphenyl phosphonate PR3 inhibitors. Occupancy of the S1 subsite of PR3 by a nVal residue and of the S4-S5 subsites by a biotinylated Val residue as obtained in biotin-VYDnV (O-C H -4-Cl) enhanced the second-order inhibition constant k /[I] toward PR3 by more than 10 times ( k /[I] = 73000 ± 5000 M s ) as compared to the best phosphonate PR3 inhibitor previously reported. This inhibitor shows no significant inhibitory activity toward human neutrophil elastase and resists proteolytic degradation in sputa from cystic fibrosis patients. It also inhibits macaque PR3 but not the PR3 from rodents and can thus be used for in vivo assays in a primate model of inflammation.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:In-Data-Review
[do] DOI:10.1021/acs.jmedchem.7b01416

  5 / 4745 MEDLINE  
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[PMID]: 29431693
[Au] Autor:Masuta Y; Yamamoto T; Natsume-Kitatani Y; Kanuma T; Moriishi E; Kobiyama K; Mizuguchi K; Yasutomi Y; Ishii KJ
[Ad] Address:Laboratory of Adjuvant Innovation, Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
[Ti] Title:An Antigen-Free, Plasmacytoid Dendritic Cell-Targeting Immunotherapy To Bolster Memory CD8 T Cells in Nonhuman Primates.
[So] Source:J Immunol;200(6):2067-2075, 2018 Mar 15.
[Is] ISSN:1550-6606
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The priming, boosting, and restoration of memory cytotoxic CD8 T lymphocytes by vaccination or immunotherapy in vivo is an area of active research. Particularly, nucleic acid-based compounds have attracted attention due to their ability to elicit strong Ag-specific CTL responses as a vaccine adjuvant. Nucleic acid-based compounds have been shown to act as anticancer monotherapeutic agents even without coadministration of cancer Ag(s); however, so far they have lacked efficacy in clinical trials. We recently developed a second-generation TLR9 agonist, a humanized CpG DNA (K3) complexed with schizophyllan (SPG), K3-SPG, a nonagonistic Dectin-1 ligand. K3-SPG was previously shown to act as a potent monoimmunotherapeutic agent against established tumors in mice in vivo. In this study we extend the monoimmunotherapeutic potential of K3-SPG to a nonhuman primate model. K3-SPG activated monkey plasmacytoid dendritic cells to produce both IFN-α and IL-12/23 p40 in vitro and in vivo. A single injection s.c. or i.v. with K3-SPG significantly increased the frequencies of activated memory CD8 T cells in circulation, including Ag-specific memory CTLs, in cynomolgus macaques. This increase did not occur in macaques injected with free CpG K3 or polyinosinic-polycytidylic acid. Injection of 2 mg K3-SPG induced mild systemic inflammation, however, levels of proinflammatory serum cytokines and circulating neutrophil influx were lower than those induced by the same dose of polyinosinic-polycytidylic acid. Therefore, even in the absence of specific Ags, we show that K3-SPG has potent Ag-specific memory CTL response-boosting capabilities, highlighting its potential as a monoimmunotherapeutic agent for chronic infectious diseases and cancer.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180306
[Lr] Last revision date:180306
[St] Status:In-Data-Review
[do] DOI:10.4049/jimmunol.1701183

  6 / 4745 MEDLINE  
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[PMID]: 29202201
[Au] Autor:Roth T; Sammak R; Foley J
[Ad] Address:Department of Medicine and Epidemiology, University of California Davis, Davis, CA.
[Ti] Title:Prevalence and Seasonality of Fleas Associated With California Ground Squirrels and the Potential Risk of Tularemia in an Outdoor Non-Human Primate Research Facility.
[So] Source:J Med Entomol;55(2):452-458, 2018 Feb 28.
[Is] ISSN:1938-2928
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Ectoparasites at primate research centers may be difficult to control, e.g. without exposing non-human primates (NHPs) to toxicants, but their impact on NHP health is poorly understood. In 2010, there was an epizootic of tularemia at the California National Primate Research Center (CNPRC) in Yolo County, California that resulted in 20 confirmed and suspect clinical cases in outdoors housed rhesus macaques (Macaca mulatta [Zimmermann]) and a 53% seroprevalence in the southern section of the colony. We studied ectoparasite burdens at the CNPRC in order to understand possible conditions at the time of the epizootic and provide data for the management of ectoparasites for the future. In 2015, we recorded 52 California ground squirrel (Otospermophilus beecheyi [Richardson]) burrow systems in the southern colony and collected 560 fleas. The largest number of fleas (n = 184) was collected in October and the most common species were Hoplopsyllus anomalus (Baker) (n = 331), Oropsylla montana (Baker) (n = 158), Echidnophaga gallinacea (Westwood) (n = 60), and Ctenocephalides felis (Bouché) (n = 11), all of which are opportunistically anthropophilic. Free, non-host-associated fleas included 12 H. anomalus, 9 C. felis, 6 O. Montana, and 1 E. gallinacea. We collected 1 H. anomalus from a rhesus macaque. Our results suggest a high potential for the rapid spread of zoonotic infectious diseases via flea transmission in primate facilities with ground squirrels and that flea control measures should be given a high priority.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[St] Status:In-Data-Review
[do] DOI:10.1093/jme/tjx201

  7 / 4745 MEDLINE  
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[PMID]: 29352993
[Au] Autor:Yiu G; Wang Z; Munevar C; Tieu E; Shibata B; Wong B; Cunefare D; Farsiu S; Roberts J; Thomasy SM
[Ad] Address:Department of Ophthalmology & Vision Science, University of California, Davis, Sacramento, CA, United States. Electronic address: gyiu@ucdavis.edu.
[Ti] Title:Comparison of chorioretinal layers in rhesus macaques using spectral-domain optical coherence tomography and high-resolution histological sections.
[So] Source:Exp Eye Res;168:69-76, 2018 Mar.
[Is] ISSN:1096-0007
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Nonhuman primates are important preclinical models of retinal diseases because they uniquely possess a macula similar to humans. Ocular imaging technologies such as spectral-domain optical coherence tomography (SD-OCT) allow noninvasive, in vivo measurements of chorioretinal layers with near-histological resolution. However, the boundaries are based on differences in reflectivity, and detailed correlations with histological tissue layers have not been explored in rhesus macaques, which are widely used for biomedical research. Here, we compare the macular anatomy and thickness measurements of chorioretinal layers in rhesus macaque eyes using SD-OCT and high-resolution histological sections. Images were obtained from methylmethacrylate-embedded histological sections of 6 healthy adult rhesus macaques, and compared with SD-OCT images from 6 age-matched animals. Thicknesses of chorioretinal layers were measured across the central 3 mm macular region using custom semi-automated or manual software segmentation, and compared between the two modalities. We found that histological sections provide better distinction between the ganglion cell layer (GCL) and inner plexiform layer (IPL) than SD-OCT imaging. The first hyperreflective band between the external limiting membrane (ELM) and retinal pigment epithelium (RPE) appears wider on SD-OCT than the junction between photoreceptor inner and outer segments seen on histology. SD-OCT poorly distinguishes Henle nerve fibers from the outer nuclear layer (ONL), while histology correctly identifies these fibers as part of the outer plexiform layer (OPL). Overall, the GCL, inner nuclear layer (INL), and OPL are significantly thicker on histology, especially at the fovea; while the ONL, choriocapillaris (CC), and outer choroid (OC) are thicker on SD-OCT. Our results show that both SD-OCT and high-resolution histological sections allow reliable measurements of chorioretinal layers in rhesus macaques, with distinct advantages for different sublayers. These findings demonstrate the effects of tissue processing on chorioretinal anatomy, and provide normative values for chorioretinal thickness measurements on SD-OCT for future studies of disease models in these nonhuman primates.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180301
[Lr] Last revision date:180301
[St] Status:In-Data-Review

  8 / 4745 MEDLINE  
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[PMID]: 29467430
[Au] Autor:Kato F; Ishida Y; Kawakami A; Takasaki T; Saijo M; Miura T; Hishiki T
[Ad] Address:Laboratory of Primate Model, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
[Ti] Title:Evaluation of Macaca radiata as a non-human primate model of Dengue virus infection.
[So] Source:Sci Rep;8(1):3421, 2018 Feb 21.
[Is] ISSN:2045-2322
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Dengue virus (DENV) causes a wide range of illnesses in humans, including dengue fever and dengue haemorrhagic fever. Current animal models of DENV infection are limited for understanding infectious diseases in humans. Bonnet monkeys (Macaca radiata), a type of Old World monkey, have been used to study experimental and natural infections by flaviviruses, but Old World monkeys have not yet been used as DENV infection models. In this study, the replication levels of several DENV strains were evaluated using peripheral blood mononuclear cells. Our findings indicated that DENV-4 09-48 strain, isolated from a traveller returning from India in 2009, was a highly replicative virus. Three bonnet monkeys were infected with 09-48 strain and antibody responses were assessed. DENV nonstructural protein 1 antigen was detected and high viraemia was observed. These results indicated that bonnet monkeys and 09-48 strain could be used as a reliable primate model for the study of DENV.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180227
[Lr] Last revision date:180227
[St] Status:In-Data-Review
[do] DOI:10.1038/s41598-018-21582-9

  9 / 4745 MEDLINE  
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[PMID]: 29228218
[Au] Autor:Veazey RS; Lackner AA
[Ad] Address:Division of Comparative Pathology, Tulane National Primate Research Center, Tulane University School of Medicine.
[Ti] Title:Nonhuman Primate Models and Understanding the Pathogenesis of HIV Infection and AIDS.
[So] Source:ILAR J;58(2):160-171, 2017 Dec 01.
[Is] ISSN:1930-6180
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Research using nonhuman primates (NHPs) as models for human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) has resulted in tremendous achievements not only in the prevention and treatment of HIV, but also in biomedical research more broadly. Once considered a death sentence, HIV infection is now fairly well controlled with combination antiretroviral treatments, almost all of which were first tested for efficacy and safety in nonhuman primates or other laboratory animals. Research in NHP has led to "dogma changing" discoveries in immunology, infectious disease, and even our own genetics. We now know that many of our genes are retroviral remnants, or developed in response to archaic HIV-like retroviral infections. Early studies involving blood from HIV patients and in experiments in cultured tissues contributed to confusion regarding the cause of AIDS and impeded progress in the development of effective interventions. Research on the many retroviruses of different NHP species have broadened our understanding of human immunology and perhaps even our origins and evolution as a species. In combination with recent advances in molecular biology and computational analytics, research in NHPs has unique potential for discoveries that will directly lead to new cures for old human and animal diseases, including HIV/AIDS.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180221
[Lr] Last revision date:180221
[St] Status:In-Data-Review
[do] DOI:10.1093/ilar/ilx032

  10 / 4745 MEDLINE  
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[PMID]: 29457675
[Au] Autor:Ogonuki N; Inoue H; Matoba S; Kurotaki YK; Kassai H; Abe Y; Sasaki E; Aiba A; Ogura A
[Ad] Address:RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.
[Ti] Title:Oocyte-Activating Capacity of Fresh and Frozen-Thawed Spermatids in the Common Marmoset (Callithrix jacchus).
[So] Source:Mol Reprod Dev;, 2018 Feb 19.
[Is] ISSN:1098-2795
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The common marmoset (Callithrix jacchus) represents a promising nonhuman primate model for the study of human diseases because of its small size, ease of handling, and availability of gene-modified animals. Here, we aimed to devise reproductive technology for marmoset spermatid injection using immature males for a possible rapid generational turnover. Spermatids at each step could be identified easily by their morphology under differential interference microscopy: thus, early round spermatids had a round nucleus with a few nucleolus-like structures and abundant cytoplasm, as in other mammals. The spermatids acquired oocyte-activating capacity at the late round spermatid stage, as confirmed by the resumption of meiosis and Ca oscillations upon injection into mouse oocytes. The spermatids could be cryopreserved efficiently with a simple medium containing glycerol and CELL BANKER®. Late round or elongated spermatids first appeared at 10-12 months of age, 6-8 months before sexual maturation. Marmoset oocytes microinjected with frozen-thawed late round or elongated spermatids retrieved from a 12-month-old male marmoset developed to the 8-cell stage without the need for artificial oocyte activation stimulation. Thus, it might be possible to shorten the intergeneration time by spermatid injection, from 2 years (by natural mating) to 13-15 months including gestation. This article is protected by copyright. All rights reserved.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180219
[Lr] Last revision date:180219
[St] Status:Publisher
[do] DOI:10.1002/mrd.22971


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