Bartonella quintana in cynomolgus monkey (Macaca fascicularis).
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ABSTRACT:
SUBMITTER: O'Rourke LG
PROVIDER: S-EPMC3367614 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Nonhuman primates have been a common animal model to evaluate experimentally induced malformations. Reports on spontaneous malformations are important in determining the background incidence of congenital anomalies in specific species and in evaluating experimental results. Here we report on a stillborn cynomolgus monkey (Macaca fascicularis) with multiple congenital anomalies from the colony maintained at the Southwest National Primate Research Center at the Texas Biomedical Research Institute, San Antonio, Texas. Physical findings included low birth weight, craniorachischisis, facial abnormalities, omphalocele, malrotation of the gut with areas of atresia and intussusception, a Meckel diverticulum, arthrogryposis, patent ductus arteriosus, and patent foramen ovale. The macaque had normal male external genitalia, but undescended testes. Gestational age was unknown but was estimated from measurements of the limbs and other developmental criteria. Although cytogenetic analysis was not possible due to the tissues being in an advanced state of decomposition, array Comparative Genomic Hybridization analysis using human bacterial artificial chromosome clones was successful in effectively eliminating aneuploidy or any copy number changes greater than approximately 3-5 Mb as a cause of the malformations. Further evaluation of the animal included extensive imaging of the skeletal and neural tissue defects. The animal's congenital anomalies are discussed in relation to the current hypotheses attempting to explain the frequent association of neural tube defects with other abnormalities.
| S-EPMC3678351 | biostudies-literature
Project description:Bartonella quintana is a zoonotic pathogen with a worldwide distribution. Humans and non-human primates are considered to be natural reservoir hosts for B. quintana. However, information on the molecular epidemiology of this organism is very limited in regard to long-tailed macaques (Macaca fascicularis) in Thailand. Therefore, this study aimed to investigate the occurrence and genetic diversity of Bartonella spp. among long-tailed macaques in Thailand. In total, 856 blood samples were collected from long-tailed macaques in Thailand. All specimens were screened for Bartonella spp. using a polymerase chain reaction (PCR) assay targeting the 16S rRNA, gltA and ftsZ genes. All positive samples were further analyzed based on nucleotide sequencing, phylogenetic analysis and multiple sequence alignment analysis. Only one macaque showed a positive result in the PCR assays based on the 16S rRNA, gltA and ftsZ genes. Nucleotide sequencing and phylogenetic analysis revealed that the obtained sequences were closely related to B. quintana previously detected in non-human primates. Single-nucleotide polymorphisms (SNPs) were detected in the gltA and ftsZ gene sequences. This study revealed that long-tailed macaques in Thailand carried B. quintana. Despite the low infection rate detected, long-tailed macaques may be a reservoir of B. quintana.
| S-EPMC8160695 | biostudies-literature
Project description:The aim was to analyze the morphological differences of the intervertebral disc and endplates at different levels. Forty-five vertebral motion segments were obtained from the spine of nine 3 to 4-year-old cynomolgus monkeys (Macaca fascicularis). From every spine, five discs were sectioned (C5-C6, T3-T4, T9-T10, L2-L3, L4-L5). In all the groups, tissue samples were collected and sections were stained with Masson's trichrome, Safranine-O and van Gieson's connective tissue stain to analyze the intervertebral discs. Immunohistochemistry was performed, using specific antibodies to detect collagens I and II. The intervertebral disc height, the maximum nucleus pulposus height, the superior and inferior endplate heights were histomorphometrically measured and different indexes were calculated to compare the differences between specimens of the same animal and between discs of the same level, and finally the differences between groups of discs of different levels. There were no differences existing in annular fibers anchoring on the endplate between discs of different levels. A positive immune reaction for type I collagen was observed in the longitudinal ligaments and in the annular region adjacent to them. Collagen II immune reactivity was found in the annulus close to the nucleus pulposus, in the endplates and in the nucleus. There were no differences between discs of different levels in the collagen I and II localization. The height of the discs varied along the spine. The smallest value was measured in T3-T4, with a larger increase caudally than cranially. The highest value was measured in L2-L3. A cervical disc was 55% the height of a lumbar one. The endplate height increased along the length of the spine. The inferior EP was always higher than the superior. The study provides a detailed structural characterization of the intervertebral disc and may be useful for further investigations on the disc degeneration process.
| S-EPMC2276588 | biostudies-other
Project description:The central region of the primate retina is called macula. The fovea is located at the center of the macula, where the photoreceptors are concentrated to create neural network adapted for high visual acuity. Damage to the fovea by macular dystrophies and age-related macular degeneration (AMD) can reduce the central visual acuity. The molecular mechanisms leading to these diseases are most likely dependent on the proteins in macula differ from that in peripheral retina in expression level. Previously, we reported an early onset macular degeneration with drusen in cynomolgus monkey pedigrees. These monkeys show similar fundus findings of early stage of AMD at 2 years after birth. To elucidate mechanism of drusen formation and to find disease biomarkers for early stage of AMD, we performed plasma proteome analysis. Plasma samples were collected from four affected and control monkeys within the same pedigree. Successful fractionation of the plasma proteins by ProteoMiner and Gelfree8100 were confirmed by SDS-PAGE. Total of 245 proteins were identified from eight samples. From the results of spectral counting, we selected some proteins, Apolipoprotein E, Histidine-rich glycoprotein, and Retinol-binding protein 4 as candidate proteins that would be related with drusen formation. Candidate proteins would be potentially beneficial as biomarkers for human AMD. One of the identified proteins, Apolipoprotein E (ApoE), is structural component of drusen and also related with other neurodegenerative disease like Alzheimer disease. In this plasma proteome analysis, ApoE would be one of the possible factors of early drusen formation in these cynomolgus monkey pedigrees.
| S-EPMC4206734 | biostudies-literature
Project description:Retroposition is an RNA-mediated mechanism to generate gene duplication, and is believed to play an important role in genome evolution and phenotypic adaptation in various species including primates. Previous studies suggested an elevated rate of recent retroposition in the rhesus macaque genome. To better understand the impact of retroposition on macaque species which have undergone an adaptive radiation approximately 3-6 million years ago, we developed a bioinformatics pipeline to identify recently derived retrocopies in cynomolgus monkeys. As a result, we identified seven experimentally validated young retrocopies, all of which are polymorphic in cynomolgus monkeys. Unexpectedly, five of them are also present in rhesus monkeys and are still segregating. Molecular evolutionary analysis indicates that the observed inter-specific polymorphism is attribute to ancestral polymorphism. Further population genetics analysis provided strong evidence of balancing selection on at least one case (Crab-eating monkey retrocopy 6, or CER6) in both species. CER6 is in adjacent with an immunoglobulin related gene and may be involved in host-pathogen interaction, a well-known target of balancing selection. Altogether, our data support that retroposition is an important force to shape genome evolution and species adaptation.
| S-EPMC5013489 | biostudies-literature
Project description:MicroRNAs (miRNAs) present in tissues and biofluids are emerging as sensitive and specific safety biomarkers. MiRNAs have not been thoroughly described in M. fascicularis, an animal model used in pharmaceutical industry especially in drug safety evaluation. Here we investigated the miRNAs in M. fascicularis. For Macaca mulatta, a closely related species of M.fascicularis, 619 stem-loop precursor miRNAs (pre-miRNAs) and 914 mature miRNAs are available in miRBase version 21. Using M. mulatta miRNAs as a reference list and homology search tools, we identified 604 pre-miRNAs and 913 mature miRNAs in the genome of M.fascicularis. In order to validate the miRNAs identified by homology search we attempted to sequence miRNAs expressed in kidney cortex from M. fascicularis. MiRNAs expressed in kidney cortex may indeed be released in urine upon kidney cortex damage and be potentially used to monitor drug induced kidney injury. Hence small RNA sequencing libraries were prepared using kidney cortex tissues obtained from three naive M. fascicularis and sequenced. Analysis of sequencing data indicated that 432 out of 913 mature miRNAs were expressed in kidney cortex tissues. Assigning these 432 miRNAs to pre-miRNAs revealed that 273 were expressed from both the -5p and -3p arms of 150 pre-miRNAs and 159 miRNAs expressed from either the -5p or -3p arm of 176 pre-miRNAs. Mapping sequencing reads to pre-miRNAs also facilitated the detection of twenty-two new miRNAs. To substantiate miRNAs identified by small RNA sequencing, 313 miRNAs were examined by RT-qPCR. Expression of 262 miRNAs in kidney cortex tissues ware confirmed by TaqMan microRNA RT-qPCR assays. Analysis of kidney cortex miRNA targeted genes suggested that they play important role in kidney development and function. Data presented in this study may serve as a valuable resource to assess the renal safety biomarker potential of miRNAs in Cynomolgus monkeys.
2016-09-13 | GSE86836 | GEO
Project description:Hematogenous metastases are enhanced by platelet aggregation induced by tumor cell-platelet interaction. Podoplanin is a key molecule to enhance the platelet aggregation and interacts with C-type lectin-like receptor 2 (CLEC-2) on platelet via PLAG domains. Our previous reports have shown that blocking podoplanin binding to platelets by neutralizing antibody specific to PLAG4 domain strongly reduces hematogenous metastasis. However, podoplanin is expressed in a variety of normal tissues such as lymphatic vessels and the question remains whether treatment of tumors with anti-podoplanin neutralizing antibodies would be toxic. Monkeys are the most suitable species for that purpose. PLAG3 and PLAG4 domains had high homology among various monkey species and human. PLAG domain deleted mutants were indicated that monkey PLAG4 domain played a more crucial role in podoplanin-induced platelet aggregation than did the PLAG3 domain as in human. Moreover, newly established neutralizing antibodies (1F6, 2F7, and 3F4) targeting the monkey PLAG4 domain blocked interaction between monkey podoplanin and CLEC-2. Especially, the 2F7 neutralizing antibody strongly suppressed platelet aggregation and pulmonary metastasis. Furthermore, inhibiting podoplanin function with 2F7 neutralizing antibody exhibited no acute toxicity in cynomolgus monkeys. Our results suggested that targeting podoplanin with specific neutralizing antibodies may be an effective anticancer treatment.
| S-EPMC6161800 | biostudies-other
Project description:A 2-year-old male cynomolgus monkey (Macaca fascicularis) showed neurological symptoms during quarantine for importation into Japan, and was euthanized due to poor prognosis. Gross anatomical examination revealed a hemorrhagic lesion around the lateral ventricle in the cerebrum. Histologically, severe diffused suppurative meningitis and ventriculitis were detected with numerous Gram-negative bacilli in the cerebrum. Immunohistochemically, the bacilli were positively stained with an antibody against Klebsiella pneumoniae. The bacterium was isolated from the liver, and it was confirmed to be K. pneumoniae by 16S rDNA sequencing. The isolate displayed a hypermucoviscosity phenotype, was positive for the rmpA and k2A genes, and demonstrated multidrug resistance. These results suggest that invasive K. pneumoniae can cause septicemic infection, characterized by severe diffused suppurative meningoencephalitis in monkeys.
| S-EPMC5559359 | biostudies-other
Project description:Cynomolgus monkeys (Macaca fascicularis; MF) are commonly used as nonhuman primate models for pharmaceutical product testing. In their habitat range, monkeys have close contact with humans, allowing the possibility of bidirectional transmission of tuberculosis (TB) between the two species. Although the intradermal tuberculin skin test (TST) is used for TB detection in MF, it has limitations. Herein, we established the mIGRA, combining human QuantiFERON-TB Gold-Plus and monkey IFN-γ ELISApro systems, and used it to investigate 39 captive MF who were cage-mates or lived in cages located near a monkey who died from the naturally TB infection. During a 12-month period of study, 14 (36%), 10 (26%), and 8 (21%) monkeys showed TB-positive results using the mIGRA, the TST, and TB culture, respectively. Among the 14 mIGRA-positive monkeys, 8 (57.1%) were TST-positive and 7 (50%) were culture-positive, indicating early TB detection in the latent and active TB stages with the mIGRA. Interestingly, 3 (37.5%) of the TST-negative monkeys were culture-positive. Our study showed that the mIGRA offers many advantages, including high sensitivity and high throughput, and it requires only one on-site visit to the animals. The assay may be used as a supplementary tool for TB screening in MF.
| S-EPMC7541520 | biostudies-literature
Project description:Labyrinthitis is inflammation of the membranous and bony labyrinth of the inner ear. Typical portals of entry includehematogenous spread from the cochlear vasculature, passage of otitis media pathogens through the round window, and mostcommonly, meningogenic spread from the subarachnoid space. The sequela of chronic inner ear inflammation is labyrinthitisossificans, in which inner ear structures are replaced by fibrous and osseous tissues. Labyrinthitis in humans has been reportedconcurrently with infection due to various viruses (for example, varicella-zoster, measles, mumps) and bacteria (for example,Treponema pallidum, Streptococcus pneumoniae) and may be associated with vertebrobasilar ischemia and meningitis. Profoundsensorineural hearing loss is a common, serious complication of this disease. Here, we report a case of labyrinthitisossificans in a cynomolgus macaque (Macaca fascicularis) with a potential infectious etiology. Historically, this animal hadan indwelling femoral intravenous catheter for more than 4 y. He presented with a right-sided head tilt and incoordinationof 2 mo duration. The macaque was treated with NSAID and antibiotics, which corrected the incoordination but not the headtilt. MRI revealed right-sided labyrinthitis, and euthanasia was elected due to clinical signs that were refractory to treatment.Gross pathology was unremarkable, but histopathology revealed chronic labyrinthitis ossificans with local fibroplasia andvestibuloauditory neuritis. We describe here the clinical features, imaging, and histologic lesions of labyrinthitis in a macaque.
| S-EPMC6008717 | biostudies-literature