scholarly journals The adult oligodendrocyte can participate in remyelination

2018 ◽  
Vol 115 (50) ◽  
pp. E11807-E11816 ◽  
Author(s):  
Ian D. Duncan ◽  
Abigail B. Radcliff ◽  
Moones Heidari ◽  
Grahame Kidd ◽  
Benjamin K. August ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Multiple Sclerosis ◽  
Nonhuman Primates ◽  
Light And Electron Microscopy ◽  
Vitamin B ◽  
Oligodendrocyte Progenitor Cells ◽  
Large Animal ◽  
Myelin Sheaths ◽  
Large Animal Models ◽  
2D And 3D

Endogenous remyelination of the CNS can be robust and restore function, yet in multiple sclerosis it becomes less complete with time. Promoting remyelination is a major therapeutic goal, both to restore function and to protect axons from degeneration. Remyelination is thought to depend on oligodendrocyte progenitor cells, giving rise to nascent remyelinating oligodendrocytes. Surviving, mature oligodendrocytes are largely regarded as being uninvolved. We have examined this question using two large animal models. In the first model, there is extensive demyelination and remyelination of the CNS, yet oligodendrocytes survive, and in recovered animals there is a mix of remyelinated axons interspersed between mature, thick myelin sheaths. Using 2D and 3D light and electron microscopy, we show that many oligodendrocytes are connected to mature and remyelinated myelin sheaths, which we conclude are cells that have reextended processes to contact demyelinated axons while maintaining mature myelin internodes. In the second model in vitamin B12-deficient nonhuman primates, we demonstrate that surviving mature oligodendrocytes extend processes and ensheath demyelinated axons. These data indicate that mature oligodendrocytes can participate in remyelination.

scholarly journals Rapid Heterotrophic Ossification with Cryopreserved Poly(ethylene glycol-) Microencapsulated BMP2-Expressing MSCs

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Jennifer Mumaw ◽  
Erin T. Jordan ◽  
Corinne Sonnet ◽  
Ronke M. Olabisi ◽  
Elizabeth A. Olmsted-Davis ◽  
...  
Keyword(s):  
Bone Formation ◽  
Ethylene Glycol ◽  
Light And Electron Microscopy ◽  
Long Bone ◽  
Large Animal ◽  
Poly Ethylene Glycol ◽  
Large Animal Models ◽  
Bone Nonunion ◽  
Transgene Delivery ◽  
Poly Ethylene

Autologous bone grafting is the most effective treatment for long-bone nonunions, but it poses considerable risks to donors, necessitating the development of alternative therapeutics. Poly(ethylene glycol) (PEG) microencapsulation and BMP2 transgene delivery are being developed together to induce rapid bone formation. However, methods to make these treatments available for clinical applications are presently lacking. In this study we used mesenchymal stem cells (MSCs) due to their ease of harvest, replication potential, and immunomodulatory capabilities. MSCs were from sheep and pig due to their appeal as large animal models for bone nonunion. We demonstrated that cryopreservation of these microencapsulated MSCs did not affect their cell viability, adenoviral BMP2 production, or ability to initiate bone formation. Additionally, microspheres showed no appreciable damage from cryopreservation when examined with light and electron microscopy. These results validate the use of cryopreservation in preserving the viability and functionality of PEG-encapsulated BMP2-transduced MSCs.

Fibrosarcoma with Metastasis in a Rhesus Monkey

1973 ◽  
Vol 10 (4) ◽  
pp. 342-346 ◽  
Author(s):  
G. C. Todd ◽  
W. J. Griffing ◽  
G. R. Koenig
Keyword(s):  
Electron Microscopy ◽  
Rhesus Monkey ◽  
Nonhuman Primates ◽  
Light And Electron Microscopy ◽  
Axillary Lymph Nodes ◽  
Malignant Neoplasms ◽  
Axillary Lymph ◽  
Naturally Occurring ◽  
Primary Neoplasm ◽  
Male Rhesus

Malignant neoplasms that metastasize are uncommon in nonhuman primates. A naturally occurring fibrosarcoma of the forearm with metastasis to the axillary lymph nodes was found in an adult male Rhesus monkey. The primary neoplasm grew rapidly to a size of 8 x 10 x 18 cm. Diagnosis was based on characteristic morphologic findings by light and electron microscopy.

scholarly journals Insular Amyloidosis in Spontaneously Diabetic Nonhuman Primates

1982 ◽  
Vol 19 (7_suppl) ◽  
pp. 181-192 ◽  
Author(s):  
J. L. Palotay ◽  
C. F. Howard
Keyword(s):  
Diabetes Mellitus ◽  
Electron Microscopy ◽  
Alcian Blue ◽  
Nonhuman Primates ◽  
Effective Means ◽  
Light And Electron Microscopy ◽  
Fibrillar Structure ◽  
Islet Amyloid ◽  
Transmission Electron ◽  
Amyloid Accumulation

Sections of pancreas from 21 nonhuman primates with diabetes mellitus were examined by light and electron microscopy. All monkeys showed amyloid accumulation in the islets of Langerhans. Amyloid was identified by its dichroism with three different stains: Congo red, changing from red to yellowish-green; standardized toluidine blue, changing from blue to red; and sulfated alcian blue, changing from blue-green to pink. Sulfated alcian blue was a rapid and effective means of detecting amyloid. The characteristic fibrillar structure of amyloid was seen with transmission electron microscopy. Deposition of islet amyloid was independent of the presence or absence of amyloid in other organs. Results indicate that nonhuman primates offer a model for studying the sequential development of insular amyloidotic diabetes mellitus.

scholarly journals Japanese Macaque Rhadinovirus Encodes a Viral MicroRNA Mimic of the miR-17 Family

2016 ◽  
Vol 90 (20) ◽  
pp. 9350-9363 ◽  
Author(s):  
Rebecca L. Skalsky ◽  
Sarah A. Barr ◽  
Andrew J. Jeffery ◽  
Tiffany Blair ◽  
Ryan Estep ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Japanese Macaque ◽  
Large Animal ◽  
Primate Model ◽  
Sequence Comparisons ◽  
Necrosis Factor Alpha ◽  
Viral Mirnas ◽  
Large Animal Models

ABSTRACTJapanese macaque (JM) rhadinovirus (JMRV) is a novel, gamma-2 herpesvirus that was recently isolated from JM with inflammatory demyelinating encephalomyelitis (JME). JME is a spontaneous and chronic disease with clinical characteristics and immunohistopathology comparable to those of multiple sclerosis in humans. Little is known about the molecular biology of JMRV. Here, we sought to identify and characterize the small RNAs expressed during lytic JMRV infection using deep sequencing. Fifteen novel viral microRNAs (miRNAs) were identified in JMRV-infected fibroblasts, all of which were readily detectable by 24 h postinfection and accumulated to high levels by 72 h. Sequence comparisons to human Kaposi's sarcoma-associated herpesvirus (KSHV) miRNAs revealed several viral miRNA homologs. To functionally characterize JMRV miRNAs, we screened for their effects on nuclear factor kappa B (NF-κB) signaling in the presence of two proinflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β). Multiple JMRV miRNAs suppressed cytokine-induced NF-κB activation. One of these miRNAs, miR-J8, has seed sequence homology to members of the cellular miR-17/20/106 and miR-373 families, which are key players in cell cycle regulation as well as inflammation. Using reporters, we show that miR-J8 can target 3′ untranslated regions (UTRs) with miR-17-5p or miR-20a cognate sites. Our studies implicate JMRV miRNAs in the suppression of innate antiviral immune responses, which is an emerging feature of many viral miRNAs.IMPORTANCEGammaherpesviruses are associated with multiple diseases linked to immunosuppression and inflammation, including AIDS-related cancers and autoimmune diseases. JMRV is a recently identified herpesvirus that has been linked to JME, an inflammatory demyelinating disease in Japanese macaques that mimics multiple sclerosis. There are few large-animal models for gammaherpesvirus-associated pathogenesis. Here, we provide the first experimental evidence of JMRV miRNAsin vitroand demonstrate that one of these viral miRNAs can mimic the activity of the cellular miR-17/20/106 family. Our work provides unique insight into the roles of viral miRNAs during rhadinovirus infection and provides an important step toward understanding viral miRNA function in a nonhuman primate model system.

scholarly journals Bimodal Endocytic Probe for Three-Dimensional Correlative Light and Electron Microscopy

2021 ◽  
Author(s):  
Job Fermie ◽  
Leanne de Jager ◽  
Helen Foster ◽  
Tineke Veenendaal ◽  
Cecilia de Heus ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Bovine Serum Albumin ◽  
Fluorescence Microscopy ◽  
Light And Electron Microscopy ◽  
Three Dimensional ◽  
Fiducial Marker ◽  
Regions Of Interest ◽  
Dynamic Information ◽  
Endosomal System ◽  
2D And 3D

Correlative light and electron microscopy (CLEM) can infer molecular, functional and dynamic information to ultrastructure by linking information of different imaging modalities. One of the main challenges, especially in 3D-CLEM, is the accurate registration of fluorescent signals to electron microscopy (EM). Here, we present fluorescent BSA-gold (fBSA-Au), a bimodal endocytic tracer as fiducial marker for 2D and 3D CLEM applications. fBSA-Au consists of colloidal gold (Au) particles stabilized with fluorescent bovine serum albumin (BSA). The conjugate is efficiently endocytosed and distributed throughout the 3D endo-lysosomal network of the cells, and has an excellent visibility both in fluorescence microscopy (FM) and EM. We demonstrate the use of fBSA-Au in several 2D and 3D CLEM applications using Tokuyasu cryosections, resin-embedded material, and cryo-EM. As a fiducial marker, fBSA-Au facilitates rapid registration of regions of interest between FM and EM modalities and enables accurate (50-150 nm) correlation of fluorescence to EM data. Endocytosed fBSA-Au benefits from a homogenous 3D distribution throughout the endosomal system within the cell, and does not obscure any cellular ultrastructure. The broad applicability and visibility in both modalities makes fBSA-Au an excellent endocytic fiducial marker for 2D and 3D (cryo-)CLEM applications.

Sustained correction of disease in naive and AAV2-pretreated hemophilia B dogs: AAV2/8-mediated, liver-directed gene therapy

Blood ◽  
2005 ◽  
Vol 105 (8) ◽  
pp. 3079-3086 ◽  
Author(s):  
Lili Wang ◽  
Roberto Calcedo ◽  
Timothy C. Nichols ◽  
Dwight A. Bellinger ◽  
Aaron Dillow ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Nonhuman Primates ◽  
Liver Toxicity ◽  
Factor Ix ◽  
Hemophilia B ◽  
Transduction Efficiency ◽  
Large Animal ◽  
Adeno Associated Virus ◽  
Large Animal Models ◽  
High Level

AbstractAdeno-associated virus 8 (AAV8), a new member of the AAV family isolated from nonhuman primates, is an attractive candidate for hepatic gene transfer applications because of 10- to 100-fold improved transduction efficiency in mouse liver models. Additionally, AAV8 has lesser frequency of pre-existing immunity in humans. These properties could solve some of the problems associated with AAV2 vectors. The benefits of AAV8 demonstrated in mouse models, however, have not been confirmed in larger animals. In this study, we evaluate the efficacy and safety of AAV2/8 vector in both naive and AAV2-pretreated hemophilia B dogs. Two naive hemophilia B dogs that received a single intraportal administration of AAV2/8 vector have achieved sustained expression of 10% and 26% of normal levels of canine factor IX (cFIX) for more than a year. In an AAV2-pretreated hemophilia B dog, cFIX expression increased from less than 1% to 16% of normal levels when treated with an AAV2/8 vector, and a high level of expression has lasted for more than 2 years. No significant liver toxicity or cFIX-specific antibodies have been detected in these animals. Studies here have demonstrated the safety and improved efficacy of AAV2/8 vector in large-animal models for liver-directed gene therapy.

The Morphology of Vacuolated Cells in the Liver Following Administration of Vitamin A.

1973 ◽  
Vol 31 ◽  
pp. 408-409
Author(s):  
Odell T. Minick ◽  
Hidejiro Yokoo ◽  
Fawzia Batti
Keyword(s):  
Electron Microscopy ◽  
Body Weight ◽  
Vitamin A ◽  
Light And Electron Microscopy ◽  
Liver Cells ◽  
Prominent Feature ◽  
Vascular Space ◽  
Vacuolated Cell ◽  
Vacuolated Cells ◽  
Vacuolated Cytoplasm

Vacuolated cells in the liver of young rats were studied by light and electron microscopy following the administration of vitamin A (200 units per gram of body weight). Their characteristics were compared with similar cells found in untreated animals.In rats given vitamin A, cells with vacuolated cytoplasm were a prominent feature. These cells were found mostly in a perisinusoidal location, although some appeared to be in between liver cells (Fig. 1). Electron microscopy confirmed their location in Disse's space adjacent to the sinusoid and in recesses between liver cells. Some appeared to be bordering the lumen of the sinusoid, but careful observation usually revealed a tenuous endothelial process separating the vacuolated cell from the vascular space. In appropriate sections, fenestrations in the thin endothelial processes were noted (Fig. 2, arrow).

Control of Autogenous Vein Grafts Prior to Reimplantation, By Electron Microscopy

1972 ◽  
Vol 30 ◽  
pp. 106-107
Author(s):  
John H. L. Watson ◽  
John L. Swedo ◽  
M. Vrandecic
Keyword(s):  
Electron Microscopy ◽  
Light And Electron Microscopy ◽  
Physiological Saline ◽  
Experimental Conditions ◽  
Vein Grafts ◽  
Arterial Blood ◽  
Saphenous Veins ◽  
Autogenous Vein ◽  
Control Of Parameters ◽  
Post Implantation

The ambient temperature and the nature of the storage fluids may well have significant effects upon the post-implantation behavior of venus autografts. A first step in the investigation of such effects is reported here. Experimental conditions have been set which approximate actual operating room procedures. Saphenous veins from dogs have been used as models in the experiments. After removal from the dogs the veins were kept for two hours under four different experimental conditions, viz at either 4°C or 23°C in either physiological saline or whole canine arterial blood. At the end of the two hours they were prepared for light and electron microscopy. Since no obvious changes or damage could be seen in the veins by light microscopy, even with the advantage of tissue specific stains, it was essential that the control of parameters for successful grafts be set by electron microscopy.

Ultrastructure of two neoplasms in culture compared with original biopsies

1984 ◽  
Vol 42 ◽  
pp. 50-51
Author(s):  
Joseph M. Harb ◽  
James T. Casper ◽  
Vlcki Piaskowski
Keyword(s):  
Electron Microscopy ◽  
Tissue Culture ◽  
Biopsy Specimen ◽  
Cultured Cells ◽  
Light And Electron Microscopy ◽  
Human Tumor ◽  
Soft Agar ◽  
Human Tumor Cells ◽  
Morphological Distinction ◽  
Tumor Types

The application of tissue culture and the newer methodologies of direct cloning and colony formation of human tumor cells in soft agar hold promise as valuable modalities for a variety of diagnostic studies, which include morphological distinction between tumor types by electron microscopy (EM). We present here two cases in which cells in culture expressed distinct morphological features not apparent in the original biopsy specimen. Evaluation of the original biopsies by light and electron microscopy indicated both neoplasms to be undifferentiated sarcomas. Colonies of cells propagated in soft agar displayed features of rhabdomyoblasts in one case, and cultured cells of the second biopsy expressed features of Ewing's sarcoma.

The Effect of Vitamin A on the Intermittent Nitrogen Dioxide Gas Exposure in Hamsters

1976 ◽  
Vol 34 ◽  
pp. 176-177
Author(s):  
J.C.S. Kim ◽  
M.G. Jourden ◽  
E.S. Carlisle
Keyword(s):  
Electron Microscopy ◽  
Vitamin A ◽  
Nitrogen Dioxide ◽  
Chronic Exposure ◽  
Light And Electron Microscopy ◽  
Specific Effect ◽  
Deficient Diet ◽  
Intermittent Exposure ◽  
Hypovitaminosis A ◽  
Gas Exposure

Chronic exposure to nitrogen dioxide in rodents has shown that injury reaches a maximum after 24 hours, and a reparative adaptive phase follows (1). Damage occurring in the terminal bronchioles and proximal portions of the alveolar ducts in rats has been extensively studied by both light and electron microscopy (1).The present study was undertaken to compare the response of lung tissue to intermittent exposure to 10 ppm of nitrogen dioxide gas for 4 hours per week, while the hamsters were on a vitamin A deficient diet. Ultrastructural observations made from lung tissues obtained from non-gas exposed, hypovitaminosis A animals and gas exposed animals fed a regular commercially prepared diet have been compared to elucidate the specific effect of vitamin A on nitrogen dioxide gas exposure. The interaction occurring between vitamin A and nitrogen dioxide gas has not previously been investigated.

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