8 research outputs found

    In vivo MRI is sensitive to remyelination in a nonhuman primate model of multiple sclerosis

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    Remyelination is crucial to recover from inflammatory demyelination in multiple sclerosis (MS). Investigating remyelination in vivo using magnetic resonance imaging (MRI) is difficult in MS, where collecting serial short-interval scans is challenging. Using experimental autoimmune encephalomyelitis (EAE) in common marmosets, a model of MS that recapitulates focal cerebral inflammatory demyelinating lesions, we investigated whether MRI is sensitive to, and can characterize, remyelination. In six animals followed with multisequence 7 T MRI, 31 focal lesions, predicted to be demyelinated or remyelinated based on signal intensity on proton density-weighted images, were subsequently assessed with histopathology. Remyelination occurred in four of six marmosets and 45% of lesions. Radiological-pathological comparison showed that MRI had high statistical sensitivity (100%) and specificity (90%) for detecting remyelination. This study demonstrates the prevalence of spontaneous remyelination in marmoset EAE and the ability of in vivo MRI to detect it, with implications for preclinical testing of pro-remyelinating agents

    Extraocular muscle damage from dental implant penetration to the orbit

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    Purpose: To demonstrate an unusual case of orbital trauma due to dental surgery complication. Observations: An elderly patient who underwent dental implantation to the zygomatic bone was hospitalized in the ophthalmology department with impaired abduction of her right eye, also evident on ocular examination. Head computed tomography demonstrated damage to the lateral rectus and to the inferior oblique muscles. Clinical assessment determined these muscles could not be repaired and reattached. The extent of irreversible damage in the patient was permanent limitation in movement of her affected eye with subsequent strabismus. Conclusions and importance: Accurate pre-operative planning of dental zygomatic implant insertion, as well as selecting the size and direction of the implant, are imperative. Moreover, performing surgery in multidisciplinary centers with oculofacial plastic surgeons in such cases, may reduce risk of this complication, make it a safer procedure, and allow immediate treatment when required

    Bovine immune response to inoculation with Neospora caninum surface antigen SRS2 lipopeptides mimics immune response to infection with live parasites

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    Infection of cattle with Neospora caninum protozoa, the causative agent of bovine protozoal abortion, results in robust cellular and humoral immune responses, particularly CD4(+) T-lymphocyte activation and gamma interferon (IFN-gamma) secretion. In the present study, N. caninum SRS2 (NcSRS2) T-lymphocyte-epitope-bearing subunits were incorporated into DNA and peptide preparations to assess CD4(+) cell proliferation and IFN-gamma T-lymphocyte-secretion immune responses in cattle with predetermined major histocompatibility complex (MHC) genotypes. In order to optimize dendritic-cell processing, NcSRS2 DNA vaccine was delivered with granulocyte macrophage-colony-stimulating factor and Flt3 ligand adjuvant. The synthesized NcSRS2 peptides were coupled with a palmitic acid molecule (lipopeptide) and delivered with Freund's adjuvant. Cattle vaccinated with NcSRS2 DNA vaccine alone did not induce T-lymphocyte activation or IFN-gamma secretion, whereas subsequent booster inoculation with NcSRS2-lipopeptides induced robust NcSRS2-specific immune responses. Compared to the response in control animals, NcSRS2-lipopeptide-immunized cattle had significantly increased NcSRS2-specific T-lymphocyte proliferation, numbers of IFN-gamma-secreting peripheral blood mononuclear cells, and immunoglobulin G1 (IgG1) and IgG2a antibody levels. The findings show that N. caninum NcSRS2 subunits bearing T-lymphocyte epitopes induced cell-mediated immune responses similar to the protective immune responses previously described against live parasite infection, namely T-lymphocyte activation and IFN-gamma secretion. The findings support the investigation of NcSRS2 immunogens for protection against N. caninum-induced fetal infection and abortion in cattle

    Ophthalmic manifestations of multiple myeloma

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    PurposeTo describe ophthalmic manifestations in a series of patients with multiple myeloma (MM) and review the literature.DesignRetrospective case series.MethodsReview of all cases with ophthalmic manifestations of MM seen at the Department of Ophthalmology, Royal Adelaide Hospital, between 1987 and 2002.ResultsOf all patients with MM who were managed at the Royal Adelaide Hospital in the study period, only 8 were referred to the Ophthalmology Department with ophthalmic manifestations. Five males and 3 females with a mean age of 61.25 years (range 42-78) who exhibited ophthalmic manifestations were studied. Six patients (75%) had known MM at the time of their ophthalmic evaluation. Four patients (50%) had neuro-ophthalmic symptoms resulting in diplopia or visual disturbances. Three patients (37.5%) presented with orbital involvement and 1 (12.5%) with hyperviscosity retinopathy. Five patients (62.5%) died within 2 months of their ophthalmic presentation.ConclusionOphthalmic manifestations of MM are uncommon and diverse. They may appear at the initial presentation of the disease or occur late in the disease process. Awareness of the possible manifestations may lead to an earlier diagnosis and have a positive influence on the disease course

    mTORC1 as a Regulator of Mitochondrial Functions and a Therapeutic Target in Cancer

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