Primary histiocytic sarcoma in the brain with renal metastasis causing internal ophthalmoparesis and external ophthalmoplegia in a Maine Coon cat.

CASE SUMMARY: An 11-year-old neutered male Maine Coon cat was presented for investigation of anisocoria and depression. Neurological examination was consistent with a lesion at the level of the middle cranial fossa, and biochemistry was indicative of moderate renal functional impairment. MRI of the brain identified an extra-axial mass lesion at the level of the middle cranial fossa, T2-weighted hyperintense and strongly homogeneously contrast enhancing with dural tail. The cat was euthanased after 6 weeks of palliative treatment with corticosteroids. Histopathology and immunohistochemistry of the brain, the intra-cranial mass and the renal masses found on necropsy were consistent with histiocytic sarcoma. RELEVANCE AND NOVEL INFORMATION: Central nervous system histiocytic sarcoma is a rare finding in cats. This original case report describes the neurological presentation, novel MRI characteristics and pathological findings of suspected primary histiocytic sarcoma affecting the brain with renal metastasis in a cat

Conformational epitopes of myelin oligodendrocyte glycoprotein are targets of potentially pathogenic antibody responses in multiple sclerosis

<p>Abstract</p> <p>Background</p> <p>Myelin/oligodendrocyte glycoprotein (MOG) is a putative autoantigen in multiple sclerosis (MS). Establishing the pathological relevance and validity of anti-MOG antibodies as biomarkers has yielded conflicting reports mainly due to different MOG isoforms used in different studies. Because epitope specificity may be a key factor determining anti-MOG reactivity we aimed at identifying <it>a priori </it>immunodominant MOG epitopes by monoclonal antibodies (mAbs) and at assessing clinical relevance of these epitopes in MS.</p> <p>Methods</p> <p>Sera of 325 MS patients, 69 patients with clinically isolated syndrome and 164 healthy controls were assayed by quantitative, high-throughput ELISA for reactivity to 3 different MOG isoforms, and quantitative titers correlated with clinical characteristics. mAbs defined unique immunodominant epitopes distinct to each of the isoforms.</p> <p>Results</p> <p>In the majority of human samples anti-MOG levels were skewed towards low titers. However, in 8.2% of samples high-titer anti-MOG antibodies were identified. In contrast to anti-MOG reactivity observed in a mouse model of MS, in patients with MS these never reacted with ubiquitously exposed epitopes. Moreover, in patients with relapsing-remitting MS high-titer anti-MOG IgG correlated with disability (EDSS; Spearman r = 0.574; p = 0.025).</p> <p>Conclusions</p> <p>Thus high-titer reactivity likely represents high-affinity antibodies against pathologically relevant MOG epitopes, that are only present in a small proportion of patients with MS. Our study provides valuable information about requirements of anti-MOG reactivity for being regarded as a prognostic biomarker in a subtype of MS.</p

Distribution of Renin Activity and Angiotensinogen in Rat Brain Effects of Dietary Sodium Chloride Intake on Brain Renin

Abstract The purpose of this study was to investigate the biochemistry and the regulation of the brain renin-angiotensin system in the Sprague-Dawley rat. Renin activity and angiotensinogen concentrations (direct and indirect radioimmunoassays) were measured in several brain areas and in neuroendocrine glands. Regional renin activities were measured in separate groups of rats on high and low NaCl diets. Mean tissue renin activities ranged from 2.2±0.6 to 54.4±19.7 fmol/mg protein per h (mean of 7±SD), with the highest amounts in pineal, pituitary, and ponsmedulla. NaCl depletion increased renin activity in selected regions; based on estimates of residual plasma contamination (despite perfusion of brains with saline), increased renin activity of pineal gland and posterior pituitary was attributed to higher plasma renin. To eliminate contamination by plasma renin, 16-h-nephrectomized rats were also studied. In anephric rats, NaCl depletion increased renin activity by 92% in olfactory bulbs and by 97% in anterior pituitary compared with NaCI-replete state. These elevations could not be accounted for by hyperreninemia. Brain renin activity was low and was unaffected by dietary NaCl in amygdala, hypothalamus, striatum, frontal cortex, and cerebellum. In contrast to renin, highest angiotensinogen concentrations were measured in hypothalamus and cerebellum. Overall, angiotensinogen measurements with the direct and the indirect assays were highly correlated (n = 56, r = 0.96, P &lt; 0.001). We conclude that (a) NaCl deprivation increases renin in olfactory bulbs and anterior pituitary of the rat, unrelated to contamination by plasma renin; and (b) the existence of angiotensinogen, the precursor of angiotensins, is demonstrated by direct radioimmunoassay throughout the brain and in neuroendocrine glands

Human Nerve Growth Factor Protects Common Marmosets against Autoimmune Encephalomyelitis by Switching the Balance of T Helper Cell Type 1 and 2 Cytokines within the Central Nervous System

Multiple sclerosis is a demyelinating disorder of the central nervous system (CNS), in which an immune attack directed against myelin constituents causes myelin destruction and death of oligodendrocytes, the myelin-producing cells. Here, the efficacy of nerve growth factor (NGF), a growth factor for neurons and oligodendrocytes, in promoting myelin repair was evaluated using the demyelinating model of experimental allergic encephalomyelitis (EAE) in the common marmoset. Surprisingly, we found that NGF delayed the onset of clinical EAE and, pathologically, prevented the full development of EAE lesions. We demonstrate by immunocytochemistry that NGF exerts its antiinflammatory effect by downregulating the production of interferon γ by T cells infiltrating the CNS, and upregulating the production of interleukin 10 by glial cells in both inflammatory lesions of EAE and normal-appearing CNS white matter. Thus, NGF, currently under investigation in human clinical trials as a neuronal trophic factor, may be an attractive candidate for therapy of autoimmune demyelinating disorders

The Effects of Intradermal Vaccination with DNA Encoding for the T-cell Receptor on the Induction of Experimental Autoimmune Encephalomyelitis in B10.PL Mice

Intradermal gene administration was found to induce a more profound immune response than direct intramusclular gene injection. We performed intradermal vaccination of B10.PL mice with DNA encoding for the Vβ8.2 region of the T-cell receptors (TCR). Three weeks later, these mice were immunized with rat myelin basic protein (MBP). Daily mean clinical scores and mortality rate were lower in this group compared with controls. The proliferative responses of lymph node cells to rat MBP were slightly less in the vaccination groups than in the control groups (p<0.05). However, we detected no differences between the two groups with regard to the production of MBP-specific IgG, IgG1, & IgG2a antibodies. The levels of cytokine mRNA expression in the vaccination groups were observed higher than in the control groups without antigen-specific stimulation, but all of cytokine expressions between the vaccination and control groups after antigen-specific stimulation were identical. These results demonstrate that intradermal DNA vaccines encoding for TCR might prove to be useful in the control of autoimmune disease

Myoclonus and hypercalcemia in a dog with poorly differentiated lymphoproliferative neoplasia.

A 1-year, 8-month-old Rhodesian Ridgeback was presented with obtundation, ambulatory tetraparesis, and myoclonus. Initial clinical findings included ionized hypercalcemia with an apparent marked increase in parathyroid hormone, thrombocytopenia, and nonregenerative anemia. Low numbers of circulating atypical cells were noted on blood film evaluation. Brain magnetic resonance imaging identified an extra-axial contrast enhancing subtentorial lesion, and cerebrospinal fluid (CSF) analysis documented a marked atypical lymphocytic pleocytosis. Flow cytometry performed on the CSF demonstrated expression of only CD45, CD90, and MHC class II, with Pax5 positivity on subsequent immunohistochemistry. The final diagnosis was of B-cell lymphoblastic lymphoma or acute leukemia, given the distribution of disease and the presence of significant bone marrow infiltration alongside an aggressive clinical course. The unusual immunophenotype of the neoplastic cells and hypercalcemia presented antemortem diagnostic challenges, highlighting the need for a multidisciplinary approach and caution in the interpretation of clinical abnormalities in cases with multiple comorbidities

Comparative anatomy and angiography of the cardiac coronary venous system in four species: human, ovine, porcine, and canine.

INTRODUCTION: The coronary arterial system has been the subject of greater investigation than its venous system due to the importance of human coronary artery disease. With the advent of new percutaneous treatments, the anatomy of the coronary venous system has increasing relevancy. We compared the organization of the coronary venous circulation in three species commonly used in research and compared these to normal humans using both macroscopic anatomic and angiographic studies. ANIMALS: The anatomy of five explanted hearts from healthy dogs, pigs, and sheep were studied macroscopically, and 10 explanted hearts per animal species and 10 clinically normal human were examined by angiography. METHODS: Animal hearts were injected with latex and dissected macroscopically. The coronary venous system of humans was evaluated from clinical angiographic studies. In the animal hearts, a retrograde angiographic study was performed via a Foley catheter in the coronary sinus. RESULTS: The general organization of the coronary venous circulation was similar among humans, dogs, sheep, and pigs. Despite overall similarities to humans, animal hearts demonstrated the absence of the oblique vein of the left atrium and differences in position and organization of venous valves; venous diameters; number of tributary veins; and presence of an anastomosis between the left and right (human anterior and posterior) venous tree. The left azygos of the pig and sheep joined the coronary sinus. CONCLUSIONS: Anatomical differences must be considered when planning biomedical and veterinary studies incorporating cardiac veins. This study provides baseline data regarding structure and organization of the cardiac venous system

A defect of sphingolipid metabolism modifies the properties of normal appearing white matter in multiple sclerosis

Maintaining the appropriate complement and content of lipids in cellular membranes is critical for normal neural function. Accumulating evidence suggests that even subtle perturbations in the lipid content of neurons and myelin can disrupt their function and may contribute to myelin and axonal degradation. In this study, we determined the composition and quantified the content of lipids and sterols in normal appearing white matter (NAWM) and normal appearing grey matter (NAGM) from control and multiple sclerosis brain tissues by electrospray ionization tandem mass spectrometry. Our results suggest that in active-multiple sclerosis, there is a shift in the lipid composition of NAWM and NAGM to a higher phospholipid and lower sphingolipid content. We found that this disturbance in lipid composition was reduced in NAGM but not in NAWM of inactive-multiple sclerosis. The pattern of disturbance in lipid composition suggests a metabolic defect that causes sphingolipids to be shuttled to phospholipid production. Modelling the biophysical consequence of this change in lipid composition of NAWM indicated an increase in the repulsive force between opposing bilayers that could explain decompaction and disruption of myelin structure