In situ hybridization of feline leukemia virus in a primary neural B-cell lymphoma.

An 8-y-old castrated male, outdoor European shorthair cat was presented with a history of hindlimb weakness and paralysis. Disease progression was continuous from the onset; deep algesia disappeared at the final stage. Radiography of the vertebral column was unremarkable; along with patient history and physical examination results, magnetic resonance imaging suggested inflammatory lesions in the spinal cord, although neoplasia could not be ruled out. Feline leukemia virus (FeLV) positivity was confirmed by a serum ELISA prior to euthanasia. Upon postmortem examination, hemorrhages were present in the spinal cord at the level of vertebrae T7-8. Histologic and immunohistochemical analysis revealed primary diffuse large B-cell lymphoma of the spinal cord with multifocal myelomalacia and hemorrhages. To determine the presence of a pathogen within the lesion, we developed a novel in situ hybridization protocol for FeLV (RNAscope). The reaction revealed large amounts of FeLV viral RNA in the tumor cells.

Porcine circovirus type 3 detection in a Hungarian pig farm experiencing reproductive failures.

Porcine circovirus 3 (PCV3) infection has been reported in piglets and sows with porcine dermatitis and nephropathy syndrome, reproductive failure, and cardiac and multisystemic inflammation. Few studies linked PCV3 infection to increased incidence of abortion and weak-born piglets. This is the first report of a detection of PCV3 Hungarian strain in several organs of aborted and weak-born piglets, including the thymus, lymph node, placenta, spleen, kidney and the liver. The tissue tropism of PCV3 in affected litters was analysed using real-time quantitative PCR, and the result showed the highest load of viral DNA in the thymus and lymph nodes. The ORF2 of Hungarian PCV3 strains was 524 nucleotides in length, and the sequence identity to GenBank sequences ranged from 98.5 per cent to 99.2 per cent. The results suggest that PCV3 may have a relevant role in reproductive failure in gilts.

[The first organisation to accept drug addicts in Budapest].

No abstract available.

mTORC1 activation blocks BrafV600E-induced growth arrest but is insufficient for melanoma formation.

Braf(V600E) induces benign, growth-arrested melanocytic nevus development, but also drives melanoma formation. Cdkn2a loss in Braf(V600E) melanocytes in mice results in rare progression to melanoma, but only after stable growth arrest as nevi. Immediate progression to melanoma is prevented by upregulation of miR-99/100, which downregulates mTOR and IGF1R signaling. mTORC1 activation through Stk11 (Lkb1) loss abrogates growth arrest of Braf(V600E) melanocytic nevi, but is insufficient for complete progression to melanoma. Cdkn2a loss is associated with mTORC2 and Akt activation in human and murine melanocytic neoplasms. Simultaneous Cdkn2a and Lkb1 inactivation in Braf(V600E) melanocytes results in activation of both mTORC1 and mTORC2/Akt, inducing rapid melanoma formation in mice. In this model, activation of both mTORC1/2 is required for Braf-induced melanomagenesis.

GM1-gangliosidosis in American black bears: clinical, pathological, biochemical and molecular genetic characterization.

G(M1)-gangliosidosis is a rare progressive neurodegenerative disorder due to an autosomal recessively inherited deficiency of lysosomal ß-galactosidase. We have identified seven American black bears (Ursus americanus) found in the Northeast United States suffering from G(M1)-gangliosidosis. This report describes the clinical features, brain MRI, and morphologic, biochemical and molecular genetic findings in the affected bears. Brain lipids were compared with those in the brain of a G(M1)-mouse. The bears presented at ages 10-14 months in poor clinical condition, lethargic, tremulous and ataxic. They continued to decline and were humanely euthanized. The T(2)-weighted MR images of the brain of one bear disclosed white matter hyperintensity. Morphological studies of the brain from five of the bears revealed enlarged neurons with foamy cytoplasm containing granules. Axonal spheroids were present in white matter. Electron microscopic examination revealed lamellated membrane structures within neurons. Cytoplasmic vacuoles were found in the liver, kidneys and chondrocytes and foamy macrophages within the lungs. Acid ß-galactosidase activity in cultured skin fibroblasts was only 1-2% of control values. In the brain, ganglioside-bound sialic acid was increased more than 2-fold with G(M1)-ganglioside predominating. G(A1) content was also increased whereas cerebrosides and sulfatides were markedly decreased. The distribution of gangliosides was similar to that in the G(M1)-mouse brain, but the loss of myelin lipids was greater in the brain of the affected bear than in the brain of the G(M1) mouse. Isolated full-length cDNA of the black bear GLB1 gene revealed 86% homology to its human counterpart in nucleotide sequence and 82% in amino acid sequence. GLB1 cDNA from liver tissue of an affected bear contained a homozygous recessive T(1042) to C transition inducing a Tyr348 to His mutation (Y348H) within a highly conserved region of the GLB1 gene. The coincidence of several black bears with G(M1)-gangliosidosis in the same geographic area suggests increased frequency of a founder mutation in this animal population.

Endometrial decidualization and deciduosis in aged rhesus macaques (Macaca mulatta).

Superficial decidualization of the endometrial stroma is an essential feature of the implantation stage of pregnancy in rhesus macaques and other primates. Decidualization involves proliferation of the endometrial stromal cells, with differentiation into morphologically distinct decidual cells. Previous reports involving nonpregnant rhesus monkeys have described local- ized and widespread endometrial decidualization in response to administration of progesterone and synthetic progestogens. Ectopic decidua or 'deciduosis' describes the condition in which groups of decidual cells are located outside of the endometrium, most often in the ovaries, uterus and cervix but also in various other organs. In humans, most cases of deciduosis are associated with normal pregnancy, and ectopic decidua can be found in the ovary in nearly all term pregnancies. Here we describe pronounced endometrial decidualization in 2 rhesus macaques. Both macaques had been treated long-term with medroxyprogesterone acetate for presumed endometriosis, which was confirmed in one of the macaques at postmortem examination. In one animal, florid extrauterine and peritoneal serosal decidualization was admixed multifocally with carcinomatosis from a primary colonic adenocarcinoma. Cells constituting endometrial and serosal decidualization reactions were immunopositive for the stromal markers CD10, collagen IV, smooth muscle actin, and vimentin and immunonegative for cytokeratin. In contrast, carcinomatous foci were cytokeratin-positive. To our knowledge, this report describes the first cases of serosal peritoneal decidualization in rhesus macaques. The concurrent presentation of serosal peritoneal decidualization with carcinomatosis is unique.

CHRONIC NEONATAL DIAZOXIDE THERAPY IS NOT ASSOCIATED WITH ADVERSE EFFECTS.

Diazoxide is an ATP-sensitive potassium channel (KATP) agonist that has been shown to neuroprotective effects. These observations raise the possibility that diazoxide may have potential as a therapeutic agent for other applications. This study investigated (1) the long term effects of chronic neonatal administration of diazoxide and (2) the role of KATP on murin behavior and neurohistology. C57B/6J pups were injected daily with diazoxide (10, 20 or 50 mg kg-1) or vehicle from Postnatal days 2 (P2) through P12. Pups were allow to mature and underwent behavioral testing at 5-7 months of age. After behavioral testing, animals were euthanized and morphology of the brains was assessed. No long term adverse effects of neonatal diazoxide therapy on physical characteristics, visual acuity, sensori-motor reflexes, spontaneous locomotor activity, motor coordination/balance or motor learning and memory were observed. In addition, no morphological changes were observed on brains. However, we did observe that diazoxide therapy causes depressive-like phenotypes in female murine mice. Chronic neonatal diazoxide therapy does not cause deficits or enhancements in mice behavior. Diazoxide does not cause abnormal morphological changes in brain anatomy. However, diazoxide does cause gender specific depressive-like phenotype in mice.

Prevention of paclitaxel-induced peripheral neuropathy by lithium pretreatment.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect that occurs in many patients undergoing chemotherapy. It is often irreversible and frequently leads to early termination of treatment. In this study, we have identified two compounds, lithium and ibudilast, that when administered as a single prophylactic injection prior to paclitaxel treatment, prevent the development of CIPN in mice at the sensory-motor and cellular level. The prevention of neuropathy was not observed in paclitaxel-treated mice that were only prophylactically treated with a vehicle injection. The coadministration of lithium with paclitaxel also allows for administration of higher doses of paclitaxel (survival increases by 60%), protects against paclitaxel-induced cardiac abnormalities, and, notably, does not interfere with the antitumor effects of paclitaxel. Moreover, we have determined a mechanism by which CIPN develops and have discovered that lithium and ibudilast inhibit development of peripheral neuropathy by disrupting the interaction between paclitaxel, neuronal calcium sensor 1 (NCS-1), and the inositol 1,4,5-trisphosphate receptor (InsP3R) to prevent treatment-induced decreases in intracellular calcium signaling. This study shows that lithium and ibudilast are candidate therapeutics for the prevention of paclitaxel-induced neuropathy and could enable patients to tolerate more aggressive treatment regimens.

Western-style diets induce oxidative stress and dysregulate immune responses in the colon in a mouse model of sporadic colon cancer.

A Western-style diet (WD), defined by high-fat, low-calcium, and vitamin D content, is associated with increased risk of human colorectal cancer. Understanding molecular mechanisms altered by the WD is crucial to develop preventive and therapeutic strategies. Effects of a WD on the colonic transcriptome of C57Bl/6J mice, a model for sporadic colon cancer, were studied at endpoints before tumors occur. To assess whether a WD induces inflammatory changes, expression profiles of a broad spectrum of inflammatory proteins were performed and numbers of lamina propria macrophages were determined with semiquantitative morphometry. Transcriptome changes were translated into molecular interaction network maps and pathways. Pathways related to oxidative stress response; lipid, glutathione, and xenobiotic metabolism; and the immune response were perturbed by the WD. Several nuclear factor-erythroid 2-related factor 2- and aryl hydrocarbon receptor-dependent genes, including those coding for enzymes involved in phase 1 and 2 drug metabolism and oxidative stress responses, were induced. Oxidative stress was demonstrated by measurements of endogenous colonic redox-sensitive compound concentrations. Perturbations in immune response-related pathways, expression of inflammatory proteins, and increased numbers of lamina propria macrophages showed that the WD significantly alters the local colonic immune response. Collectively, these data suggest that consumption of a WD interferes with networks of related biological response pathways involving colonic lipid metabolism, oxidative stress, and the immune response. These new findings impact our understanding of links between consumption of WD and colon carcinogenesis, providing additional information for developing preventive means for decreasing colorectal cancer risk.

[Knowledge about the relationship through protagonist-director interactions in psychodrama groups]. / A kapcsolati tudás a protagonista és a rendezo interakcióin keresztül pszichodráma csoportokban.

This report follows emotional behavior in two psychodrama groups from the "present moment" until "moment of contact" using the Consensus Rorschach method. In the analysis of verbal and nonverbal material of protagonist-director dyads the following patterns were distinguished: a) early relationship patterns; b) affective attunement; c) fit of knowledge about the relationship. The author describes the relationship between the concept of "present moment" in therapy and the role of eye contact. Eye contact produces emotional tension in the context of the "present moment". Moments of contact, however, require implicit and explicit knowledge about the relationship to be constructed simultaneously as well as development of affective interactions. Emotional impulses are stored in implicit memory, which has no immediate availability. However, therapy--including psychodrama--attaches words to behaviors that are beyond the verbal levels as well, and therefore it extends the domain of memory. This is the way in which non-symbolized emotional behavior (including eye contact) and the play's verbal level with symbolic representations of memories are interconnected.