Browsing by Subject "Scrapie"

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    Abnormal periodic acidSchiff (PAS)-positive substance in the islets of Langerhans, pituitaries and adrenal glands of 139H scrapie-infected hamsters
    (Murcia : F. Hernández, 1999) Ye, X.; Scallet, A.; Carp, R.I.
    Previous studies showed that the 139H strain of scrapie injected intra-cerebrally in hamsters caused obesity, and extensive histopathological changes in islets of Langerhans and pituitaries. In the current study, we report that an abnormal granular substance, which stained positively with periodic acid-Schiff (PASpositive substance; PPS), was found in the islets of Langerhans, pituitaries, adrenal glands, in the lumens of blood vessel cores (BVCs) and in blood vessels in 139Hinfected hamsters, but not in either 263K-infected or control hamsters. This substance was found in the endocrine organs, forming grape-like or plaque-like structures, which were small, round to ovoid, and homogenous measuring up to 7pm in diameter and usually grouped in clusters. PPS was not found in the brains of control or scrapie-infected hamsters. Using immunostaining for amyloid protein (PrP, 13A4), as well as Congo red and thioflavin-S stains, no evidence was found of amyloid plaque formation in the islets of Langerhans, the adrenal glands, or the pituitaries of 139H- or 263K-infected hamsters. PPS might relate to the pathological changes in the endocrine organs in 139H-infected hamsters.
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    Comparison of NADPH diaphorase activity in the brains of hamsters infected with scrapie strains 139H or 263K or with normal hamster brain homogenate
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Ye, X.; Meeker, H. C.; Scallet, A. C.; Carp, R. I.
    Previous studies showed that the histopathological changes found in the brains of scrapieinfected animals included amyloid plaque formation, vacuolation , gliosis and neuronal and neurite degeneration. There were differences in the histopathological findings as a function of the scrapie strain-host combination. NADPH-diaphorase (NADPHd) has been shown to be a selective histoch emical marker for neurons containing nitric oxide (NO) synthase. Neuronal cell damage caused by NOS in brain has been reported to be associated with many neurodegenerative diseases. In this study, we used NADPH-d histostaining to investigate changes in the NOS system in brains of 139H- and 263K-infected hamsters and compared the results to normal hamster brain (NHB) injected animals. We observed that some of the NADPH-d histostaining neurons in the cortex of scrapie-infected hamsters appeared to be atrophic: the neurons were smaller and had fewer neurites. The NADPH-d histostaining intensity of neurons or astrocytes in septum, thalamus, hypothalamus and amygdala of 139H- and 263K-infected hamsters was greater than in control hamsters. Astrocytes in the thalamus, hypothalamus and lower part of the cortex (layers 4 to 6) in 263K-infected hamsters were more intensely stained for NADPH-d than in either 139Hinfected hamsters or controls. Our results suggest that changes in NADPH-d system might playa role in the diversity of scrapie induced neurodegenerative changes.
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    Histopathological changes in the islets of Langerhans in hamsters infected with the 139H strain of scrapie: semi-thin section study
    (Murcia : F. Hernández, 1996) Ye, X.; Carp, R.I.
    Using histopathological analysis of semi-thin sections stained with toluidine blue, we observed profound pathological changes in the islets of Langerhans of hamsters infected with the scrapie agent (strain 139H). These included cytoplasmic vesicles, nuclear swelling, and vacuolization in the islet cells. Two types of vacuolization were seen. "Localized vacuolization" (LV) has a distinct edge and is restricted or confined within the cell. "Diffuse vacuolization" (DV) has no distinct edge and is scattered within tissues either inside or outside of cells. DV may span intracellular and extracellular regions of the islet tissues. There were abnormal structures which we temed blood vessel cores (BVCs) in the islets of 139H-infected hamsters. BVC is a hollow space filled up with blood cells. Immunocytochemical staining for insulin antibody suggested that BVC was surrounded by the B cells of the islet. In the present study, we observed that many inflammatory cells passed through the blood-tissue barriers using pathways between cell-junction in the lumen of BVC. We also observed many necklace-like hollow spaces between islet cells. They are the pockets of extracellular space. A novel concept of "the accordion effect" was described to explain a function of the extracellular space. Under normal physiological conditions, as the synthesis of insulin increase in B cells, the volume of the B cells will increase while the volume of the extracellular space will decrease. After a synchronized secretory response from the stimulated B cells, the secretory product would move from the intracellular space into the extracellular space, the volume of the B cells would be decreased and the volume of the extracellular space would be increased. Most of the secretory product might be released into the blood stream immediately, causing an insulin releasing peak in the blood stream, whereas the rest would remain in the enlarged extracellular space. As the cycle repeat, the increasing volume of the B cells will squeeze the remaining insulin into the blood stream gradually. Thus, the expandable extracellular space would serve as buffer system and a reservoir to collect and store some secretory products for future use. We refer to this concept as "the accordion effect". The concept of "the accordion effect" may also be true in other endocrine organs such as pituitary gland and adrenal gland.
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    Immunohistochemical study of macrophage and cytokine dynamics in the gut of scrapie-infected mice
    (Murcia : F. Hernández, 2010) Romero-Trevejo, José Lorenzo; Gómez-Villamandos, J. C.; Pedrera, Mirian; Blanco, Alfonso; Bautista, María José; Sánchez-Cordón, Pedro José
    To study numerical changes in intestinal macrophages and variations in cytokine production by immune cells in the intestine, conventional C57BL/6J mice were orally infected with the Rocky Mountain Laboratory strain of scrapie. Animals were sacrificed at different timepoints, and samples were taken and processed by routine methods for morphological and immunohistochemical analysis. The results point to a possible role for macrophages in the uptake and transport of the infective agent to Peyer’s patches. The observed increase in macrophage numbers in subepithelial sites, taken in conjunction with a drop in tumour necrosis factor-α production at these sites, suggests a possible secretory inhibition that could be induced by the disease-associated prion protein (PrPd). On the other hand, cytokine dynamics indicated the presence of an impaired Th1-Th2 cell mediated response, which could facilitate the spread of PrPd to the central nervous system. Further research is required to confirm these hypotheses.
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    Neuroectodermal grafting: A new tool for the study of neurodegenerative diseases
    (Murcia : F. Hernández, 1996) Isenmann, S.; Brandner, S.; Aguzzi, A.
    Transgenic and knockout mice have contributed much to our current understanding of the role played by single genes during development and in pathological processes of the CNS, such as neurodegeneration. However, embryonic lethality resulting from the disruption of important genes has often hindered the interpretation of such experiments. Grafting of immature cells from genetically modified organisms into healthy recipients promises to efficiently bypass this problem. We have used neural transplantation techniques which allow us to keep CNS tissue of knockout and transgenic mice viable for a prolonged period of time in the brain or in the kidney capsule of healthy recipients. We have characterized biological parameters such as growth, proliferation and differentiation and also the formation of an intact blood-brain barrier (BBB) after grafting of wild-type telencephalic anlage in this system. We have also employed this technique to study the longterm properties of neuroepithelial tissue derived from knockout mice. The results of our studies are discussed in the context of neurodegenerative diseases.
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    The pathological changes in peripheral organs of scrapie-infected animals
    (Murcia : F. Hernández, 1995) Ye, X.; Carp, R.I.
    Scrapie is an unconventional neurodegenerative disease in sheep and goats that has been known in Europe for over 260 Years. The scrapie agents affect the brain and are transmissible from animal to animal. Key features of scrapie infections are abnormal behavior and deficits in motor function. These clinical findings can be related to the damage found in the central nervous system. In some scrapie strain-host model systems there are other manifestations of disease that appear to be related to pathological changes found in the peripheral organs. especially in the endocrine organs such as pituitary, adrenal glands, the islet of Langerhans and ovary. In those model systems in which extensive histopathological changes have been seen in peripheral organs, the titers of scrapie infectivity nd the levels of the scrapie specific protein, PrPSc, are relatively low in the affected organs. These data suggest but do not prove that changes in peripheral organs are secondary to the scrapie-induced neurodegeneration that is occurring in the brain. In some scrapie strain-host combinations, obesity and aberrant glucose metabolism are seen in the preclinical and clinical phases of the incubation period. There appear to be two pathways that lead to these particular clinical manifestations. In SJL mice infected by the ME7 or 22L strains of mouseadapted scrapie and in some scrapie-infected sheep, the mechanism is related to changes induced in the hypothalamic-pituitary-adrenal axis. The other pathway is exemplified by hamsters infected with two hamsteradapted scrapie strains, 139H and 22CH: it appears that lesions found in the hypothalamic-islets of Langerhans axis are critical. A number of reviews on the pathological changes in the central nervous system have been published and therefore, in this review article, we focus on the gross and histopathological changes in peripheral organs in severa1 scrapie strain-host combinations. The changes induced in peripheral organs in a number of scrapie strain-host combinations expand Offprint requests to: Dr. Xuemin Ye, Neurotoxicology Division, National Center for Toxicological Research, 3900 NCTR Drive, Jefferson, AR 72079, USA the number of diseases in which the unconventional slow infections could serve as a model. Further work in this area could help us to understand the mechanisms and pathways of the pathological changes found in the peripheral organs of the scrapie-infected animals