992 resultados para Schwann, Theodor


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Kirjallisuusarvostelu

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Dedicated to: Carl Cronstedt, Carl Gustaf Tessin, Theodor Ankarkrona, Otto Reinhold Wrangel, Olof Sandberg, Jacob von Hökerstedt, Carl von Groot, Carl Friedrich Piper, Olof von Törne, Petter Drufwa, Johan Löwen, Swen Cederström, Johan Maurits Klinkowström, Leonhard Klinkowström, Reinholdt Berndt Hauswolff, Christopher Christopherssen, Johan Williamsson, Olof Malmer, Johan Adam Petersson, Gustaf Kierman, Anders Plomgren.

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Kirjallisuusarvostelu

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Neurofibromatosis type 1 (NF1) is an autosomal dominant cancer predisposition syndrome that affects about 1 in 3500 individuals worldwide. NF1 is caused by mutations in the NF1 gene that encodes the tumor suppressor protein neurofibromin, an inactivator of the Ras oncogene. The hallmarks of NF1 include pigmentary lesions of the skin, Lisch nodules of the iris and cutaneous neurofibromas. Cutaneous neurofibromas are benign tumors composed of all the cell types of normal peripheral nerve. The traditional view of neurofibroma development has been that cutaneous neurofibromas arise from the disruption of the small nerve tributaries of the skin and subsequent proliferation of the resident cells. The second hit mutation in the NF1 gene has been considered as a prerequisite for neurofibroma development. The second hit is detectable in a subpopulation of primary Schwann cells cultured from neurofibromas. This thesis challenges the traditional concept of neurofibroma development. The results show that cutaneous neurofibromas are intimately associated with hair follicular structures and contain multipotent precursor cells (NFPs), suggesting that neurofibromas may arise from the multipotent cells which reside in hair follicles. Furthermore, this study presents that neurofibroma-derived Schwann cells that harbor bi-allelic inactivation in the NF1 gene express HLA class II genes and may act as nonprofessional antigen presenting cells. The CD4- and FoxP3-positive cells detected in cutaneous neurofibromas suggest that these cells may represent regulatory T cells (Tregs) which interact with HLA II –positive cells and aid the tumor cells in hiding from the immune system and are thus mediators of immune tolerance. This thesis also investigated neurofibroma development in the oral cavity and the use of different biomarkers to characterize cellular differentiation in neurofibromas. The results revealed that oral neurofibromas are not rare, but they usually appear as solitary lesions contrary to multiple cutaneous neurofibromas and present high heterogeneity within and between tumors. The use of class III beta-tubulin as a marker for neuronal differentiation led to an unexpected finding showing that multiple cell types express class III beta-tubulin during mitosis. The increased understanding of the multipotency of tumor cells, cellular differentiation and ability to hide from immune system will aid in the development of future treatments. Specifically, targeting Tregs in NF1 patients could provide a novel therapeutic approach to interfere with the development of neurofibromas.

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Tämä pro gradu –tutkielma on tapaustutkimus Pollesta potkua –yhdistyksen ja KSL-opintokeskuksen yhteistyössä järjestämästä opinnollisen mielenterveyskuntoutuksen kurssista nimeltä Ole muutos, jonka haluat nähdä. Tutkielmassa pyrin kuvaamaan kurssia ja vastaamaan seuraaviin tutkimuskysymyksiin: Mitä merkityksiä kuntoutumiselle annettiin kyseisellä kurssilla? Miten kurssi toimi kuntoutumisen tukena? Kurssin opetusmenetelmistä nostan erityisesti esiin kuntouttavan musiikkitoiminnan. Tutkielmalla osallistun keskusteluun vapaan sivistystyön mahdollisista voimauttavista vaikutuksista. Tarkastelen kurssia myös kriittisen kasvatussosiologian viitekehyksessä Stephen Brookfieldin ja Theodor W. Adornon teorioiden kautta. Totean, että vapaan sivistystyön kentällä tapahtuvalla opinnollisella kuntoutuksella on mahdollisuuksia voimauttaa yksilöitä ja myös antaa mahdollisuuksia kriittisen teorian peräänkuuluttamaan kriittiseen reflektioon.

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Suomennos.

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Impr.: C. R. Lindberg.

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Schwann cells produce and release trophic factors that induce the regeneration and survival of neurons following lesions in the peripheral nerves. In the present study we examined the in vitro ability of developing rat retinal cells to respond to factors released from fragments of sciatic nerve. Treatment of neonatal rat retinal cells with sciatic-conditioned medium (SCM) for 48 h induced an increase of 92.5 ± 8.8% (N = 7 for each group) in the amount of total protein. SCM increased cell adhesion, neuronal survival and glial cell proliferation as evaluated by morphological criteria. This effect was completely blocked by 2.5 µM chelerythrine chloride, an inhibitor of protein kinase C (PKC). These data indicate that PKC activation is involved in the effect of SCM on retinal cells and demonstrate that fragments of sciatic nerve release trophic factors having a remarkable effect on neonatal rat retinal cells in culture.

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Peripheral axonal regeneration was investigated in adult male mice of the C57BL/6J (C), BALB/cJ (B) and A/J (A) strains and in their F1 descendants using a predegenerated nerve transplantation model. Four types of transplants were performed: 1) isotransplants between animals of the C, B and A strains; 2) donors of the C strain and recipients of the C x B and C x A breeding; 3) donors of the B strain and recipients of the C x B breeding, and 4) donors of the A strain and recipients of the C x A breeding. Donors had the left sciatic nerve transected and two weeks later a segment of the distal stump was transplanted into the recipient. Four weeks after transplantation the regenerated nerves were used to determine the total number of regenerated myelinated fibers (TMF), diameter of myelinated fibers (FD) and myelin thickness (MT). The highest TMF values were obtained in the groups where C57BL/6J mice were the donors (C to F1 (C x B) = 4658 ± 304; C to F1 (C x A) = 3899 ± 198). Also, A/J grafts led to a significantly higher TMF (A to F1 (C x A) = 3933 ± 565). Additionally, isotransplant experiments showed that when the nerve is previously degenerated, C57BL/6J mice display the largest number of myelinated fibers (C to C = 3136 ± 287; B to B = 2759 ± 170, and A to A = 2835 ± 239). We also observed that when C57BL/6J was the graft donor, FD was the highest and MT did not differ significantly when compared with the other groups. These morphometric results reinforce the idea that Schwann cells and the nerve environment of C57BL/6J provide enough support to the regenerative process. In this respect, the present results support the hypothesis that the non-neuronal cells, mainly Schwann cells, present in the sciatic nerve of C57BL/6J mice are not the main limiting factor responsible for low axonal regeneration.