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Autoimmune ovarian damage in adolescent girls, the impact antiovarian antibodies to irregular menstrual cycles and fertility
Kosová, Hana ; Hořejší, Jan (advisor) ; Grim, Miloš (referee) ; Fučíková, Terezie (referee) ; Ulčová-Gallová, Zdeňka (referee)
pou~i II "Iaylnr madt: Ihcra ", ledy pouá\ <iní malých, kontrolm':lné individuálních djvek lmg"nú. mbJcuovaných po I. ji ~ li:' lIf pOLdní pl'<Jlilerac \ honnonálni fun kč n í cytol(lgii rroge~lt:rnnCIl1 O ú...pé hu na~ í terapie jsme se pfcw~ dč iJi pn detekl: hladin) antio\'ariálních protilmek. kdy Isme v 40. 16 r l<unamell"li ...níLení a u J ().9~'k pac'ientck ymiLenl protiljtek. lento rakt je Jol ,zen i tim. ze u , ě l šiny paci nt k pi'i této terapii se objekt i vně I.lcpšil ,tav vnitr'ních rodidel, seKundární h p0hlavn ích znakú . Za zcela zjsadoí PO\ 37Ukjc "Ol/čas né Lkpšení koslní d' n, i t~" 8, SHRNUTÍ );,Iedky naší studie a mapování výskytu sérových anlio\'ari:ílních prulil51c:k mis vcde k přesvědče n í. ze výskyt autoprotilátek proli ovariu kore<;pondujc , dříve č i pOldiíji ,e prclcntu jícími klinickými přízn ak y . On ' mocnění múže propuknou v obdohí od puherty po celé reprod u kč ní období. Zavedení adekvátní léč by (v na' i studi i s ' osvědčilo použití HRT) podle našich poznatku vedlo ke snížení autoimunního ro ~ kole ní ovaria na minimum, k L:lchování jeho hormonáln ích funkcí a pIedevším k zachování zdl'avé ovariální tkáně, n.:Lb)lné pro budoucí rertilitu pacientky. Naše tudie tedy potvrdila nepochyhně obrovsky význam vča s n é diagnostiky a léčb y autoimunitního one muc ně ní uvaria, Z...
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Genetic Regulation of Limb Development
Šnajdr, Pavel ; Grim, Miloš (advisor) ; Peterka, Miroslav (referee) ; Slípka, Jaroslav (referee)
Lx in SHR.Lx rat manifests in homozygotes as hindlimb preaxial polydactyly. We showed that a 2,964-bp deletion in Plzf (Promyelocytic leukemia zinc finger) intron 2 is the only candidate for Lx. The deletion removes the most deeply conserved CNE with putative regulatory influence on Plzf expression. Using in situ hybridization we found reduced expression pattern of Plzf in Lx/Lx limb and anterior expansion of expression domains of Plzf targets Hoxd10-13 genes and Bmp2, in the absence of ectopic Shh expression. Rat hd manifests in homozygotes as reduction or loss of digits II and III on both hind and forelimb and impairment of spermatogenesis leading to male infertility. We showed that hd mutation is caused by an insertion of an endogenous retrovirus into intron 10 of the Cntrob gene resulting in the translation of a truncated protein. In situ hybridization showed that expression of cartilage condensation marker Sox9, and Bmp receptor Bmpr1b is absent from the distal parts of the digit condensations II and III. Studying spermatogenesis we showed that centrobin (protein of Cntrob) localizes to the centrosome, manchette, and the marginal ring of the spermatid acroplaxome. Mutant spermatids show a disruption of head-tail coupling apparatus leading to spermatid decapitation . We demonstrated distinct...
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Differentiation of adult stem cells into insulin-producing beta cells
Koblas, Tomáš ; Saudek, František (advisor) ; Grim, Miloš (referee) ; Štechová, Kateřina (referee)
Ph.D. Thesis abstract: Diabetes mellitus is a chronic disease characterized by a metabolic disorder in which there is a low level or complete lack of the insulin. Diabetes mellitus type 1 (DM1) is caused by an autoimmune reaction leading to the destruction of the insulin producing beta cells in the pancreas. In consequence, low or non-existent insulin production leads to a complete dependence on exogenous insulin supplementation. DM1 causes serious long-term complications. Although strict control of blood sugar could prevent the onset and development of diabetic complications only 5% of diabetic patients are able to achieve such control. Hence it is evident that the current methods of treatment are neither sufficient to treat this disease, nor prevent late complications in most patients. The most promising therapeutic approach in the treatment of diabetes is the restoring of insulin production. One such method is the transplantation of insulin-producing tissue. However, a lack of available insulin- producing tissue limits such therapeutic approach. Therefore an alternative source of insulin producing cells have to be found to obtain a sufficient amount of safe and efficient insulin producing tissue. Pancreatic stem/progenitor cells could represent such an available alternative source. Despite the evidence...
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Cell therapy in animal models - preclinical studies
Juhásová, Jana ; Motlík, Jan (advisor) ; Grim, Miloš (referee) ; Jendelová, Pavla (referee)
The progress of cell therapy can be greatly facilitated by using suitable experimental models. It is essential to verify the clinical usefulness of new healing procedures obtained in studies on laboratory animals by using a large animal model. One of suitable models well acceptable in medical community is undoubtedly the miniature pig, which resembles humans in terms of physiology and body proportions. This PhD thesis presents the summary of our experimental studies relating to possible exploitation of mesenchymal and neural stem cells in the healing of locomotive apparatus and neural tissue disorders in humans or animals. The first part of the thesis briefly describes the current issue of cell therapy and animal models, mesenchymal cells and/or their combination with new types of scaffolds, neurogenesis, neural stem cells and their potential application in therapy of spinal cord injury. The second part is focused on the goals and methodology, the individual publications being listed in the third part. Our experiments with iatrogenic physeal defect in rabbits, which served as a model of the occurrence of valgous deformation in the clinical practice, showed the positive preventive and therapeutical effects of a new type of scaffolds seeded with allogeneic mesenchymal stem cells in animals without...
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Molecular mechanisms regulating participation of neural crest on developmental processes and homeostasis in selected localizations
Krejčí, Eliška ; Grim, Miloš (advisor) ; Hampl, Aleš (referee) ; Jendelová, Pavla (referee)
This PhD thesis focuses on the study of neural crest (NC) properties and mechanisms regulating its development. It is based on four original papers, two of which are wholy concerning NC. In the first project we showed that transcription factor C-MYB is expressed in majority of cells in the developing chick embryo. Its expression level is elevated in neural folds and migrating NC cells. Other experiments showed that this elevated level of intracellular c-Myb influences induction and epithelial-mesenchymal transformation of NC cells, and that c-Myb lies within the BMP4 signalling cascade. In the second project we explored the spatio-temporal specification along the antero-posterior axis of the limb bud - a mechanism significantly regulating also NC development. We showed that deletion of regulatory element of Plzf transcription repressor gene caused decrease of Plzf expression in the limb buds followed by anterior expansion of its downstream genes (Hoxd10-13) expression domains only in the hind limb, with a resulting additional finger. The third paper studies developmental origin of medial border of mammalian scapula. We showed that its cells originate from somites and not in NC. In the last project we studied NC stem cells isolated from human adult hair follicles. These cells express NC stem cell...
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Genetic Regulation of Limb Development
Šnajdr, Pavel ; Grim, Miloš (advisor) ; Peterka, Miroslav (referee) ; Slípka, Jaroslav (referee)
Lx in SHR.Lx rat manifests in homozygotes as hindlimb preaxial polydactyly. We showed that a 2,964-bp deletion in Plzf (Promyelocytic leukemia zinc finger) intron 2 is the only candidate for Lx. The deletion removes the most deeply conserved CNE with putative regulatory influence on Plzf expression. Using in situ hybridization we found reduced expression pattern of Plzf in Lx/Lx limb and anterior expansion of expression domains of Plzf targets Hoxd10-13 genes and Bmp2, in the absence of ectopic Shh expression. Rat hd manifests in homozygotes as reduction or loss of digits II and III on both hind and forelimb and impairment of spermatogenesis leading to male infertility. We showed that hd mutation is caused by an insertion of an endogenous retrovirus into intron 10 of the Cntrob gene resulting in the translation of a truncated protein. In situ hybridization showed that expression of cartilage condensation marker Sox9, and Bmp receptor Bmpr1b is absent from the distal parts of the digit condensations II and III. Studying spermatogenesis we showed that centrobin (protein of Cntrob) localizes to the centrosome, manchette, and the marginal ring of the spermatid acroplaxome. Mutant spermatids show a disruption of head-tail coupling apparatus leading to spermatid decapitation . We demonstrated distinct...
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název v anglickém jazyce není uveden
Kolesová, Hana ; Grim, Miloš (advisor) ; Slípka, Jaroslav (referee) ; Nečas, Emanuel (referee)
Branchial arches region and its blood vessels are extensively transformed in the embryonic development. Aim of this study is to investigate mechanisms of the branchial arches region development and to study how a morphogen Sonic hed gehog (Shh) participate on the formation and remodeling of branchial arches and their blood vessels. Influence of Shh was evaluated based on the changes caused by its inhibition in vivo. Shh function was inhibited with an anti-Shh antibody, which was produced into the embryo from the applied hybridoma cells. Shh signaling cascade was also inhibited by cyclopamine. Results show that Shh is important for dc novo format,ion of the blood vessels in the branchial arches region. Further Shh is necessary for stabilization of the vessel wall, mainly for anterior cardinal vein. Shh also alfects later vessel development and transformation, which includes i.e. fusion of the dorsal aorta, branching of the internal carotid artery and outflow tract development. Short time inhibition of Shh has minor effect on the apoptosis and proliferation activity of the branchial arches region mesenchymal cells. We assume that Shh signals directly to the blood vessels endothelial cells, as Shh receptor ptel is also expressed in endothelial cells and its signal is reduced with Shh inhibition. In studied...
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