• MeSH
• chirurgie MeSH
• Publikační typ
• biografie MeSH

• O autorovi
• Procházka, Jaroslav, 1913-2003 Autorita

• MeSH
• dějiny 20. století MeSH
• duševní zdraví dějiny   MeSH
• lékařství MeSH
• lidé MeSH
• Ministerstvo zemědělství USA MeSH
• veřejné zdravotnictví dějiny   metody   zákonodárství a právo   MeSH
• Check Tag
• dějiny 20. století MeSH
• lidé MeSH
• Publikační typ
• biografie MeSH
• Geografické názvy
• Československo MeSH

• O autorovi
• Procházka, Ladislav Prokop, 1872-1955 Autorita

• Publikační typ
• biografie MeSH

• Konspekt
• Fyziologie člověka a srovnávací fyziologie
• NLK Obory
• fyziologie

• O autorovi
• Procháska, Jiří, 1749-1820 Autorita

Diamond-Blackfan anemia (DBA) is a rare genetic disorder affecting the bone marrow's ability to produce red blood cells, leading to severe anemia and various physical abnormalities. Approximately 75% of DBA cases involve heterozygous mutations in ribosomal protein (RP) genes, classifying it as a ribosomopathy, with RPS19 being the most frequently mutated gene. Non-RP mutations, such as in GATA1, have also been identified. Current treatments include glucocorticosteroids, blood transfusions, and hematopoietic stem cell transplantation (HSCT), with HSCT being the only curative option, albeit with challenges like donor availability and immunological complications. Gene therapy, particularly using lentiviral vectors and CRISPR/Cas9 technology, emerges as a promising alternative. This review explores the potential of gene therapy, focusing on lentiviral vectors and CRISPR/Cas9 technology in combination with non-integrating lentiviral vectors, as a curative solution for DBA. It highlights the transformative advancements in the treatment landscape of DBA, offering hope for individuals affected by this condition.

• MeSH
• CRISPR-Cas systémy genetika   MeSH
• Diamondova-Blackfanova anemie * genetika   terapie   MeSH
• editace genu metody   MeSH
• genetická terapie * metody   MeSH
• genetické vektory MeSH
• Lentivirus genetika   MeSH
• lidé MeSH
• mutace genetika   MeSH
• ribozomální proteiny genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Prof. MUDr. Jaroslav Procházka, DrSc., český chirurg, byl významnou osobností československé medicíny. Byl zakladatelem moderní plicní chirurgie již koncem 40. let 20. stol., později se podílel na rozvoji srdeční chirurgie v našem státě i v zahraničí. Kniha přináší pohled na Procházkovo dětství a mládí, na začátky a vývoj jeho práce v chirurgii, na závěr aktivního života. Je mozaikou složenou z jeho vlastních rukopisů a ze vzpomínek kolegů a přátel, které dokreslují Procházkovu osobnost a atmosféru na Chirurgické klinice LF UK a FN v H. Králové. Čtenáři zde naleznou nejen poutavé vylíčení převratných dob medicíny, ale také přehled operací provedených profesorem Procházkou, bibliografii jeho prací, soupis ocenění, vyznvyznamenání a členství v odborných společnostech.

• MeSH
• kardiochirurgické výkony dějiny   MeSH
• lékaři MeSH
• významné osobnosti MeSH
• Publikační typ
• autobiografie MeSH
• biografie MeSH

• Konspekt
• Ortopedie. Chirurgie. Oftalmologie
• NLK Obory
• kardiologie
• chirurgie
• dějiny lékařství

• O autorovi
• Procházka, Jaroslav, 1913-2003 Autorita

Canonical RNA interference (RNAi) is sequence-specific mRNA degradation guided by small interfering RNAs (siRNAs) made by RNase III Dicer from long double-stranded RNA (dsRNA). RNAi roles include gene regulation, antiviral immunity or defense against transposable elements. In mammals, RNAi is constrained by Dicer's adaptation to produce another small RNA class-microRNAs. However, a truncated Dicer isoform (ΔHEL1) supporting RNAi exists in mouse oocytes. A homozygous mutation to express only the truncated ΔHEL1 variant causes dysregulation of microRNAs and perinatal lethality in mice. Here, we report the phenotype and canonical RNAi activity in DicerΔHEL1/wt mice, which are viable, show minimal miRNome changes, but their endogenous siRNA levels are an order of magnitude higher. We show that siRNA production in vivo is limited by available dsRNA, but not by Protein kinase R, a dsRNA sensor of innate immunity. dsRNA expression from a transgene yields sufficient siRNA levels to induce efficient RNAi in heart and muscle. DicerΔHEL1/wt mice with enhanced canonical RNAi offer a platform for examining potential and limits of mammalian RNAi in vivo.

• MeSH
• DEAD-box RNA-helikasy genetika   metabolismus   MeSH
• dvouvláknová RNA * metabolismus   genetika   MeSH
• malá interferující RNA * genetika   metabolismus   MeSH
• mikro RNA genetika   metabolismus   MeSH
• myši MeSH
• protein - isoformy genetika   metabolismus   MeSH
• ribonukleasa III * genetika   metabolismus   MeSH
• RNA interference * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• chirurgie MeSH
• Publikační typ
• biografie MeSH

• O autorovi
• Procházka, Jaroslav, 1913-2003 Autorita

Tooth formation requires complex signaling interactions both within the oral epithelium and between the epithelium and the underlying mesenchyme. Previous studies of the Wnt/β-catenin pathway have shown that tooth formation is partly inhibited in loss-of-function mutants, and gain-of-function mutants have perturbed tooth morphology. However, the stage at which Wnt signaling is first important in tooth formation remains unclear. Here, using an Fgf8-promoter-driven, and therefore early, deletion of β-catenin in mouse molar epithelium, we found that loss of Wnt/β-catenin signaling completely deletes the molar tooth, demonstrating that this pathway is central to the earliest stages of tooth formation. Early expression of a dominant-active β-catenin protein also perturbs tooth formation, producing a large domed evagination at early stages and supernumerary teeth later on. The early evaginations are associated with premature mesenchymal condensation marker, and are reduced by inhibition of condensation-associated collagen synthesis. We propose that invagination versus evagination morphogenesis is regulated by the relative timing of epithelial versus mesenchymal cell convergence regulated by canonical Wnt signaling. Together, these studies reveal new aspects of Wnt/β-catenin signaling in tooth formation and in epithelial morphogenesis more broadly.

• MeSH
• beta-katenin metabolismus   MeSH
• epitel metabolismus   MeSH
• epitelové buňky cytologie   metabolismus   MeSH
• mezoderm metabolismus   MeSH
• moláry cytologie   růst a vývoj   metabolismus   MeSH
• morfogeneze fyziologie   MeSH
• myši MeSH
• odontogeneze genetika   fyziologie   MeSH
• proliferace buněk MeSH
• signální dráha Wnt fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH

Achondroplasia is the most common form of human dwarfism caused by mutations in the FGFR3 receptor tyrosine kinase. Current therapy begins at 2 years of age and improves longitudinal growth but does not address the cranial malformations including midface hypoplasia and foramen magnum stenosis, which lead to significant otolaryngeal and neurologic compromise. A recent clinical trial found partial restoration of cranial defects with therapy starting at 3 months of age, but results are still inconclusive. The benefits of achondroplasia therapy are therefore controversial, increasing skepticism among the medical community and patients. We used a mouse model of achondroplasia to test treatment protocols aligned with human studies. Early postnatal treatment (from day 1) was compared with late postnatal treatment (from day 4, equivalent to ~5 months in humans). Animals were treated with the FGFR3 inhibitor infigratinib and the effect on skeleton was thoroughly examined. We show that premature fusion of the skull base synchondroses occurs immediately after birth and leads to defective cranial development and foramen magnum stenosis in the mouse model to achondroplasia. This phenotype appears significantly restored by early infigratinib administration when compared with late treatment, which provides weak to no rescue. In contrast, the long bone growth is similarly improved by both early and late protocols. We provide clear evidence that immediate postnatal therapy is critical for normalization of skeletal growth in both the cranial base and long bones and the prevention of sequelae associated with achondroplasia. We also describe the limitations of early postnatal therapy, providing a paradigm-shifting argument for the development of prenatal therapy for achondroplasia.

• MeSH
• achondroplazie * patologie   farmakoterapie   MeSH
• lebka patologie   účinky léků   MeSH
• lidé MeSH
• modely nemocí na zvířatech * MeSH
• myši MeSH
• receptor fibroblastových růstových faktorů, typ 3 * genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Cancer cells facilitate tumor growth by creating favorable tumor micro-environments (TME), altering homeostasis and immune response in the extracellular matrix (ECM) of surrounding tissue. A potential factor that contributes to TME generation and ECM remodeling is the cytoskeleton-associated human death-associated protein kinase 1 (DAPK1). Increased tumor cell motility and de-adhesion (thus, promoting metastasis), as well as upregulated plasminogen-signaling, are shown when functionally analyzing the DAPK1 ko-related proteome. However, the systematic investigation of how tumor cells actively modulate the ECM at the tissue level is experimentally challenging since animal models do not allow direct experimental access while artificial in vitro scaffolds cannot simulate the entire complexity of tissue systems. Here, we used the chorioallantoic membrane (CAM) assay as a natural, collagen-rich tissue model in combination with all-optical experimental access by multiphoton microscopy (MPM) to study the ECM remodeling potential of colorectal tumor cells with and without DAPK1 in situ and even in vivo. This approach demonstrates the suitability of the CAM assay in combination with multiphoton microscopy for studying collagen remodeling during tumor growth. Our results indicate the high ECM remodeling potential of DAPK1 ko tumor cells at the tissue level and support our findings from proteomics.

• Publikační typ
• časopisecké články MeSH