Tissue precursor
Dotaz
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Východisko. Přestože byly již popsány bodové mutace v genu pro prekurzor amyloidního proteinu u nemocných s Alzheimerovou demencí, stále existuje část nemocných, u nichž nebyla tato mutace nalezena a nebyla rovněž nalezena vazba k dalším uvažovaným genetickým lokusům na chromozomech 14 a 19. Proto byla skupina osob s Alzheimerovou demencí podrobena testování na přítomnost mutace v APP genu (v pozici 717). Metody a výsledky. U vybrané skupiny osob s Alzheimerovou demencí (AD) jsou nacházeny mutace v genu pro prekurzor amyloidního proteinu v pozici 717 jeho transmembránové domény. Analyzovali jsme genomovou DNA mozkové tkáně osob české národnosti pro přítomnost této mutace pomocí polymerázové řetězové reakce s následným ověřením sekvenační analýzou. U každé osoby byla prováděna genetická analýza z mozkových oblastí lobus frontalis, lobus temporalis, lobus parietalis a hippocampus. Použité metody byly polymerázová řetězová reakce (PCR), sekvenace. Z celkového počtu 18 osob s prokázanou Alzheimerovou demencí a 6 nepříbuzných osob bez histopatologických znaků Alzheimerovy demence po 90. roce života, byly nalezeny 3 sekvenační změny v pozici 717 exonu 17 transmembránové domény prekurzoru beta-4 amyloidního glykoproteinu. V prvním případě se jednalo o záměnu thyminu za adenin v kodonu 717, ve druhém případě se jednalo o záměnu cytosinu za thymin, ve třetím případě byla nalezena sporadická mutace guaninu za thymin v kodonu 717. Závěry. Ukazuje se, že kodon 717 by mohl být tzv. hot-spot místem preferovaným pro přednostní vznik mutací v kodonu 717 genu pro amyloidní proteinový prekurzor (APP).
Background. Although locus mutations in the gene for the amyloid precursor protein were already described in patients with Alzheimer's disease, there still are some patients where this mutation was not found and no link was found with other possible genetic loci on chromosomes 14 and 19. Therefore a group of subjects with Alzheimer's disease was subjected to tests for the presence of a mutation in the APP gene (in position 717). Methods and Results. In a selected group of subjects with Alzheimer's disease (AD) in the gene for amyloid precursor protein in position 717 mutations of its transmembraneous region are found. The authors analyzed the genome DNA of cerebral tissue of Czech subjects for the presence of this mutation by means of the polymerase chain reaction with subsequent verification by sequencing analysis. In every subject genetic analyses from cerebral areas of the frontal lobe, temporal lobe, parietal lobe and hippocampus were performed. The methods used were the polymerase chain reaction (PCR) and sequencing. From the total number of 18 subjects with confirmed Alzheimer's disease and six non-related subjects without histopathological signs of Alzheimer's disease after the age of 90 years, three sequencing changes were found in position 717 of exon 17 of the transmembranous region of the precursor of beta-4 amyloid glycoprotein. In the first case it was substitution of thymin for adenine in codon 717, in the second case substitution of cytosine for thymine, in the third case a sporadic mutation of guanine for thymine in codon 717 was found. Conclusions. It was revealed that codon 717 could be a so-called hot spot site preferred for the preferential development of mutations in codon 717 in the gene for the amyloid precursor protein (APP).
Strany 193-206 : ilustrace ; 24 cm
- MeSH
- antigeny MeSH
- modely nemocí na zvířatech MeSH
- protilátky MeSH
- sérologické testy MeSH
- tkáně MeSH
- tvorba protilátek MeSH
- Konspekt
- Biologické vědy
- NLK Obory
- biologie
- alergologie a imunologie
- experimentální medicína
- NLK Publikační typ
- separáty
The expression of CD27 and CD44 correlate with the genotype of B-precursor acute lymphoblastic leukemia (ALL). Based on the expression of these antigens, we identified counterparts of TEL/AML1(pos) and TEL/AML1(neg) leukemic cells in nonmalignant bone marrow. Although CD27 is known as a marker of mature memory B cells, we recently showed that CD27 is also expressed by malignant and nonmalignant B precursors. Here, we show that CD27 and CD44 delineate stages of B-precursor development. Well-established differentiation markers showed that the developmental sequence starts from undetermined progenitors, expressing CD44. Upon B-lineage commitment, cells gain CD27 and lose CD44. The CD27(pos)CD44(neg) (CD27 single positive, 27SP) cells are the earliest stage within CD10(pos)CD19(pos) B precursors and express RAG-1 and TDT. These cells correspond to TEL/AML1(pos) ALL (1/4 pediatric B-precursor ALL). The development follows to CD27/CD44 double-positive (27/44DP) stage, 44SP stage and CD27/CD44 double-negative (27/44DN) stage. Before exit to periphery, CD44 is reexpressed. The 27/44DP cells are mostly large and profoundly suppress RAG-1. Despite their presumably high proliferation potential, 27/44DP cells rarely dominate in leukemia. At 44SP stage, which corresponds to TEL/AML1(neg) leukemias, RAG-1 is reexpressed and Ig light chain gene starts to be rearranged.
- MeSH
- antigeny CD27 biosyntéza fyziologie genetika MeSH
- antigeny CD44 biosyntéza fyziologie genetika MeSH
- dítě MeSH
- financování organizované MeSH
- genová přestavba B-lymfocytů imunologie MeSH
- imunofenotypizace MeSH
- leukemie B-buněčná diagnóza genetika imunologie MeSH
- lidé MeSH
- lymfopoéza genetika imunologie MeSH
- prekurzorové B-lymfoidní buňky cytologie imunologie patologie MeSH
- vývojová regulace genové exprese MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
Despite existing knowledge about the role of the A Disintegrin and Metalloproteinase 10 (ADAM10) as the α-secretase involved in the non-amyloidogenic processing of the amyloid precursor protein (APP) and Notch signalling we have only limited information about its regulation. In this study, we have identified ADAM10 interactors using a split ubiquitin yeast two hybrid approach. Tetraspanin 3 (Tspan3), which is highly expressed in the murine brain and elevated in brains of Alzheimer´s disease (AD) patients, was identified and confirmed to bind ADAM10 by co-immunoprecipitation experiments in mammalian cells in complex with APP and the γ-secretase protease presenilin. Tspan3 expression increased the cell surface levels of its interacting partners and was mainly localized in early and late endosomes. In contrast to the previously described ADAM10-binding tetraspanins, Tspan3 did not affect the endoplasmic reticulum to plasma membrane transport of ADAM10. Heterologous Tspan3 expression significantly increased the appearance of carboxy-terminal cleavage products of ADAM10 and APP, whereas N-cadherin ectodomain shedding appeared unaffected. Inhibiting the endocytosis of Tspan3 by mutating a critical cytoplasmic tyrosine-based internalization motif led to increased surface expression of APP and ADAM10. After its downregulation in neuroblastoma cells and in brains of Tspan3-deficient mice, ADAM10 and APP levels appeared unaltered possibly due to a compensatory increase in the expression of Tspans 5 and 7, respectively. In conclusion, our data suggest that Tspan3 acts in concert with other tetraspanins as a stabilizing factor of active ADAM10, APP and the γ-secretase complex at the plasma membrane and within the endocytic pathway.
- MeSH
- amyloidový prekurzorový protein beta genetika metabolismus MeSH
- buněčná membrána metabolismus MeSH
- endocytóza MeSH
- endozomy chemie metabolismus MeSH
- HEK293 buňky MeSH
- kadheriny genetika metabolismus MeSH
- lidé MeSH
- membránové proteiny genetika metabolismus MeSH
- mozek - chemie MeSH
- mozek metabolismus MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- neurony cytologie metabolismus MeSH
- preseniliny genetika metabolismus MeSH
- protein ADAM10 genetika metabolismus MeSH
- proteiny nervové tkáně genetika metabolismus MeSH
- receptory Notch genetika metabolismus MeSH
- regulace genové exprese MeSH
- sekretasy genetika metabolismus MeSH
- signální transdukce MeSH
- techniky dvojhybridového systému MeSH
- tetraspaniny genetika metabolismus MeSH
- transport proteinů MeSH
- vazba proteinů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A three dimensional magnetic patterning of two cell types was realised in vitro inside an additive manufactured magnetic scaffold, as a conceptual precursor for the vascularised tissue. The realisation of separate arrangements of vascular and osteoprogenitor cells, labelled with biocompatible magnetic nanoparticles, was established on the opposite sides of the scaffold fibres under the effect of non-homogeneous magnetic gradients and loading magnetic configuration. The magnetisation of the scaffold amplified the guiding effects by an additional trapping of cells due to short range magnetic forces. The mathematical modelling confirmed the strong enhancement of the magnetic gradients and their particular geometrical distribution near the fibres, defining the preferential cell positioning on the micro-scale. The manipulation of cells inside suitably designed magnetic scaffolds represents a unique solution for the assembling of cellular constructs organised in biologically adequate arrangements.
- MeSH
- biokompatibilní materiály chemie MeSH
- biologické modely MeSH
- chemické modely MeSH
- endoteliální buňky pupečníkové žíly (lidské) fyziologie MeSH
- fyziologická neovaskularizace fyziologie MeSH
- lidé MeSH
- magnetické nanočástice chemie MeSH
- magnetické pole MeSH
- mezenchymální kmenové buňky fyziologie MeSH
- nanomedicína metody MeSH
- osteogeneze fyziologie MeSH
- ověření koncepční studie MeSH
- počítačová simulace MeSH
- regenerace kostí MeSH
- testování materiálů MeSH
- tkáňové inženýrství metody MeSH
- tkáňové podpůrné struktury chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Native hyaluronan (HA) has been oxidized to polyaldehyde polymers with a degree of substitution (DS) of up to 50%. Two different procedures enabling the control of the degree of substitution were followed in this study. Selective oxidation of primary hydroxyl groups of N-acetyl-D-glucosamine of hyaluronan was performed either in an aqueous solution containing AcNH-TEMPO/NaBr/NaOCl or in an aprotic solvent containing Dess-Martin periodinane (DMP). It was found that a change of reaction parameters (reaction time and temperature, type of catalyst, oxidant-to-HA ratio, presence of nitrogen, buffer type, and concentration) had an influence on the degree of substitution and molecular weight. The derivatives were characterized by MS, NMR spectroscopy, and SEC-MALLS. Degradation of hyaluronic acid by the oxidant was observed and confirmed by SEC. The effect of oxidized derivatives of hyaluronan on cells was studied by means of NIH 3T3 fibroblast viability, which indicates that prepared hyaluronan polyaldehydes are biocompatible and suitable for medical applications and tissue engineering. The function of polyaldehyde as precursor for other modification was illustrated in the reaction with lysine.
- MeSH
- acetylglukosamin chemie MeSH
- aldehydy chemická syntéza farmakologie MeSH
- biokompatibilní materiály chemická syntéza farmakologie MeSH
- biopolymery chemie farmakologie MeSH
- bromidy chemie MeSH
- buňky NIH 3T3 MeSH
- chlornan sodný chemie MeSH
- cyklické N-oxidy chemie MeSH
- dusík chemie MeSH
- iminopyranosy chemie MeSH
- katalýza MeSH
- kyselina hyaluronová analogy a deriváty chemická syntéza farmakologie MeSH
- magnetická rezonanční spektroskopie MeSH
- molekulová hmotnost MeSH
- myši MeSH
- oxidace-redukce MeSH
- sloučeniny sodíku chemie MeSH
- teplota MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
