hyperproliferation
Dotaz
Zobrazit nápovědu
Etiopatogeneze psoriázy zahrnuje čtyři charakteristické rysy: zánět, hyperproliferaci keratinocytů s jejich abnormální diferenciací, hyperproliferaci endotelií a inhibici apoptózy keratinocytů. Vzhledem k familiárnímu výskytu psoriázy je nutné předpokládat v etiopatogenezi psoriázy účast genetických faktorů. Na základě statistické analýzy distribuce genotypů ve vybraných genetických polymorfismech několika genů jsme v české populaci našli několik DNA markerů pro psoriázu, zejména genotypy AG a GG polymorfismu 2184 G/A RAGE (advanced glycation end products receptor, odds ratio = 2,25, P=0,00004) a heterozygotní genotyp A/AA v polymorfismu A39526AA v genu pro retinoidní receptor Xα u žen s psoriázou oproti mužům s psoriázou (odds ratio=2,22, P=0,002). Jako rizikový pro psoriatické pacienty s pozitivní rodinnou anamnézou jsme určili také heterozygotní genotyp GA v polymorfismu -596 G/A v genu pro interleukin 6 (odds ratio=l,83, P=0,008). Všechny tyto rizikové genotypy mohou zakládat různou odpovídavost na terapii psoriázy.
Etiopathogenesis of psoriasis includes four characteristic features – inflammation, hyperproliferation of keratinocytes with their abnormal differentiation, hyperproliferation of endothelia and inhibition of keratinocyte apoptosis. Because of familial occurrence of psoriasis, a contribution of genetic factors to etiopathogenesis must be considered. As a result of statistical analysis of genotyping of psoriatic patients as well as control subjects in selected gene polymorphisms, several DNA markers for psoriasis were proved in the Czech population. There are genotypes AG and GG in 2184 G/A RAGE (advanced glycation end products receptor, odds ratio = 2.25, P=0.00004) and the heterozygote genotype A/AA in A39526AA retinoid X receptor α polymorphism in women with psoriasis against the men with psoriasis (odds ratio=2.22, P=0.002). Further, the risk heterozygote genotype GA in polymorphism -596 G/A of interleukin 6 gene was found (odds ratio=1.83, P=0.008) for psoriatic patients with positive family history. All these risk genotypes can cause different responsiveness to psoriasis therapy.
Elejalde syndrome (McKusick 200995), also known as acrocephalopolydactylous dysplasia, is a rare condition. We describe a sixth patient with this syndrome which is characterized by craniosynostosis and hyperproliferation of fibroblasts in many tissues including skin, liver, kidney, and pancreas. The cause of the syndrome is the homozygous state of an autosomal recessive mutation. We present a hypothesis that Elejalde syndrome might be associated with an inactivating FGFR gene mutation. (c) 2006 Wiley-Liss, Inc.
- MeSH
- financování organizované MeSH
- játra patologie MeSH
- kraniosynostózy genetika patologie radiografie MeSH
- kůže patologie MeSH
- ledviny patologie MeSH
- lidé MeSH
- mnohočetné abnormality genetika patologie radiografie MeSH
- novorozenec MeSH
- pankreas patologie MeSH
- syndrom MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Cíl studie: Laparoskopické ošetření velmi vzácné ovariální implantace po IVF a ET.Typ studie: Kazuistika.Název a sídlo pracoviště: Ústav pro péči o matku a dítě, Centrum prenatální diagnostiky a léčby a Centrum trofoblastické nemoci, Katedra gynekologie a porodnictví, IPVZ Praha.Závěr: Pozorovali jsme implantovaný produkt koncepce v ovariu 35 dnů po IVF a ET. Při laparoskopickém vyšetření plodové vejce připomínalo hemoragickou cystu ovaria v průměru 2 cm. Po disekci bylo v amniovém váčku pozorováno amorfní avaskulární embryo délky 2 mm a žloutkový váček v průměru asi 3 mm. Hyperproliferační trofoblast byl klasifikován jako proliferující mola.
Objective: Case report of a very rare case of ovarian implantation after IVF and ET treated by laparoscopy.Design: Case report.Setting: Institute for the Care of Mother and Child, Prenatal Diagnostic Centre and Trophoblastic Disease Centre, Prague, Institute for Postgraduate Medical Education, Prague.Results: We observed implanted product of conception found within the ovarian stroma 35 days after ET. At laparoscopy, the genital sac appeared as an inconspicious haemorrhagic cyst, 2 cm in diameter. After dissection, in the intact sac appeared amorphous 2 mm embryo and 3 mm yolk sac. The trophoblast of the anchoring chorionic villi exhibited marked hyperproliferation and was classified as a proliferating mole.Conclusion: The intact early product of conception exhibited trophoblastic hyperplasia.
Balneotherapy is a modern and perspective method of treatment of some skin diseases. Enhanced proliferation of epidermal cells in psoriatic plaques can be influenced by many different procedures. The objective of the present work was to evaluate in vivo the effect of hydrogen sulphide water, which is used for balneotherapeutic procedures in 10 patients with chronic stationary psoriasis vulgaris. The authors investigated the receptor characteristics at keratinocytic binding sites in psoriatic plaques before the balneotherapeutic application of hydrogen sulphide water and after its termination. They found that this method of balneotherapy reduces the pathologically enlarged number of receptors for the epidermal growth factor on keratinocytes to a level which corresponds to findings in normal subjects. The described experiments can contribute to the explanation of favourable therapeutic effects of hydrogen sulphide water on reduced hyperproliferation of keratinocytes in the psoriatic epidermis and thus have a favourable effect on psoriatic changes.
Helicobacter pylori infection is a major risk factor for the development of gastric cancer. The bacteria reside in close proximity to gastric surface mucous as well as stem and progenitor cells. Here, we take advantage of wild-type and genetically engineered murine gastric organoids and organoid-derived monolayers to study the cellular targets of H. pylori-induced DNA damage and replication stress and to explore possible interactions with preexisting gastric cancer driver mutations. We find using alkaline comet assay, single-molecule DNA fiber assays, and immunofluorescence microscopy of DNA repair foci that H. pylori induces transcription-dependent DNA damage in actively replicating, Leucine-rich-repeat containing G-Protein-Coupled Receptor 5 (Lgr5)-positive antral stem and progenitor cells and their Troy-positive corpus counterparts, but not in other gastric epithelial lineages. Infection-dependent DNA damage is aggravated by Apc inactivation, but not by Trp53 or Smad4 loss, or Erbb2 overexpression. Our data suggest that H. pylori induces DNA damage in stem and progenitor cells, especially in settings of hyperproliferation due to constitutively active Wnt signaling.
- MeSH
- Helicobacter pylori * genetika MeSH
- infekce vyvolané Helicobacter pylori * genetika mikrobiologie MeSH
- kmenové buňky MeSH
- lidé MeSH
- myši MeSH
- nádory žaludku * patologie MeSH
- poškození DNA MeSH
- receptory spřažené s G-proteiny genetika MeSH
- tumor supresorové geny MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Mnohopočetný myelóm (MM) je nádorová choroba, ktorú spôsobuje nekontrolovaná monoklonová proliferácia abnormálnych nádorových buniek B-lymfocytového radu. Expanzia nádoru prebieha dominantne v kostnej dreni a kosti. Sprevádza ju produkcia monoklonového imunoglobulínu (M-proteínu), ktorý je dokázateľný v moči alebo v sére. Nádorová hyperproliferácia a jej produkty spôsobujú poruchy funkcie orgánov, bolesti kostí a zlomeniny, neurologické príznaky, prípadne hemokoagulačné abnormality a hyperviskózny syndróm. MM sa môže prejaviť náhlou zmenou zdravotného stavu, respektíve ako náhla situácia, napríklad kompresia miechy, patologická fraktúra, hyperviskozita, sepsa alebo hyperkalcémia. Nenápadný a často pozvoľný rozvoj choroby spolu s pestrosťou klinického obrazu a laboratórnych a diagnostických nálezov môže komplikovať včasné rozpoznanie MM.
Multiple myeloma is a malignant disease characterized with uncontroled monoclonal abnormal B-lymphocyte proliferation. Tumor expansion involves mainly bone marrow and bones. There is monoclonal immunoglobulin (M-protein) production in myeloma cells, which could be detected in urine or in serum. Malignant hyperproliferation and its products cause distrurbances of organ functions, bone pains and fractures, neurological signs, hemostasis abnormalities and hyperviscosity syndrome. Multiple myeloma can present with sudden change in condition or as an medical emergency, e.g. spinal cord compression, pathological fracture, hyperviscosity, sepsis or hypercalcemia. Insidious and frequently slow development, together with a wide range of different clinical symptoms and laboratory-diagnostic findings have potential to make early multiple myeloma diagnosis difficult.
Psoriatic lesions are characterized by hyperproliferation, aberrant differentiation of keratinocytes resistant to apoptosis and inflammation. miR-31 plays pro-proliferative, pro-differentiative and pro-inflammatory roles and modulates apoptosis in psoriatic keratinocytes. Endothelin-1 (ET-1) is produced by psoriatic keratinocytes and suppresses apoptosis. Inflammation increases the production of ET-1, which in turn leads to the chronic stimulation of keratinocyte proliferation. The aim of this study was to identify the putative link between two potential biomarkers (miR-31 and ET-1) in patients with psoriasis. The study design included experimental group (29 patients with psoriasis), and the control group (22 blood donors). The PASI score evaluated the state of the disease (median: 18.6; interquartile range 14.5-20.9). Both, the serum level of ET-1 and the whole blood level of miR-31 were significantly increased (p<0.001 and p<0.05, respectively) in patients compared to the controls. However, a significant negative relationship between ET-1 and miR-31 was observed (Spearman's rho=-037, p=0.05). It is possible that a negative feedback loop will be present between miR-31 and ET-1. Our results indicate that miR-31 and ET-1, potential biomarkers of the disease, play significant roles in the pathophysiology of psoriasis.
- MeSH
- biologické markery krev MeSH
- cirkulující mikroRNA krev genetika MeSH
- dospělí MeSH
- endotelin-1 krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA krev genetika MeSH
- mladiství MeSH
- mladý dospělý MeSH
- psoriáza krev diagnóza genetika patofyziologie MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- stupeň závažnosti nemoci MeSH
- upregulace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The homeostasis of the gut epithelium relies upon continuous renewal and proliferation of crypt-resident intestinal epithelial stem cells (IESCs). Wnt/β-catenin signaling is required for IESC maintenance, however, it remains unclear how this pathway selectively governs the identity and proliferative decisions of IESCs. Here, we took advantage of knock-in mice harboring transgenic β-catenin alleles with mutations that specifically impair the recruitment of N- or C-terminal transcriptional co-factors. We show that C-terminally-recruited transcriptional co-factors of β-catenin act as all-or-nothing regulators of Wnt-target gene expression. Blocking their interactions with β-catenin rapidly induces loss of IESCs and intestinal homeostasis. Conversely, N-terminally recruited co-factors fine-tune β-catenin's transcriptional output to ensure proper self-renewal and proliferative behaviour of IESCs. Impairment of N-terminal interactions triggers transient hyperproliferation of IESCs, eventually resulting in exhaustion of the self-renewing stem cell pool. IESC mis-differentiation, accompanied by unfolded protein response stress and immune infiltration, results in a process resembling aberrant "villisation" of intestinal crypts. Our data suggest that IESC-specific Wnt/β-catenin output requires selective modulation of gene expression by transcriptional co-factors.
- MeSH
- algoritmy MeSH
- beta-katenin chemie metabolismus MeSH
- buněčná diferenciace MeSH
- chromatin metabolismus MeSH
- fenotyp MeSH
- genetická transkripce * MeSH
- homeostáza MeSH
- hyperplazie MeSH
- JNK mitogenem aktivované proteinkinasy metabolismus MeSH
- kmenové buňky metabolismus MeSH
- messenger RNA genetika metabolismus MeSH
- mutace genetika MeSH
- mutantní proteiny metabolismus MeSH
- myši MeSH
- organoidy metabolismus MeSH
- proliferace buněk MeSH
- restrukturace chromatinu MeSH
- sekvence nukleotidů MeSH
- signální transdukce MeSH
- střevní sliznice cytologie MeSH
- transkripční faktory metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Wnt/β-catenin signaling plays an essential role in the retinal pigment epithelium (RPE) determination. Since activity of Pax6 (together with Pax2) is also required for the RPE determination, we investigated a possible genetic interaction between Pax6 and Wnt/β-catenin signaling pathway by analyzing Pax6, β-catenin, and Pax6/β-catenin conditional knockout mice. Although Pax6 inactivation alone had no impact on initial specification determined by the expression of Mitf and Otx2, melanin pigmentation was reduced in the RPE. This suggests that along with Mitf and Otx2, Pax6 is required for the full differentiation of RPE. Reporter gene assays in vitro suggest that hypopigmentation is at least in part due to the direct regulation of genes encoding enzymes involved in melanin synthesis by Pax6, Mitf, and β-catenin. The RPE of a β-catenin/Pax6 double mutant was differentiated into the neural retina; however, the tissue was thinner than that of the conditional β-catenin mutant due to reduced proliferation. Together, our data demonstrate that Pax6 is required for the RPE differentiation by regulating pigmentation and accountable for hyperproliferation in the transdifferentiated RPE. In this context, Pax6 appears to function as a pleiotropic regulator, directing development of ocular tissues in concert with the signaling pathway and, at the same time, regulating expression of structural component of the eye, such as shielding pigment.
- MeSH
- beta-katenin genetika metabolismus MeSH
- homeodoménové proteiny genetika metabolismus MeSH
- myši transgenní MeSH
- myši MeSH
- oční proteiny genetika metabolismus MeSH
- represorové proteiny genetika metabolismus MeSH
- retina cytologie metabolismus MeSH
- retinální pigmentový epitel metabolismus MeSH
- signální dráha Wnt * MeSH
- transdiferenciace buněk MeSH
- transkripční faktory paired box genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
