The present study was undertaken to provide more information on the peripheral RNA containing ring of ringshaped nucleoli (RSNo). Human lymphocytes of blood donors and patients suffering from B chronic lymphocytic leukemia mostly characterized by RSNo represented very convenient cell models for such study. According to the light microscopy the peripheral RNA ring possessed several highly condensed foci. Such regions represented accumulated dense RNA fibrillar components (DFCs) seen by the electron microscopy. In contrary, the incidence of dense granular RNA-containing components (GCs) in surrounding portions of the RNA ring was small. Thus, the structural and morphological organization of the peripheral RNA ring of RSNo apparently reflects sites of micro-segregated foci of DFCs and a small incidence of GCs. That structural organization of the peripheral RNA ring of RSNo appeared to be a prerequisite for further regressive nucleolar changes resulting in the development of micronucleoli in terminal lymphocytes.
- MeSH
- buněčné jadérko * ultrastruktura patologie MeSH
- chronická lymfatická leukemie * patologie MeSH
- dárci krve * MeSH
- lidé MeSH
- lymfocyty * patologie MeSH
- RNA MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
Anémie je v celosvětovém měřítku nejčastějším hematologickým onemocněním vůbec. U nemocných s chronickými zánětlivými chorobami gastrointestinálního traktu (GIT) je často přítomna kombinace několika příčin podílejících se na vzniku anémie. Sideropenická složka vzniká zejména v důsledku zvýšených ztrát z poškozené sliznice GIT, může se na ní podílet i porušená resorpce železa z trávicího traktu. Současně se na anémii u chronických zánětů střevních podílejí i mechanizmy vedoucí k rozvoji anémie při chronickém onemocnění (ACD – anemia of chronic disease). Zvýšená hladina cytokinů (IL‑1, IL‑6), jež je přítomna u zánětů, vede ke zvýšené sekreci regulačního hormonu hepcidinu, jejímž důsledkem je blokáda výdeje zásobního železa do cirkulace pro potřeby erytropoézy. V diagnostice sideropenie se uplatňuje zejména kombinace hladiny feritinu v séru a saturace transferinu. U stavů s kombinovanou poruchou metabolizmu železa je třeba k odhalení sideropenie většinou použít vyšetření několika parametrů (feritin v séru, cirkulující transferinový receptor, event. hepcidin v séru). V léčbě sideropenie se uplatňuje substituce přípravky obsahujícími železo. Parenterální podávání železa je indikováno u stavů s porušenou resorpcí železa ze střeva, jako velmi efektivní se u těchto stavů ukazuje být podání nových přípravků s vysokou využitelností díky rovnoměrnému postupnému uvolňování i vysokému obsahu železa v molekule (např. Fe3+ v komplexu s karboxymaltózou). Klíčová slova: anémie – nedostatek železa – hepcidin – choroby střeva – diagnóza – léčba
Anemia represents the most frequent hematological disorder in the world. In patiens with inflammatory bowel disease (IBD) several factors may contribute to development of anemia. Increased iron loss from the damaged intestinum surface is the most frequent cause of iron deficiency together with decreased rate of iron absorption from the gut. Simultaneously, the mechanisms involved in development of anemia of chronic disease (ACD) are also present in IBD. Increased level of inflammatory cytokines (IL‑1, IL‑6) stimulates secretion of hepcidin, a regulatory hormone that leads to retention of iron in the stores and blocks iron release in circulation for the need of erythropoiesis. A combination of serum ferritin level and transferin saturation represents the most effective laboratory tool for diagnosis of iron deficiency. A combination of several parameters (eg. serum ferritin, circulating transferrin receptor, serum hepcidin) is usually necessary for an exact diagnosis of iron deficiency in diseases with combined disorder of iron metabolism. Iron deficiency may be corrected with administration of mediactions containing iron salts. Parenteral administration of iron is indicated in patients with altered iron absorption from gut, new drugs with bioavailability due to relatively random and gradual release of even high content of iron in molecule (eg. ferric carboxymaltose) may effectively correct iron depletion. Key words: anemia – iron deficiency – hepcidin – intestinal disease – diagnosis – treatment
- MeSH
- anemie * diagnóza etiologie farmakoterapie metabolismus MeSH
- chronická nemoc MeSH
- cytokiny MeSH
- diferenciální diagnóza MeSH
- ferritiny diagnostické užití krev MeSH
- gastrointestinální nemoci komplikace metabolismus MeSH
- hepcidiny diagnostické užití krev metabolismus MeSH
- hypochromní anemie * diagnóza etiologie farmakoterapie metabolismus MeSH
- idiopatické střevní záněty komplikace MeSH
- lidé MeSH
- makrofágy metabolismus MeSH
- maltosa aplikace a dávkování MeSH
- sérum MeSH
- železité sloučeniny * aplikace a dávkování terapeutické užití MeSH
- železo aplikace a dávkování metabolismus terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Perinucleolar region was studied in lymphocytes of patients suffering from chronic B lymphocytic leukemia to provide more information on the perinucleolar-condensed chromatin - heterochromatin - during the maturation of these cells. The perinucleolar heterochromatin of lymphocytes in smear preparations was visualized using a simple, but sensitive cytochemical method for the demonstration of DNA. The perinucleolar heterochromatin was also easily visible as unstained perinucleolar regions in specimens stained for RNA. In addition, the perinucleolar heterochromatin of lymphocytes was distinct and apparent in the transmission electron microscope using conventional as well as cytochemical methods for visualization of chromatin structures. Despite the great variability, the maturation of leukemic lymphocytes was accompanied by an increased width of the perinucleolar heterochromatin shell. It seems to be also interesting that the perinucleolar region of both immature as well as mature leukemia lymphocytes contains heterochromatin bodies about 2µm in diameter. They appeared to be a regular component of the perinucleolar heterochromatin shell and were apparently different from other nuclear bodies present at the nucleolus. In contrary to other known nuclear bodies, perinucleolar heterochromatin bodies in leukemia lymphocytes consisted only of conglomerates of DNA containing chromatin fibrils and did not contain other structural components including RNA. The presence of perinucleolar heterochromatin bodies in the perinucleolar region of leukemia lymphocytes is not contradictory with the present knowledge on that nuclear territory. They might be associated with presumed special perinucleolar DNA loci, which according some previous studies were more expressed in malignant cells.
- MeSH
- B-lymfocyty patologie MeSH
- buněčné jadérko genetika patologie MeSH
- chromatin genetika patologie MeSH
- chronická lymfatická leukemie genetika patologie MeSH
- DNA analýza genetika MeSH
- lidé MeSH
- organizátor jadérka MeSH
- RNA analýza genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Our study explored the role of extrapituitary prolactin (PRL) and toll-like receptors (TLR)2 and TLR4 in defense reaction of immune system to bacterial infection. Forty-two patients diagnosed with sepsis were recruited and blood samples were withdrawn after patients' admission to hospital, after the end of acute phase of sepsis and after the sepsis has been resolved, respectively. Seventeen patients died of sepsis; thus, only one sample collected just before death could be processed. PRL and TLR2/4 mRNA levels were measured in CD14+ blood monocytes by QPCR and PRL -1149 G/T SNP genotyped. The TLRs mRNA expression was markedly elevated in all patients groups in comparison to healthy controls mRNA levels; the highest upregulation of monocytic TLR2 in sepsis (16.4 times, P<0.0001) was detected in patients who did not survive septic complications. PRL mRNA expression in monocytes from non-survivors tended to be lower (4.5 fold decrease, P=NS) compared to control levels and it was 6.2 times reduced compared to PRL mRNA expression in second blood sample from survivors (P<0.05). The PRL -1149 G/T SNP had no effect on PRL mRNA response during sepsis. Our data suggest that increased prolactin mRNA expression in monocytes is associated with better outcome and improved survival rate in sepsis with no apparent effect of PRL -1149 G/T SNP on monocytic prolactin response.
- MeSH
- bakteriální infekce krev MeSH
- hematologické nádory krev MeSH
- hypofýza imunologie MeSH
- leukocyty mononukleární imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- prolaktin krev MeSH
- sepse krev MeSH
- toll-like receptor 2 krev MeSH
- toll-like receptor 4 krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: Recently, mutations in DNMT3A gene have been described in about 25% acute myeloid leukemia (AML) cases, preferentially in monocytic AML. They were found to predict worse overall survival (OS) of mutated patients. PATIENTS AND METHODS: RT-PCR followed by direct sequencing was used to test the presence of DNMT3A mutations in 226 AML patients with an intermediate-risk (IR) cytogenetics. RESULTS: Sixty-seven patients of 226 (29.6%) carried a mutation in the DNMT3A gene. Occurrence of DNMT3A mutations was associated with female sex (P = 0.027) and with the presence of FLT3/ITD (P = 0.003), but not with particular FAB subtypes. Patients with DNMT3A mutation had higher initial WBC counts than those without it (P = 0.064) only because of higher incidence of FLT3/ITD within these cases. There was no difference between mutated and wild-type groups in reaching complete remission (CR) (P = 0.380). OS was not affected by DNMT3A mutation (P = 0.251), but OS of patients who reached CR was longer in DNMT3A negative cases (P = 0.025). Patients with DNMT3A mutation had a higher relapse rate (P = 0.007). Patients carrying both the DNMT3A mutation and FLT3/ITD relapsed more often than either patients with single DNMT3A mutation (P = 0.044) or patients with FLT3/ITD only (P = 0.058). DNMT3A mutations were associated with higher relapse rate even within the FLT3/ITD-negative group (P = 0.072). After reaching CR, these two genetic factors were independent predictors of relapse at multivariate analysis (P < 0.001). Only three of 30 'double-mutated' (FLT3/ITD+, DNMT3A+) patients are still alive, all of them having undergone hematopoietic stem cell transplant. CONCLUSIONS: We have confirmed the high incidence of DNMT3A mutations in patients with AML with IR cytogenetics. Patients with DNMT3A mutations relapse more often and have inferior OS when only patients achieving CR are analyzed. 'Double-mutated' patients have a very poor prognosis.
- MeSH
- akutní myeloidní leukemie genetika mortalita MeSH
- chromozomální aberace MeSH
- DNA-(cytosin-5-)methyltransferasa genetika MeSH
- dospělí MeSH
- incidence MeSH
- indukce remise MeSH
- Kaplanův-Meierův odhad MeSH
- kodon MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace MeSH
- prognóza MeSH
- recidiva MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- tyrosinkinasa 3 podobná fms metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The appearance of heterochromatin is generally accepted as a useful tool for the evaluation of the cell state including pathology; however, information on the heterochromatin DNA condensation state expressed by the image optical density in interphase nuclear regions and mitotic chromosomes with silent genes is very limited. Since human proliferating myeloblasts are a very convenient model, they were studied in the bone marrow of leukemic patients and established cell cultures using computer assisted image densitometry at the single cell level after heterochromatin visualization by a simple but sensitive cytochemical procedure for demonstration of DNA. As was expected, a high DNA image optical density was noted in central heterochromatin regions in contrast to the nuclear periphery at the nuclear envelope. Similarly, a high nuclear DNA image optical density was also expressed in mitotic chromosomes. Thus the possibility exists that the large heterochromatin DNA condensation expressed by the large image optical density in central nuclear regions, as in mitotic chromosomes, is related to silent gene locations. The similar width of mitotic chromosomes and chromatin fibrils in the heterochromatin regions in the interphase nuclei supports that explanation. The chromatin DNA fibrils in the central heterochromatin nuclear regions of interphase cells might just represent masked silent chromosomal segments. Such a conclusion is in harmony with “classical” cytology in the first part of the last century, which suggests the chromosome continuity from the mitotic division to the interphase where each chromatin region (“Kernbezirk”) actually represents a chromosomal territory.
- MeSH
- barvení a značení MeSH
- chromatin genetika izolace a purifikace MeSH
- chromozomy genetika MeSH
- DNA nádorová genetika MeSH
- financování organizované MeSH
- heterochromatin genetika izolace a purifikace MeSH
- leukemie etiologie genetika MeSH
- lidé MeSH
- mikroskopie metody využití MeSH
- nádorové buněčné linie MeSH
- prekurzorové buňky granulocytů cytologie imunologie MeSH
- proliferace buněk MeSH
- struktury buněčného jádra genetika MeSH
- Check Tag
- lidé MeSH
