Acetylcholine (ACh)-mediated vagal transmission as well as nonneuronal ACh release are considered cardioprotective in pathological situations with increased sympathetic drive such as ischemia-reperfusion and cardiac remodeling. ACh action is terminated by hydrolysis by the cholinesterases (ChEs), acetylcholinesterase, and butyrylcholinesterase. Both ChEs exist in multiple molecular variants either soluble or anchored by specific anchoring proteins like collagen Q (ColQ) anchoring protein and proline-rich membrane anchoring protein (PRiMA). Here we assessed the expression of specific ChE molecular forms in different heart compartments using RT-qPCR. We show that both ChEs are expressed in all heart compartments but display different expression patterns. The acetylcholinesterase-T variant together with PRiMA and ColQ is predominantly expressed in rat atria. Butylcholinesterase is found in all heart compartments and is accompanied by both PRiMA and ColQ anchors. Its expression in the ventricular system suggests involvement in the nonneuronal cholinergic system. Additionally, two PRiMA variants are detected throughout the rat heart.
- MeSH
- acetylcholin metabolismus MeSH
- acetylcholinesterasa analýza metabolismus MeSH
- butyrylcholinesterasa analýza metabolismus MeSH
- GPI-vázané proteiny analýza metabolismus MeSH
- izoenzymy analýza metabolismus MeSH
- kolagen analýza metabolismus MeSH
- krysa rodu rattus MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- membránové proteiny analýza metabolismus MeSH
- myokard enzymologie MeSH
- potkani Wistar MeSH
- proteiny nervové tkáně analýza metabolismus MeSH
- stanovení celkové genové exprese MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Optimal discrimination between leukemic blasts and normal B-cell precursors (BCP) is critical for treatment monitoring in BCP acute lymphoblastic leukemia (ALL); thus identification of markers differentially expressed on normal BCP and leukemic blasts is required. METHODS: Multicenter analysis of CD73, CD86 and CD304 expression levels was performed in 282 pediatric BCP-ALL patients vs. normal bone marrow BCP, using normalized median fluorescence intensity (nMFI) values. RESULTS: CD73 was expressed at abnormally higher levels (vs. pooled normal BCP) at diagnosis in 71/108 BCP-ALL patients (66%), whereas CD304 and CD86 in 119/202 (59%) and 58/100 (58%) patients, respectively. Expression of CD304 was detected at similar percentages in common-ALL and pre-B-ALL, while found at significantly lower frequencies in pro-B-ALL. A significant association (p = 0.009) was found between CD304 expression and the presence of the ETV6-RUNX1 fusion gene. In contrast, CD304 showed an inverse association with MLL gene rearrangements (p = 0.01). The expression levels of CD73, CD86 and CD304 at day 15 after starting therapy (MRD15) were stable or higher than at diagnosis in 35/37 (95%), 40/56 (71%) and 19/41 (46%) cases investigated, respectively. This was also associated with an increased mean nMFI at MRD15 vs. diagnosis of +24 and +3 nMFI units for CD73 and CD86, respectively. In addition, gain of expression of CD73 and CD86 at MRD15 for cases that were originally negative for these markers at diagnosis was observed in 16% and 18% of cases, respectively. Of note, CD304 remained aberrantly positive in 63% of patients, despite its levels of expression decreased at follow-up in 54% of cases. CONCLUSIONS: Here we show that CD73, CD86 and CD304 are aberrantly (over)expressed in a substantial percentage of BCP-ALL patients and that their expression profile remains relatively stable early after starting therapy, supporting their potential contribution to improved MRD analysis by flow cytometry.
- MeSH
- 5'-nukleotidasa analýza biosyntéza MeSH
- antigeny CD86 analýza biosyntéza MeSH
- dítě MeSH
- GPI-vázané proteiny analýza biosyntéza MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- neuropilin-1 analýza biosyntéza MeSH
- pre-B-buněčná leukemie patologie MeSH
- předškolní dítě MeSH
- prekurzorové B-lymfoidní buňky patologie MeSH
- reziduální nádor MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
The presence of proinflammatory monocytes/macrophages (CD14+CD16+) has been documented in conditions of inflammation, such as atherosclerosis. We analysed the proportion of proinflammatory monocytes/macrophages in perirenal and perivascular fat in healthy living kidney donors with regard to sex and age reflecting reproductive status in women; therefore, women were further divided to younger and older group (younger and older than 51 years) reflecting potential age of menopause. Monocyte/macrophages were identified as CD14+ mononuclear cells and divided into subpopulations based on the co-expression of CD16. We found no differences in the monocyte/macrophage content between men (n = 15) and women (n = 28). Conversely, we observed a higher proportion of double positive CD14+CD16+ monocytes/macrophages in older women (n = 14) compared to younger women (n = 14). In addition, a strong correlation was found between the monocyte/macrophage content in fat and age only in older women. Therefore, proinflammatory monocytes/macrophages (CD14+CD16+) should be evaluated according to the sex and age.
- MeSH
- biologické markery analýza MeSH
- disparity zdravotního stavu * MeSH
- dospělí MeSH
- GPI-vázané proteiny analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipopolysacharidové receptory analýza MeSH
- makrofágy imunologie MeSH
- postmenopauza MeSH
- premenopauza MeSH
- receptory IgG analýza MeSH
- rizikové faktory MeSH
- rozmnožování * MeSH
- senioři MeSH
- sexuální faktory MeSH
- stárnutí imunologie MeSH
- tuková tkáň imunologie MeSH
- věkové faktory MeSH
- zánět imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Účel studie: Cílem práce je studium výskytu a významu sérových protilátek proti zymogenovému glykoproteinu 2 (anti-GP2) u nemocných s idiopatickými střevními záněty (Inflammatory Bowel Disease, IBD). Metody: Vyšetřili jsme 81 nemocných s diagnózou IBD – 66 pacientů s Crohnovou nemocí (CN) a 15 pacientů s ulcerózní kolitidou (UC), kontrolní skupinu 20 nemocných s neléčenou celiakií a 50 zdravých dárců krve. Všichni vyšetření pacienti s IBD byli léčeni infliximabem. Testování anti-GP2 IgG/IgA bylo provedeno ve vzorcích z nultého (W0) a desátého (W10) týdne léčby. Výsledky: Pozitivita anti-GP2 alespoň v jednom izotypu byla nalezena u 52 % nemocných s CN, ale jen u 13 % pacientů s UC (p = 0,007). V obou kontrolních skupinách byl výskyt anti-GP2 zanedbatelný. Pacienti s CN dosahovali ve srovnání s UC signifikantně vyšších koncentrací anti-GP2 (p = 0,001 pro anti-GP2 IgG a W0 a p < 0,001 pro anti-GP2 IgA a W0). V průběhu deseti týdnů biologické léčby nedošlo u nemocných s IBD k signifikantním změnám koncentrací sledovaných autoprotilátek. Nebyla prokázána souvislost výskytu anti-GP2 IgG ani IgA s pohlavím, věkem, místem a typem postižení ani s aktivitou zánětlivého onemocnění střev. Jediná signifikantní souvislost byla nalezena u anti-GP2 IgA s formou postižení CN, kdy strikturující a fistulující forma byla spojena s častějším výskytem a vyššími titry anti-GP2 IgA. Závěry: Anti-GP2 se vyskytují přibližně u poloviny pacientů s CN. Výskyt anti-GP2 nekoreluje s místem, formou ani typem postižení zažívacího ústrojí, nesouvisí s aktivitou nemoci a koncentrace autoprotilátek se v průběhu biologické terapie IBD zásadně nemění.
Purpose of the study: The aim of the study is to examine the incidence and significance of serum antibodies against zymogen glycoprotein 2 (anti-GP2) in patients with inflammatory bowel disease (IBD). Methods: Eighty-one patients with IBD were examined, 66 patients with Crohn's disease (CD) and 15 with ulcerative colitis (UC); there was also a control group of 20 patients with untreated coeliac disease and 50 healthy blood donors. All examined patients with IBD were treated with infliximab. Analyses of anti-GP2 IgG/IgA were performed in samples from week 0 (W0) and week 10 (W10) of the treatment. Results: Anti-GP2 in at least one isotype were found in 52% of patients with CD, but only in 13% of patients with UC (p = 0.007). In both control groups, the incidence of anti-GP2 was minimal. Compared to UC patients, individuals with CD achieved significantly higher concentrations of anti-GP2 (p = 0.001 for anti-GP2 IgG at W0 and p < 0.001 for anti-GP2 IgA at W0). No significant changes in concentrations of autoantibodies were observed during 10 weeks of the biological treatment. No evidence of anti-GP2 IgG/IgA association with gender, age, location or type of IBD, or with the activity of the disease was proven. The only significant correlation was found in anti-GP2 IgA with CD damage when stricturing and fistulizing form was related to more frequent incidence and higher anti-GP2 IgA titres. Conclusions: Anti-GP2 occure in approximately half of patients with CD. The incidence of anti-GP2 does not correlate with CD location, form or type of the alimentary tract damage; it is not related to the disease activity and concentrations of autoantibody concentrations do not change significantly during the IBD biological treatment.
- Klíčová slova
- biologická léčba,
- MeSH
- autoprotilátky * imunologie krev MeSH
- biologická terapie MeSH
- Crohnova nemoc imunologie krev MeSH
- dospělí MeSH
- ELISA MeSH
- fluorescenční protilátková technika MeSH
- GPI-vázané proteiny analýza imunologie MeSH
- idiopatické střevní záněty * imunologie krev MeSH
- imunoglobulin A imunologie MeSH
- imunoglobulin G imunologie MeSH
- infliximab MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové glykoproteiny * analýza imunologie MeSH
- mladý dospělý MeSH
- monoklonální protilátky terapeutické užití MeSH
- prediktivní hodnota testů MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- statistika jako téma MeSH
- studie případů a kontrol MeSH
- TNF-alfa MeSH
- ulcerózní kolitida imunologie krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
