The selection of a suitable combination of reference genes (RGs) for data normalization is a crucial step for obtaining reliable and reproducible results from transcriptional response analysis using a reverse transcription-quantitative polymerase chain reaction. This is especially so if a three-dimensional multicellular model prepared from liver tissues originating from biologically diverse human individuals is used. The mRNA and miRNA RGs stability were studied in thirty-five human liver tissue samples and twelve precision-cut human liver slices (PCLS) treated for 24 h with dimethyl sulfoxide (controls) and PCLS treated with β-naphthoflavone (10 μM) or rifampicin (10 μM) as cytochrome P450 (CYP) inducers. Validation of RGs was performed by an expression analysis of CYP3A4 and CYP1A2 on rifampicin and β-naphthoflavone induction, respectively. Regarding mRNA, the best combination of RGs for the controls was YWHAZ and B2M, while YWHAZ and ACTB were selected for the liver samples and treated PCLS. Stability of all candidate miRNA RGs was comparable or better than that of generally used short non-coding RNA U6. The best combination for the control PCLS was miR-16-5p and miR-152-3p, in contrast to the miR-16-5b and miR-23b-3p selected for the treated PCLS. Our results showed that the candidate RGs were rather stable, especially for miRNA in human PCLS.
- MeSH
- beta-2-mikroglobulin genetika metabolismus MeSH
- beta-naftoflavon farmakologie MeSH
- cytochrom P-450 CYP1A2 genetika metabolismus MeSH
- cytochrom P-450 CYP3A genetika metabolismus MeSH
- dimethylsulfoxid farmakologie MeSH
- dospělí MeSH
- játra účinky léků metabolismus MeSH
- kvantitativní polymerázová řetězová reakce normy MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- mikro RNA genetika metabolismus MeSH
- proteiny 14-3-3 genetika metabolismus MeSH
- referenční standardy MeSH
- rifampin farmakologie MeSH
- senioři MeSH
- stanovení celkové genové exprese normy MeSH
- systém (enzymů) cytochromů P-450 farmakologie MeSH
- transkriptom 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
In follicular lymphoma (FL), no prognostic index has been built based solely on a cohort of patients treated with initial immunochemotherapy. There is currently a need to define parsimonious clinical models for trial stratification and to add on biomolecular factors. Here, we confirmed the validity of both the follicular lymphoma international prognostic index (FLIPI) and the FLIPI2 in the large prospective PRIMA trial cohort of 1135 patients treated with initial R-chemotherapy ± R maintenance. Furthermore, we developed a new prognostic tool comprising only 2 simple parameters (bone marrow involvement and β2-microglobulin [β2m]) to predict progression-free survival (PFS). The final simplified score, called the PRIMA-PI (PRIMA-prognostic index), comprised 3 risk categories: high (β2m > 3 mg/L), low (β2m ≤ 3 mg/L without bone marrow involvement), and intermediate (β2m ≤ 3 mg/L with bone marrow involvement). Five-year PFS rates were 69%, 55%, and 37% in the low-, intermediate-, and high-risk groups, respectively (P < .0001). In addition, achieving event-free survival (EFS) or not at 24 months (EFS24) was a strong posttreatment prognostic parameter for subsequent overall survival, and the PRIMA-PI was correlated with EFS24. The results were confirmed in a pooled external validation cohort of 479 patients from the FL2000 LYSA trial and the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence Molecular Epidemiology Resource. Five-year EFS in the validation cohort was 77%, 57%, and 44% in the PRIMA-PI low-, intermediate-, and high-risk groups, respectively (P < .0001). The PRIMA-PI is a novel and easy-to-compute prognostic index for patients initially treated with immunochemotherapy. This could serve as a basis for building more sophisticated and integrated biomolecular scores.
- MeSH
- beta-2-mikroglobulin metabolismus MeSH
- folikulární lymfom * metabolismus mortalita patologie terapie MeSH
- imunoterapie * MeSH
- kostní dřeň metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- nádorové proteiny metabolismus MeSH
- přežití bez známek nemoci MeSH
- protokoly protinádorové kombinované chemoterapie aplikace a dávkování MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Research Support, N.I.H., Extramural MeSH
- Klíčová slova
- dialyzační amyloidóza (Aβ2M), vzácné hereditární amyloidózy,
- MeSH
- amyloidóza * chemicky indukované prevence a kontrola terapie MeSH
- beta-2-mikroglobulin * metabolismus MeSH
- chronická renální insuficience terapie MeSH
- dialýza ledvin * škodlivé účinky MeSH
- familiární amyloidóza genetika terapie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
OBJECTIVE: The current study aimed to evaluate plasma calprotectin levels and clearance end-stage renal disease (ESRD) patients with and without acute infection undergoing chronic hemodialysis (HD). MATERIALS AND METHODS: Blood samples from 54 HD patients were obtained before and after the HD and 42 healthy blood donors were examined as controls. The blood levels of calprotectin, procalcitonin, C-reactive protein (CRP), and intracellular production of interleukins 10 and 12 in monocytes were determined in both groups. RESULTS: The concentrations of plasma calprotectin in ESRD patients were significantly higher than in healthy controls (p < 0.05). No differences between pre- and post-HD calprotectin plasma levels were observed (p = 0.07 for two-tailed test). Plasma calprotectin levels were not significantly influenced by the presence of acute infection (p = 0.19) or diabetes (p = 0.42). A significant positive correlation of plasma calprotectin to plasma beta-2 microglobulin was proven (p < 0.05). Procalcitonin (PCT), CRP, IL-10, and IL-12 were not correlated with plasma calprotectin before or after HD. The elevation of plasma calprotectin was correlated strongly to the hemodialysis vintage (r = 0.55, p < 0.01). CONCLUSIONS: Significantly elevated levels of plasma calprotectin in ESRD patients occur without an acute infectious cause and are not affected by the presence of diabetes. By analogy to plasma beta-2 microglobulin, a close relation of plasma calprotectin to HD vintage was shown.
- MeSH
- beta-2-mikroglobulin metabolismus MeSH
- C-reaktivní protein metabolismus MeSH
- chronické selhání ledvin krev MeSH
- dialýza ledvin MeSH
- ELISA MeSH
- interleukin-10 biosyntéza MeSH
- interleukin-12 biosyntéza MeSH
- kalcitonin krev MeSH
- leukocytární L1-antigenní komplex krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- monocyty metabolismus MeSH
- proteinové prekurzory krev MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
Nestr. ; 32 cm
Míra účinku PTH na kost je ovlivňována různými faktory z nich bychom chtěli zkoumat pohlavní hormony.Pomocí DEXA a biochemických markerů remodulace skeletu u našich nemocných s PHP bychom chtěli zjistit vztah mezi PTH a hladinami pohlavních hormonů . Práce má i praktickou stránku,operovat nebo neoperovat nemocné s mírnými změnami na kostech a možnosti léčení takových to nemocných estrogeny.; With the help of bone densinometry and biochemical parameters of bone remodeling in our pre and post-menopausal patients with PHP we should want to find out relationship between PTH and levels of gonadal steroids and severity of bone disease. In prospective study we want to evaluate the effect of PHP on biochemical and bone densitometric indicies in some patiens followed without parathyroidectomy. We want to study the correlation between the levels of beta 2 microglobulin and tartrate-resistant acid phosphatase in our patiens with PHP.
- MeSH
- beta-2-mikroglobulin metabolismus MeSH
- biologické markery MeSH
- hyperparatyreóza metabolismus MeSH
- modely nemocí na zvířatech MeSH
- remodelace kosti MeSH
- selektivní modulátory estrogenních receptorů MeSH
- tamoxifen terapeutické užití MeSH
- Konspekt
- Fyziologie člověka a srovnávací fyziologie
- NLK Obory
- endokrinologie
- vnitřní lékařství
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
73 s. : il. ; 32 cm
U primární a druhotné osteoporózy bude studován patogenetický význam hormonální nerovnováhy se zvláštním zaměřením na růstové faktory Budou hledány imunologické a genetické odchylky u osteoporózy a sledovány možnosti jejich využití v časné diagnostice choroby
- MeSH
- beta-2-mikroglobulin metabolismus MeSH
- insulinu podobný růstový faktor I metabolismus farmakologie MeSH
- kalcitriol metabolismus farmakologie MeSH
- melatonin metabolismus MeSH
- minerálová a kostní nemoc při chronickém onemocnění ledvin terapie MeSH
- osteoporóza metabolismus patofyziologie MeSH
- poruchy metabolismu vápníku MeSH
- Konspekt
- Lékařské vědy. Lékařství
- NLK Obory
- ortopedie
- vnitřní lékařství
- endokrinologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
A disturbing interaction of PAN membranes and the bradykinin generation system particularly in the presence of angiotensin converting enzyme inhibitors has been described. A modified new membrane, SPAN (special PAN), was produced by varying the polymer components in type and composition, in particular by a reduction in Na-Methallylsulfonate. Although the SPAN membrane successfully averted the bradykinin generating ability of PAN, it was important to determine whether such a modification did not lead to a loss of the satisfactory biocompatibility profile characteristic of the parent membrane. For this purpose, we conducted the present clinical study in nine patients comparing 3 membranes; (i) a polysulphone membrane (F60S); (ii) PAN; and (iii) SPAN, to examine the clinical biocompatibility profile and performance of the new membrane. A small increase in C5a with F60S and SPAN was found which is in the range expected for highly biocompatible synthetic membranes. The three dialysers had a similar inert profile for terminal complement complex arterial values, and had similar venous values. A minimal nonsignificant decline in white cell count was observed at 15 min for all dialysers, but otherwise WBC counts were unchanged. Platelet counts were unchanged throughout treatment for the three dialysers. Arterial and venous thrombin-anti-thrombin complex values were similar for all three dialysers. F60S and SPAN dialysers had similar urea clearances.(ABSTRACT TRUNCATED AT 250 WORDS)
- MeSH
- beta-2-mikroglobulin metabolismus MeSH
- biokompatibilní materiály chemie terapeutické užití MeSH
- chronické selhání ledvin metabolismus terapie MeSH
- dialýza ledvin * přístrojové vybavení MeSH
- dospělí MeSH
- komplement C5a metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- membranolytický komplex metabolismus MeSH
- membrány umělé * MeSH
- mladiství MeSH
- močovina metabolismus MeSH
- počet leukocytů MeSH
- senioři MeSH
- trombin metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- senioři MeSH
- Publikační typ
- klinické zkoušky MeSH
- randomizované kontrolované studie MeSH