BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2>0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13). CONCLUSIONS: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk. PATIENT SUMMARY: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.

• MeSH
• celogenomová asociační studie MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• hodnocení rizik MeSH
• homeostáza telomer * MeSH
• jednonukleotidový polymorfismus * MeSH
• karcinom z renálních buněk krev   genetika   patologie   MeSH
• leukocyty chemie   MeSH
• lidé MeSH
• mendelovská randomizace MeSH
• nádory ledvin krev   genetika   patologie   MeSH
• odds ratio MeSH
• rizikové faktory MeSH
• studie případů a kontrol MeSH
• telomery genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

The discovery of tyrosine kinase inhibitors (TKIs) brought a major breakthrough in the treatment of patients with chronic myeloid leukemia (CML). Pathogenetic CML events are closely linked with the Bcr-Abl protein with tyrosine kinase activity. TKIs block the ATP-binding site; therefore, the signal pathways leading to malignant transformation are no longer active. However, there is limited information about the impact of TKI treatment on the metabolome of CML patients. Using liquid chromatography mass spectrometric metabolite profiling and multivariate statistical methods, we analyzed plasma and leukocyte samples of patients newly diagnosed with CML, patients treated with hydroxyurea and TKIs (imatinib, dasatinib, nilotinib), and healthy controls. The global metabolic profiles clearly distinguished the newly diagnosed CML patients and the patients treated with hydroxyurea from those treated with TKIs and the healthy controls. The major changes were found in glycolysis, the citric acid cycle, and amino acid metabolism. We observed differences in the levels of amino acids and acylcarnitines between those patients responding to imatinib treatment and those who were resistant to it. According to our findings, the metabolic profiling may be potentially used as an additional tool for the assessment of response/resistance to imatinib.

• MeSH
• aminokyseliny metabolismus   MeSH
• chronická myeloidní leukemie krev   metabolismus   MeSH
• citrátový cyklus účinky léků   MeSH
• glykolýza účinky léků   MeSH
• hydroxymočovina farmakologie   terapeutické užití   MeSH
• imatinib mesylát farmakologie   terapeutické užití   MeSH
• inhibitory proteinkinas farmakologie   MeSH
• krevní plazma chemie   metabolismus   MeSH
• leukocyty chemie   metabolismus   MeSH
• lidé MeSH
• metabolom * MeSH
• metabolomika metody   MeSH
• monitorování léčiv metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Flow cytometry represents an attractive approach for developing currently unavailable screening tests for prion diseases. Several studies have reported significant differences in the binding of antibodies directed against cellular prion protein (PrP(C)) to blood cells of prion-infected subjects compared with healthy controls. However, flow cytometry data usually show large individual variations in detected PrP(C) levels in both infected and control groups, rendering the interpretation of individual patient data difficult. OBJECTIVES: To determine how pre-analytical variables, such as the choice of anticoagulant, whether or not the blood was stored, and the storage temperature, affect the detection of PrP(C) in blood cells. METHODS: Blood from healthy donors was collected in EDTA or citrate anticoagulant and processed either immediately or after storage overnight at room temperature or at 4°C. The expression of PrP(C) by T cells, B cells, NK cells, monocytes and circulating dendritic cells was evaluated using quantitative flow cytometry with the PrP(C) monoclonal antibodies AG4 and AH6. RESULTS: The anticoagulation of blood with citrate resulted in decreased levels of PrP(C) on monocytes but not the other cell types. The storage of blood prior to analysis led to a significant decrease in the levels of PrP(C) on the cells studied, although there were substantial differences between the cell populations. This decrease was more pronounced when using mAb AG4, which targets the N-terminal portion of the PrP(C) molecule, or following storage at room temperature. Moreover, we identified platelet satellitism on leukocytes, especially on monocytes and granulocytes, as an additional factor contributing to the heterogeneity of PrP(C) detection in stored blood. CONCLUSIONS: Our study demonstrates that the storage of blood prior to analysis greatly affects the detection of PrP(C) by flow cytometry. To limit the inclusion of storage-generated artifacts, we recommend the processing of blood samples immediately after their collection.

• MeSH
• antikoagulancia farmakologie   MeSH
• dendritické buňky chemie   MeSH
• dospělí MeSH
• EDTA farmakologie   MeSH
• kyselina citronová farmakologie   MeSH
• leukocyty chemie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• odběr vzorku krve metody   MeSH
• priony analýza   MeSH
• průtoková cytometrie metody   MeSH
• trombocyty MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• analýza spermatu MeSH
• antibakteriální látky terapeutické užití   MeSH
• epididymitida diagnóza   etiologie   farmakoterapie   komplikace   MeSH
• leukocyty chemie   MeSH
• lidé MeSH
• mužská infertilita * etiologie   komplikace   MeSH
• orchitida diagnóza   etiologie   farmakoterapie   komplikace   MeSH
• prostatitida * diagnóza   etiologie   farmakoterapie   komplikace   MeSH
• uretritida * diagnóza   etiologie   farmakoterapie   komplikace   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• směrnice pro lékařskou praxi MeSH

INTRODUCTION: Monitoring of circulating melanoma cells in the peripheral blood is a promising method for identifying a subgroup of patients with minimal residual disease. OBJECTIVES: To evaluate the prognostic impact of melanoma-associated antigens by multimarker real-time RT-PCR for disease-specific survival time. METHODS: Five melanoma markers: Melan-A, gp 100, MAGE-3, MIA and tyrosinase were detected by a quantitative multimarker real-time reverse transcription-PCR (RT-PCR). We included 65 patients with resected melanoma in stage II-III. Peripheral blood samples were examined every 3 months for 2 years. The expression of melanoma markers in 2925 RT-PCR assays was correlated with clinical staging results in total of 5 years. RESULTS: Twenty-seven patients relapsed during the study period and 26 of them revealed positive markers. MAGE-3 was the most sensitive progression marker in single occurrence or in combination with MIA and gp 100. The time distribution of metastases during the screened period was as follows: progression in the first year was observed in 40.7% patients, second year in 25.9%, third year in 18.6%, fourth and fifth year in 7.4% equally. CONCLUSIONS: Statistically significant tumor marker elevation during the first 2 years after the surgical treatment correlates with a worse prognosis of patients. In contrast, the group showing negative real-time RT-PCR results in 24 months serial blood testing was associated with prolonged 5-year disease-specific survival. Therefore, quantitative detection of melanoma-specific molecular markers in the presented setting represents a useful tool for selecting patients in a higher risk of disease recurrence.

• MeSH
• antigeny nádorové genetika   MeSH
• antigeny sacharidové asociované s nádorem genetika   MeSH
• dospělí MeSH
• exprese genu genetika   MeSH
• leukocyty chemie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• MART-1 antigen genetika   MeSH
• melanom diagnóza   metabolismus   patologie   chirurgie   MeSH
• melanomové antigeny genetika   MeSH
• melanomový antigen gp100 genetika   MeSH
• mladý dospělý MeSH
• nádorové proteiny genetika   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• přežití po terapii bez příznaků nemoci MeSH
• prognóza MeSH
• progrese nemoci MeSH
• senioři MeSH
• staging nádorů MeSH
• tyrosinasa genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH

The mitochondrial DNA (mtDNA) amount in cells as the basis for mitochondrial energy generating system, which produces ATP, plays an important role in the fetal development and postnatal morbidity. Isolated human cord blood leukocytes (HCBL) contribute very little to the overall metabolic turnover, but they may serve as easily available marker cells for the study of the mtDNA amount changes in cord blood during fetal development. The aim of our study was to analyze the mtDNA amount in HCBL. HCBL were isolated from cord blood samples of 107 neonates born between the 25th and 41st week of gestation. The mtDNA amount was analyzed by the real-time PCR method. The significant negative correlations were found between the relative mtDNA amount in HCBL and gestational age (r = -0.54, p<0.01) and birth weight (r = -0.43, p<0.01), respectively. The results revealed that the mtDNA content per cell decreases in HCBL with progressing fetal development. This may be explained by gradual shift of the hematopoiesis from fetal liver to bone marrow during the second half of pregnancy presumably accompanied by decreasing cell volume of HCBL as it was shown similarly in red blood cells.

• Klíčová slova
• Mitochondrial DNA, Human cord blood leukocytes, Real-time PCR,
• MeSH
• down regulace MeSH
• fetální krev cytologie   MeSH
• financování organizované MeSH
• gestační stáří MeSH
• leukocyty chemie   MeSH
• lidé MeSH
• mitochondriální DNA krev   MeSH
• novorozenec MeSH
• polymerázová řetězová reakce MeSH
• porodní hmotnost MeSH
• reprodukovatelnost výsledků MeSH
• senzitivita a specificita MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH

A single dose of IMUNOR, a low-molecular-weight immunodulator prepared from disintegrated and ultrafiltered pig leukocytes, was found to enhance recovery of murine pool of hemopoietic progenitor cells for granulocytes and macrophages damaged by a single injection of cytotoxic drugs 5-fluorouracil or cisplatin. The best results were obtained after the treatment with IMUNOR on days 3 or 4 after the injection of 5-fluorouracil or cisplatin. These results together with previous findings obtained in our laboratory suggest that IMUNOR has the potential to become a part of treatment schemes in oncological practice aimed at alleviation of myelosuppression evoked by cytotoxic anti-tumor therapy.

• MeSH
• antimetabolity antitumorózní MeSH
• antitumorózní látky MeSH
• buňky kostní dřeně imunologie   účinky léků   MeSH
• cisplatina MeSH
• financování organizované MeSH
• fluorouracil MeSH
• granulocyty imunologie   účinky léků   MeSH
• hematopoéza účinky léků   MeSH
• imunologické faktory farmakologie   chemie   MeSH
• kmenové buňky účinky léků   MeSH
• leukocyty chemie   imunologie   MeSH
• myši inbrední ICR MeSH
• myši MeSH
• nemoci kostní dřeně farmakoterapie   chemicky indukované   MeSH
• prasata MeSH
• ultrafiltrace MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH

The aim of our study was to define mutations causing familial hypercholesterolemia (FH) phenotype in Czech hypercholesterolemic individuals. A combination of heteroduplex analysis, SSCP, DGGE, DNA sequencing and PCR/restriction analysis was used for this purpose. Molecular searching in the promoter region and coding sequence of the low density lipoprotein receptor (LDLR) gene in 130 patients from 68 unrelated families resulted in the identification of 37 sequence variations. Thirty of them are most likely disease causing mutations. Nineteen mutations were novel (two nonsense, five missense, six nucleotide(s) insertions and six nucleotide(s) deletions). Their pathological effect can be predicted on the basis of their position with respect to previously reported mutations with an estimated reduction of the receptor activity and/or premature termination of translation. These results expand our knowledge of mutations responsible for FH. Seven nucleotide variations were characterized as silent polymorphisms.

• MeSH
• cholesterol krev   MeSH
• DNA krev   genetika   MeSH
• dospělí MeSH
• heteroduplexní analýza MeSH
• hyperlipoproteinemie typ II krev   epidemiologie   genetika   MeSH
• leukocyty chemie   MeSH
• lidé MeSH
• mutace genetika   MeSH
• receptory LDL genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• upravené články MeSH
• Geografické názvy
• Česká republika MeSH

• MeSH
• antisérum MeSH
• chemokiny MeSH
• hematologické testy MeSH
• leukocyty chemie   imunologie   MeSH
• mediátory zánětu imunologie   chemie   MeSH
• Publikační typ
• vysokoškolské kvalifikační práce MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biochemie
• alergologie a imunologie
• hematologie a transfuzní lékařství

• MeSH
• CD antigeny chemie   klasifikace   MeSH
• klasifikace MeSH
• leukocyty chemie   imunologie   MeSH
• mezinárodní spolupráce MeSH
• terminologie jako téma MeSH