Coherent vibration states in biological systems excited in nonlinear electrically polar structures by metabolic energy supply were postulated by H. Frohlich. Frohlich's requirements for coherent vibrations and generation of electromagnetic field are satisfied by microtubules whose subunits are electric dipoles. Static electric field around mitochondria and "wasted energy" efflux from them provide nonlinear conditions and coherent excitation. Numerical models are used for analysis of coherent vibration states. A hypothesis is presented that dysfunction of mitochondria (i.e., extinction of the zones of the static electric field and of the efflux of "wasted energy") and disintegration of the cytoskeleton on the pathway of cancer transformation result in disturbances of coherence of the cellular electrically polar oscillations and of the generated electromagnetic field with consequences in cellular organization and interactions between cells. Local invasion, detachment, and metastasis of cancer cells are subsequent events of disturbed electromagnetic interactions.

• MeSH
• biofyzikální jevy MeSH
• biologické modely MeSH
• cytoskelet metabolismus   účinky záření   MeSH
• elektromagnetická pole škodlivé účinky   MeSH
• lidé MeSH
• mitochondrie metabolismus   účinky záření   MeSH
• nádorová transformace buněk MeSH
• nádorové buněčné linie MeSH
• nádory patologie   MeSH
• nelineární dynamika MeSH
• vibrace MeSH
• Check Tag
• lidé MeSH

Mechanical interaction of cell with extracellular environment affects its function. The mechanisms by which mechanical stimuli are sensed and transduced into biochemical responses are still not well understood. Considering this, two finite element (FE) bendo-tensegrity models of a cell in different states are proposed with the aim to characterize cell deformation under different mechanical loading conditions: a suspended cell model elucidating the global response of cell in tensile test simulation and an adherent cell model explicating its local response in atomic force microscopy (AFM) indentation simulation. The force-elongation curve obtained from tensile test simulation lies within the range of experimentally obtained characteristics of smooth muscle cells (SMCs) and illustrates a nonlinear increase in reaction force with cell stretching. The force-indentation curves obtained from indentation simulations lie within the range of experimentally obtained curves of embryonic stem cells (ESCs) and exhibit the influence of indentation site on the overall reaction force of cell. Simulation results have demonstrated that actin filaments (AFs) and microtubules (MTs) play a crucial role in the cell stiffness during stretching, whereas actin cortex (AC) along with actin bundles (ABs) and MTs are essential for the cell rigidity during indentation. The proposed models quantify the mechanical contribution of individual cytoskeletal components to cell mechanics and the deformation of nucleus under different mechanical loading conditions. These results can aid in better understanding of structure-function relationships in living cells.

• MeSH
• analýza metodou konečných prvků * MeSH
• biologické modely * MeSH
• biomechanika MeSH
• cytoskelet metabolismus   MeSH
• eukaryotické buňky cytologie   metabolismus   MeSH
• mechanické jevy * MeSH
• mikrofilamenta metabolismus   MeSH
• mikrotubuly metabolismus   MeSH
• pevnost v tahu MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Hypothesis of coherent vibration states in biological systems based on nonlinear interaction between longitudinal elastic and electric polarization fields with metabolic energy supply was formulated by Frohlich. Conditions for excitation of coherent states and generation of electromagnetic fields are satisfied in microtubules which form electrical polar structures. Numerical models are used for analysis of Frohlich's vibration states in cells. Reduction of activity and of energy production in mitochondria, and disintegration of cytoskeleton structures by phosphorylation on the pathway of cancer trasformation can diminish excitation of the Frohlich's vibration states and of the generated electromagnetic field, which results in disturbances of the interaction forces between cells. Interaction forces between cancer cells may be smaller than interaction forces between healthy cells and cancer cells as follows from numerical models. Mechanism of malignity, i.e. local invasion, detachment of cancer cells, and metastasis, is assumed to depend on the electromagnetic field.

• MeSH
• biofyzika metody   MeSH
• biologické modely MeSH
• buňky 3T3 MeSH
• cytoskelet metabolismus   MeSH
• elektromagnetická pole MeSH
• elektromagnetické jevy MeSH
• lidé MeSH
• mikroskopie atomárních sil MeSH
• mikrotubuly metabolismus   MeSH
• mitochondrie metabolismus   MeSH
• myši MeSH
• nádory metabolismus   MeSH
• pružnost MeSH
• Saccharomyces cerevisiae metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

OBJECTIVE: Individuals with decreased thiopurine methyltransferase (TPMT) activity are at risk of adverse effects of thiopurine administration whereas its increased activity may inactivate drugs faster. We evaluated genotype-phenotype correlations in patients with suspected hematological malignancies and inflammatory bowel disease from our region based on findings of nonlinear TPMT enzyme kinetics previously unreported. PATIENTS AND METHODS: The study group comprised 267 individuals. They were screened for the most common variants of low TPMT activity. TPMT activity was measured in erythrocytes using the HPLC rate-blanked method. RESULTS: Thirty-three patients (12.4%) were heterozygous (26 were TPMT*1/*3A, 5 TPMT*1/*2, 2 TPMT *1/*3C) and 1 was a compound heterozygote (*2/*3A). Normal and low normal TPMT activities substantially overlapped in wild-type and heterozygous individuals, whereas high activities were found in 29 wild-type genotyped patients. Extreme and life-threatening toxicity was observed in the compound heterozygote patient. CONCLUSION: Activity measurement performed at diagnosis provides clinicians with information on immediate pharmacokinetic-related adverse events and/or hypermetabolism, and genotyping may indicate the rate of pharmacodynamic thioguanine nucleotide accumulation due to slower overall thiopurine metabolism.

• MeSH
• asparaginasa terapeutické užití   MeSH
• cyklofosfamid terapeutické užití   MeSH
• cytarabin terapeutické užití   MeSH
• daunomycin terapeutické užití   MeSH
• erytrocytární membrána enzymologie   MeSH
• genetické asociační studie MeSH
• idiopatické střevní záněty krev   MeSH
• lidé MeSH
• lymfoblastická leukemie-lymfom z prekurzorových T-buněk farmakoterapie   genetika   MeSH
• merkaptopurin terapeutické užití   MeSH
• methotrexát terapeutické užití   MeSH
• methyltransferasy nedostatek   genetika   metabolismus   MeSH
• mladiství MeSH
• polymerázová řetězová reakce MeSH
• prednison terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• vinkristin terapeutické užití   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH