Human early erythroid precursors classified according to the nuclear size were studied to provide information on nucleoli in these cells using simple cytochemical procedures for demonstration of RNA and proteins of silver-stained nucleolar organizers. K2 cells with nuclear diameter larger than 13 microm and K1 cells with nuclear diameter larger than 9 microm corresponding to proerythroblasts and macroblasts (large basophilic erythroblasts) mostly possessed large irregularly shaped nucleoli with multiple fibrillar centres representing "active nucleoli". K1/2 cells with nuclear diameter smaller than 9 microm corresponding to small basophilic erythroblasts were usually characterized by the presence of micronucleoli representing "inactive nucleolar types". On the other hand, a few K1/2 cells contained large nucleoli with multiple fibrillar centres similar to those present in K2 cells and thus appeared as "microproerythroblasts". The nucleolar asynchrony expressed by the presence of large irregularly shaped nucleoli with multiple nucleoli (active nucleoli) and ring-shaped nucleoli (resting nucleoli) in one and the same nucleus of K2 or K1 cells was not exceptional and might reflect a larger resistance of these cells to negative factors influencing the erythropoiesis. The intranucleolar translocation of silver-stained nucleolus organized regions was noted in K2 cells and might indicate the premature aging of these cells without further differentiation. More studies, however, are required in this direction.

• MeSH
• barvení stříbrem MeSH
• buněčná diferenciace fyziologie   MeSH
• buněčné jadérko fyziologie   ultrastruktura   MeSH
• buněčné jádro fyziologie   ultrastruktura   MeSH
• buněčný rodokmen fyziologie   MeSH
• erytroblasty klasifikace   cytologie   fyziologie   MeSH
• erytrocyty cytologie   fyziologie   MeSH
• erytropoéza fyziologie   MeSH
• jaderné proteiny metabolismus   MeSH
• lidé MeSH
• transport proteinů fyziologie   MeSH
• tvar buňky fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• jaderné proteiny MeSH

Considering the effects of alcohol on cardiac electrical behavior as well as the important role of the inward rectifier potassium current I(K1) in arrhythmogenesis, this study was aimed at the effect of acetaldehyde, the primary metabolite of ethanol, on I(K1) in rat ventricular myocytes. Acetaldehyde induced a reversible inhibition of I(K1) with IC(50) = 53.7+/-7.7 microM at -110 mV; a significant inhibition was documented even at clinically-relevant concentrations (at 3 microM by 13.1+/-3.0 %). The inhibition was voltage-independent at physiological voltages above -90 mV. The I(K1) changes under acetaldehyde may contribute to alcohol-induced alterations of cardiac electrophysiology, especially in individuals with a genetic defect of aldehyde dehydrogenase where the acetaldehyde level may be elevated.

• MeSH
• acetaldehyd farmakologie   MeSH
• draslíkové kanály dovnitř usměrňující antagonisté a inhibitory   metabolismus   MeSH
• kardiomyocyty účinky léků   metabolismus   MeSH
• metoda terčíkového zámku MeSH
• otrava alkoholem metabolismus   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetaldehyd MeSH
• draslíkové kanály dovnitř usměrňující MeSH

On a simple model of a reaction-chain from the pharmacon-receptor complex (RA) formation the formation of a ternal complex with substrate (S) and its activation to a product the authors investigate the meaning of the term "affinity" and "internal activity" and the behaviour of the model with substrate and velocity limits at various sites. If K1 = dissociation constant of the complex RA, K2 = dissociation constant of the complex RAS, then at S1 much greater than R1 (i.e. without receptor reserve) the obtained value ED50 described usually as KA = K1K2: (K2 + [St]) and if K1 is constant it is variable in relation to the substrate concentration. In this way continuous differences of apparent affinity of the same substance to the same receptor under different biological conditions are possible. At R1 much greater than St (i.e. with receptor reserve) apparent KA = K1K2: (K2 + [Rt]) and thus K1 can be assessed by blocking receptors with an irreversible antagonist. The authors describe the calculation and very simple graphical method for assessment of basic parameters using an irreversible antagonist. After linear plotting of ED50 (= KA) on the chi-axis and maximal effects on the gamma-axis and after extrapolation of the connecting line of the two points (results without antagonist and results with antagonist) the intersecting point with the chi-axis gives value K1. This makes it possible, among others, to assess also the "intrinsic efficacy" of the substance, the ratio of receptors eliminated by the antagonist, prediction of the behaviour of typical curves during gradual elimination of receptors by a blocker and to assess possibly also the half-life of binding of the irreversible blocker with the receptor.

• MeSH
• receptory léků * MeSH
• teoretické modely MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• receptory léků * MeSH

The magnetic structures of the Ho-based i-MAX phase (Mo2/3Ho1/3)2GaC were studied with neutron powder diffraction at low temperature. (Mo2/3Ho1/3)2GaC crystallizes in the orthorhombic space group Cmcm. The material undergoes two successive antiferromagnetic transitions at TN1 = 10 K and TN2 = 7.2 K. The magnetic structure below TN1 is incommensurate with the propagation vector k1 = (0, ky, 0) with ky = 0.696 (1) at 9 K. For the analysis of the magnetic structure, a group-theoretical approach based on the space group of the nuclear structure and its subgroups was employed. A model in the (3+1)D superspace group Cmcm.1'(0β0)s0ss yielded the most accurate results in neutron powder diffraction refinements. The determined structure was found to be an incommensurate longitudinal amplitude-modulated magnetic structure. Below TN2, additional magnetic satellites develop. They could be indexed by a propagation vector k2 = (τx, 0, 0) with the τx value increasing below TN2 until it stabilizes at approximately 3 K at 0.075. A magnetic structure determination considering two propagation vectors k1 and k2 was carried out using the superspace formalism by building the corresponding (3+2)D model. The determination was based on the observation that the additional magnetic peaks emerge exclusively in the vicinity of the incommensurate magnetic peaks with propagation vector k1, and not in the vicinity of nuclear peaks. This indicates that only mixed-index reflections were observed, and not reflections purely related to k2. The magnetic superspace group (MSSG) that was determined is Amma.1' (0,β,0)00s0 (0,0,γ)ss0s. The structure can be described as a longitudinal amplitude-modulated structure, which itself is amplitude-modulated in a perpendicular direction. This represents a very unusual case of a 2-k magnetic structure with no symmetry relation between the propagation vectors.

• Klíčová slova
• incommensurate structures, magnetic superspace groups, neutron diffraction, rare-earth i-MAX phases,
• Publikační typ
• časopisecké články MeSH

Inward rectifier potassium currents (I Kir,x) belong to prominent ionic currents affecting both resting membrane voltage and action potential repolarization in cardiomyocytes. In existing integrative models of electrical activity of cardiac cells, they have been described as single current components. The proposed quantitative model complies with findings indicating that these channels are formed by various homomeric or heteromeric assemblies of channel subunits with specific functional properties. Each I Kir,x may be expressed as a total of independent currents via individual populations of identical channels, i.e., channels formed by the same combination of their subunits. Solution of the model equations simulated well recently observed unique manifestations of dual ethanol effect in rat ventricular and atrial cells. The model reflects reported occurrence of at least two binding sites for ethanol within I Kir,x channels related to slow allosteric conformation changes governing channel conductance and inducing current activation or inhibition. Our new model may considerably improve the existing models of cardiac cells by including the model equations proposed here in the particular case of the voltage-independent drug-channel interaction. Such improved integrative models may provide more precise and, thus, more physiologically relevant results.

• Klíčová slova
• Cardiomyocytes, Dual effect, Ethanol, I K1, Inward rectifier potassium currents, Quantitative model,
• MeSH
• akční potenciály * MeSH
• alosterická regulace MeSH
• draslíkové kanály dovnitř usměrňující chemie   metabolismus   MeSH
• ethanol farmakologie   MeSH
• kardiomyocyty účinky léků   metabolismus   fyziologie   MeSH
• krysa rodu Rattus MeSH
• modely kardiovaskulární MeSH
• multimerizace proteinu MeSH
• srdce - funkce komor MeSH
• srdeční komory cytologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• draslíkové kanály dovnitř usměrňující MeSH
• ethanol MeSH

The ERK (extracellular signal-regulated kinases) cascade has an evolutionarily conserved three tier architecture consisting of protein kinases Raf, MEK (MAPK/ERK kinase) and ERK. Following activation, ERK phosphorylates various cellular elements leading to diverse cellular responses. Downstream of ERK the family of p90 ribosomal S6 kinases (RSKs) has been proven to be an important conveyor of ERK signaling, however, little is known if ERK and RSK coordinate their functions to generate a specific biological response. Here we show that in epithelial cells conditional activation of the ERK pathway causes phenotypic conversion of epithelial cells to autonomously migrating cells. This process involves two sequential steps characterized by loss of apical-basal polarity followed by cell scattering. The activation of ERK, but not RSK, is sufficient for the execution of the first step and it requires calpain mediated remodeling of actin cytoskeleton. Conversely, RSK regulates the successive stage characterized by cell-cell contact weakening and increased cellular migration. Thus, ERK and RSK regulate different cellular subprograms and coordinated execution of these subprograms in time generates a relevant biological response. Our data also suggest that the mechanism by which the ERK pathway controls a cellular response may be distributed between ERK and RSK, rather than being elicited by a single effector kinase.

• Klíčová slova
• 4-hydroxytamoxifen, 4HT, ALLM, ALLN, Calpain, Cell–cell junctions, EMT, ER, MAPK/ERK, MDCK, Madin–Darby Canine Kidney, Migration, N-Acetyl-l-leucine-l-leucine-l-norleucinal, N-Acetyl-l-leucyl-l-leucyl-l-methional, Polarity, RSK, epithelial–mesenchymal transition, ligand binding domain of estrogen receptor,
• MeSH
• buněčné linie MeSH
• epitelové buňky cytologie   metabolismus   MeSH
• extracelulárním signálem regulované MAP kinasy metabolismus   MeSH
• kadheriny metabolismus   MeSH
• kalpain metabolismus   MeSH
• kinasy ribozomálního proteinu S6, 90-kDa metabolismus   MeSH
• lidé MeSH
• MAP kinasový signální systém MeSH
• mezibuněčné spoje metabolismus   MeSH
• pohyb buněk MeSH
• polarita buněk MeSH
• psi MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• extracelulárním signálem regulované MAP kinasy MeSH
• kadheriny MeSH
• kalpain MeSH
• kinasy ribozomálního proteinu S6, 90-kDa MeSH

Common voles (Microtus arvalis) in groups of nine to 10 animals were inoculated per os with a dose of 1, 10, 1x10(2), 1x10(3), and of the K1 strain of Toxoplasma gondii. All the common voles inoculated with 1 to 1 x 10(3) oocysts remained subclinical and survived. Three of the 10 voles inoculated with 1 x 10(4) oocysts died between days 7 and 12 post inoculation (p.i.). Antibodies were demonstrated in all the infected voles killed on day 60 p.i. The highest antibody titres in voles detected by the dye test (DT) and latex agglutination test (LAT) were 1,024 and 1,280, respectively.

• MeSH
• Arvicolinae krev   imunologie   parazitologie   MeSH
• barevná diluční technika veterinární   MeSH
• imunologická odpověď na dávku MeSH
• latex fixační testy veterinární   MeSH
• náchylnost k nemoci veterinární   MeSH
• nemoci hlodavců krev   imunologie   MeSH
• oocyty MeSH
• protilátky protozoální krev   MeSH
• Toxoplasma imunologie   MeSH
• toxoplazmóza zvířat krev   imunologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• protilátky protozoální MeSH

Capillary electrophoresis separation and synchronous fluorescence spectral detection was used off-line to reveal the nature of fluorescent adducts formed in vivo in the collagen molecule and their distribution in the molecule. It was shown that by using the delta lamda in the area of the Stokes shift for the analyzed entities (approximately 10 nm for pentosidine, 4,5(E)-epoxy-2(E)-heptenal and 4,5(E)-epoxy-2(E)-decenal lysine adducts) a distinct profile of spectral bands can be obtained allowing for differentiation of the several entities involved. In combination with capillary electrophoretic separation of the CNBr peptides the location of individual adducts was possible: while pentosidine (and, perhaps, pentosidine related compounds K1-K4) is found in the large alpha 1(I)CB6 and alpha 2(I)CB3.5 peptides along with a complete set of the other fluorescent adducts, low-molecular-mass peptides originating from the terminal region of the molecule are devoid of any fluorescence. All other parts of the molecule possess synchronous fluorescence profiles corresponding to the intact molecule except that they are devoid of pentosidine. The results indicate random distribution of fluorescent adducts in the collagen molecule and, in a broader context, indicate the usefulness of multicomponent analysis by means of combining synchronous luminescence spectra and capillary electrophoresis.

• MeSH
• algoritmy MeSH
• bromkyan MeSH
• elektroforéza kapilární MeSH
• fluorescenční barviva MeSH
• fluorescenční spektrometrie MeSH
• glykosylace MeSH
• kolagen analýza   MeSH
• krysa rodu Rattus MeSH
• kůže chemie   MeSH
• luminiscenční měření MeSH
• peptidy analýza   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bromkyan MeSH
• fluorescenční barviva MeSH
• kolagen MeSH
• peptidy MeSH

Alcohol consumption may result in electrocardiographic changes and arrhythmias. Important role of modifications of the inward rectifier potassium current I(K1) in arrhythmogenesis is well established. Considering lack of relevant data, we aimed at studying the effect of 0.2-200 mM ethanol on I(K1) in enzymatically isolated rat right ventricular myocytes using the whole cell patch-clamp technique at 23±1°C. Ethanol reversibly affected I(K1) in a dual way. At a very low concentration of 0.8 mM (≈~0.004%), ethanol significantly decreased IK1 by 6.9±2.7%. However, at concentrations of ethanol ≥20 mM (≈0.09%), I(K1) was conversely significantly increased (by 16.6±4.0% at 20 mM and 24.5±2.4% at 80 mM). The steady-state I(K1) increase was regularly preceded by its transient decrease at the beginning of ethanol application. Under 2 and 8 mM ethanol, I(K1) was decreased at the steady-state in some cells but increased in others. Both effects were voltage-independent. In agreement with the observed effects of ethanol on I(K1), a transient action potential (AP) prolongation followed by its final shortening were observed after the application of ethanol in a low concentration of 8 mM (≈0.04%). Under the effect of 0.8 mM ethanol, only AP prolongation was apparent which agreed well with the above described I(K1) decrease. Other AP characteristics remained unaltered in both concentrations. These observations corresponded with the results of mathematical simulations in a model of the rat ventricular myocyte. To summarize, changes of the cardiac I(K1) under ethanol at concentrations relevant to the current alcohol consumption were first demonstrated in ventricular myocytes in this study. The observed dual ethanol effect suggests at least two underlying mechanisms that remain to be clarified. The ethanol-induced I(K1) changes might contribute to the reported alterations of cardiac electrophysiology related to alcohol consumption.

• MeSH
• akční potenciály účinky léků   MeSH
• draslíkové kanály dovnitř usměrňující fyziologie   MeSH
• ethanol farmakologie   MeSH
• kardiomyocyty účinky léků   fyziologie   MeSH
• potkani Wistar MeSH
• srdeční komory cytologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• draslíkové kanály dovnitř usměrňující MeSH
• ethanol MeSH

BACKGROUND: Targeted oncology therapy with inhibitors of epidermal growth factor receptor is associated with numerous cutaneous side effects. Acneiform eruptions are the most frequent skin toxicities reported. They may lead to impairment of patients' quality of life and sometimes may even become severe enough to necessitate the interruption or cessation of therapy. OBJECTIVE: To assess the possible effect of topical phytomenadione (vitamin K1 ) pre-treatment in diminishing the extent and severity of acne-like follicular rash associated with epidermal growth factor receptor inhibitor therapy. METHODS: A series of 20 patients with colorectal cancer or head and neck cancer were pre-treated with phytomenadione cream (0.05% in seven patients and 0.1% in 13 patients), starting morning before the first infusion of cetuximab or panitumumab, and followed up for the development of therapy-associated folliculitis. The cream was prepared from phytomenadione solution added to a hydrophilic cream base, oil in water, to obtain the concentration of 0.05% or 0.1%. RESULTS: Majority of patients (15 out of 20, 75%) pre-treated with phytomenadione cream experienced only mild, grade I acneiform eruptions. Five patients (25%) had grade II rash, which included two of seven patients pre-treated with 0.05% phytomenadione cream and three of 13 patients who used 0.1% phytomenadione cream. Topical phytomenadione cream was well tolerated and no abnormalities in blood coagulation were observed. CONCLUSIONS: Topical pre-treatment with phytomenadione cream might become useful in epidermal growth factor inhibitor-associated acneiform eruptions.

• MeSH
• antitumorózní látky škodlivé účinky   terapeutické užití   MeSH
• cetuximab MeSH
• dospělí MeSH
• erbB receptory antagonisté a inhibitory   MeSH
• folikulitida chemicky indukované   farmakoterapie   MeSH
• humanizované monoklonální protilátky škodlivé účinky   terapeutické užití   MeSH
• kolorektální nádory farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky škodlivé účinky   terapeutické užití   MeSH
• nádory hlavy a krku farmakoterapie   MeSH
• panitumumab MeSH
• senioři MeSH
• vitamin K 1 terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky MeSH
• cetuximab MeSH
• erbB receptory MeSH
• humanizované monoklonální protilátky MeSH
• monoklonální protilátky MeSH
• panitumumab MeSH
• vitamin K 1 MeSH