OBJECTIVE: To investigate the prevalence and the temporal structure of bilateral coherence in physiological (PT) and essential (ET) hand tremor. METHODS: Triaxial accelerometric recordings from both hands in 30 healthy subjects and 34 ET patients were analyzed using spectral coherence and wavelet coherence methods. In 12 additional healthy subjects, the relation between the hand tremor and the chest wall acceleration was evaluated using partial coherence analysis. RESULTS: The majority of both PT and ET subjects displayed significant bilateral coherence. While in PT, bilateral coherence was most frequently found in resting hand position (97% of subjects), in ET the prevalence was comparable for resting (54%) and postural (49%-57%) positions. In both PT and ET, epochs of strong coherence lasting several to a dozen seconds were separated by intervals of insignificant coherence. In PT, bilateral coherence at the main tremor frequency (8-12Hz) was coupled with the ballistocardiac rhythm. CONCLUSION: The oscillations of the two hands are intermittently synchronized in both PT and ET. We propose that in postural PT, bilateral coherence at the main tremor frequency arises from transient simultaneous entrainment of the left and right hand oscillations to ballistocardiac forcing. SIGNIFICANCE: Bilateral coherence of hand kinematics provides a sensitive measure of synchronizing influences on the left and right tremor oscillators.
- MeSH
- biomechanika MeSH
- dospělí MeSH
- elektromyografie MeSH
- esenciální tremor patofyziologie MeSH
- funkční lateralita * MeSH
- lidé středního věku MeSH
- lidé MeSH
- pohyb MeSH
- ruka inervace patofyziologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- tremor patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Neuromyelitis optica, známá také jako Devicova nemoc, je autoimunitní onemocnění centrálního nervového systému charakterizované atakami optické neuritidy a myelitidy. Po objevu protilátek proti akvaporinu 4 (AQP4-IgG/NMO-IgG) specifických pro tuto chorobu se rozšířilo spektrum klinických příznaků tohoto onemocnění. Zejména se jedná o singultus se zvracením, parézu hlavových nervů a poruchy osmotické rovnováhy při postižení hypotalamu. Stanovení AQP4-IgG v séru spolu s magnetickou rezonancí mozku a míchy mají nezastupitelný význam v diagnostice tohoto onemocnění již v okamžiku první manifestace choroby. Na druhou stranu negativita protilátek AQP4-IgG diagnózu NMO nevylučuje, což pak v klinické praxi vyžaduje širší diferenciálně diagnostický postup.
Neuromyelitis optica, also known as Devic‘s disease is an autoimmune disease of the central nervous system characterized by attacks of optic neuritis and myelitis. After the discovery of disease specific antibodies against aquaporin 4 (AQP4-IgG/NMO-IgG) the spectrum of clinical symptoms of this disease was broadened. In particular, these symptoms include singultus, vomiting, cranial nerve palsy and disorders of osmotic balance in hypothalamus involvement. Determination of AQP4-IgG in serum along with magnetic resonance imaging of the brain and spinal cord are indispensable in diagnosis of this disease at the time of the first manifestation of the disease. On the other hand, AQP4 negativity does not exclude the diagnosis of NMO-IgG, which then requires a broader differential diagnosis in clinical practice.
- Klíčová slova
- longitudinálně extenzivní myelitida,
- MeSH
- akvaporin 4 imunologie MeSH
- autoprotilátky krev MeSH
- glukokortikoidy terapeutické užití MeSH
- imunosupresiva terapeutické užití MeSH
- intravenózní imunoglobuliny terapeutické užití MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mícha patologie MeSH
- mozek patologie MeSH
- mozkomíšní mok cytologie MeSH
- myelitida diagnóza MeSH
- neuromyelitis optica * diagnóza etiologie terapie MeSH
- optická koherentní tomografie MeSH
- plazmaferéza MeSH
- zánět zrakového nervu diagnóza MeSH
- zrakové evokované potenciály MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
This study describes a screening system for future brewing yeasts focusing on non-Saccharomyces yeasts. The aim was to find new yeast strains that can ferment beer wort into a respectable beer. Ten Torulaspora delbrueckii strains were put through the screening system, which included sugar utilization tests, hop resistance tests, ethanol resistance tests, polymerase chain reaction fingerprinting, propagation tests, amino acid catabolism and anabolism, phenolic off-flavour tests and trial fermentations. Trial fermentations were analysed for extract reduction, pH drop, yeast concentration in bulk fluid and fermentation by-products. All investigated strains were able to partly ferment wort sugars and showed high tolerance to hop compounds and ethanol. One of the investigated yeast strains fermented all the wort sugars and produced a respectable fruity flavour and a beer of average ethanol content with a high volatile flavour compound concentration. Two other strains could possibly be used for pre-fermentation as a bio-flavouring agent for beers that have been post-fermented by Saccharomyces strains as a consequence of their low sugar utilization but good flavour-forming properties.
- MeSH
- aminokyseliny analýza MeSH
- biologické modely MeSH
- chuť MeSH
- DNA fingerprinting MeSH
- DNA fungální chemie izolace a purifikace MeSH
- fermentace MeSH
- koncentrace vodíkových iontů MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- metabolismus sacharidů MeSH
- odoranty MeSH
- pivo analýza mikrobiologie normy MeSH
- technika náhodné amplifikace polymorfní DNA MeSH
- teplota MeSH
- Torulaspora chemie cytologie genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
Classical homocystinuria is caused by mutations in the cystathionine β-synthase (CBS) gene. Previous experiments in bacterial and yeast cells showed that many mutant CBS enzymes misfold and that chemical chaperones enable proper folding of a number of mutations. In the present study, we tested the extent of misfolding of 27 CBS mutations previously tested in E. coli under the more folding-permissive conditions of mammalian CHO-K1 cells and the ability of chaperones to rescue the conformation of these mutations. Expression of mutations in mammalian cells increased the median activity 16-fold and the amount of tetramers 3.2-fold compared with expression in bacteria. Subsequently, we tested the responses of seven selected mutations to three compounds with chaperone-like activity. Aminooxyacetic acid and 4-phenylbutyric acid exhibited only a weak effect. In contrast, heme arginate substantially increased the formation of mutant CBS protein tetramers (up to sixfold) and rescued catalytic activity (up to ninefold) of five out of seven mutations (p.A114V, p.K102N, p.R125Q, p.R266K, and p.R369C). The greatest effect of heme arginate was observed for the mutation p.R125Q, which is non-responsive to in vivo treatment with vitamin B(6). Moreover, the heme responsiveness of the p.R125Q mutation was confirmed in fibroblasts derived from a patient homozygous for this genetic variant. Based on these data, we propose that a distinct group of heme-responsive CBS mutations may exist and that the heme pocket of CBS may become an important target for designing novel therapies for homocystinuria.
- MeSH
- arginin farmakologie MeSH
- CHO buňky MeSH
- Cricetulus MeSH
- cystathionin-beta-synthasa genetika metabolismus MeSH
- fenotyp MeSH
- fibroblasty účinky léků enzymologie MeSH
- genetická predispozice k nemoci MeSH
- hem farmakologie MeSH
- homocystinurie diagnóza farmakoterapie enzymologie genetika MeSH
- homozygot MeSH
- katalytická doména MeSH
- konformace proteinů MeSH
- lidé MeSH
- molekulární chaperony farmakologie MeSH
- molekulární modely MeSH
- mutace * MeSH
- poruchy proteostázy diagnóza farmakoterapie enzymologie genetika MeSH
- sbalování proteinů MeSH
- substrátová specifita MeSH
- transfekce MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
BACKGROUND: Thymic stromal lymphopoietin (TSLP) has been reported to activate myeloid dendritic cells (mDCs) to induce Th2 T lymphocyte responses. Its effect on plasmacytoid dendritic cells (pDCs) with TLR ligands has not yet been studied. We investigated the effects of TSLP and TLR ligands on mDCs and pDCs subsets. MATERIAL AND METHODS: Myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC) were stimulated by TLR ligands (mDC with TLR1/2 LTA, TLR2 PGN, TLR3 poly I: C, TLR4 LPS, TLR5 Flagellin) (pDC with TLR9 CpG2006, CpG 2216, TLR7 loxoribine) in the presence or absence of TSLP. Supernatants from mDCs and pDCs were analyzed for cytokine production. mDCs and pDCs were collected and cultured with allogeneic naïve T cells and after 7 days of co-culture. DC-primed CD4+ T cells were washed and restimulated with PMA and ionomycin. Cytokine production in supernatants from restimulated cells - IL-4, IL-5, IL-10, IL-13, TNF-a was analyzed by Luminex. RESULTS: TSLP alone induced the expression of maturation markers on mDCs and increased their ability to polarize lymphocytes into the Th2 phenotype. We demonstrated that pDCs also have the capacity to become even more potent inducers of Th2 immune responses, but only after combined treatment with TSLP and TLR ligands, particularly with TLR9 ligand CpG 2006. CONCLUSIONS: TSLP plays a major role in Th2 polarization of immune response mediated by myeloid DCs. Here, we demonstrate that plasmacytoid DCs, exposed to TSLP together with TLR ligands, acquire significant potential towards Th2 polarization.
- MeSH
- cytokiny biosyntéza metabolismus MeSH
- dendritické buňky metabolismus fyziologie MeSH
- lidé MeSH
- ligandy MeSH
- průtoková cytometrie MeSH
- Th2 buňky fyziologie MeSH
- toll-like receptory agonisté metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Misfolding and aggregation of mutant enzymes have been proposed to play role in the pathogenesis of homocystinuria due to cystathionine β-synthase (CBS) deficiency. Chemical chaperones have been recently shown to facilitate proper assembly of several CBS mutants. To asses the number of patients that may respond to chaperone therapy, we examined the effect of selected CBS ligands and osmolytes on assembly and activity of 27 CBS mutants that represent 70% of known CBS alleles. The mutant enzymes were expressed in a bacterial system, and their properties were assessed by native Western blotting and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) assay, respectively. We studied the chaperoning activity of δ-aminolevulinic acid (δ-ALA)-a heme precursor-and of three osmolytes betaine, 2-aminoethanesulfonic acid (taurine), and glycerol. Fourteen mutants responded by at least 30% increase in the amount of correctly assembled tetramers and enzymatic activity to the coexpressional presence of either 0.5 mM δ-ALA, 100 mM betaine, and/or 750 mM glycerol. Eight of these mutants (p.R266K, p.P49L, p.R125Q, p.K102N, p.R369C, p.V180A, p.P78R, p.S466L) were rescuable by all of these three substances. Four mutants showed increased formation of tetramers that was not accompanied by changes in activity. Topology of mutations appeared to determine the chaperone responsiveness, as 11 of 14 solvent-exposed mutations were substantially more responsive than three of 13 buried mutations. This study identified chaperone-responsive mutants that represent 56 of 713 known patient-derived CBS alleles and may serve as a basis for exploring pharmacological approaches aimed at correcting misfolding in homocystinuria.
- MeSH
- alely MeSH
- betain farmakologie terapeutické užití MeSH
- cystathionin-beta-synthasa chemie účinky léků genetika metabolismus MeSH
- Escherichia coli metabolismus MeSH
- glycerol farmakologie MeSH
- homocystinurie farmakoterapie genetika metabolismus MeSH
- jednonukleotidový polymorfismus fyziologie MeSH
- konformace proteinů účinky léků MeSH
- kyselina aminolevulová farmakologie terapeutické užití MeSH
- lidé MeSH
- ligandy MeSH
- molekulární chaperony farmakologie terapeutické užití MeSH
- multimerizace proteinu účinky léků MeSH
- mutantní proteiny chemie účinky léků metabolismus MeSH
- sbalování proteinů účinky léků MeSH
- taurin farmakologie terapeutické užití MeSH
- vazba proteinů MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
Cystathionine β-synthase (CBS) deficiency is usually confirmed by assaying the enzyme activity in cultured skin fibroblasts. We investigated whether CBS is present in human plasma and whether determination of its activity in plasma could be used for diagnostic purposes. We developed an assay to measure CBS activity in 20 μL of plasma using a stable isotope substrate - 2,3,3-(2)H serine. The activity was determined by measurement of the product of enzyme reaction, 3,3-(2)H-cystathionine, using LC-MS/MS. The median enzyme activity in control plasma samples was 404 nmol/h/L (range 66-1,066; n = 57). In pyridoxine nonresponsive CBS deficient patients, the median plasma activity was 0 nmol/ho/L (range 0-9; n = 26), while in pyridoxine responsive patients the median activity was 16 nmol/hour/L (range 0-358; n = 28); this overlapped with the enzyme activity from control subject. The presence of CBS in human plasma was confirmed by an in silico search of the proteome database, and was further evidenced by the activation of CBS by S-adenosyl-L-methionine and pyridoxal 5'-phosphate, and by configuration of the detected reaction product, 3,3-(2)H-cystathionine, which was in agreement with the previously observed CBS reaction mechanism. We hypothesize that the CBS enzyme in plasma originates from liver cells, as the plasma CBS activities in patients with elevated liver aminotransferase activities were more than 30-fold increased. In this study, we have demonstrated that CBS is present in human plasma and that its catalytic activity is detectable by LC-MS/MS. CBS assay in human plasma brings new possibilities in the diagnosis of pyridoxine nonresponsive CBS deficiency.
- MeSH
- biochemická analýza krve metody normy MeSH
- chromatografie kapalinová MeSH
- cystathionin-beta-synthasa nedostatek metabolismus MeSH
- homocystinurie krev diagnóza enzymologie MeSH
- imunoenzymatické techniky metody normy MeSH
- kalibrace MeSH
- krevní plazma chemie enzymologie metabolismus MeSH
- lidé MeSH
- pyridoxalfosfát farmakologie MeSH
- S-adenosylmethionin farmakologie MeSH
- stabilita enzymů MeSH
- studie případů a kontrol MeSH
- tandemová hmotnostní spektrometrie metody normy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
- validační studie MeSH
The author of the article addresses care of seniors in a region with one ogf the highest aging index in the Czech Republic. The clients of the facility are often immobile and therefore dependent on care provided by others. This care requires enough nursing staff and technical support which is not possible to assure without sufficient financing.
