Microtubules of all eukaryotic cells are formed by α- and β-tubulin heterodimers. In addition to the well known cytoplasmic tubulins, a subpopulation of tubulin can occur in the nucleus. So far, the potential function of nuclear tubulin has remained elusive. In this work, we show that α- and β-tubulins of various organisms contain multiple conserved nuclear export sequences, which are potential targets of the Exportin 1/CRM1 pathway. We demonstrate exemplarily that these NES motifs are sufficient to mediate export of GFP as model cargo and that this export can be inhibited by leptomycin B, an inhibitor of the Exportin 1/CRM1 pathway. Likewise, leptomycin B causes accumulation of GFP-tagged tubulin in interphase nuclei, in both plant and animal model cells. Our analysis of nuclear tubulin content supports the hypothesis that an important function of nuclear tubulin export is the exclusion of tubulin from interphase nuclei, after being trapped by nuclear envelope reassembly during telophase.
- MeSH
- aktivní transport - buněčné jádro fyziologie MeSH
- buněčné jádro metabolismus MeSH
- buněčné linie MeSH
- cytoplazma metabolismus MeSH
- eukaryotické buňky metabolismus MeSH
- karyoferiny metabolismus MeSH
- lidé MeSH
- mikrotubuly metabolismus MeSH
- protein exportin 1 MeSH
- receptory cytoplazmatické a nukleární metabolismus MeSH
- tabák metabolismus MeSH
- transport proteinů fyziologie MeSH
- tubulin metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- karyoferiny MeSH
- receptory cytoplazmatické a nukleární MeSH
- tubulin MeSH
Microtubule drugs such as paclitaxel, colchicine, vinblastine, trifluralin, or oryzalin form a chemically diverse group that has been reinforced by a large number of novel compounds over time. They all share the ability to change microtubule properties. The profound effects of disrupted microtubule systems on cell physiology can be used in research as well as anticancer treatment and agricultural weed control. The activity of microtubule drugs generally depends on their binding to α- and β-tubulin subunits. The microtubule drugs are often effective only in certain taxonomic groups, while other organisms remain resistant. Available information on the molecular basis of this selectivity is summarized. In addition to reviewing published data, we performed sequence data mining, searching for kingdom-specific signatures in plant, animal, fungal, and protozoan tubulin sequences. Our findings clearly correlate with known microtubule drug resistance determinants and add more amino acid positions with a putative effect on drug-tubulin interaction. The issue of microtubule network properties in plant cells producing microtubule drugs is also addressed.
- MeSH
- druhová specificita MeSH
- houby MeSH
- lidé MeSH
- mikrotubuly účinky léků metabolismus MeSH
- modulátory tubulinu farmakologie MeSH
- rostliny MeSH
- taxoidy farmakologie MeSH
- tubulin účinky léků genetika fyziologie MeSH
- vinca alkaloidy farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- modulátory tubulinu MeSH
- taxoidy MeSH
- tubulin MeSH
- vinca alkaloidy MeSH
The severity of streptococcal infections depends upon different virulence of individual strains of its causative agent. The most important species are beta-haemolytic group A streptococci (GAS). Clinical manifestations include skin affections, respiratory tract infections and, in particular, serious systemic invasive infections. The pathogenicity of GAS is derived from cell wall components and extracellular products, especially toxins with properties of the so-called superantigens. Less invasive forms of the disease are include necrotizing fasciitis, myositis, pneumonia, sepsis without focus, arthritis, meningitis, puerperal sepsis, streptococcal toxic shock syndrome (STSS) and severe course of erysipelas and cellulitis with blood culture positive for GAS. In most cases, soft tissue infections dominate, often accompanied by chronic diseases of lower extremities in elderly patients. The other clinical forms are rather rare. In children, the condition is clearly frequently related to chickenpox. The generally accepted therapeutic management comprises comprehensive intensive care, early administration of penicillin in combination with clindamycin, and surgical intervention. The use of intravenous immunoglobulins (IVIG), elimination methods and hyperbaric oxygen are under discussion. The slight increase in cases and ineffective prevention require rapid assessment of diagnosis and adequate treatment as a protracted course of the condition is connected with a high mortality rate.
In a randomized prospective multi-centre study, we evaluated the cognitive performances of a group of 41 non-demented patients, all with advanced Parkinson's disease (PD) and a current depressive episode, in whom the effects of pramipexole (PPX) and pergolide (PRG) in an add-on to l-dopa therapy were also studied and published with regard to motor symptoms of PD, motor complications and depression. The Trail Making Test, the Stroop test and four subtests (arithmetic, picture completion, digit symbols and similarities) of the Wechsler Adult Intelligence Scale-Revised were performed prior to and 8 months after the administration of either PPX or PRG. We found no statistically significant difference between the two tested drugs or between the first and the last visit in any of the above-listed neuropsychological tests. All patients' motor outcomes significantly improved and we conclusively demonstrated the anti-depressive effect of PPX. The dissociation of dopaminomimetic effects on the different tested domains indicates that there are different pathological mechanisms of cognitive, motor and affective disturbances in advanced PD patients. In our non-demented group of fluctuating depressed PD subjects, both PPX and PRG administration in combination with l-dopa were safe in terms of the effect on cognitive performance.
- MeSH
- agonisté dopaminu terapeutické užití MeSH
- analýza rozptylu MeSH
- deprese komplikace farmakoterapie psychologie MeSH
- kognitivní poruchy komplikace farmakoterapie psychologie MeSH
- kombinovaná farmakoterapie MeSH
- levodopa terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- neparametrická statistika MeSH
- Parkinsonova nemoc komplikace farmakoterapie psychologie MeSH
- prospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
- Názvy látek
- agonisté dopaminu MeSH
- levodopa MeSH
The diagnosis of Lyme disease in 18 patients has been proved by detection of Borrelia burgdorferi sensu lato when using immunoelectron microscopy or detecting its nucleic acid by PCR in the plasma or the cerebrospinal fluid. The positive results occurred in the plasma or in the cerebrospinal fluid in the period of 4-68 months after an antibiotic treatment. The typical clinical manifestations of Lyme disease were observed in 9 patients and non-specific symptoms in another 9 patients. According to presented results we can recommend repeated examination using PCR of the plasma and other biological specimens in the individuals with persistent or recurring complaints after an acute form of Lyme disease and its antibiotic treatment. Also examination of the cerebrospinal fluid with non-specific symptoms and simultaneously displayed pathology electroencephalogram and/or magnetic resonance imaging findings can be advantageous.
- MeSH
- antibakteriální látky terapeutické užití MeSH
- Borrelia burgdorferi komplex izolace a purifikace ultrastruktura MeSH
- časové faktory MeSH
- dítě MeSH
- DNA bakterií analýza MeSH
- dospělí MeSH
- imunoelektronová mikroskopie metody MeSH
- imunoglobulin G krev MeSH
- imunoglobulin M krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymeská nemoc diagnóza farmakoterapie imunologie MeSH
- mladiství MeSH
- polymerázová řetězová reakce metody MeSH
- western blotting MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- antibakteriální látky MeSH
- DNA bakterií MeSH
- imunoglobulin G MeSH
- imunoglobulin M MeSH
An 8-month multicentre prospective randomized study aimed at comparing the effects of dopamine receptor agonists pramipexole (PPX; Mirapexin) and pergolide (PRG; Permax) as add-on to L-dopa therapy on depression [Montgomery and Asberg Depression Rating Scale (MADRS)] in 41 non-demented patients (25 men, 16 women) suffering from both mild or moderate depression and advanced Parkinson's disease (PD). The assessment was performed by a blinded independent observer. Motor symptoms (UPDRS III), motor complications (UPDRS IV), activities of daily living (UPDRS II and VI) and depressive symptoms as measured by Self - Rating Depression Scale by Zung were evaluated in an open-label design. The average value of Zung scores decreased significantly in both groups with no statistical difference between both groups. A significant decrease in the average value of MADRS scores was present only in the PPX group. The average UPDRS scores decreased significantly with no statistical difference between both groups at the comparable average total daily dose of both preparations. In both cases, the total daily dose of L-dopa decreased significantly but the decrease was statistically more pronounced in the PRG group. Our results demonstrate the antidepressant effect of PPX in patients with PD while we can't make any conclusions with regard to antidepressant effect of PRG.
- MeSH
- analýza rozptylu MeSH
- antiparkinsonika škodlivé účinky terapeutické užití MeSH
- benzothiazoly MeSH
- činnosti denního života MeSH
- deprese farmakoterapie etiologie MeSH
- jednoduchá slepá metoda MeSH
- klinické křížové studie MeSH
- kombinovaná farmakoterapie MeSH
- levodopa terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- Parkinsonova nemoc komplikace MeSH
- pergolid škodlivé účinky terapeutické užití MeSH
- placebo MeSH
- pohybová aktivita MeSH
- pramipexol MeSH
- prospektivní studie MeSH
- psychiatrické posuzovací škály MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- thiazoly škodlivé účinky terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
- Názvy látek
- antiparkinsonika MeSH
- benzothiazoly MeSH
- levodopa MeSH
- pergolid MeSH
- placebo MeSH
- pramipexol MeSH
- thiazoly MeSH
PURPOSE: To determine whether parenteral or oral antibiotics given before admission to a regional hospital with a special intensive care unit (ICU) reduce the case fatality rate in patients with meningococcal disease. DESIGN: Prospective analysis of 164 consecutive patients with meningococcal disease admitted to 5 regional hospitals in the Czech Republic between August 1996 and October 2001. Main outcome measure was number of deaths from meningococcal disease. Fisher's exact test was used for statistical analysis. MAIN FINDINGS: Nine out of 116 patients (8%) given antibiotics before admission died, compared with five deaths in 48 patients (10%) admitted without such a treatment (p = 0.55). None of 19 patients given oral or combined oral and parenteral pre-admission antibiotics died. CONCLUSION: Parenteral and probably also oral antibiotics given before admission to a regional hospital and an adequate treatment of shock can reduce the case fatality rate from meningococcal disease.
- MeSH
- antibakteriální látky aplikace a dávkování MeSH
- antibiotická profylaxe * MeSH
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- meningokokové infekce farmakoterapie mortalita MeSH
- mladiství MeSH
- Neisseria meningitidis účinky léků MeSH
- předškolní dítě MeSH
- příjem pacientů * MeSH
- prospektivní studie MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Názvy látek
- antibakteriální látky MeSH
- MeSH
- bakteriální infekce komplikace diagnóza terapie MeSH
- diabetes mellitus imunologie MeSH
- gynekologická onemocnění komplikace diagnóza terapie MeSH
- infekce močového ústrojí komplikace diagnóza terapie MeSH
- komplikace diabetu * MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Percutaneous endoscopic gastrostomy (PEG) is an efficient endoscopic method that ensures enteral nutrition for a longer period of time in patients who cannot take food per os. This method is also indicated in patients suffering from disorders of the central or peripheral nervous system which developed suddenly, such as a stroke or craniocerebral injuries, or gradually, such as amyotrophic lateral sclerosis (ALS), dementia, and multiple sclerosis. It has become common practice in the cooperation between neurologists and a gastroenterologists to use PEG in patients hospitalized in a neurological ward with encephalomalacy and haemorrhage, or craniocerebral injuries (after the patient recovers from the acute stage of the disease and is transferred to a neurological ICU), as well as in patients with ALS in a progressive stage. We gradually extend the indications of PEG for other patients with neurological disorders such as patients suffering from dementia, progressive multiple sclerosis, Parkinson's disease, and progressive polyneuropathy. Of 62 patients hospitalized in a neurological ward during a period of 4.5 years, 56 patients suffered from sudden disorders of the nervous system (strokes and craniocerebral injuries) and 6 patients had gradually progressing neurological diseases (ALS, multiple sclerosis, Parkinson's disease, dementia, and polyneuropathy).
- MeSH
- dospělí MeSH
- endoskopie * MeSH
- enterální výživa * MeSH
- gastrostomie * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- nemoci nervového systému * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
The immunoblot was prepared from genotypes Borrelia afzelii (KC 90), Borrelia garinii (M 192) and Borrelia burgdorferi sensu stricto (B 31). Sera of 63 patients with different forms of Lyme borreliosis were examined and 40 healthy donors in the endemic area of the disease. In class IgM in the group of patients significantly more frequently antibodies against OspC, p39, p41 B. afzelii, p39, p41, p66, p83 B. garinii and OspC1, OspA, B. burgdorferi sensu stricto were found. In class IgG there were antibodies against p39, p41, p93 B. afzelii, p14, p41, p93 B. garinii and OspA, OspC p93 B. burgdorferi sensu lato. Based on the assembled results by means of discrimination analysis and logistic regression the most suitable combinations of antigens for evaluation of immunoblots in different genotypes were determined. Furthermore evaluation was suggested using a combination of antigens of several genotypes which led to an increased sensitivity and specificity of the immunoblot. Tables were prepared for easier evaluation of newly examined sera samples.
- MeSH
- antigeny bakteriální MeSH
- Borrelia burgdorferi komplex imunologie MeSH
- dítě MeSH
- dospělí MeSH
- ELISA MeSH
- imunoglobulin G analýza MeSH
- imunoglobulin M analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- logistické modely MeSH
- lymeská nemoc diagnóza MeSH
- mladiství MeSH
- předškolní dítě MeSH
- protilátky bakteriální analýza MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- sérologické testy MeSH
- western blotting * MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigeny bakteriální MeSH
- imunoglobulin G MeSH
- imunoglobulin M MeSH
- protilátky bakteriální MeSH
