BACKGROUND: The existence and prognosis of T1LG (T1 low-grade) bladder cancer is controversial. Also, because of data paucity, it remains unclear what is the clinical history of bacillus Calmette-Guérin (BCG) treated T1LG tumors and if it differs from other NMIBC (non-muscle-invasive bladder cancer) representatives. The aim of this study was to analyse recurrence-free survival (RFS) and progression-free survival (PFS) in patients with T1LG bladder cancers treated with BCG immunotherapy. METHODS: A multi-institutional and retrospective study of 2510 patients with Ta/T1 NMIBC with or without carcinoma in situ (CIS) treated with BCG (205 T1LG patients) was performed. Kaplan-Meier estimates and log-rank test for RFS and PFS to compare the survival between TaLG, TaHG, T1LG, and T1HG NMIBC were used. Also, T1LG tumors were categorized into EAU2021 risk groups and PFS analysis was performed, and Cox multivariate model for both RFS and PFS were constructed. RESULTS: The median follow-up was 52 months. For the T1LG cohort, the estimated RFS and PFS rates at 5-year were 59.3% and 89.2%, respectively. While there were no differences in RFS between NMIBC subpopulations, a slightly better PFS was found in T1LG NMIBC compared to T1HG (5-year PFS; T1LG vs. T1HG: 82% vs. 89%; P<0.001). A heterogeneous classification of patients with T1LG NMIBC was observed when EAU 2021 prognostic model was applied, finding a statistically significant worse PFS in patients classified as high-risk T1LG (5-year PFS; 81.8%) compared to those in intermediate (5-year PFS; 93,4%), and low-risk T1LG tumors (5-year PFS; 98,1%). CONCLUSIONS: The RFS of T1LG was comparable to other NMIBC subpopulations. The PFS of T1LG tumors was significantly better than of T1HG NMIBC. The EAU2021 scoring model heterogeneously categorized the risk of progression in T1LG tumors and the high-risk T1LG had the worst PFS.

• MeSH
• BCG vakcína terapeutické užití   MeSH
• imunoterapie MeSH
• karcinom z přechodných buněk * MeSH
• lidé MeSH
• Mycobacterium bovis * MeSH
• nádory močového měchýře * farmakoterapie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Mycobacterium tuberculosis is the main etiological agent of tuberculosis. The Bacillus Calmette-Guérin (BCG) microbes that are primarily used as a vaccine against tuberculosis also constitute the dominant infection model for studying the interaction of mycobacteria with the host cell types. The majority of interaction experiments have been conducted using macrophages and monocytes as prototype phagocyte cell types. Here, we report that M. bovis BCG infects mouse primary B cells as well as human B cell line. The complement receptors, along with B cell receptors, are engaged in the process of bacterial entry into the host B cells. Once inside the B cells, the intracellular trafficking of BCG follows the complete endocytic pathway of the ingested particles, which is in contrast to the events taking place during ingestion of BCG by macrophages. In vivo infection of mice with M. bovis BCG activated peritoneal as well as splenic B cells to produce proinflammatory cytokines. This paper further supports the evidence that B cells are involved in a host's early interactions with intracellular bacterial pathogens and participate in the induction of innate defense responses.

• MeSH
• B-lymfocyty * imunologie   mikrobiologie   MeSH
• BCG vakcína MeSH
• cytokiny metabolismus   MeSH
• lidé MeSH
• Mycobacterium bovis imunologie   MeSH
• myši MeSH
• primární buněčná kultura MeSH
• přirozená imunita MeSH
• tuberkulóza imunologie   mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Investigating genetically-structured diversity in pathogen populations over time is important to better understand disease maintenance and spread. Herd-level surveillance of Mycobacterium bovis genotypes (multi-locus VNTR analysis types, MLVA types) from all culture-confirmed bovine tuberculosis (TB) herd cases was undertaken in Northern Ireland (NI), generating an unparalleled, longitudinal, population-level 14-year survey for this pathogen. Across this population, 295 genetically-distinct M. bovis MLVA types were identified in the 19,717 M. bovis isolates surveyed. Of these, the most frequent was MLVA type 002 (23.0%); 151 MLVA types were represented more than once, in groups ranging from 2 to 4438 isolates. Only 23 MLVA types were isolated in all 14 years. Investigating inter-annual frequency of M. bovis MLVA types, examples of statistically-significant expansions (MLVA types 002, 004, 006, 009 and 027), contractions (MLVA types 001, 007 and 011) and maintenance (MLVA types 003 and 005) were disclosed, during a period of fluctuating bovine TB herd-level incidence at the NI scale. The fixed period frequency distribution of MLVA types remained highly right-skewed. Novel VNTR copy number variant MLVA types (N = 242; an average of 17 per annum) were identified throughout the survey. The MLVA type distribution in the landscape was not random; MLVA types showed statistically-significant geographical localization and strong spatial associations with Divisional Veterinary Office (DVO) regions. There was also evidence of differential risk of particular MLVA types across breeds (Holstein/Friesian vs. other), age-class, and sex and some evidence of an association between the number of animals testing positive for bovine TB during the disclosing test and particular MLVA types, although there was substantial variation.

• MeSH
• chov MeSH
• genotypizační techniky veterinární   MeSH
• longitudinální studie MeSH
• minisatelitní repetice * MeSH
• multilokusová sekvenční typizace veterinární   MeSH
• Mycobacterium bovis klasifikace   genetika   růst a vývoj   izolace a purifikace   MeSH
• rizikové faktory MeSH
• skot MeSH
• surveillance populace MeSH
• tuberkulóza skotu diagnóza   epidemiologie   MeSH
• variabilita počtu kopií segmentů DNA MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• skot MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Severní Irsko MeSH

• MeSH
• aplikace intravezikální MeSH
• BCG vakcína terapeutické užití   MeSH
• lidé MeSH
• Mycobacterium bovis * MeSH
• nádory močového měchýře * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• komentáře MeSH
• úvodníky MeSH

Mycobacterium bovis is a re-emerging zoonosis; it was diagnosed in five Abyssinian cats in a breeding cattery in Italy. The infection entered the cattery with an imported kitten (cat A); it had a suspected bite wound on its leg that had been treated at a veterinary clinic in Kiev, Ukraine, which is probably where it became infected with M. bovis. When the kitten arrived in Italy, there were four cats in the cattery; an adult female, her two kittens and a kitten imported from Russia. These were all healthy, and had no outdoor access. All five cats developed tuberculous interstitial pneumonia; in cat A this occurred 6 weeks after importation, the others were diagnosed 4-6 weeks later. Three cats were euthanised with deteriorating pneumonia while two cats remained clinically well on antibiotic therapy (marbofloxacin, doxycycline and azithromycin). The latter cases were euthanised after 5 weeks, as required by Italian law once M. bovis infection was suspected. Changes consistent with tuberculosis on gross post-mortem examination included mesenteric and mediastinal lymphadenopathy, splenomegaly and hepatomegaly, and the presence of disseminated focal white lesions on the cut surface of the spleen, liver and lungs. Visible acid-fast bacteria (cats A, B and C) were confirmed as Mycobacterium tuberculosis complex by PCR (cats A, B, C, D and E), refined to M. bovis (cats A, B and D), spoligotype SB0950 (cats A and D).

• MeSH
• epidemický výskyt choroby veterinární   MeSH
• importované infekce epidemiologie   mikrobiologie   přenos   veterinární   MeSH
• kočky MeSH
• Mycobacterium bovis fyziologie   MeSH
• nemoci koček epidemiologie   mikrobiologie   přenos   MeSH
• tuberkulóza epidemiologie   mikrobiologie   přenos   veterinární   MeSH
• zvířata MeSH
• Check Tag
• kočky MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Itálie MeSH
• Ukrajina MeSH

Disease control strategies can have both intended and unintended effects on the dynamics of infectious diseases. Routine testing for the harmful pathogen Bovine Tuberculosis (bTB) was suspended briefly during the foot and mouth disease epidemic of 2001 in Great Britain. Here we utilize bTB incidence data and mathematical models to demonstrate how a lapse in management can alter epidemiological parameters, including the rate of new infections and duration of infection cycles. Testing interruption shifted the dynamics from annual to 4-year cycles, and created long-lasting shifts in the spatial synchrony of new infections among regions of Great Britain. After annual testing was introduced in some GB regions, new infections have become more de-synchronised, a result also confirmed by a stochastic model. These results demonstrate that abrupt events can synchronise disease dynamics and that changes in the epidemiological parameters can lead to chaotic patterns, which are hard to be quantified, predicted, and controlled.

• MeSH
• časoprostorová analýza * MeSH
• epidemický výskyt choroby * MeSH
• epidemiologické monitorování MeSH
• incidence MeSH
• Mycobacterium bovis izolace a purifikace   MeSH
• skot MeSH
• statistické modely * MeSH
• stochastické procesy MeSH
• tuberkulóza skotu epidemiologie   mikrobiologie   přenos   MeSH
• zvířata MeSH
• Check Tag
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Spojené království MeSH

In this study, a 50-membered library of substituted 4-hydroxyquinolin-2(1H)-ones and two closely related analogues was designed, scored in-silico for drug likeness and subsequently synthesized. Thirteen derivatives, all sharing a common 3-phenyl substituent showed minimal inhibitory concentrations against Mycobacterium tuberculosis H37Ra below 10 μM and against Mycobacterium bovis AN5A below 15 μM but were inactive against faster growing mycobacterial species. None of these selected derivatives showed significant acute toxicity against MRC-5 cells or early signs of genotoxicity in the Vitotox™ assay at the active concentration range. The structure activity study relation provided some insight in the further favourable substitution pattern at the 4-hydroxyquinolin-2(1H)-one scaffold and finally 6-fluoro-4-hydroxy-3-phenylquinolin-2(1H)-one (38) was selected as the most promising member of the library with a MIC of 3.2 μM and a CC50 against MRC-5 of 67.4 μM.

• MeSH
• antituberkulotika chemická syntéza   chemie   farmakologie   MeSH
• chinolony chemická syntéza   chemie   farmakologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• molekulární struktura MeSH
• Mycobacterium bovis účinky léků   růst a vývoj   MeSH
• Mycobacterium tuberculosis účinky léků   růst a vývoj   MeSH
• racionální návrh léčiv * MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Bovinní tuberkulóza je způsobovaná dvěma obligátně patogenními druhy: Mycobacterium bovis a M. caprae, které vyvolávají závažná onemocnění zvířat a lidí. Přitom orální cesta infekce stojící za mimoplicní formou onemocnění je u lidí častější než aerogenní infekce způsobující plicní tuberkulózu. K významným rizikovým faktorům podmiňujícím vznik onemocnění u lidí patří především konzumace nedostatečně tepelně ošetřeného mléka, případně masa od infikovaných zvířat. Česká republika patří od roku 2004 mezi státy EU, které jsou oficiálně prosté bovinní tuberkulózy u skotu. S ohledem na stoupající počty jiných druhů infikovaných zvířat (zejm. jelenů lesních a prasat divokých) bovinní tuberkulózou v okolních státech je nutné na tuto situaci upozornit.

Bovine tuberculosis is caused by two obligate pathogenic species, Mycobacterium bovis and M. caprae, that cause severe disease in animals and humans. The oral route of infection causing extrapulmonary forms of the disease in humans is more common than aerogenic infection causing pulmonary tuberculosis. Significant risk factors for the development of diseases in humans are mainly consuming insufficiently heat-treated milk or meat from infected animals. Since 2004, the Czech Republic has been listed among the EU countries that are officially free of bovine tuberculosis in cattle. In light of the increasing numbers of other animal species (esp. red deer and wild boars) infected with bovine tuberculosis in neighboring countries, it is necessary to draw attention to this situation.

• MeSH
• bezpečnost potravin * MeSH
• epidemiologické studie MeSH
• lidé MeSH
• Mycobacterium bovis * patogenita   MeSH
• Mycobacterium patogenita   MeSH
• prasata mikrobiologie   MeSH
• přežvýkavci mikrobiologie   MeSH
• tuberkulóza skotu * epidemiologie   přenos   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH

All organisms have the capacity to sense and respond to environmental changes. These signals often involve the use of second messengers such as cyclic adenosine monophosphate (cAMP). This second messenger is widely distributed among organisms and coordinates gene expression related with pathogenesis, virulence, and environmental adaptation. Genomic analysis in Mycobacterium tuberculosis has identified 16 adenylyl cyclases (AC) and one phosphodiesterase, which produce and degrade cAMP, respectively. To date, ten AC have been biochemically characterized and only one (Rv0386) has been found to be important during murine infection with M. tuberculosis. Here, we investigated the impact of hsp60-driven Rv2212 gene expression in Mycobacterium bovis Bacillus Calmette-Guerin (BCG) during growth in vitro, and during macrophage and mice infection. We found that hsp60-driven expression of Rv2212 resulted in an increased capacity of replication in murine macrophages but an attenuated phenotype in lungs and spleen when administered intravenously in mice. Furthermore, this strain displayed an altered proteome mainly affecting proteins associated with stress conditions (bfrB, groEL-2, DnaK) that could contribute to the attenuated phenotype observed in mice.

• MeSH
• adenylátcyklasy genetika   metabolismus   MeSH
• bakteriální proteiny genetika   metabolismus   MeSH
• buněčné linie MeSH
• chaperon hsp60 genetika   metabolismus   MeSH
• lidé MeSH
• makrofágy mikrobiologie   MeSH
• Mycobacterium bovis genetika   metabolismus   patogenita   MeSH
• Mycobacterium tuberculosis enzymologie   genetika   patogenita   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• plíce mikrobiologie   MeSH
• proteom genetika   metabolismus   MeSH
• slezina mikrobiologie   MeSH
• tuberkulóza mikrobiologie   MeSH
• virulence MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Mycobacterium bovis BCG slouží k očkování proti tuberkulóze. BCG kmen vznikl z plně virulentního kmene M. bovis zásluhou Francouzů Calmetta a Guérina. Odtud synonymum „kalmetizace“ pro vakcinaci proti tuberkulóze. Poprvé byla provedena v roce 1921. K jejímu rozšíření došlo až po druhé světové válce. Na území České republiky se začali plošně očkovat novorozenci v roce 1953. Největší změna v očkování proti tuberkulóze u nás nastala 1.11.2010. Od tohoto data se povinně očkují pouze rizikoví novorozenci, jejichž vymezení udává vyhláška č. 299/2010 Sb. M. bovis BCG je silně imunogenní, čehož se využívá v léčbě karcinomu močového měchýře. V laboratořích vzniklo několik subtypů původního francouzského kmene M. bovis BCG. Zajímavé je, že ač odvozeny od M. bovis, morfologií se podobají M. tuberculosis.

Mycobacterium bovis BCG is used for vaccination against tuberculosis. The BCG strain was derived from a fully virulent strain of M. bovis by French scientists Calmette and Guérin. And the former is from where the word calmettization used as a synonym for vaccination against tuberculosis comes. The procedure was first used in 1921. It only became widespread after World War 2. In the Czech Republic, mass vaccination of newborns started in 1953. The greatest change in this regard happened on 1 November 2010 since when only at risk newborns have been vaccinated on a compulsory basis as required by Regulation No. 299/2010. M. bovis BCG is strongly immunogenic and thus also has potential in urinary bladder cancer treatment. Several subtypes of the original French M. bovis BCG strain have been derived in some laboratories. It is interesting to note that although derived from M. bovis, they are similar morphologically to M. tuberculosis.

• MeSH
• aplikace lokální MeSH
• BCG vakcína * aplikace a dávkování   terapeutické užití   MeSH
• dítě MeSH
• dospělí MeSH
• genetické inženýrství trendy   MeSH
• kojenec MeSH
• mladiství MeSH
• močové katétry využití   MeSH
• Mycobacterium bovis MeSH
• Mycobacterium tuberculosis MeSH
• nádory močového měchýře farmakoterapie   MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři MeSH
• vakcíny proti tuberkulóze MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH