BACKGROUND: Clinical studies of type 2 (T2) cytokine-related neutralizing antibodies in asthma have identified a substantial subset of patients with low levels of T2 inflammation who do not benefit from T2 cytokine neutralizing antibody treatment. Non-T2 mechanisms are poorly understood in asthma but represent a redefined unmet medical need. OBJECTIVE: We sought to gain a better understanding of genetic contributions to T2-low asthma. METHODS: We utilized an unbiased genome-wide association study of patients with moderate to severe asthma stratified by T2 serum biomarker periostin. We also performed additional expression and biological analysis for the top genetic hits. RESULTS: We identified a novel protective single nucleotide polymorphism at chr19q13.41, which is selectively associated with T2-low asthma and establishes Kallikrein-related peptidase 5 (KLK5) as the causal gene mediating this association. Heterozygous carriers of the single nucleotide polymorphisms have reduced KLK5 expression. KLK5 is secreted by human bronchial epithelial cells and elevated in asthma bronchial alveolar lavage. T2 cytokines IL-4 and IL-13 downregulate KLK5 in human bronchial epithelial cells. KLK5, dependent on its catalytic function, induces epithelial chemokine/cytokine expression. Finally, overexpression of KLK5 in airway or lack of an endogenous KLK5 inhibitor, SPINK5, leads to spontaneous airway neutrophilic inflammation. CONCLUSION: Our data identify KLK5 to be the causal gene at a novel locus at chr19q13.41 associated with T2-low asthma.

• MeSH
• bronchiální astma * genetika   MeSH
• celogenomová asociační studie * MeSH
• chemokiny genetika   MeSH
• cytokiny metabolismus   MeSH
• interleukin-13 genetika   MeSH
• interleukin-4 genetika   MeSH
• kalikreiny genetika   metabolismus   MeSH
• lidé MeSH
• neutralizující protilátky genetika   MeSH
• zánět genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH

Hot water extract from biomass of heterotrophic mutant green alga Parachlorella kessleri HY1 (Chlorellaceae) was deproteinised, and three polysaccharidic fractions were obtained by preparative chromatography. The low-molecular fraction (1.5 × 104g mol-1) was defined mainly as branched O-2-β-xylo-(1→3)-β-galactofuranan where xylose is partially methylated at O-4. Two high-molecular fractions (3.05 × 105 and 9.84 × 104g mol-1) were complex polysaccharides containing α-l-rhamnan and xylogalactofuranan parts in different ratios. The polysaccharides were well soluble in hot water and, upon cooling, tended to self-segregate. Immunomodulatory activities of the obtained fractions were preliminary tested using ELISA, FACS and ImmunoSpot kits. The polysaccharides increased the TNF-α production in melanoma bearing mice with much higher intensity than in healthy mice. This was in agreement with the FACS results on T and B cells indicating their possibly secondary activation by innate immunity cells.

• MeSH
• B-lymfocyty účinky léků   imunologie   patologie   MeSH
• CD antigeny genetika   imunologie   MeSH
• Chlorophyta chemie   MeSH
• imunologické faktory chemie   izolace a purifikace   farmakologie   MeSH
• interferon gama genetika   imunologie   MeSH
• interleukin-2 genetika   imunologie   MeSH
• interleukin-4 genetika   imunologie   MeSH
• lipopolysacharidy antagonisté a inhibitory   farmakologie   MeSH
• melanom imunologie   patologie   MeSH
• metylace MeSH
• molekulová hmotnost MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádory kůže imunologie   patologie   MeSH
• polysacharidy chemie   izolace a purifikace   farmakologie   MeSH
• primární buněčná kultura MeSH
• regulace genové exprese účinky léků   MeSH
• rostlinné extrakty chemie   MeSH
• rozpustnost MeSH
• sacharidové sekvence MeSH
• T-lymfocyty účinky léků   imunologie   patologie   MeSH
• TNF-alfa genetika   imunologie   MeSH
• voda MeSH
• xylosa chemie   izolace a purifikace   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Genetic factors, especially those related to immune system functioning, have been intensively studied to determine their role in the development of recurrent aphthous stomatitis (RAS). The aim of the present study was to analyze gene variability in interleukin (IL)2, IL4 (and its receptor α, IL4Rα), IL10, and IL13, which were selected based on literature review and/or their functional relevance, in Czech patients with RAS and in healthy controls. In total, 252 subjects (178 controls and 74 patients with RAS) were enrolled in this case-control study, and their detailed anamnestic, clinical, and laboratory data were obtained. Nine polymorphisms in the genes encoding interleukins were determined using PCR techniques. There were no significant differences in allele or genotype frequencies of the IL2, IL4, IL4Rα, IL10, and IL13 polymorphisms rs2069762/rs2069763, rs2243250/rs79071878, rs1801275, rs1800896, and rs1800925, respectively, between controls and patients with RAS. The minority alleles rs1800871 and rs1800872, which encode variants of IL10, were associated with a statistically significantly higher risk of RAS, as confirmed by the results of genotype and haplotype analyses. We suggest that variability in the IL10 gene may play an important role in the development of RAS in the Czech population.

• MeSH
• aftózní stomatitida epidemiologie   imunologie   MeSH
• alely MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genetická variace * MeSH
• genotyp MeSH
• haplotypy MeSH
• interleukin-10 genetika   metabolismus   MeSH
• interleukin-13 genetika   metabolismus   MeSH
• interleukin-2 genetika   MeSH
• interleukin-4 genetika   metabolismus   MeSH
• interleukiny genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• molekulární epidemiologie * MeSH
• polymerázová řetězová reakce MeSH
• polymorfismus genetický MeSH
• receptor interleukinu-4 - alfa-podjednotka genetika   metabolismus   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Středně těžká až těžká atopická dermatitida (atopický ekzém, AE) představuje významnou fyzickou a psychologickou zátěž pro pacienty v mnoha směrech, dále je také nezanedbatelný ekonomický dopad na pečovatele a plátce. Za posledních 15 let od schválení dvou lokálních inhibitorů kalcineurinu (takrolimu a pimekrolimu) nebyly schváleny žádné nové terapie zaměřené na léčbu AE, což pro pacienty, u nichž stávající dostupná léčebná strategie nebyla úspěšná, bylo velmi traumatické. První nově dostupnou látkou v této oblasti je dupilumab, který se vyznačuje cíleným mechanismem účinku, takže na rozdíl od existujících nespecifických imunosupresivních látek, které mají nepříznivé vedlejší účinky, může být používán dlouhodobě. Dupilumab je lidská monoklonální protilátka třídy IgG4, která se specificky váže na podjednotku receptoru IL‑4Ra a přerušuje signalizační kaskádu zprostředkovanou cytokiny IL‑4 a IL‑13. Dupilumab tak účinně blokuje specificky tento úsek Th2 řízené imunitní odpovědi. Léčba dupilumabem vede k potlačení aberantního zánětu a k částečné normalizaci profilu genové exprese kůže AE. Dupilumab zlepšuje kožní bariéru díky up‑regulaci genů kódujících proteiny, které se podílejí na epidermální struktuře, a také díky svému účinku na snížení intenzity svrbění. Stejně tak terapie dupilumabem vede i k redukci rizika kožní infekce. Klinické studie ukázaly, že terapie dupilumabem výrazně zmírňuje symptomy AE (včetně pruritu a vlivu na spánek), což následně způsobilo klinicky významný pokles výskytu úzkosti a deprese a tím také celkové zlepšení kvality života.

Atopic dermatitis (AD) is a chronic, systemic immune‑mediated disease marked by persistent underlying inflammation. Patients with AD experience extensive eczematous skin lesions and debilitating symptoms, including intense pruritus, pain & discomfort, and significant sleep disruption. Patients with AD often experience symptoms of anxiety and/or depression. The disease is associated with higher health care resource utilization and productivity loss than in less severe forms of the disease. In the last 15 years, since the approval of two local calcineurin inihibitors (tacrolimus and pimecrolimus), no new therapies for AE treatment were approved which was very frustrating for patients in whom no available therapy was successful. Dupilumab is a novel recombinant human immunoglobulin IgG4 monoclonal antibody that inhibits interleukin‑4 (IL‑4) and interleukin‑13 (IL‑13) signaling by specifically binding to the IL‑4Rα subunit shared by the IL‑4 and IL‑13 receptor complexes and is the first treatment to target the underlying type 2 (including Th2) inflammation associated with AD. In adults with moderate to severe AD, in combination with topical corticosteroids or in monotherapy, dupilumab provides rapid and sustained improvements in lesion extent and severity, pruritus and sleep disturbance. Treatment with Dupixent® leads to a reversal in both the gene expression profile of atopic dermatitis, and specific markers of inflammation and reduces the frequency of exacerbations and skin infections. Clinical studies have shown that the therapy with dupilumab significantly lowers AE symptoms (including pruritus and sleep disturbances) that leads to clinically pronounced decrease in depression and anxiety and the overall quality of life.

• MeSH
• atopická dermatitida * diagnóza   etiologie   terapie   MeSH
• farmakoterapie metody   normy   trendy   MeSH
• genetická predispozice k nemoci genetika   MeSH
• hodnocení léčiv metody   normy   MeSH
• hormony kůry nadledvin MeSH
• humanizované monoklonální protilátky * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• imunosupresiva aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• interleukin-13 genetika   izolace a purifikace   škodlivé účinky   MeSH
• interleukin-4 genetika   izolace a purifikace   škodlivé účinky   MeSH
• klinický obraz nemoci * MeSH
• komorbidita MeSH
• kožní manifestace MeSH
• lidé MeSH
• metaanalýza jako téma MeSH
• pruritus farmakoterapie   terapie   MeSH
• statistika jako téma MeSH
• věkové faktory MeSH
• Check Tag
• lidé MeSH

Atopická dermatitida (AD) je běžné zánětlivé kožní onemocnění postihující dospělé a děti. Základem lokální léčby AD jsou emoliencia, kortikosteroidy a inhibitory kalcineurinu. Pro pacienty s těžší formou AD jsou využívána celková imunosupresiva. Rozvoj znalostí v oblasti mechanismu vzniku AD vede k širokému využití nových, cílených možností léčby.

Atopic dermatitis (AD) is a common, inflammatory skin disease affecting adults and children. Topical agents including emollients, corticosteroids and calcineurin inhibitors are the mainstay of AD therapy. For more severely affected subjects, systemically administered immunosuppresant drugs are used. Our improved understanding about the mechanism for development of AD is leading to an expanding use of new targeted treatment interventions.

• MeSH
• antiflogistika nesteroidní aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• aplikace lokální MeSH
• atopická dermatitida * diagnóza   farmakoterapie   terapie   MeSH
• biologická terapie metody   trendy   MeSH
• cytokiny antagonisté a inhibitory   terapeutické užití   MeSH
• emoliencia * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• hormony kůry nadledvin aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• humanizované monoklonální protilátky * aplikace a dávkování   škodlivé účinky   MeSH
• imunosupresiva aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• interleukin-13 genetika   izolace a purifikace   škodlivé účinky   MeSH
• interleukin-4 genetika   izolace a purifikace   škodlivé účinky   MeSH
• Janus kinasy antagonisté a inhibitory   aplikace a dávkování   terapeutické užití   MeSH
• lidé MeSH
• statistika jako téma MeSH
• vitamin D terapeutické užití   MeSH
• Check Tag
• lidé MeSH

Chronic periodontitis (CP) is an inflammatory disease of the teeth-supporting tissues in which genetic predisposition, dental plaque bacteria, and immune mechanisms all play important roles. The aim of this study was to evaluate the occurrence of IL-4 gene polymorphisms in chronic periodontitis and to investigate the association between polymorphisms and cytokines production after bacterial stimulation. Sixty-two subjects (47 CP patients and 15 healthy controls) with detected two polymorphisms in the IL-4 gene (-590C/T and intron 3 VNTR) were examined. Production of cytokines (IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-17, TNFα, INFγ, and VEGF) was studied after in vitro stimulation of isolated peripheral blood by mitogens (Pokeweed mitogen, Concanavalin A), dental plaque bacteria (Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Porphyromonas gingivalis, and Prevotella intermedia), and Heat Shock Protein (HSP) 70 by the Luminex multiplex cytokine analysis system. The results were correlated with IL-4 genotypes in patients with CP and healthy controls. The mononuclear cells isolated from peripheral blood of CP patients with selected IL-4 polymorphisms significantly altered the production of IFNγ, IL-10, IL-1β, IL-1α, TNFα, and IL-6 after stimulation by HSP 70 or selected bacteria (from P < 0.001 to P < 0.05). IL-4 gene polymorphisms may influence the function of mononuclear cells to produce not only interleukin-4 but also other cytokines, especially in patients with CP.

• MeSH
• Aggregatibacter actinomycetemcomitans MeSH
• chronická nemoc MeSH
• cytokiny metabolismus   MeSH
• dospělí MeSH
• genotyp MeSH
• imunitní systém MeSH
• interleukin-4 genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitogeny chemie   MeSH
• parodontitida metabolismus   MeSH
• polymorfismus genetický * MeSH
• Porphyromonas gingivalis MeSH
• Prevotella intermedia MeSH
• sekvenční analýza DNA MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• zánět MeSH
• zubní plak mikrobiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

AIMS: We studied the influence of IL-4 gene polymorphisms on the IPF phenotype, i.e., extent of radiological changes (HRCT interstitial (IS) and alveolar (AS) score) and histopathological markers from lung biopsies. PATIENTS AND METHODS: 46 IPF patients underwent genotyping, 43 of them had HRCT and 14 patients had a surgical lung biopsy. The HRCT scans were evaluated for AS and IS. The histopathological evaluation comprised myofibroblast foci (MF), intensity of inflammation and fibrosis (Ashcroft score) and numbers of eosinophils and granulomas. For immunohistochemical evaluation primary antibodies against PAR-2, CD124, TGF beta, YY-1 and TSLP were used. The IL-4 and IL-4 R alpha gene polymorphisms were characterized. RESULTS: We found a correlation between eosinophils in lung biopsies and AS. The Ashcroft score was higher in IL-4 HA 2 GCC and MF were more frequent in IL-4 HA 2 TCC carriers. A relationship was found between IL-4 (-1098) A2 T and PAR-2 expression and IL-4 (-590) A1 T, IL-4 HA1TTT and CD124 expression. AS was lower in IL-4 (-590) A1 C, in IL-4 HA1 TCC and in IL-4RA (+1902) A1 A carriers. CONCLUSIONS: We suggest that the polymorphisms of IL-4 genes might influence the phenotype of IPF reflected by histopathological changes in lung biopsies and HRCT score.

• MeSH
• alely MeSH
• biologické markery MeSH
• biopsie MeSH
• dospělí MeSH
• eozinofily metabolismus   MeSH
• fenotyp MeSH
• genotyp MeSH
• idiopatická plicní fibróza diagnóza   genetika   MeSH
• interleukin-4 genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágy metabolismus   MeSH
• plíce imunologie   metabolismus   patologie   MeSH
• počet leukocytů MeSH
• polymorfismus genetický * MeSH
• receptor interleukinu-4 - alfa-podjednotka genetika   metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři 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
• práce podpořená grantem MeSH

CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs) and CD1d-restricted invariant natural killer T (iNKT) cells are two cell types that are known to regulate immune reactions. Depletion or inactivation of Tregs using specific anti-CD25 antibodies in combination with immunostimulation is an attractive modality especially in anti-tumour immunotherapy. However, CD25 is not expressed exclusively on Tregs but also on subpopulations of activated lymphocytes. Therefore, the modulatory effects of the specific anti-CD25 antibodies can also be partially attributed to their interactions with the effector cells. Here, the effector functions of iNKT cells were analysed in combination with anti-CD25 mAb PC61. Upon PC61 administration, α-galactosylceramide (α-GalCer)-mediated activation of iNKT cells resulted in decreased IFN-γ but not IL-4 production. In order to determine whether mutual interactions between Tregs and iNKT cells take place, we compared IFNγ production after α-GalCer administration in anti-CD25-treated and "depletion of regulatory T cell" (DEREG) mice. Since no profound effects on IFNγ induction were observed in DEREG mice, deficient in FoxP3(+) Tregs, our results indicate that the anti-CD25 antibody acts directly on CD25(+) effector cells. In vivo experiments demonstrated that although both α-GalCer and PC61 administration inhibited TC-1 tumour growth in mice, no additive/synergic effects were observed when these substances were used in combination therapy.

• MeSH
• antigeny CD1d imunologie   metabolismus   MeSH
• ELISA MeSH
• experimentální nádory farmakoterapie   imunologie   patologie   MeSH
• exprese genu účinky léků   imunologie   MeSH
• forkhead transkripční faktory imunologie   metabolismus   MeSH
• galaktosylceramidy aplikace a dávkování   imunologie   farmakologie   MeSH
• interferon gama genetika   imunologie   metabolismus   MeSH
• interleukin-4 genetika   imunologie   metabolismus   MeSH
• Kaplanův-Meierův odhad MeSH
• mezibuněčné signální peptidy a proteiny genetika   imunologie   metabolismus   MeSH
• monoklonální protilátky aplikace a dávkování   imunologie   farmakologie   MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• NKT buňky účinky léků   imunologie   metabolismus   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• průtoková cytometrie MeSH
• receptor interleukinu-2 - alfa-podjednotka imunologie   metabolismus   MeSH
• regulační T-lymfocyty účinky léků   imunologie   metabolismus   MeSH
• tumor burden účinky léků   imunologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

N-acetyl-D-glucosamine-coated polyamidoamine dendrimer (GN8P), exerting high binding affinity to rodent recombinant NKR-P1A and NKR-P1C activating proteins, was shown previously to delay the development of rat colorectal carcinoma as well as mouse B16F10 melanoma, and to potentiate antigen-specific antibody formation in healthy C57BL/6 mice via NK cell stimulation. In this study, we investigated whether GN8P also modulates tumor-specific B cell responses. Serum anti-B16F10 melanoma IgG levels, IgG2a mRNA expression, antibody dependent cell-mediated cytotoxicity (ADCC), and counts of plasma as well as antigen presenting B cells were evaluated in tumor-bearing C57BL/6 mice treated with GN8P and in respective controls. To reveal the mechanism of GN8P effects, the synthesis of interferon-gamma (IFN-γ) and interleukin-4 (IL-4), cytokines involved in regulation of immunoglobulin class switch, was determined. The GN8P treatment significantly elevated IgG, and particularly IgG2a, response against B16F10 melanoma, which led to augmented ADCC reaction. The significant increase in production of IFN-γ, which is known to support IgG2a secretion, was observed solely in NK1.1 expressing cell populations, predominantly in NK cells. Moreover, GN8P raised the number of plasma cells, and promoted antigen presenting capacity of I-A/I-E-positive B lymphocytes by up-regulation of their CD80 and CD86 co-stimulatory molecule expression. These results indicate that GN8P-induced enhancement of tumor-specific antibody formation is triggered by NK cell activation, and contributes to complexity of anticancer immune response involving lectin-saccharide interaction.

• MeSH
• acetylglukosamin chemie   farmakologie   MeSH
• antigeny CD80 biosyntéza   genetika   MeSH
• antigeny CD86 biosyntéza   genetika   MeSH
• B-lymfocyty účinky léků   imunologie   metabolismus   MeSH
• buněčná cytotoxicita závislá na protilátkách účinky léků   imunologie   MeSH
• buňky NK účinky léků   imunologie   metabolismus   MeSH
• dendrimery chemie   farmakologie   MeSH
• imunoglobulin G biosyntéza   krev   genetika   imunologie   MeSH
• interferon gama biosyntéza   genetika   MeSH
• interleukin-4 biosyntéza   genetika   MeSH
• melanom experimentální genetika   imunologie   metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• upregulace účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Cytokine gene polymorphisms are known to influence the susceptibility and disease course of many chronic disorders. Recently, interleukin (IL)-4 gene polymorphisms were associated with aggressive periodontitis. The aim of this study was to test differences in the distribution of the IL-4 alleles, genotypes, and haplotypes between patients with chronic periodontitis (CP) and healthy controls in a Czech population. METHODS: The association study was conducted using an age- and smoking status-matched case-control design in patients with CP (n = 194) and healthy controls (n = 158) using the polymerase chain reaction-restriction fragment length polymorphism methods for the -590C/T, -33C/T, and intron 3 variable number tandem repeat (VNTR) variants of the IL-4 gene. RESULTS: No significant differences between patients and controls were found in allele and genotype frequencies of all three polymorphisms. Nevertheless, complex analysis revealed significant differences in haplotype frequencies between the groups (P = 0.005). The haplotype T(-590)/T(-33)/allele 2 VNTR (70 base pairs)(2) of the IL-4 gene was significantly more frequent in patients with CP than in controls (17.0% versus 11.0%; odds ratio = 1.85; 95% confidence interval: 1.19 to 2.87). CONCLUSION: The three polymorphisms in the IL-4 gene act in a cooperative fashion and suggest that the high-production IL-4 haplotype was associated with an increased risk for CP in the Czech population.

• MeSH
• 5' přiléhající oblast DNA genetika   MeSH
• alely MeSH
• chronická parodontitida genetika   imunologie   MeSH
• cytosin MeSH
• dospělí MeSH
• exony genetika   MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci genetika   MeSH
• genotyp MeSH
• haplotypy genetika   MeSH
• interleukin-4 genetika   MeSH
• introny genetika   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• párování bází genetika   MeSH
• polymerázová řetězová reakce MeSH
• polymorfismus délky restrikčních fragmentů MeSH
• polymorfismus genetický genetika   MeSH
• studie případů a kontrol MeSH
• tandemové repetitivní sekvence genetika   MeSH
• thymin MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH