Venózní tromboembolizmus je multifaktoriální onemocnění a je častou příčinou morbidity a mortality. Absolutní riziko je menší než 1/10 000 u žen v reprodukčním věku, avšak hormonální antikoncepce patří mezi časté příčiny venózního tromboembolizmu v této části populace. Riziko trombózy záleží na mnoha faktorech, a to jak na straně ženy, tak na typu antikoncepce. Hematolog může pomoci při výběru antikoncepce u žen s vrozenou trombofilií a u žen po prodělané trombóze – jako velmi výhodné se jeví intrauterinní tělísko s levonorgestrelem.

Venous thromboembolism is a multifactorial dis ease and major cause of morbidity and mortality. Absolute risk of venous thromboembolism is less than 1 per 10,000 per year in women of reproductive age. Hormonal contraception is a common risk situation for venous thromboembolism in this part of the population. The risk of venous thrombosis depends on many factors, mainly female characteristics and also the type of contraception. Hematologists can help with the choice of contraception in females with inherited thrombophilia and females experiencing thrombosis. Intrauterine devices with levonorgestrel seem to be the best option in these settings.

• MeSH
• hodnocení rizik MeSH
• hormonální antikoncepce * klasifikace   škodlivé účinky   MeSH
• lidé MeSH
• nitroděložní tělíska hormonální klasifikace   MeSH
• rezistence k aktivovanému proteinu C diagnóza   genetika   MeSH
• trombofilie chemicky indukované   diagnóza   etiologie   vrozené   MeSH
• žilní tromboembolie * diagnóza   etiologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

We report a very unusual case of melanocytic neoplasm appearing clinically as a 0.5-cm dome-shaped pigmented papule on the chest of a 63-year-old man. Microscopically, it was an asymmetric, entirely dermally based neoplasm characterized by a multinodular, vaguely plexiform architecture composed of moderately pleomorphic spindled melanocytes with ample, dusty pigmented cytoplasm and scattered multinucleated cells. The tumor cells were strongly positive for Melan-A, HMB45, S100, and PRAME, whereas p16 showed diffuse nuclear loss. β-catenin presented a strong and diffuse cytoplasmic staining, while nuclei were negative. Despite an increased cellularity, mitotic count was low (1/mm 2 ). Fluorescence in situ hybridization revealed no copy number alteration in melanoma-related genes ( CDKN2A, MYB, MYC, CCND1 and RREB1 ). DNA and RNA sequencing identified KIT c.2458G>T and APC c.6709C>T mutations. No further genetic alteration was detected including TERT-promoter (TERT-p ) hot-spot mutation. A re-excision was performed. A sentinel lymph node biopsy was negative. Clinical investigations revealed no extracutaneous involvement. The patient is disease-free after a follow-up period of 8 months. Given the peculiar morphologic and molecular findings, we hypothesize the lesion may represent a novel subtype of an intermediate grade melanocytic tumor (melanocytoma).

• MeSH
• antigeny nádorové MeSH
• biopsie sentinelové lymfatické uzliny MeSH
• hybridizace in situ fluorescenční MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanocyty patologie   MeSH
• melanom * patologie   MeSH
• mutace MeSH
• nádory kůže * patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Antigen-presenting cells (APCs) are master regulators of the immune response by directly interacting with T cells to orchestrate distinct functional outcomes. Several types of professional APC exist, including conventional dendritic cells, B cells and macrophages, and numerous other cell types have non-classical roles in antigen presentation, such as thymic epithelial cells, endothelial cells and granulocytes. Accumulating evidence indicates the presence of a new family of APCs marked by the lineage-specifying transcription factor retinoic acid receptor-related orphan receptor-γt (RORγt) and demonstrates that these APCs have key roles in shaping immunity, inflammation and tolerance, particularly in the context of host-microorganism interactions. These RORγt+ APCs include subsets of group 3 innate lymphoid cells, extrathymic autoimmune regulator-expressing cells and, potentially, other emerging populations. Here, we summarize the major findings that led to the discovery of these RORγt+ APCs and their associated functions. We discuss discordance in recent reports and identify gaps in our knowledge in this burgeoning field, which has tremendous potential to advance our understanding of fundamental immune concepts.

• MeSH
• antigen prezentující buňky metabolismus   MeSH
• endoteliální buňky MeSH
• jaderné receptory - podrodina 1, skupina F, člen 3 * metabolismus   MeSH
• lidé MeSH
• lymfocyty * MeSH
• přirozená imunita MeSH
• transportní proteiny metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The combination of Turner's syndrome, factor 5 Leiden and fibrinogen 1 deficiency is extremely rare. The modified Bentall procedure is a viable option for the management of aortic aneurysms and bicuspid aortic valves in Turner's syndrome to minimise the risks associated with high-risk surgical interventions. We report details of the successful implementation of the Bentall operation in a patient with Turner's syndrome complicated by aortic aneurysm, bicuspid aorta, factor 5 Leiden and fibrinogen deficiency.

Kombinace Turnerova syndromu, leidenské mutace (mutace faktoru V Leiden) a deficitu fibrinogenu 1 se vyskytuje velmi vzácně. Modifikovaná Bentallova operace představuje proveditelný způsob řešení aneurysmat aorty a dvojcípých aortálních chlopní u Turnerova syndromu s cílem omezit na minimum rizika spojená s vysoce rizikovými chirurgickými výkony. V této kazuistice podrobně popisujeme úspěšné provedení Bentallovy operace u pacienta s Turnerovým syndromem komplikovaným aneurysmatem aorty, dvojcípou aortální chlopní, mutací faktoru V Leiden a deficitem fi brinogenu 1.

• MeSH
• afibrinogenemie patologie   MeSH
• aortální stenóza * etiologie   patologie   MeSH
• diagnostické zobrazování metody   MeSH
• dospělí MeSH
• kardiochirurgické výkony * metody   MeSH
• lidé MeSH
• rezistence k aktivovanému proteinu C komplikace   MeSH
• Turnerův syndrom * komplikace   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Control mechanisms of spindle assembly and chromosome segregation are vital for preventing aneuploidy during cell division. The mammalian germ cells and embryos are prone to chromosome segregation errors, and the resulting aneuploidy is a major cause of termination of development or severe developmental disorders. Here we focused on early mouse embryos, and using combination of methods involving microinjection, immunodetection and confocal live cell imaging, we concentrated on the Spindle Assembly Checkpoint (SAC) and Anaphase Promoting Complex/Cyclosome (APC/C). These are two important mechanisms cooperating during mitosis to ensure accurate chromosome segregation, and assessed their activity during the first two mitoses after fertilization. Our results showed, that in zygotes and 2-cell embryos, the SAC core protein Mad1 shows very low levels on kinetochores in comparison to oocytes and its interaction with chromosomes is restricted to a short time interval after nuclear membrane disassembly (NEBD). Exposure of 2-cell embryos to low levels of spindle poison does not prevent anaphase, despite the spindle damage induced by the drug. Lastly, the APC/C is activated coincidentally with NEBD before the spindle assembly completion. This early onset of APC/C activity, together with precocious relocalization of Mad1 from chromosomes, prevents proper surveillance of spindle assembly by SAC. The results contribute to the understanding of the origin of aneuploidy in early embryos.

• Publikační typ
• časopisecké články MeSH

The aim of this study was to determine the thrombogenicity of lupus anticoagulant (LA) antibodies using a modified thrombin generation assay (TGA) with the addition of activated protein C (APC) in a group of 85 patients with LA-positive samples. Of these, 58 patients had clinical manifestations of antiphospholipid syndrome (APS) according to the Sydney criteria classification, i.e., each patient had thrombosis or foetal loss, and 27 patients did not show any clinical manifestations of APS. A comparison of the two groups' TGA results revealed statistically significant differences (Fisher's test p = 0.0016). The group of patients exhibiting clinical manifestations of APS showed higher thrombogenicity in 56.9% of patients, while the group of patients not yet exhibiting clinical manifestations of APS showed higher thrombogenicity in 25.9% of patients. There were no significant differences in the specificity of the TGA test between the groups of patients exhibiting similar clinical manifestations. Receiver operating characteristic curve analysis showed a more significant relationship (p = 0.0060) for TGA than for LA titre (p = 0.3387). These data suggest that the determination of LA thrombogenicity with the TGA assay leads to an increased prediction of the manifestation of a thromboembolic event. Our findings appear to be particularly relevant for the prediction of thrombotic events in patients with laboratory-expressed APS and no clinical manifestations.

• Publikační typ
• časopisecké články MeSH

The aim of this study was to determine the effects of Tarantula cubensis alcoholic extract (TCAE) on tumour development pathways in azoxymethane (AOM)-induced colorectal cancer in rats by molecular methods. Eighteen paraffin-embedded intestinal tissues, six from each group, were studied in the healthy control (C), cancer control (CC), cancer + TCAE (C-TCAE) groups. Sections of 5 μm thickness were taken from the paraffin blocks and submitted to staining with haematoxylin-eosin. In the histopathological examination, the number of crypts forming aberrant crypt foci (ACF) and the degree of dysplasia in the crypts were scored. Real-time PCR analysis was completed to determine β-catenin, KRAS (Kirsten rat sarcoma virus), APC (adenomatous polyposis coli) and P53 expressions on samples from each paraffin block. The grading scores of the number of crypts forming ACF and dysplasia in the crypts showed an evident decrease in the C-TCAE group in comparison to the CC group (P < 0.05). In real-time PCR analysis, mRNA expression levels of P53 (P > 0.05) and APC (P < 0.001) genes were found to be increased in the C-TCAE group according to the CC group. The expression levels of KRAS (P < 0.01) and β-catenin (P < 0.005) mRNA were found significantly decreased in the C-TCAE group. In conclusion, the effects of TCAE on AOM-induced colorectal cancer (CRC) in rats were evaluated molecularly; TCAE was found to modulate some changes in CRC developmental pathways, inhibiting tumour development and proliferation, and stimulating non-mutagenic tumour suppressor genes. Thus, it can be stated that TCAE is an effective chemopreventive agent.

Vysokoškolská učebnica, ktorá sa zameriava na trombofíliu a žilový tromboembolizmus.

• MeSH
• hematologie MeSH
• kardiologie MeSH
• trombofilie MeSH
• žilní tromboembolie MeSH

• Konspekt
• Patologie. Klinická medicína
• Učební osnovy. Vyučovací předměty. Učebnice
• NLK Obory
• angiologie
• hematologie a transfuzní lékařství
• NLK Publikační typ
• učebnice vysokých škol

Antiphospholipid syndrome (APS) is a hypercoagulable state accompanied by the presence of heterogeneous antiphospholipid antibodies (aPL), which nonspecifically affect hemostasis by the presence of lupus anticoagulans (LA), anticardiolipin antibodies (aCL), antibodies against β2-glycoprotein-I (anti-β2GPI), but also non-criteria antibodies such as antibodies against β2-glycoprotein-I domain I (anti-DI), anti-phosphatidylserine/prothrombin (anti-PS/PT), anti-annexin V, and many others. The main target of the antibodies is the activated protein C (APC) system, the elimination of which can manifest itself as a thrombotic complication. The aim of this study was to determine the thrombogenicity of antibodies using a modified protein C-activated thrombin generation assay (TGA) on a group of 175 samples suspected of APS. TGA was measured with/without APC and the ratio of both measurements was evaluated (as for APC resistance), where a cut-off was calculated ≤4.5 (90th percentile) using 21 patients with heterozygous factor V Leiden mutation (FV Leiden heterozygous). Our study demonstrates the well-known fact that multiple positivity of different aPLs is a more severe risk for thrombosis than single positivity. Of the single antibody positivity, LA antibodies are the most serious (p value < 0.01), followed by aCL and their subgroup anti-DI (p value < 0.05). Non-criteria antibodies anti-annexin V and anti-PT/PS has a similar frequency occurrence of thrombogenicity as LA antibodies but without statistical significance or anti-β2GPI1 positivity. The modified TGA test can help us identify patients in all groups who are also at risk for recurrent thrombotic and pregnancy complications; thus, long-term prophylactic treatment is appropriate. For this reason, it is proving increasingly beneficial to include the determination antibodies in combination with modified TGA test.

• MeSH
• antifosfolipidové protilátky MeSH
• antifosfolipidový syndrom * komplikace   MeSH
• antikardiolipinové protilátky MeSH
• beta-2-glykoprotein I MeSH
• fosfatidylseriny MeSH
• lidé MeSH
• protein C MeSH
• protrombin MeSH
• těhotenství MeSH
• trombin MeSH
• trombóza * etiologie   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

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• MeSH
• cévní endotel patologie   MeSH
• fibrin-fibrinogen - produkty degradace analýza   MeSH
• heparin nízkomolekulární aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• heparin aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• INR metody   MeSH
• komplikace těhotenství * etiologie   MeSH
• lidé MeSH
• natriuretický peptid typu B MeSH
• radiografie MeSH
• rezistence k aktivovanému proteinu C komplikace   patologie   MeSH
• rizikové faktory MeSH
• trombektomie metody   MeSH
• warfarin farmakologie   škodlivé účinky   toxicita   MeSH
• žilní tromboembolie farmakoterapie   patofyziologie   MeSH
• žilní trombóza * farmakoterapie   patofyziologie   MeSH
• Check Tag
• lidé MeSH