We evaluated the genetic contribution of the T cell-restricted intracellular antigen-1 gene (TIA1) in a European cohort of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) patients. Exonic resequencing of TIA1 in 1120 patients (693 FTD, 341 ALS, 86 FTD-ALS) and 1039 controls identified in total 5 rare heterozygous missense variants, affecting the TIA1 low-complexity domain (LCD). Only 1 missense variant, p.Met290Thr, identified in a familial FTD patient with disease onset at 64 years, was absent from controls yet received a combined annotation-dependent depletion score of 11.42. By contrast, 3 of the 4 variants also detected in unaffected controls, p.Val294Glu, p.Gln318Arg, and p.Ala381Thr, had combined annotation-dependent depletion scores greater than 20. Our findings in a large European patient-control series indicate that variants in TIA1 are not a common cause of ALS and FTD. The observation of recurring TIA1 missense variants in unaffected individuals lead us to conclude that the exact genetic contribution of TIA1 to ALS and FTD pathogenesis remains to be further elucidated.

• MeSH
• amyotrofická laterální skleróza genetika   MeSH
• běloši genetika   MeSH
• frekvence genu MeSH
• frontotemporální demence genetika   MeSH
• kohortové studie MeSH
• lidé MeSH
• missense mutace MeSH
• T-buněčný intracelulární antigen 1 genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Prezentujeme případ 54 leté ženy s dediferencovaným karcinomem ovária. Makroskopicky byla obě ovária prostoupena nádorovými strukturami dosahujícími v největším rozměru 25 mm (pravé ovárium) a 220 mm (levé ovárium). Mikroskopicky se jednalo o nádory tvořené strukturami dobře diferencovaného endometroidního karcinomu. V levém ováriu však byla kromě toho ještě zastižena nediferencovaná solidní komponenta tvořená většími buňkami. Při imunohistochemickém vyšetření byla tato komponenta difúzně pozitivní při průkazu vimentinu a fokálně při průkazu cytokeratinu 18. Ostatní vyšetřované markery včetně PAX8, estrogenních a progesteronových receptorů byly negativní. Dediferencované karcinomy ovária jsou vzácné nádory tvořené komponentou nediferencovaného karcinomu a endometroidního karcinomu grade 1 nebo 2. Klinicky se jedná o agresivní nádory se špatnou prognózou, které se častěji vyskytují spíše v endometriu, v ováriu bylo dosud popsáno pouze 6 případů.

We report the case of a 54-year-old female with dedifferentiated carcinoma of the ovary. Grossly, both ovaries were affected by a tumor of up to 25 mm (right ovary) and 220 mm (left ovary) in diameter. Microscopically, the tumors of both ovaries showed features of well differentiated endometrioid carcinoma with mucinous differentiation. Moreover, in the left ovary there was an undifferentiated solid component consisting of larger cells. Immunohistochemically, the undifferentiated component showed diffuse vimentin positivity and focal expression of cytokeratin 18. Other markers examined including PAX8, estrogen receptors and progesterone receptors were all negative. Dedifferentiated carcinomas consist of an undifferentiated epithelial component and a component of endometrioid carcinoma of FIGO grade 1 or 2. Clinically, they represent aggressive tumors with unfavorable prognosis mostly occurring in the endometrium. To the best of our knowledge, thus far only 6 cases arising in the ovary have been reported in the literature.

• MeSH
• endometroidní karcinom * diagnóza   klasifikace   patologie   MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory vaječníků * diagnóza   patologie   MeSH
• prognóza MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• práce podpořená grantem MeSH

Lipasin is a recently identified lipokine expressed predominantly in liver and in adipose tissue. It was linked to insulin resistance in mice and to type 1 and type 2 diabetes (T1D, T2D) in humans. No metabolic studies concerning lipasin were performed yet in rats. Therefore, we used rat model of T2D and insulin resistance, Goto-Kakizaki (GK) rats, to determine changes of lipasin expression in liver and in white adipose tissue (WAT) over 52 weeks in the relation to glucose tolerance, peripheral tissue insulin sensitivity and adiposity. GK rats were grossly glucose intolerant since the age of 6 weeks and developed peripheral insulin resistance at the age of 20 weeks. Expression of lipasin in the liver did not differ between GK and Wistar rats, declining with age, and it was not related to hepatic triacylglycerol content. In WAT, the lipasin expression was significantly higher in Wistar rats where it correlated positively with adiposity. No such correlation was found in GK rats. In conclusion, lipasin expression was associated neither with a mild age-related insulin resistance (Wistar), nor with severe genetically-based insulin resistance (GK).

• MeSH
• angiopoetinu podobné proteiny metabolismus   MeSH
• bílá tuková tkáň metabolismus   MeSH
• druhová specificita MeSH
• inzulinová rezistence fyziologie   MeSH
• játra metabolismus   MeSH
• krysa rodu rattus MeSH
• orgánová specificita fyziologie   MeSH
• peptidové hormony metabolismus   MeSH
• potkani Wistar MeSH
• regulace genové exprese fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Aging-related tau astrogliopathy (ARTAG) is a recently introduced terminology. To facilitate the consistent identification of ARTAG and to distinguish it from astroglial tau pathologies observed in the primary frontotemporal lobar degeneration tauopathies we evaluated how consistently neuropathologists recognize (1) different astroglial tau immunoreactivities, including those of ARTAG and those associated with primary tauopathies (Study 1); (2) ARTAG types (Study 2A); and (3) ARTAG severity (Study 2B). Microphotographs and scanned sections immunostained for phosphorylated tau (AT8) were made available for download and preview. Percentage of agreement and kappa values with 95% confidence interval (CI) were calculated for each evaluation. The overall agreement for Study 1 was >60% with a kappa value of 0.55 (95% CI 0.433-0.645). Moderate agreement (>90%, kappa 0.48, 95% CI 0.457-0.900) was reached in Study 2A for the identification of ARTAG pathology for each ARTAG subtype (kappa 0.37-0.72), whereas fair agreement (kappa 0.40, 95% CI 0.341-0.445) was reached for the evaluation of ARTAG severity. The overall assessment of ARTAG showed moderate agreement (kappa 0.60, 95% CI 0.534-0.653) among raters. Our study supports the application of the current harmonized evaluation strategy for ARTAG with a slight modification of the evaluation of its severity.

• MeSH
• astrocyty metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• proteiny tau metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stárnutí patologie   MeSH
• stupeň závažnosti nemoci MeSH
• tauopatie patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The Heidenhain form of Creutzfeldt-Jakob disease (CJD) is a rare CJD variant with predominantly visual symptoms in the early stages. Clinical manifestations of metamorphopsia, hemianopia and Balint's syndrome correlate with the involvement of the posterior cortical regions. A 71-year old healthy and very active man was admitted because of impaired visual acuity, hemianopia, and gait disturbance progressing over one week. MRI found typical cortical hyperintensities in the occipital regions while rhythm slowing and sharp waves were seen in the occipital regions on EEG. Protein 14-3-3 was detected in the cerebrospinal fluid. Postmortem neuropathology revealed typical histopathological changes consistent with CJD. Moreover, we found deposits of phosphorylated tau protein in the limbic regions that met the criteria for primary age-related tauopathy (PART); representing an additional and interesting finding in our case.

• MeSH
• Creutzfeldtova-Jakobova nemoc diagnóza   patologie   MeSH
• diferenciální diagnóza MeSH
• difuzní magnetická rezonance MeSH
• elektroencefalografie MeSH
• fatální výsledek MeSH
• fosforylace MeSH
• komorbidita MeSH
• lidé MeSH
• mozek patologie   MeSH
• neurologické vyšetření MeSH
• poruchy zraku diagnóza   patologie   MeSH
• proteiny 14-3-3 MeSH
• proteiny tau chemická syntéza   MeSH
• senioři MeSH
• tauopatie diagnóza   patologie   MeSH
• týlní lalok patologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

• MeSH
• biopsie přístrojové vybavení   metody   MeSH
• cerebelární ataxie diagnóza   etiologie   patologie   chirurgie   MeSH
• Creutzfeldtova-Jakobova nemoc komplikace   diagnóza   patologie   chirurgie   MeSH
• diferenciální diagnóza MeSH
• fatální výsledek MeSH
• lidé středního věku MeSH
• lidé MeSH
• mozek diagnostické zobrazování   patologie   chirurgie   MeSH
• point of care testing * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

PURPOSE: Wilms tumor gene 1 (WT1), a zinc-finger transcription factor essential for testis development and function, along with other genes, was investigated for their role in the pathogenesis of testicular germ cell tumors (TGCT). METHODS: In total, 284 TGCT and 100 control samples were investigated, including qPCR for WT1 expression and BRAF mutation, p53 immunohistochemistry detection, and massively parallel amplicon sequencing. RESULTS: WT1 was significantly (p < 0.0001) under-expressed in TGCT, with an increased ratio of exon 5-lacking isoforms, reaching low levels in chemo-naïve relapsed TGCT patients vs. high levels in chemotherapy-pretreated relapsed patients. BRAF V600E mutation was identified in 1% of patients only. p53 protein was lowly expressed in TGCT metastases compared to the matched primary tumors. Of 9 selected TGCT-linked genes, RAS/BRAF and WT1 mutations were frequent while significant TP53 and KIT variants were not detected (p = 0.0003). CONCLUSIONS: WT1 has been identified as a novel factor involved in TGCT pathogenesis, with a potential prognostic impact. Distinct biologic nature of the two types of relapses occurring in TGCT has been demonstrated. Differential mutation rate of the key TGCT-related genes has been documented.

• MeSH
• down regulace MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• geny ras * MeSH
• germinální a embryonální nádory enzymologie   genetika   patologie   MeSH
• imunohistochemie MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• mutace * MeSH
• mutační analýza DNA metody   MeSH
• nádorové biomarkery genetika   MeSH
• nádorové buněčné linie MeSH
• nádorový supresorový protein p53 genetika   MeSH
• prospektivní studie MeSH
• proteiny WT1 genetika   MeSH
• protoonkogenní proteiny B-raf genetika   MeSH
• protoonkogenní proteiny c-kit genetika   MeSH
• retrospektivní studie MeSH
• studie proveditelnosti MeSH
• testikulární nádory enzymologie   genetika   patologie   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakt z konference MeSH

• MeSH
• alfa-synuklein metabolismus   MeSH
• frontotemporální lobární degenerace patologie   MeSH
• lidé MeSH
• mozek patologie   MeSH
• multisystémová atrofie patologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH
• práce podpořená grantem MeSH

Meta-analysis of existing genome-wide association studies on Alzheimer's disease (AD) showed subgenome-wide association of an intronic variant in the sequestosome 1 (SQSTM1) gene with AD. We performed targeted resequencing of SQSTM1 in Flanders-Belgian AD patients selected to be enriched for a genetic background (n = 435) and geographically matched nonaffected individuals (n = 872) to investigate the role of both common and rare SQSTM1 variants. Results were extended to the European early-onset dementia cohorts (926 early-onset Alzheimer's disease [EOAD] patients and 1476 nonaffected individuals). Of the 61 detected exonic variants in SQSTM1, the majority were rare (n = 57). Rare variant (minor allele frequency <0.01) burden analysis did not reveal an increased frequency of rare variants in EOAD patients in any of the separate study populations nor when meta-analyzing all cohorts. Common variants p.D292= and p.R312= showed nominal association with AD (odds ratiop.D292= = 1.11 [95% confidence interval = 1-1.22], p = 0.04), only when including the Flanders-Belgian cohort in the meta-analysis. We cannot exclude a role of SQSTM1 genetic variability in late-onset AD, but our data indicate that SQSTM1 does not play a major role in the etiology of EOAD.

• MeSH
• adaptorové proteiny signální transdukční genetika   MeSH
• Alzheimerova nemoc epidemiologie   genetika   MeSH
• genetická variace genetika   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• metaanalýza jako téma MeSH
• riziko MeSH
• sekvenční analýza DNA MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Belgie MeSH