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Abstract Background Epstein-Barr virus (EBV) is the causative agent of immunosuppression associated lymphoproliferations such as post-transplant lymphoproliferative disorder (PTLD), AIDS related immunoblastic lymphomas (ARL) and immunoblastic lymphomas in X-linked lymphoproliferative syndrome (XLP). The reported overall mortality for PTLD often exceeds 50%. Reducing the immunosuppression in recipients of solid organ transplants (SOT) or using highly active antiretroviral therapy in AIDS patients leads to complete remission in 23–50% of the PTLD/ARL cases but will not suffice for recipients of bone marrow grafts. An additional therapeutic alternative is the treatment with anti-CD20 antibodies (Rituximab) or EBV-specific cytotoxic T-cells. Chemotherapy is used for the non-responding cases only as the second or third line of treatment. The most frequently used chemotherapy regimens originate from the non-Hodgkin lymphoma protocols and there are no cytotoxic drugs that have been specifically selected against EBV induced lymphoproliferative disorders. Methods As lymphoblastoid cell lines (LCLs) are well established in vitro models for PTLD, we have assessed 17 LCLs for cytotoxic drug sensitivity. After three days of incubation, live and dead cells were differentially stained using fluorescent dyes. The precise numbers of live and dead cells were determined using a custom designed automated laser confocal fluorescent microscope. Results Independently of their origin, LCLs showed very similar drug sensitivity patterns against 29 frequently used cytostatic drugs. LCLs were highly sensitive for vincristine, methotrexate, epirubicin and paclitaxel. Conclusion Our data shows that the inclusion of epirubicin and paclitaxel into chemotherapy protocols against PTLD may be justified.

Az online térben nagy népszerűségnek örvend a világ egyik legnagyobb videómegosztó platformja, a YouTube, ahol a nézők véleményezhetik a videókat és azok témáit. A tanulmány célja annak vizsgálata, hogy a napjaink gazdasági-társadalmi változásaival párhuzamosan egyre nagyobb figyelmet kapó feltétel nélküli alapjövedelemmel kapcsolatban hazánkban milyen értékek és vélemények rajzolódnak ki a YouTube ilyen témájú videóinak kommentszekciójában. Kutatásunk vegyes módszerrel dolgozik, az adatok gyűjtése, tárolása, szentimentanalízise és a szózsák módszere informatikai eljárásokkal valósult meg, míg a kategorizálás kézi kódolás révén. A szentimentanalízis eredménye mutatja, hogy a pozitív érvek kisebb arányban merülnek fel a megjegyzésekben. Olyan értékjellemzőkkel bírnak, mint a befogadás, a létjogán elv, az igazságosság és a szabadság hangsúlyozása. A pozitív érvek közül a legmagasabb támogatottságot a megvalósíthatóság képezi. A negatív kategóriájú értékek gyakrabban merülnek fel, így a másodrangú lét, igazságtalanság, kirekesztés, megfizethetetlenség és a teljesítményelvűség értékeinek hangsúlyozása domináns az elemzett megjegyzésekben.

The geology of the NE Hungarian Darnó Unit is rather complicated, as it is composed mostly of a Jurassic accretionary mélange complex, according to the most recent investigations. The magmatic and sedimentary rock blocks of the mélange represent products of different evolutionary stages of the Neotethys; including Permian and Triassic sedimentary rocks of marine rifting related origin, Triassic pillow basalt of advanced rifting related origin and Jurassic pillow basalt originated in back-arc-basin environment. This small unit contains a copper-gold occurrence in the Permian marly-clayey limestone, an iron enrichment in the Triassic sedimentary succession, a copper-silver ore occurrence in Triassic pillow basalts and a copper ore indication, occurring both in the Triassic and Jurassic pillow basalts. The present study deals with the Cu(-Ag) occurrence in the Triassic basalt and the Fe occurrence in the Triassic sedimentary succession. The former shows significant similarities with the Michigan-type mineralizations, while the latter has typical characteristics of the Fe-SEDEX deposits. All the above localities fit well into the new geological model of the investigated area. The mineralizations represent the different evolutionary stages of the Neotethyan rifting and an epigenetic, Alpine metamorphism-related process and their recent, spatially close position is the result of the accretionary mélange formation. Thus, the Darnó Unit represents a perfect natural laboratory for studying and understanding the characteristic features of several different rifting related ore forming processes.

Abstract Background Peutz-Jeghers syndrome (PJS) is a rare autosomal dominantly inherited disease characterized by gastrointestinal hamartomatous polyposis and mucocutaneous pigmentation. The genetic predisposition for PJS has been shown to be associated with germline mutations in the STK11/LKB1 tumor suppressor gene. The aim of the present study was to characterize Hungarian PJS patients with respect to germline mutation in STK11/LKB1 and their association to disease phenotype. Methods Mutation screening of 21 patients from 13 PJS families were performed using direct DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). Comparative semi-quantitative sequencing was applied to investigate the mRNA-level effects of nonsense and splice-affecting mutations. Results Thirteen different pathogenic mutations in STK11, including a high frequency of large genomic deletions (38%, 5/13), were identified in the 13 unrelated families studied. One of these deletions also affects two neighboring genes (SBNO2 and GPX4), located upstream of STK11, with a possible modifier effect. The majority of the point mutations (88%, 7/8) can be considered novel. Quantification of the STK11 transcript at the mRNA-level revealed that the expression of alleles carrying a nonsense or frameshift mutation was reduced to 30-70% of that of the wild type allele. Mutations affecting splice-sites around exon 2 displayed an mRNA processing pattern indicative of co-regulated splicing of exons 2 and 3. Conclusions A combination of sensitive techniques may assure a high (100%) STK11 mutation detection frequency in PJS families. Characterization of mutations at mRNA level may give a deeper insight into the molecular consequences of the pathogenic mutations than predictions made solely at the genomic level.

The known susceptibility genes for breast cancer, including BRCA1 and BRCA2, only account for a minority of the familial aggregation of the disease. A recent study of 77 multiple case breast cancer families from Scandinavia found evidence of linkage between the disease and polymorphic markers on chromosome 13q21. We have evaluated the contribution of this candidate "BRCA3" locus to breast cancer susceptibility in 128 high-risk breast cancer families of Western European ancestry with no identified BRCA1 or BRCA2 mutations. No evidence of linkage was found. The estimated proportion (alpha) of families linked to a susceptibility locus at D13S1308, the location estimated by Kainu et al. [(2000) Proc. Natl. Acad. Sci. USA 97, 9603-9608], was 0 (upper 95% confidence limit 0.13). Adjustment for possible bias due to selection of families on the basis of linkage evidence at BRCA2 did not materially alter this result (alpha = 0, upper 95% confidence limit 0.18). The proportion of linked families reported by Kainu et al. (0.65) is excluded with a high degree of confidence in our dataset [heterogeneity logarithm of odds (HLOD) at alpha = 0.65 was -11.0]. We conclude that, if a susceptibility gene does exist at this locus, it can only account for a small proportion of non-BRCA1/2 families with multiple cases of early-onset breast cancer.