Paweł P Liberski

..Neuropathologically, kuru is characterized by the presence of amyloid "kuru" plaques...

..In several families with GSS the responsible mutations are unknown...

..The enormous impact of structural biological studies is also stressed...

..In addition, we show here for the first time confocal laser microscopy studies of co-localization of PrPd- amyloid plaques and GFAP-expressing astrocytes...

..On a basis of ultrastructural studies, we suggest that autophagy plays a major role in transmissible spongiform encephalopathies (TSEs) and may even participate in a formation of spongiform change...

..It was one of the greatest discoveries in biomedical sciences of the 20th century...

..For obvious reasons, we should hope for the botanical alternative...

..This study confirms the TSE-specificity of TVS, the morphology of which suggests a possible pathogenetic role and relationship to recently described virion-like arrays of 25nm particles in scrapie-infected tissue cultures...

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..An analogous network of narrow cisterns was seen to surround whole segments of the myelinated fibers...

..On the basis of ultrastructural studies, we suggest that autophagy may play a major role in transmissible spongiform encephalopathies and may even participate in the formation of spongiform change...

..And perhaps most importantly, the realization of 'protein-misfolding diseases', including not only the neurodegenerative but also an increasing number of non-neurological disorders, would have been delayed by decades...

..Vin Zigas to Dr. John Gunter in 1956. In March 1957, Gajdusek joined Zigas, who at that time was a medical patrol officer in Kainantu, Eastern Highland District of the Territory of Papua New Guinea...

..Finally, a large area of the cytoplasm was transformed into a collection of autophagic vacuoles of different sizes. Virtually identical alterations, albeit with much lower frequency, were seen in terminally ill CJD-affected hamsters...

..Several mylinated fibres were clearly engulfed by the cytoplasm of a macrophage containing unusual annulate lamellae...

..The third, and most striking, consisted of perineuronal deposits. These formed small dots and coarser globules which were densely situated on the neuronal membrane on both cell bodies and their processes...

..None of these observations distinguish between TVS as an entity critical to the infectious process, or as a highly specific ultrastructural epiphenomenon, but their consistent presence in all TSEs demands further research...

..In the second part of this review the experimental data using experimental models of GSS in transgenic mice are summarised as well as structural biology of mutated PrP in GSS...

..Ultrastructurally, plaques were recognised as areas of low electron density containing haphazardly-oriented fibrils which, when immunogold techniques were applied, were heavily decorated with PrP-conjugated gold particles...

..The composition of TVS is unknown but they are not composed of PrP. Their consistent presence in all TSEs suggests the role at least of TSE pathogenesis...

..However, recently developed techniques and the careful examination of the molecular processes leading to different types of cell death should provide the answer in future...

..An interesting interaction between astrocytes and oligodendrocytes is discussed in detail as well as a particular form of astrocytic reaction in panencephalopathic form of TSEs...

..The authors conclude that autophagy is an important part of neuropathology in prion disease. They also suggest that spongiform vacuoles, a hallmark for the whole group of prion diseases, may in reality originate from autophagic vacuoles...

..We suggested that vacuoles may develop through process of autophagy...

..We also review the peculiarities of kuru, variant Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker disease...

..Occasional dystrophic neurites containing electron-dense inclusion bodies were seen within the plaque perimeter, which always remained PrP-negative...

..In contrast, mice infected with the panencephalopathic Fujisaki strain of CJD exhibited much more elaborate changes of myelinated fibres...

..We conclude that TVS are readily found in FFI, vCJD and sCJD and that widespread neuritic degeneration is a part of ultrastructural pathology in prion diseases...

..Thus, we discuss the nature of tubulovesicular structures (TVS), the only diseases-specific particles known so far and the association between TVS and PrP fibrils which was recently discovered...

..While the nosological position of these diseases is well understood, the nature of the agent is still a matter of dispute. There is no doubt, however, that the gene for PrP plays a major role in the whole group of neurodegenerations...

..e., composed of dystrophic neurites with little or no amyloid, were found only in a P102L case from the original Austrian family. In 2 cases of sporadic CJD, the kuru stellate plaque predominated...

..In mice infected with the Fujisaki strain of GSS, fibres had undergone demyelination with stripping of the myelin lamellae, while others showed vesicular myelin degeneration...

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..If all the advice is taken and measures enforced there is a prospect that BSE can be eliminated from countries and regions as a prelude to eradication from the world...

..g. Glia-Derived Neurotrophic Factor [GDNF]) or proinflammatory and neurotoxic (e.g. tumour necrosis factor alpha [TNF-α], interleukin 1β [IL-1β], nitric oxide [NO], superoxide, eicosanoids, quinolinic acid)...

..In a few specimens there were round electron-dense structures that we identified as aggresomes. Aggresomes are not membrane-bound and were found in the cytoplasm of a few neurons...

..3% were homozygous for methionine, 13.3% homozygous for valine and 13.3% were heterozygous. The novel missense mutation (ATG-->ACG) at codon 232 was identified in one of the samples with a GSS phenotype...

..It is of special note that in the cytoplasm of several cells as well as the axoplasm numerous autophagic vacuoles were seen...

..A precise estimation of the exact significance of particular polymorphisms in BPSD etiology requires future studies on large populations...

..Some microglial cells were observed in close contact with PrP-positive plaques, and secondary lysosomes within these cells were heavily decorated with gold particles...

..A significant difference appeared also between early-onset (<70 years) and late-onset (> or = 70 years) AD patients in the PRND genotypes...

..As already reported, a few spongiform vacuoles were visible in the same area by conventional H and E staining. In several other sections, vacuoles were visible but no PrPd staining could be detected...

..PrP immunohistochemistry reveals different types of PrP(Sc) deposits - the most common is the synaptic-type, but perivacuolar, perineuronal and plaque-like deposits may be also detected...

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..In this review, we summarize some data on the epidemiology, neuropathology and clinical picture of kuru...

..PcG genes play an important role in developmental processes; they are also involved in the self-renewal of hematopoietic and neural stem cells as well as in malignant transformation...

..We suggest that the incidence of TP53 mutations in pleomorphic xanthoastrocytoma may be underestimated and that molecular approaches should be used for greater diagnostic precision...

..Thus, GAPDH may be recommended for data normalization in gene expression studies in astrocytomas. Nevertheless, a preliminary validation of reference gene stability is required prior to every study...

..Collectively, they are more similar to neuritic plaques of Alzheimer's disease than to kuru plaques of kuru--Creutzfeldt-Jakob disease--Gerstmann-Sträussler-Sheinker disease...

..In this review I covered recent data on the vCJD and BSE epidemic, the mode of BSE spreading to humans and, finally, the data on the PRNP analogue--the doppel gene (PRND)...

..Occasional dystrophic neurites containing electron-dense inclusion bodies were seen within the plaque perimeter, which always remained PrP-negative...

..Tubulovesicular structures (TVS) were found in every case including FFI and nvCJD. Thus, TVS, as we suggested previously are important pathologic structure which significance should be more extensively studied...

..The very existence of TVS and their correlation with infectivity, therefore, urgently needs an explanation...

..Secondary glioblastomas retained clear stigmata of astrocytic tumor but the nuclei seemed to be more intended, cisterns of the endoplasmic reticulum appeared to be distended and frequently intranuclear pseudoinclusions were observed...

..The developed computer system will collect and store image data and exchange them by network with other collaborated systems...

..In a case of anaplastic meningioma, a mitotic figure was found. In another case, empty rectangular spaces in the cytoplasm, suggestive of pre-existing crystalloid structures, were seen...

..Our work confirmed that the neuronal differentiation of GBM was inhibited at the stage of the neuronal intermediate phenotype. Moreover, we showed that the oligodendrocytic differentiation of GBM cells is very inefficient...

..There was no coexistence of mutations in both analyzed genes. Our analysis confirms the presence of the hSNF5/INI1 mutations and proves involvement of TP53 mutations in sporadic cases of CPC...

..Unusual crystalloids were observed in the white matter. In conclusion, experimental BSE in pigs demonstrated ultrastructural pathology in keeping with that observed in other spongiform encephalopathies...

..012 with a standard deviation (SD) of 0.032, for medulloblastomas 0.021 (SD 0.04), for ependymomas 0.001 (SD 0.002) and for anaplastic ependymomas 0.004 (SD 0.003)...

..According to ROC curve analysis the maximum accuracy in discriminating MCI versus both controls and AD subjects has been achieved using a cut-off value of 3.8...

..Recently published data showed discrepancies between P53 cDNA and DNA sequencing in glioblastomas. We hypothesised that similar discrepancies may be observed in other human cancers...

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..These cases were reclassified as gangliogliomas (GG). None of the 11 tumors recognized as GG was reclassified as PA. The overall 5-year survival was 88.89% in the PA and 70% in GG groups...

..This theory had been recently extended to cover other neurodegenerations which are caused by misfolded proteins; these disease are called prionoids...

..Therefore, the role of the PRND gene in CJD and other diseases still remains unexplained...

..We argue that recognition of the gene or genes important in MB tumorigenesis depends in part on defining an appropriate control...

..The most intriguing ultrastructural finding was abundant presence of autophagic vacuoles. In 4 cases, multivesicular bodies were observed. All of the tumors with multivesicular bodies also contained abundant autophagic vacuoles...

..Moreover, there may be multiple sufficient risk sets for AD. Looking at multiple genes together rather than analyzing them individually, may improve identification of risk alleles...

..Of note, glial and neuronal cells showed a very large heterogeneity of PrP(c) expression. Our results provide the basis for studying the role of PrP(c) in cell differentiation and neurogenesis from human GFAP-positive progenitor cells...

..Autophagic vacuoles are formed in many synapses in all categories of human transmissible encephalopathies. We conclude that synaptic autophagy contributes to overall synaptic loss in brains affected in prion diseases...

..These results strongly suggest that some sort of mechanism(s) favouring mutated over wild-type P53 mRNA exists in glioblastoma cells with heterozygous mutations of this gene...

..05). Our data provide evidence that use of molecular genetic analyses of chromosomes 1p, 19q, and 10q might improve the diagnosis of gliomas...

..These results improve the understanding of the regulation of the Prnp gene promoter, a DNA regulatory element controlling the expression of PrP(C), a protein involved in several neurological diseases...

..However, considering the extreme divergence of results obtained by different authors, a clear connection between the CYP46 gene and AD is questionable...

..To this end, we strived to obtain stabilized protocol of NHA cells differentiation - allowing for an increase in percentage yield of neuronal cells...

..43%, p=0.03). The association between the hCV1558625 G allele and susceptibility for AD at relatively young ages needs to be confirmed in other samples...

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..We conclude that patients with incompletely removed DNT may suffer local recurrence of that tumour. In rare cases development of a secondary, histologically different neoplasm may also occur...

..Further, it may constitute a new distinct clinicopathological entity with neoplastic and hamartomatous features...

..LOH on 10q and 17p was found in both primary and recurrent tumor, while losses on 11p, 16p, and 16q occurred only in the recurrent tumor. No evidence of alteration in TP53 exon 4 was identified...

..Loss of heterozygosity (LOH) on 1p and 19q is observed in most oligodendroglial tumors. LOH on 10q appears to be less common in these tumors as compared to other gliomas...

..Compared to the extensive neuronal loss (30-50%), the number of apoptotic cells detected by in situ end labelling seems to be very low, and the process of neuronal death become more intensive during the progression of the disease...

..INI1 (hSNF5) mutations are linked to rhabdoid tumours, but mutations in meningiomas with hot spot mutations in position 377 have also been reported...