Biomedical subjects

P P Liberski

Publications and source records attributed to P P Liberski.

At least 19 recordsLinked to original sources

PubMed2005

Ultrastructural pathology of prion diseases revisited: brain biopsy studies.

We report here a detailed ultrastructural comparison of brain biopsies from 13 cases of Creutzfeldt-Jakob disease (CJD) and from one case of fatal familial insomnia (FFI). The latter disease has not heretofore benefited from ultrastructural study. In particular, we searched for tubulovesicular structures (TVS), 35-nm particles regarded as the only disease-specific structures at the level of thin-section electron microscopy. Our material consisted of brain biopsies obtained by open surgery from one FFI case from a new French family, one case of variant CJD (vCJD), nine cases of sporadic CJD (sCJD), two cases of iatrogenic (human growth hormone) CJD and one case of hereditary CJD (Val203Iso). The ultrastructural picture of the cerebral cortex of the FFI patient was virtually indistinguishable from that of CJD. TVS were found, albeit only after prolonged search. Typical spongiform change was observed, consisting of intracellular membrane-bound vacuoles containing secondary chambers (vacuoles within vacuoles) and amorphous material. Neuronal degeneration was widespread: some processes contained degenerating mitochondria and lysosomal electron-dense bodies and these met the criteria for neuroaxonal dystrophy. Other processes contained branching cisterns; still others were filled with electron-dense masses and amorphous vesicles. The overall ultrastructural appearance of variant CJD was similar to that of FFI cerebral cortex, except for a much higher number of cellular processes containing TVS. We detected TVS in the majority of sCJD cases that, in addition to typical spongiform change and robust astrocytic reaction, showed widespread neuritic and synaptic degeneration and autophagic vacuoles. 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.

Adult↗

PubMed2004

Polymorphisms within the prion (PrP) and prion-like protein (Doppel) genes in AD.

The authors present a study on the association of PRNP and PRND gene polymorphisms with the occurrence and age at onset of Alzheimer's disease (AD). DNA from 79 Polish patients with probable AD and 107 healthy control subjects was studied. The PRNP codon 129 homozygosity seemed to be associated with the occurrence of AD: In AD patients, the percentage of Val/Val and Met/Met genotypes was higher than in the control subjects. A significant difference appeared also between early-onset (<70 years) and late-onset (> or = 70 years) AD patients in the PRND genotypes.

Age of Onset↗

PubMed2003

Molecular heterogeneity of meningioma with INI1 mutation.

BACKGROUND: INI1 (hSNF5) mutations are linked to rhabdoid tumours, but mutations in meningiomas with hot spot mutations in position 377 have also been reported. AIMS: To analyse the INI1 gene in meningioma. METHODS: Exons 1, 4, 5, and 9 of the INI1 gene were analysed by the polymerase chain reaction and direct sequencing in 80 meningiomas. For all cases, western blotting of the INI1 protein was performed. RESULTS: Only one of the 80 samples showed a cytosine insertion in codon 376. This mutation changed the open reading frame in almost the whole exon 9 and resulted in a longer hSNF5 protein. Complex analysis of the above described tumour sample by western blotting, DNA sequencing, and loss of heterozygosity (LOH) analysis showed that this particular meningioma consisted of heterogeneic cellular components. One of these components had a mutated INI1 gene, whereas in the other component INI1 was intact. CONCLUSIONS: INI1 mutation is a rare event in the molecular pathology of meningiomas. It is possible for the INI1 gene to be mutated in only a proportion of meningioma cells.

Amino Acid Sequence↗

PubMed2001

Deposition patterns of disease-associated prion protein in captive mule deer brains with chronic wasting disease.

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) in captive and free-ranging cervids in the USA; its origin is obscure. Archival formalin-fixed and paraffin-embedded specimens of 16 captive mule deer brains with CWD were analyzed using immunocytochemistry for the disease-associated prion protein (PrP). The most prominent pattern of PrP deposition were plaque-like structures, a substantial proportion of which were florid plaques surrounded by a rim of spongiform vacuoles. The percentage of florid plaques was highly variable according to region, ranging from 0% to 52.7%. The highest percentage was observed in the medulla and basal ganglia, the lowest in the cerebral cortex. Only three brains contained no florid plaques. There were also punctate synaptic-type and perivascular deposits, particularly in areas of severe spongiform change, and subpial and subependymal plaque-like deposits, whereas cerebellar involvement was mild. Thus, CWD brain pathology prominently features florid PrP plaques, as does variant Creutzfeldt-Jakob disease (vCJD), but differs in other characteristics from vCJD.

Amino Acid Sequence↗

PubMed2001

Apoptosis in relation to neuronal loss in experimental Creutzfeldt-Jakob disease in mice.

Apoptosis constitutes a genetically determined process to eliminate superfluous or damaged cells in tissues. Deficiencies in apoptosis regulation are involved in different pathologies including prion diseases. Some experimental studies show that neuronal loss--one of the hallmarks of prion diseases may be accomplished by apoptosis. We evaluated twenty five mice infected experimentally with the Fujisaki strains of CJD and sacrified sequentially in one week intervals. Apoptotic cells in various brain regions were detected by in situ end labelling (TUNEL) and electron microscopy in comparison with neuronal cell loss. The number of labelled cells per brain was very low--from a few labelled cells 6 weeks after inoculation to a maximum of 14 in the terminal stage. The number of neurones counted in 8 selected areas were considerably lower in terminally sick animals (20 and 21 week of incubation period) than in control mice. The mean value of loss of neuronal cells was 32%. The greatest loss (55%) of neurones was noted in the septal nuclei of the paraterminal body and the least lost (16%) in the hypothalamus. 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.

Animals↗

PubMed2001

Codon 129 polymorphism of the PRNP gene in normal Polish population and in Creutzfeldt-Jakob disease, and the search for new mutations in PRNP gene.

Polymorphism at codon 129 of the prion protein gene (PRNP) is implicated both in susceptibility and phenotype of human prion diseases. We characterized the valine and methionine allele frequency at codon 129 in 109 individuals representing the normal Polish population and in 15 Polish CJD cases. The distribution of the genotype was 45% Met/Met, 39% Met/Val, and 16% Val/Val in the control group whereas, of the CJD cases, 73.3% 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.

Amino Acid Substitution↗

PubMed2001

Clinico-pathological analysis of pilocytic astrocytomas and gangliogliomas.

A pathological analysis of 58 pilocytic astrocytomas (PA) and 11 gangliogliomas (GG) was performed using immunohistochemistry. Antibodies against neuronal and glial markers (GFAP, SYN, NFP) were used. An analysis of survivors using the Kaplan Meier curve was also performed and compared with the literature reports. During the retrospective review of 58 cases recognized primarily as PA, 11 verified neoplasms demonstrated strong, immunopositive reaction for SYN or NFP or both antibodies. 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.

Adolescent↗

PubMed2001

[Prions, epidemic of Creutzfeldt-Jakob variant disease and global emergency].

We present here the current understanding of "prion" theory and global risk for epidemics of variant Creutzfeldt-Jakob disease (vCJD). Prion is the infectious agent of all transmissible spongiform encephalopaties (TSEs). It is regarded as an aggregate of a pathological conformer (PrPSc) of a normal cellular glycoprotein (PrPC) encoded by a gene, in humans on chromosome 20. The differences between PrPSc and PrPC are largely if not exclusively conformational; PrPC is mostly alpha-helical while PrPSc, beta-pleeted. Furthermore, mutations within the coding sequence (open reading frame) of PrP gene are linked with phenotypic expression of CJD, Gerstmann-Straussler-Scheinker disease (GSS) and fatal familial insomnia (FFI). VCJD is caused by transmission from cattle infected with bovine spongiform encephalopathy (BSE). PrP purified from vCJD-affected brains is characterised by the so called fourth type of glycosylation pattern. The neuropathological hallmark of vCJD is the florid plaque, an amyloid plaque surrounded by a corona of spongiform change. VCJD affects mostly young people (range: 13-74 years) and it is clinically distinguishable from sporadic CJD. The extent of epidemics is currently unknown; but its dynamic (102 cases until July 2001) may suggest "the worst" scenario.

Amyloid↗

PubMed2001

A special report I. Prion protein (Prp)--amyloid plaques in the transmissible spongiform encephalopathies (TSEs) or prion disease revisited.

We present a retrospective analysis of PrP-amyloid plaques encountered in CJD and GSS. In human TSEs (kuru, CJD and GSS) several PrP-immunopositive plaques and plaque-like deposits were detected. In kuru, plaques were typical "kuru" plaques--stellate structures deposited mostly in the granular and Purkinje cell layer of the cerebellum. Many smaller or larger clusters were visible but, in contrast to GSS, they never have merged together to form multicentric plaques. In all cases of GSS, plaques were located in the granular and Purkinje cell layer and in the molecular layer. There were many different forms of plaques: from kuru plaques (unicentric stellate plaques) to clusters of unicentric plaques which by merging eventually formed "multicentric plaques". The latter are the hallmark of this disease. By electron microscopy several types of amyloid plaques, which corresponded to those seen by PrP immunohistochemistry were observed. The first type, unicentric kuru plaque consisted of stellate arrangements (stars or cores) of amyloid bundles emanating from a densely interwoven center. Amyloid stars were surrounded by astrocytic processes and invaded by microglial cells but dystrophic neurites were only rarely seen. In contrast multicentric plaques were often surrounded by dystrophic neurites. The rarest type of plaque, were neuritic plaques. In 263K and 22C-H scrapie-infected hamster brains, on the light microscopy of the semi-thin (1 micron) sections, discrete PrP-immunopositive plaques were observed in the subependymal region but not in the deep brain neuroparenchyma. These plaques were not discernible by routine HE staining. Ultrastructurally, plaques were recognized as areas of low electron density containing haphazardly-oriented fibrils and not as stellate compact structures typical of plaques in human cases of CJD and GSS. These plaques were located beneath the basal border of the ependymal cells and adjacent blood vessels. Occasional dystrophic neurites containing electron-dense inclusion bodies were seen within the plaque perimeter, which always remained PrP-negative.

Animals↗

PubMed2001

A special report I. Prion protein (PrP)--amyloid plaques in the transmissible spongiform encephalopathies, or prion diseases revisited.

We present a retrospective analysis of PrP-amyloid plaques encountered in CJD and GSS. In human TSEs (kuru, CJD and GSS) several PrP-immunopositive plaques and plaque-like deposits were detected. In kuru, plaques were typical "kuru" plaques--stellate structures deposited mostly in the granular- and Purkinje-cell layer of the cerebellum. Many smaller or larger clusters were visible but, in contrast to GSS, they never merged together to form multicentric plaques. In all cases of GSS, plaques were localised in the granular- and Purkinje-cell layer and the molecular cell layer. There were many different forms of plaques: from kuru plaques (unicentric stellate plaques) to clusters of unicentric plaques, which by merging eventually formed "multicentric plaques". The latter are the hallmark of this disease. By electron microscopy, several types of amyloid plaques, which corresponded to those seen by PrP immunohistochemistry, were observed. The first type, unicentric "kuru" plaque, consisted of stellate arrangements (stars or cores) of amyloid bundles emanating from a densely interwoven centre. Amyloid stars were surrounded by astrocytic processes and invaded by microglial cells but dystrophic neurites were only rarely seen. In contrast, multicentric plaques were often surrounded by dystrophic neurites. The rarest type of plaque were neuritic plaques. In 263K- and 22C-H scrapie-infected hamster brains, by light microscopy and semi-thin (1 microm) sections, discrete PrP-immunopositive plaques were observed in the subependymal region but not in the deep brain neuroparenchyma. These plaques were not discernible by routine H & E staining. Ultrastructurally, plaques were recognised as areas of low electron density containing haphazardly-oriented fibrils and not as stellate compact structures typical of plaques in human cases of CJD and GSS. These plaques were located beneath the basal border of the ependymal cells and adjacent blood vessels. Occasional dystrophic neurites containing electron-dense inclusion bodies were seen within the plaque perimeter, which always remained PrP-negative.

Amyloid↗

PubMed2001

Tropical spastic paraparesis.

Human T-cell lymphotropic virus type I (HTLV-I) is the cause of endemic tropical spastic paraparesis (TSP) or HTLV-I-associated myelopathy (HAM). Because TSP/HAM is not a fatal disease, the neuropathology of this disease, albeit relatively well understood, is based on the examination of just a few incidental cases. We summarise our experience with the neuropathology of tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM). We studied three cases of TSP/HAM from different parts of the world. We demonstrated peculiar lamellated structures, called "multilamellar bodies" (MLB). It is tempting to suggest that MLB may represent specific ultrastructural markers of TSP/HAM. The pathology of the anteriorand posterior horns was similar and comprised axonal degeneration, accompanied by extensive astrocytic gliosis. Lymphocytic infiltration, particularly observed as "cuffs" around blood vessels, was scattered among other cellular elements. Ultrastructurally, myelin sheaths were relatively well preserved, and some demyelinated but not remyelinated fibres were observed. Moreover, axons with abnormal accumulations of neurofilaments, suggestive of axonal degeneration, were detected. Several axons contained Hirano bodies. In many samples glial processes replaced most of the remaining neuropil.

Ganglia, Spinal↗

PubMed2001

[Clinical application of proton magnetic resonance spectroscopy for differential diagnosis of pediatric posterior fossa tumors].

We report here on a correlation between proton magnetic resonance spectroscopy (MRS) spectra obtained in children with posterior fossa tumors and tumor histology and grading. Twenty-six children (age 1-16) were investigated before surgery by using single-voxel proton MRS. All examination were performed on a 1.5 T MR scanner by using single-voxel (8 cm3) with PRESS sequence (TR 1600 ms, TE 270 ms, NEX 256). Spectra of N-acetylaspartate (NAA), choline containing compounds (Cho), creatine and phosphocreatine (Cr) and lactate (Lac) were evaluated. Absolute concentrations of the metabolites were measured and their ratios were calculated. Correlation between these and tumor histology and grading were then determined. Concentration of Cho and Lac, and Cho/NAA ratio were the major statistically significant parameters for discrimination between benign (WHO grade I and II) and malignant tumors (WHO grade III and IV), in particular between pilocytic astrocytomas and medulloblastomas. Discrimination between individual histological types within malignant and benign tumor groups was not possible. Proton MRS of pediatric posterior fossa tumors seems to be helpful in prediction of tumor grading and histology. Specific character of the examination requires establishing of the individual standards for every MR scanner.

Adolescent↗

PubMed2001