PubMed Health⌕ Search

Biomedical subjects

Paweł P Liberski

Publications and source records attributed to Paweł P Liberski.

At least 19 recordsLinked to original sources
PubMed2006

Variant CJD (vCJD) and bovine spongiform encephalopathy (BSE): 10 and 20 years on: part 1.

From 1986 more than 184,000 cattle in the UK and islands (of which >1,880 have been detected by active surveillance using rapid tests) and approaching 5,500 elsewhere have been confirmed with BSE. The original 1988 ban on the use of ruminant-derived protein in ruminant feed has been upgraded and now prohibits the use of any processed animal protein in feed for any farmed food animal. As a result of rigorous enforcement this reinforced ban is now regarded as fully effective from 1 Aug. 1996. Reasons are given for the substantial slippage that occurred initially and for the small but diminishing number of cases that have occurred in cattle born after 1 Aug. 1996. The 1989 offal ban, initially introduced to protect public health, has likewise been progressively strengthened and since 1995 has been effectively enforced by the Meat Hygiene Service, thus protecting the consumer. It is now extended as the specified risk material (SRM) ban throughout the EU. BSE continues to decline towards elimination in the UK and is being dealt with effectively in other Member States of the European Union (EU) and Switzerland with an extensive (and very expensive) range of edicts. The improving situation in the EU has encouraged the EC to draft a TSE Roadmap outlining possible reduction in control measures whilst still protecting the consumer. The situation on a global basis still causes concern as, although cases are less frequent than in the UK, surveillance, legislation and enforcement are not clearly as extensive and effective as in the EU. The risk of primary transmission of BSE to man from cattle to cause variant CJD (vCJD) is examined with reference to up-to-date assessments of bovine tissue infectivity and is now regarded as unlikely in the EU and Switzerland.

Animal Feed↗
PubMed2006

Variant CJD (vCJD) and bovine spongiform encephalopathy (BSE): 10 and 20 years on: part 2.

Up until February 2006, variant CJD (vCJD), the human disease associated with transmission of BSE from cattle, has been confirmed in 160 patients resident in the UK and 28 elsewhere, some of whom have never visited the UK. Cases have been reported in France (16 cases), Ireland (3), USA (2), Canada, Italy, Japan, The Netherlands, Portugal, Saudi Arabia and Spain (1 each). The presumed main period of hazard for ingestion of the BSE agent in bovine products in the UK is 1984-89, or perhaps up to 1995-6 but at a reduced level. Debated incubation periods for vCJD are discussed, with special reference to the wide, but currently reducing, range of predicted further primary cases in the UK. The primary disease seems to be preferentially acquired by, and expressed in, relatively young people. All but one of the British cases examined so far were homozygous for methionine at the polymorphic codon 129 of the prion protein PRNP gene. Tests of appendix specimens from large numbers of otherwise normal subjects at the time of appendicectomy have revealed lymphoreticular accumulations of PrP(Sc) in a few samples. Furthermore, three patients who died of vCJD had appendices removed by appendicectomy whilst healthy. Two of these appendices were retrospectively shown to be positive for PrP(Sc) and one removed 10 years before clinical onset was negative. This has led to worries regarding the possibility of pre-clinical or sub-clinical prion-associated disease in an unknown proportion of the population. To date, there has been no known association of primary vCJD with occupation, medicines, immunising agents, gelatine, or surgery (including the use of catgut sutures), or exposure to bovine products other than by ingestion. There is much concern that human-to-human (secondary) vCJD infection is transferred by blood transfusion. A possible risk is also perceived from infected blood products, human organs and tissues, or via contaminated surgical instruments or devices though, so far as is known, no cases have yet arisen in this way. Steps have been taken to reduce the risks and much research is in hand in this field. Continued TSE surveillance, the maintenance of adequate preventive controls, attention to possible parenteral challenges, and further research studies are of paramount importance.

Animals↗
PubMed2005

Plasma levels of alpha beta peptides are altered in amnestic mild cognitive impairment but not in sporadic Alzheimer's disease.

Plasma alpha beta levels have been examined in sporadic Alzheimer's disease yielding conflicting results; both no difference and an increase in plasma concentrations of alpha beta42 and alpha beta40 in sporadic cases of AD as compared to controls have been reported. Elevated plasma alpha beta42 levels may be detected several years before the onset of symptoms (in mild cognitive impairment stadium). Levels of alpha beta40 and alpha beta42 were measured in plasma from 54 patients with AD, 39 subjects with MCI and 35 controls using a commercially available ELISA. Mean plasma alpha beta42 levels were significantly higher in MCI as compared to both AD (P < 0.001) and control subjects (P < 0.001), while alpha beta40 did not differ between the groups. No correlations were observed between alpha beta levels and age, MMSE scores or gender. 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.

Aged↗
PubMed2005

Complement factors C1q and C3b in brains with Creutzfeldt-Jakob disease.

Neuronal loss in Creutzfeldt-Jakob disease (CJD) is due to apoptosis and autophagy, however the apoptotic cell death may be related to the influence of cytokines. The role of complement system in induction of this process was recently postulated. In our study we examined the immunoreactivity for "early activation" complement factors C1q and C3b in the brains of the patients with CJD. We showed the positive immunoreactivity for C1q and C3b in neurons mainly in areas of spongiform change, in Purkinje cells, molecular layer and granular layer of cerebellum, and in prion protein positive plaques. The evident positive reactivity of two complement factors may suggest the role of complement system in neurodegeneration in CJD.

Astrocytes↗
PubMed2005

Microglial cells in neurodegenerative disorders.

Microglia are resident immune cells of the CNS. They are involved in the pathogenesis of diverse neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, prion diseases as well as multiple sclerosis, amyotrophic lateral sclerosis and AIDS dementia complex. It is widely accepted that microglia contribute to the neurodegeneration through a release of a variety of proinflammatory substances. In fact, they are not the only cells which contribute to immunological processes inside the nervous system. The CNS is composed of different cell populations that answer to pathological factors and influence each other and modulate their reactions. These complex interactions are responsible for the development of brain pathology. This paper reviews the available information on microglial cells contribution to AD, PD and prion diseases development.

Alzheimer Disease↗
PubMed2004

Fate of myelinated fibres in the optic nerves in experimental Creutzfeldt-Jakob disease in rodents: an ultrastructural study.

We report the ultrastructural appearances of myelinated fibres of the optic nerves from mice infected with the Fujisaki strain of Gerstmann-Sträussler-Scheinker (GSS) disease and from Echigo-1 strain of Creutzfeldt-Jakob disease (CJD). Optic nerves from CJD- and GSS-infected rodents showed severe pathological changes. Theses changes were qualitatively indistinguishable from each other but were more robust in the Fujisaki GSS model than in the hamsters inoculated with Echigo-1. The most characteristic finding was the distension with the attenuation of the myelin sheath forming a vacuole while shrunken axon was attached to the innermost layer of the myelin. With high power electron microscopy, we could observe the splitting of the myelin lamellae at the major dense or intraperiod lines to form complex openings that extended to line the vacuole. This finding suggests that myelin lamellae participate in the formation of vacuoles.

Animals↗
PubMed2004

Kuru: a half-opened window onto the landscape of neurodegenerative diseases.

Kuru, the first human neurodegenerative disease classified as a transmissible spongiform encephalopathy (TSE), prion disease or, in the past, as a slow unconventional virus disease, was first reported to Western medicine in 1957 by Gajdusek and Zigas. A complete bibliography of kuru through 1975 has been published by Alpers et al. The solution of the kuru riddle opened a novel field of biomedical sciences and initiated more than a quarter of century of research that has already resulted in two Nobel prizes (to D. Carleton Gajdusek in 1976 and to Stanley B. Prusiner in 1997) and was linked to a third (to Kurt Wüthrich who determined the structure of the prion protein). Kuru research has impacted the concepts of nucleation-polymerization "protein cancers", and "conformational disorders". This paper is dedicated to Dr. Carleton Gajdusek on the occasion of his 80th birthday. "Kuru" in the Fore (Fig. 1) language means to shiver from fever or cold. The Fore used the noun of the kuru-verb to describe the always fatal disease which decimated their children and adult women but rarely men. It has been and still is restricted to natives of the Fore linguistic group at Papua New Guinea's Eastern Highlands and those neighboring linguistic groups which exchange women with Fore people (Auiana, Awa, Usurufa, Kanite, Keiagana, late, Kamano, Kimi; Fig. 2). Neighboring groups into which kuru-affected people did not settle through marriage or adoption, such as the Anga (Kukukuku), and remote lagaria, Kamano and Auiana people, were not affected. It seems that Kuru first appeared at or shortly after the turn of XX century in Uwami village of Keiagana people and spread to the Awande in the North Fore where the Uwami had social contacts. Within 20 years it had spread further into the Kasokana (in 1922 according to Lindebaum) and Miarasa villages of North Fore, and a decade later had reached the South Fore at the Wanikanto and Kamira villages. Kuru became endemic in all villages that it entered and became hyperendemic in the South Fore region. All native informants stressed the relatively recent origin of kuru. Interestingly enough, when kuru first appeared, it was considered poetically by Fore as similar to "the swaying of casuarinas tree" and kuru was labeled cassowary disease to stress the similarity between cassowary quills and "waving casuarinas fronds". Gajdusek first learned about kuru from Dr. Roy Scragg, director of Public Health in Port Mosby, who had already read a report sent by Dr. 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.

Adult↗
PubMed2004

Molecular approaches to mechanisms of prion diseases.

Prion diseases such as scrapie in sheep, bovine spongiform encephalopathy in cattle, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease and fatal familial insomnia in man are neurodegenerative disorders. In humans, the diseases can be sporadic, inherited, or acquired by infection. The underlying pathogenic event in prion diseases is a conformational modification of the cellular isoform prion protein (PrP(C)) to the pathogenic isoform (PrP(SC)) that accumulates in the central nervous system. However, in humans, in some inherited cases the pathological PrP is not PrP(Sc), but a transmembrane form of prion protein, (Ctm)PrP. Prion protein is encoded by the cellular gene, PRNP, which has been mapped to human chromosome 20p21. Familial prion diseases are thought to result from a change in structure of the prion protein produced by the mutated PRNP gene. Furthermore, polymorphic codon 129 of the PRNP gene encodes either methionine or valine and appears to influence the susceptibility of patients to iatrogenic and sporadic CJD as well as the neuropathological phenotype in these forms of CJD. Polymorphisms in the promoter region of PRNP gene or disturbances in prion protein metabolism, such as incorrect activity of cellular chaperones or proteasomes are considered as susceptibility factors in human prion diseases.

Amyloid↗
PubMed2004

Doppel: the prion's double.

Doppel (Dpl) is a PrP-like protein, coded by a gene named PRND, located near the PRNP (prion proten coding gene) locus. Human Dpl is a 179-amino acid protein showing approximately 25% sequence identity with the carboxyproximal two thirds of the human cellular prion protein (PrPC). A comparison of the structures of Dpl and PrP(C) reveals similarities in the secondary structure and topology. Apart from their structural similarities, the PrP and Dpl proteins seem to have different functions. The Prnd gene is expressed in mouse embryos; in adult mice its transcripts are present in heart, mammary gland, spleen, testes and, in contrast to Prnp, only at very low levels in the adult CNS. Moreover, the Dpl protein is not capable of enhancing the propagation of the pathological prion protein (PrP(Sc)). The Dpl protein has been identified as a regulator of acrosome function and male gametogenesis. The human PRND open reading frame has been shown to contain polymorphic codons, but research on a correlation between the PRND polymorphic sequences and neurodegenerative disorders carried out to date in different populations have shown contradictory results. Therefore, the role of the PRND gene in CJD and other diseases still remains unexplained.

Animals↗
PubMed2004

Bovine spongiform encephalopathy (BSE): the end of the beginning or the beginning of the end?

Bovine spongiform encephalopathy (BSE) is a zoonosis being the origin of variant Creutzfeldt-Jakob disease and an important cattle disease in its own right. This association has driven both the research into the disease and extensive epidemiological investigations of practical value. Not only has the occurrence of BSE has a serious effect on animal health and public health, it has also seriously interrupted trade in cattle and cattle products from affected countries. Since 2001, several additional European countries, Japan, Israel and Canada have reported BSE in native-born stock and this has led to a concern about the BSE status of countries that have imported cattle and cattle products from any affected country. A single case recently reported in the USA was in a cow imported from Canada, thus extending the risk of BSE occurrence into the North American continent as a whole. Extensive feed and offal bans have protected the food and feed chains in all countries with BSE, even though initially they tended to be leaky. Application of newly-developed, approved 'Rapid' tests for misfolded PrP in central nervous tissue of targeted, high-risk animals and slaughter cattle now provides the tools whereby the real incidence of the disease (and to a degree, infection) can be determined in an active surveillance programme. 'Rapid' testing also enables the progress of epidemics to be monitored in response to applied measures. In the EU, over 10 million cattle are tested annually. Analysis of the extensive data shows that it is the beginning of the end of the BSE epidemic in the UK; most European countries, Israel and Japan are close behind. The epidemic in North America (two cases to date) is at the beginning. Significant measures had already been adopted there to reduce the risk from recycling of infection via feed but it remains to be seen if they are watertight. Advice has been given to ensure that public health is protected and to monitor the epidemic by strategic use of approved 'Rapid' tests to determine that the epidemic is in fact trivial as believed, or otherwise to identify weaknesses in measures that can be corrected. It is imperative that all countries conduct risk assessments for BSE, follow the OIE recommendations and do not unreasonably disrupt international trade. There is a responsibility for all countries with BSE to ensure that infection is not exported to any country, particularly through live cattle and especially via meat-and-bone-meal, which is the acknowledged vehicle of transmission. There is also a responsibility placed upon all countries to protect, not only their cattle populations, but also their human populations from exposure to this economically important fatal disease. 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.

Animals↗
PubMed2004

An outline of the neuropathology of transmissible spongiform encephalopathies (prion diseases).

We review here the basic neuropathology of transmissible spongiform encephalopathies (TSE) or prion diseases. The classic hallmark of TSE neuropathology is a combination (in different proportions in different diseases) of spongiform change, astrocytosis, neuronal loss and amyloid plaques. Immunohistochemically, accumulation of the abnormal isoform of prion protein (PrP(sc) or PrP(d)) is regarded as a diagnostic for TSE. We also review the peculiarities of kuru, variant Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker disease.

Animals↗
PubMed2004

Spongiform change--an electron microscopic view.

Spongiform change is a hallmark of transmissible spongiform encephalopathies (TSEs) in prion diseases. They are defined as small round or oval empty spaces in the neuropil. When confluent, they merge to form "morula-like" structures. Their neuroanatomical distribution and grading within each of defined neuroanatomical areas underlie the lesion profile method used to discriminate strains in rodents and in cattle. Ultrastructurally, vacuoles develop within neuronal elements. They are membrane-bound and contain secondary vacuoles and "curled" membrane fragments. Separate type of vacuoles are those develop within myelin sheath. Those vacuoles develop through complicated opening at the major-dense and intraperiod lines. The histogenesis of spongiform vacuoles is unclear and the only hypothesis that they develop through the formation of abnormal configuration of plasma membranes (ACPMs) has never been substantiated. We suggested that vacuoles may develop through process of autophagy.

Animals↗
PubMed2004

Astrocytes in transmissible spongiform encephalopathies (prion diseases).

Astrocytosis is one of the hallmarks of neuropathology of transmissible spongiform encephalopathies (TSEs) or prion diseases. In this review, we summarize data on astrocytic reaction, including naturally occurring or experimentally induced TSEs. A particular form of astrocytic reaction is known as gliocytosis and it is typical for experimental scrapie in mouse or in hamsters. Also, astrocytes participate in the formation of amyloid plaques. 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.

Animals↗
PubMed2004

Tubulovesicular structures--the ultrastructural hallmark for transmissible spongiform encephalopathies or prion diseases.

Tubulovesicular structures (particles--TVS) are the only ultrastructural marker for all transmissible spongiform encephalopathies (TSEs) or prion disease as seen by thin section electron microscopy. The latter is stressed as opposed to negative-staining techniques. TVS are spheres or short rods of approximately 27-35 nm in diameter. What is particularly interesting, this size of TVS is also the size of filter cut-off as judged from ultrafiltration studies and the size of the smallest infectious unit as recently estaimated. TVS have been found in all naturally occurring and experimentally induced TSEs, including variant Creutzfeldt-Jakob disease and human familial TSEs--fatal familial insomnia and Gerstmann-Sträussler-Scheinker disease. In longitudinal studies, the number of neuronal processes containing TVS correlates roughly with the incubation period and with infectivity. Hence, they are readily found in hamsters infected with the 263K strain of scrapie but it is very difficult to find them in human TSEs where titre is lower. 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.

Animals↗
PubMed2004

Amyloid plaques in transmissible spongiform encephalopathies (prion diseases).

Amyloid plaques are encountered in all cases of kuru and Gerstmann-Straussler-Scheinker disease (GSS) and in some 10-15% of sporadic Creutzfeldt-Jakob disease (sCJD) cases. In variant Creutzfeldt-Jakob (vCJD) the particular type of plaque known as "florid" or "daisy" plaque exists in 100% of cases. By electron microscopy several types of amyloid plaque were delineated, corresponding to those seen by PrP immunohistochemistry. Unicentric "kuru" plaques consisted of stellate arrangements (stars or cores) of amyloid bundles emanating from a dense interwoven centre. A proportion of kuru plaques formed very dense stars, reminiscent of sea urchins in shape. Others presented a looser pattern. Amyloid stars were enveloped by astrocytic processes. High-power electron micrographs revealed that amyloid bundles were concealed within grooves of obscure cellular origin. Interestingly, basement membranes lined with electron-dense material were observed at the periphery of many amyloid plaques of GSS. Dystrophic neurites were seen only rarely. Microglial cells formed a significant part of the amyloid plaques. Occasionally clusters composed of several kuru plaques were found. These were intermediate forms to multi-centric plaques, which consisted of several merging stellate cores. Smaller amyloid deposits surrounded larger cores. In contrast to the kuru plaques, associated with a limited number of dystrophic neurites (DN), numerous such structures were seen at the periphery. The DN were filled with abnormal organelles such as electron-dense bodies, multi-vesicular bodies and multilamellar bodies and thus were indistinguishable from those seen in scrapie and CJD or Alzheimer's disease, except that they did not contain paired helical filaments (PHF). Instead, piled neurofilaments were often detected in the centres of DN. Similar DN were observed but these were not associated with any plaques. The last and, by the same token, the rarest type of plaque was the purely neuritic plaque. These consisted of large areas filled with DN of different sizes and shapes (sometimes bizarre) but not amyloid bundles. Analogously to the kuru and multi-centric plaques, astrocytic processes were observed at the periphery. By means of light microscopy and semi-thin (1 microm) sections discrete PrP-immunopositive plaques were observed (data not shown), in the subependymal region but not in the deep brain neuroparenchyma, in both 263K and 22C-H scrapie-infected hamster brains. These plaques were not discernible by routine haematoxylin and eosin staining. 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.

Animals↗
PubMed2004

Gerstmann-Sträussler-Scheinker disease. I. Human diseases.

Gerstmann-Sträussler-Scheinker disease (GSS) is a slowly progressive hereditary autosomal dominant disease (OMIM: 137440) and the first human transmissible spongiform encephalopathy (TSE) in which a mutation in a gene encoding for prion protein (PrP) was discovered. Its true prevalence is difficult to estimate but figures within the range of 1-10/100,000,000 are quoted. GSS is defined as a neurodegenerative disease "in family with dominantly inherited progressive ataxia and/or dementia): encephalo(myelo)pathy with multi-centric PrP plaques". In this review, we summarise data on all the families with GSS. The hallmark of the GSS neuropathology is the multi-centric plaque but the pattern varies between families. 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.

Animals↗