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D Seilhean

Publications and source records attributed to D Seilhean.

At least 37 records · Page 2Linked to original sources
PubMed1998

[Diseases transmitted by non-conventional agents ("prions"): nosology and diagnosis].

Transmissible non conventional agents are currently called "Prions". This is not a neutral terminology: the attractive Prion hypothesis (the infectious agent being a protein able to replicate in the absence of DNA or RNA) due to Stanley Prusiner is the prevalent one, and has shown to be heuristic, but has not been formally proven and does not easily explain all the data, unless modified and expanded. No simple account has been given for the very unusual physical, chemical, and biological properties of non conventional agents. These infectious agents are associated with degenerative diseases of the nervous system that are either the consequence of a genetic mutation or develop spontaneously in apparently normal individuals, and then can be transmitted to various susceptible hosts, including man. Thus, non conventional agents cannot be considered only as fascinating biological enigmas. They constitute a challenge for public health. The changing characteristics of prion-associated diseases has led to a renewing of their clinical and neuropathological diagnostic criteria. A brief survey of the nosology and neuropathology of prions diseases, with emphasis on new data and on difficulties, is provided. A simple classification based on the familial, sporadic or infectious variety of the disease is suggested. Familial diseases can be named according to the genetic disorder. Sporadic and infectious diseases can be classified following the main clinical symptoms and signs, and the presence or absence of amyloid plaques in the brain, until new tools (analysis of the glycosylation pattern of PrP, strain recognition) allow a more precise nomenclature. The new epidemiology of Prion disorders allowed by these new approaches relies on a full study of Prion diseases affected patients, which necessarily involves their genetic study, and the analysis of brain tissue. This, for practical and ethical reasons, is better achieved by autopsy.

Diagnosis, Differential↗
PubMed1998

[Neuropathologic markers in degenerative dementias].

The number of neuropathological markers used for the diagnosis of degenerative dementias is rapidly increasing, and this is somewhat confusing: some lesions described a long time ago, such as ballooned cells, proved to be less specific than they were supposed to be; this is also the case for Lewy bodies, that have been recognised in a larger spectrum of disorders than thought a few years ago. On the contrary, for an increasing number of neuropathologists, Pick bodies are now mandatory for the diagnosis of Pick disease, and this contrasts with the prevalent opinions of the late sixties or seventies. There are a number of reasons for the changing significance of neuropathological markers. Three of them can be easily identified: 1) the burst of immunohistochemistry into neuropathology allowed an easier recognition, a better delineation and new pathophysiological approaches to old lesions, and a dramatic increase in the description of new markers, especially in glial cells; 2) in some conditions characterized by the number and distribution of some lesions rather than by their mere presence, such as aging and Alzheimer disease, a better neuroanatomical point of view permitted new insights into the concept of disease versus age-related changes; 3) more accurate clinicopathologic correlations showed clearly the need of grouping or lumping together some entities: for example, obvious relationship aroused between progressive supranuclear palsy and corticobasal degeneration; in contrast, distinguishing different disorders in the frontal lobe dementias grouped together into "Pick disease" was felt necessary. This review summarizes the main criteria for identification, and the presumed meaning of the chief markers indicating the presence of abnormally phosphorylated tau proteins, A beta peptides, and PrP proteins. Abnormally phosphorylated tau proteins can be stored in the neurons, and participate in the constitution of many lesions (neurofibrillary tangles, neuropil threads, abnormal processes of the crown of neuritic senile plaques, Pick bodies, granulo-vacuolar degeneration, argyrophilic grains). When seen in neuroglia, they are the chief constituents of various lesions that affect mainly astrocytes (abnormal tufts of fibres, astrocytic plaques, thorn-shaped astrocytes, spiny astrocytes) and also oligodendrocytes (oligodendroglial threads and coils, glial cytoplasmic inclusions). A beta peptides, in "preamyloid" and amyloid conformations, can be seen in the extracellular space (plaques, of the neuritic or non-neuritic varieties, diffuse, focal and granular deposits) and in the vascular walls (amyloid angiopathies). Some PrP deposits are also of the amyloid variety (kuru type, multicentric or florid plaques), but immunohistochemistry, far more sensitive than conventional studies, revealed a number of other lesions (perivacuolar, neuronal, "synaptic" deposits...). Numerous markers are easily detected by ubiquitin immunohistochemistry. Lewy bodies, Pick bodies, neurofibrillary tangles had already be identified by other methods. In contrast, some ubiquitin-positive inclusions are shown, by this technique only, in amyotrophic lateral sclerosis and other conditions which were thus related to this disease. Finally, this review deals with two classic markers, ballooned cells ("Pick cells") and spongiosis seen in disorders due to non conventional agents or prions (spongiform encephalopathies).

Biomarkers↗
PubMed1997

Dissociation of Alzheimer type pathology in a disconnected piece of cortex.

A woman with Alzheimer's disease died at the age of 85 years. A left sphenoid meningioma had been removed 27 years earlier. The tumor and the operation had severely altered the white matter of the frontal lobe and of the anterior part of the temporal lobe on the left side and massively disconnected a small piece of frontal cortex. There were numerous senile plaques and neurofibrillary tangles in the limbic and isocortical samples. The white matter lesions, on the operated (left) side, were associated with a lower density of neuritic plaques and of neuropil threads and with a higher density of beta-amyloid (A beta) deposits. The density of tau-positive neuritic plaques, neurofibrillary tangles and neuropil threads was close to zero, whereas the diffuse deposits of A beta were abundant, in the small disconnected piece of cortex. In this area, the white matter was severely damaged, as in the adjoining cortex, but the continuity of the cortical ribbon was also disrupted. These data show that neuritic and A beta pathologies may be dissociated and suggest that the neuritic alterations mainly involved cortico-cortical fibers coursing tangentially in the cortical ribbon.

Aged↗
PubMed1997

Tumor necrosis factor-alpha, microglia and astrocytes in AIDS dementia complex.

The pathogenesis of HIV-associated cognitive changes is poorly understood. Cytokines such as tumor necrosis factor-alpha (TNF-alpha) have been postulated to contribute to the mechanism of the neurological complications of HIV infection. One of the effects of TNF-alpha is to induce astrocyte proliferation in vitro. The purpose of this study was to look for a correlation between the expression of TNF-alpha, astrogliosis and the degree of cognitive impairment in 12 prospectively assessed AIDS cases without focal brain lesion, 8 of whom were demented. They were compared with 6 control patients without neurological disease. Neuropathological examination showed myelin pallor in 5 of the 8 demented patients. TNF-alpha expression was detected by immunohistochemistry in the midfrontal cortex, subcortical and deep white matter, and basal ganglia. Not only perivascular macrophages but also some microglial and endothelial cells were labeled. Most TNF-alpha-positive cells were in close contact with glial fibrillary acidic protein-positive astrocytes. They were more numerous than gp41-positive cells. Their density increased with increasing cognitive impairment and in parallel to the astrogliosis in the frontal cortex, basal ganglia and deep white matter. These findings further support the hypotheses that lesions of the deep white matter, driven by TNF-alpha, are associated with cognitive alteration, and that indirect effects of HIV infection in the brain participate in the development of HIV-associated dementia through a diffuse immune activation, mediated by cytokines.

AIDS Dementia Complex↗
PubMed1997

AIDS-related primary brain lymphomas: histopathologic and immunohistochemical study of 51 cases. The French Study Group for HIV-Associated Tumors.

Fifty-one cases of acquired immunodeficiency syndrome (AIDS)-related primary brain lymphomas (AR-PBL) were investigated for clinical characteristics; human immunodeficiency virus (HIV)-associated disorders; histopathologic features; immunophenotype; Epstein-Barr virus (EBV) infection; and, when frozen tissue was available, oncogene rearrangements. AR-PBL occurred late in the course of AIDS and were usually associated with other systemic or cerebral disorders and with a low level of CD4 lymphocytes. All cases were high grade lymphomas according to the Working Formulation or updated Kiel classification, and often displayed a multifocal pattern. Thirty cases were classified as immunoblastic with plasmacytic differentiation, 18 cases were large cell lymphomas with an immunoblastic component or centroblastic polymorphic lymphomas, and 2 were small noncleaved non-Burkitt lymphomas (Working Formulation). This latter category is classified as Burkitt's-like lymphoma in the REAL nomenclature. One case could not be classified because of necrosis. AR-PBL showed a high level expression of activation and adhesion molecules. The presence of EBV was detected in most cases, and, when PCR was used, this was a constant finding. bcl-2 oncoprotein and latent membrane protein-1 (LMP-1) were strongly expressed. None of the tested cases expressed p53, or were rearranged for bcl-2 or c-myc oncogenes. This study confirms the immunophenotypic specificity of AR-PBL, which may reflect the special immune status of the brain.

Adult↗
PubMed1997

Human immunodeficiency virus type 1 DNA and RNA load in brains of demented and nondemented patients with acquired immunodeficiency syndrome.

The relationship between dementia and human immunodeficiency virus type 1 (HIV-1) cerebral load is not clearly understood. We used immunohistochemistry and competitive polymerase chain reaction to evaluate the density ofgp 41 immunostained cells and the amount of HIV-1 DNA and RNA in the midfrontal gyrus of 21 HIV-1 infected patients, nine of whom were demented. The amounts of HIV-1 DNA and RNA, and the density of gp 41-positive cells were significantly linked. In this small series of cases, (1) although as a mean, there was a larger viral load in demented patients than in nondemented, this did not reach the significance level (2) discrepancies appeared in the population under study, some demented patients having low viral loads.

AIDS Dementia Complex↗
PubMed1997

Astrocytic adhesion molecules are increased in HIV-1-associated cognitive/motor complex.

Half of AIDS dementia cases are associated with HIV-encephalitis or myelin pallor. Another half die with no HIV-related neuropathological changes. Previous observations suggest that cerebral dysfunction may result from more subtle cellular interactions. and that some of them may be mediated by cell adhesion molecules. In the present study the expression by astrocytes and endothelial cells of intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) was analysed as a function of the neuropathological diagnosis, the density of astrogliosis and of HIV-1 positive cells, and of the mental status. Twelve AIDS cases, without focal brain lesion, eight of whom were demented, were selected from a prospective study. They were compared with six control cases with multiple sclerosis, and with six control patients without neurological disease. ICAM-1 and VCAM-1 expression was localized by immunofluorescence and confocal microscopy. HIV protein gp41 was detected by immunohistochemistry on adjacent sections. Endothelial expression of ICAM-1 and VCAM-1 was significantly up-regulated in all AIDS patients. VCAM-1 only was related to myelin pallor. The density of VCAM-1 or ICAM-1 positive astrocytes increased in demented AIDS patients, independently of the neuropathological findings or the density of gp41 positive cells. Expression of cell adhesion molecules, together with other secondary mechanisms such as secretion of cytokines may play a role in the pathogenesis of white matter lesions leading to HIV-1-associated cognitive changes.

AIDS Dementia Complex↗
PubMed1996

The neuropathologic diagnostic criteria of frontal lobe dementia revisited. A study of ten consecutive cases.

Ten successive cases from the Neuropathology Laboratory of La Salpêtrière Hospital in Paris, were selected on the presence of: dementia and prominent symptoms and signs of the frontal type; a degenerative disease without markers other than Pick cells, Pick bodies or ubiquitin-labelled non argyrophilic inclusions. We propose the following steps to diagnose the degenerative dementia associated with symptoms and signs of the frontal type: 1. If there is severe frontotemporal atrophy, severe neuronal loss and astrogliosis, many ballooned neurons and characteristic inclusions that are both tau and ubiquitin positive, the diagnosis is Pick disease. 2. If signs of motor involvement (sometimes unnoticed by the clinician) are present with mild cortical atrophy and mild spongiosis of layers II-III, the diagnosis of frontal lobe degeneration associated with motor neuron disease is warranted. Ubiquitin positive inclusions are useful, but non specific, markers. 3. When there are neither Pick inclusions nor motor neuron disease, the diagnosis may be frontal lobe atrophy lacking distinctive histology.

Adult↗
PubMed1996

Myelination by transplanted human and mouse central nervous system tissue after long-term cryopreservation.

Human and mouse oligodendrocytes were transplanted, after a long period of cryostorage, into newborn mouse brain. Tissue fragments were obtained from brain and spinal cord of 10-week-old human fetuses and from the periventricular zone of embryonic and newborn mouse brains. Samples were stored at -180 degrees C for periods of 3 days to over 5 years. Frozen or fresh fragments were transplanted into the brains of newborn shiverer mutant mice, which are deficient in myelin basic protein (MBP). Normal myelin, produced by grafted oligodendrocytes, was detected by immunohistochemistry with an anti-MBP antiserum. The best results were obtained with isospecific grafts. The timing of myelin appearance did not depend significantly on the species or age of the donor. Myelination obtained with mouse grafts was more profuse when the donor was younger (embryonic versus newborn). Cryopreservation over 5 years did not impede the graft's ability to produce myelin and can be considered for long-term storage of oligodendrocytes in view of cell therapy.

Animals↗
PubMed1996

Inconstant apolipoprotein E (ApoE)-like immunoreactivity in amyloid beta protein deposits: relationship with APOE genotype in aging brain and Alzheimer's disease.

The aim of this study was to analyze the relationship between apolipoprotein E (ApoE) and amyloid beta-protein (A beta) deposits in 29 brains from a series of elderly women, whose intellectual status had been prospectively assessed by the Blessed test score (BTS). In three cases the APOE genotype was epsilon 3/4, in one epsilon 2/2, in 25 epsilon 3/3. ApoE-like immunoreactive lesions resembling a classic senile plaque (ApoE-SP) or a diffuse deposit (ApoE-DD) were quantitatively assessed in the first temporal gyrus (Brodmann's area 22). The density of ApoE-positive deposits (ApoE-SP+ApoE-DD) was correlated with BTS (negative correlation R2 = 0.36, P = 0.0006). The correlation of the density of ApoE-DD with BTS (R2 = 0.26, P = 0.0051) was weaker than that of ApoE-SP (R2 = 0.50, P < 0.0001). The density of ApoE deposits was correlated with that of A beta-immunoreactive lesions (positive correlation R2 = 0.57, P < 0.0001). ApoE immunohistochemistry labeled fewer deposits than A beta immunohistochemistry but showed as many senile plaques (ApoE-SP) as tau immunohistochemistry and the Gallyas and Bodian techniques. Two of the three cases with the epsilon 3/4 allele had Alzheimer's disease (AD) with numerous ApoE-immunoreactive senile plaques. In contrast, the brain of the third epsilon 3/4 case, whose intellectual status was normal, contained numerous A beta deposits but lacked ApoE-like immunoreactivity. The presence of ApoE may, thus, not be a prerequisite for A beta deposition, even in cases with the epsilon 3/4 allele. The density of ApoE-SP peaked in layer III, whereas that of ApoE-DD was maximal in deeper cortical layers. This contrast in the laminar distribution indicates that only some ApoE-DD may evolve into ApoE-SP. ApoE deposition was linked to the intellectual decline and was constant in the most severely demented patients, in whom numerous ApoE-positive (and A beta-positive) neuritic plaques were surrounded by dystrophic neurites. ApoE may accumulate in neuritic senile plaques during the progression of AD.

Aged↗
PubMed1996

[Alzheimer's disease lesions: from morphology to cell biology].

Four different approaches to Alzheimer disease changes have been successively applied, and allowed a permanent feed forward-feed back enrichment of knowledge: morphologists described neurofibrillary tangles, senile plaques, amyloid angiopathy; with the help of immunohistochemical and biochemical techniques, they recognised A beta- and tau-associated pathologies; this, in turn, allowed more precise analysis of the lesions, and permitted recognising new ones such as neuropil threads; molecular genetics and molecular biology provided new insights, allowing the discovery of additional pathologic proteins, the relevance of which to physiology and pathology of the nervous system has now to be settled down. The increasingly intricate complex of lesions of Alzheimer syndrome is reviewed. A more comprehensive understanding is urgently needed for initiating efficient therapeutic researches. It will require together continuing a multidisciplinary approach, and a renewal of research in neuropathology.

Alzheimer Disease↗
PubMed1995

ApoE immunoreactivity and microglial cells in Alzheimer's disease brain.

The spatial relationship of apolipoprotein E (apoE)-like immunoreactivity (IR) to amyloid beta-peptide (A beta), astrocytes and microglial cells in the brain of Alzheimer's disease was studied by double immunolabelling. Diffuse apoE-like IR was seen in A beta diffuse deposits, and markedly increased in the core of classic senile plaques. Microglial cells, sometimes immunoreactive for apoE, were frequent in areas of apoE-like IR, where they often grouped into clusters in the core of apoE-labelled senile plaques. Although astrocytic processes were seen within these senile plaques, the cell bodies were always at a distance from the core. None of these astrocytes expressed apoE-like IR. Microglial cells, some of them immunoreactive for apoE, were seen in the center of apoE-labelled senile plaques. These data suggest that microglial cells play a more significant role than astrocytes in apoE deposition in senile plaques of Alzheimer disease.

Aged↗
PubMed1995

High expression of latent membrane protein 1 of Epstein-Barr virus and BCL-2 oncoprotein in acquired immunodeficiency syndrome-related primary brain lymphomas.

Nearly all primary brain lymphomas in acquired immunodeficiency syndrome (AIDS) patients are associated withEpstein-Barr virus (EBV). The role of EBV in lymphomagenesis is not totally elucidated. One possible mechanism is the overexpression of the BCL-2 oncoprotein, because the latent membrane protein 1 (LMP1) has been reported to transactivate the bcl-2 gene in vitro. To study the interrelationship beetween LMP1 and BCL-2 in vivo, we have analyzed and compared their expression in 11 AIDS-related primary brain lymphomas and 57 AIDS-related systemic lymphomas by immunoperoxidase technique on frozen sections. In AIDS-related primary brain lymphoma, LMP1 and BCL-2 were expressed in all cases but 1. All positive cases exhibited morphologic immunoblastic features. In contrast, the only negative case was histologically close to Burkitt's lymphoma. In systemic lymphomas, LMP1 was expressed in 21 cases, whereas BCL-2 was positive in only 3 cases, all of which were extranodal. These results indicate that, in addition to the histologic type, the role of EBV genes and BCL-2 expression in lymphomatous cells differ as a function of their localization. In AIDS-related primary brain lymphomas, this correlation between LMP1 and BCL-2 overexpression may have a major implication in lymphomagenesis.

Base Sequence↗
PubMed1995

[HIV and dementia: neuropathology].

Cognitive disorders associated with HIV infection may be due to focal lesions (lymphoma, toxoplasmosis, progressive multifocal leukoencephalitis, etc.), metabolic encephalopathy (e.g. hepatic insufficiency) or psychiatric disorders (depression). In the absence of such causes a "cognitive and motor syndrome associated with HIV infection" has been defined on clinical criteria (Working group of the American Academy of Neurology, 1991). This syndrome is not consistently associated with any specific lesion. Neither the multifocal encephalitis of HIV or CMV infection nor the diffuse leukoencephalopathy associated with HIV are the only causes. The existence of a neocortical neuronal loss has been suggested by several retrospective studies, but our prospective study has not shown cortical or subcortical atrophy. Measurement of neuronal density in Brodmann's areas 4,9 and 40 has not revealed a significant loss either global, by layer, or by column. The only constant lesion was gliosis of the cortex and white matter. Neuronal loss, therefore, is not indispensable to the occurrence of cognitive disorders in AIDS. The mechanism of dementia might be: dysfunction of cortical neurons (dendritic abnormalities, virus/neurotransmitter competition); subcortical dysfunction, as suggested by the high density of microglial nodules in that region; white matter lesions which could be due to abnormalities in the blood-brain barrier. The expression of cell adhesion molecules (VCAM-1, VLA-4, ICAM-1 and LFA-1) by endothelial cerebral cells is not significantly different in AIDS patients, demented or not, and in patients with multiple sclerosis. In contrast, the expression of VCAM-1 by astrocytes is significantly increased in demented AIDS patients compared with non demented ones.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex↗
PubMed1995

[Pathologic anatomy of cytomegalovirus encephalomyelitis and varicella-zona virus encephalomyelitis].

Cytomegalovirus (CMV) infection of the nervous system is frequent in acquired immunodeficiency syndrome (AIDS) and can be responsible for encephalitis, encephalomyelitis, meningoradiculitis or polyradiculo-neuropathy. Encephalitis is characterized at microscopy by its periventricular and cerebellar location, and by the presence of cytomegalic cells, containing intranuclear and/or intracytoplasmic inclusions, microglial nodules and necrotic foci. The virus can infect almost all types of cells. Coexistence of CMV and HIV has been observed in giant cells of macrophagic origin. It has been suggested that the two viruses could act in synergy. The nervous system is seldom infected by the varicella-zoster virus (VZV) in AIDS. The infection can be responsible for multifocal leukoencephalitis, ventriculitis, vascular lesions associated or not with cerebral infarction, or with meningomyeloradiculitis. In almost all cell types Cowdry's type A intranuclear inclusions have been found. The virus can be demonstrated by immunohistochemistry or in situ hybridization. VZV antigens have been reported in the walls of vessels damaged by a non inflammatory obliterating vasculopathy or by a granulomatous angiitis. Coexistence of VZV and HIV has been observed in giant cells of macrophagic origin, and synergy between those two viruses has been suspected.

AIDS-Related Opportunistic Infections↗
PubMed1995

[Fatal familial insomnia and prion diseases].

Fatal familial insomnia has recently enlarged the group of prion diseases. The disease starts between 35 and 60 years of age, is inherited as an autosomic dominant trait, and leads to death within 7 to 32 months. Clinical symptoms and signs include insomnia dysautonomia, cognitive and motor alteration. The discrete topography of the lesions in fatal familial insomnia underlines the role of the thalamus in the regulation of the sleep-wake cycle. Atrophy, neuronal loss and gliosis are prominent in the anterior and dorsomedial nuclei of the thalamus. Spongiosis, which is usually found in prion diseases, is absent in fatal familial insomnia. An abnormal prion protein (PrPsc) is detected in the brain. There is a mutation at codon 178 of the gene encoding this protein. Fatal insomnia is distinct from Creutzfeldt-Jakob disease on clinical, histopathologic and molecular grounds. It provides new information about genetics of prion diseases which share the characteristics of being altogether inherited and, in most cases, transmissible. The recent finding of abnormal PrP in diffuse subcortical gliosis suggests that other degenerative disorders could actually be prion diseases.

Adult↗