Les glioblastomes, un exemple de recherche translationnelle?
Kroonen, Jérôme ; Nguyen-Khac, Minh-Tuan ; Deprez, Manuel et al
in Revue Médicale de Liège (2008), 63(5-6), 251-6
Among patients which develop glioblastoma multiform (GBM), recurrence is the rule despite continuous progress in surgery, radiotherapy and chemotherapy. In the adult, GBM is the most frequent and most ... [more ▼]
Among patients which develop glioblastoma multiform (GBM), recurrence is the rule despite continuous progress in surgery, radiotherapy and chemotherapy. In the adult, GBM is the most frequent and most aggressive tumour of the Central Nervous System. A better understanding of the mechanisms by which these tumours relapse could promote the use of preventive therapy and could increase patients' survival. GBM stem cells have been recently described and it was demonstrated that they are specifically implied in the experimental tumorigenesis. It is thus very attractive to speculate on a possible relationship between these GBM stem cells and the neural stem cells which are persisting in the neurogenic zones of the adult brain. In this review, we formulate and discuss the hypothesis by which, in a patient with GBM, malignant stem cells might be present in the neurogenic zones, away from the tumour mass. This hypothesis could explain the tumour relapse observed after the first treatments. [less ▲]Detailed reference viewed: 134 (47 ULg)
Mucormycose invasive du poumon et du rachis dorsal.
De Pasqual, Aurelie ; Deprez, Manuel ; Ghaye, Benoît et al
in Revue Médicale de Liège (2008), 63
Nous rapportons le cas d'un patient de 67 ans atteint d'un syndrome myélodysplasique et qui a développé une mucormycose pulmonaire avec extension tout à fait exceptionnelle vers le rachis dorsal ... [more ▼]
Nous rapportons le cas d'un patient de 67 ans atteint d'un syndrome myélodysplasique et qui a développé une mucormycose pulmonaire avec extension tout à fait exceptionnelle vers le rachis dorsal responsable d'un paraplégie aiguë. Après échec d'un traitement probabiliste anti-aspergillaire, c'est finalement l'analyse des prélèvements obtenus lors de la laminectomie décompressive qui a fourni le diagnostic mycologique. En raison d'une altération majeure de l'état général, la lobectomie prévue n'a pu être réalisée et malgré l'adaptation du traitement antifongique (Abelcet, Posaconazole), le patient est décédé. La mucormycose (ou zygomycose) pulmonaire est une infection fongique peu commune qui touche essentiellement les patients immuno-déprimés. Le champignon pathogène fait partie des zygomycètes dont la caractéristique principale est la capacité d'angio-invasion. L'invasion périneurale est une autre voie de propagation récemment mise en évidence. Les difficultés thérapeutiques associées à cette pathologie sont liées au terrain d'immunodépression, aux difficultés d'obtenir rapidement un diagnostic précis ainsi qu'à l'absence de sensibilité du Mucor aux antifongiques récemment introduits (V-Fend, Cancidas). Ceci souligne le risque inhérent à un traitement antifongique empirique par ces agents et la nécessité d'un prélèvement biopsique précoce en cas de non-réponse au traitement. [less ▲]Detailed reference viewed: 180 (11 ULg)
Management of diffuse glioma in children: a retrospective study of 27 cases and review of literature.
Piette, Caroline ; Deprez, Manuel ; et al
in Acta Neurologica Belgica (2008), 108(2), 35-43
Gliomas are the most common CNS tumours in children and present either as circumscribed tumours or diffusely infiltrative neoplasms. Diffuse gliomas develop both in the cerebral hemispheres and the ... [more ▼]
Gliomas are the most common CNS tumours in children and present either as circumscribed tumours or diffusely infiltrative neoplasms. Diffuse gliomas develop both in the cerebral hemispheres and the brainstem and have a poor prognosis. Guidelines for the therapy of these tumours are still debated. In this study, we reviewed the clinical features of 27 consecutive patients with diffuse gliomas admitted to the Department of Paediatrics of CHR Citadelle, University of Liege, between 1985 and 2005. We review their clinical presentation, diagnosis, treatment and outcome with reference to the published literature. [less ▲]Detailed reference viewed: 59 (7 ULg)
Absence d'hypogonadisme chez un patient masculin avec prolactinome géant : un paradoxe clinique
; Daly, Adrian ; Deprez, Manuel et al
in Annales d'Endocrinologie (2008), 69(1), 47-52
Background Impotence and decreased libido are the cardinal features of prolactinomas in males. We describe the unusual clinical, pathological and biochemical features in a male patient with a giant ... [more ▼]
Background Impotence and decreased libido are the cardinal features of prolactinomas in males. We describe the unusual clinical, pathological and biochemical features in a male patient with a giant prolactinoma and normal gonadal function. Case Report A 57 year-old man presented with visual symptoms related to a 30 × 25 × 60 mm tumor of the sella and skull base. Biopsy revealed a pituitary adenoma and subsequent hormone profiles demonstrated grossly elevated serum prolactin (131,412 ng/ml), LH at the upper limit of normal and normal testosterone. The patient had no symptoms of decreased libido or impotence related to this giant prolactinoma. Immunohistochemistry revealed a tumor that was positive for prolactin, alpha-subunit and LH. Cabergoline greatly reduced prolactin levels but these remained above normal. LH, testosterone and alpha-subunit levels were decreased in parallel. Loss of libido and impotence became apparent when testosterone fell below normal, a situation that resolved with further cabergoline treatment and prolactin inhibition and testosterone therapy. Conclusions Sexual dysfunction is a hallmark of prolactinomas in males. Tumors that co-secrete prolactin and LH are extremely rare and this is the first such case reported in an adult male. In this case, normal testosterone was maintained by intact LH levels even in the face of the highest prolactin level reported to date. [less ▲]Detailed reference viewed: 82 (4 ULg)
Chromosomal profiles of gene expression in Huntington's disease.
; ; et al
in Brain : A Journal of Neurology (2008), 131(Pt 2), 381-8
Recent studies suggested that Huntington's disease is due to aberrant interactions between mutant huntingtin protein, transcription factors and transcriptional co-activators resulting in widespread ... [more ▼]
Recent studies suggested that Huntington's disease is due to aberrant interactions between mutant huntingtin protein, transcription factors and transcriptional co-activators resulting in widespread transcriptional dysregulation. Mutant huntingtin also interacts with histone acetyltransferases, consequently interfering with the acetylation and deacetylation states of histones. Because histone modifications and chromatin structure coordinate the expression of gene clusters, we have applied a novel mathematical approach, Chromowave, to analyse microarray datasets of brain tissue and whole blood to understand how genomic regions are altered by the effects of mutated huntingtin on chromatin structure. Results show that, in samples of caudate and whole blood from Huntington's disease patients, transcription is indeed deregulated in large genomic regions in coordinated fashion, that transcription in these regions is associated with disease progression and that altered chromosomal clusters in the two tissues are remarkably similar. These findings support the notion of a common genome-wide mechanism of disruption of RNA transcription in the brain and periphery of Huntington's disease patients. [less ▲]Detailed reference viewed: 31 (2 ULg)
Experimental anti-angiogenesis causes upregulation of genes associated with poor survival in glioblastoma.
; ; Bellahcene, Akeila et al
in International Journal of Cancer = Journal International du Cancer (2008), 122(10), 2187-98
Vascular endothelial growth factor (VEGF) inhibitors are the most promising anti-angiogenic agents used increasingly in the clinic. However, to be efficient, anti-VEGF agents need to be associated with ... [more ▼]
Vascular endothelial growth factor (VEGF) inhibitors are the most promising anti-angiogenic agents used increasingly in the clinic. However, to be efficient, anti-VEGF agents need to be associated with classic chemotherapy. Exploring gene regulation in tumor cells during anti-angiogenesis might help to comprehend the molecular basis of response to treatment. To generate a defined anti-angiogenic condition in vivo, we transfected human glioma cells with short-interfering RNAs against VEGF-A and implanted them on the chick chorio-allantoic membrane. Gene regulation in avascular tumors was studied using human Affymetrixtrade mark GeneChips. Potentially important genes were further studied in glioma patients. Despite strong VEGF inhibition, we observed recurrent formation of small, avascular tumors. CHI3L2, IL1B, PI3/elafin and CHI3L1, which encodes for YKL-40, a putative prognosticator for various diseases, including cancer, were strongly up-regulated in avascular glioma. In glioblastoma patients, these genes showed coregulation and their expression differed significantly from low-grade glioma. Importantly, high levels of CHI3L1 (p = 0.036) and PI3/elafin mRNA (p = 0.0004) were significantly correlated with poor survival. Cox regression analysis further confirmed that PI3 and CHI3L1 levels are survival markers independent from patient age and sex. Elafin-positive tumor cells were only found in glioblastoma, where they were clustered around necrotic areas. PI3/elafin is strongly induced by serum deprivation and hypoxia in U87 glioma cells in vitro. Our results indicate that anti-angiogenesis in experimental glioma drives expression of critical genes which relate to disease aggressiveness in glioblastoma patients. In particular, CHI3L1 and PI3/elafin may be useful as new prognostic markers and new therapeutic targets. [less ▲]Detailed reference viewed: 57 (3 ULg)
Analysis of alpha-synuclein, dopamine and parkin pathways in neuropathologically confirmed parkinsonian nigra.
; ; et al
in Acta Neuropathologica (2007), 113(3), 253-63
The identification of mutations that cause familial Parkinson's disease (PD) provides a framework for studies into pathways that may be perturbed also in the far more common, non-familial form of the ... [more ▼]
The identification of mutations that cause familial Parkinson's disease (PD) provides a framework for studies into pathways that may be perturbed also in the far more common, non-familial form of the disorder. Following this hypothesis, we have examined the gene regulatory network that links alpha-synuclein and parkin pathways with dopamine metabolism in neuropathologically verified cases of sporadic PD. By means of an in silico approach using a database of eukaryotic molecular interactions and a whole genome transcriptome dataset validated by qRT-PCR and histological methods, we found parkin and functionally associated genes to be up-regulated in the lateral substantia nigra (SN). In contrast, alpha-synuclein and ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) gene expression levels were significantly reduced in both the lateral and medial SN in PD. Gene expression for Septin 4, a member of the GTP-binding protein family involved in alpha-synuclein metabolism was elevated in the lateral parkinsonian SN. Additionally, catalase and mitogen-activated protein kinase 8 and poly(ADP-ribose) polymerase family member 1 (PARP1) known to function in DNA repair and cell death induction, all members of the dopamine synthesis pathway, were up-regulated in the lateral SN. In contrast, two additional PD-linked genes, glucocerebrosidase and nuclear receptor subfamily 4, group A, member 2 (NR4A2) showed reduced expression. We show that in sporadic PD, parkin, alpha-synuclein and dopamine pathways are co-deregulated. Alpha-synuclein is a member of all three gene regulatory networks. Our analysis results support the view that alpha-synuclein has a central role in the familial as well as the non-familial form of the disease and provide steps towards a pathway definition of PD. [less ▲]Detailed reference viewed: 12 (2 ULg)
The lack of expression of the peripheral benzodiazepine receptor characterises microglial response in anaplastic astrocytomas.
; ; et al
in Journal of neuro-oncology (2007), 85(1), 95-103
The peripheral benzodiazepine receptor (PBR) is a 18 kDa molecule mainly involved in cholesterol transport through the mitochondrial membrane. In microglia, PBR is expressed from the earliest stages of ... [more ▼]
The peripheral benzodiazepine receptor (PBR) is a 18 kDa molecule mainly involved in cholesterol transport through the mitochondrial membrane. In microglia, PBR is expressed from the earliest stages of activation and appears to exert a pro-inflammatory function. This molecule is commonly up-regulated in inflammatory, degenerative, infective and ischaemic lesions of the central nervous system but it has never been reported in glioma-infiltrating microglia. We examined two anaplastic astrocytomas showing minimal contrast-enhancement and therefore little damage of the blood brain barrier to minimise the presence of blood borne macrophages within tumour tissue. The two lesions were studied in vivo using positron emission tomography (PET) with the specific PBR ligand [(11)C](R)-PK11195 and the corresponding tumour tissue was investigated with an anti-PBR antibody. Glioma-infiltrating microglia were characterised for molecules involved in antigen presentation and cytotoxic activity. As comparison, PBR was investigated in three brains with multiple sclerosis (MS) and three with Parkinson's disease (PD). The expression profile of four anaplastic astrocytomas was also exploited and results were compared to the profile of eleven samples of normal temporal lobe and nine cases of PD. PET studies showed that [(11)C](R)-PK11195 binding was markedly lower in tumours than in the contralateral grey matter. Pathological investigation revealed that glioma-infiltrating microglia failed to express PBR and cytotoxic molecules although some cells still expressed antigen presenting molecules. PBR and cytotoxic molecules were highly represented in MS and PD. Evaluation of microarray datasets confirmed these differences. Our results demonstrated PBR suppression in glioma-infiltrating microglia and suggested that PBR may have a relevant role in modulating the anti-tumour inflammatory response in astrocytic tumours. [less ▲]Detailed reference viewed: 6 (2 ULg)
Treating gliomas with glucocorticoids: from bedside to bench
Piette, Caroline ; Munaut, Carine ; Foidart, Jean-Michel et al
in Acta Neuropathologica (2006), 112(6), 651-664
Glucocorticoids are used in the treatment of gliomas to decrease tumour-associated oedema and to reduce the risk of acute encephalopathy associated with radiotherapy. However, the mechanisms by which ... [more ▼]
Glucocorticoids are used in the treatment of gliomas to decrease tumour-associated oedema and to reduce the risk of acute encephalopathy associated with radiotherapy. However, the mechanisms by which glucocorticoids work are still largely unknown. In this paper, we survey the experimental and clinical evidence for the effects of glucocorticoids on tumour cell proliferation, apoptosis and sensitivity to chemotherapy, angiogenesis and vascular permeability. We then review current guidelines on the choice of molecule, dose and duration of glucocorticoid treatment for gliomas. [less ▲]Detailed reference viewed: 36 (6 ULg)
Spontaneous pneumocephalus caused by the association of pneumosinus dilatans and meningioma - Case illustration
; ; Deprez, Manuel et al
in Journal of Neurosurgery (2006), 105(6), 934Detailed reference viewed: 29 (6 ULg)
Chromosomal patterns of gene expression from microarray data: methodology, validation and clinical relevance in gliomas.
; ; Hennuy, Benoît et al
in BMC Bioinformatics (2006), 7
BACKGROUND: Expression microarrays represent a powerful technique for the simultaneous investigation of thousands of genes. The evidence that genes are not randomly distributed in the genome and that ... [more ▼]
BACKGROUND: Expression microarrays represent a powerful technique for the simultaneous investigation of thousands of genes. The evidence that genes are not randomly distributed in the genome and that their coordinated expression depends on their position on chromosomes has highlighted the need for mathematical approaches to exploit this dependency for the analysis of expression data-sets. RESULTS: We have devised a novel mathematical technique (CHROMOWAVE) based on the Haar wavelet transform and applied it to a dataset obtained with the Affymetrix HG-U133_Plus_2 array in 27 gliomas. CHROMOWAVE generated multi-chromosomal pattern featuring low expression in chromosomes 1p, 4, 9q, 13, 18, and 19q. This pattern was not only statistically robust but also clinically relevant as it was predictive of favourable outcome. This finding was replicated on a data-set independently acquired by another laboratory. FISH analysis indicated that monosomy 1p and 19q was a frequent feature of tumours displaying the CHROMOWAVE pattern but that allelic loss on chromosomes 4, 9q, 13 and 18 was much less common. CONCLUSION: The ability to detect expression changes of spatially related genes and to map their position on chromosomes makes CHROMOWAVE a valuable screening method for the identification and display of regional gene expression changes of clinical relevance. In this study, FISH data showed that monosomy was frequently associated with diffuse low gene expression on chromosome 1p and 19q but not on chromosomes 4, 9q, 13 and 18. Comparative genomic hybridisation, allelic polymorphism analysis and methylation studies are in progress in order to identify the various mechanisms involved in this multi-chromosomal expression pattern. [less ▲]Detailed reference viewed: 26 (5 ULg)
A phase 1-2, prospective, double blind, randomized study of the safety and efficacy of Sulfasalazine for the treatment of progressing malignant gliomas: study protocol of [ISRCTN45828668].
Robe, Pierre ; Martin, Didier ; Albert, Adelin et al
in BMC Cancer (2006), 6
BACKGROUND: The prognosis of patients suffering from WHO grade 3 and 4 astrocytic glioma remains poor despite surgery, radiation therapy and the use of current chemotherapy regimen. Indeed, the median ... [more ▼]
BACKGROUND: The prognosis of patients suffering from WHO grade 3 and 4 astrocytic glioma remains poor despite surgery, radiation therapy and the use of current chemotherapy regimen. Indeed, the median survival of glioblastoma multiforme (WHO grade 4) patients is at best 14.6 month with only 26.5 percent of the patients still alive after 2 years and the median survival of anaplastic astrocytomas (WHO grade 3) is 19.2 month. Recent evidence suggests that the transcription factor NF-kappaB is constitutively expressed in malignant gliomas and that its inhibition by drugs like Sulfasalazine may block the growth of astrocytic tumors in vitro and in experimental models of malignant gliomas. DESIGN: ULg_GBM_04/1 is a prospective, randomized, double blind single-center phase 1-2 study. A total of twenty patients with progressive malignant glioma despite surgery, radiation therapy and a first line of chemotherapy will be recruited and assigned to four dosage regimen of Sulfasalazine. This medication will be taken orally t.i.d. at a daily dose of 1.5-3-4 or 6 g, continuously until complete remission, evidence of progression or drug intolerance. Primary endpoints are drug safety in the setting of malignant gliomas and tumor response as measured according to MacDonald's criteria. An interim analysis of drug safety will be conducted after the inclusion of ten patients. The complete evaluation of primary endpoints will be conducted two years after the enrollment of the last patient or after the death of the last patient should this occur prematurely. DISCUSSION: The aim of this study is to evaluate the safety and efficacy of Sulfasalazine as a treatment for recurring malignant gliomas. The safety and efficacy of this drug are analyzed as primary endpoints. Overall survival and progression-free survival are secondary endpoint. [less ▲]Detailed reference viewed: 69 (16 ULg)
The epileptic syndromes with continuous spikes and waves during slow sleep: definition and management guidelines.
; ; et al
in Acta Neurologica Belgica (2006), 106(2), 52-60
The authors propose to define the epileptic syndromes with continuous spikes and waves during slow sleep (CSWS) as a cognitive or behavioral impairment acquired during childhood, associated with a strong ... [more ▼]
The authors propose to define the epileptic syndromes with continuous spikes and waves during slow sleep (CSWS) as a cognitive or behavioral impairment acquired during childhood, associated with a strong activation of the interictal epileptiform discharges during NREM sleep--whatever focal or generalized--and not related to another factor than the presence of CSWS. The type of syndrome will be defined according to the neurological and neuropsychological deficit. These syndromes have to be classified among the localization-related epileptic syndromes. Some cases are idiopathic and others are symptomatic. Guidelines for work-up and treatment are proposed. [less ▲]Detailed reference viewed: 76 (4 ULg)
Spontaneous pneumocephalus caused by the association of pneumosinus dilatans and meningioma. Case illustration.
; ; Deprez, Manuel et al
in Journal of Neurosurgery (2006), 105(6), 934Detailed reference viewed: 19 (0 ULg)
Increased incidence of sporadic Creutzfeldt-Jakob disease in the age groups between 70 and 90 years in Belgium.
; ; et al
in European Journal of Epidemiology (2006), 21(6), 443-7
From 1998 a prospective surveillance study of Creutzfeldt-Jakob disease (CJD) has been initiated in Belgium. In addition to epidemiological data, information on cerebrospinal fluid biomarkers, prion ... [more ▼]
From 1998 a prospective surveillance study of Creutzfeldt-Jakob disease (CJD) has been initiated in Belgium. In addition to epidemiological data, information on cerebrospinal fluid biomarkers, prion protein gene and brain neuropathology was collected. From 1-1-1998 to 31-12-2004, 188 patients were referred to the surveillance system. In 85 patients a 'definite' diagnosis of sporadic CJD (sCJD) could be made, whereas 26 patients remained 'probable'. We further identified two unrelated patients with an E200K mutation, and two patients with a seven octapeptide repeat insertion in one family. In one patient a familial history was noted but genetic analysis was not performed. In 72 patients different final diagnoses were made, Alzheimer's disease being the most frequent (N = 20). The demographic parameters of the Belgian population were similar to those observed in the rest of Europe. We did notice a significantly increased age-specific incidence (> 6/10(6)/year) of sCJD patients between 70 and 90 years old in the period 2002-2004 compared to 1998-2001 and retrospectively obtained data (1990-1997, p < 0.01). We undertook a detailed clinical and biochemical analysis to investigate this increase but could not identify any reason other than an increased vigilance for the diagnosis.In conclusion, our study identified that in the past sCJD may have been underestimated in patients over age 70 although these patients are both clinically and neurobiochemically similar to the general sCJD phenotype. [less ▲]Detailed reference viewed: 8 (0 ULg)
Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson's disease.
; ; Deprez, Manuel et al
in Neurogenetics (2006), 7(1), 1-11
We have used brain tissue from clinically well-documented and neuropathologically confirmed cases of sporadic Parkinson's disease to establish the transcriptomic expression profile of the medial and ... [more ▼]
We have used brain tissue from clinically well-documented and neuropathologically confirmed cases of sporadic Parkinson's disease to establish the transcriptomic expression profile of the medial and lateral substantia nigra. In addition, the superior frontal cortex was analyzed in a subset of the same cases. DNA oligonucleotide microarrays were employed, which provide whole human genome coverage. A total of 570 genes were found to be differentially regulated at a high level of significance. A large number of differentially regulated expressed sequence tags were also identified. Levels of mRNA sequences encoded by genes of key interest were validated by means of quantitative real-time polymerase chain reaction (PCR). Comparing three different normalization procedures, results based on the recently published GeneChip Robust Multi Array algorithm were found to be the most accurate predictor of real-time PCR results. Several new candidate genes which map to PARK loci are reported. In addition, the DNAJ family of chaperones is discussed in the context of Parkinson's disease pathogenesis. [less ▲]Detailed reference viewed: 8 (1 ULg)
Pathologie inflammatoire de l'hypophyse et grossesse
Hansen, Isabelle ; Vroonen, Laurent ; et al
in Pathologie hypophysaire et grossesse (2006)
Les affections hypophysaires, tumorales ou non tumorales, sont classiquement responsables d'infertilité. Grâce aux progrès des traitements médicaux et chirurgicaux développés pour le traitement de ces ... [more ▼]
Les affections hypophysaires, tumorales ou non tumorales, sont classiquement responsables d'infertilité. Grâce aux progrès des traitements médicaux et chirurgicaux développés pour le traitement de ces affections hypophysaires, les grossesses sont de plus en plus fréquentes chez les patientes ayant en particulier un adénome hypophysaire sécrétant ou une insuffisance anté-hypophysaire ou un diabète insipide central. Cependant, les conséquences de l'affection hypophysaire et des traitements pour la mère ou le f¿tus sont toujours discutés par les endocrinologues, les gynécologues, les obstétriciens et les pédiatres. Le but de cet ouvrage unique en français est une mise au point de nos connaissances sur le sujet, et tout particulièrement sur le diagnostic hormonal et radiologique d'un syndrome d'hypersécrétion ou d'une insuffisance hypophysaire au cours d'une grossesse, ainsi que sur la prise en charge des patientes présentant une pathologie hypophysaire tumorale ou non tumorale, désirant ou présentant une grossesse. [less ▲]Detailed reference viewed: 74 (2 ULg)
Comparative study of commercially available anti-alpha-synuclein antibodies.
; ; Deprez, Manuel et al
in Neuropathology & Applied Neurobiology (2006), 32(3), 351-6
Immunohistochemistry for alpha-synuclein has become the histological technique of choice for the diagnosis for Parkinson's disease, Dementia with Lewy bodies and Multiple System Atrophy (http://www.ICDNS ... [more ▼]
Immunohistochemistry for alpha-synuclein has become the histological technique of choice for the diagnosis for Parkinson's disease, Dementia with Lewy bodies and Multiple System Atrophy (http://www.ICDNS.org). Nevertheless, no standardised protocol has been proposed. We have reviewed 242 of the 270 studies published until June 2005 that mentioned immunohistochemistry for anti-alpha synuclein on human tissue and we found that only 75 (31%) used commercial antibodies. We also noted that protocols, particularly dilution and antigen unmasking, varied between studies, even when the same antibody was employed. In order to establish a standardised protocol for alpha-synuclein immunohistochemistry, which can be applied in diagnostic neuropathology we tested seven commercial monoclonal antibodies in brains of subjects with Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, multiple sclerosis with incidental Lewy bodies and aged-matched normal brain and determined for each antibody the best suited protocol for antigen unmasking. We evaluated the intensity of immunolabelling in Lewy bodies, neuropil threads, dendrites, pre-synaptic terminals, granular cytoplasmic positivity, peri-axonal positivity, glial inclusions and non-specific immunolabelling. Although our results showed that all the antibodies detected alpha-synuclein inclusions, differences were noted between antibodies, particularly with regard to the detection of glial inclusions. From our study, the best antibodies of the seven tested appeared to be those directed against amino acids 116-131 and 15-123 and we suggest them to be used in routine diagnostic practice for alpha-synucleinopathies. [less ▲]Detailed reference viewed: 8 (0 ULg)
Transcriptome analysis reveals link between proteasomal and mitochondrial pathways in Parkinson's disease.
; ; et al
in Neurogenetics (2006), 7(3), 139-48
There is growing evidence that dysfunction of the mitochondrial respiratory chain and failure of the cellular protein degradation machinery, specifically the ubiquitin-proteasome system, play an important ... [more ▼]
There is growing evidence that dysfunction of the mitochondrial respiratory chain and failure of the cellular protein degradation machinery, specifically the ubiquitin-proteasome system, play an important role in the pathogenesis of Parkinson's disease. We now show that the corresponding pathways of these two systems are linked at the transcriptomic level in Parkinsonian substantia nigra. We examined gene expression in medial and lateral substantia nigra (SN) as well as in frontal cortex using whole genome DNA oligonucleotide microarrays. In this study, we use a hypothesis-driven approach in analysing microarray data to describe the expression of mitochondrial and ubiquitin-proteasomal system (UPS) genes in Parkinson's disease (PD). Although a number of genes showed up-regulation, we found an overall decrease in expression affecting the majority of mitochondrial and UPS sequences. The down-regulated genes include genes that encode subunits of complex I and the Parkinson's-disease-linked UCHL1. The observed changes in expression were very similar for both medial and lateral SN and also affected the PD cerebral cortex. As revealed by "gene shaving" clustering analysis, there was a very significant correlation between the transcriptomic profiles of both systems including in control brains. Therefore, the mitochondria and the proteasome form a higher-order gene regulatory network that is severely perturbed in Parkinson's disease. Our quantitative results also suggest that Parkinson's disease is a disease of more than one cell class, i.e. that it goes beyond the catecholaminergic neuron and involves glia as well. [less ▲]Detailed reference viewed: 8 (1 ULg)
Connexin 30 expression in high grade gliomas : correlation with survival and resistance to ionizing radiation.
Robe, Pierre ; Nguyen Khac, Minh-Tuan ; Deprez, Manuel et al
Conference (2005, March)Detailed reference viewed: 28 (1 ULg)