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: 16 (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: 35 (1 ULg)
Immunoquantitative PCR for prion protein detection in sporadic Creutzfeldt-Jakob disease.
Gofflot, Stéphanie ; Deprez, Manuel ; Elmoualij, Benaïssa et al
in Clinical Chemistry (2005), 51(9), 1605-11
BACKGROUND: The most common human prion disorder is Creutzfeldt-Jakob disease (CJD); it includes sporadic, familial, iatrogenic, and variant subtypes. Diagnostic tests aim at detection with the highest ... [more ▼]
BACKGROUND: The most common human prion disorder is Creutzfeldt-Jakob disease (CJD); it includes sporadic, familial, iatrogenic, and variant subtypes. Diagnostic tests aim at detection with the highest specificity of very small deposits of abnormal prion protein (PrP). METHODS: We used immunoquantitative PCR (iqPCR) to detect proteinase K-resistant PrP (PrPRes) in tissue from the middle frontal gyrus of 7 patients with sporadic CJD and 7 non-CJD cases. We compared iqPCR with routine optimized ELISA, Western blotting, and immunohistochemical analyses. RESULTS: The 4 methods showed similar 100% sensitivity and specificity for the diagnosis of CJD. Along with high specificity, however, iqPCR had a threshold for PrP(Res) detection at least 10-fold lower than that of the classic ELISA. CONCLUSIONS: iqPCR is a new method for PrPRes detection that combines 100% specificity with a detection threshold at least 10-fold lower than classic techniques. This method may improve the detection of minute PrPRes deposits in tissues and body fluids and thus be useful for diagnostic and sterilization applications. [less ▲]Detailed reference viewed: 214 (18 ULg)
Comment j'explore. . . une vascularite du systeme nerveux peripherique
Iserentant, Cynthia ; Bouquiaux, Olivier ; Deprez, Manuel et al
in Revue Médicale de Liège (2005), 60(10), 805-10
Vasculitic neuropathies require early diagnosis and therapy since their prognosis is potentially severe. The following features are usually suggestive of a vasculitic neuropathy: painful multiple ... [more ▼]
Vasculitic neuropathies require early diagnosis and therapy since their prognosis is potentially severe. The following features are usually suggestive of a vasculitic neuropathy: painful multiple mononeuropathy with an acute/subacute course, signs and symptoms of multisystem involvement (arthritis, asthma, renal and skin involvement), biological evidence of an inflammatory syndrome. In one third of patients however, vasculitic neuropathies present as a polyneuropathy. For other patients, peripheral neuropathy is the presentation mode of a necrotizing vasculitis, in the absence of biological inflammatory syndrome. A combined muscle and nerve biopsy, will usually demonstrate the vasculitic process. Vasculitic neuropathies often have a favourable prognosis when immunosuppressive therapy (corticosteroids and/or cyclophosphamide) is initiated at an early stage. [less ▲]Detailed reference viewed: 115 (9 ULg)
Intrinsic structural failure of polyester (Dacron) vascular grafts. A general review.
Van Damme, Hendrik ; Deprez, Manuel ; Creemers, Etienne et al
in Acta Chirurgica Belgica (2005), 105(3), 249-55
Intrinsic structural failure of Dacron prostheses is a late exceptional complication, resulting from a loss of structural integrity of the graft. The authors report six cases of non-anastomotic false ... [more ▼]
Intrinsic structural failure of Dacron prostheses is a late exceptional complication, resulting from a loss of structural integrity of the graft. The authors report six cases of non-anastomotic false aneurysms in the mid-portion of a vascular Dacron graft, observed at a mean of 12 years after insertion. It concerns four femoro-popliteal bypass grafts, one cross-over graft and a branch of a bifurcated aorto-bifemoral graft, implanted between 1980 and 1990. This represents 0.2% of all vascular Dacron grafts implanted in authors' department since 1980. The degenerated prosthesis was excised, and a new bypass graft was inserted. In three cases, histological analysis revealed a foreign body giant cell reaction against fragmented Dacron fibers. In none of the cases there was evidence of graft infection. The authors discuss the evidence and etiopathogeny of this late, unusual complication, inherent to the Dacron graft material. The most probable causative factor is material fatigue, leading to gradual breakdown and fragmentation of individual fibers, and subsequent biodegradation of the basic material. Such an intrinsic weakness of prosthetic fabric has only be observed in first and second generation Dacron grafts. [less ▲]Detailed reference viewed: 41 (1 ULg)
Recurrent intracranial melanocytoma associated with a nevus of Ota.
; ; Kaschten, Bruno et al
in Acta Neurochirurgica (2005), 147(3), 313-5315Detailed reference viewed: 15 (1 ULg)
Primary temporal bone angiosarcoma: a case report.
; ; et al
in Journal of neuro-oncology (2005), 75(2), 121-5
We present a rare case of temporal bone angiosarcoma diagnosed in a 26-year-old female patient at 36 week of pregnancy. The patient was referred with a 2 months history of left otalgia and tinnitus with a ... [more ▼]
We present a rare case of temporal bone angiosarcoma diagnosed in a 26-year-old female patient at 36 week of pregnancy. The patient was referred with a 2 months history of left otalgia and tinnitus with a tender swelling above the mastoid. Cranial imaging studies showed a 7 x 5 x 4 cm hypervascularized mass located in the left middle fossa with lysis of the temporal bone and extension to the subcutis. After the baby was delivered by caesarean section, the patient entered the oncology protocol. Selective embolization of the feeding vessels was followed by gross total surgical resection using a combined supra- and infra-tentorial approach. Pathological findings were those of a poorly differentiated, highly malignant sarcoma with a large epitheloid component and immunohistochemical evidence of endothelial differentiation (CD31, Factor VIII related antigen, CD34), consistent with an angiosarcoma with epitheloid features. No extra-cranial tumor was found after extensive staging. The patient received adjuvant radiotherapy followed by a course of chemotherapy consisting of 6 cycles of paclitaxel. At 15 months follow-up, she developed multiple distant metastasis to a left postauricular lymph node and to the lungs and ribs. The patient was given a second line chemotherapy using doxorubicine and ifosfamide. Despite an initial good response, she died with metastatic disease 26 months after diagnosis. We present a rare case of primary temporal bone angiosarcoma and report our experience with a multimode therapeutic approach combining surgery, radiotherapy and chemotherapy. [less ▲]Detailed reference viewed: 19 (0 ULg)
Primary central nervous system lymphoma - Report of 32 cases and review of the literature
Dubuisson, Annie ; Kaschten, Bruno ; Lenelle, Jacques et al
in Clinical Neurology & Neurosurgery (2004), 107(1), 55-63
We retrospectively analyzed 32 cases of primary central nervous system lymphoma (PCNSL). Five cases were diagnosed in the period 1987-1994, for 27 cases in the period 1995-2002. There were 17 men and 15 ... [more ▼]
We retrospectively analyzed 32 cases of primary central nervous system lymphoma (PCNSL). Five cases were diagnosed in the period 1987-1994, for 27 cases in the period 1995-2002. There were 17 men and 15 women whose median age was 69 years. Three patients were immunodeficient. The commonest symptoms were focal deficit (16 patients) and cognitive/behaviour disturbances (14 patients). Radiologically, a total of 47 contrast-enhancing lesions were observed in 32 patients; 18 patients had deep-seated lesions. All but two patients underwent histological diagnosis following craniotomy (11 patients) and/or stereotaxic biopsy (22 patients); diagnosis was obtained on CSF cytology in one patient with a third ventricle tumour. In the last patient, the diagnosis was based on the finding of marked tumour shrinkage under corticotherapy, despite two negative histological examinations. Treatment included surgical resection (10 patients), chemotherapy (25 patients) and/or radiotherapy (12 patients). According to the therapeutic recommendations of the GELA (Groupe d'Etude des Lymphomes de l'Adulte), 19 patients received at least two courses of high-dose methotrexate; intrathecal chemotherapy was used in 20 patients with methotrexate and/or cytosine arabinoside. Radiation therapy consisted of whole brain irradiation followed by a boost on tumour site. Nine patients received a combined treatment of chemotherapy and radiotherapy. Twelve patients showed rapid progression to death. At the time of last contact, 28/32 patients (88%) had died, all from PCNSL disease or from complications due to its treatment. The median Survival time was 13.9 months. We conclude that PCNSL is an increasingly frequent tumour. The diagnosis is obtained by stereotactic biopsy in the majority of cases. The prognosis appears dismal despite an intensive multidisciplinary therapeutic approach. (C) 2004 Elsevier B.V. All rights reserved. [less ▲]Detailed reference viewed: 84 (15 ULg)
In vitro and in vivo activity of the nuclear factor-kappa B inhibitor sulfasalazine in human glioblastomas.
Robe, Pierre ; ; et al
in Clinical Cancer Research : An Official Journal of the American Association for Cancer Research (2004), 10(16), 5595-603
Glioblastomas, the most common primary brain cancers, respond poorly to current treatment modalities and carry a dismal prognosis. In this study, we demonstrated that the transcription factor nuclear ... [more ▼]
Glioblastomas, the most common primary brain cancers, respond poorly to current treatment modalities and carry a dismal prognosis. In this study, we demonstrated that the transcription factor nuclear factor (NF)-kappaB is constitutively activated in glioblastoma surgical samples, primary cultures, and cell lines and promotes their growth and survival. Sulfasalazine, an anti-inflammatory drug that specifically inhibits the activation of NF-kappaB, blocked the cell cycle and induced apoptosis in several glioblastoma cell lines and primary cultures, as did gene therapy with a vector encoding a super-repressor of NF-kappaB. In vivo, sulfasalazine also significantly inhibited the growth of experimental human glioblastomas in nude mice brains. Given the documented safety of sulfasalazine in humans, these results may lead the way to a new class of glioma treatment. [less ▲]Detailed reference viewed: 62 (8 ULg)
Vascular endothelial growth factor expression correlates with matrix metalloproteinases MT1-MMP, MMP-2 and MMP-9 in human glioblastomas.
Munaut, Carine ; Noël, Agnès ; Hougrand, Olivier et al
in International Journal of Cancer = Journal International du Cancer (2003), 106(6), 848-55
Vascular endothelial growth factor (VEGF) is the major endothelial mitogen in central nervous system neoplasms and it is expressed in 64-95% of glioblastomas (GBMs). Tumour cells are the main source of ... [more ▼]
Vascular endothelial growth factor (VEGF) is the major endothelial mitogen in central nervous system neoplasms and it is expressed in 64-95% of glioblastomas (GBMs). Tumour cells are the main source of VEGF in GBMs whereas VEGF receptors (VEGFR-1, its soluble form sVEGFR-1, VEGFR-2 and neuropilin-1) are expressed predominantly by endothelial cells. Infiltrating tumour cells and newly-formed capillaries progress through the extracellular matrix by local proteolysis involving matrix metalloproteinases (MMPs). Recent studies have shown that VEGF expression and bioavailability can be modulated by MMPs. We reported previously that the expression of MT1-MMP in human breast cancer cells was associated with an enhanced VEGF expression. We used quantitative RT-PCR, Western blot, gelatin zymography and immunohistochemistry to study the expression of VEGF, VEGFR-1, VEGFR-2, sVEGFR-1, neuropilin-1, MT1-MMP, MMP-2, MMP-9 and TIMP-2 in 20 human GBMs and 5 normal brains. The expression of these MMPs was markedly increased in most GBMs with excellent correlation between mRNA and protein levels; activated forms of MMP-2 and MMP-9 were present in 8/18 and 7/18 of GBMs. A majority of GBMs (17/20) also expressed high levels of VEGF, as previously reported, with strong correlation between VEGF and MT1-MMP gene expression levels, and double immunostaining showed that VEGF and MT1-MMP peptides co-localize in tumour and endothelial cells. Our results suggest that the interplay between metalloproteinases and VEGF previously described in experimental tumours may also be operative in human GBMs. Because of its dual ability to activate MMP-2 and to up-regulate VEGF, MT1-MMP might be of central importance in the growth of GBMs and represent an interesting target for anti-cancer treatments. [less ▲]Detailed reference viewed: 56 (26 ULg)
Estrogens reduce the expression of YKL-40 in the retina: Implications for eye and joint diseases
Rakic, Jean-Marie ; Lambert, Vincent ; Deprez, Manuel et al
in Investigative Ophthalmology & Visual Science (2003), 44(4), 1740-1746
PURPOSE. To identify modifications in the gene expression profile of the ocular posterior segment in ovariectomized (OVX) mice with and without substitutive estradiol therapy and to select differentially ... [more ▼]
PURPOSE. To identify modifications in the gene expression profile of the ocular posterior segment in ovariectomized (OVX) mice with and without substitutive estradiol therapy and to select differentially expressed genes that could be relevant to the natural history of human age-related macular degeneration (AMD). METHODS. Chorioretinal tissues from two groups of 25 treated and untreated OVX mice were analyzed by using cDNA array technology. The expression level of selected genes was confirmed in triplicate by RT-PCR and related to the estrogenic status of the animals. Expression of the YKL-40 gene was further investigated in intact or diseased human retinas and in a murine model of experimental choroidal neovascularization (CNV), using laser pressure catapulting. RESULTS. Of the approximately, 10,000 genes screened, only YKL-40 expression was significantly downregulated by 17-beta-estradiol. YKL-40 was expressed in intact human neural retina and in the RPE. The expression of YKL-40 was upregulated in experimental CNV and in neovascular membranes extracted from patients affected by the exudative form of AMD. CONCLUSIONS. These observations indicate that YKL-40 expression in the retina is modulated by serum levels of estradiol. This protein could be relevant to the development of AMD and is also a new mediator to take into account when evaluating the broad consequences of hormonal replacement therapy. [less ▲]Detailed reference viewed: 81 (21 ULg)
The extraforaminal juxtafacet cyst as a rare cause of L5 radiculopathy: a case report.
; Deprez, Manuel ; Stevenaert, Achille et al
in Spine (2003), 28(19), 405-7
STUDY DESIGN: This is a report of a case. OBJECTIVE: To document the clinical, radiographic, and histologic characteristics of a lumbar extraforaminal juxtafacet cyst. SUMMARY OF BACKGROUND DATA: Spinal ... [more ▼]
STUDY DESIGN: This is a report of a case. OBJECTIVE: To document the clinical, radiographic, and histologic characteristics of a lumbar extraforaminal juxtafacet cyst. SUMMARY OF BACKGROUND DATA: Spinal juxtafacet cysts develop most frequently at the dorsal aspect of the zygapophysial joint, sometimes in the posterolateral area of the canal. In one case, they have been described in the foraminal and extraforaminal region. METHODS: Description of the case report. RESULT: The authors report one case of a strictly extraforaminal juxtafacet cyst responsible for L5 sciatica. CONCLUSIONS: Juxtafacet cysts of the spine represent an infrequent cause of sciatica, usually when they grow in the canal, or more exceptionally when they occupy the foraminal or extraforaminal areas. [less ▲]Detailed reference viewed: 24 (0 ULg)
Duane anomaly, congenital myopathy and severe scoliosis in sibs: new AR syndrome?
; Misson, Jean-Paul ; Gillet, Philippe et al
in Annales de Génétique (2003), 46(4), 449-52
We report on two sisters who show a similar pattern of anomalies consisting of bilateral Stilling-Turk-Duane retraction syndrome (type 3), non-progressive hypotonia with delayed motor milestones but ... [more ▼]
We report on two sisters who show a similar pattern of anomalies consisting of bilateral Stilling-Turk-Duane retraction syndrome (type 3), non-progressive hypotonia with delayed motor milestones but normal intelligence, severe, early onset scoliosis, and short stature. Muscular biopsy revealed numerous regenerating fibers, but no specific abnormalities among the non-regenerating fibers. This combination of anomalies has not been previously reported, and could represent a new autosomal recessive syndrome. The only differential diagnosis is Crisfield-Dretakis-Sharpe syndrome, a combination of lateral gaze palsy, ptosis, and scoliosis without hypotonia, recessively inherited. [less ▲]Detailed reference viewed: 22 (0 ULg)
Macrophage migration inhibitory factor (MIF) expression in human glioblastomas correlates with vascular endothelial growth factor (VEGF) expression
Munaut, Carine ; Boniver, Jacques ; Foidart, Jean-Michel et al
in Neuropathology & Applied Neurobiology (2002), 28(6), 452-460
Macrophage migration inhibitory factor (MIF) is a peptide released upon hypothalamo-pituitary stimulation that acts as a potent endogenous antagonist of the glucocorticoid inhibition of acute inflammatory ... [more ▼]
Macrophage migration inhibitory factor (MIF) is a peptide released upon hypothalamo-pituitary stimulation that acts as a potent endogenous antagonist of the glucocorticoid inhibition of acute inflammatory response and subsequent antigen-specific response. MIF also sustains tumour growth as it promotes angiogenesis, overcomes p53-mediated cell growth arrest and inhibits tumour-specific immune responses. Using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry, we studied MIF expression in 35 human glioblastomas and two normal brains. We compared these results with the expression of vascular endothelial growth factor (VEGF), the most potent angiogenic factor in glioblastomas. We detected MIF in normal cortical neurons and glial cells. All glioblastomas were positive for MIF mRNA with expression levels similar to or higher than those of normal brain. MIF immunoreactivity was seen mainly in tumour cells and less frequently in hyperplastic endothelial cells. The expressions of MIF and VEGF mRNA were strongly correlated (P < 0.0001). Our results demonstrate the expression of MIF in human glioblastomas, and indicate a close relationship with VEGF expression. This is of particular interest given the potential modulation of MIF by glucocorticosteroids. [less ▲]Detailed reference viewed: 67 (3 ULg)
Primary cerebral lymphoma. A retrospective study of 32 patients
Dubuisson, Annie ; Kaschten, Bruno ; Lenelle, Jacques et al
Conference (2002, April 25)Detailed reference viewed: 8 (1 ULg)
Maladie de Horton et atteintes arterielles extratemporales: utilite de la tomographie par emission de positons au 18FDG. A propos de trois observations et d'une revue de la litterature
; ; Delanaye, Pierre et al
in Revue de Médecine Interne (2002), 23(7), 584-91
PURPOSE: We report three cases of Horton's disease, in which F18-Fluorine-2-Deoxy-D-Glucose (18FDG) positron emission tomography (PET) demonstrated a clinically unsuspected extra-cranial vessels ... [more ▼]
PURPOSE: We report three cases of Horton's disease, in which F18-Fluorine-2-Deoxy-D-Glucose (18FDG) positron emission tomography (PET) demonstrated a clinically unsuspected extra-cranial vessels hypermetabolism. METHODS: Fully corrected whole-body PET was performed in three patients (two women, one man) for exploring a marked inflammatory syndrome. Scanning was acquired 60 min after i.v. injection of 222 MBq of 18FDG in average. RESULTS: In two patients with histologically proven Horton's disease, PET alone showed increased glucose metabolism involving the carotid and sub-clavian arteries as well as the ascending aorta, aortic arch, thoracic and abdominal aorta, and the iliac and femoral arteries. In the third patient, by detecting cervical, thoracic and abdominal vessel hypermetabolism, PET non-invasively contributed to the diagnosis of giant cell arteritis. All patients had complete clinical and biological response to corticoids. PET controls performed 3- to 6-months post-treatment, confirmed the disappearance of the metabolic stigma. CONCLUSION: 18FDG PET may show an increased glucose metabolism in asymptomatic extracranial vessels locations of Horton's arterities. If these observations are confirmed on controlled trials, PET could be particularly useful for non-invasive diagnosing, staging and monitoring atypical clinical forms of Horton's disease. The metabolic imaging could also contribute to a better understanding of the pathogenesis of GCA. [less ▲]Detailed reference viewed: 215 (9 ULg)
Forme péronière d‘une dystrophie musculaire facio-scapulo-humérale liée au chromosome 4q35
; SADZOT, Bernard ; Deprez, Manuel et al
Conference (2002)Detailed reference viewed: 21 (0 ULg)
Intravascular malignant lymphomatosis: report of 2 neurological cases
; Dioh, Alioune ; Maertens De Noordhout, Alain et al
in Acta Neurologica Belgica (2002), 102(2), 76-81
We report two cases of intravascular malignant lymphomatosis (IML) with a clinical expression limited to the central nervous system. The first patient presented with signs of cerebral, cerebellar and ... [more ▼]
We report two cases of intravascular malignant lymphomatosis (IML) with a clinical expression limited to the central nervous system. The first patient presented with signs of cerebral, cerebellar and spinal cord involvement. The second had an isolated involvement of the spinal cord. In both cases the diagnosis was made at post-mortem examination; pre-mortem examination of biopsy tissue from peripheral nerve and muscle in the first case, spleen and liver in the second were unhelpful for the diagnosis of lymphoma. We review the published literature on IML, its ante-mortem diagnosis and treatment. [less ▲]Detailed reference viewed: 38 (7 ULg)
Global democratic consensus on neuropathological disease criteria.
; ; et al
in Lancet Neurology (2002), 1(6), 340Detailed reference viewed: 27 (1 ULg)