Pharmacological Modulation of the Bystander Effect in the Herpes Simplex Virus Thymidine Kinase/Ganciclovir Gene Therapy System: Effects of Dibutyryl Adenosine 3',5'-Cyclic Monophosphate, Alpha-Glycyrrhetinic Acid, and Cytosine Arabinoside
Robe, Pierre ; ; Martin, Didier et al
in Biochemical Pharmacology (2000), 60(2), 241-9
The herpes simplex virus type 1 thymidine kinase (HSV1-tk) suicide gene/ganciclovir system was first applied to the treatment of glioblastoma tumors, but was hampered by the low gene transfection yield ... [more ▼]
The herpes simplex virus type 1 thymidine kinase (HSV1-tk) suicide gene/ganciclovir system was first applied to the treatment of glioblastoma tumors, but was hampered by the low gene transfection yield. Fortunately, the gap junction-dependent diffusion of phosphorylated ganciclovir metabolites from transfected cells to their neighbors proved to enhance the overall benefit of this strategy. However, as tumor cells are often gap junction-deficient, we sought to restore this property pharmacologically and hence to improve the efficacy of the treatment. We demonstrated that this approach was feasible in glioblastoma cells using dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) (100 microM) as a pharmacological inducer of gap junctions. alpha-Glycyrrhetinic acid (25 microM), on the other hand, strongly inhibited both gap junction-mediated intercellular communication and the bystander effect, thus confirming the role of gap junctions in HSV-tk-mediated bystander killing. Using cytosine arabinoside as a growth inhibitor, we underlined the role of tumor cell proliferation in the sensitivity of HSV-tk-transfected cells to ganciclovir and demonstrated its correlation with the importance of the bystander effect. [less ▲]Detailed reference viewed: 74 (16 ULg)
Unruptured intracranial aneurysm-risk of rupture and risks of surgical intervention.
Conference (2000, May 04)Detailed reference viewed: 17 (0 ULg)
Le syndrome centro-médullaire: corrélation clinique et radiologique. A propos d'une série de 18 cas.
; Martin, Didier ; Lenelle, Jacques et al
Conference (2000, March 18)Detailed reference viewed: 36 (4 ULg)
Major histocompatibility complex class II expression by activated microglia caudal to lesions of descending tracts in the human spinal cord is not associated with a T cell response.
; ; et al
in Acta Neuropathologica (2000), 100(5), 528-36
Lesion-induced microglial/macrophage responses were investigated in post-mortem human spinal cord tissue of 20 patients who had died at a range of survival times after spinal trauma or brain infarction ... [more ▼]
Lesion-induced microglial/macrophage responses were investigated in post-mortem human spinal cord tissue of 20 patients who had died at a range of survival times after spinal trauma or brain infarction. Caudal to the spinal cord injury or brain infarction, a strong increase in the number of activated microglial cells was observed within the denervated intermediate grey matter and ventral horn of patients who died shortly after the insult (4-14 days). These cells were positive for the leucocyte common antigen (LCA) and for the major histocompatibility complex class II antigen (MHC II), with only a small proportion staining for the CD68 antigen. After longer survival times (1-4 months), MHC II-immunoreactivity (MHC II-IR) was clearly reduced in the grey matter but abundant in the white matter, specifically within the degenerating corticospinal tract, co-localising with CD68. In this fibre tract, elevated MHC II-IR and CD68-IR were still detectable 1 year after trauma or stroke. It is likely that the subsequent expression of CD68 on MHC II-positive microglia reflects the conversion to a macrophage phenotype, when cells are phagocytosing degenerating presynaptic terminals in grey matter target regions at early survival times and removing axonal and myelin debris in descending tracts at later survival times. No T or B cell invasion or involvement of co-stimulatory B7 molecules (CD80 and CD86) was observed. It is possible that the up-regulation of MHC II on microglia that lack the expression of B7 molecules may be responsible for the prevention of a T cell response, thus protecting the spinal cord from secondary tissue damage. [less ▲]Detailed reference viewed: 34 (0 ULg)
Les traumatismes de la moelle épinière. Aspects cliniques et expérimentaux.
Post doctoral thesis (2000)Detailed reference viewed: 17 (2 ULg)
Confrontation anatomo-clinique. A propos d'un cas de carcinome renal a cellules claires
; Delbecque, Katty ; Delvenne, Philippe et al
in Revue Médicale de Liège (1999), 54(11), 859-63
The authors report the case of a patient with a history of hypertension and multiple intracerebral hemorrhages who was found at post mortem examination to have a renal cell carcinoma. The relationship ... [more ▼]
The authors report the case of a patient with a history of hypertension and multiple intracerebral hemorrhages who was found at post mortem examination to have a renal cell carcinoma. The relationship between renal carcinoma and hypertensive intracerebral hemorrhages is discussed. [less ▲]Detailed reference viewed: 40 (2 ULg)
Grafts of Meningeal Fibroblasts in Adult Rat Spinal Cord Lesion Promote Axonal Regrowth
Franzen, Rachelle ; Martin, Didier ; et al
in Neuroreport (1999), 10(7), 1551-6
We have studied the morphological consequences of implantation into the injured adult rat spinal cord of fibroblasts derived from the meninges overlying the cerebral cortex. Our initial objective was to ... [more ▼]
We have studied the morphological consequences of implantation into the injured adult rat spinal cord of fibroblasts derived from the meninges overlying the cerebral cortex. Our initial objective was to reproduce the well known post-traumatic fibroadhesive scar observed in the clinical situation. One month after implantation, instead of having formed a fibroadhesive scar, fibroblasts had promoted the regeneration of peptidergic axons originating from dorsal root afferents and, to a lesser extent, of supraspinal serotonergic fibers at the periphery of the grafts. Using RT-PCR we were able to identify in cultures of meningeal-derived fibroblasts mRNAs for beta-NGF, NT3, aFGF and bFGF, which suggests that the promoting effect on axonal regeneration of these cells is at least in part due to their capacity to synthesize neurotrophic factors. [less ▲]Detailed reference viewed: 30 (0 ULg)
Les encéphalocèles antérieurs: à propos de deux cas.
; Martin, Didier ; Stevenaert, Achille
Conference (1999, March 13)Detailed reference viewed: 9 (0 ULg)
Posterior epidural migration of sequestered lumbar disc fragments. Report of two cases.
Robe, Pierre ; Martin, Didier ; Lenelle, Jacques et al
in Journal of Neurosurgery (1999), 90(2 Suppl), 264-6
The posterior epidural migration of sequestered lumbar disc fragments is an uncommon event. The authors report two such cases in which patients presented with either intense radicular pain or cauda equina ... [more ▼]
The posterior epidural migration of sequestered lumbar disc fragments is an uncommon event. The authors report two such cases in which patients presented with either intense radicular pain or cauda equina syndrome. The radiological characteristics were the posterior epidural location and the ring enhancement of the mass after injection of contrast material. The major diagnostic pitfalls are discussed. [less ▲]Detailed reference viewed: 102 (7 ULg)
Les traumatismes du rachis et de la moelle épinière
Scientific conference (1998, May)Detailed reference viewed: 9 (0 ULg)
Analyse des facteurs pronostiques des gliomes cérébraux
Kaschten, Bruno ; Dubuisson, Annie ; Lenelle, Jacques et al
Conference (1998, March 14)Detailed reference viewed: 32 (3 ULg)
Effects of Macrophage Transplantation in the Injured Adult Rat Spinal Cord: A Combined Immunocytochemical and Biochemical Study
Franzen, Rachelle ; Schoenen, Jean ; Leprince, Pierre et al
in Journal of Neuroscience Research (1998), 51(3), 316-27
Early and robust invasion by macrophages may be one of the reasons why axonal regeneration is more effective in the PNS than in the CNS. Therefore, we have grafted autologous peritoneal macrophages ... [more ▼]
Early and robust invasion by macrophages may be one of the reasons why axonal regeneration is more effective in the PNS than in the CNS. Therefore, we have grafted autologous peritoneal macrophages labeled with fluorescent latex microspheres into spinal cord compression lesions. At various survival times, we have studied their effect on the expression of neuronal (neurofilaments [NF], calcitonin gene-related peptide [CGRP], 5-hydroxytryptamine [5-HT]) and nonneuronal markers (myelin-associated glycoprotein [MAG], glial fibrillary acidic protein [GFAP], laminin) by using semiquantitative Western blot and immunohistochemical techniques. After 1 month, we observed a significant decrease of the expression of MAG as well as an important invasion of the lesion site by neurites, chiefly peptidergic axons of presumed dorsal root origin, in macrophage-grafted animals compared with controls. In addition, angiogenesis and Schwann cell infiltration were more pronounced after macrophage grafts, providing an increase in laminin, a favorable substrate for axonal regrowth. By using reverse transcription-polymerase chain reaction (RT-PCR), mRNAs for tumor necrosis factor-alpha (TNF-alpha) were detected in the transplanted cells, whereas results were negative for nerve growth factor (NGF), neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), or acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF). Thus, macrophage grafts may represent an interesting strategy to promote axonal regeneration in the CNS. Our study suggests that they may exert their beneficial effects by degrading myelin products, which inhibit axonal regrowth, and by promoting a permissive extracellular matrix containing notably laminin. No evidence for a direct synthesis of neurotrophic factors by the transplanted macrophages was found in this study, but resident glial cells could secrete such factors as a result of stimulation by macrophage-released cytokines. [less ▲]Detailed reference viewed: 19 (1 ULg)
Comparative Evaluation of Cerebral Aneurysms with Selective Arterially Enhanced Ct and Dsa
; ; et al
in European Radiology (1998), 8(7), 1181-6
The purpose of our study was to compare selective arterially enhanced spiral computed tomographs (ACT) with digital subtraction angiographies (DSA) in the presurgical assessment of cerebral aneurysms. A ... [more ▼]
The purpose of our study was to compare selective arterially enhanced spiral computed tomographs (ACT) with digital subtraction angiographies (DSA) in the presurgical assessment of cerebral aneurysms. A total of 24 aneurysms in 18 patients were explored in a prospective study by ACT and DSA, using an interactive combined CT-angiography suite. Dimensions of the aneurysm, its relation to the parent vessel, and the aneurysmal index were defined on DSA and on surface-shaded display of 3D reformatted images obtained from ACT. Results were correlated with surgical findings. Three aneurysms suspected on DSA were not confirmed by ACT. One fusiform aneurysm suspected on DSA corresponded to a sacciform aneurysm on ACT. Surgical findings confirmed 20 sacciform aneurysms. The aneurysmal index could be measured in all 20 cases of sacciform aneurysms on ACT and could not be determined with confidence in 55 % of the cases on DSA. DSA and ACT gave identical results in 35 % of cases. In 10 %, the index measured by ACT was superior to that determined by DSA for aneurysms which had a diameter of less than 3 mm. In conclusion, the combination of DSA and ACT improved the results of DSA alone. ACT is a reliable method to measure the aneurysmal index in aneurysms with a diameter superior to 3 mm. [less ▲]Detailed reference viewed: 17 (1 ULg)
Spontaneous longitudinally orientated axonal regeneration is associated with the Schwann cell framework within the lesion site following spinal cord compression injury of the rat.
; ; Franzen, Rachelle et al
in Journal of Neuroscience Research (1998), 53(1), 51-65
Spontaneous cellular reorganisation at the lesion site has been investigated following massive spinal cord compression injury in adult rats. By 2 days post operation (p.o.), haemorrhagic necrosis ... [more ▼]
Spontaneous cellular reorganisation at the lesion site has been investigated following massive spinal cord compression injury in adult rats. By 2 days post operation (p.o.), haemorrhagic necrosis, widespread axonal degeneration, and infiltration by polymorphnuclear granulocytes and OX42-positive macrophages were observed in the lesion site. By 7 days p.o., low affinity nerve growth factor receptor-positive Schwann cells, from activated spinal roots, were identified as they migrated far into the lesion. Between 7 and 14 days p.o., the overlapping processes of Schwann cells within the macrophage-filled lesion formed a glial framework which was associated with extensive longitudinally orientated ingrowth by many neurofilament-positive axons. Relatively few of these axons were calcitonin gene-related peptide (CGRP)-, substance P (SP)-, or serotonin (5HT)-positive; however, many were glycinergic or gamma aminobutyric acid (GABA)ergic. At 21 and 28 days p.o. (the longest survival times studied), a reduced but still substantial amount of orientated Schwann cells and axons could be detected at distances of up to 5 mm within the lesion. Glial fibrillary acidic protein (GFAP) immunoreactivity demonstrated the slow formation of astrocytic scarring which only became apparent at the lesion interface between 21 and 28 days p.o. The current data suggest the possibility of developing future therapeutic strategies designed to maintain or even enhance these spontaneous and orientated regenerative events. [less ▲]Detailed reference viewed: 19 (0 ULg)
Spontaneous axonal regeneration into the lesioned site following closed contusion injury to the adult rat spinal cord.
; ; et al
Conference (1997, October)Detailed reference viewed: 4 (0 ULg)