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Biomedical subjects

B Devaux

Publications and source records attributed to B Devaux.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Surgical removal of radio-induced lesions after radiosurgery of cerebral arteriovenous malformations].

Radioinduced lesions after radiosurgery of cerebral arteriovenous malformations may be associated with an increased signal on T2-weighted and gadolinium enhancement on T1-weighted MR images. They do not have necessarily a poor prognosis. These lesions are mostly asymptomatic. But in a few cases they can be associated with severe clinical symptoms which can become corticodependant or corticoresistant. We present the 5 cases of such cerebral arteriovenous malformations treated by radiosurgery, out of our series of 705 patients. The removal was easier than that of untreated cerebral arteriovenous malformations, and led to a complete recovery of symptoms and progressive decrease of imaging abnormalities. Such surgery should be proposed in case of symptomatic radioinduced lesions which fail to respond to steroids.

Adult↗
PubMed2001

[Evolution of epileptic seizures associated with cerebral arteriovenous malformations after radiosurgery].

The goal of this study is to evaluate the response of epileptic seizures associated with cerebral arteriovenous malformations following radiosurgery and determine the factors associated with a positive outcome. The series included 210 patients (123 men, 87 women) with a mean age of 33. One hundred seventy three patients out of 210 were controlled after radiosurgery. Seizures completely disappeared in 58% of cases and decreased in 18%. Anti-epileptic treatment was stopped in 44%. Sex and age upon seizure appearance were not found as determining factors in patients whose seizures disappeared after radiosurgery. Generalized seizures disappeared following radiosurgery in 90.7%, partial secondary generalized seizures in 53.5%, and partial seizures in only 39.6%. Frontal or temporal malformations are associated with a better response after radiosurgery than sylvian or rolandic location. Seizure disappearance was maximal in case of isolated seizure prior to the radiosurgery (84.4%), was reduced to 61.2% when seizures were limited to 2 to 20, and disappeared in 21.4% in severe seizures. Epilepsy present less than 3 years prior to radiosurgery disappeared in 71.9%; was reduced to 45% when the delay was over 3 years. Seizures disappeared in 64.4% when the malformation was obliterated, they were reduced to 46.9% when malformations persisted. The persistence of severe seizures following radiosurgery was linked to persistence of the malformation. On the other hand early seizures occurred in 3.3% during the first 48 hours following radiosurgery; they disappeared in 72.2% after that period. De novo seizures also occurred in 1.7% and disappeared in all these cases. In conclusion, seizures associated with cerebral arteriovenous malformations respond well to radiosurgery; the malformation obliteration evokes its association with the seizure; the seizure disappearance in spite of persistence of the malformation evokes the positive effect of radiotherapy on epileptic seizures.

Adolescent↗
PubMed2001

[Course of headaches associated with cAVMs after radiosurgery].

The purpose of this study is to evaluate the response of headaches associated with cerebral arteriovenous malformations following radiosurgery and determine the factors that are associated with a positive outcome. From our series of 700 patients whose cAVM was treated by radiosurgery, this study includes 109 patients (48 males, 61 females) with a mean age of 32 when radiosurgery was performed. Headaches resolved in 37 patients (53.7%), decreased in 14 patients (20.3%), persisted in 16 patients (23.2%), and even increased in frequency in 2 (2.9%). Headaches disappeared 2 years following radiosurgery in the majority of patients (31 out of 37: 83.3%). The disappearance rate of headaches was better when it was the only sign of the malformation (64%) or preceded an epileptic seizure (60%) with respect to the case when it preceded cerebral hemorrhage (34.8%). Headaches having the best response were those with 1 to 2 episodes per month (64.9%) and whose episode duration was less than 3 hours (67.6%). Unilateral headaches accounted for 86.5% of resolved headaches whereas bilateral headaches were only 8.1% and even less were the diffuse ones (5.4%). The best evolution was obtained for those associated with a parietal location of the cerebral arteriovenous malformation, followed by rolandic (respectively 55.5% and 50%). Occipital malformation was associated with headache disappearance in 38.1% and temporal with 34.3%, whereas frontal location was associated with headache disappearance in only 25% of the cases. Headache disappearance was often correlated with cerebral arteriovenous malformation outcome after radiosurgery (64.9% of disappearance in case of complete obliteration). However, in 24.8%, headaches disappeared prior to the malformation obliteration and were associated with a decrease of the flow, of the nidus volume or with the nidus disappearance with the persistence of a precocious venous drainage. Headaches disappeared in spite of the malformation persistence in 5.4% of the cases. We found de novo headaches in one patient one year following RS. Another patient presented an episode of headache 12 hours following RS. The course of headaches associated with cerebral arteriovenous malformations after radiosurgery is positive in the majority of cases and correlated to the malformation outcome. This correlation suggests a link between cerebral arteriovenous malformations and headaches and the equal benefit of radiosurgery on both of them.

Adolescent↗
PubMed2001

[Treatment of cerebral arteriovenous malformations: decision making strategy].

We have evaluated our therapeutic strategy through the results of modalities used alone or in association. Should the place of each modality be modified? What could be the influence of the first consulting physician? We feel at the present time that small cerebral arteriovenous malformations could be treated by radiosurgery, surgery and embolization according to their characteristics and location. For middle size and some large cerebral arteriovenous malformations, we consider that embolization and/or surgery are adjuvant modalities, specifically when the cerebral arteriovenous malformation is located in an eloquent area.

Case Management↗
PubMed2001

Dysembryoplastic neuroepithelial tumors: CT, MR findings and imaging follow-up: a study of 53 cases.

PURPOSE: To evaluate CT and MRI features and long term imaging follow-up of a large series of dysembryoplastic neuroepithelial tumors (DNTS). PATIENTS AND METHODS: We retrospectively analyzed CT (100%) and MR imaging (83%) findings of 53 patients with complex (n = 14), simple (n = 6) or non specific histological forms (n = 33) of DNTS. All patients underwent epilepsy surgery for the treatment of drug resistant partial seizures. Preoperative radiological follow-up from two to 10 years (81%) and a post-operative follow-up from one to 13 years (92%) were available. RESULTS: DNTs are intracortical tumors with no mass effect and no peritumoral edema. An associated deformity of the overlying skull was observed in 44% of the 34 patients with a cortical lesion of the convexity. We found a contrast enhancement of the lesion in 21% of cases, a calcic hyperdensity in 36% of cases and a cystic part in 7.5% of cases. DNTs were hypodense (82%) on CT examinations and had a decreased signal on the T1 Weighted Images (95%) and a hypersignal in T2 Weighted Images (100%) on MR imaging. Eighty-one percent of patients had a mean preoperative radiological follow-up of four years and the tumor was stable in size in all cases; 92% of patients had a mean post-operative radiological follow-up of 4.5 years and no recurrence was seen. CONCLUSION: Three radiological features of DNTs are helpful for the diagnosis: cortical location, absence of mass effect and no surrounding edema. Clinical, radiological and histopathological findings have to be considered together in order to assess the diagnosis and to differentiate DNTs, which are stable lesions from gliomas.

Adult↗
PubMed2000

Broad specificity of GDNF family receptors GFRalpha1 and GFRalpha2 for GDNF and NTN in neurons and transfected cells.

The glial cell line-derived neurotrophic factor (GDNF) family of ligands binds to lipid anchored proteins termed GDNF family receptor (GFR)alphas, and then activates the RET receptor tyrosine kinase, by ligand GFRalpha. The binding of soluble GFRalphas to transfected cells suggested that different GFRalphas were dedicated to particular ligands, with GDNF acting primarily or entirely through GFRalpha1, and neurturin (NTN), through GFRalpha2. More recent evidence has suggested the possibility of cross-talk between these ligands and the two receptors. We examined here whether crosstalk between the GDNF ligands and the GFRalphas is biologically relevant, using midbrain dopaminergic, and parasympathetic, submandibular gland neurons. By biochemical and genetic addition and/or deletion of GFRalpha1 and 2, we show that in both neuronal cell types, robust biological activities of GDNF or NTN can be mediated by either GFRalpha1 or GFRalpha2, although GDNF is slightly more potent in dopaminergic (DA) neurons which normally express GFRalpha1, and NTN in submandibular neurons which normally express GFRalpha2. Throughout the body, GDNF and NTN are likely to have important biological actions on both GFRalpha1- and GFRalpha2-expressing cells.

Animals↗
PubMed2000

Increased expression of cytoskeletal, linkage, and extracellular proteins in failing human myocardium.

Experimental studies have shown that in hypertrophy and heart failure, accumulation of microtubules occurs that impedes sarcomere motion and contributes to decreased ventricular compliance. We tested the hypothesis that these changes are present in the failing human heart and that an entire complex of structural components, including cytoskeletal, linkage, and extracellular proteins, are involved in causing functional deterioration. In explanted human hearts failing because of dilated cardiomyopathy (ejection fraction </=20%), expression of alpha- and beta-tubulin, desmin, vinculin, fibronectin, and vimentin was determined by Northern and Western blot analysis and compared with normal myocardium from explants not used for transplantation. The mRNA for alpha- and beta-tubulin was increased to 2.4-fold (P<0.01) and 1.25-fold (NS), respectively; for desmin, 1.2-fold (P<0.05); for fibronectin, 5-fold (P<0.001); and for vimentin, 1.7-fold (P<0.05). Protein levels for alpha-tubulin increased 2.6-fold (P<0.02); for beta-tubulin, 1.2-fold (P<0.005); for desmin, 2.1-fold (P<0.001); for vinculin, 1.2-fold (P<0.005); for fibronectin, 2.9-fold (P<0.001); and for vimentin, 1.5-fold (P<0. 005). Confocal microscopy showed augmentation and disorganization of all proteins studied. In combination with the loss of myofilaments and sarcomeric skeleton previously reported, these changes suggest cardiomyocyte remodeling. Increased fibronectin and elevated interstitial cellularity (vimentin labeling) indicate progressive fibrosis. The present results suggest a causative role of cytoskeletal abnormalities and myofilament loss for intrinsic contractile and diastolic dysfunction in failing hearts.

Adult↗
PubMed2000

Mammalian-cell-produced neurturin (NTN) is more potent than purified Escherichia coli-produced NTN.

Neurturin (NTN) is a recently identified homologue of glial-cell-line-derived neurotrophic factor. Both factors promote the survival of dopaminergic (DA) neurons. We investigated the biological activity of mammalian-cell-produced NTN versus purified Escherichia coli-produced NTN. Baby hamster kidney cells were engineered to stably secrete mature human NTN. Mammalian-cell-derived NTN enhanced the activity of embryonic DA neurons in vitro, with greater potency (maximum effect achieved in the picogram range) than purified E. coli-produced NTN. Cell-based delivery of NTN (less than 10 ng/day) was also shown to be biologically active in vivo. These results suggest that mammalian-cell-derived NTN, synthesized de novo and delivered in small quantities to the parenchyma at the target site, may be as active as much larger quantities of purified, E. coli-produced NTN, delivered by other means.

Animals↗
PubMed2000

Characterization of novel neutralizing monoclonal antibodies specific to human neurturin.

Neurturin (NTN) a structural and functional relative of glial cell line-derived neurotrophic factor, was originally identified based on its ability to support the survival of sympathetic neurons in culture. Similar to glial cell line-derived neurotrophic factor (GDNF), Neurturin has been shown to bind to a high affinity glycosylphosphatidylinositol (GPI)-linked receptor (GFRalpha2) and induce phosphorylation of the tyrosine kinase receptor Ret, resulting in the activation of the mitogen activated protein kinase (MAPK) signalling pathway. A panel of six novel murine monoclonal antibodies (MAbs) specific to human Neurturin has been developed and characterized. Four of the MAbs tested inhibit, to varying degrees, binding of NTN to the GPI-linked GFRalpha2 receptor. Three MAbs cross-react with the murine homolog. These antibodies have been shown to be useful reagents for Western blotting, immunohistochemistry, and also for the development of a sensitive, quantitative enzyme-linked immunosorbent assay (ELISA) for human NTN. Novel, specific MAbs with varying epitope specificities and blocking activity will be valuable tools for both the in vitro and in vivo characterization of NTN and its relationship to the GFRalpha2 and Ret receptors.

Animals↗
PubMed2000

Stereoelectroencephalography in focal cortical dysplasia: a 3D approach to delineating the dysplastic cortex.

Focal cortical dysplasia (FCD) is an increasingly recognized cause of intractable epilepsy. Surgical data suggest that the dysplastic cortex should be removed to obtain freedom from seizures, but the prognosis remains poor as FCD is difficult to delineate by imaging. We retrospectively analysed a series of 28 patients (aged 5-41 years, median 16.5 years) with FCD who had been investigated by stereoelectroencephalography (SEEG) between 1964 and 1995. Neurophysiological data were correlated with histological findings and surgical outcome. MRI was available for only seven patients. Severe partial epilepsy of early onset, pre-existing neurological deficit (68%) and cognitive impairment were the main clinical features. FCD was distributed equally between all lobes except for the temporal lobe, and was found predominantly on the mesial aspect of the cerebral hemispheres. SEEG findings provided evidence of dysplastic tissue epileptogenicity, as demonstrated by intralesional rhythmic spike discharges, the onset of ictal discharges and a low epileptogenic threshold. The epileptogenic zone corresponded to histologically defined FCD in 82% of the cases. Despite the lack of adequate neuroimaging in most cases, 64% of the patients became seizure-free after surgery. The main predictors of a favourable outcome were complete removal of the epileptogenic zone (P< 0.01) and complete removal of the dysplastic cortex (P< 0.01). These results emphasize the usefulness of neurophysiological data in accurately assessing the extent of the FCD.

Adolescent↗
PubMed2000

Use of phage display for the generation of human antibodies that neutralize factor IXa function.

The use of libraries of phage-displayed human single-chain antibody fragments (scFv) has become a new, powerful tool in rapidly obtaining therapeutically useful antibodies. Here, we describe the generation of human scFv and F(ab')2 directed against the gamma-carboxyglutamic acid (Gla) domain of coagulation factor IX. A large library of human scFv, displayed either on M13 phage or expressed as soluble proteins, was screened for binding to human Gla-domain peptide (Tyr1-Lys43). Among a panel of scFv that bound to the factor IX-Gla domain, six scFv clones recognized full-length factor IX and exhibited strong inhibitory activity of factor IX in vitro. After reformatting as F(ab')2, the affinity for factor IX of three selected clones was determined: 10C12 Kd = 1.6 nmol/l, 13D1 Kd = 2.9 nmol/l, and 13H6 Kd = 0.46 nmol/l. The antibodies specifically bound to factor IX and not to other coagulation factors, as assessed by enzyme-linked immunosorbent-type and human plasma clotting assays. The complementarity determining region amino acid sequences of clones 10C12 and 13D1 only differed at a single residue, whereas 13H6 showed little homology, suggesting that 13H6 binds to a different epitope within the factor IX-Gla domain. Despite the slightly lower affinity of 10C12 F(ab')2 versus 13H6 F(ab')2, 10C12 was consistently more potent than 13H6 in prolonging the activated partial thromboplastin time (APTT), in inhibiting platelet-mediated plasma clotting, and in inhibiting factor X activation by the intrinsic Xase complex. Finally, 10C12 F(ab')2 also recognized and neutralized factor IX/factor IXa of different species, as demonstrated by the specific APTT prolongation of dog, mouse, baboon and rabbit plasma. In summary, the results validate the usefulness of scFv phage-displayed libraries to rapidly generate fully human antibodies as potential new therapeutics for thrombotic disorders.

Amino Acid Sequence↗
PubMed1999

Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2.

Apoptosis is implicated in the generation and resolution of inflammation in response to bacterial pathogens. All bacterial pathogens produce lipoproteins (BLPs), which trigger the innate immune response. BLPs were found to induce apoptosis in THP-1 monocytic cells through human Toll-like receptor-2 (hTLR2). BLPs also initiated apoptosis in an epithelial cell line transfected with hTLR2. In addition, BLPs stimulated nuclear factor-kappaB, a transcriptional activator of multiple host defense genes, and activated the respiratory burst through hTLR2. Thus, hTLR2 is a molecular link between microbial products, apoptosis, and host defense mechanisms.

Antibodies, Monoclonal↗
PubMed1999

Protection and regeneration of nigral dopaminergic neurons by neurturin or GDNF in a partial lesion model of Parkinson's disease after administration into the striatum or the lateral ventricle.

Both glial cell line-derived neurotrophic factor (GDNF) and its recently discovered congener, neurturin (NTN), have been shown to exert neuroprotective effects on lesioned nigral dopamine (DA) neurons when administered at the level of the substantia nigra. In the present study, we have explored the relative in vivo potency of these two neurotrophic factors using two alternative routes of administration, into the striatum or the lateral ventricle, which may be more relevant in a clinical setting. In rats subjected to an intrastriatal (IS) 6-hydroxydopamine (6-OHDA) lesion, GDNF and NTN were injected every third day for 3 weeks starting on the day after the 6-OHDA injection. GDNF provided almost complete (90-92%) protection of the lesioned nigral DA neurons after both IS and intracerebroventricular (ICV) administration. NTN, by contrast, was only partially effective after IS injection (72% sparing) and totally ineffective after ICV injection. Although the trophic factor injections protected the nigral neurons from lesion-induced cell death, the level of expression of the phenotypic marker, tyrosine hydroxylase (TH), was markedly reduced in the rescued cell bodies. The extent of 6-OHDA-induced DA denervation in the striatum was unaffected by both types of treatment; consistent with this observation, the high rate of amphetamine-induced turning seen in the lesioned control animals was unaltered by either GDNF or NTN treatment. In the GDNF-treated animals, and to a lesser extent also after IS NTN treatment, prominent axonal sprouting was observed within the globus pallidus, at the level where the lesioned nigrostriatal axons are known to end at the time of onset of the neurotrophic factor treatment. The results show that GDNF is highly effective as a neuroprotective and axon growth-stimulating agent in the IS 6-OHDA lesion model after both IS and ICV administration. The lower efficacy of NTN after IS, and particularly ICV, administration may be explained by the poor solubility and diffusion properties at neutral pH.

Amphetamine↗
PubMed1999

Selective cloning of cell surface proteins involved in organ development: epithelial glycoprotein is involved in normal epithelial differentiation.

Coordinating the activities of neighboring cells during development in multicellular organisms requires complex cellular interactions involving secreted, cell surface, and extracellular matrix components. Although most cloning efforts have concentrated on secreted molecules, recent work has emphasized the importance of membrane-bound molecules during development. To identify developmental genes, we raised antibodies to normal embryonic pancreatic epithelial cell surface proteins. These antibodies were characterized and used to clone the genes coding for the proteins by a panning strategy. Using this approach, we cloned the rat homologue of the mouse epithelial glycoprotein (EGP). Our immunohistochemistry data, describing the expression of EGP during rat development, as well as our in vitro data, looking at the effect of the anti-EGP antibody and the extracellular domain of EGP on embryonic pancreatic epithelial cell number and volume, strongly suggest a role for EGP during pancreatic development.

Amino Acid Sequence↗
PubMed1999

A human antibody that binds to the gamma-carboxyglutamic acid domain of factor IX is a potent antithrombotic in vivo.

10C12, a human antibody F(ab')2, which specifically binds to the Gla domain of factor IX, interfered with all known coagulation processes that involve factor IX/IXa. These include the function of the intrinsic Xase complex and the activation of zymogen factor IX by factor XIa and by the tissue factor:factor VIla complex. Furthermore, 10C12 potently inhibited activated partial thromboplastin clotting times (APTT) in plasma of guinea pig and rat, thus enabling in-vivo evaluation. In guinea pigs, a bolus administration of 10C12 (10 microg/kg) prevented cyclic flow variations in damaged carotid arteries without affecting coagulation or bleeding parameters. At a 100-fold higher dose, 10C12 had no effect on normal hemostasis as assessed by the cuticle bleeding time. At this dose, 10C12 was also efficacious in a rat arterial thrombosis model, substantially reducing clot weight and duration of vessel occlusion while prolonging ex-vivo APTT only 1.2-fold. The dose of heparin required to produce comparable antithrombotic effects prolonged the APTT by 12-fold and increased the tail bleeding time (TBT) by 8-fold. In contrast, 10C12 had no effect on TBT. However, rat tails showed a tendency for rebleeding which 10C12 exacerbated. In conclusion, the antithrombotic potency of the 10C12 antibody in two species provides evidence for an important role of F.IX, and its Gla domain in particular, during thrombogenesis under arterial flow conditions. The relative safety at effective doses of this fully human antibody suggests that it may have therapeutic value for treatment of thrombotic disorders.

1-Carboxyglutamic Acid↗
PubMed1998

Experimental autoimmune encephalomyelitis induced with a combination of myelin basic protein and myelin oligodendrocyte glycoprotein is ameliorated by administration of a single myelin basic protein peptide.

Multiple sclerosis is an autoimmune disease of the central nervous system in which T cell reactivity to several myelin proteins, including myelin basic protein (MBP), proteolipid protein, and myelin oligodendrocyte glycoprotein (MOG), has been implicated in the perpetuation of the disease state. Experimental autoimmune encephalomyelitis (EAE) is used commonly as a model in which potential therapies for multiple sclerosis are evaluated. The ability of T cell epitope-containing peptides to down-regulate the disease course is well documented for both MBP- and proteolipid protein-induced EAE, and recently has been shown for MOG-induced EAE. In this study, we describe a novel EAE model, in which development of severe disease symptoms in (PL/J x SJL)F1 mice is dependent on reactivity to two different immunizing Ags, MBP and MOG. The disease is often fatal, with a relapsing/progressive course in survivors, and is more severe than would be predicted by immunization with either Ag alone. The MOG plus MBP disease can be treated postinduction with a combination of the MOG 41-60 peptide (identified as the major therapeutic MOG epitope for this strain) and the MBP Ac1-11[4Y] peptide. A significant treatment effect can also be obtained by administration of the MBP peptide alone, but this effect is strictly dose dependent. This MBP peptide does not treat the disease induced only with MOG. These results suggest that peptide immunotherapy can provide an effective means of mitigating disease in this model, even when the treatment is targeted to only one component epitope or one component protein Ag of a diverse autoimmune response.

Animals↗
PubMed1998

[The place of radiosurgery in the treatment of hypophyseal adenoma].

Since 1984, the neurosurgical team of Sainte-Anne Hospital in Paris has taken in charge almost 750 patients for linear accelerator radiosurgery. But only a small percentage of them were harbouring a pituitary tumor. That is why the present paper is based mostly on literature data. Pituitary adenoma radiosurgery (RS) is a second intention therapeutic method. It should be recommended only after failure of medical and/or surgical treatment. Two main methods can be used: linear accelerator-radiosurgery and Cobalt-60 gamma unit. Both procedures provide equivalent results in terms of dosimetry, accuracy and clinical data. Results of various series presented in recent and updated literature have been studied and analysed. They show and confirm the efficiency of radiosurgery on tumor and hormone secretion controls, with few cases of pituitary insufficiency. However, results were disappointing concerning visual disorders, particularly if visual dysfunction and impairment existed before radiosurgery. All authors agree nowadays on different points: a) indications: invasive adenomas, with an incomplete resection, or adenomatous recurrences, b) contraindications: tumoral size > 20 mm, distance to visual pathways < 5 mm, c) imperative precautionary measures: less than 8 Gray must be delivered on visual pathways, less than 40 Gray on oculomotor nerves. In some cases, stereotactic fractioned radiotherapy may be an alternative treatment for large tumors close to visual pathways.

Adenoma↗