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Biomedical subjects

J Sahel

Publications and source records attributed to J Sahel.

At least 19 recordsLinked to original sources
PubMed2006

Subretinal electrode implantation in the P23H rat for chronic stimulations.

BACKGROUND: In age related macular degeneration and inherited dystrophies, preservation of retinal ganglion cells has been demonstrated. This finding has led to the development of various models of subretinal or epiretinal implant in order to restore vision. This study addresses the development of a polyimide subretinal electrode platform in the dystrophic P23H rat in vivo. METHODS: A technique was developed for implanting a subretinal electrode into the subretinal space and stabilising the distal extremity of the cabling on the rat cranium in order to allow future electrical stimulations of the retina. RESULTS: In vivo imaging of the retina with the scanning laser ophthalmoscope demonstrated reabsorption of the surgically induced retinal detachment and the absence of major tissue reactions. These in vivo observations were confirmed by retinal histology. The extraocular fixation system on the rat cranium was effective in stabilising the distal connector for in vivo stimulation. CONCLUSION: This study demonstrates that a retinal implant can be introduced into the subretinal space of a dystrophic rat with a stable external connection for repeatable electrical measurements and stimulation. This in vivo model should therefore allow us to evaluate the safety and efficacy of electrical stimulations on dystrophic retina.

Animals↗
PubMed2005

Systolodiastolic variations of blood flow during central retinal vein occlusion: exploration by dynamic angiography.

BACKGROUND/AIM: In patients with acute central retinal vein occlusion (CRVO), dynamic angiography may reveal the presence of pulsatile flow (termed here pulsatile venular outflow, PVO) within first order veins (that is, the large veins). The main goal of this study was to investigate the mechanism underlying PVO. METHODS: 10 patients with CRVO and PVO were included. Quantitative and qualitative analysis of venous flow on dynamic angiograms allowed the correlation, temporally, of second and first order vein flow on the one hand, and venous flow and systolic cycle on the other. RESULTS: Analysis of the time-velocity curve showed that (1) the onset of arterial systole preceded the onset of PVO by less than 0.08 seconds (n = 5); (2) PVO onset was simultaneous to the time of onset of minimal flow (Vmin) in first order veins (n = 10); (3) the time of onset of maximal flow (Vmax) in first order veins occurred 0.20-0.44 seconds after the onset of PVO (n = 6). CONCLUSIONS: During CRVO with severe reduction in blood flow, the presence of PVO is the result of the existence of a distinct haemodynamic regimen in first and second order veins. These data support the hypothesis that second order veins flow is synchronous with the arterial flow, while the delayed peak flow in first order veins may reflect the consequences of the delayed IOP curve and/or of intermittent venous compression.

Acute Disease↗
PubMed2002

[Multifocal electroretinogram for assessing sun damage following the solar eclipse of 11 August 1999].

Following the eclipse of 11 August 1999, the ophthalmological clinic of Strasbourg cared for 4 patients who suffered from sun damage. The multifocal electroretinogram (ERG) carried out on our first patient enabled us to not only confirm the existence of a residual maculopathy as shown by the static visual field, but also, and above all to quantify the foveolar deficit. Moreover, with the other 3 patients, the multifocal ERG enabled us to detect a foveolar deficit completely overlooked by the other usual tests. In light of our clinical study, we can assert that the multifocal ERG has yet to be equaled by any other test for analysis of macular function.

Adolescent↗
PubMed2001

Alternate FGF2-ERK1/2 signaling pathways in retinal photoreceptor and glial cells in vitro.

Basic fibroblast growth factor (FGF2) stimulates photoreceptor survival in vivo and in vitro, but the molecular signaling mechanism(s) involved are unknown. Immunohistochemical and immunoblotting analyses of pure photoreceptors, inner retinal neurons, and Müller glial cells (MGC) in vitro revealed differential expression of the high affinity FGF receptors (FGFR1-4), as well as many cytoplasmic signaling intermediates known to mediate the extracellular signal-regulated kinase (ERK1/2) pathway. FGF2-induced tyrosine phosphorylation in vitro exhibited distinct profiles for each culture type, and FGF2-induced ERK1/2 activation was observed for all three preparations. Whereas U0126, a specific inhibitor of ERK kinase (MEK), completely abolished FGF2-induced ERK1/2 tyrosine phosphorylation and survival in cultured photoreceptors, persistent ERK1/2 phosphorylation was observed in cultured inner retinal cells and MGC. Furthermore U0126 treatment entirely blocked nerve growth factor-induced ERK1/2 activation in MGC, as well as FGF2-induced ERK1/2 activation in cerebral glial cells. Taken together, these data indicate that FGF2-induced ERK1/2 activation is entirely mediated by MEK within photoreceptors, which is responsible for FGF2-stimulated photoreceptor survival. In contrast, inner retina/glia possess alternative, cell type, and growth factor-specific MEK-independent ERK1/2 activation pathways. Hence signaling and biological effects elicited by FGF2 within retina are mediated by cell type-specific pathways.

Animals↗
PubMed2001

Molecular cloning and characterization of dystrophin and Dp71, two products of the Duchenne Muscular Dystrophy gene, in zebrafish.

Dystrophin, the protein responsible for Duchenne Muscular Dystrophy (DMD), plays a critical role in the maintenance of the muscle membrane integrity. There are several forms of dystrophin derived from the DMD gene by alternative promoter usage. In addition to full-length dystrophin (Dp427), four shorter transcripts have been identified: Dp260, Dp140, Dp116 and Dp71. The functional role played by the different products of the DMD gene is not yet determined. To get insight into the function of dystrophin and related products, we have investigated the presence of dystrophin in zebrafish. This choice takes advantage of large-scale mutagenesis screens in zebrafish, which have led to the identification of several mutants with motility defects. The identification and characterization of the genes affected by these mutations is likely to provide relevant information for the understanding of the molecular mechanisms of muscle development and function. Two cDNA clones encoding the homologues of dystrophin and Dp71 in zebrafish were identified and characterized. Both transcripts exhibit a high degree of sequence homology with the dystrophin and Dp71 proteins described in higher vertebrates. In addition, three alternative spliced transcripts that occur at the C-terminal end of the zebrafish DMD gene have been identified. These transcripts exhibit different patterns of tissue expression. We have also determined the chromosomal localization of dystrophin on the radiation hybrid map of the zebrafish genome. Our results indicate that the dystrophin gene is localized to linkage group one. Altogether, these results give new insights on the physiological role played by dystrophin and related proteins, and provide new tools for the identification of mutated genes associated with muscle defects in zebrafish.

Alternative Splicing↗
PubMed2001

Differential distribution of the members of the dystrophin glycoprotein complex in mouse retina: effect of the mdx(3Cv) mutation.

Dystrophin glycoprotein complex (DGC) assembly and function require mediation by dystrophin in skeletal muscle. The existence of such complexes and the correlation with DMD phenotypes are not yet established in the central nervous system. Here we have studied the expression of DMD gene mRNAs and proteins in retina from C57BL/6 and mdx(3Cv) mouse strains. Then we have comparatively investigated the localization of dystrophin and dystrophin-associated proteins (DAPs) in both strains to analyze the repercussion of the mdx(3Cv) mutation on the retinal distributions of alpha/beta-dystroglycan, alpha1-syntrophin, alpha-dystrobrevin, and delta/gamma-sarcoglycan. Results showed that DMD gene product deficiency affects the expression of dystroglycan assembly exclusively at the outer plexiform layer without an apparent effect on the other DAPs. We conclude that the localization of members of the DGC could be independent of the presence of the DMD gene products and/or utrophin.

Animals↗
PubMed2001

Isolated late-onset cone-rod dystrophy revealing a familial neurogenic muscle weakness, ataxia, and retinitis pigmentosa syndrome with the T8993G mitochondrial mutation.

PURPOSE: To report a late-onset cone-rod dystrophy that revealed a familial neurogenic muscle weakness, ataxia, and retinitis pigmentosa syndrome as a consequence of the T8993G mitochondrial mutation. METHODS: Observational case series. A 42-year-old female disclosed a late-onset retinal dystrophy. The family history revealed that her three sons, one of them deceased at the age of 4, had mental and neurologic impairment of variable severity. The retinal dystrophy of the mother was classified as a cone-rod dystrophy. Retinal dystrophy was subsequently diagnosed in the two surviving sons. Screening for mutation in the mitochondrial DNA (mtDNA) was performed because of the combination of neurologic involvement and retinal dystrophy in this family. RESULTS: Molecular analysis of the mtDNA revealed the ATPase-6 gene T8993G mutation in the mother and the two sons. CONCLUSION: This family illustrates the remarkably variable expression of retinal and systemic manifestations related to the T8993G mutation ranging from an isolated late-onset cone-rod dystrophy to a severe neurodegenerative process with a dramatic outcome. Genetic counseling for retinal dystrophies requires careful evaluation of the familial medical history.

Adenosine Triphosphatases↗
PubMed2001

Dystrophin and Dp71, two products of the DMD gene, show a different pattern of expression during embryonic development in zebrafish.

Dystrophin, the protein defective in Duchenne muscular dystrophy (DMD), plays a critical role in the formation and maintenance of the neuromuscular junction. In addition to dystrophin, activation of internal promoters of the DMD gene leads to the production of several short products. Among these, Dp71, which consists of the C-terminal domain of dystrophin, is the most abundant product of the gene in non-muscle tissues and brain. In this report, we compare the temporal and regional expression patterns of dystrophin and Dp71 at different stages of embryonic development and during retinal differentiation in zebrafish. The Dp71 transcripts are the earliest to be expressed at 9-10 h post-fertilization (hpf) in the axial mesoderm. As development proceeds, intense Dp71 staining is observed in the notochord, the developing brain, the marginal regions of the somites and the eye primordium. At the completion of retinal differentiation, Dp71 is expressed in the ganglion and inner nuclear layers. Transcripts encoding dystrophin have a slightly later onset of expression, 13-14 hpf, and remain restricted to the transverse myosepta through all the developmental stages examined. The complementary patterns of expression of dystrophin and Dp71 suggest that these two proteins exert different functions during embryonic development in zebrafish.

Animals↗
PubMed2001

[Conservative treatment of choroidal melanoma using iodine-125 brachytherapy, technique and preliminary analysis of 78 patients].

PURPOSE: Iodine 125 curietherapy is one of the conservative treatments of uveal melanoma. The technique used to achieve these results was simplified through the physical characteristics of the radioelement and the optimized-dosimetry program employed. PATIENTS AND METHODS: 78 patients with choroidal melanoma were treated with iodine 125. About 100 Gy were delivered to the superior pole of the tumour. The minimal length of follow-up was 17 months and the average, 67 months. RESULTS: There was 88% local control, leading to lowered visual acuity in 76% of the cases. Radiation retinopathy, directly related to proximity to the macula, is the principle etiology. Seven patients died of hepatic metastasis, five patients were enucleated. Four patients were further treated with protontherapy to make up for noncontrol locally. CONCLUSION: One dose of 100 Gy to the superior pole of the tumor seemed to lead to good local control, with the exception of complications related to proximity to the macula and the optic nerve. In this attempt to optimize irradiation, the time lapse between any benefit in local control derived from irradiation and posttherapeutic complications observed remains insufficient to evaluate any relationship.

Adult↗
PubMed2001

Biliopancreatic fistulas complicating pancreatic pseudocysts: a report of three cases demonstrated by endoscopic retrograde cholangiopancreatography.

Three patients were found to have fistulation of the pancreatic and common bile ducts, complicating chronic pancreatitis in one patient and acute pancreatitis in two patients. Closure of the fistula was achieved with biliary and pancreatic stenting in one patient; the other two patients were treated surgically because endoscopic treatment had failed. The clinical and radiological features of this exceptional complication are presented, with a brief review of the topic.

Aged↗
PubMed2001

Intraductal papillary or mucinous tumors (IPMT) of the pancreas: report of a case series and review of the literature.

OBJECTIVE: Despite a better understanding of these conditions, intraductal papillary or mucinous tumors (IPMT) of the pancreas still present difficulty relating to the predictive factors of malignancy and the risk of relapse after surgical resection. The aim of this study was to report on our experience and to compare it to previously published cases. METHODS: We studied retrospectively 26 patients (mean age 60.3 yr) presenting with IPMT. Of the 26 patients, 19 had surgical resection and seven did not. The main clinical feature was acute pancreatitis occurring in 38% of the patients. Segmental pancreatectomy was performed in all the cases. At pathological assessment of resection margins, tumor resection was considered as complete in 17 cases. Margins exhibited benign mucinous involvement, and resection was considered to be incomplete in one multifocal case and in one case with diffuse spread of the tumor. RESULTS: A total of 11 tumors were benign and five were malignant. Carcinomas were invasive in four cases (two invading the pancreatic parenchyma, one the duodenum, and one the peripancreatic nodes) and in situ in one case. Malignancy was not diagnosed preoperatively except when invasion was evident (duodenal spread). Although main pancreatic duct type and obstructive jaundice appeared as suggestive features for the risk of malignancy, no reliable preoperative predictive factors for malignancy could be identified as regarding to clinical parameters, biological examinations, carcinoembryonic antigen or CA19-9 levels in serum or in pure pancreatic juice, imaging, and cytological methods. Within 40.8 months mean follow-up after surgery (range 2-96 months), three patients (16%), two with malignant and one with benign tumor, had tumor relapse after respectively 7, 27, and 14 months. Margins were positive without malignant features in the two malignant cases and negative in the other case. Tumor relapse was malignant with diffuse spreading in the three cases, and the patients died within 34 months after surgical resection. CONCLUSIONS: Our series and the review of the literature indicate that preoperative indicators of malignancy in IPMT are still lacking. Concerning resection margins, complete tumor resection is usually possible by segmental pancreatectomy. Malignant relapses are not exceptional. Incomplete resection and diffuse or multifocal tumor represent poor prognostic factors. Total pancreatectomy should be considered in such cases.

Adenocarcinoma, Mucinous↗
PubMed2001

Selective excitotoxic degeneration of adult pig retinal ganglion cells in vitro.

PURPOSE: Excitotoxicity is proposed to play a prominent role in retinal ganglion cell (RGC) death ensuing from diseases such as glaucoma and ischemia, but cell culture studies have used tissue from newborn rodents, yielding conflicting data that implicate either N-methyl D-aspartate (NMDA) or non-NMDA glutamate (Glu) receptor-mediated pathways. Excitotoxic RGC death was examined in vitro in this study, using adult pigs, a large-animal model for human retina. METHODS: Adult pig retina (and for comparative purposes young and adult rat retina) were dissociated and maintained in monolayer culture. Medium was supplemented with Glu or pharmacologic agonists or antagonists, and surviving RGCs and other retinal neurons were quantified using specific immunolabeling methods. Electrophysiological responses to externally applied Glu of RGCs in culture were recorded using whole-cell patch-clamp techniques. RESULTS: Application of Glu led to selective, dose-dependent losses in large RGCs (maximal 37% decrease at 1 mM; median effective dose [ED50], approximately 80 microM) and neurite damage in surviving RGCs. Application of Glu agonists and Glu receptor subclass antagonists showed that large RGC death was mediated through both NMDA and non-NMDA receptor pathways. Small RGCs, amacrine cells, and all other retinal neurons were resistant to Glu-induced death. By comparison, rat retinal cultures displayed heightened RGC vulnerability to Glu, mediated exclusively by non-NMDA receptor-mediated pathways. Amacrine cells were unaffected by NMDA but were very sensitive to kainate application (>90% loss). Other retinal neurons were unaffected by any treatment. CONCLUSIONS: The molecular pathways underlying excitotoxic RGC death in vitro (non-NMDA or NMDA-preferring Glu receptors) vary among species and developmental stages. The selective elimination of adult pig large RGCs by NMDA receptor-mediated pathways more closely resembles human and animal glaucoma in vivo than other published culture models, providing a simplified experimental system for investigating the pharmacologic and toxicologic bases of glaucoma-like neuronal death.

Animals↗
PubMed2000

GABAC receptors are localized with microtubule-associated protein 1B in mammalian cone photoreceptors.

Protein MAP1B was recently reported to link GABA(C) receptors to the cytoskeleton at neuronal synapses. This interaction was demonstrated in the mammalian retina, where GABA(C) receptors were thought to be exclusively expressed in bipolar cells. Our previous studies on cultured photoreceptors suggested however the presence of GABA(C) receptors in cones. To further investigate GABA(C) receptor expression in cones, we measured GABA responses in mammalian photoreceptors in situ, and we examined the distribution of the receptor and that of protein MAP1B in the mammalian outer retina. Photoreceptors were recorded from flat-mounted retinas of retinal degeneration mice at an age when the retina becomes cone-dominated after rod cell death. GABA(A) and GABA(C)-gated currents were produced only in cones but not rods. Recording freshly dissociated retinal cells from wild-type C57 mice confirmed the presence of GABA(A) and GABA(C) receptors in cones. Immunohistochemical labeling of mouse and rat retinal sections localized GABA(C) receptors to cone terminals that were identified by peanut agglutinin lectin staining. As expected from previous studies on bipolar cells, the punctate immunostaining was not restricted to cone terminals in the outer plexiform layer. MAP1B immunolabeling was obtained in rat and pig retinas and was similarly found in cone terminals identified by the peanut agglutinin lectin staining. These results provide physiological and histological evidence that cones receive a GABA feedback in the mammalian retina and are consistent with the notion that protein MAP1B links GABA(C) receptors to the cytoskeleton at postsynaptic sites.

Animals↗
PubMed2000

[Pancreatic intubation ifn pancreas divisum].

AIM: Long-term results of endoscopic pancreatic stenting in pancreas divisum is still debated. The aim of this retrospective study was to evaluate the efficacy of dorsal duct stenting in patients presenting with acute recurrent pancreatitis. PATIENTS AND METHODS: Between 1980 and 1998, among 34 patients presenting with recurrent acute pancreatitis associated with pancreas divisum, 21 were treated by pancreatic stenting during a mean time of 11 months. There were 13 men and eight women (mean age: 50 years). RESULTS: The median follow-up was 50 (range 11-105) months. The number of patients presenting with acute pancreatitis before pancreatic stenting, at the end of stenting and at the end of the follow-up was respectively 21/21 (100%), 2/19 (10%) and 2/18 (11%) (P < 0.01). The number of patients presenting with chronic pain before stenting, at the end of stenting and at the end of the follow-up was respectively 17/21 (80%), 6/19 (31%) and 5/18 (27%) (P = 0.07). The overall morbidity rate was 8/21 patients (38%) including mainly acute pancreatitis (three cases); all but one complication were managed conservatively. CONCLUSION: In patients with pancreas divisum, dorsal duct stenting decreases the rate of recurrent acute pancreatitis but the improvement of chronic pain appears less obvious.

Acute Disease↗
PubMed2000

[Extra-ocular etiologic factors in retinal vein occlusion. Retrospective study of 24 patients].

PURPOSE: Retinal vein occlusion has several causes. Cardiovascular risk factors, particularly systemic hypertension; as well as thrombophilia appear to be involved in the development of retinal vein occlusion. METHODS: In a retrospective study we analyzed these factors in 24 patients, admitted for retinal vein occlusion and isovolaemic hemodilution in an internal medicine unit. RESULTS: In patients over 50 years of age, cardiovascular risk factors predominate; while in patients under 50, one patient out of two has biological features indicating a risk for thrombosis. CONCLUSION: Serological abnormalities could be involved in the physiopathology of retinal vein occlusion in young patients.

Adult↗