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Biomedical subjects

P David

Publications and source records attributed to P David.

At least 19 recordsLinked to original sources
PubMed1999

Liquid chromatographic determination of imazosulfuron in drinking water and in soil using ultraviolet detection.

Reversed-phase liquid chromatography (LC) is used to determine a relatively new sulfonylureic herbicide, imazosulfuron, 1-(2-chloroimidazo-[1,2-a] pyridin-3-ylsulfonyl)-3-(4,6-dimethoxy-2-pyrimidinyl)-urea (TH-913), in drinking water and in soil. TH-913 is extracted from water using solid-phase extraction on C18 bonded silica. Soil samples (20 g) are extracted with 300 ml of methanol-water (50:50) and the acidified extracts are transferred onto Sep-Pak C18 and processed as described for water samples. Off-line desorption is done with 20 ml of methanol-water (50:50). The eluate is evaporated to dryness, the residue dissolved in acetonitrile and analysed by LC with UV detection at 238 nm. The recoveries of TH-913 from water were over 95% (at 0.05 microg/l level) and from soil over 90% (at 0.005 mg/kg level).

Chromatography, Liquid↗
PubMed1999

The presence of the alternatively spliced A2 cassette in the vacuolar H+-ATPase subunit A prevents assembly of the V1 catalytic domain.

Vacuolar ATPases (V-ATPases) are multisubunit enzymes that couple the hydrolysis of ATP to the transport of H+ across membranes, and thus acidify several intracellular compartments and some extracellular spaces. Despite the high degree of genetic and pharmacological homogeneity of V-ATPases, cells differentially modulate the lumenal pH of organelles and, in some cells, V-ATPases are selectively targetted to the plasma membrane. Although the mechanisms underlying such differences are not known, the subunit isoform composition of V-ATPases could contribute to altered assembly, targeting or activity. We previously identified an alternatively spliced variant of the chicken A subunit in which a 30 amino acid cassette (A1) containing the Walker consensus sequence for ATP binding is replaced by a 24 amino acid cassette (A2) that lacks this feature. We have examined the ability of chimeric yeast/chicken A subunits containing either the A1 or the A2 cassette to restore the V-ATPase activity of yeast that lack the A subunit. The A1-containing chimeric subunit, but not the chimera that contains the A2 cassette, partially restores the ability of the mutated yeast to grow at neutral pH. Both chimeric proteins are expressed, although at lower levels than the similarly transfected yeast A subunit. The A2-containing subunit fails to associate with the vacuolar membrane or support the assembly of V-ATPase complexes. Thus, the substitution of the A1 sequence by A2 not only removes the Walker nucleotide binding sequence but also compromises the ability of the A subunit to assemble with other V-ATPase subunits.

Adenosine Triphosphate↗
PubMed1999

A quantitative model of the relationship between phenotypic variance and heterozygosity at marker loci under partial selfing.

Negative relationships between allozyme heterozygosity and morphological variance have often been observed and interpreted as evidence for increased developmental stability in heterozygotes. However, inbreeding can also generate such relationships by decreasing heterozygosity at neutral loci and redistributing genetic variance at the same time. I here provide a quantitative genetic model of this process by analogy with heterozygosity-fitness relationships. Inbreeding generates negative heterozygosity-variance relationships irrespective of the genetic architecture of the trait. This holds for fitness traits as well as neutral traits, the effect being stronger for fitness traits under directional dominance or overdominance. The order of magnitude of heterozygosity-variance regressions is compatible with empirical data even with very low inbreeding. Although developmental stability effects cannot be excluded, inbreeding is a parsimonious explanation that should be seriously considered to explain correlations between heterozygosity and both mean and variance of phenotypes in natural populations.

Animals↗
PubMed1999

Traumatic epidural hematoma of the cervical spine: magnetic resonance imaging diagnosis and spontaneous resolution: case report.

OBJECTIVE AND IMPORTANCE: Demonstration of interest of medical treatment of cervical epidural hematomas. CLINICAL PRESENTATION: A young patient developed cervical pain after experiencing cervical trauma. Computed tomography and magnetic resonance imaging demonstrated an epidural cervical hematoma. A spontaneous resolution of the clinical symptoms and the radiological abnormalities was observed. CONCLUSION: Although surgical decompression is generally regarded as mandatory in selected patients with incomplete and nonprogressing deficits, conservative management may be possible.

Adult↗
PubMed1999

[The place of MRI in the study of cerebrospinal fluid fistulas].

Results of CT and MRI explorations in 8 patients with cerebrospinal fluid (CSF) fistulae are reported and compared with surgical findings in 7. Sensitivity of MRI (CISS and fast T2 spin-echo sequences) was excellent giving perfect correlations with surgical findings in 7/7 cases. CT and MRI were found to provide complementary information suggesting they should be used in combination as first intention explorations of suspected CSF fistulae. Computerized cisternography should be used if MRI is contraindicated or if a clinically and biologically proven CSF fistulae is not visualized by CT or MRI.

Adolescent↗
PubMed1999

[Treatment of syringomyelia].

Treatment of syringomyelia utilizes two operative approaches: posterior fossa decompression and syrinx shunting (including subarachnoid, pleural and peritoneal shunting). MRI study is nowadays the indispensable tool for the evaluation of patients with syringomyelia and allows to choose the best therapeutic option. Posterior fossa decompression is regarded as the procedure of choice for syringomyelia with Chiari. After intradural exploration, additional steps may be necessary as excision of the cerebellar tonsils. Other therapeutic alternatives are associated with higher complication rates. Patients with persistent focal syrinxes after PFD respond best to syringoperitoneal shunts. For the management of post-traumatic syringomyelia, a large decompressive laminectomy at the fracture site is recommended; the use of a drain does not offer any long-term therapeutic advantage. Syringoperitoneal shunting is the treatment of post-infection syringomyelia but good long-term result is rare in this type of syrinx.

Budd-Chiari Syndrome↗
PubMed1999

[Periventricular leukomalacia in premature infants: prognostic role of ultrasonography and MRI].

PURPOSE: To evaluate the role of cranial US and MRI to establish the neurological prognosis of premature infants with periventricular leukomalacia (PVL). PATIENTS AND METHODS: Follow-up results of cranial US and early MRI evaluation (before 25 weeks*) of 28 premature infants were retrospectively reviewed and compared to the neurological outcome at 18 months* (*corrected age). RESULTS: Follow-up by cranial US was more sensitive (8/28) than early MRI to detect cystic PVL lesions because of the transient nature of these cysts. This has prognostic implications since all patients (8/8) with cystic PVL lesions had neurological sequelae. MRI was useful, as a complement to cranial US, for the evaluation of non-cystic PVL lesions. Indeed, patients with evidence of hemorrhage or paucity of white matter at MRI had a higher risk of neurological sequelae (9/11) than infants with echogenic periventricular white matter at US without evidence of white matter abnormality at MRI (p < 0.013). CONCLUSION: MRI was useful, as a complement to cranial US, to evaluate the prognosis of infants with non-cystic PVL lesions.

Developmental Disabilities↗
PubMed1998

Heterozygosity-fitness correlations: new perspectives on old problems.

Heterozygosity-fitness correlations (HFC) have been studied in various organisms for more than two decades, but they are not universal. Although their detectability is limited by several factors (null alleles, inaccuracy of the phenotypic description of fitness, small sample sizes) the correlations appear intrinsically weak and often inconsistent across samples. Determining the origins of HFC is therefore a complex task. However, this issue might soon be resolved provided clear hypotheses and definitions are used (especially, if the problem of the neutrality of allozyme variation is not identified with the related issue of HFC), as well as new empirical (molecular markers) & theoretical (statistical models) tools.

Alleles↗
PubMed1998

Lower clivus and foramen magnum anterolateral meningiomas: surgical strategy.

Lower clivus and anterolateral foramen magnum meningiomas are rare but challenging tumors. Indeed, all access routes to their intradural anterolateral implantation appear unsafe since highly-functional local structures may not be sacrified or even retracted. Anterior and posterior surgical approaches have specific advantages and limitations. Different lateral extensions of the posterior approach have been described. They include a transposition of the vertebral artery, a partial occipital condylectomy and even the exposure and the section of the sigmoid sinus. Such posterolateral approaches offer the optimal access to anterolateral foramen magnum meningiomas and allow a total removal with a minimal morbidity. We report the surgical strategy that we applied for the last 6 anterolateral foramen magnum meningiomas in our department.

Aged↗
PubMed1998

Perisylvian dysgenesis. Clinical, EEG, MRI and glucose metabolism features in 10 patients.

We studied 10 patients who had neurological disorders with a MRI-based diagnosis of perisylvian dysgenesis based on the fact that the parasagittal and centrifugal extremity of the sylvian fissure was abnormally mesial. This abnormality was bilateral in seven cases; in the other three patients, the contralateral sylvian fissure appeared either normal (two cases) or enlarged (open operculum). The perisylvian cortex had a polymicrogyric appearance in most patients. Potential aetiopathogenic factors were determined in four patients. In two of them, ischaemia at mid-gestation was ascribed to death of a co-twin in a context of monozygotic twinning. In the other two patients, who were siblings, genetic factors were suspected. Pseudobulbar palsy was found in eight patients and epilepsy in five patients. We used PET with [18F]fluorodeoxyglucose to test the hypothesis that, despite this clinical and MRI heterogeneity, regional cerebral glucose distribution could have common features in these patients. The analysis of PET data was performed by visual inspection in two cases and by using statistical parametric mapping (SPM) in eight patients compared with a control group. Segmented grey matter MRIs of seven out these patients were also analysed using SPM. We found that the abnormal perisylvian cortex had normal grey matter activity in eight patients and in the other two there was a heterogeneous pattern with areas of preserved metabolism and of decreased metabolism. Metabolic changes were also detected outside the polymicrogyric-like cortex; three patients had hypometabolic areas in cortical regions where the MRI appeared normal and had a normal intensity. When polymicrogyria extended into the white matter, this ectopic dysgenetic cortex was associated with a grey matter pattern within the white matter territory, and was detected by SPM as areas of PET hypermetabolism and MRI hyperintensity. In order to detect possible metabolic changes undetected by the individual analyses, the group of patients was compared with the control group. This comparison revealed bilateral hypometabolism in the frontal opercular cortex. We propose that these PET data be considered in light of the presumed cyto-architectonic pattern of perisylvian dysgenesis, i.e. polymicrogyria. In this malformation, two dense cell layers are separated by a necrotic sparse cell layer. We speculate that the amount of synaptic activity preserved in these dense cell layers depends on the importance and timing of the necrotic process; this hypothesis accounts for the large range of metabolic patterns found, from profoundly decreased glucose metabolism to nearly normal activity.

Adolescent↗
PubMed1998

Microsatellites, transposable elements and the X chromosome.

Variability at microsatellite (MS) loci is generally perceived as resulting from an interaction between mutation and genetic drift and, to a lesser extent, selection and recombination. Less investigated has been the reason for MS accumulation in genomes. We present here a simple model that could account for the variation in density of MS loci, assuming that they are created either through replication slippage or in association with transposable elements. Microsatellites then evolve under the forces cited above. We use this framework to revisit two results obtained from high-density genomic maps of the human and mouse genomes built with thousands of CA repeats: MS loci are (1) less variable and (2) less dense on the X chromosome than on autosomes. The first result is most likely explained by differential mutation on the X chromosome and the autosomes. The second result may be explained by differential mutation, provided the distributions of MS loci are still not at equilibrium. Selection, acting either directly on large allele size or indirectly on the transposable elements associated with MS, may explain the same result. The framework developed here is a first step toward more rigorous models, calling for additional data.

Animals↗
PubMed1998

Metabolic capacities in cultured human hepatocytes obtained by a new isolating procedure from non-wedge small liver biopsies.

A new isolating procedure of human hepatocytes has been developed using two-step collagenase digestion by a non-perfusion procedure (NP) of non-wedge liver biopsies. 1. A yield of 2-7 x 10(6) hepatocytes/g liver, 52-95% viability and 13-75% attachment were obtained from liver biopsies weighing 6-60 g, comparable to that obtained when using the classical perfusion procedure (P) to isolate human hepatocytes from wedge liver samples of 50-150 g. 2. In culture, human hepatocytes obtained by NP remained attached to plastic for up to 5 days and displayed the usual morphological characteristics. Their metabolic capacities, assessed by liver-specific albumin and urea synthesis and by CYP-dependent and conjugation pathways, were equivalent to those of human hepatocytes obtained by P. In addition, they responded adequately to specific CYP inducers, demonstrating that they constitute a model in which human drug metabolism and toxicity studies can be performed.

Adult↗
PubMed1998

Dual-mode presentation and its effect on implicit and explicit memory.

We empirically investigated whether the auditory and visual subsystems mediating priming interact. We examined the hypothesis that processing in the visual subsystem during an implicit memory test permits access to memories in the auditory subsystem that were stored concurrently with visual memories. We did so by comparing priming in visual perceptual identification following both visual and auditory presentation (multimodal priming), only visual presentation (within-modality priming), or only auditory presentation (cross-modality priming). We focused on the comparison between multimodal and within-modality priming because multimodal priming should be larger than within-modality priming under our hypothesis. However, multimodal priming was approximately equal to within-modality priming in four experimental conditions. These results are consistent with the view that there is limited interaction between the visual and auditory subsystems mediating priming.

Auditory Perception↗
PubMed1998

[Von Hippel-Lindau disease and central nervous system hemangioblastoma. Progress in genetics and clinical management].

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder, predisposing to the development of various tumors (central nervous system and retinal hemangioblastomas, endolymphatic sac tumors, renal cell carcinoma and/or renal cysts, pheochromocytomas, pancreatic cysts and/or tumors). Incidence of the disease is 1/36,000. Central nervous system hemangioblastomas and renal cell carcinoma are the main causes of death. The VHL gene, located on chromosome 3p25-26, is a tumor-suppressor gene encoding for a 213 amino acid protein which plays a major role in regulation of VEGF expression. Germline mutations of the VHL gene are identified in about 75-80% of the patients. Somatic mutations of the VHL gene are found in both sporadic central nervous system hemangioblastomas and sporadic "clear" renal cell carcinomas. For neurosurgeons search for VHL disease should be imperative in presence of a patient with apparently "sporadic" central nervous system or endolymphatic sac tumor.

Central Nervous System Neoplasms↗
PubMed1997

DNA replication and postreplication mismatch repair in cell-free extracts from cultured human neuroblastoma and fibroblast cells.

DNA synthesis and postreplication mismatch repair were measured in vitro using cell-free extracts from cultured human SY5Y neuroblastoma and WI38 fibroblast cells in different growth states. All extracts, including differentiated SY5Y and quiescent WI38 fibroblasts, catalyzed SV40 origin-dependent DNA synthesis, totally dependent on SV40 T-antigen. Thus, although differentiated neuroblastoma and quiescent fibroblasts cells were essentially nondividing, their extracts were competent for DNA replication using DNA polymerases delta, alpha, and possibly epsilon, with proliferating cell nuclear antigen. Nonreplicative DNA synthesis and lesion bypass by either alpha- or beta-polymerases were detected independently in extracts using primed or gapped single-stranded DNA templates. Long-patch postreplication mismatch repair was measured for the first time in neuroblastoma cell-free extracts. Extracts from subconfluent and high-density SY5Y cells catalyzed postreplication mismatch repair with efficiencies comparable to those of HeLa cell extracts. No significant differences were observed in repair between SY5Y differentiated and undifferentiated cell extracts. Mismatch repair efficiencies were threefold lower in extracts from subconfluent WI38 cells, and repair in WI38 quiescent cells was fourfold less than in subconfluent cells, suggesting that mismatch repair may be regulated. The spectrum of mismatch repair in SY5Y extracts closely resembled the mismatch removal specificities of HeLa extracts: T . G and G . G mismatches were repaired most efficiently; C . A, A . A, A . G and a five-base loop were repaired with intermediate efficiency; repair of G . A, C . C, and T . T mismatches was extremely inefficient.

Antineoplastic Agents↗
PubMed1997

Stereotactic brain biopsy guided by positron emission tomography (PET) with [F-18]fluorodeoxyglucose and [C-11]methionine.

The aim of the present study was to compare the contribution of the labelled tracers [C-11]methionine (Met) and [F-18]-fluorodeoxyglucose (FDG) in positron emission tomography (PET)-guided stereotactic biopsy of non resectable brain lesions. Twenty-five patients underwent combined Met-PET-, FDG-PET- and computerized tomography (CT)- or magnetic resonance (MR)-guided stereotactic biopsy according to a previously described technique for stereotactic FDG-PET. Met-PET and FDG-PET images were analyzed to determine which tracer offers the best information to guide at least one stereotactic biopsy trajectory. Histological diagnosis was obtained in all patients (23 tumours and 2 non-tumorous lesions). All tumours had an area of abnormal Met uptake and were biopsied under PET-guidance. FDG uptake in the tumour was higher than in the grey matter and was used for target selection in 12 of 23 tumours. Eleven of them were located in the basal ganglia or the brainstem. Met was used for target selection in 11 of 23 tumours where there was no FDG uptake or where FDG uptake was equivalent to that of the grey matter. Ten of them were located in the cortex. Two nontumoral lesions had no Met uptake and were biopsied under CT- or MR-guidance only. Forty-three out of 53 stereotactic trajectories obtained in these 25 patients were based on PET-defined targets and had an area of abnormal Met uptake. These trajectories always yielded a diagnosis of tumour. Moreover, all tumorous trajectories had an area of abnormal Met uptake. Finally, all non-diagnostic trajectories (n = 4) were CT/MR-defined because there was no area of abnormal Met uptake. These results suggest that patients who can benefit the most from Met-PET guidance could be selected pre-operatively. In conclusion, this work shows that Met is a good alternative to FDG for target selection in PET-guided stereotactic brain biopsy.

Adolescent↗
PubMed1997

Context-dependent survival differences among electrophoretic genotypes in natural populations of the marine bivalve Spisula ovalis.

We investigated the relationships between allozyme genotypes at nine polymorphic loci and survival in a natural population of the bivalve Spisula ovalis sampled on three occasions (1993, 1994, and 1995) in three different sites (2855 individuals analyzed). This species displays annual growth lines allowing identification of annual cohorts. Therefore we could avoid cohort mixing, a frequent bias in such studies, and evaluate the consistency of the observed effects across cohorts and sites. Significant viability differences were observed both among alleles and between heterozygotes and homozygotes at some loci. Multiple-locus heterozygosity was positively correlated with viability in the 1993-1994 period, but not in the 1994-1995 interval. The observed selective effects were significantly dependent on the cohort and the site considered. A bibliographic survey suggests that such variability is a common feature of studies analyzing heterozygosity-survival relationships. Two explanations are consistent with our results. First, allozyme genotypes may have direct effects on viability that interact with subtle environmental variation in a complex and unpredictable way. Second, allozyme genotypes may be transiently associated with other viability genes responsible for heterotic effects. In any case, the results militate against allozyme loci being themselves consistently overdominant for viability in natural populations.

Alleles↗