Biomedical subjects

F Michel

Publications and source records attributed to F Michel.

At least 91 records · Page 5Linked to original sources

PubMed1998

Semantic priming in major depressive state.

We studied semantic priming in 20 major depressive subjects. The methodology used was a visual lexical decision task. Semantic priming is the facilitation of target word recognition (shortening of response time) by the prior presentation of a semantically related context (a prime word). It relies on semantic processing of words and context, facilitating early cognitive stages of response. Varying the temporal interval between prime and target words onset allows us to distinguish between two priming mechanisms, relying on more automatic (test 1) or more controlled (i.e. attention dependent) (test 2) information processing. We observe a significant retardation for words and pseudo-words in depressives (in relation to controls) in both tests. In spite of a general retardation and increase of response times in depressives, semantic priming is evident in both groups and both tests, and does not differ significantly between depressive and control groups in either automatic or controlled conditions. Theses results confirm that semantic processing is not impaired in depression, and are discussed with regard to the hypothesis of an effortful processing impairment in depression, and to depressive retardation.

Adult↗

PubMed1998

Anomia in major depressive state.

Anomia, or word finding difficulty, is a frequent clinical symptom of the depressive state. This study investigates naming and lexicalization processes (or word production processes) in 11 depressive patients (major depressive state), through a picture naming task of 53 images corresponding to low frequency words. Depressives showed significantly more anomia and made more naming errors (semantically related substitution words) than control subjects. Tip-of-the-tongue (TOT) states, which correspond to an impairment at a later stage of phonological encoding with partial activation of phonological shape, remained rare in depressives despite the increase of lexicalization difficulties observed. Anomia observed in depressives could thus be related to an impairment at the early stage of lexicalization or word production processes (pre-phonological item selection and access, or storage of the semantic lexical item in Working Memory for further phonological encoding), without lexical-semantic disorganization. We discuss the relationship between such an elementary speech production disorder and cognitive impairments demonstrated in the depressive state (deficit of effortful and attentional processes, impairment in activation or initiation of cognitive processes and responses).

Adult↗

PubMed1998

Brain regions involved in the perception of gaze: a PET study.

Mutual gaze may be described as a psychological process during which two persons have the feeling of a brief link between their two minds. In the monkey, specific cell assemblies in the superior temporal cortex of the brain are responsive to gaze. This suggests that the brain may have evolved mechanisms for interpreting direct eye contact. These mechanisms could depend on the activation of specific brain regions. Positron emission tomography was used to measure activity in brain regions in healthy volunteers while they were looking at faces featuring, respectively, eye contact, averted gaze, or no gaze. As expected a region known to be involved in face processing was found to be activated in the ventral occipito-temporal region, especially in the right hemisphere. Averted gaze and mutual gaze triggered blood flow responses in similar areas which were different from those involved in face processing. These areas included the occipital part of the fusiform gyrus, the right parietal lobule, the right inferior temporal gyrus, and the middle temporal gyrus in both hemispheres. These results are consistent with the hypothesis that perception of eyes regardless of the direction of the gaze is subserved by a distributed network. However, no conclusive evidence was found for specific area(s) devoted to mutual gaze processing.

Adult↗

PubMed1998

Dependence of color on context in a case of cortical color vision deficiency.

Color constancy depends on sensitivity to change in both illumination spectral properties and object position. We investigated this latter form of color constancy by asking a cerebral achromatopsic to name the colors of papers that were presented atop black, gray or white backgrounds under identical illumination. Comparison of color names across background conditions reveals poor constancy, characterized by a contrasting of foreground and background values that is not corrected by proper anchoring.

Brain Diseases↗

PubMed1998

Group I-like ribozymes with a novel core organization perform obligate sequential hydrolytic cleavages at two processing sites.

A new category of self-splicing group I introns with conserved structural organization and function is found among the eukaryotic microorganisms Didymium and Naegleria. These complex rDNA introns contain two distinct ribozymes with different functions: a regular group I splicing-ribozyme and a small internal group I-like ribozyme (GIR1), probably involved in protein expression. GIR1 was found to cleave at two internal sites in an obligate sequential order. Both sites are located 3' of the catalytic core. GIR1-catalyzed transesterification reactions could not be detected. We have compared all available GIR1 sequences and propose a common RNA secondary structure resembling that of group I splicing-ribozymes, but with some important differences. The GIR1s lack most peripheral sequence components, as well as a P1 segment, and, at approximately 160-190 nt, they are the smallest functional group I ribozymes known from nature. All GIR1s were found to contain a novel 6-bp pseudoknot (P15) within their catalytic core region. Experimental support of the proposed structure was obtained from the Didymium GIR1 by RNA structure probing and site-directed mutagenesis. Three-dimensional modeling indicates a compactly folded ribozyme with the functionally essential P15 exposed in the cleft between the two principal domains P3-P8 and P4-P6.

Animals↗

PubMed1998

Differential chemical probing of a group II self-splicing intron identifies bases involved in tertiary interactions and supports an alternative secondary structure model of domain V.

Dimethyl sulfate modification was used to probe for tertiary structural elements in the group II intron PI.LSU/2 from the mitochondrial pre-ribosomal RNA of the brown alga Pylaiella littoralis. Modification of the lariat form of the intron under conditions that allow both native folding and conformational homogeneity is found to be generally consistent with secondary and tertiary structural features identified previously for group II ribozymes. A comparison of chemical probing at temperatures just below and above the first melting transition illustrates the cooperative unfolding of tertiary structure and identifies novel candidates for tertiary interactions in addition to defining elements of secondary structure. Substitution of the GAAA terminal loop of domain V is shown to be compatible with retention of conformational homogeneity (despite the loss of an important tertiary interaction), but produces a concise methylation footprint in domain I at the site previously shown to harbor the receptor for that loop. The analysis also identified two nucleotide positions in domain V with novel secondary and potential tertiary structural roles. The proposed refinement of domain V secondary structure is supported by an expanded comparative analysis of group II sequences and bears increased resemblance to U2:U6 snRNA pairing in the spliceosome.

Alkylating Agents↗

PubMed1998

Complete sparing of high-contrast color input to motion perception in cortical color blindness.

It is widely held that color and motion are processed by separate parallel pathways in the visual system, but this view is difficult to reconcile with the fact that motion can be detected in equiluminant stimuli that are defined by color alone. To examine the relationship between color and motion, we tested three patients who had lost their color vision following cortical damage (central achromatopsia). Despite their profound loss in the subjective experience of color and their inability to detect the motion of faint colors, all three subjects showed surprisingly strong responses to high-contrast, moving color stimuli--equal in all respects to the performance of subjects with normal color vision. The pathway from opponent-color detectors in the retina to the motion analysis areas must therefore be independent of the damaged color centers in the occipitotemporal area. It is probably also independent of the motion analysis area MT/V5, because the contribution of color to motion detection in these patients is much stronger than the color response of monkey area MT.

Adult↗

PubMed1998

Synthetic porous ceramic compared with autograft in scoliosis surgery. A prospective, randomized study of 341 patients.

We have evaluated the use of a synthetic porous ceramic (Triosite) as a substitute for bone graft in posterior spinal fusion for idiopathic scoliosis. In a prospective, randomised study 341 patients at five hospitals in the UK and France were randomly allocated either to autograft from the iliac crest or rib segments (171) or to receive Triosite blocks (170). All patients were assessed after operation and at 3, 6, 12 and 18 months. The two groups were similar with regard to all demographic and baseline variables, but the 184 treated in France (54%) had Cotrel-Dubouset instrumentation and the 157 treated in the UK usually had Harrington-Luque implants. In the Triosite group the average Cobb angle of the upper curve was 56 degrees, corrected to 24 degrees (57%). At 18 months, the average was 26 degrees (3% loss). In the autograft group the average preoperative upper curve of 53 degrees was corrected to 21 degrees (60%). At 18 months the mean curve was 25 degrees (8% loss). Pain levels after operation were similar in the two groups, being mild in most cases. In the Triosite group only three patients had problems of wound healing, but in the autograft group, 14 patients had delayed healing, infection or haematoma in the spinal wound. In addition, 15 autograft patients had pain at the donor site at three months. Seven had infections, two had haematoma and four had delayed healing. The haematological and serum biochemistry results showed no abnormal trends and no significant differences between the groups. There were no adverse events related to the graft material and no evidence of allergenicity. Our results suggest that Triosite synthetic porous ceramic is a safe and effective substitute for autograft in these patients. Histological findings on biopsy indicate that Triosite provides a favourable scaffolding for the formation of new bone and is gradually incorporated into the fusion mass.

Adolescent↗

PubMed1998

Metanephric adenoma of the kidney. A clinicopathologic, immunohistochemical and electron microscopic study of two cases.

We report two cases of metanephric adenoma in 40 and 48 year-old women. These rare kidney tumors were composed of cuboidal epithelial cells forming tubules, glomeruloid structures and sheets. Ultrastructural and immunohistochemical studies revealed that the tumor cells are similar to epithelial cells of developing nephrons. These features differentiate the metanephric adenoma from tubulo-papillary renal carcinoma, nephroblastoma, and cortical adenoma. According to its invariably benign course, the metanephric adenoma treatment could be restricted to a simple tumorectomy.

Adenoma↗

PubMed1998

[Isolated leiomyomatosis of the right renal vein associated with hepatic myelolipoma: diagnostic and therapeutic problems].

The authors report a case of isolated intravenous leiomyomatosis involving a vein of the right renal hilum associated with operated hepatic myelolipoma with a diagnosis of metastatic renal cancer. These tumours are very rare and are usually diagnosed on histological examination of the resection specimen. Although they have a benign histology, they have a very different prognosis and therapeutic management. Although the association of these two exceptional tumours may appear to be purely incidental, a common aetiological factor may nevertheless exist.

Angiography↗

PubMed1997

A group II self-splicing intron from the brown alga Pylaiella littoralis is active at unusually low magnesium concentrations and forms populations of molecules with a uniform conformation.

We have investigated the reactivity of three of the seven group II introns encoded by the mitochondrial genome of the brown alga Pylaiella littoralis. While the first intron in the protein-coding cox1 gene could not be induced to self-splice under any of the conditions tested, the first two introns in the gene encoding the large ribosomal subunit are reactive in vitro and splice primarily by the standard group II two-step transesterification pathway. Intron 2 proved to be of exceptional interest, because in contrast to all group II molecules known so far, its optimal magnesium concentration is less than 10 mM and it still carries out accurate splicing at concentrations as low as 0.1 mM magnesium. Analysis of reaction products under optimal conditions showed no evidence of hydrolysis at the 5' splice site and up to 90% of precursor molecules could be converted into excised lariat intron, which migrated as a single band on non-denaturing polyacrylamide gels. Absorbance versus temperature profiles generated from the lariat form of intron 2 reveal the existence of an early melting component, the amplitude of which does not depend on the way the molecules were purified, i.e. with or without a denaturation step. This highly cooperative transition, whose position along the temperature axis changes with the concentration of magnesium, is proposed to consist of the unfolding of the tertiary structure of the molecule. We conclude that group II introns, which are the largest known ribozymes, can form conformationally homogeneous populations of molecules suitable for physical-chemical studies of higher-order structure.

Electron Transport Complex IV↗

PubMed1997

Rules for RNA recognition of GNRA tetraloops deduced by in vitro selection: comparison with in vivo evolution.

Terminal loops with a GNRA consensus sequence are a prominent feature of large self-assembling RNA molecules. In order to investigate tertiary interactions involving GNRA loops, we have devised an in vitro selection system derived from a group I ribozyme. Two selections, destined to isolate RNA sequences that would recognize two of the most widespread loops (GUGA and GAAA), yielded variants of previously identified receptors for those loops, and also some yet unrecognized, high-affinity binders with novel specificities towards members of the GNRA family. By taking advantage of available crystal structures, we have attempted to rationalize these results in terms of RNA-RNA contacts and to expose some of the structural principles that govern GNRA loop-mediated tertiary interactions; the role of loop nucleotide 2 in ensuring specific recognition by receptors is emphasized. More generally, comparison of the products of in vitro and natural selection is shown to provide insights into the mechanisms underlying the in vivo evolution of self-assembling RNA molecules.

Binding Sites↗

PubMed1997

Molecular characterization and role in T cell activation of staphylococcal enterotoxin A binding to the HLA-DR alpha-chain.

Superantigens bind to MHC class II-positive cells and stimulate T lymphocytes expressing specific V beta regions of the TCR. Two distinct regions of staphylococcal enterotoxin A superantigen (SEA) have been shown to affect the binding to MHC class II molecules. Results presented here demonstrate for the first time that the SEA-DR interaction can be affected by mutations on the class II alpha-chain. Furthermore, we have precisely mapped the interaction of the SEA N-terminal domain with the alpha1 domain of HLA-DR. Scatchard analysis using DAP cells transfected with mutant class II molecules showed a role for residue DR alpha K39 in the binding of SEA. Also, complementation experiments using mutant SEA molecules revealed an interaction between SEA residue F47 and position alphaQ18 on an outer loop of HLA-DR. These interactions between SEAF47 and the DR alpha-chain are critical, as they allow the recognition by an otherwise nonreactive V beta1+ T cell hybridoma and induction of tyrosine phosphorylation through the TCR.

Animals↗

PubMed1997

Multiple tertiary interactions involving domain II of group II self-splicing introns.

The ribozyme core of group II introns is organized into six domains of secondary structure. Of these, domain II was long thought to be relatively unimportant for group II self-splicing. However, we now demonstrate the existence, in both major subdivisions of the group II family, of essential tertiary interactions involving domain II. theta-theta' is a novel tertiary interaction between the terminal loop of the IC1 stem of domain I and the basal stem of domain II. The theta-theta' interaction appears to stabilize the group II ribozyme core: it is essential for efficient self-splicing at elevated temperatures but, as shown by the use of a bimolecular reaction system, molecules with a defective theta-theta' contact are not affected in catalysis. An interaction, eta-eta', between domains II and VI of subgroup IIB introns was recently reported to mediate a conformational rearrangement between the two steps of the self-splicing reaction. We now show that domains II and VI of subgroup IIA introns also contact each other, although in a somewhat different way. Reinforcement of the eta-eta' interaction of a subgroup IIA intron prevents the use of a specific 2'-hydroxyl group in domain VI to initiate splicing by transesterification at the 5' splice site; the 5' intron-exon junction is hydrolyzed instead. Since disruption of eta-eta' has exactly opposite effects, and promotes reversal of the first transesterification step, it is concluded that formation of eta-eta' mediates a conformational change in subgroup IIA introns as well. Just like the eta-eta' interaction of subgroup IIB introns, the eta-eta' interaction of subgroup IIA introns (and the theta-theta' interaction) involves terminal loops of the GNRA family and their RNA receptors. Therefore, these motifs are used by nature not only to stabilize three-dimensional RNA architectures, but also in situations that require dynamic interactions.

Base Sequence↗

PubMed1997

Suppressors of cis-acting splicing-deficient mutations that affect the ribozyme core of a group II intron.

Many of the cis-dominant mutations that lead to respiratory deficiency by preventing maturation of specific yeast mitochondrial transcripts are found to affect the ribozyme core of group I and group II introns. We have searched for suppressors of mutations in the ribozyme-encoding sections of a group II intron, the first intron in the COX1 gene of Saccharomyces cerevisiae, which was independently subjected to in vitro site-directed mutagenesis. Three of the original mutants bore multiple mutations, which act synergistically, since for most individual mutations, suppressors could be obtained that ensured at least partial recovery of respiratory competence and splicing. Out of a total of ten suppressor mutations that were identified, three were second-site substitutions that restored postulated base-pairings in the ribozyme core. Remarkably, and as is observed for group I introns, at least half of the cis-dominant mutations in the first two group II introns of the COX1 gene affect sites that have been shown to participate in RNA tertiary interactions. We propose that this bias reflects cooperativity in the formation of ribozyme tertiary but not secondary structure, on the one hand, and the need for synergistic effects in order to generate a respiratory-deficient phenotype in the laboratory on the other. Finally, a novel in vivo splicing product of mutant cells is attributed to bimolecular splicing at high concentrations of defective transcripts.

Base Sequence↗

PubMed1997

Cholesterol biosynthesis in normocholesterolemic patients after cholesterol removal by plasmapheresis.

Plasmapheresis and low-density lipoprotein (LDL)-apheresis are recognized procedures for the treatment of hyperlipidemia resistant to diet and lipid-lowering drugs and provide information on cholesterol synthesis in hypercholesterolemic patients. However, cholesterol synthesis after acute cholesterol removal from plasma has never been investigated in normocholesterolemic patients. In this study, cholesterol synthesis was evaluated in three normocholesterolemic patients by determination of plasma lathosterol, lathosterol-to-cholesterol ratio, and plasma mevalonic acid. In a short-term kinetic study, samples were collected before and after plasmapheresis and every 6 hours during 24 hours. In the second part of the study, cholesterol synthesis was evaluated daily for 3 days. In normocholesterolemic patients, cholesterol returns to basal levels in 3 days. However, cholesterol removal did not result in a significant increase in lathosterol-to-cholesterol ratio or in plasma mevalonic acid, despite a slight increase in lathosterol. In contrast, when repeated plasma exchanges induced a dramatic hypocholesterolemia (< 1 mmol/liter), an acute but transient stimulation of cholesterol synthesis was observed (lathosterol/cholesterol ratio and MVA, respectively, increase from 8.2 to 22.3 and from 28 nmol/liter to 98 nmol/liter). This study shows that cholesterol synthesis is not stimulated by plasmapheresis in normocholesterolemic patients but is enhanced in dramatic hypocholesterolemic patients (< 1 mmol/liter).

Cholesterol↗

PubMed1997

Enrichment of antigen-specific T lymphocytes by panning on immobilized MHC-peptide complexes.

Numerous studies have focused on characterizing and monitoring antigen-specific T cells during the course of an immune response. Mostly indirect methods were used to circumvent the low frequency of T cell precursors and the inherent complexity of T cell receptor (TcR)-MHC-peptide interactions. Here, we took advantage of peptide-specific adhesion induced by immobilized MHC-peptide complexes. We describe a simple technique which allows enrichment in antigen-specific T lymphocytes among a heterogeneous CD8+ T cell population. Enrichment of T cells according to their specificity should facilitate their characterization and provide an attractive tool for immunotherapy.

Animals↗

PubMed1997

Simultaneous functional expression of swelling and forskolin-activated chloride currents in primary cultures of rabbit distal convoluted tubule.

Ionic Cl- currents induced by cell swelling and forskolin were studied in primary cultures of rabbit distal convoluted tubule (DCTb) by the whole-cell patch clamp technique. We identified a Cl- conductance activated by cell swelling with an hyperosmotic pipette solution. The initial current exhibited an outwardly rectifying 1-V relationship, whereas steady state current showed strong decay at depolarized membrane potentials. The ion selectivity was I- > Br- > Cl- > > glutamate. The forskolin-activated Cl- conductance demonstrated a linear I-V relationship and its ion selectivity was Br- > Cl- > I- > glutamate. This last conductance could be related to the CFTR (cystic fibrosis transmembrane conductance regulator) previously identified in these cells. NPPB inhibited both Cl- currents, and DIDS inhibited only the swelling-activated Cl- current. Forskolin had no effect on the activation of the swelling-activated Cl- current. In DCTb cells which exhibited swelling-activated Cl- currents subsequently inhibited by DIDS, forskolin could activate CFTR related Cl- currents. In the continuous presence of I- which inhibited CFTR conductance, forskolin did not modify the swelling-activated current. The results suggest that both Cl- conductances could be co-expressed in the same DCTb cell and that CFTR did not modulate the swelling-activated conductance.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗