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Biomedical subjects

F Michel

Publications and source records attributed to F Michel.

At least 37 records · Page 2Linked to original sources
PubMed2002

Characteristics of sleep apnea syndrome in tetraplegic patients.

OBJECTIVE: To include a larger number of tetraplegics than in previous studies, in order to more reliably characterize the pathogenesis and predisposing factors of sleep apnea in tetraplegia. METHODS: Sleep breathing data and oxymetric values were investigated in 50 randomly selected tetraplegic patients and discussed in context with age, gender, BMI, neck circumference, type and height of lesion, time after injury, spirometric values and medication. A non-validated short questionnaire on daytime complaints was added. RESULTS: Thirty-one patients out of 50 had an RDI > or =15, defined as sleep disordered breathing (SDB); 24 of them combined with an apnea index of 5 or more, these cases were diagnosed as sleep apnea syndrome (SAS). SAS was apparent in 55% and 20% of the studied men and women, respectively. Regression analyses showed no significant correlation between RDI and lesion level, ASIA impairment scale or spirometric values. In contrast, a significant correlation between RDI and age, BMI, neck circumference and time after injury could be shown. Kruskal-Wallis test for dichotomous non-parametric factors, such as gender, cardiac medication and daytime complaints, showed significant differences with regard to RDI. In contrast to able-bodied people with SAS, daytime complaints were only present in tetraplegic patients with severe pathology (RDI>40). CONCLUSION: Incidence of SAS is high in tetraplegia, particularly in older male patients with large neck circumference, long standing spinal cord injury and under cardiac medication. As tetraplegics with RDI between 15 and 40 reported no daytime complaints and often have normal BMI, these tetraplegics are not clinically suspicious for SAS. The increased use of cardiac medication in tetraplegics with SAS may implicate a link between SAS and cardiovascular morbidity, one of the leading causes of death in tetraplegia.

Adult↗
PubMed2002

Native vs. damaged milk fat globules: membrane properties affect the viscoelasticity of milk gels.

The storage modulus G' of rennet and acid milk gels filled with milk fat globules was measured as a function of the fat globule surface composition (native milk fat globule membrane, caseins and whey proteins, or a mixture of the three due to mechanical treatments) and surface area (i.e., the fat globule size). By different technological procedures, it was possible to obtain fat globules of constant surface composition but various sizes, and vice-versa, which had never been done. For both rennet and acid gels, a critical fraction of the fat globule surface covered by caseins and whey proteins was identified (approximately 40%), beyond which G' increased. Below this threshold, the gel viscoelasticity was unaffected by mechanical treatments. When the diameter of native milk fat globules decreased, the G' of rennet gels increased slightly, whereas that of acid gels decreased sharply. For both types of gels, G' increased when the diameter of partially disrupted fat globules decreased. For recombined globules completely covered with caseins and few whey proteins, G' increased with fat globule surface area for rennet gels whereas it decreased for acid gels. With the help of confocal microscopy and in the light of general structural differences between rennet and acid gels, a mechanism is proposed for the effect of fat globule damage and diameter on G', depending on the interactions the globules can undergo with the casein network.

Animals↗
PubMed2001

Crystal structure of the ankyrin repeat domain of Bcl-3: a unique member of the IkappaB protein family.

IkappaB proteins associate with the transcription factor NF-kappaB via their ankyrin repeat domain. Bcl-3 is an unusual IkappaB protein because it is primarily nucleoplasmic and can lead to enhanced NF-kappaB-dependent transcription, unlike the prototypical IkappaB protein IkappaBalpha, which inhibits NF-kappaB activity by retaining it in the cytoplasm. Here we report the 1.9 A crystal structure of the ankyrin repeat domain of human Bcl-3 and compare it with that of IkappaBalpha bound to NF-kappaB. The two structures are highly similar over the central ankyrin repeats but differ in the N-terminal repeat and at the C-terminus, where Bcl-3 contains a seventh repeat in place of the acidic PEST region of IkappaBalpha. Differences between the two structures suggest why Bcl-3 differs from IkappaBalpha in selectivity towards various NF-kappaB species, why Bcl-3 but not IkappaBalpha can associate with its NF-kappaB partner bound to DNA, and why two molecules of Bcl-3 but only one of IkappaBalpha can bind to its NF-kappaB partner. Comparison of the two structures thus provides an insight into the functional diversity of IkappaB proteins.

Amino Acid Sequence↗
PubMed2001

Exercise-induced inflammatory reaction affects electromyographic changes in skeletal muscle during dynamic contractions in humans.

In order to assess the role of exercise-induced inflammatory reactions on electromyographic (EMG) changes in humans, we have recorded, during a 3-min dynamic handgrip exercise at a high strength (112 w), the surface EMG and the compound evoked muscle action potential (M-wave) in control conditions, and this after ingestion of a well known cyclooxygenase blocker i.e. acetylsalicylic acid (ASA), either as a single dose treatment (10 mg/kg) and as a 3-day treatment (30 mg/kg per day). The power spectrum density function of EMG allowed us to compute both the median frequency (MF) and the energies in a low- and a high-frequency band. We estimated the lactic acid concentration from blood samples drawn from an antecubital vein and we noted that its production was not affected by ASA (single dose or 3-day treatment). We observed at the end of exercise that no change in M-wave duration and conduction time occurred though the median frequency always fell. However, we noted that the slope of the MF vs. time regression line was halved after the 3-day ASA treatment which may indicate that inflammatory reactions are elicited by exhausting contractions and affect the EMG changes.

Action Potentials↗
PubMed2001

Differential roles of Lck and Itk in T cell response to antigen recognition revealed by calcium imaging and electron microscopy.

Ag recognition triggered at the interface between a T cell and an APC is conditioned by cell-cell adhesion and cytoskeletal remodeling. The role played in these phenomena by Lck and Itk, two protein tyrosine kinases essential for T cell signaling, was examined. Early T cell responses (membrane ruffling, Ca(2+) response, APC-T cell adhesion) were monitored in T cells overexpressing kinase-defective (KD) Lck and Itk mutants by combining fluorescence imaging and electron microscopy. Neither Lck nor Itk appears to be involved in the Ag-independent formation of a small and labile contact interface between T cells and APCS: By contrast, the Ag-induced Ca(2+) response in a cell population is similarly blunted in both KD transfectants. However, the underlying mechanisms are strikingly different for the two kinases. The major effect of Lck-KD is to reduce the probability of giving rise to quasi-normal Ca(2+) responses, whereas overexpression of Itk-KD results in a tuning down of all single-cell Ca(2+) responses. In addition, Lck, but not Itk, is required for the formation of a stable T/APC conjugate and for T cell polarization after Ag stimulation. Overall, our results lead to a clear distinction between Lck and ITK: Lck plays an ignition role, controlling all the downstream events tested here, whereas Itk amplifies the Ca(2+) response, but is dispensable for APC-induced adhesive and morphological responses.

Animals↗
PubMed2001

A receptor-based biosensor for lipoprotein docking at the endothelial surface and vascular matrix.

Proteoheparan sulfate can be adsorbed to a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. Due to electrostatic repulsion, its anionic glycosaminoglycan side chains are stretched out into the blood substitute solution, representing a receptor site for specific lipoprotein binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques showing that HDL has a high binding affinity to the receptor and a protective effect on interfacial heparan sulfate proteoglycan layers, with respect to LDL and Ca(2+) complexation. LDL was found to deposit strongly at the proteoheparan sulfate, particularly in the presence of Ca(2+), thus creating the complex formation "proteoglycan-low density lipoprotein-calcium". This ternary complex build-up may be interpreted as arteriosclerotic nanoplaque formation on the molecular level responsible for the arteriosclerotic primary lesion. On the other hand, HDL bound to heparan sulfate proteoglycan protected against LDL docking and completely suppressed calcification of the proteoglycan-lipoprotein complex. In addition, HDL and aqueous garlic extract were able to reduce the ternary complex deposition and to disintegrate HS-PG/LDL/Ca(2+) aggregates. Although much remains unclear regarding the mechanism of lipoprotein depositions at proteoglycan-coated surfaces, it seems clear that the use of such systems offers possibilities for investigating lipoprotein deposition at a "nanoscopic" level under close to physiological conditions. In particular, Ca(2+)-promoted LDL deposition and the protective effect of HDL, even at high Ca(2+) and LDL concentrations, agree well with previous clinical observations regarding risk and beneficial factors for early stages of atherosclerosis. Therefore, we believe that the system can be of some use in investigations, e.g. of the interplay between different lipoproteins in arteriosclerotic plaque formation, as well as in high throughput screening of candidate drugs to atherosclerosis in a biosensor application.

Arteriosclerosis↗
PubMed2001

The membrane-microfilament linker ezrin is involved in the formation of the immunological synapse and in T cell activation.

Dynamic interactions between membrane and cytoskeleton components are crucial for T cell antigen recognition and subsequent cellular activation. We report here that the membrane-microfilament linker ezrin plays an important role in these processes. First, ezrin relocalizes to the contact area between T cells and stimulatory antigen-presenting cells (APCs), accumulating in F-actin-rich membrane protrusions at the periphery of the immunological synapse. Second, T cell receptor (TCR)-mediated intracellular signals are sufficient to induce ezrin relocalization, indicating that this protein is an effector of TCR signaling. Third, overexpression of the membrane binding domain of ezrin perturbs T cell receptor clustering in the T cell-APC contact area and inhibits the activation of nuclear factor for activated T cells (NF-AT).

Cell Communication↗
PubMed2001

CD28 as a molecular amplifier extending TCR ligation and signaling capabilities.

Evidence has gathered that CD28 costimulation facilitates T cell activation by potentiating TCR intrinsic-signaling. However, the underlying molecular mechanism is largely unknown. Here we show that, by enhancing T cell/APC close contacts, CD28 facilitates TCR signal transduction. Moreover, the signal supplied by CD28 does not lead to increased Zap-70 and Lat phosphorylation, but amplifies PLCgamma1 activation and Ca(2+) response. We provide evidence that the PTK Itk controls the latter function. Our data suggest that CD28 binding to B7 contributes to setting the level of TCR-induced phosphorylated Lat for recruiting signaling complexes, whereas the CD28 signal boosts multiple pathways by facilitating PLCgamma1 activation. These results should provide a conceptual framework for understanding quantitative and qualitative aspects of CD28-mediated costimulation.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Associations of cardiovascular disease and its risk factors with age-related macular degeneration: the POLA study.

The POLA study (June 1995 through July 1997) is a population-based study on cataract and age-related macular degeneration (AMD) and their risk factors in 2584 residents of Séte (South of France), aged 60--95 years. Classification of AMD was performed on 50 degrees fundus photographs, according to an international classification. The presence of cardiovascular disease and its risk factors was determined by interviewer-based questionnaire, clinical examination (anthropometry, blood pressure) and fasting plasma measurements. Using a logistic model adjusted for age and gender, late AMD was not significantly associated with a history of cardiovascular disease, diabetes, use of hypocholesterolemic drugs, hypertension, blood pressure or plasma lipids. Obese subjects (body mass index greater than 30 kg/m( 2)) had a 2.29-fold (95% confidence interval (CI): 1.00--5.23) and 1.54-fold (CI: 1.05--2.26) increased risk of late AMD and pigmentary abnormalities in comparison with lean subjects. Finally, the risk of soft drusen was decreased in those subjects with a history of cardiovascular disease (odds-ratio (OR) = 0.72, CI: 0.54--0.97), and increased with increasing levels of HDL-cholesterol (OR = 1.52, CI: 1.14--2.02). None of these results were modified by further adjustments for smoking, educational level and plasma alpha-tocopherol. These results need to be confirmed by other studies, which ideally should be longitudinal and prospective.

Aged↗
PubMed2001

Bone density, ultrasound measurements and body composition in early ankylosing spondylitis.

OBJECTIVES: In this cross-sectional study, we evaluated bone density using both dual-energy X-ray absorptiometry (DEXA) and quantitative ultrasound (QUS) techniques and examined the changes in body composition in patients with ankylosing spondylitis (AS). METHODS: Seventy-one patients were compared with seventy-one sex- and age-matched controls. Bone mineral density (BMD) was evaluated at the lumbar spine and femoral neck with a Lunar device. Total body measurements were also performed, giving BMD and bone mineral content (BMC) of the whole body, and fat and lean masses. Broadband ultrasound attenuation (BUA), speed of sound and stiffness were measured at the calcaneus using an Achilles ultrasound device. RESULTS: The patients had significantly lower lumbar spine, femoral neck and total body BMD as compared with controls (all P < 0.05). Total body BMC was also decreased in AS (P = 0.002). On the contrary, fat and lean masses did not differ between patients and controls as observed for QUS values. Mild to good correlations were found between BMD and QUS parameters (r ranging from 0.22 to 0.53; all P < or = 0.01). When applying the World Health Organization (WHO) definition for osteoporosis, we found that 46.5% of patients had lumbar spine osteopenia and/or osteoporosis, while 26.8% had femoral neck osteopenia and/or osteoporosis (controls: 23.9 and 10%; P = 0.001 and 0.08, respectively). No relationships between disease activity (as evaluated by erythrocyte sedimentation rate, serum C-reactive protein levels and BASDAI, a clinical index of disease activity) and BMD measurements were found and only femoral neck BMD correlated with disease duration (r = -0.25; P = 0.04). Finally, the presence of talalgia in AS did not influence the QUS values. CONCLUSION: These results confirm that AS patients have decreased BMD values at both the spine and femur, and also in total body measurements, reflecting a generalized bone loss. On the contrary, soft tissue composition does not seem to be influenced by the disease. QUS parameters were found to be similar between patients and controls, suggesting that the QUS method did not provide additive information to DEXA. As it is thought that QUS provides information about qualitative properties of bone, the normal results of QUS values in our patient series argue against modifications in AS bone micro-architecture.

Absorptiometry, Photon↗
PubMed2001

Mutually exclusive distribution of IS1548 and GBSi1, an active group II intron identified in human isolates of group B streptococci.

The present study shows that active, self-splicing group II intron GBSi1 is located downstream of the C5a-peptidase gene, scpB, in some group B streptococcus (GBS) isolates that lack insertion sequence IS1548. IS1548 was previously reported to be often present at the scpB locus in GBS isolated in association with endocarditis. Since none of 67 GBS isolates examined, 40 of which were of serotype III, harbored both IS1548 and GBSi1, these two elements are suggested to be markers for different genetic lineages in GBS serotype III. The DNA region downstream of scpB in GBS isolates harboring either GBSi1, IS1548, or none of these mobile elements was found to encode the laminin binding protein, Lmb, which shows sequence similarities to a family of streptococcal adhesins. IS1548 is inserted 9 bp upstream of the putative promoter for lmb, while the insertion site for GBSi1 is located 88 bp further upstream. Sequences highly similar to GBSi1 exist also in Streptococcus pneumoniae. An inverted repeat sequence, with features typical of transcription terminators, was identified immediately upstream of the insertion site for the group II intron both in the GBS and S. pneumoniae sequences. This motif is suggested to constitute a target for the GBS intron as well as for rather closely related introns in Bacillus halodurans, Pseudomonas alcaligenes, and Pseudomonas putida. When transcripts containing the GBSi1 intron were incubated at high concentrations of ammonium and magnesium, a major product with the expected length and sequence for the ligated exons was generated. Unlike, however, all members of group II investigated so far, the excised intron was in linear, rather than in a branched (lariat), form.

Adhesins, Bacterial↗
PubMed2000

CD28 utilizes Vav-1 to enhance TCR-proximal signaling and NF-AT activation.

The mechanism through which CD28 costimulation potentiates TCR-driven gene expression is still not clearly defined. Vav-1, an exchange factor for Rho GTPases thought to regulate, mainly through Rac-1, various signaling components leading to cytokine gene expression, is tyrosine phosphorylated upon CD28 engagement. Here, we provide evidence for a key role of Vav-1 in CD28-mediated signaling. Overexpression of Vav-1 in Jurkat cells in combination with CD28 ligation strongly reduced the concentration of staphylococcus enterotoxin E/MHC required for TCR-induced NF-AT activation. Surprisingly, upon Vav-1 overexpression CD28 ligation sufficed to activate NF-AT in the absence of TCR engagement. This effect was not mediated by overexpression of ZAP-70 nor of SLP-76 but necessitated the intracellular tail of CD28, the intactness of the TCR-proximal signaling cascade, the Src-homology domain 2 (SH2) domain of Vav-1, and SLP-76 phosphorylation, an event which was favored by Vav-1 itself. Cells overexpressing Vav-1 formed lamellipodia and microspikes reminiscent of Rac-1 and Cdc42 activation, respectively, for which the SH2 domain of Vav-1 was dispensable. Together, these data suggest that CD28 engagement activates Vav-1 to boost TCR signals through a synergistic cooperation between Vav-1 and SLP-76 and probably via cortical actin changes to facilitate the organization of a signaling zone.

Adaptor Proteins, Signal Transducing↗
PubMed2000

A three-dimensional perspective on exon binding by a group II self-splicing intron.

We have used chemical footprinting, kinetic dissection of reactions and comparative sequence analysis to show that in self-splicing introns belonging to subgroup IIB, the sites that bind the 5' and 3' exons are connected to one another by tertiary interactions. This unanticipated arrangement, which contrasts with the direct covalent linkage that prevails in the other major subdivision of group II (subgroup IIA), results in a unique three-dimensional architecture for the complex between the exons, their binding sites and intron domain V. A key feature of the modeled complex is the presence of several close contacts between domain V and one of the intron-exon pairings. These contacts, whose existence is supported by hydroxyl radical footprinting, provide a structural framework for the known role of domain V in catalysis and its recently demonstrated involvement in binding of the 5' exon.

Base Sequence↗
PubMed2000

Barrier-wave-internal-wave interference and airy minima in 16O16+O elastic scattering

Taking 16O+16O elastic scattering at 124 MeV as an example, we show that a barrier-wave-internal-wave decomposition of the elastic scattering amplitude provides valuable information on the light heavy-ion interaction and complements the more conventional nearside-farside decomposition. In particular, we show that the Airy minima present in the angular distributions are due to a barrier-wave-internal-wave interference mechanism, which sheds additional light on the exceptional transparency displayed by some light heavy-ion scattering systems. Extension of these ideas to other fields, like atomic and molecular collision physics, could prove rewarding.

Journal Article↗
PubMed2000

Able to name, unable to compare: the visual abilities of a posterior split-brain patient.

A patient with a lesion of the posterior half of the corpus callosum correctly named simple (e.g. colors) and complex (e.g. faces) stimuli whether presented to one or both hemifields. Although proficient at these tasks, and also able to make same/different judgements for stimuli within an hemifield, he failed dramatically when required to compare stimuli between the two hemifields. These results indicate that, while the posterior portion of the corpus callosum may not be essential for naming visual stimuli, it is essential for comparing stimuli between the two visual fields.

Adult↗
PubMed2000

Increased protein synthesis after T cell activation in presence of cyclosporin A.

BACKGROUND: The immunosuppressive drug, cyclosporin A (CsA), blocks immune responses by inhibiting the calcineurin-dependent dephosphorylation of the nuclear factor of activated T cells (NFAT). We have previously reported that T cells activated in presence of CsA exhibit particular properties. In our study, we have tested the hypothesis that T cells activated in presence of CsA display a differential pattern of gene expression. METHODS: T lymphocytes were activated in vitro by Concanavalin A with or without CsA. The cells were: (1) pulsed with 35S-methionine to label the newly synthesized proteins that in turn were revealed by 2D-gel electrophoresis; (2) analyzed by flow cytometry for activation markers expression; and (3) examined by gel electrophoresis for early tyrosine phosphorylation events. RESULTS: The proteomic patterns of T lymphocytes activated by Concanavalin A, with or without CsA, were compared. In keeping with the well-known effect of the immunosuppressor, many polypeptides were not found in its presence. Remarkably, several newly synthesized polypeptides were detected only when activation was carried out in presence of CsA. In addition, immunologically relevant proteins, such as CD44 and CD69, escape CsA-inhibitory action. Furthermore, CsA did not modify the early protein tyrosine phosphorylation events resulting from T cell triggering. CONCLUSIONS: The present data show that the effect of CsA on protein synthesis is more complex than anticipated. Signaling provided by T cell activation and the blockade of the calcineurin-dependent pathway by CsA results in an altered program of gene expression.

Animals↗