Biomedical subjects

D Muller

Publications and source records attributed to D Muller.

At least 19 recordsLinked to original sources

PubMed2006

Dynamics of Puumala virus infection in bank voles in Ardennes department (France).

The hantaviruses (genus Hantavirus, family Bunyaviridae) include human pathogens and occur worldwide. In Western and Central Europe, the predominant serotype is Puumala (PUU) virus, which causes epidemic nephropathy. Voles are considered to be the main reservoir and the vector of PUU virus. A total of 719 rodents (mainly Clethrionomys glareolus, Apodemus sp.) trapped by capture-mark-recapture (CMR) in four sites in Ardennes department (France) between April 2004 and October 2005 were tested for the presence of PUU virus antibodies by enzyme-linked immunosorbent assay (ELISA). The predominant species, C. glareolus (86.5% [622 of 719]), also had the highest antibody prevalence (37.6% [291 of 773]). In C. glareolus, the antibody prevalence rate increased with age (weight) in site A, B and D, reaching more than 50% in the heaviest weight, and suggesting that horizontal infection may be important.

Animals↗

PubMed2006

Damped precession of the magnetization vector of superparamagnetic nanoparticles excited by femtosecond optical pulses.

The ultrafast magnetization and electron dynamics of superparamagnetic cobalt nanoparticles, embedded in a dielectric matrix, have been investigated using femtosecond optical pulses. Our experimental approach allows us to bypass the superparamagnetic thermal fluctuations and to observe the trajectory of the magnetization vector which exhibits a strongly damped precession motion. The magnetization precession is damped faster in the superparamagnetic particles than in cobalt films or when the particle size decreases, suggesting that the damping is enhanced at the metal dielectric interface. Our observations question the gyroscopic nature of the magnetization pathway when superparamagnetic fluctuations take place as we discuss in the context of Brown's model.

Journal Article↗

PubMed2006

Cyclin L1 (CCNL1) gene alterations in human head and neck squamous cell carcinoma.

We evaluated the expression and amplification of cyclin L1 (CCNL1) gene, a potential oncogene localised in the commonly amplified 3q25-28 region, in human head and neck squamous cell carcinomas (HNSCCs). Overexpression was observed in 55 out of 96 cases (57%) and amplification in nine out of 35 tumours (26%) with no relationships to the clinico-pathological parameters. The Cyclin L1 antibody we developed labels nuclear speckles in tumour cells compatible with a role for CCNL1 in RNA splicing.

Carcinoma, Squamous Cell↗

PubMed2006

Head and neck squamous cell carcinoma transcriptome analysis by comprehensive validated differential display.

Head and neck squamous cell carcinoma (HNSCC) is common worldwide and is associated with a poor rate of survival. Identification of new markers and therapeutic targets, and understanding the complex transformation process, will require a comprehensive description of genome expression, that can only be achieved by combining different methodologies. We report here the HNSCC transcriptome that was determined by exhaustive differential display (DD) analysis coupled with validation by different methods on the same patient samples. The resulting 820 nonredundant sequences were analysed by high throughput bioinformatics analysis. Human proteins were identified for 73% (596) of the DD sequences. A large proportion (>50%) of the remaining unassigned sequences match ESTs (expressed sequence tags) from human tumours. For the functionally annotated proteins, there is significant enrichment for relevant biological processes, including cell motility, protein biosynthesis, stress and immune responses, cell death, cell cycle, cell proliferation and/or maintenance and transport. Three of the novel proteins (TMEM16A, PHLDB2 and ARHGAP21) were analysed further to show that they have the potential to be developed as therapeutic targets.

Amino Acid Sequence↗

PubMed2006

Role of the sodium-dependent phosphate co-transporters and of the phosphate complexes of uranyl in the cytotoxicity of uranium in LLC-PK1 cells.

Although uranium is a well-characterized nephrotoxic agent, very little is known at the cellular and molecular level about the mechanisms underlying the uptake and toxicity of this element in proximal tubule cells. The aim of this study was thus to characterize the species of uranium that are responsible for its cytotoxicity and define the mechanism which is involved in the uptake of the cytotoxic fraction of uranium using two cell lines derived from kidney proximal (LLC-PK(1)) and distal (MDCK) tubule as in vitro models. Treatment of LLC-PK(1) cells with colchicine, cytochalasin D, concanavalin A and PMA increased the sodium-dependent phosphate co-transport and the cytotoxicity of uranium. On the contrary, replacement of the extra-cellular sodium with N-methyl-D-glucamine highly reduced the transport of phosphate and the cytotoxic effect of uranium. Uranium cytotoxicity was also dependent upon the extra-cellular concentration of phosphate and decreased in a concentration-dependent manner by 0.1-10 mM phosphonoformic acid, a competitive inhibitor of phosphate uptake. Consistent with these observations, over-expression of the rat proximal tubule sodium-dependent phosphate co-transporter NaPi-IIa in stably transfected MDCK cells significantly increased the cytotoxicity of uranium, and computer modeling of uranium speciation showed that uranium cytotoxicity was directly dependent on the presence of the phosphate complexes of uranyl UO(2)(PO(4))(-) and UO(2)(HPO(4))(aq). Taken together, these data suggest that the cytotoxic fraction of uranium is a phosphate complex of uranyl whose uptake is mediated by a sodium-dependent phosphate co-transporter system.

Animals↗

PubMed2006

Identification and quantification of microstructures formed during nanocrystallization of amorphous (Fe, Co)-Nb-(Si, B) systems.

The effect of addition of Si and variation of the Fe/Co ratio on the evolution of the nanostructure was studied in a modification of the Fe-Nb-B system. The entire system (Fe, Co)(73)Nb(7)(Si, B)(20) was prepared in an amorphous state by rapid quenching using the planar flow casting method over a wide range of Fe/Co atomic ratios, ranging from 0 to 1. Nanocrystallization was investigated by evolution of the electrical resistivity with time and temperature. The microstructural analysis was performed using transmission electron microscopy as well as electron and X-ray diffraction. The results from microscopy observations were used to determine the distribution of grain size, which in these alloys attain very small dimensions of approximately 5-8 nm. New algorithms of microscope image analysis were used for grain size determination, crucial for quantifying the microprocesses controlling nucleation and growth from the amorphous rapidly quenched phase.

Journal Article↗

PubMed2006

The contribution of germline rearrangements to the spectrum of BRCA2 mutations.

BACKGROUND: Few germline BRCA2 rearrangements have been described compared with the large number of germline rearrangements reported in the BRCA1 gene. However, some BRCA2 rearrangements have been reported in families that included at least one case of male breast cancer. OBJECTIVE: To estimate the contribution of large genomic rearrangements to the spectrum of BRCA2 defects. METHODS: Quantitative multiplex PCR of short fluorescent fragments (QMPSF) was used to screen the BRCA2 gene for germline rearrangements in highly selected families. QMPSF was previously used to detect heterozygous deletions/duplications in many genes including BRCA1 and BRCA2. RESULTS: We selected a subgroup of 194 high risk families with four or more breast cancers with an average age at diagnosis of < or = 50 years, who were recruited through 14 genetic counselling centres in France and one centre in Switzerland. BRCA2 mutations were detected in 18.6% (36 index cases) and BRCA1 mutations in 12.4% (24 index cases) of these families. Of the 134 BRCA1/2 negative index cases in this subgroup, 120 were screened for large rearrangements of BRCA2 using QMPSF. Novel and distinct BRCA2 deletions were detected in three families and their boundaries were determined. We found that genomic rearrangements represent 7.7% (95% confidence interval 0% to 16%) of the BRCA2 mutation spectrum. CONCLUSION: The molecular diagnosis of breast cancer predisposition should include screening for BRCA2 rearrangements, at least in families with a high probability of BRCA2 defects.

Exons↗

PubMed2005

Inhibition of T-type calcium channels protects neurons from delayed ischemia-induced damage.

Intracellular calcium increase is an early key event triggering ischemic neuronal cell damage. The role of T-type voltage-gated calcium channels in the neuronal response to ischemia, however, has never been studied. Using an in vitro model of ischemia-induced delayed cell death in rat organotypic hippocampal slice cultures, we show that T-type calcium channels inhibitors drastically reduce ischemic cell damage. Immunostaining studies reveal the existence of Ca(V)3.1 and Ca(V)3.2 types of low-voltage-activated calcium channels in rat organotypic hippocampal cultures. Low extracellular calcium (100 nM) or increase of intracellular calcium buffering ability by BAPTA-acetoxymethyl ester significantly reduced ischemia-induced neuronal damage. Pharmacological inhibition of the T-type calcium current by mibefradil, kurtoxin, nickel, zinc, and pimozide during the oxygen-glucose deprivation episode provided a significant protection against delayed neuronal death. Mibefradil and nickel exerted neuroprotective effects, not only if administrated during the oxygen-glucose deprivation episode but also in conditions of postischemic treatment. These data point to a role of T-type calcium currents in ischemia-induced, calcium-mediated neuronal cell damage and suggest a possible new pharmacological approach to stroke treatment.

Animals↗

PubMed2005

Direct measurements of Ab and Ac using vertex and kaon charge tags at the SLAC detector.

Exploiting the manipulation of the SLAC Linear Collider electron-beam polarization, we present precise direct measurements of the parity-violation parameters A(c) and A(b) in the Z-boson-c-quark and Z-boson-b-quark coupling. Quark-antiquark discrimination is accomplished via a unique algorithm that takes advantage of the precise SLAC Large Detector charge coupled device vertex detector, employing the net charge of displaced vertices as well as the charge of kaons that emanate from those vertices. From the 1996-1998 sample of 400 000 Z decays, produced with an average beam polarization of 73.4%, we find A(c)=0.673+/-0.029(stat)+/-0.023(syst) and A(b)=0.919+/-0.018(stat)+/-0.017(syst).

Journal Article↗

PubMed2005

Cisplatin-induced genes as potential markers for thyroid cancer.

Despite the uncontested role of p53 in cycle arrest/cell death after cisplatin treatment, to date the question whether wild-type p53 confers a resistant or sensitive status on the cell is still a matter of debate. Isogenic and isophenotypic human thyroid papillary carcinoma cell line variants for p53 differently expressed cycle genes after cisplatin treatment. Seven genes (CDC6-related protein, CCNC, GAS1, TFDP2, MAPK10/JNK3, WEE1, RPA1) selected after expression on an Atlas human cell cycle array were analyzed by quantitative real-time PCR. While cisplatin treatment increased their expression in p53 wild-type cells it decreased it in cells with inactivated p53 and had no or less effect on cells with mutated p53. These results show that in a well-defined system, different alterations of p53 can lead to a different regulation of genes and hence to either resistance or sensitivity to cisplatin. Moreover for the first time, MAPK10/JNK3 was identified in human thyroid cells and tissue. Four of the genes (CDC6-related protein, CCNC, GAS1 and TFDP2) were decreased in human papillary carcinoma tissues. Relevance of these genes (especially a decrease in GAS1 in thyroid papillary carcinoma) in various malignant pathologies has already been shown. These genes may be explored as new markers in advanced thyroid cancer such as metastatic and anaplastic forms displaying p53 alterations.

Antineoplastic Agents↗

PubMed2004

Loss of HOP tumour suppressor expression in head and neck squamous cell carcinoma.

We report that homeodomain-only protein (HOP) is expressed in the suprabasal layer of normal upper aerodigestive tract epithelium and expression strongly decreases in hypopharyngeal carcinoma. Interestingly, HOP has very recently been shown to be a tumour suppressor involved in differentiation, suggesting that HOP may have a similar role in head and neck squamous cell carcinoma (HNSSC).

Biomarkers, Tumor↗

PubMed2004

Recovery of evoked potentials, metabolic activity and behavior in a mouse model of somatosensory cortex lesion: role of the neural cell adhesion molecule (NCAM).

Understanding the processes that underlie functional recovery after cortical injury is a major challenge for neurobiology and clinical neurology. The aim of the present study was to establish a mouse model of functional recovery that would facilitate the investigation of the molecular and cellular events involved in cortical dynamics. We show that a focal injury of approximately 0.5 mm of diameter and 1 mm depth made in the barrel cortex of adult mice induced a transitory deficit that could be characterized using somatosensory evoked potential (SEP), metabolic mapping and a behavioral test. SEP recordings of short latency responses using an epicranial multi-array system showed a decreased cortical activity in the peri-lesion regions 2 weeks after the injury and a partial recovery to normal pattern 6 weeks after the lesion. Delayed SEP signals over the motor cortex were not altered by the injury. Metabolic mapping with [14C]deoxyglucose uptake in the surround of the injury reproduced the time course of deficit and recovery. Finally, a deficit in vibrissae related performance in a gap-crossing test 1 week after injury was followed by a functional recovery in the following 2 weeks. We show in addition that the recovery process is deficient and significantly delayed in NCAM knockout mice lacking all isoforms of NCAM (neural cell adhesion molecule)and PSA-NCAM. These results support the hypothesis that impairment and recovery of functions after focal cortical lesion involves remodeling of intact circuits surrounding the lesion and that the NCAM molecule participate in this process. The model opens new possibilities for investigating the role of candidate molecules in functional recovery using genetically modified mice.

Animals↗

PubMed2004

Local gamma-aminobutyric acid and glutamate circuit control of hypophyseotrophic corticotropin-releasing factor neuron activity in the paraventricular nucleus of the hypothalamus.

Paraventricular corticotropin-releasing factor (CRF) neurons play a pivotal role in regulating neuroendocrine responses to stress. The mechanisms by which synaptic inputs control the activity of these neurons are not well understood. The present study was undertaken to determine the role of the intrinsic gamma-aminobutyric acid (GABA)- and glutamatergic neural circuits of the hypothalamic paraventricular nucleus (PVN) in the control of CRF neural activity. We show that in organotypic cultures of the PVN, blockade of the intrinsic GABAergic neurotransmission by the GABAA receptor antagonist bicuculline resulted in a significant increase in CRF secretion. The bicuculline-induced CRF secretory activity was abolished by the coadministration of the selective alpha-amino-3-hydroxy-5-methyl-4-isoxazoleprionic acid (AMPA)/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Electrical stimulation of the CRF cell division elicited glutamatergic extracellular field potentials that were dramatically enhanced by bicuculline and were suppressed by CNQX. These results show that the functional activity of CRF neurons in organotypic cultures of the PVN is under a tonic inhibitory influence of an intrinsic GABAergic circuit. Suppression of GABAergic transmission appears to have a permissive role for inducing an increased secretory activity of CRF neurons that is driven by an excitatory glutamatergic network via AMPA/kainate receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2004

[Structural organisation of CA1 zone in the hippocampus of rats in the experimental brain ischemia].

The dynamic of structural and ultrastructural changes of CA1 area of the hippocampus was examined in rats after 10 or 15 min of global ischemia (4 vessels occlusion, 4VO) followed by reperfusion. In the early period of reperfusion (15 min, 2 h), the structural changes in synaptic terminals were observed, without any significant signs of neuronal damage. These changes consisted in (i) the increase of the relative number of perforated and multiple synapses, and (ii) the synaptic vesicles rearrangement. Clear neuronal damage appeared morphologically at 24 h, and then developed for 3-6 days and resulted in the delayed damage and death of the hippocampal neurons.

Animals↗

PubMed2004

Improved method for the detection of TATP after explosion.

TATP in post explosion exhibits was reported earlier to be best recovered from vapor phase. A typical procedure includes its adsorption on Amberlite XAD-7, elution with acetonitrile and analysis by GC/MS. In this work, improved recovery of TATP from the vapor phase was achieved by SPME using PDMS/DVB fiber and immediate sampling to GC/MS. The recovery of TATP by SPME was compared with headspace and with adsorption on Amberlite XAD-7 by spiking onto filter paper put in a 100 mL beaker. The limit of detection of TATP was 6.4 ng in these conditions, few orders magnitude more than in the other tested methods. Recovery of TATP in the presence of various solvents was also studied. Acetone, water, and mixtures of water:alcohols (1:1) were found to reduce the recovery of TATP. Using SPME, TATP has been identified in dozens of post-explosion cases.

Acetone↗

PubMed2003

Differential expression profiling of head and neck squamous cell carcinoma (HNSCC).

Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in men with an incidence of about 780000 new cases per year worldwide and a poor rate of survival. There is a need for a better understanding of HNSCC, for the development of rational targeted interventions and to define new prognostic or diagnostic markers. To address these needs, we performed a large-scale differential display comparison of hypopharyngeal HNSCCs against histologically normal tissue from the same patients. We have identified 70 genes that exhibit a striking difference in expression between tumours and normal tissues. There is only a limited overlap with other HNSCC gene expression studies that have used other techniques and more heterogeneous tumour samples. Our results provide new insights into the understanding of HNSCC. At the genome level, a series of differentially expressed genes cluster at 12p12-13 and 1q21, two hotspots of genome disruption. The known genes share functional relationships in keratinocyte differentiation, angiogenesis, immunology, detoxification, and cell surface receptors. Of particular interest are the 13 'unknown' genes that exist only in EST, theoretical cDNA and protein databases, or as chromosomal locations. The differentially expressed genes that we have identified are potential new markers and therapeutic targets.

Aged↗

PubMed2003

Improved direct measurement of the parity-violation parameter Ab using a mass tag and momentum-weighted track charge.

We present an improved direct measurement of the parity-violation parameter A(b) in the Z boson-b-quark coupling using a self-calibrating track-charge technique applied to a sample enriched in Z-->bb events via the topological reconstruction of the B hadron mass. Manipulation of the Stanford Linear Collider electron-beam polarization permits the measurement of A(b) to be made independently of other Z-pole coupling parameters. From the 1996-1998 sample of 400,000 hadronic Z decays, produced with an average beam polarization of 73.4%, we find A(b)=0.906+/-0.022(stat)+/-0.023(syst).

Journal Article↗

PubMed2003

2,3-Dimercaptopropane-1-sulfonic acid and meso-2,3-dimercaptosuccinic acid increase mercury- and cadmium-induced inhibition of delta-aminolevulinate dehydratase.

Compounds derived from Dimercaprol, such as meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid (DMPS), are becoming common agents for treating humans exposed to heavy metals. Heavy metals such as Pb(2+), Hg(2+) and Cd(2+) can inhibit delta-aminolevulinate dehydratase (delta-ALA-D) activity. Delta-ALA-D catalyzes the condensation of two delta-aminolevulinic acid (delta-ALA) molecules with the formation of porphobilinogen, a heme precursor. The effects of DMSA and DMPS alone or in combination with Cd(2+), Hg(2+), or Pb(2+) on hepatic delta-ALA-D were examined. DMPS and DMSA caused a dose-dependent inhibition of hepatic delta-ALA-D. In the presence of Hg(2+) or Cd(2+) the inhibitory potency of DMPS increased. Similarly, the inhibitory effects of Hg(2+) and Cd(2+) were markedly increased in the presence of DMSA. In contrast, the inhibitory effect of DMPS was not changed by inclusion of Pb(2+). As observed with DMSA, Zn(2+) did not modified the inhibitory effect of DMPS. Data of the present report support the idea that the complexes formed (metals-DMSA or DMPS) were more inhibitory than the metal (Hg(2+) and Cd(2+)) or the chelating agent alone to the hepatic delta-ALA-D activity, in vitro. The mechanism of hepatic delta-ALA-D inhibition by Hg(2+)-DMPS/DMSA and Cd(2+)-DMPS/DMSA complexes involve the essential thiol groups of the enzyme.

Animals↗