Biomedical subjects

C Bernard

Publications and source records attributed to C Bernard.

At least 37 records · Page 2Linked to original sources

PubMed2003

Toxicological comparison of diverse Cylindrospermopsis raciborskii strains: evidence of liver damage caused by a French C raciborskii strain.

The freshwater cyanobacterium Cylindrospermopsis raciborskii is known to produce toxic effects in several countries. Acute and chronic exposures to C. raciborskii in Australia have been linked to liver damage (hepatotoxicity) with concomitant effects on the kidneys, adrenal glands, small intestine, lungs, thymus, and heart. The alkaloid cylindrospermopsin, which produces these toxic effects, is thought to be a potent inhibitor of protein synthesis. C. raciborskii strains producing cylindrospermopsin or analogue alkaloids have also been reported in Florida, USA, and Thailand. Brazilian isolates of C. raciborskii are also toxic but act by a different mechanism, causing acute death in mice with neurotoxic symptoms similar to those induced by the saxitoxins. In this article we compare the toxicity in the mouse of a C. raciborskii French strain with C. raciborskii strains from various other sources (Australia, Brazil, Mexico, and Hungary). We tested the toxicity of cell extracts by a mouse bioassay. Acute, fatal neurotoxicity was produced by the Brazilian strain, which was confirmed by liquid chromatography with fluorescence detection of the cell extracts, which revealed the presence of saxitoxin, neosaxitoxin, and decarbamoylsaxitoxin, along with two unidentified compounds. Acute hepatotoxicity with severe liver, kidney, and thymus damage was observed with the Australian cylindrospermopsin-producing strain. The Mexican and Hungarian strains were not found to be toxic to mice in our experimental conditions. No animals died after exposure to the extracts of the French C. raciborskii strain. Histological examination of the liver revealed moderate, multifocal necrosis characterized by small areas of hepatocellular necrosis, combined with disorganization of the parenchyma and congestion of the inner sinusoid. These symptoms and lesions resembled those induced by cylindrospermopsin, but the chemical analysis performed by liquid chromatography coupled with either a diode array detector or a mass spectrometer demonstrated that this toxin was not present in our culture extract.

Animals↗

PubMed2003

[Clinical characteristics and diagnosis of Smith-Lemli-Opitz syndrome and tentative phenotype-genotype correlation: report of 45 cases].

INTRODUCTION: SLO (Smith-Lemli-Opitz) syndrome is an autosomal recessive multiple congenital malformations syndrome, including mental retardation, failure to thrive, craniofacial abnormalities, incomplete development of male genitalia, limb anomalies and various internal organ abnormalities. This syndrome is caused by a deficiency of cholesterol biosynthesis at the distal step of 7-dehydrocholesterol reductase (7DHCR). PATIENTS AND METHODS: We have reviewed 45 cases of SLO syndrome and showed the large clinical spectrum of this syndrome. RESULTS: The prenatal diagnosis should be considered when dealing with antenatal growth retardation and visceral malformations. At birth, a normal weight does not systematically exclude the diagnosis. Diagnosis was more difficult for older children especially for girls and should be suspected on the association of mental retardation, autism, short stature and microcephaly. We found a correlation between low plasmatic cholesterol measurement and clinical severity. Phenotype-genotype correlation was difficult to establish. However, homozygosity for IVS8-1G > C splice site mutation was associated with severe phenotype. CONCLUSION: Better understanding of the 7DHCR gene regulation factors and of the compensatory mechanism of foeto-maternal cholesterol transfer are necessary to explain the wide clinical spectrum of the SLO syndrome.

Adolescent↗

PubMed2003

Distance-dependent modifiable threshold for action potential back-propagation in hippocampal dendrites.

In hippocampal CA1 pyramidal neurons, action potentials generated in the axon back-propagate in a decremental fashion into the dendritic tree where they affect synaptic integration and synaptic plasticity. The amplitude of back-propagating action potentials (b-APs) is controlled by various biological factors, including membrane potential (Vm). We report that, at any dendritic location (x), the transition from weak (small-amplitude b-APs) to strong (large-amplitude b-APs) back-propagation occurs when Vm crosses a threshold potential, x. When Vm > x, back-propagation is strong (mostly active). Conversely, when Vm < x, back-propagation is weak (mostly passive). x varies linearly with the distance (x) from the soma. Close to the soma, x << resting membrane potential (RMP) and a strong hyperpolarization of the membrane is necessary to switch back-propagation from strong to weak. In the distal dendrites, x >> RMP and a strong depolarization is necessary to switch back-propagation from weak to strong. At approximately 260 micrometer from the soma, 260 approximately RMP, suggesting that in this dendritic region back-propagation starts to switch from strong to weak. x depends on the availability or state of Na+ and K+ channels. Partial blockade or phosphorylation of K+ channels decreases x and thereby increases the portion of the dendritic tree experiencing strong back-propagation. Partial blockade or inactivation of Na+ channels has the opposite effect. We conclude that x is a parameter that captures the onset of the transition from weak to strong back-propagation. Its modification may alter dendritic function under physiological and pathological conditions by changing how far large action potentials back-propagate in the dendritic tree.

Action Potentials↗

PubMed2002

Stage-dependent activation of cell cycle and apoptosis mechanisms in the right ventricle by pressure overload.

The molecular basis of the intrinsic vulnerability of the compliant right ventricle to chronic pressure overload is poorly understood. Extensive apoptosis, possibly coupled with aberrant cell cycle reentry, in response to unrestrained biomechanical stress may account for this phenotypic flaw. To address this issue we have studied changes in expression of the cell cycle and apoptosis regulators in the right ventricle following induction of pulmonary hypertension in the rat by injection of monocrotaline. Hypertrophy, apoptosis and cell cycle events, as well as expression of their regulator genes were documented during a period of 31 days. The hypertrophy index reached 127% at day 31. At the early stage both apoptosis and cell proliferation pathways were coincidentally activated. The level of cyclin A and E transcripts steadily increased, the labeling index was 4.8% at day 31, and expression of the caspase-3 gene peaked at day 14. Until day 21 execution of apoptosis was prevented, probably by a high level of Bcl-2. At this time point Bcl-2 collapsed, cyclin D1 was upregulated, the differentiation gatekeeper p27Kip1 was downregulated, pro-caspase-3 was activated and extensive apoptosis developed. These results indicate that the right ventricle is especially vulnerable to apoptotic pressure-dependent stimuli, and that the cell cycle and apoptosis pathways were co-activated in this experimental model.

Angiotensin II↗

PubMed2002

Environmental context of Cylindrospermopsis raciborskii (Cyanobacteria) blooms in a shallow pond in France.

Cylindrospermopsis raciborskii, a potentially toxic blooming cyanobacterium (blue-green alga), responsible for public health problems in Australia, was identified in France in 1994 in a shallow pond south of Paris. A program monitoring the occurrence of C. raciborskii in this pond was conducted from July 1998 to October 1999. The phytoplankton assemblages were studied, and limnological parameters (water temperature, dissolved oxygen, pH, conductivity, and dissolved inorganic nutrients) were measured. By multivariate analysis (principal component analysis), we showed that sufficiently high temperatures to allow the germination of akinetes, relatively low nutrient concentrations (soluble reactive phosphorus with a mean concentration of 1 microM and nitrate between 0 and 5 microM, except in February 1999 (21 microM)) and a characteristic high and constant sulfate concentration (8981+/-471 microM) seemed to be the main factors involved in the proliferation of C. raciborskii in the "Francs-Pêcheurs" (FP) pond. In the light of these findings and of bibliographic data, C. raciborskii would seem to be characterized by good adaptability, but also by low competitiveness with other phytoplanktonic species in the temperate study area.

Adaptation, Physiological↗

PubMed2002

Second and subsequent lines of chemotherapy for metastatic breast cancer: what did we learn in the last two decades?

Despite almost 30 years of clinical cancer research, the true impact of second and subsequent lines of chemotherapy on the outcome of metastatic breast cancer patients, especially on the duration of survival, is still unknown. In the virtually incurable metastatic setting, issues like quality of life and patients' preferences gain particular relevance. At the turn of the century, in-depth rethinking of the design of clinical trials run in this challenging disease setting appears to be warranted.

Breast Neoplasms↗

PubMed2001

Early development of neuronal activity in the primate hippocampus in utero.

Morphological studies suggest that the primate hippocampus develops extensively before birth, but little is known about its functional development. Patch-clamp recordings of hippocampal neurons and reconstruction of biocytin-filled pyramidal cells were performed in slices of macaque cynomolgus fetuses delivered by cesarean section. We found that during the second half of gestation, axons and dendrites of pyramidal cells grow intensively by hundreds of micrometers per day to attain a high level of maturity near term. Synaptic currents appear around midgestation and are correlated with the level of morphological differentiation of pyramidal cells: the first synapses are GABAergic, and their emergence correlates with the growth of apical dendrite into stratum radiatum. A later occurrence of glutamatergic synaptic currents correlates with a further differentiation of the axodendritic tree and the appearance of spines. Relying on the number of dendritic spines, we estimated that hundreds of new glutamatergic synapses are established every day on a pyramidal neuron during the last third of gestation. Most of the synaptic activity is synchronized in spontaneous slow ( approximately 0.1 Hz) network oscillations reminiscent of the giant depolarizing potentials in neonatal rodents. Epileptiform discharges can be evoked by the GABA(A) receptor antagonist bicuculline by the last third of gestation, and postsynaptic GABA(B) receptors contribute to the termination of epileptiform discharges. Comparing the results obtained in primates and rodents, we conclude that the template of early hippocampal network development is conserved across the mammalian evolution but that it is shifted toward fetal life in primate.

Animals↗

PubMed2001

An anion-induced regio- and chemoselective acylation and its application to the synthesis of an anticancer agent.

[reaction--see text] An efficient Grignard- and organolithium-induced regio- and chemoselective anionic acylation is reported. A number of tricyclic ketones are prepared in good to excellent yields via this method. This method is complementary to the Frieldel-Crafts acylation for electron-deficient substrates. A novel anisole-based Grignard reagent was developed to effect the cyclization of sterically hindered substrates. This novel reagent has been successfully applied to the synthesis of Sch 66336, a candidate for oncologic treatment.

Acylation↗

PubMed2001

Solution structure of Ptu1, a toxin from the assassin bug Peirates turpis that blocks the voltage-sensitive calcium channel N-type.

Ptu1 is a toxin from the assassin bug Peirates turpis which has been demonstrated to bind reversibly the N-type calcium channels and to have lower affinity than the omega-conotoxin MVIIA. We have determined the solution structure of Ptu1 by use of conventional two-dimensional NMR techniques followed by distance-geometry and molecular dynamics. The calculated structure of Ptu1 belongs to the inhibitory cystin knot structural family (ICK) that consists of a compact disulfide-bonded core from which four loops emerge. Analysis of the 25 converged solutions indicates that the molecular structure of Ptu1 contains a 2-stranded antiparallel beta-sheet (residues 24-27 and 31-34) as the only secondary structure. The loop 2 that has been described to be critical for the binding of the toxin on the channel is similar in Ptu1 and MVIIA. In this loop, the critical residue, Tyr13, in MVIIA is retrieved in Ptu1 as Phe13, but the presence of an acidic residue (Asp16) in Ptu1 could disturb the binding of Ptu1 on the channel and could explain the lower affinity of Ptu1 toward the N-type calcium channel compared to the one of MVIIA. Analysis of the electrostatic charge's repartition gives some insights about the importance of the basic residues, which could interact with acidic residues of the channel and then provide a stabilization of the toxin on the channel.

Amino Acid Sequence↗

PubMed2001

Structural basis for alpha-K toxin specificity for K+ channels revealed through the solution 1H NMR structures of two noxiustoxin-iberiotoxin chimeras.

Noxiustoxin (NxTX) and iberiotoxin (IbTX) exhibit extraordinary differences in their ability to inhibit current through the large-conductance calcium-activated potassium (maxi-K) and voltage-gated potassium (Kv1.3) channels. The three-dimensional structures of NxTX and IbTX display differences in their alpha/beta turn and in the length of the alpha-carbon backbone. To understand the role of these differences in defining specificity, we constructed two NxTX mutants, NxTX-IbTX I and NxTX-IbTX II, and solved their solution structures by 1H NMR spectroscopy. For NxTX-IbTX I, seven amino acids comprising the alpha/beta turn in NxTX are replaced with six amino acids from the corresponding alpha/beta turn in IbTX (NxTX-YGSSAGA21-27FGVDRF21-26). In addition, NxTX-IbTX II contained the S14W mutation and deletion of the N- and C-terminal residues. Both NxTX-IbTX I and NxTX-IbTX II exhibit an alpha/beta scaffold structure typical of the alpha-K channel toxins. A helix is present from residues 10 to 19 in NxTX-IbTX I and from residues 13 to 19 in NxTX-IbTX II. The beta-sheet, defined by three antiparallel strands, is one residue longer in NxTX-IbTX I relative to NxTX-IbTX II. The two toxins also differ in the structure of the alpha/beta turn with NxTX-IbTX I resembling that of IbTX and with NxTX-IbTX II resembling that of NxTX. These differences in the beta-sheet and alpha/beta turn alter the dimensions of the toxin-channel interaction surface and provide insight into how these NxTX mutations alter K+ channel specificity for the maxi-K and Kv1.3 channels.

Amino Acid Sequence↗

PubMed2001

Hyalinizing trabecular adenoma versus papillary thyroid carcinoma in a child.

Hyalinizing trabecular adenoma (HTA) of the thyroid gland is a rare, benign neoplasm predominantly diagnosed in middle-aged women. There is mounting evidence in the medical literature, however, to suggest that HTA may represent an encapsulated variant of papillary thyroid carcinoma (PTC). This report describes an unusual case of PTC in a child initially diagnosed as HTA. Establishing an accurate diagnosis has important management implications for the pediatric patient.

Adenoma↗

PubMed2001

CCK expression in enteroendocrine cell is regulated by soluble factor(s) from underlying fibroblasts.

Studies on the cross-talk between the intestinal epithelium and the underlying connective tissue have concentrated on enterocytes. In contrast, little is known about the interactions between the mesenchymal compartment and the enteroendocrine cells, scattered among the other cell types of the epithelium. To address this question, a panel of coculture systems between the enteroendocrine STC-1 cell line and three intestinal myofibroblastic cell lines (MIC) was used in order to assess different levels of regulation, namely cell-cell and cell-matrix interactions, and the role of diffusible factors. We demonstrate that the expression of cholecystokinin, a typical intestinal hormone produced by STC-1 cells, is up-regulated in the presence of a fibroblastic environment through a paracrine pathway involving FGF2. Concomitantly, STC-1 cell morphology and proliferation were also modulated, but through distinct mechanisms according to the origin of fibroblasts. The results reveal definite epithelio-mesenchymal interactions that may be critical for the maintenance of phenotype and function of enteroendocrine cells.

Animals↗

PubMed2001

Symptomatic splenic hamartoma with renal, cutaneous, and hematological abnormalities.

BACKGROUND: There is a rare association between splenic hamartomas and hematological abnormalities with, to our knowledge, only 24 reported cases in the English literature. PATIENTS AND METHODS: We report a case of a splenic hamartoma in a 14-year-old boy associated with membranoproliferative glomerulonephritis, multiple lobular capillary hemangiomas of the skin, hypertension, and anemia. Following imaging with ultrasonography, MRI, and nuclear scans, a hamartoma was suspected, but malignancy could not be excluded. The lesion was removed by partial splenectomy, and pathological examination confirmed the presence of a red pulp splenic hamartoma. RESULTS: The renal, hematological, and dermatological abnormalities resolved following removal of the splenic hamartoma. This is the first reported case of a splenic hamartoma associated with renal, cutaneous, and hematological abnormalities and only the second reported case of a symptomatic splenic hamartoma treated by partial splenectomy.

Adolescent↗

PubMed2001

Characterization of new mutations in the coding sequence and 5'-untranslated region of the human prostacylcin synthase gene (CYP8A1).

Inheritable interindividual differences in prostacyclin production may be implicated in the pathogenesis of several human vascular diseases. Using a polymerase chain reaction/single-strand conformation polymorphism strategy, we screened for mutations in the gene encoding cytochrome P450 prostacyclin synthase (CYP8A1). DNA samples from healthy French volunteers (n = 130) of Caucasian origin were examined. Five mutations, comprising two previously reported silent mutations and three novel rare missense mutations (P38L, S118R, and R379S), were identified in the coding sequence of the gene. In the 5'-proximal region, we also found a variable number of tandem repeats (VNTR) polymorphism that consisted of four different alleles with 4-6 tandem repeats of a 9-bp unit containing a putative Spl transcriptional factor binding site. One of these (R6), a frequent allele (23.6% of alleles tested) harboring six repeats, is novel, whereas the other three are known. In vitro analysis of the effect of each VNTR allele on promoter activity of a reporter gene was performed by a transient transfection assay. Data confirmed the modulator effect of the VNTR polymorphism on reporter gene transcription. Furthermore, the data demonstrate that allele R6 has the most potent inducing effects in the A549 cell line and, after IL-6 stimulation, in human pulmonary artery endothelial cells. Overall, the data demonstrate that CYP8A1 is polymorphic in Caucasians, and that a polymorphism affecting the 5'-proximal region may result in interindividual differences in CYP8A1 transcriptional regulation in vivo. Additional factors, such as the presence of inflammatory mediators, may be required to modulate transcription of the CYP8A1 gene.

5' Untranslated Regions↗

PubMed2001

Oxidising and disinfecting by hydrogen peroxide produced in a two-electrode cell.

Hydrogen peroxide was produced by direct current electrolysis using two electrodes only, a carbon felt cathode and a dimensional stabilised anode (titanium coated with RuO2), without adding any chemical. The required oxygen was supplied by water oxidation and by transfer from the atmosphere. The intensity should be maintained under a maximum value to avoid peroxide reduction. High peroxide production rate and concentration were then reached. Electroperoxidation partially removed dissolved organic carbon (DOC) contained in solutions of phenol, salicylic acid, benzoic acid and humic acids. The DOC removal in effluent of municipal sewage plant corresponded to a breakage of the double bonds. Real effluents were significantly disinfected owing to the direct effect of electric current and the indirect effect of peroxide. Moreover, a remnant effect was ensured.

Cell Division↗

PubMed2001

Changes in neuronal excitability and synaptic function in a chronic model of temporal lobe epilepsy.

Long-term potentiation and depression of glutamatergic synaptic responses are accompanied by an increased firing probability of neurons in response to a given excitatory input. This property, named excitatory postsynaptic potential/spike potentiation, has also been described in epileptic tissue and has pro-epileptic consequences. In this study, we show that excitatory postsynaptic potential/spike potentiation can be reversed in the kainic acid lesioned rat hippocampus, a chronic model of temporal lobe epilepsy. Simultaneous in vitro extracellular recordings in stratum radiatum and stratum pyramidale were performed in the CA1 area of the kainic acid lesioned rat hippocampal slices. Fifteen minutes, application of the K(+) channel blocker tetraethylammonium resulted in excitatory postsynaptic potential/spike potentiation (measured 90min after the start of the washout period) which could be reversed by subsequent low-frequency or tetanic stimuli. Excitatory postsynaptic potential/spike potentiation and its subsequent reversal by an electrical conditioning stimulus were found to have a N-methyl-D-aspartate receptor-independent component. Tetraethylammonium treatment also resulted in excitatory postsynaptic potential/spike potentiation of pharmacologically isolated N-methyl-D-aspartate receptor-mediated responses which could be reversed by subsequent low-frequency or tetanic stimuli. We conclude that excitatory postsynaptic potential/spike potentiation can be reversed in epileptic tissue, even in the absence of synaptic plasticity. These results suggest the presence of endogenous regulatory mechanisms which are able to decrease cell excitability.

Action Potentials↗

PubMed2001

[Successful endovascular embolization in the vertebral artery after failed surgery in a patient with severe hemorrhagic shock].

Injury of the vertebral artery following penetrating trauma is rare and treatment is usually a surgical double ligation. We report a case of a 19-year old man, suffering from potentially fatal haemorrhage related to a penetrating trauma of the left vertebral artery. After failure of surgery, bleeding has been successfully stopped by endovascular embolization. The patient did not suffer any ischaemic cerebral complication and was discharged from intensive care unit 24 hours later.

Adult↗

PubMed2001

Presynaptic kainate receptors that enhance the release of GABA on CA1 hippocampal interneurons.

We report that kainate receptors are present on presynaptic GABAergic terminals contacting interneurons and that their activation increases GABA release. Application of kainate increased the frequency of miniature inhibitory postsynaptic currents recorded in CA1 interneurons. Local applications of glutamate but not of AMPA or NMDA also increased GABA quantal release. Application of kainate as well as synaptically released glutamate reduced the number of failures of GABAergic neurotransmission between interneurons. Thus, activation of presynaptic kainate receptors increases the probability of GABA release at interneuron-interneuron synapses. Glutamate may selectively control the communication between interneurons by increasing their mutual inhibition.

Animals↗