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C Chambon

Publications and source records attributed to C Chambon.

At least 19 recordsLinked to original sources
PubMed2006

Proteomic analysis of ovine muscle hypertrophy.

Two-dimensional electrophoresis was used to investigate the effects of a QTL for muscle hypertrophy on sarcoplasmic protein expression in ovine muscles. In the Belgian Texel breed, the QTL for muscle hypertrophy is localized in the myostatin-encoding gene. Based on microsatellite markers flanking the myostatin gene, we compared the hypertrophied genotype with the normal genotype. The average age of the sheep was 3 mo. Among the 4 muscles studied, in the hypertrophied genotype only the vastus medialis was normal, whereas the semimembranosus, tensor fasciae latae, and LM were hypertrophied. In the hypertrophied genotype, these muscles showed upregulation of enzymes involved in glycolytic metabolism together with oxidative metabolism in LM. Certain chaperone proteins, including glutathione S-transferase-Pi, heat shock protein-27, and heat shock cognate-70, were also more highly expressed, probably due to increased use of energetic pathways. Expression of the iron transport protein transferrin was increased. Alpha-1-antitrypsin was the only protein showing a similar pattern of expression (i.e., less expressed) in all 4 muscles of the hypertrophied genotype. It is suggested that transferrin and alpha-1-antitrypsin may interact to reinforce myogenic proliferative signaling.

Animals↗
PubMed2005

Time course of behavioral changes following basal forebrain cholinergic damage in rats: Environmental enrichment as a therapeutic intervention.

The present experiment was designed to study changes in behavior following immunolesioning of the basal forebrain cholinergic system. Rats were lesioned at 3 months of age by injection of the 192 IgG-saporin immunotoxin into the medial septum area and the nucleus basalis magnocellularis, and then tested at different times after surgery (from days 7-500) on a range of behavioral tests, administered in the following order: a nonmatching-to-position task in a T-maze, an object-recognition task, an object-location task, and an open-field activity test. The results revealed a two-way interaction between post-lesion behavioral testing time and memory demands. In the nonmatching-to-position task, memory deficits appeared quite rapidly after surgery, i.e. at a post-lesion time as short as 1 month. In the object-recognition test, memory impairments appeared only when rats were tested at late post-lesion times (starting at 15 months), whereas in the object-location task deficits were apparent at early post-lesion times (starting from 2 months). Taking the post-operative time into account, one can hypothesize that at the shortest post-lesion times, behavioral deficits are due to pure cholinergic depletion, while as the post-lesion time increases, one can speculate the occurrence of a non-cholinergic system decompensation process and/or a gradual degeneration process affecting other neuronal systems that may contribute to mnemonic impairments. Interestingly, when middle-aged rats were housed in an enriched environment, 192 IgG-saporin-lesioned rats performed better than standard-lesioned rats on both the nonmatching-to-position and the object-recognition tests. Environment enrichment had significant beneficial effects in 192 IgG-saporin-lesioned rats, suggesting that lesioned rats at late post-lesion times (over 1 year) still have appreciable cognitive plasticity.

Acetylcholine↗
PubMed2001

Photoaffinity labeling of human sex hormone-binding globulin using 17alpha-alkylamine derivatives of 3beta-androstanediol substituted with azidonitrophenylamido, azidonitrophenylamino, or trifluoroazidonitrophenylamino chromophores. Localization of Trp-84 in the vicinity of the steroid-binding site.

Purified human SHBG was photoaffinity labeled with 17alpha-aminomethyl (M), 17alpha-aminoethyl (E), and 17alpha-aminopropyl (P) derivatives of [3alpha-(3)H]-5alpha-androstane-3beta,17beta-diol coupled to 5-azido-2-nitrobenzoylamido (ANB), 4-azido-2-nitrophenylamino (ANP), and 5-azido-2-nitro-3,4,6-trifluorophenylamino (ANTFP) chromophores. Successful labeling was achieved in all cases except for the two photoreagents with the shortest side chains, namely, ANP-M and ANTFP-M derivatives. Edman sequencing and mass spectrometry of immunopurified photolabeled tryptic fragments revealed that radioactivity was present either on the sequence of residues 73-94, uniquely at the level of Trp-84 (stable covalent labeling), or on one of the two overlapping sequences of residues 126-134 and 126-135, at the level of Pro-130 (labile labeling) and Lys-134 (either stable or partially labile labeling), respectively. The same Trp-84 was photolabeled with the three ANB derivatives of increasing lengths, and by the ANP-P photoreagent. This residue was the exclusive target for the shortest [(3)H]ANB-M photoreagent but was a minor site for the longest [(3)H]ANB-P photoreagent, essentially recovered at the level of Pro-130. The [(3)H]ANB-E photoreagent of intermediate size also labeled exclusively Trp-84, except in some experiments in which photolabeling was recovered predominantly at the level of Pro-130. The [(3)H]ANP-P photoreagent with an overall length similar to that of the ANB-P photoreagent labeled simultaneously Trp-84 (minor site) and Lys-134. The other [(3)H]ANP-E, [(3)H]ANTFP-E, and [(3)H]ANTFP-P derivatives labeled in all cases Lys-134. These findings indicate that the conserved Trp-84 and the two Pro-130 and Lys-134 residues are all located in the vicinity of the D ring of steroid ligands and remain freely accessible from the C17alpha position, thus providing biochemical data delineating the corresponding region of the steroid-binding site.

Affinity Labels↗
PubMed2000

Synthesis of (5-azido-2-nitrobenzoyl)amido, (4-azido-2-nitrophenyl)amino, and (5-azido-2-nitro-3,4, 6-trifluorophenyl)amino derivatives of 17alpha-methylamino-, 17alpha-ethylamino-, and 17alpha-propylamino-5alpha-dihydrotestosterone as reagents of different linker lengths for the photoaffinity labeling of sex hormone binding globulins and androgen receptors.

The photoactivable aryl azide reagents, N-(5-azido-2-nitrobenzoyl)oxysuccinimide, 4-azido-1-fluoro-2-nitrobenzene, and 4-azido-1-nitro-2,4,5, 6-tetrafluorobenzene have been condensed at the extremity of three 17alpha-aminomethyl, 17alpha-aminoethyl, and 17alpha-aminopropyl side-chains introduced on (17S)-spiro-(3, 3-dimethoxy)-5alpha-androstan-17beta,2'-oxirane either directly, by ammonolysis, in the first case, or by conversion to nitrile intermediates with cyano or cyanomethyl anions and subsequent reduction to amines with lithium aluminum hydride, in the two other cases. The 3,3-dimethoxy group of these photoreagents was cleaved by acidolysis to a 3-ketone, which was reduced with sodium borohydride to a 3beta-alcohol. All of these compounds were characterized by (1)H- and (13)C-NMR as well as by (1)H, (13)C heteronuclear 2D NMR, which helped to resolve ambiguous assignments. Significant differences of substituent-induced effects on (13)C NMR signals were observed according to the 17alpha-side-chain length, the structure of the terminal aryl azide groups, and the solvent, showing a different behavior of N-5-azido-2-nitrobenzoyl derivatives as compared with 4-azido-2-nitrophenylamino and 5-azido-2-nitro-3,4, 6-trifluorophenylamino derivatives. The N-5-azido-2-nitrobenzoyl conjugates of the three 17alpha-aminomethyl, aminoethyl, and aminopropyl derivatives of 5alpha-dihydrotestosterone were tested as ligands for purified human sex hormone-binding globulin and for the cytosolic androgen receptor of rat ventral prostate by competition experiments with tritiated 5alpha-dihydrotestosterone. The increasing lengths of the aminomethyl, aminoethyl, and aminopropyl spacer arms of N-5-azido-2-nitrobenzoyl conjugates were found to correspond to decreasing relative binding affinities for sex hormone-binding globulin (0.76, 0.47, and 0.10, respectively, versus 1.00 for 5alpha-dihydrotestosterone) while only the longer aminoethyl and aminopropyl conjugates interacted significantly with the androgen receptors (0.05 and 0.10, respectively).

Animals↗
PubMed1998

Photoaffinity labeling of homologous Met-133 and Met-139 amino acids of rabbit and sheep sex hormone-binding globulins with the unsubstituted Delta 6-testosterone photoreagent.

Purified rabbit and sheep sex hormone-binding globulins (SHBGs) were photolabeled by Delta 6-testosterone. The maximal levels of specific incorporation were respectively 0.33 and 0.30 mol of label/mol of homodimer. Tryptic cleavage of photolabeled SHBGs gave a single radioactive peptide for rabbit SHBG and two major radioactive peptides S1 and S2 for sheep SHBG. Edman sequencing of the photolabeled peptide of rabbit SHBG revealed a single sequence corresponding to peptidic fragment Leu-118-Lys-134. Subcleavage of this peptide with elastase led to a single radioactive peptidic fragment corresponding to dipeptide Met-133-Lys-134, identified by mass spectrometry, while deletion of the C-terminal residue with carboxypeptidase B showed that all the radioactivity remained on peptide Leu-118-Met-133, thus demonstrating that photolabeling occurred exclusively on Met-133, the only residue common to the two radioactive subcleaved peptides. Edman sequencing of peptides S1 and S2 of sheep SHBG showed a same single sequence corresponding to residues Gln-126-Arg-140 which contained no identifiable phenylthiohydantoin derivative at cycle 14, thus indicating that in both cases the corresponding Met-139 residue is the main site of photolabeling, as confirmed for peptide S1 by the presence at this cycle of a major peak of radioactivity while in peptide S2 the photoattachment of Delta 6-testosterone was found labile in the conditions of sequencing. The photolabeled peptide S1 was characterized by mass spectrometry which showed the covalent fixation of one mole of Delta 6-testosterone and the presence of a biantennary oligosaccharide attached at Asn-133, which suggests that the steroid-binding site is probably not deeply buried in the SHBG homodimer.

Amino Acid Sequence↗
PubMed1997

Arbitrary primed PCR rules out Clostridium difficile cross-infection among patients in a haematology unit.

Eight out of 20 (40%) patients with haematological malignancies hospitalized in the same unit of our hospital from 24 January to 24 April 1995, suffered from diarrhoea due to Clostridium difficile. The C. difficile isolates were characterized by serotyping and by arbitrary primed polymerase chain reaction (AP-PCR) using three different 10-mer oligonucleotides. It was found by serotyping that five patients had non-typeable isolates and three had serogroup H isolates. The AP-PCR typed all the isolates and yielded various patterns suggesting that there had been no cross-transmission between the patients. Control faecal sample cultures showed that two patients were still carrying the same isolates after specific treatment with vancomycin or metronidazole, and that one patient had acquired an isolate with a new AP-PCR type. AP-PCR was found to be a rapid, effective discriminative method for the immediate epidemiological tracking of hospital-acquired infections due to C difficile.

Adult↗
PubMed1997

Liver positive enhancement after injection of superparamagnetic nanoparticles: respective role of circulating and uptaken particles.

Superparamagnetic nanoparticles have both high r1 and r2 relaxivities responsible for positive or negative enhancement properties. The aim of this study was to investigate to what extent perfusion (circulating particles) and uptake (clustered particles) mechanisms contribute to liver positive or negative enhancement using two different particles, superparamagnetic iron oxides (ferumoxides, AMI 25) and ultrasmall superparamagnetic iron oxides (ferumoxtran, AMI-227). Uptake kinetics were studied after intravenous injection of 20 micromol Fe/kg ferumoxtran on a washout liver model. Livers of 82 rats were surgically isolated and washed with saline infusion. Imaging was performed ex vivo at 0.5T with T1- and T2-weighted sequences. Enhancement kinetics of the liver were studied in vivo using MRI up to 180 min post injection of 20 micromol Fe/kg ferumoxtran (time response study) or 10, 20, 40 micromol Fe/kg ferumoxtran and 20 micromol Fe/kg ferumoxides (dose response study.) Particle uptake occurred early and resulted in a negative enhancement of the washed livers 15 min after injection of both T1 and T2 sequences. In vivo, a positive enhancement was only seen during the first five min with the lowest dose of ultrasmall superparamagnetic iron oxides and the T1 sequence. Uptake and clustering of the particles induced a negative liver enhancement. During the first minutes after injection, when uptake has not significantly occurred, perfusion imaging of the liver at a dose of 10 micromol Fe/kg results in a positive enhancement with T1-weighted sequences.

Analysis of Variance↗
PubMed1996

[Functional magnetic resonance imaging (MRI) of hepatic ischemia in the rabbit. Contribution of a particulated contrast agent (AMI-25)].

A functional approach of the rabbit portal ischemia was performed on five New Zealand rabbits using magnetic-resonance (MR) imaging and an MR-specific contrast agent for the liver. The hepatic vascularization and the functionality of the phagocytosis cells were both studied with a single low dose of a unique contrast agent-superparamagnetic iron oxide particles (SPIOs). After a rapid i.v. injection of SPIOs, functional vessels and normally perfused liver parenchyma appeared with positive signal enhancement, whereas the ischemic area remained dark (cold spot). After the intravascular time period, the well-known negative enhancement induced by these particles on normal parenchyma was observed, with the difference of the ischemic liver, and could be related to the uptake of SPIOs by functional Kupffer cells.

Animals↗
PubMed1996

Pharmacokinetic profile of iobitridol.

Iobitridol (Xenetix) is a new triiodinated monomer, nonionic, low-osmolality contrast agent. Animal pharmacokinetic studies (rats, rabbits, dogs) and in vitro studies show that it is a marker of extracellular fluid, i.e. it is distributed in the interstitial space, it does not penetrate into cells, it does not cross the healthy blood-brain barrier (BBB), it does not bind to proteins, and it is eliminated by glomerular filtration without secretion or reabsorption. These characteristics determine its use as an urography and angiography contrast agent as well as the precautions necessary to be taken, which are classical for contrast agents of this classification, related to administration in pathophysiologic populations (patients with renal failure, pregnant women or nursing mothers, neonates, etc. )

Animals↗
PubMed1996

Time course of biodistribution and changes in density following administration of iobitridol in rabbits. A comparative study vs iohexol.

PURPOSE: A new nonionic low-osmolality contrast medium, iobitridol (Xenetix 350) was compared with iohexol (Omnipaque) after i.v. injection in anesthetized rabbits to assess efficacy in CT examinations and biodistribution. MATERIAL AND METHODS: The densities in test tubes and the pharmacogenetics and biodistribution of iobitridol 350 and iohexol were compared in rabbits. CT of the brain, liver, the abdominal aorta and the kidneys was performed before and after injection of the contrast media. RESULTS: In aqueous medium, iobitridol absorbed roentgen rays in a manner exactly identical to that of iohexol. Within 15 min following injection of iohexol and iobitridol at a dose of 300 mg I/kg, both contrast agents resulted in aortic enhancement which decreased with time. An increased attenuation of the liver also occurred, decreasing with time. There was no significant enhancement in the brain but enhancement was found in the renal pelvocalyceal cavities 10 min postinjection. No significant difference was found between the 2 contrast agents under the study conditions. CONCLUSION: As could be expected from its behavior as a tracer of extracellular fluid, iobitridol resulted in significant changes in the signal, corresponding to its vascular, hepatic and renal pharmacokinetics in rabbits.

Animals↗
PubMed1995

Down-regulation of mitochondrial mRNAs in the mdx mouse model for Duchenne muscular dystrophy.

In our search for genes up- or down-regulated genes in the mdx mouse model for Duchenne muscular dystrophy, we isolated a down-regulated mitochondrial DNA clone. In addition to this clone, all protein-coding mitochondrial genes tested had tissue-specific and age independent down-regulated expression. This implied mechanisms at the RNA level since no change in the mitochondrial DNA contents were detected. Cytochrome c oxidase activity showed the same range of down-regulated expression. These data provide a molecular basis for energetic metabolism modifications in mdx mice.

Aging↗
PubMed1995

High-performance liquid chromatographic determination of iobitridol in plasma, urine and bile.

Iobitridol is a new non-ionic, low-osmolality contrast medium for urography and angiography. We have developed a method for determining iobitridol in body fluids using high-performance liquid chromatography with ultraviolet detection. The method, which is specific and reproducible, does not require an internal standard. Determinations can be carried out in body fluids against a set of standards in ethanol. The method was validated for the quantification of iobitridol in biological samples obtained during pharmacokinetic studies.

Animals↗
PubMed1995

A new mutation of the ALAS2 gene in a large family with X-linked sideroblastic anemia.

X-linked sideroblastic anemia is a genetic disorder characterized by a hypochromic microcytic anemia of variable intensity with the presence of ring sideroblasts in the bone marrow of the patients. Two different mutations have been reported in the ALAS2 gene in patients with this disease. We have studied a large kindred with a pyridoxine-sensitive form of X-linked sideroblastic anemia. Sequencing amplified cDNA of the proband revealed a guanine-to-adenine change at nucleotide 871 of the coding sequence (exon 7 of the gene). This results in a glycine to serine substitution that is responsible for a marked decrease in the enzymatic activity of the mutated protein. A polymerase chain reaction assay demonstrated the presence of the same mutation in three affected males and two female carriers in the kindred. The carrier status was excluded in eight females at risk. Early detection of the mutant allele in family members may thus be important for the prevention of anemia in males and of iron overload both in affected males and carrier females.

Adolescent↗
PubMed1995

Intraarticular tolerability and kinetics of gadolinium tetra-azacyclododecane tetraacetic acid.

RATIONALE AND OBJECTIVES: We assessed the tolerability and the intraarticular kinetics of gadolinium tetra-azacyclododecane tetraacetic acid (Gd-DOTA) using magnetic resonance (MR) imaging. METHODS: Twelve of 18 dogs received an intraarticular injection of Gd-DOTA solution. Pathologic examination of all joints was performed with assessment of Gd-DOTA bone absorption. Effects of Gd-DOTA on chondrocyte viability and proliferation in vitro were determined using cultures of rabbit chondrocytes. Four dogs underwent MR imaging of the stifle joint before and after intraarticular injection of 0.8 ml Gd-DOTA at a concentration of 2 mmol/l (300 mOsm/l). Intraarticular kinetics of Gd-DOTA were determined from quantitative measurements using repeated sagittal spin-echo T1-weighted images. RESULTS: No microscopic changes of the joints or Gd-DOTA bone absorption were detected. No cytotoxicity for chondrocytes was observed at a concentration of 5 mmol/l, but a decreased cell count was observed at a high concentration (50 mmol/l). The intraarticular Gd-DOTA concentration decreased with time according to a logarithmic curve with an intraarticular half-life of 103-152 min (M = 127 min). CONCLUSION: Gd-DOTA is a safe intraarticular contrast agent with a long half-life in the joint cavity.

Absorption↗
PubMed1995

Comparative study of the dialysability of iobitridol and iohexol in the rat with impaired renal function.

PURPOSE: To assess the dialysability of iobitridol, a comparative study with iohexol was conducted in the rat over 4 hours. MATERIAL AND METHODS: After ligature of the renal veins and arteries, a group of animals was submitted to continuous peritoneal dialysis, while the remainder were not. RESULTS: In the event of total renal failure, biliary excretion rose from 0.4 to 9% for iobitridol and from 2 to 16% for iohexol. In the rats submitted to peritoneal dialysis, biliary excretion decreased to 5% in the iobitridol group and to 13% in the iohexol group. Further, 18% of the test substances were eliminated in the dialysis liquid. CONCLUSIONS: As their physicochemical characteristics are very similar, the differences between the biliary excretion levels of these 2 media may be caused by a factor related to their respective molecular conformations.

Animals↗
PubMed1994

Evaluation of intrarenal distribution of ultrasmall superparamagnetic iron oxide particles by magnetic resonance imaging and modification by furosemide and water restriction.

RATIONALE AND OBJECTIVES: The steady-state intrarenal distribution of ultrasmall superparamagnetic iron oxide (USPIO) particles in the cortex, the outer medulla (OM), and the inner medulla (IM) was investigated using magnetic resonance imaging in the normal rabbit kidney and in situations that modify the corticopapillary osmotic gradient. METHODS: Experiments were performed on rabbit kidneys with T2-weighed spin-echo sequence and T2-weighted gradient-recalled-echo sequence. The intravenous dose was 27 mumole/kg of iron in all rabbits. Three groups were studied: normally hydrated rabbits (n = 5), after water restriction (n = 5) to increase the osmotic gradient, and after furosemide injection (n = 5) to decrease the osmotic gradient. The signal intensity (SI) was quantified by region of interest placed on the cortex, the OM and the IM. RESULTS: In normally hydrated rabbits, a maximal decrease of the SI after USPIO was noted in the medulla, without significant difference between the OM and the IM on spin-echo sequences. The decrease of the SI was maximal in the IM on gradient-recalled echo sequences. In dehydrated animals, the maximum SI loss was in the OM. The furosemide-induced transient enhancement of the IM lasted a few minutes. CONCLUSIONS: The observed SI changes due to the distribution of the USPIO between OM and IM were not based on modifications of the osmotic gradient. The authors suggest that these SI changes were mostly dependent on the vascular density.

Animals↗
PubMed1994

Whole body quantitative autoradiographic study of the biodistribution of iobitridol in rats.

RATIONALE AND OBJECTIVES: Iobitridol is a new nonionic low-osmolality contrast medium. During preclinical development of this agent, it was of interest to verify that it behaves like other urographic and angiographic contrast agents (i.e., as a tracer of extracellular fluid). METHODS: Male and female rats were imaged using a quantitative autoradiographic method after intravenous administration of iodine-125-labeled product at a dose of 300 mg iodine/kg. RESULTS: The radioactivity was rapidly distributed with substantial uptake in the thyroid, kidneys, and skin after 10 minutes. The central nervous system showed no uptake. The radioactivity was rapidly eliminated (i.e., after 24 and 48 hours, only traces were found) except in the thyroid (because of free radiolabeled iodides present in small quantities in the administered solution). The considerable renal uptake after administration can be attributed to urinary excretion of the radioactivity (86% of the administered dose after 24 hours). Total elimination was achieved after 48 hours. No sex-related effects were observed. CONCLUSION: The absence of a target organ, the abundant and rapid urinary elimination, and the absence of transfer across the blood-brain barrier suggest that iobitridol is a tracer of extracellular fluid.

Animals↗