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Biomedical subjects

C Faure

Publications and source records attributed to C Faure.

At least 55 records · Page 3Linked to original sources

Quantification of alpha 1-adrenoceptor subtypes in human tissues by competitive RT-PCR analysis.

Alpha 1-Adrenoceptors are a heterogeneous subfamily of receptors comprising at least three pharmacologically- and structurally- distinct subtypes named alpha 1a-, alpha 1b- and alpha 1d-adrenoceptors. A competitive reverse transcription-polymerase chain reaction methodology using subtype selective competitor RNAs as reference internal standards was adopted to determine the absolute amounts of each of the three cloned to date alpha 1-adrenoceptor subtype encoding mRNAs in selected human tissues. Our data demonstrated that each of these alpha 1-adrenoceptor subtypes exhibits a distinctive tissular expression pattern.

Base Sequence

MRI of intramedullary cavernous haemangiomas.

We reviewed 11 cases of intramedullary cavernous haemangiomas (IMCH) studied by MRI, to assess its diagnostic value in these lesions. Follow-up MRI was obtained in five patients 7 days-2 years following the initial study. In one case a postoperative examination was obtained. The diagnosis was pathologically proven in ten cases, and supported in the last by a family and personal history of cavernous haemangiomas. A reticulate appearance with areas of mixed signal intensity in both T1- and T2-weighted images was the most common finding. Homogeneous high, low or intermediate signal intensity was each found in one case. Two small lesions gave low signal. A rim of low signal was less common than in cerebral cavernous haemangiomas. In one case, the brain showed more than 20 lesions with the MRI appearances of cavernous haemangiomas. In two of five patients, serial preoperative MRI showed progressive disappearance of high-signal areas on both T1- and T2-weighted images. To find a haemorrhagic intramedullary lesion on MRI is not rare. Although the appearances are not pathognomonic, an IMCH can be suggested. We suggest that the following characteristics may help: (1) a personal and/or family history of cavernous haemangiomas; (2) typical MRI appearances of mixed acute, subacute and chronic haemorrhage; (3) a tendency for signal intensity to decrease on follow-up; (4) normal spinal angiography; and (5) associated brain lesions.

Adult

[Treatment of gastroesophageal reflux].

Several therapeutic means are available for the treatment of pathological gastroesophageal reflux (GOR): positional therapy, thickening the feedings, dietetic modifications, antacids, mucosa-protecting agents, gastrokinetic drugs, antisecretory drugs, and surgery. In uncomplicated GOR, simple measures must be used first, associating positional therapy, thickening the feedings and a mucosa-protecting agent or an antacid; a gastrokinetic drug will be added if these measures are insufficient after 2 or 3 weeks. Peptic esophagitis requires a more drastic treatment, using antacid, prekinetic and antisecretory drugs; in addition, its cure should be assessed by esophagoscopy. When GOR is associated with life-threatening events, treatment may be completed with an atropine derivative in case of vagal hypertonia, and its efficiency must be verified by monitoring of oesophageal pH under treatment. In infants, the medical treatment should be maintained until complete cure, which usually occurs when walking is achieved. Surgery is indicated in complicated GOR (esophagitis, life-threatening event, pulmonary complication) with failure of the medical treatment, or as first-line treatment in the case of severe esophagitis in children with severe psychomotor impairment.

Child

Structure and expression of endogenous retroviral sequences in the permanent LMH chicken cell line.

From DNA mapping data, four endogenous proviral loci have been observed in the chicken permanent cell line LMH. The locus corresponding to endogenous virus (ev) ev1 is present in duplicate whereas the locus corresponding to ev3 is present in one copy. The other loci are probably ev6 and a solitary long terminal repeat. A RNA Northern blot analysis revealed both ev3 and ev6 transcripts but no ev1 transcript was detected. Using avian leukosis virus (ALV)-based vectors, transcomplementing assays were performed. They demonstrate the correct expression and maturation of endogenous env proteins and the absence of production of functional gag and pol components, indicating that these cells are not competent for viral production.

Animals

Modulation of the gamma-aminobutyric acid type A receptor by the antiepileptic drugs carbamazepine and phenytoin.

We report here that carbamazepine and phenytoin, two widely used antiepileptic drugs, potentiate gamma-aminobutyric acid (GABA)-induced Cl- currents in human embryonic kidney cells transiently expressing the alpha 1 beta 2 gamma 2 subtype of the GABAA receptor and in cultured rat cortical neurons. In cortical neuron recordings, the current induced by 1 microM GABA was enhanced by carbamazepine and phenytoin with EC50 values of 24.5 nM and 19.6 nM and maximal potentiations of 45.6% and 90%, respectively. The potentiation by these compounds was dependent upon the concentration of GABA, suggesting an allosteric modulation of the receptor, but was not antagonized by the benzodiazepine (omega) modulatory site antagonist flumazenil. Carbamazepine and phenytoin did not modify GABA-induced currents in human embryonic kidney cells transiently expressing binary alpha 1 beta 2 recombinant GABAA receptors. The alpha 1 beta 2 recombinant is known to possess functional barbiturate, steroid, and picrotoxin sites, indicating that these sites are not involved in the modulatory effects of carbamazepine and phenytoin. When tested in cells containing recombinant alpha 1 beta 2 gamma 2, alpha 3 beta 2 gamma 2, or alpha 5 beta 2 gamma 2 GABAA receptors, carbamazepine and phenytoin potentiated the GABA-induced current only in those cells expressing the alpha 1 beta 2 gamma 2 receptor subtype. This indicates that the nature of the alpha subunit isoform plays a critical role in determining the carbamazepine/phenytoin pharmacophore. Our results therefore illustrate the existence of one or more new allosteric regulatory sites for carbamazepine and phenytoin on the GABAA receptor. These sites could be implicated in the known anticonvulsant properties of these drugs and thus may offer new targets in the search for novel antiepileptic drugs.

Animals

[In vitro study of the properties of bioresorbable lactic acid polymer materials].

PURPOSE OF THE STUDY: The potential applications of biodegradable osteosynthesis implants present many advantages over conventional metallic devices. Polyesters of the poly and hydroxy-acid type were recognized early as serious candidates. These polymers have demonstrated a very good biocompatibility and are biodegradable in vivo. After biological and chemical testing poly L. lactic acid 98 (PLA 98) was selected as a candidate. We used a static and dynamic investigation in vitro to assess firstly the material properties of PLA 98 and secondly how its characteristics could be modified within a physiological environment. MATERIAL: Michel Vert and colleagues have shown that polymers of lactic acid have a similar time to resorption providing they contain 98 per cent of the "L" form of the polymer. In vitro studies were assessed on bars made in PLA 98. METHODS: In a first time in vitro studies in traction and flexion on bars allowed an assessment of mechanical properties of PLA 98. In a second time stresses were applied on bars using a physiological environment (Haemacel - 37 degrees C). In a third time we assessed the mechanical properties at the temperature of 37 degrees C with dynamic tests on bars in traction and flexion. RESULTS: The stress-strain curves on bars showed that the material is fragile. Sterilisation with ethylene-oxide did not affect the mechanical properties. When bars were placed in a thermostatically controlled (37 degrees C) physiological environment, the stress-strain curve showed that the material became ductile. With a temperature of 37 degrees C and with a frequency better than one hertz, the dynamic tests on bars showed that the material endurance is good up to 20,000 cycles. At 37 degrees C and at the end of one month, the Young modulus and the maximal strain before breaking lose 50 per cent of their initial value. DISCUSSION: All things considered and as the digital value showed, the PLA 98 appear to be ten times less strong than steel. In a physiological environment the mechanical properties improved due to hydratation of the polymer. The material become quickly ductile or malleable. This allowed transient loading without causing breakage. CONCLUSION: The mechanical properties of bioresorbable materials are very different from those of stainless steel and there is a learning curve in their utilisation. The PLA 98 polymer has demonstrated a very good biocompatibility and is totally biodegradable in vivo. With these results we think that PLA 98 can be used in clinical practice. Indications and clinical use should remain limited to bones regions with low applied stresses.

Biocompatible Materials

[Primary amyloidosis of bones. MRI aspects].

Primary systemic amyloidosis is a rare cause of vertebralcollapse. We describe a patient who presented multiplecollapsed vertebrae. Magnetic resonance imaging (MRI) demonstrated a diffuse bone marrow abnormality. A diffuse low signal throughout the vertebral bodies on T1 and T2 weighted spin-echo images were observed. A bone biopsy confirmed the suspected diagnosis of vertebral involvementby amyloid. MR imaging can be of interest to evaluate the bone spreading of a known amyloidosis and to help in the diagnosis of amyloidosis in the case of non traumatical vertebral fractures.

Amyloidosis

Expression of alpha 1-adrenoceptor subtypes in rat tissues: implications for alpha 1-adrenoceptor classification.

We report here the mapping of the mRNA distribution of three different alpha 1-adrenoceptor subtypes (alpha 1b, alpha 1c and alpha 1d) in various rat tissues. cDNA fragments covering the region from the fifth to seventh putative transmembrane spanning domains of these three alpha 1-adrenoceptor subtypes were generated from rat hippocampus using reverse transcription coupled to polymerase chain reaction (PCR). These three alpha 1-adrenoceptor cloned cDNA fragments were then used as subtype-selective cDNA probes in Northern blot analysis. Of the three specific DNA probes only the rat alpha 1b-adrenoceptor probe hybridized to mRNA of rat liver. The rat alpha 1c-adrenoceptor probe hybridized to a mRNA species of 3.7 kb in tissues that have been reported to contain the classical pharmacologically-defined alpha 1A-adrenoceptor such as hippocampus, vas deferens, lung and salivary gland. Also, a major mRNA transcript of 2.7 kb was detected in hippocampus, vas deferens and lung, using the rat alpha 1d-adrenoceptor probe. In addition, pharmacological characterization of [3H]prazosin binding to three stably transfected mammalian cell-lines expressing one of the three alpha 1-adrenoceptor subtypes cloned to date (namely, alpha 1b--of the hamster smooth muscle DDT1-MF2 cell-line, the bovine brain alpha 1c--and the rat cerebral cortical alpha 1d-adrenoceptors) was performed. Of the three cloned alpha 1-adrenoceptor subtypes that alpha 1c-adrenoceptor showed a similar pharmacological profile to that of the classical alpha 1A-adrenoceptor of rat salivary gland. Our data on the pharmacological profile and expression pattern of the alpha 1c-adrenoceptor indicate, in contrast to earlier claims (Schwinn et al., J. Biol. Chem. 265, 1990), that this subtype is in fact the classical pharmacologically-defined alpha 1A-adrenoceptor subtype.

Amino Acid Sequence

Pharmacokinetics of intravenous omeprazole in children.

This study was undertaken to define the pharmacokinetics of omeprazole in children and included 13 patients, heterogeneous in terms of age (0.3 to 19 years), underlying disease and biological constants, indication of omeprazole administration and associated therapy. The dose administered ranged from 36.9 to 139 mg.1.73 m-2. The pharmacokinetic parameters of omeprazole were: systemic clearance, 0.23 l.kg-1.h-1; volume of distribution, 0.45 l.kg-1; elimination half life 0.86 h; but were highly variable between individuals. Dosage, differences in hepatic and renal function and associated therapy may contribute to inter-individual variability. Within the range of doses administered, the pharmacokinetic parameters were similar to those reported in adults. The drug has been well tolerated in all children.

Adolescent

Identification of alpha 1-adrenoceptor subtypes present in the human prostate.

alpha 1-Adrenoceptors (ARs) play an important role in mediating human prostatic smooth muscle contraction. In the present study cDNA fragments covering different domains of 3 alpha 1-AR subtypes (alpha 1b, alpha 1c and alpha 1d) were generated from human prostate by reverse transcription coupled to the polymerase chain reaction (RT-PCR). The reconstituted partial sequence (349 amino acids) of the human prostatic alpha 1c-AR PCR products showed 94% identity at the amino acid level with that of the corresponding region of the cloned bovine brain alpha 1c-AR. Using human alpha 1-AR subtype selective cDNA probes in Northern blot analysis, the co-expression of mRNA transcripts corresponding to alpha 1b-, alpha 1c- and alpha 1d-AR subtypes was detected in 4 different regions (apex, base, periurethra and lateral lobe) of the human prostate. Competitive inhibition experiments of [3H]-prazosin binding to membrane preparations of human prostate revealed that the non-selective alpha 1-subtype antagonist, alfuzosin, produced a monophasic inhibition curve, whereas oxymetazoline produced a 2-component inhibition curve with pKi values of 8.54 and 5.46. The high-affinity alpha 1-AR component of the oxymetazoline inhibition curve was predominant (57%-66%) and showed an affinity for oxymetazoline comparable to that of the alpha 1c-AR subtype. As such our results illustrate the expression of different alpha 1-AR subtypes in human prostate and importantly that alpha 1c represents the predominant alpha 1-AR subtype present in this tissue.

Adenoma

Duodenal and esophageal manometry in total colonic aganglionosis.

Eleven children with total colonic aganglionosis were studied by esophageal and duodenal manometry. They were separated into two groups: group 1, with ileal involvement, and group 2, without ileal involvement. The results of the digestive motility studies were compared with the extent of ileal involvement of the aganglionosis and with the amount of artificial nutritional support required. All children showed abnormalities on both esophageal and duodenal manometry, suggesting complete digestive tract motility involvement. Recent advances in understanding Hirschsprung's disease and manometrial abnormalities suggest a primary motility disorder in children with total colonic aganglionosis.

Child, Preschool

Manometrical evaluation in visceral neuropathies in children.

Manometrical recordings were made at three levels of the digestive tract in 20 children with chronic intestinal pseudoobstruction (CIPO) defined clinically and histopathologically by deep biopsies showing a neuropathic process. Duodenal manometry showed severe abnormalities with hypomotility in all cases and absence of migrating motor complex in 13 of 20 cases. There was no relation between the histopathologic type and the motility pattern, but the most severe abnormalities were seen in the patients with extensive involvement of the digestive tract and the most severe clinical course. Esophageal manometry was abnormal in 18 of 19 patients, with altered peristalsis consisting of simultaneous, short-lasting, or low-amplitude waves. Rectoanal manometry showed the presence of the rectosphincteric inhibitory reflex in all patients. In conclusion, there is a high frequency of small bowel manometrical abnormalities in CIPO which seem to correlate with the extent of the pathological process and the prognosis of the disease. Esophageal manometry is useful for defining the extent of dysmotility and confirming the diagnosis of CIPO in some cases.

Anal Canal

[Contribution of genetic typing for the diagnosis of familial adenomatous polyposis in pediatrics].

BACKGROUND: The gene responsible for familial adenomatous polyposis, (APC), has been recently cloned and genetic map with several polymorphic markers has been established. POPULATION AND METHODS: Blood samples (20 ml) were taken from 34 subjects belonging to four families at risk for familial adenomatous polyposis. Nineteen of these 34, less than 20 years old, had one parent having polyposis or dead because of it. Polyposis was diagnosed, in ten of these 19 by endoscopy. Genomic DNA was extracted from peripheral leukocytes and Southern blot analyses were performed in each family, using RFLPs on both sides of the APC locus. RESULTS: DNA analysis identified normal and mutant haplotypes at the APC locus in each family. It was thus possible to follow the segregation of mutant alleles. These results were compared with the anamnestic and endoscopic data. Bearing in mind the risk of recombination when using extragenic markers, RFLPs allowed early diagnosis of APC in pre and/or asymptomatic patients. CONCLUSIONS: Genetic analysis can be used to diagnose APC in affected families, provided the risk of recombination is taken into account. Intragenic microsatellites markers will soon be available. These will provide more information on the APC gene, and hence direct molecular diagnosis of APC.

Adenomatous Polyposis Coli

Use of helper cells with two host ranges to generate high-titer retroviral vectors.

We have recently described Avian Leukosis Virus (ALV)-based packaging cell lines that can produce helper-free ALV-based retrovirus vectors with A, B, C, and E envelope host ranges. Here, we report that lacZ retroviral vectors of subgroup C or E can infect helper cells of subgroup A (Isolde) which are then able to produce high titers of lacZ recombinant viruses of subgroup A. Superinfection of helper cells by lacZ recombinant virus was performed by cocultivating packaging cells with two subgroup specificities (A and E), but this did not result in increased recombinant virus titers. This "ping-pong" process caused the emergence of replication-competent (RC) viruses which are shown to result from recombination between the viral sequences of the helper cell lines and the cis-acting sequences of the lacZ recombinant virus.

Avian Leukosis Virus