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Biomedical subjects

A Laurent

Publications and source records attributed to A Laurent.

At least 73 records · Page 4Linked to original sources

Expression of myotonic dystrophy protein kinase gene during in vivo and in vitro mouse myogenesis.

Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disorder characterized by a great variability in its clinical manifestations. The mutational basis underlying DM consists of an unstable (CTG)n trinucleotide repeat in the 3' untranslated region of the myotonic dystrophy protein kinase gene (DMPK). Conflicting results on DMPK gene expression in congenitally affected infants (CDM) have been published. Moreover, the prominence of satellite cells seen in muscle of CDM infants supports the notion that the congenital form is associated with an arrest in muscle development and suggests a role for the DMPK gene during differentiation and maturation of muscle. In order to clarify these findings, a comparative study of DMPK and myogenic factor mRNA levels was performed in developing mouse muscle tissues and cultured muscle cells at different developmental stages. Results show that DMPK gene expression is upregulated at a late stage of muscular development. This upregulation does not seem to depend on a given muscle specific bHLH factor.

Animals↗

Myotonic dystrophy protein kinase gene expression in skeletal muscle from congenitally affected infants.

Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disorder characterized by marked variability of its clinical manifestations. The mutational basis of DM is an unstable (CTG)n trinucleotide repeat in the 3' untranslated region of the myotonic dystrophy protein kinase gene (DMPK). We used quantitative RT-PCR to determine DMPK mRNA levels in muscular biopsies from three congenitally affected (CDM) and two control infants. The CDM infants had increased DMPK mRNA levels, which were not correlated to increased expression of the mutant allele. This increase may be the consequence of a maturational muscular arrest, which may maintain an elevated level of DMPK mRNA until birth.

Case-Control Studies↗

Fibrinogen binding and platelet retention: relationship with the thrombogenicity of catheters.

One of the major problems in the use of catheters is their thrombogenicity, since the embolization of clots near the central nervous system or the coronary arteries can cause permanent damage. In this work we have compared the in vivo thrombogenicity of four different angiography catheters and their in vitro activation of fibrinogen binding and platelet retention. The thrombogenicity of catheters has been evaluated in angiographic conditions by kinetic evaluation of the reduction of blood flow rate through the catheters. The binding of adhesive proteins (fibrinogen and von Willebrand factor [vWF] was studied in vitro using a direct-ELISA technique after circulation of anticoagulated whole blood through sections of catheters. The retention of platelets was studied in vitro using 111Indium-labelled platelets. Fibrinogen binding and platelet retention both seem to be good predictors of catheter thrombogenicity, fibrinogen being the better of the two. The most thrombogenic material has the highest fibrinogen and platelet retention rate. This study also confirms the inefficiency of albumin precoating for the prevention of fibrinogen deposition. The determination of fibrinogen deposition by direct-ELISA technique and platelet retention rate is very useful for preclinical testing of catheters.

Biocompatible Materials↗

Histological features predictive of liver fibrosis in chronic hepatitis C infection.

AIMS: To assess which pathological features are associated with a sensitive marker of liver fibrogenesis and thus of the potential development of fibrosis in hepatitis C. METHODS: The degree of liver fibrogenesis was evaluated by quantification of type I collagen mRNA and transforming growth factor (TGF) beta 1 mRNA (a major profibrogenic cytokine) in liver biopsy specimens from 28 patients with chronic hepatitis C and five controls, using a quantitative reverse transcription polymerase chain reaction (RT-PCR) assay. Results of mRNA quantification were correlated with histological lesions scored semiquantitatively in the same specimens. RESULTS: Type I collagen mRNA was more strongly expressed in patients than in controls and correlated with the degree of fibrosis, but not with any of the necro-inflammatory lesions (portal inflammation, piecemeal necrosis, and lobular necrosis). TGF beta 1 mRNA concentration was higher in patients than in controls and correlated with histological grade of activity and lobular necrosis. This result was confirmed by in situ hybridisation experiments which showed that TGF beta 1 mRNA was mainly expressed in areas of focal lobular necrosis in chronic hepatitis C. CONCLUSION: This study shows that fibrosis, rather than necro-inflammatory lesions or activity scores, is associated with fibrogenesis and thus with potential aggravation of the fibrous deposit in chronic hepatitis C. Lobular necrosis is an important predictor of prognosis in chronic hepatitis C, as shown by its strong association with TGF beta 1 mRNA expression.

Adult↗

Treatment of brain arteriovenous malformations by embolization and radiosurgery.

Embolization was used to reduce the size of brain arteriovenous malformations (AVMs) prior to radiosurgical treatment in 125 patients who were poor surgical candidates or had refused surgery. Of these patients, 81% had suffered hemorrhage, and 22.4% had undergone treatment at another institution. According to the Spetzler-Martin scale, the AVMs were Grade II in 9.6%, Grade III in 31.2%, Grade IV in 30.4%, and Grades V to VI in 28.8% of the cases. Most embolizations were performed using cyanoacrylate delivered by flow-guided microcatheters. Radiosurgery was performed using a linear accelerator in 62 patients treated by the authors, and 34 patients were treated at other institutions using various methods. Embolization produced total occlusion in 11.2% of AVMs and reduced 76% of AVMs enough to allow radiosurgery. Radiosurgery produced total occlusion in 65% of the partially embolized AVMs (79% when the residual nidus was < 2 cm in diameter). Embolizations resulted in a mortality rate of 1.6% and a morbidity rate of 12.8%. No complications were associated with radiosurgery. The hemorrhage rate for partially embolized AVMs was 3% per year. No patient with a completely occluded AVM experienced rehemorrhage. Angiographic follow-up review of AVMs embolized with cyanoacrylate demonstrated a 11.8% revascularization rate, occurring within 1 year. It is concluded that after partial embolization with cyanoacrylate, the risk of hemorrhage from the residual nidus is comparable to the natural history of AVMs and that the residual nidus can be irradiated with results almost as good as for a native AVM of the same size.

Adolescent↗

Role of liver extracellular matrix in transcriptional and post-transcriptional regulation of apolipoprotein A-I by hepatocytes.

Apolipoprotein A-I, a protein produced mainly by hepatocytes, is of major importance in prevention of atherosclerosis. Its serum level varies according to the degree of liver fibrosis and the mechanism of this regulation is unknown. The aim of this study was to investigate the role of extracellular matrix in the regulation of apolipoprotein A-I by the liver. Primary mouse hepatocytes were cultured on different extracellular matrix components. The apolipoprotein A-I mRNA level was quantified in these different culture conditions by a sensitive quantitative RT-PCR procedure and compared according to the extracellular matrix component used as substrate. A significant decrease in the apolipoprotein A-I mRNA level was observed when cells were plated on fibronectin by comparison with cells cultured on all other components. Potential binding of apolipoprotein A-I to the different matrix components was also studied in vitro. We demonstrated that apolipoprotein A-I significantly bound to fibronectin in a concentration-dependent, saturable and specific manner. Thus, fibronectin, a major liver extracellular matrix component, can interact with apolipoprotein A-I both by downregulating its mRNA level in liver cells and by binding this molecule after its secretion in the extracellular space. Since fibronectin is the first matrix component to be produced in excess and deposited in liver fibrosis, it could be involved in the decrease in serum apolipoprotein A-I in alcoholic patients with liver fibrosis and cirrhosis.

Animals↗

Trisacryl gelatin microspheres for therapeutic embolization, I: development and in vitro evaluation.

PURPOSE: To develop a precisely calibrated, perfectly spherical, stainable, soft, and implantable but nonresorbable particulate embolization material. METHODS: Calibrated particles with a trisacryl gelatin polymer core and hydrophilic surface characteristics were obtained by reversed emulsion synthesis followed by application of a wet-sieving technique. Particles were suspended in saline, bottled, and sterilized. Quality control included analysis of particle diameters before and after sieving and of suspension sterility and apyrogenicity. Particles were subsequently tested to ascertain their compatibility with commercially available microcatheters. RESULTS: The resulting embolization material consisted of spherical, stainable microspheres of medical grade with diameters ranging from 130 microns to 1200 microns. Sieving the suspension produced particle groups of homogeneous size (accuracy, +/- 20-100 microns). At injection, the particles showed no tendency to build aggregates or to obstruct the microcatheters. CONCLUSION: Precisely calibrated and easy-to-use microspheres were obtained that satisfied the biomedical requirements for implantation as an embolization material.

Animals↗

Trisacryl gelatin microspheres for therapeutic embolization, II: preliminary clinical evaluation in tumors and arteriovenous malformations.

PURPOSE: To evaluate an embolic agent that is precisely calibrated, perfectly spherical in shape, and soft but nonresorbable for use in the embolization of vascular disease of the head, neck, and spine in humans. METHODS: We used supple, hydrophilic, and calibrated trisacryl gelatin microspheres 200, 400, 600, 800 and 1000 microns in diameter for superselective embolization in 105 patients (27 tumors, 14 facial arteriovenous malformations [AVMs], 37 spinal cord AVMs, 21 cerebral AVMs, and 6 miscellaneous diseases). We used particles in 200 to 600 microns in diameter for tumors and for facial AVMs, particles 400 to 600 microns in diameter for spinal cord AVMs, and particles over 1000 micros in diameter for cerebral AVMs. RESULTS: Delivery of the embolic material was easy: microspheres did not aggregate and catheters did not become obstructed by particles. It was possible to control the embolization through precise accounting of the amount of microspheres and matching of the particle size to the size of the pathologic vascular network. CONCLUSION: The microspheres are easy to use and allow precise control of the embolization procedure. Their physical characteristics make them a safe embolic agent.

Adolescent↗

Cloning of a new member of the insulin gene superfamily (INSL4) expressed in human placenta.

A new member of the insulin gene superfamily was identified by screening a subtracted cDNA library of first-trimester human placenta and, hence, was tentatively named early placenta insulin-like peptide (EPIL). In this paper, we report the cloning and sequencing of the EPIL cDNA and the EPIL gene (INSL4). Comparison of the deduced amino acid sequence of the early placenta insulin-like peptide revealed significant overall and structural homologies with members of the insulin-like hormone superfamily. Moreover, the organization of the early placenta insulin-like gene, which is composed of two exons and one intron, is similar to that of insulin and relaxin. By in situ hybridization, the INSL4 gene was assigned to band p24 of the short arm of chromosome 9. RT-PCR analysis of EPIL tissue distribution revealed that its transcripts are expressed in the placenta and uterus.

Amino Acid Sequence↗

Expression of human chorionic gonadotropin beta subunit genes in superficial and invasive bladder carcinomas.

Increased serum levels of human chorionic gonadotropin beta subunit (hCG beta) were described previously in patients with bladder cancer. To obtain insight into such production of hCG beta, the expression of hCG beta 7, 8, 5, and 3 genes in bladder carcinomas and normal urothelia was investigated by reverse transcription PCR. Surprisingly, hCG beta mRNAs were detected in both normal urothelial and carcinomatous cells. However, tumor progression was characterized by different patterns of transcription of the hCG beta genes; the beta 7 gene was the only gene transcribed in normal urothelia and Ta tumors included in this study, whereas in addition to beta 7, genes beta 5, 8, and 3 were transcribed in T1 to T4 tumors. Moreover, transcription levels of the latter three genes increased with the stage of the disease. These observations showed that dramatic modifications in the expression of hCG beta genes accompany progression of bladder carcinomas.

Base Sequence↗

[Reflections on international adoption].

In paediatric psychiatry, we often encounter French families who have chosen for international adoption of foreign children. From our clinical cases and a review of the literature, we have cited several circumstances which can lead to separation following adoption, either due to a rejection of the adopted by the adopting family or vica-versa: cases in which the adopted children are older or even young adolescents, simultaneous adoption of more than one child, adoption of psychologically disturbed children with a history of neglect or abuse by a previous guardian, cases in which the adopting parents are inadequately prepared due to international adoption procedures allowing the rapid accession of the adoption and cases with a poor understanding of the adoption legislation on the part of the biological parents or the child being adopted. These risque factors, relatively specific to international adoption, can in isolation or by a combination of factors lead to failure in the adoption. Subsequent separation after adoption often leads to institutionalization and further rejection.

Adoption↗

[Interventional neuroradiology. Drug treatment, monitoring and function tests].

Specialized monitoring as well as function tests and drug therapy play an ever growing role in neuroradiological procedures. The particular route of administration and the territories involved in neuroradiology require special precautions. Anaesthesia must enable the operators to monitor the central nervous system since the patients must remain totally immobilized for several hours. Catheterization is made safe by careful asepsia and antibiotic prophylaxis and by preventing embolic events, particularly in neuro-cervico-facial interventions where an anticoagulant protocol is important. Arterial spasms can be prevented or cured with calcium inhibitors. The safety of the procedure itself is guaranteed by various function tests including sensitivity to ischaemia using anaesthetic barbiturates, controlled clampings or the lidocaine test. Undesirable effects of both emboli (e.g. toxicity of cyanoacrylate glue) and embolization (e.g. subsequent venous thrombosis) can be prevented by adapted anti-inflammatory drugs. Herein, we describe the routine monitoring conditions, drugs prescribed and function tests performed at the Therapeutic Angiography Department of the Lariboisière Hospital, Paris.

Anesthesia, Local↗

Tubal sterilization by selective catheterization in an animal model.

RATIONAL AND OBJECTIVES: The feasibility of tubal occlusion by selective salpingography was tested in an animal model; three novel occluding materials also were tested for this application. METHODS: Unilateral selective salpingography was performed in three groups of six rabbits; fallopian tubes were embolized with ethanol (group 1), a hydrogel (group 2), or an occluding emulsion (Ethibloc, Laboratoire Princeps, Neuilly sur Seine, France) (group 3). Animals were killed 2 days or 30 days after the procedure, according to randomization; tubal patency and histologic modifications were evaluated. RESULTS: Selective tubal catheterization was obtained in 100% of the cases. In group 1, no satisfactory occlusion was obtained; in group 2, 65% of the tubes were occluded with little histologic damage; in group 3, 80% of the tubes were occluded, but significant inflammation and tissue necrosis were noted. CONCLUSION: Selective salpingography proved a suitable method for gaining access to the fallopian tube and allowed selective injection of occluding materials. More research is needed to determine a suitable occluding material, focusing on biocompatibility and on long-term efficacy.

Animals↗

Selective tubal sterilization in rabbits: experience with a hydrogel combined with a sclerosing agent.

PURPOSE: To test a method of nonsurgical sterilization. MATERIALS AND METHODS: A hydrogel that forms an in situ plug by phase inversion of a polymer solution was placed into fallopian tubes of eight rabbits by means of transvaginal rabbits by means of transvaginal fluoroscopic fallopian tube catheterization. The rabbits were bred, and the presence of embryos was confirmed with palpation and at autopsy. RESULTS: Seven of the eight rabbits became pregnant. Six of these rabbits contained embryos in the control uterus but not in the uterus on the side of the hydrogel injection. The seventh rabbit had embryos in both uteri, but the hydrogel had been expelled. All seven tubes that contained hydrogel showed evidence of acute and chronic salpingitis and a foreign-body reaction. The tube from which hydrogel had been expelled and the eight control tubes were not inflamed. CONCLUSION: Transcervical catheter methods of tubal occlusion and sterilization are promising, but a non-reactive material is needed.

Acrylonitrile↗

Acute and long-term effects of subthalamic nucleus stimulation in Parkinson's disease.

In animal models of Parkinson's disease (PD), it is postulated that the excessive output from the subthalamic nucleus (STN) plays a critical role. Selective lesions or high frequency electrical stimulation of the STN can alleviate parkinsonian symptoms in MPTP-treated monkeys. We decided to carry out STN stimulation in patients suffering from severe akinetic forms of PD. After approval of the institutional ethical committee, we operated on a parkinsonian patient aged 51, suffering for 8 years from a strongly disabling akinetorigid form of PD, complicated by an on-off effect (Hoehn and Yahr stage 5 in the worst-off motor phase). Stereotactic surgery was done on one side under local anesthesia. The theoretical target was chosen according to stereotactic atlases, based on ventriculographic landmarks such as anterior and posterior commissures (AC and PC). The final position of the chronic electrodes was optimized using electrophysiological recording and stimulation along with clinical assessment and surface EMG of agonist and antagonist muscles of the examined limbs. A spontaneous increase in neuronal activity was recorded in an area located 2-4 mm under the level of the intercommissural plane, 10 mm from the midline, at mid-distance between AC and PC. Within the same place, a 130-Hz stimulation induced acute and reversible akinesia alleviation mainly on the contralateral limbs, comparable to that obtained with dopaminergic drugs. No dyskinesia, such as hemiballism, was induced by introduction of electrodes or by stimulation. Then a long-term quadripolar DBS Medtronic electrode was inserted in this area. Studies of the effects of chronic stimulation were extensively performed to determine the best spatiotemporal and electrical stimulation variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Electric Stimulation Therapy↗