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Biomedical subjects

E Arnaud

Publications and source records attributed to E Arnaud.

At least 19 recordsLinked to original sources
PubMed2001

Brown fat UCP1 is specifically expressed in uterine longitudinal smooth muscle cells.

Until now, uncoupling protein 1 (UCP1) was considered as unique to brown adipocytes. It supports a highly regulated uncoupling of oxidative phosphorylation that is associated with diet as well as with non-shivering thermogenesis. Here we report that UCP1 is not specific to brown adipocytes and can be expressed in longitudinal smooth muscle layers. In the uterus, this conclusion was drawn from different convergent data. A specific antibody against mouse UCP1 revealed, in mitochondrial fractions, a protein with the same molecular weight as brown fat UCP1. Sensitive and specific reverse transcriptase-polymerase chain reaction detected a mRNA whose sequence was totally homologous to that of brown fat UCP1 mRNA. Antibody against UCP1 as well as a UCP1 antisense probe specifically stained uterine longitudinal smooth muscles. UCP1 was also expressed in longitudinal smooth muscle of digestive and male reproductive tracts but was never expressed in other types of smooth muscle, including those of arterial vessels. In uterine tract, UCP1 content was increased after cold exposure or beta-adrenergic agonist treatment. It was also up-regulated during the postovulatory period after sexual cycle synchronization. Its content transiently increased during gestation and decreased markedly after birth. These regulations strongly argue about a role for UCP1 in thermogenesis as well as in relaxation of longitudinal smooth muscle layers.

Adipose Tissue, Brown↗
PubMed2001

Nrh, a human homologue of Nr-13 associates with Bcl-Xs and is an inhibitor of apoptosis.

In search of human homologues of the anti-apoptotic protein Nr-13, we have characterized a human EST clone that potentially encodes a protein, which is the closest homologue of Nr-13 among the Bcl-2 family members, to date known, in humans. Phylogenetic analyses suggest Human nrh, Mouse diva/boo and Quail nr-13 to be orthologous genes. The nrh gene has the same overall organization as nr-13 and diva/boo with one single intron interrupting the ORF at the level of the Bcl-2-homology domain BH2. RT-PCR-based analysis of nrh expression indicated that this gene is preferentially expressed in the lungs, the liver and the kidneys. Interestingly, two in frame ATG codons can lead potentially to the synthesis of two products, one of them lacking 10 aminoacids at the N-terminal end. Sequence alignment with Nr-13 and Diva/Boo in addition to secondary structure prediction of the nrh transcript suggested that the shortest protein will be preferentially synthetized. Immunohistochemical analyses have revealed that Nrh is associated with mitochondria and the nuclear envelope. Moreover, Nrh preferentially associates with the apoptosis accelerator Bcl-Xs and behaves as an inhibitor of apoptosis both in yeast and vertebrate cells.

Amino Acid Sequence↗
PubMed2001

Altered Glut4 mRNA levels in specific brain areas of hyperglycemic-hyperinsulinemic rats.

The insulin sensitive glucose transporter Glut4 is expressed in neurons of the brain among which those of hypothalamic nuclei. It has been proposed that this transporter might be involved in the hypothalamic glucose-insulin sensing mechanism and thus in the nervous regulation of metabolism. In order to get further insights into its putative role, Glut4 expression was analyzed by quantitative competitive reverse transcription-polymerase chain reaction, in hypothalamic nuclei of hyperglycemic-hyperinsulinemic (HG-HI) rats, a model characterized by alteration of the autonomic nervous system activity. Glut4 mRNA content was decreased in the lateral hypothalamic area (33%) and arcuate nucleus (27%) but significantly only in the former. It was unchanged in other structures. These results are in favor of an alteration of Glut4 expression by short-term hyperglycemia and hyperinsulinemia that, in turn, could affect autonomic nervous system activity.

Animals↗
PubMed2001

Factors V leiden and II 20210A in patients with symptomatic pulmonary embolism and deep vein thrombosis.

PURPOSE: Factor V Leiden and factor II 20210A are inherited disorders of the clotting system that occur frequently in patients with deep vein thrombosis. We conducted this study to determine whether these factors are also common in patients with pulmonary embolism. SUBJECTS AND METHODS: We determined the prevalence of factor V Leiden and factor II 20210A in 773 consecutive patients with objectively documented symptomatic deep vein thrombosis or symptomatic pulmonary embolism, or with a combination of these disorders. RESULTS: Isolated symptomatic deep vein thrombosis occurred in 345 patients; isolated symptomatic pulmonary embolism occurred in 236; and both anomalies occurred in 192. Factor V Leiden was present in 21 (9%) of the patients with isolated symptomatic pulmonary embolism, in 30 (16%) with both manifestations, and in 63 (18%) with isolated symptomatic deep vein thrombosis (P = 0.007). Factor V Leiden was more common among patients with deep vein thrombosis (odds ratio [OR] = 2.1; 95% confidence interval [CI]: 1.2 to 3.7; P = 0.006) or both pulmonary embolism and deep vein thrombosis (OR = 1.8; 95% CI: 1.0 to 3.3; P = 0.07) than among patients with isolated pulmonary embolism. Factor V Leiden was less common in massive pulmonary embolism (5% [7 of 127]) than in submassive pulmonary embolism (13% [21 of 155], P = 0.03). We found no significant difference in the prevalence of factor II 20210A among the three groups. CONCLUSION: Factors V Leiden and II 20210A vary in prevalence among patients with pulmonary embolism and deep vein thrombosis, suggesting that the risk of pulmonary embolization may vary among patients who have different causes of venous thromboses.

Adult↗
PubMed2001

[Distraction osteogenesis with double internal devices combined with early frontal facial advancement for the correction of facial craniosynostosis. Report of clinical cases].

Frontofacial monobloc advancement is a surgical procedure which corrects at the same time both frontal and facial retrusions in faciocraniosynostosis. The high risk morbidity limited its use to major exorbitism or severe breathing impairment. We report the results of a preliminary experience in five children with a mean age of 3.8 years. All patients presented with a Crouzon or Pfeiffer syndrome. The procedure performed was a frontofacial monobloc osteotomy with peroperative mobilization. Two pairs of distractors (Martin-Medizin) were implanted. The upper pair of frontal distractors was located behind the supraorbital bar. The pair of temporo-zygomatic distractors (a modification of the MicroFrance prototypes) was implanted behind the zygomatic bone. In one patient a transfacial pin was connected to the anterior part the lower distractors, to avoid facial bipartition. Distraction was performed according to classical protocols with a 1 mm advancement per day, until sufficient advancement was obtained. The correction of exorbitism and facial retrusion was obtained in all cases. An open-bite was created by the advancement in two out of the five patients. Minor infection occurred in one patient. This combination of distractors with frontofacial advancement seemed to increase the efficacy and reduce the morbidity. This might lead to a one stage strategy for faciocraniosynostosis treatment, even if minor additive procedures will be necessary when children get older and that insufficient facial growth still reoccurs.

Child, Preschool↗
PubMed2001

The clinical relevance of the citrate effect on International Normalized Ratio determinations depends on the reagent and instrument combination used.

Multiple studies have shown that the two different citrate concentrations in common use as the anticoagulant in blood collection for haemostasis assays can affect the results obtained with the prothrombin time assay. It is clear from the literature that there is considerable variability in the results obtained using different instrument-reagents combinations, but the clinical relevance of these differences is unclear. Most of the studies have used an optical system for end-point detection. This study reports on the citrate sensitivity using mechanical end-point detection. Using two different reagents, one previously shown to be citrate sensitive on optical systems (Neoplastin CI plus) and a citrate-insensitive reagent (Neoplastin CI), we demonstrate that the effect of using different citrate concentrations (0.105 or 0.129 mol/l) has statistically significant but clinically irrelevant effects on the International Normalized Ratio using a mechanical instrument (STA)-reagent combination (mean percentage difference in results, 1.9 and 3.8% respectively). This demonstrates that the citrate effect is both instrument type and reagent dependent. Every reagent and instrument combination needs to be tested to see whether any citrate effect exists. In a secondary study, it was shown that the international reference rabbit thromboplastin (CRM 149(s)) was not citrate-concentration sensitive.

Animals↗
PubMed2000

Management of craniosynostoses.

Although it is currently thought that surgery is indicated mainly for cosmetic reasons in isolated craniosynostoses, the functional aspects of the treatment must not be underestimated. Prospective studies on intracranial pressure and mental evolution of these children have shown that there were functional consequences in a significant proportion of cases even of single suture fusion. The frequency of increased intracranial hypertension and the risk of mental impairment depend on the age of the child and the type of craniosynostosis. In nonsyndromic cases, the higher risks are observed in multisutural craniosynostoses (brachycephaly, oxycephaly). In syndromic cases, the risk of intracranial hypertension is higher in Crouzon syndrome, and Apert syndrome carries the higher risk of mental retardation. The study of a personal series of 2,137 craniosynostoses shows that the functional and the cosmetic results are better after early surgery, and that the operative risks are not higher in infants than in older children.

Craniosynostoses↗
PubMed2000

Advances in cranioplasty with osteoinductive biomaterials: summary of experimental studies and clinical prospects.

The surgical repair of large calvarial defects is still a challenge for craniofacial surgeons. Since the discovery of bone growth factors, numerous studies have confirmed the interest of osteoinduction for bone repair. We summarize the findings of experimental and clinical trials carried out with composite bone substitutes. The triple mixture of TGF-beta 1, fibrin glue, and natural coral has proven effective in repairing rabbit skull defects. The same preparation was also efficient for a cranioplasty in two of three patients, age being a limiting factor. The adjunction of bone morphogenetic protein to autologous bone marrow was shown to be a potentiating factor in a rat cranioplasty model, but the combination of fibrin glue and bone marrow on a natural coral carrier was unable to achieve bone repair in children aged 6 years. Although the series were limited, stability and asepsis were important factors in promoting bony ingrowth. Cranioplasties with osteogenic biomaterials may be good option, but the most adequate dose of growth factor should be determined.

Adolescent↗
PubMed2000

Postoperative exercise tolerance after aortic valve replacement by small-size prosthesis: functional consequence of small-size aortic prosthesis.

OBJECTIVES: The objective of this study was to determine whether a small-size valve prosthesis contributes to exercise intolerance, as assessed by VO2 measurement during an exhaustive cycle ergometer exercise. BACKGROUND: The determinants of exercise capacity after mechanical aortic replacement are not well known. The selection of small valve sizes has, however, been described as an independent predictor of exercise intolerance as assessed by exercise duration. Maximal oxygen uptake (VO2max) is a good index of exercise tolerance. METHODS: Fourteen patients were eligible, with a mean age of 62 +/- 6 years. Before surgery, the mean left ventricular ejection fraction (LVEF) was 73 +/- 8%. Two valve types with small diameter (19 to 21 mm) were used: Medtronic Hall and St Jude Medical. A healthy sedentary control group (n = 14) paired for age, weight and size was constituted. After one year of follow-up, cardiorespiratory tests were performed. In addition, the gradients through the prostheses were determined by continuous pulse Doppler at rest and immediately after the cardiorespiratory test. RESULTS The exercise tolerance was not significantly different between the control group and patient group: VO2 peak (21.7 vs. 20.4 ml/kg/min; p = 0.42), workloads (115 vs. 93 W; p = 0.13) and ventilatory parameters were similar. The mean and peak gradients at rest and during exercise were not correlated with VO2max. CONCLUSIONS: Valve replacement by small aortic prosthesis does not seem to be a factor of exercise intolerance as assessed by VO2max in patients without LVEF dysfunction before surgery.

Aged↗
PubMed2000

Protective effect of a thrombin receptor (protease-activated receptor 1) gene polymorphism toward venous thromboembolism.

The human protease-activated receptor 1 (PAR-1) is activated by thrombin at the surface of platelets and endothelial cells, 2 cells that are implicated in hemostasis and thrombosis. We studied the PAR-1 gene in a large case-control study from the Paris Thrombosis Study (PATHROS), and the possible implication of polymorphisms in venous thromboembolism was evaluated. Two polymorphisms were found in the 5' regulatory region. The first is a C to T transition that is 1426 nucleotides upstream from the translation start site (-1426 C/T), and the second is a 13-bp insertion repeating the preceding -506 5'-CGGCCGCGGGAAG-3' sequence (-506 I/D, where I indicates insertion and D indicates deletion), a putative cis-acting element of the Ets family. The third polymorphism is an A to T transversion in the intervening sequence (IVS) that is 14 nucleotides upstream from the exon 2 start site (IVS-14 A/T). The distribution of the 3 polymorphisms was otherwise similar in the 250 cases and the 1214 controls. A noteworthy sex heterogeneity led us to analyze men and women separately with regard to the -506 I/D polymorphism. We found that allele I was less frequent in male cases than in male controls (0.154 versus 0.247, P<0.01), with an odds ratio at 0.52 (95% CI 0. 32 to 0.82, P<0.01). Furthermore, a reduction of prothrombin fragment 1+2 levels was observed in homozygous carriers of allele -506 I (P=0.04). Altogether, these data suggested a protective effect in men of -506 I/D polymorphism for venous thromboembolism.

Adult↗
PubMed2000

Polymorphisms in the 5' regulatory region of the tissue factor gene and the risk of myocardial infarction and venous thromboembolism: the ECTIM and PATHROS studies. Etude Cas-Témoins de l'Infarctus du Myocarde. Paris Thrombosis case-control Study.

Tissue factor (TF) is a transmembrane protein considered to be responsible for the initiation of coagulation. TF gene expression may be induced in monocytes and endothelial cells and is present in atherosclerotic plaque to initiate thrombus formation. To investigate whether individual differences in TF gene expression could predispose subjects to thrombosis, we sequenced the 5' domain of the gene up to nucleotide 2732 and found 6 different polymorphisms: 4 of them were completely concordant and defined 2 haplotypes with similar frequencies, designated as 1208 D and 1208 I. Genotyping of patients with myocardial infarction in a case-control study involving 2354 subjects showed no association between the polymorphisms and nonfatal coronary thrombosis. In another study involving 255 patients with venous thromboembolism and 1204 controls, allele D was less common in the cases (P=0.022). The odds ratio associated with the presence of at least 1 D allele was 0.72 (P=0. 031). Comparison of subgroups of control subjects who were homozygous for the D or I allele demonstrated a lower plasma TF concentration in DD homozygotes. These results indicate that the TF gene promoter exists in 2 major forms differing at 4 sites. The 1208 D haplotype is not associated with coronary thrombosis but is associated with reduced plasma TF levels and a lower risk of venous thrombosis.

5' Untranslated Regions↗
PubMed2000

Demonstration of an association between Chlamydia pneumoniae infection and venous thromboembolic disease.

Chlamydia pneumoniae infection has been linked to atherosclerosis, but a possible relationship with venous thromboembolism (VTE) has not been sought. We determined circulating anti-C. pneumoniae antibody levels in patients with VTE. We studied 176 case patients with objectively diagnosed VTE and 197 age- and sex-matched healthy controls, in a retrospective study. Acquired risk factors for VTE and frequent predisposing genetic factors (factor V Arg 506 Gln and factor II G 20210 A mutations) were assessed in all the subjects. Anti-C. pneumoniae IgG antibodies were determined by microimmunofluorescence. All positive plasma samples (titer > or =128) were precisely quantified and tested for the presence of specific IgM antibodies. Fifty-four percent of the cases and 15.9% of the controls had specific IgG titers of at least 256 (p <0.0001). The crude odds ratio for VTE was 6.2 (95% CI, 3.8-10.1), and rose to 7.7 (4.5-13.2) after excluding subjects carrying the factor V Arg 506 Gln or factor II G 20210 A mutations. The odds ratio for VTE increased with the IgG titer: the adjusted odds ratios were 2.1 (95% CI, 1.1-4.1), 5.3 (2.7-10.6) and 33.0 (4.4-248.4) for titers of 256, 512 and 1024, respectively. Only one subject (a case patient) with a high IgG titer (> or =256) also had specific IgM. High titers of anti-C. pneumoniae IgG antibodies are frequently found in patients with previous venous thromboembolism. This association deserves to be confirmed in other case-control studies and prospective studies.

Adult↗
PubMed2000

[Biomaterials and osseous regeneration].

The autologous bone graft is commonly used for the repair of bony defects, but its resorption is unpredictable, and there is an inherent morbidity of the donor site. There is a wide range of biomaterials that could be used as bone substitutes, depending on their bioactivity. Among bioactive materials, bioglasses present a linkage between their reactive surface and the adjacent bone although they cannot be colonized by bony ingrowth, moreover their fragility and resorption as particles limit their use. The osteoconductive biomaterials are either represented by the synthetized ceramics, such as hydroxyapatite (HA) or tricalcium phosphate (TCP), or either natural coral and the derived biomaterials of bony matrix. Coral exoskeleton or TCP are highly resorbable, but pure HA is only slightly. Bony ingrowth in osteoconductive materials is limited to the periphery of the implant which does not make it suitable for the repair of large defects. Research is focused on the adjunction of a biologically active substance to the osteoconductive matrix in order to enhance bony ingrowth. Osteoinductive materials such as bone growth factors in combination with a carrier can promote bone healing, especially when bone morphogenetic protein (BMP) is used. Nevertheless, even if their efficacy is demonstrated, their inocuity has not been totally confirmed. Furthermore, the dose used are far superior than in the physiological pathways. Hybrid biomaterials combine an osteoconductive carrier with bone marrow cells. Bone cell cultures could amplify to almost any extent the number of osteogenic cells for such a biomaterial. Bone substitutes will certainly be used in the future to repair bony defects.

Biocompatible Materials↗
PubMed2000

[Musculoskeletal tissue engineering with resorbable polymers].

Musculoskeletal tissues can present congenital or acquired defects as a result of disease, accidental trauma or iatrogenous causes. This loss of bony substance is traditionally treated by the replacement of bony tissue (grafts or flaps), or by synthetic materials. Each of these methods of treatment, however, entails its specific disadvantages, limitations and complications. The recent approach for treatment of musculoskeletal defects has been the development of the growing of neotissues derived from autogenous cells, and artificial biodegradable matrixes. This method assumed the name "tissue engineering" in the late 1980s. Tissue Engineering, or TE, has employed advances made in the area of cellular culture, intercellular matrix biology, and also, in the area of biomaterial science. TE is an multi-disciplinary approach. Musculoskeletal TE, although in its preliminary stages, should allow access to treatments of the future.

Biocompatible Materials↗
PubMed1999

Intravitreous transplantation of encapsulated fibroblasts secreting the human fibroblast growth factor 2 delays photoreceptor cell degeneration in Royal College of Surgeons rats.

We developed an experimental approach with genetically engineered and encapsulated mouse NIH 3T3 fibroblasts to delay the progressive degeneration of photoreceptor cells in dark-eyed Royal College of Surgeons rats. These xenogeneic fibroblasts can survive in 1. 5-mm-long microcapsules made of the biocompatible polymer AN69 for at least 90 days under in vitro and in vivo conditions because of their stable transfection with the gene for the 18-kDa form of the human basic fibroblast growth factor (hFGF-2). Furthermore, when transferred surgically into the vitreous cavity of 21-day-old Royal College of Surgeons rats, the microencapsulated hFGF-2-secreting fibroblasts provoked a local delay of photoreceptor cell degeneration, as seen at 45 days and 90 days after transplantation. This effect was limited to 2.08 mm2 (45 days) and 0.95 mm2 (90 days) of the retinal surface. In both untreated eyes and control globes with encapsulated hFGF-2-deficient fibroblasts, the rescued area (of at most 0.08 mm2) was significantly smaller at both time points. Although, in a few ocular globes, surgical trauma induced a reorganization of the retinal cytoarchitecture, neither microcapsule rejection nor hFGF-2-mediated tumor formation were detected in any treated eyes. These findings indicate that encapsulated fibroblasts secreting hFGF-2 or perhaps other agents can be applied as potential therapeutic tools to treat retinal dystrophies.

3T3 Cells↗
PubMed1999

Midface surgery from Tessier to distraction.

The wall separating the face and the cranium was broken by Paul Tessier and Gérard Guiot in the 1960s, making it possible to perform a combined operation around the orbits and forehead, and opening up close cooperation between plastic surgeons and neurosurgeons, especially for treatment of the major malformations such as hypertelorism of major facial retrusions. The principles of mobilization of the orbits to correct teleorbitism or orbital dystopia are recalled with reference to the different variations and with clinical examples. Facial advancement to correct the retrusions created by faciocraniosynostosis is explained with the many possible variants, combined with a intracranial approach or not, with or without a bipartition. The indications are discussed as is the risk linked to combined advancement of face and forehead. The progressive bone elongation principle introduced by Ilizarov for the limbs has been applied to the face at the mandibular level by McCarthy, with great success. The distraction of bone structures is now also applied at the level of the midface and makes it possible to overcome the retraction of soft tissues and lower the risk of relapse of facial retrusion. Many technical problems have still to be solved, but the results are already very promising. Many other applications of the distraction principle will be developed for the midface level, with other technical improvements such as the use of absorbable mini-plates and screws.

Craniofacial Abnormalities↗
PubMed1999

Osteogenesis with coral is increased by BMP and BMC in a rat cranioplasty.

Autologous bone marrow cells (BMC), bone morphogenetic protein (BMP) and natural coral exoskeleton (CC) were used to enhance the repair of large skull bone defects in a craniotomy model. Nine millimeter calvarial defects were created in adult rats and were either left empty (control defects) or implanted with CC alone, CC-BMC, CC-BMP, or CC-BMC-BMP. After 1 or 2 months, osteogenesis was insufficient to allow union when defects were left empty or filled with CC. Addition of BMC alone to CC had no positive influence on osteogenesis at any time and increased CC resorption at 2 months (0.1 +/- 0.1 mm2 versus 0.5 +/- 0.3 mm2). In contrast addition of BM P or BM P/BMC to CC led to a significant increase in osteogenesis and allowed bone union after 1 month. At 2 months, the combination of CC-BM P-BMC was the most potent activator of osteogenesis. Filling a defect with CC-BMP-BMC resulted in significantly increased bone surface area (11 +/- 2.7 mm2) in comparison to filling a defect with CC-BMP (7.0 +/- 1.4 mm2), CC-BMC (3.5 +/- 1.1 mm2) or CC (4.5 +/- 0.4 mm2). CC resorption was significantly decreased in the presence of BMP with or without BMC at both times. These data are in accordance with the presence of progenitor cells in bone marrow that are inducible by BMP to the osteogenic pathway in a cranial site. The increase in material resorption in defects filled with CC-BMC could suggest that cells from the granulocyte-macrophage lineage survived the grafting procedure and were still active after 2 months.

Analysis of Variance↗