Biomedical subjects

P Bertrand

Publications and source records attributed to P Bertrand.

At least 55 records · Page 3Linked to original sources

PubMed2000

Differential oxidation of apolipoprotein E isoforms and interaction with phospholipids.

Accumulation of oxidized proteins has been demonstrated in the brain of patients suffering from Alzheimer's disease (AD). Among the proteins found in cerebral amyloid deposits, apolipoprotein (apo) E is a polymorphic protein which one specific isoform, apo E4, has been widely associated with AD. Apo E may be linked with AD by its isoform-specific interaction with lipids or other proteins in amyloid plaques. Using the myeloperoxidase oxidative system, we report that oxidation of the three recombinant apo E isoforms is differential (as estimated using immunoblot and high-performance liquid chromatography analysis), with apo E4 being more susceptible than apo E3, which in turn is much more susceptible than apo E2. In addition, susceptibility to thrombin proteolysis is reduced when apo E is oxidized, and oxidation of apo E decreases its incorporation into phospholipid discs by approximately 50%. Oxidation of apo E may contribute to inefficient lipid recycling in the brain, particularly regarding apo E4 and E3. Our results link and strengthen both the E4 allele linkage with AD and the role of protein oxidation in AD. The cerebral mechanisms underlying apo E oxidation and/or myeloperoxidase functions in vivo remain to be assessed.

Alleles↗

PubMed2000

Effects of pro-inflammatory cytokines on apolipoprotein E secretion by a human astrocytoma cell line (CCF-STTG1).

Apolipoprotein (apo) E has been implicated in Alzheimer's disease; however, little is known about the regulation of its secretion in astrocytes. To investigate the effects of pro-inflammatory cytokines such as interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on apoE secretion by CCF-STTG1 cells, a sensitive and specific double sandwich Enzyme-Linked ImmunoSorbent Assay (ELISA) was developed. Using a monoclonal anti-human apoE antibody as the capture antibody, this assay was carried out with commercially available reagents. The assay had a sensitivity of 0.013 ng per well, within-run and between-run variation coefficients of 6.0 and 8.6 per cent respectively. There was no cross-reactions between antibodies used and apoAI, apoAII, apoB, apoCI, apoCII and apoCIII. Low apoE concentrations were assessed using a serum-free HepG2 culture medium as secondary calibrator, containing 59 microg l(-1) of apoE. In serum-free medium, CCF-STTG1 cells secreted apoE, the accumulation of which in the cell medium increased linearly with time (27 microg per 48 h). After 48 h of incubation, apoE secretion was inhibited by TNF-alpha but not affected by IL-1beta and IFN-gamma. However, the effect of regulatory factors may depend upon culture conditions since in the presence of 10 per cent fetal calf serum, IFN-gamma significantly inhibited apoE secretion. Thus, apoE secretion by CCF-STTG1 cells is inhibited by specific pro-inflammatory cytokines. This new apoE ELISA presents the great advantage of using commercially available reagents which permit inter-laboratory comparability of results, involves relatively low cost and is adaptable for the measurement of low levels of apoE.

Apolipoproteins E↗

PubMed2000

Is there a rate-limiting step in the catalytic cycle of Ni-Fe hydrogenases?

The question of the existence of a rate-limiting step in the catalytic cycle of Ni-Fe hydrogenases was taken up by using the sets of data available in the case of two specific enzymes: the hydrogenase from Thiocapsa roseopercisina, in which isotope effects have been systematically investigated over a wide pH range, and the enzyme from Desulfovibrio fructosovorans, for which the activities and the redox properties have been studied in two different forms, the wild type and the P238C mutant. When these data are analyzed in the light of appropriate kinetic models, it is concluded that electron transfer and proton transfer are rate limiting in the H2 uptake and H2 evolution reactions, respectively. This proposal is consistent with the data available from other Ni-Fe enzymes.

Catalysis↗

PubMed2000

[Portal vein aneurysm].

In a 72-year-old female patient suffering from non specific and vague abdominal pain, an aneurysm of the portal vein was discovered. In the absence of complication, and because the risk of operation appeared too high, the decision was to abstain from surgery. With more than 3 years of regular follow-up, the patient was free of symptoms, and the portal vein aneurysm was unchanged. Sixty cases including this one are reviewed.

Abdominal Pain↗

PubMed2000

U373-MG response to interleukin-1beta-induced oxidative stress.

Oxidative stress has been involved in various neurological disorders and, in the central nervous system, astrocytes represent the cell type that contributes to neuroprotection via glutathione (GSH) metabolism, GSH-metabolizing enzymes like gamma-glutamyltransferase (GGT), and apoE secretion. In this study, using IL-1beta, a proinflammatory and prooxidant cytokine that is increased in numerous pathological situations, cells of astrocytoma cell line U373-MG were exposed to an oxidative stress, leading to c-Jun and c-Fos activation. IL-1beta decreased both GGT activity and intracellular GSH content and increased apoE secretion, initiating astroglial response to injury. We observed that antioxidants inhibit IL-1beta effects on c-Jun and c-Fos proteins, GGT activity and the GSH pool but not on apoE secretion. Our results allow us to conclude that neurological disorders associated with an IL-1beta-induced oxidative stress could be, at least experimentally, reversible in the presence of one antioxidant, N-acetylcysteine.

Acetylcysteine↗

PubMed2000

Limb salvage and popliteal aneurysms: advantages of preventive surgery.

OBJECTIVES: to assess the prognosis of atherosclerotic popliteal aneurysms (APAs), according to whether they were occluded or patent at the time of diagnosis. DESIGN: retrospective study. PATIENTS AND METHODS: fifty-two APAs were investigated in 35 patients. Nineteen were occluded (group I) and 33 patent (group II). In group I, 11 lower limbs had critical ischaemia, and eight had severe claudication. In group II, 27 were asymptomatic, 3 were painful, and 3 presented with symptomatic distal occlusion. In group I, treatment consisted of six bypasses, five thrombectomies, four thrombolyses, but for five APAs, no revascularisation was possible due to lack of runoff. In group II, 30/33 APAs were treated by graft replacement; the other three were not operated on due to the patients>> poor general condition. RESULTS: the 4-year survival rate was 72% in group I vs. 77% in group II, and the limb salvage rate was 72% in group I vs. 100% in group II, p<0.01. CONCLUSION: prophylactic treatment of asymptomatic popliteal aneurysms may avoid amputation caused by thrombosis and embolisation of runoff.

Adult↗

PubMed2000

Predictive factors for complications in children with laryngeal damage at extubation.

OBJECTIVES: To determine which factors contribute to early complications when intubated children show macroscopic lesions at extubation. STUDY DESIGN: Retrospective review of 96 consecutive medical records of children aged 1 day to 15 years. Patients were divided into three groups depending on the extent of the subsequent treatment required: medical, reintubation, and surgical. METHODS: Age, sex, clinical history, and macroscopic features of the lesions were collected and data were compared in each group. RESULTS: Underlying noninfectious respiratory diseases and young age were found to be risk factors for higher incidence of complications, but not prolonged or multiple intubations. Edema, especially in the glottic area, was a risk factor for surgical treatment. Multiple lesions were risk factors for reintubation. CONCLUSIONS: History of intubation, its cause, and lesions discovered at extubation can provide the basis for definition of an "at risk" profile for intubated children.

Adolescent↗

PubMed2000

Cavernous sinus invasion by pituitary adenoma: MR imaging.

PURPOSE: To define magnetic resonance (MR) imaging criteria for the diagnosis of cavernous sinus invasion by pituitary adenoma. MATERIALS AND METHODS: The MR images obtained in 106 patients (86 female, 20 male; age range, 16-71 years) were reviewed retrospectively by two physicians. The standard-of-reference criteria for invasion were the surgical findings. A chi(2) analysis was performed, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for nine groups of MR imaging signs were computed. RESULTS: Invasion of the cavernous sinus was certain (PPV, 100%) if the percentage of encasement of the internal carotid artery (ICA) by tumor was 67% or greater. It was highly probable if the carotid sulcus venous compartment was not depicted (PPV, 95%) or the line joining the lateral wall of the intracavernous and supracavernous ICAs was passed by the tumor (PPV, 85%). It was definitely not invaded (NPV, 100%) if the percentage of encasement of the intracavernous ICA was lower than 25% or the line joining the medial wall of the intracavernous and supracavernous ICAs was not passed by the tumor. CONCLUSION: The radiologic diagnosis of cavernous sinus invasion by pituitary adenoma remains difficult, but the above-mentioned criteria may be of assistance.

Adenoma↗

PubMed2000

Apolipoprotein E polymorphism and serum concentration in Alzheimer's disease in nine European centres: the ApoEurope study. ApoEurope group.

As part of the ApoEurope Project, apolipoprotein E (apo E) common polymorphism and serum concentration were determined in 489 Alzheimer's disease patients and 429 controls. Patients and controls were recruited through nine centres in eight European countries. Age, sex ratios and education levels of both case and control populations were similar, although discrete differences appeared between centres. The prevalence of the epsilon4 allele was higher in Alzheimer's disease than in controls (increased by 140%), while serum apo E concentration was lower by 11.2% (p<0.001). In addition, serum total cholesterol and triglyceride concentrations were lower in Alzheimer's disease (p<0.001), while that of apo Al was not affected. The decrease in serum apo E concentration was not accounted for by the epsilon4 allele, age or gender, suggesting that apo E concentration might represent an additional risk factor for Alzheimer's disease, complementary and independent of the epsilon4 allele. Further analysis will be aimed at determining whether the quantitative link between apo E concentration and Alzheimer's disease occurs through the effect of apo E genotype on lipid parameters or by other mechanisms.

Age Factors↗

PubMed2000

Apolipoprotein E polymorphisms and concentration in chronic diseases and drug responses.

Apolipoprotein (apo) E is an important circulating and tissue protein involved in cholesterol homeostasis and many other functions. The common polymorphism in the coding region of the gene, four polymorphisms in the promoter region, other additional single nucleotide polymorphisms, as well as several apo E variants have been identified. The common coding polymorphism strongly influences the lipid metabolism and the circulating concentration of apo E itself. This polymorphism is at the origin of the implication of apo E in cardiovascular and neurodegenerative diseases, but also of the relation of apo E with longevity. Probably due to its many metabolic and functional consequences, apo E polymorphism has been shown to influence the responses of patients to several drugs (fibrates, statins, hormone replacement therapy, anti-Alzheimer drugs) or environmental interventions (black tea, alcohol, diet). Apo E genotyping may be clinically helpful in defining the risk of patients and their responses to therapeutics. Finally, circulating apo E concentration appears to be altered in diseases and can be modulated by some of the drugs cited above. This parameter can thus also give interesting clinical information and could be a therapeutic target, providing it is validated. At the present time, we cannot exclude that apo E concentration may be the most prominent apo E parameter to be considered in health and disease, while apo E polymorphisms would represent only secondary parameters influencing apo E concentration.

Alleles↗

PubMed2000

Intravenous ribavirin and hyperammonemia in an immunocompromised patient infected with adenovirus.

Ribavirin is a synthetic guanosine analog with activity against DNA and RNA viruses. It was studied in human trials, and no marked adverse effect was reported beyond the potential for teratogenicity and reversible mild anemia. An 8-year-old girl received a multivisceral transplant and developed adenoviral pneumonia. She was treated with intravenous ribavirin and became hyperammonemic. Discontinuation of ribavirin led to a decrease in ammonia levels. This pattern was repeated when the drug was restarted and discontinued. We hypothesize that in a toxic environment the interaction of ribavirin with hepatocellular mitochondrial enzymes may lead to hyperammonemia.

Adenoviridae Infections↗

PubMed2000

[Diagnostic value of stress echocardiography under dobutamine and myocardial scintigraphy for restenosis at 6 months after angioplasty of the left anterior descending artery].

This study compared prospectively the diagnostic value of dobutamine echocardiography and exercise myocardial scintigraphy for restenosis at 6 months after angioplasty of the left anterior descending artery. Forty-one patients aged 58 +/- 10 years, admitted to hospital for myocardium infarction (N = 22) or unstable angina (N = 19), with single vessel disease, were treated by angioplasty of one lesion of the left anterior descending artery after initial evaluation of the left ventricular ejection fraction by echocardiography. At 6 months, left ventricular function was reassessed by echocardiography, dobutamine echocardiography and exercise myocardial scintigraphy (Thallium 201) performed without treatment. Coronary angiography was performed at the same time and showed 8 restenosis (19.5%). Overall, in this series, dobutamine echo and scintigraphy had respectively a sensitivity of 37.5% and 75%, and a specificity of 97% and 70% (p < 0.02). Nine patients had left ventricular dysfunction unchanged compared with the initial measurement without viability in the territory of the left anterior descending artery with low dose dobutamine (group 1); thirty-two patients had improved or normal left ventricular ejection fraction with myocardial viability (group 2). In group 1, no cases of restenosis were detected by dobutamine echocardiography but_of them had myocardial scintigraphic evidence of ischaemia. In group 2, the sensitivity of the two techniques was comparable but dobutamine echo was more specific than scintigraphy (96 versus 75%, p = 0.03). In conclusion, dobutamine echocardiography may be indicated in the diagnosis of restenosis of the left anterior descending artery and in cases of viability in its territory. In its absence, myocardial scintigraphy seems to be preferable.

Aged↗

PubMed2000

[Stage III and IV cancers of the oropharynx: results of a randomized study of Gortec comparing radiotherapy alone with concomitant chemotherapy].

The aim of the study was to test whether the addition of three cycles of chemotherapy during standard radiation therapy would improve disease-free survival in patients with stages III and IV oropharynx carcinoma. A total of 226 patients have been entered in a phase III multicentric randomized trial comparing radiotherapy alone (arm A) to radiotherapy with concomitant chemotherapy (arm B). Radiotherapy was identical in the two arms, delivering, with conventional fractionation, 70 Gy in 35 fractions. In arm B patients received simultaneously 3 cycles of a four-day regimen containing carboplatin (70 mg/m2/d) and 5 fluorouracil (600 mg/m2/d) continuous infusion. The two arms were equally balanced regarding to age, gender, stage, performance status, histology, and primary tumor site. Radiotherapy compliance was similar in the two arms regarding to total dose, treatment duration and treatment interruption. Grade 3 and 4 mucositis rate was significantly higher in arm B (67% versus 36%). Skin toxicity was not different. Haematologic toxicity was higher in arm B on neutrophil count and hemoglobin level. Three-year overall actuarial survival and disease-free survival rates were respectively 51% versus 31% and 42% versus 20% for patients treated with combined modality versus radiation alone (p = 0.022 and 0.043). Local and regional control rate has been improved in arm B (66% versus 42%). The statistically significant improvement in overall survival obtained support the use of concomitant chemotherapy as an adjunct to radiotherapy in the management of carcinoma of the oropharynx.

Combined Modality Therapy↗

PubMed2000

[Clinical experience in home care of children with tracheostomy].

BACKGROUND: Home care of tracheostomized children is considered a safe and low-cost alternative. AIM: To report the experience with tracheostomized children at the Pediatric Respiratory Unit of the Catholic University Hospital. PATIENTS AND METHODS: The records of 16 children (9 male) with tracheostomy (TQ) in home care between 1992 and 1998 were reviewed. RESULTS: The average age at the moment of TQ was 9 months (range 1-30 months) and the postoperative hospital management period was 5 months (range 1-11 months). The average age at discharge was 13 months (range 3 to 30 months). Surgical indication were upper airway obstruction (congenital or acquired subglottic stenosis in three, upper airway malformations in one, vocal cord palsy in one and tracheobronchomalacia in one) and chronic assisted ventilation (severe tracheobronchomalacia in four, pulmonary hypoplasia in two, myopathy in one, central nervous injury in one and bronchopulmonary dysplasia in one). Overall rate complications were 2 per 100 tracheostomy months during home care and 8 per 100 tracheostomy months during hospital care. No tracheostomy-related deaths were observed. A parenteral education program to teach about tracheostomy management and cardiopulmonary resuscitation was carried out. CONCLUSIONS: Tracheostomized children can be safely managed at home.

Child Health Services↗

PubMed2000

[Ventricular late potentials in myocardial infarction: comparison of thrombolysis, primary angioplasty, and conventional treatment].

OBJECTIVES: The aim of this study was to compare the prevalence of ventricular late potentials (VLP) during the acute phase of myocardial infarction (MI) depending on the treatment used. METHODS AND RESULTS: This retrospective study was carried out over the period January 1992 to December 1997, and involved 238 patients admitted for primary MI and treated less than six hours after the onset of symptoms by intravenous thrombolysis (rt-PA, n = 83) or primary angioplasty (ATCI, n = 82) and in those cases treated over six hours after the onset of symptoms by standard treatment (heparin, n = 73). Rt-PA perfusion was considered to be effective when the three following criteria were simultaneously present: i) pain sedation; ii) regression of the ST dysfunction > 50%; iii) creatine phosphokinase (CPK) peak before the 16th hour. Treatment success for angioplasty (ATCI+) was confirmed by a TIMI 3 (Thrombolysis in Myocardial Infarction) score for MI arterial perfusion, with residual stenosis of the MI artery of < 50%. Ventricular late potentials (VLP) were investigated between day six and 14, and considered to be present when two of the following criteria were met: total duration of filtered QRS, i.e., QRSd > 114 ms; signal amplitude in the 49 last ms of filtered QRS, i.e., RMS40 < 20 mV, duration of the terminal part of filtered QRS that was below 40 mV, i.e., LAS40 > 38 ms (40 Hz). VLP prevalence was as follows: 25% (rt-PA group), 345 (ATCI group), and 33% (standard treatment) respectively (P = NS). In the thrombolysis with reperfusion subgroup (n = 54/83, 65%), VLP incidence was 18.5% (n = 10/54) versus 35.5% (n = 27/76) in the subgroup ACTI+ (n = 76/82, 93%) (P = 0.03). CONCLUSIONS: The prevalence of VLP appears to be significantly decreased in the the case of thrombolysis with reperfusion compared to that observed in the ATCI+ group. One of the possible explanations for this abnormally high prevalence in the angioplasty group could be a dysfunction involving reocclusion after initially successful myocardial reperfusion therapy.

Action Potentials↗

PubMed1999

Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma.

BACKGROUND: We designed a randomized clinical trial to test whether the addition of three cycles of chemotherapy during standard radiation therapy would improve disease-free survival in patients with stages III and IV (i.e., advanced oropharynx carcinoma). METHODS: A total of 226 patients have been entered in a phase III multicenter, randomized trial comparing radiotherapy alone (arm A) with radiotherapy with concomitant chemotherapy (arm B). Radiotherapy was identical in the two arms, delivering, with conventional fractionation, 70 Gy in 35 fractions. In arm B, patients received during the period of radiotherapy three cycles of a 4-day regimen containing carboplatin (70 mg/m(2) per day) and 5-fluorouracil (600 mg/m(2) per day) by continuous infusion. The two arms were equally balanced with regard to age, sex, stage, performance status, histology, and primary tumor site. RESULTS: Radiotherapy compliance was similar in the two arms with respect to total dose, treatment duration, and treatment interruption. The rate of grades 3 and 4 mucositis was statistically significantly higher in arm B (71%; 95% confidence interval [CI] = 54%-85%) than in arm A (39%; 95% CI = 29%-56%). Skin toxicity was not different between the two arms. Hematologic toxicity was higher in arm B as measured by neutrophil count and hemoglobin level. Three-year overall actuarial survival and disease-free survival rates were, respectively, 51% (95% CI = 39%-68%) versus 31% (95% CI = 18%-49%) and 42% (95% CI = 30%-57%) versus 20% (95% CI = 10%-33%) for patients treated with combined modality versus radiation therapy alone (P =.02 and.04, respectively). The locoregional control rate was improved in arm B (66%; 95% CI = 51%-78%) versus arm A (42%; 95% CI = 31%-56%). CONCLUSION: The statistically significant improvement in overall survival that was obtained supports the use of concomitant chemotherapy as an adjunct to radiotherapy in the management of carcinoma of the oropharynx.

Adult↗

PubMed1999

Evidence of simple intramolecular rearrangement at polymer end groups in secondary ion mass spectrometry.

Polystyrenes with various end groups were analyzed by time-of-flight secondary ion mass spectrometry (TOF-SIMS). These end groups were obtained by termination of the active anionic group by sulfonate or chlorosilane derivatives. Characteristic end group fragments for each sulfonate derivative were observed. On the one hand, for PS capped by methyl sulfonate, or -(CH(2))(4)-O-SO(2)-CH(3), almost complete end group fragment is observed at m/z 95 and a [O-SO(2)-CH(3)](-) molecular structure. On the other hand, when PS is terminated by silyl methyl sulfonate, or -Si(CH(3))(2)-(CH(2))(3)-O-SO(2)-CH(3), the most characteristic fragment in the fingerprint secondary ion mass spectrum is located at m/z 153 with [Si(CH(3))(2)-O-SO(2)-CH(3)](+) and the complete end group peak, [Si(CH(3))(2)-(CH(2))(3)-O-SO(2)-CH(3)](+), at m/z 201, is absent. According to the molecular structure, characteristic end group secondary ions can be emitted as complete or rearranged fragments. Various silylalkyl alcohol or sulfonate functionalities are analyzed and fragmentation pathways are discussed. To our knowledge, this is the first time that such rearrangement at silyl functions has been observed and demonstrated in fingerprint secondary ion mass spectra. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗

PubMed1999

Human POMp75 is identified as the pro-oncoprotein TLS/FUS: both POMp75 and POMp100 DNA homologous pairing activities are associated to cell proliferation.

We have previously developed an assay to measure DNA homologous pairing activities in crude extracts: The POM blot. In mammalian nuclear extracts, we detected two major DNA homologous pairing activities: POMp100 and POMp75. Here, we present the purification and identification of POMp75 as the pro-oncoprotein TLS/FUS. Because of the pro-oncogene status of TLS/FUS, we studied in addition, the relationships between cell proliferation and POM activities. We show that transformation of human fibroblasts by SV40 large T antigen results in a strong increase of both POMpl00 and TLS/POMp75 activities. Although detectable levels of both POMp100 and TLS/POMp75 are observed in non-immortalized fibroblasts or lymphocytes, fibroblasts at mid confluence or lymphocytes stimulated by phytohaemaglutinin, show higher levels of POM activities. Moreover, induction of differentiation of mouse F9 line by retinoic acid leads to the inhibition of both POMp100 and TLS/POMp75 activities. Comparison of POM activity of TLS/FUS with the amount of TLS protein detected by Western blot, suggests that the POM activity could be regulated by post-translation modification. Taken together, these results indicate that POMp100 and TLS/POMp75 activities are present in normal cells but are connected to cell proliferation. Possible relationship between cell proliferation, response to DNA damage and DNA homologous pairing activity of the pro-oncoprotein TLS/FUS are discussed.

Amino Acid Sequence↗