Biomedical subjects

S Gaillard

Publications and source records attributed to S Gaillard.

At least 37 records · Page 2Linked to original sources

PubMed2001

Overexpression of simian virus 40 small-T antigen blocks centrosome function and mitotic progression in human fibroblasts.

Recombinant adenoviruses that express high levels of the simian virus 40 (SV40) small-t (ST) antigen have been used to study the requirement for ST to drive cell cycle proliferation of confluent human diploid fibroblasts. This occurs when either large-T (LT) antigen or serum is added to provide a second signal. While cells readily completed S phase in these experiments, they were found to accumulate with 4N DNA content. Cellular and nuclear morphology, as well as the biochemical status of cyclin B complexes, showed that these cells entered mitosis but were blocked prior to mitotic metaphase. The defect appears to reflect an inability of cells overexpressing ST to form organized centrosomes that duplicate and separate normally during the cell cycle and, therefore, the absence of a mitotic spindle. The ability of ST to bind protein phosphatase 2A was required for this pattern, suggesting that altered phosphorylation of key centrosomal components may occur when ST is overexpressed. Although the possible significance of ST effects on the centrosome cycle is not fully understood, these findings suggest that ST could influence chromosomal instability patterns that are a hallmark of SV40-transformed cells and LT expression.

Adenoviridae↗

PubMed2001

[Value of 18FDG-CDET in the evaluation of operable bronchial cancer].

The purpose of this study was to investigate the utility of 18fluorodeoxyglucose (FDG) coincidence detection position emission tomography (CDET) in the evaluation of metastatic mediastinal lymph nodes in patients with potentially operable non-small-cell lung cancer (NSCLC). A prospective study was performed in thirty patients with newly suspected NSCLC. Thoracic computed tomography (CT), FDG CDET, and invasive surgical staging were performed in patients. Blinded prospective interpretation was performed for each test and compared to pathological staging obtained by mediastinoscopy and/or by thoracotomy. Patients were followed for six months to detect occult metastases. The sensitivity and specificity of CDET for the detection of mediaStinal lymph nodes were 75% and 94.4% respectively. The corresponding value for CT were 50% and 80.9%. Three patients with N1 disease were classified as N0 by CDET. With regard to definitive surgical node staging, CDET could identify nodal disease in 26 patients and CT only in 18 patients (n = 30). FDG full-ring positron emission tomography (PET) is the most accurate non-invasive method for the detection and staging of lung cancer. In addition, FDG CDET shows high accuracy for the detectability of pulmonary lesions with a diameter at least 2 cm and the evaluation of lymph node in NSCLC.

Carcinoma, Non-Small-Cell Lung↗

PubMed2000

Zinedin, SG2NA, and striatin are calmodulin-binding, WD repeat proteins principally expressed in the brain.

Striatin is an intracellular protein characterized by four protein-protein interaction domains, a caveolin-binding motif, a coiled-coil structure, a calmodulin-binding domain, and a WD repeat domain, suggesting that it is a signaling or a scaffold protein. Down-regulation of striatin, which is expressed in a few subsets of neurons, impairs the growth of dendrites as well as rat locomotor activity (Bartoli, M., Ternaux, J. P., Forni, C., Portalier, P., Salin, P., Amalric, M., and Monneron, A. (1999) J. Neurobiol. 40, 234-243). Zinedin, a "novel" protein described here, and SG2NA share with striatin identical protein-protein interaction domains and the same overall domain structure. A phylogenetic analysis supports the hypothesis that they constitute a multigenic family deriving from an ancestral gene. DNA probes and antibodies raised against specific domains of each protein showed that zinedin is mainly expressed in the central nervous system, whereas SG2NA, of more widespread occurrence, is mainly expressed in the brain and muscle. All three proteins are both cytosolic and membrane-bound. All three bind calmodulin in the presence of Ca(2+). In rat brain, SG2NA and striatin are generally not found in the same neurons. Both localize to the soma and dendrites, suggesting that they share a similar type of addressing and closely related functions.

Amino Acid Sequence↗

PubMed2000

Intracellular pH changes during oligodendrocyte differentiation in primary culture.

We have studied the characteristics of pH(i) regulation at different stages of rat oligodendrocyte differentiation in primary culture. pH(i) was measured at 37 degrees C using the pH-sensitive fluorescent probe BCECF. In immature oligodendrocyte progenitor (OLP), three distinct ionic mechanisms were involved in pH(i) regulation: (i) a sodium-independent Cl(-)/HCO(-)(3) exchanger, (ii) a Na(+)/H(+) exchanger and (iii) a voltage-dependent Na(+)-HCO(-)(3) cotransporter. The two latter mechanisms were also detected in more differentiated pro-oligodendrocytes and in mature oligodendrocytes whereas the Cl(-)/HCO(-)(3) exchanger was not active in these two later stages of differentiation. The presence of this Cl(-)/HCO(-)(3) exchanger (that acts as a chronic acidifying mechanism) only in immature OLP maintains in these cells a steady-state pH(i) value significantly lower than values measured in more differentiated cells. The possible involvement of this pH(i) change in triggering cell differentiation is discussed.

Animals↗

PubMed1999

Microsatellite instability in European hepatocellular carcinoma.

Genetic instability has been detected in many types of cancers but poorly investigated in hepatocellular carcinoma (HCC). We have studied the incidence of microsatellite instability (MI) at eight highly polymorphic microsatellite markers and the poly A tract BAT26 and tested for mutations at two sites of repetitive sequence (poly-A nucleotides 709-718 and GT repeat-nucleotides 1931-1936) in the Transforming Growth Factor beta (TGFbeta) type II receptor (RII) gene, in a group of 46 European HCCs and the surrounding nontumour tissue. This analysis showed that 63% of HCCs exhibit MI in at least one chromosome locus and 41% in two or more loci. No mutations of the TGFbetaRII gene were found in the MI positive tumours. No correlation was found with clinicopathological characteristics of the tumours such as cirrhosis, etiology, number of nodules, Edmondson's grade and vascular invasion. However, in patients who had a rearranged D16S402 microsatellite in their tumour, the recurrent disease and the number of nodules were significantly higher than in the others (P<0.005 and P<0.02, respectively). We propose to consider D16S402 rearrangement in HCC as a prognostic factor to identify patients presenting a higher risk of recurrence.

Adolescent↗

PubMed1999

Postoperative aneurysm remnants: endovascular treatment as an alternative to further surgery.

Because further surgery on postoperative aneurysm remnants can be difficult and lead to significant morbidity and mortality, endovascular treatment, using controlled detachable coils, was performed in three patients with such remnants. The endovascular approach was technically more difficult in these cases than in previously untreated patients. In one case, the "remodelling" technique was necessary. Given the successful outcome in these patients, endovascular treatment can be proposed as an alternative to another operation, when further surgery appears too risky or is refused by the patient.

Adult↗

PubMed1999

Giant-cell tumour involving the cranial vault: imaging and treatment.

A giant-cell tumour involving the cranial vault was diagnosed in a 37-year-old man who presented with a large swelling at the vertex. The role of imaging in the diagnosis and treatment of this tumour is described. On CT and MRI the appearances were nonspecific and the diagnosis was established by histological examination after removal of the tumour. A preoperative angiogram showed a tumour blush and before surgery, embolisation was performed via the percutaneous and transarterial routes.

Adult↗

PubMed1999

Induction of immune tolerance with recombinant factor VIII in haemophilia A patients with inhibitors.

We report on 11 patients (nine unrelated and a brother pair) with severe haemophilia A and factor VIII (FVIII) inhibitor, in whom immune tolerance (IIT) was induced with recombinant FVIII (r-FVIII). Their age ranged from 11 months to 47 years. The number of exposure days (ED) at inhibitor detection varied from 11 to 130. Nine of the 11 patients were high responders ¿>10 Bethesda units (BU) with peak inhibitor levels ranging from 10 to 566 BU. The other two were low responders with peak levels between 0.7 and 2 BU. Before inhibitor detection, the patients had been receiving products of various purities. The IIT regimens were very heterogeneous, and the treatment schedule varied from a short period with 50 IU kg-1 every 2 days, followed by 100 IU kg-1 every 2 days and then 220 IU kg-1 daily. The outcome was considered successful when the inhibitor level fell to 0.6 BU or lower after IIT treatment. The outcome overall was successful in nine out of 11 patients (81.8%), with the nine successful cases comprising seven of the nine high responders (77.8%) and the two low responders. Definite failure of IIT was observed in one high responder after two different IIT regimens. A second high responder is still on IIT treatment. All patients in whom IIT was successful are currently receiving r-FVIII on demand or prophylactically at various dosages. Despite the variability of the patient characteristics and the IIT schedules, this study demonstrates that r-FVIII represents an effective alternative for the eradication of inhibitors through IIT.

Adolescent↗

PubMed1999

The simian virus 40 small-t and large-T antigens jointly regulate cell cycle reentry in human fibroblasts.

Focus formation in human diploid fibroblasts (HDF cells) is known to require both the simian virus 40 (SV40) large-T and small-t antigens. Similarly, both SV40 proteins were required to stimulate confluent, density-arrested HDF cells to reenter the cell cycle. This study used defective recombinant adenoviruses to examine the roles of the individual SV40 proteins in altering specific steps in the cell cycle. Small-t antigen and, to a lesser extent, large-T antigen increased the level of the S phase cyclin cyclin A but without increasing the activity of associated cyclin kinases unless the two SV40 proteins were coexpressed. The absence of kinase activity reflected the presence in density-arrested cells of high levels of the cyclin-dependent kinase inhibitors p21(WAF1) and p27(KIP1). We report here that expression of SV40 large-T antigen reduced levels of p21(WAF1), while expression of small-t antigen was required to decrease p27(KIP1). The separate effects of large-T and small-t antigens on these two inhibitors may explain the joint requirement for the two proteins to drive cell cycle reentry of HDF cells and ultimately transform these cells.

Antigens, Viral, Tumor↗

PubMed1999

[Assessment of sub-clinical thyroid disfunction in aged hospitalized patients in Limousin].

UNLABELLED: The aims of the study were to assess the prevalence of sub-clinical thyroid dysfunction in older patients and to analyze morphological and immunological thyroid abnormalities. SUBJECTS AND METHODS: The effect of aging on thyroid function morphology and immunology was studied in 102 french patients (70 women and 32 men) with a mean age of 81.7 +/- 7.3 years (65-101 years). All patients were hospitalized with different pathological conditions but without any thyroid disease. Patients with treatment or iodine substance which could modify thyroid function were excluded. Serum Free thyroxine (FT4) and TSH levels were detected by RIA. Morphological thyroid study was performed by clinical evaluation and ultrasonography. Two sub-groups of patients were distinguished according to immunological detection tests: In group A (n = 64) immunological parameter was performed by antithyroid microsomal antibodies and in group B (N = 38) by thyroid peroxidase antibodies. RESULTS: We found 4 hypothyroidisms (3.9%), 3 hyperthyroidisms (3%) and 4 marginal isolated high FT4 levels. Elevated levels of FT4 was observed in 3 patients and 1 care of low T4 was described. All patients with abnormal hormonal levels were female. Other patient had normal thyroid function: mean level FT4 was 11.2 +/- 2.2 pg/ml (N: 7-17) and mean level TSH was 1.6 +/- 0.8 mU/l (N: 0.2-4). These values are comparable to those observed in adult populations. Incidence of thyroid autoimmunity was very low (3.9%) in this series compared with previous data. From the morphological analysis, we found 32 morphological abnormalities (31.4%), without strong relation with thyroid dysfunction. Nodule prevalence was near 15% and goiter near 10%.

Aged↗

PubMed1998

Role of sodium in contrast medium-induced polymorphic ventricular tachycardia: results in a rabbit model of lengthened QT interval.

RATIONALE AND OBJECTIVES: The authors (a) compared the proarrhythmic effects of ioxaglate (152 mmol/L sodium) and iohexol (no sodium) in a rabbit model and (b) assessed the effect of adding 150 mmol/L sodium to isotonic iohexol. MATERIALS AND METHODS: Either ioxaglate (320 mg of iodine per milliliter) or iohexol (350 mg of iodine per milliliter) was selectively injected into the right coronary artery (1.5 mL over 30 seconds) of 10 rabbits, some of which also received the alpha 1-adrenergic receptor agonist methoxamine. To validate the model, the class III antiarrhythmic agent clofilium was injected intravenously during methoxamine infusion. Frontal electrocardiography was performed continuously to detect polymorphic ventricular tachycardia (PVT). In a second study, the authors assessed the frequency of arrhythmias after injection of isotonic iohexol solution (145 mg of iodine per milliliter), either alone or with 150 mmol/L sodium. RESULTS: Methoxamine significantly lengthened the QT, QTc, and RR intervals (P < .05). The use of clofilium alone induced no PVT, whereas five of eight methoxamine-infused rabbits developed PVT after clofilium injection (P = .03). Both contrast media prolonged the repolarization period. Iohexol alone induced a higher frequency of PVT than did ioxaglate alone (P = .0006). Methoxamine infusion did not potentiate the frequency of PVT in the ioxaglate-injected rabbits. The addition of sodium to isotonic iohexol prevented the occurrence of PVT (P = .0006). CONCLUSION: Although ioxaglate prolonged the repolarization period, it did not cause a higher frequency of arrhythmia when injected in association with methoxamine. Iohexol, which contains no sodium, induced a high frequency of arrhythmia. The addition of a physiologic concentration of sodium to isotonic iohexol can prevent ventricular arrhythmias.

Adrenergic alpha-Agonists↗

PubMed1998

Cell cycle progression in monkey cells expressing simian virus 40 small t antigen from adenovirus vectors.

The simian virus 40 small t antigen (small-t) is required for optimal viral replication and transformation, especially during the infection of nondividing cells, suggesting that the function of small-t is to promote cell cycle progression. The mechanism through which small-t promotes cell growth reflects, in part, its binding and inhibition of protein phosphatase 2A (PP2A). The use of recombinant adenoviruses allows small-t expression in a majority of cells in a population, thus providing a convenient source of cells for biochemical analyses. In monkey kidney CV1 cells, small-t expressed from these adenovirus vectors activated the mitogen-activated protein kinase (MAPK) pathway, induced JNK activity, and increased AP-1 DNA-binding activity, all in a PP2A-dependent manner. Expression of small-t also caused an increase in the phosphorylation of the Na+/H+ antiporter, a mitogen-activated ion exchanger whose activity correlates with its phosphorylation. At least part of the antiporter phosphorylation induced by small-t reflected activation of the MAPK pathway, as suggested by results of assays using a chemical inhibitor of the MAPK-activating kinase, MEK. Finally, small-t expression from adenovirus vectors promoted efficient cell cycle progression by growth-arrested cells. These vectors should facilitate further analysis of effects of small-t on cell cycle mediators.

Adenoviridae↗

PubMed1998

Small-t and large-T antigens cooperate to drive cell proliferation.

Optimal transformation efficiencies or tumour formation in certain target tissues require the SV40 small-t antigen in addition to the transforming protein, large-T. We have used two model systems in which small-t is required for transformation to roles of individual viral proteins in this process. These systems include anchorage-independent growth of rat fibroblasts and focus formation by primary human diploid fibroblasts. In both cases, large-T and small-t antigens work together to drive cell cycle induction. Thus, the need for both tumour antigens is apparent in the initial step of the transformation process, the stimulation of quiescent cells to enter the cell cycle.

Animals↗

PubMed1998

French previously untreated patients with severe hemophilia A after exposure to recombinant factor VIII : incidence of inhibitor and evaluation of immune tolerance.

Fifty French previously untreated patients with severe hemophilia A (factor VIII < 1%), treated with only one brand of recombinant factor VIII (rFVIII), were evaluated for inhibitor development, assessment of risk factors and outcome of immune tolerance regimen. The median period on study was 32 months (range 9-74) since the first injection of rFVIII. Fourteen patients (28%) developed an inhibitor, four of whom (8%) with a high titer (> or = 10 BU). All inhibitor patients but one continued to receive rFVIII either for on-demand treatment or for immune tolerance regimen (ITR). Among these patients, inhibitor was transient in 2 (4%), became undetectable in 6 and was still present in 6. The prevalence of inhibitor was 12%. Presence of intron 22 inversion was found to be a risk factor for inhibitor development. Immune tolerance was difficult to achieve in our series despite a follow-up period of 16 to 30 months: immune tolerance was complete in only one out of the 3 patients undergoing low dose ITR and in one out of the 5 patients with high dose ITR.

Child↗

PubMed1998

[Epidemiology and economic impact of heart failure in France].

There are little epidemiological data available about heart failure in France, despite its considerable impact on the system of health care and the fact that this problem will become even more acute in the future. Here are some important statistics: in France, there are about 500,000 people suffering from heart failure with about 120,000 new cases every year. The incidence increases from 4% in men and 3% in women of 55 to 64 years of age to 50% in men and 85% in women of 85 to 94 years of age. The average age of diagnosis is 73.5 years: two thirds of patients are over 70 years of age. There are about 3.5 million consultations and 150,000 hospital admissions for heart failure per year. The average length of hospital stay is 11 days. There are more than 32,000 deaths per year from heart failure. The cost of treating heart failure represents more than 1% of total medical expenses. Heart failure is a major problem of public health which is on the increase. This should incite physicians to provide optimal treatment for those affected and to place greater emphasis on preventive measures.

Age Factors↗

PubMed1997

Voltage-dependent Na(+)-HCO3- cotransporter and Na+/H+ exchanger are involved in intracellular pH regulation of cultured mature rat cerebellar oligodendrocytes.

Intracellular pH (pHi) was measured at 37 degrees C in mature rat cerebellar oligodendrocytes dissociated in culture by using the pH-sensitive probe BCECF. Cells were identified by anti-galactocerebroside antibody. The mean steady-state pHi was 7.02 in the absence of CO2/bicarbonate (Hepes-buffered solution) at an external pH of 7.40 and 7.04 in 5% CO2/25 mM bicarbonate-buffered solution at the same external pH; this value was modified neither by the removal of external chloride nor by the addition of the chloride-coupled transport blocker DIDS. In both external solutions steady-state pHi values were strongly dependent on external pH. In Hepes-buffered solution pHi recovery following an acid load required external Na+ and was completely inhibited by amiloride, indicating the presence of a Na+/H+ exchanger. In CO2/bicarbonate-buffered solution amiloride partially reduced the pHi recovery rate, indicating the presence of a bicarbonate-dependent pHi regulating mechanism. Membrane depolarization induced by increasing external K+ concentration elicited an alkalinization only in the presence of external Na+ and bicarbonate. Analysis of the calculated HCO3- fluxes with respect to membrane potential indicated that these fluxes were mediated by a Na(+)-HCO3- cotransport with a stoichiometry of 1:3. These results demonstrate that a Na+/H+ exchanger and a Na(+)-HCO3- cotransporter are involved in pHi regulation of mature oligodendrocytes.

Amiloride↗

PubMed1997

Strategy of craniofacial reconstruction after resection of spheno-orbital "en plaque" meningiomas.

Surgical resection of spheno-orbital "en plaque" meningiomas should be as complete as possible to prevent tumor recurrence and therefore requires a bone reconstruction. We report a series of 20 patients operated on for spheno-orbital "en plaque" meningioma between 1981 and 1993. The surgical treatment included a resection of the involved dura and a wide resection of tumoral bone using a fronto-temporal craniotomy extended to the orbitozygomaticomalar bone ridge. The craniofacial reconstruction was performed in the same operative procedure using iliac bone autograft in 11 patients, internal cortical bone from the bone flap in 8 patients, and a coral graft in 1 patient. The cosmetic result was scored according to the following criteria: superior frontal paralysis, appearance of the orbitomalar bone ridge, shape of the external temporal fossa, and projection of the eyeballs. The cosmetic result was scored as excellent or good in 17 patients, average in 2 patients, and poor in 1 patient. The iliac bone autograft appeared to be the best material for craniofacial reconstruction because it could be modeled easily to the desired shape. However, the reconstruction technique was modified as necessary according to the extent of tumor removal, clinical presentation, and age of the patient.

Bone Transplantation↗

PubMed1997

Pharmacokinetics of acyclovir in patients undergoing continuous venovenous hemodialysis.

The pharmacokinetics of acyclovir in three patients undergoing continuous venovenous hemodialysis was investigated. Acyclovir was administered as an intravenous infusion over 1 hour at a dose of 5 mg/kg daily in one patient and 10 mg/kg every 48 hours in two patients. Samples from the arterial and venous blood lines and from ultrafiltrate were collected to calculate pharmacokinetic parameters, sieving coefficient and clearance of ultrafiltration. Plasma concentrations of acyclovir were assessed by high-performance liquid chromatography. Peak plasma concentrations were 9.3 mg/l for the patient receiving 5 mg/kg daily, 29.6 mg/l and 20.7 mg/l for the two patients with 10 mg/kg every 48 hours. The elimination half-life ranged from 8.8 to 11.2 hours and was approximately half those found in patients with renal impairment. The clearance by ultrafiltration was from 17.4 to 22.3 ml/minute and reached nearly 35% of the total clearance. The sieving coefficient ranged from 0.92 to 0.98 with an average rate of removal over the dosing interval ranging from 6.7 to 13.0 mg/hour. These data should be taken into account to optimize drug therapy in patients on continuous hemodialysis. Until formal guidelines are defined, acyclovir dosage should be adjusted according to monitoring of plasma drug concentrations.

Acyclovir↗