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C Francois

Publications and source records attributed to C Francois.

At least 19 recordsLinked to original sources
PubMed2004

Epidemiological and quantitative study of GBV-C infection in french polytransfused children.

From 1999 to 2002, 246 serum samples taken from polytransfused children were tested for the presence of GB virus C (GBV-C) RNA using a real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. This assay was based on the TaqMan technology and allowed viral load determination in infected children with a dynamic range from 10(3) to 10(7) genome equivalent (gEq) copies/ml. The limit of detection was estimated to 619 gEq copies/ml with a > or = 95% probability of a positive result. Thirty five sera were found to be GBV-C RNA positive, corresponding to a prevalence of GBV-C of 14.2%. The mean viral load was high, i.e., 6 +/- 1.4 log (range 3.22-7.42) gEq copies/ml, but low viral loads were also detected. Sequencing of the 5'-untranslated region (UTR) identified a majority of genotype 2 strains (82%) distributed into two subtypes, 88.5% genotype 2a and 11.5% genotype 2b. In conclusion, GBV-C active infection is very frequent in exposed populations such as polytransfused children. GBV-C RNA quantitation using real-time assay may be useful for diagnosis and follow-up of the natural history of GBV-C infection.

Adolescent↗
PubMed2002

Arterialized venous free flaps for soft-tissue reconstruction of digits: a 40-case series.

When there is not sufficient local tissue available for reconstruction of one or multiple digital defects, distant flap reconstructions are required. Available thin flaps with defined arterial inflow and venous outflow are limited and require the sacrifice of an arterial pedicle. In addition, a functional limitation can occur at the donor site. During the last decades, experimental and clinical attempts have been made in using venous flaps, based just on the venous network for in- and outflow. A 40-case series of arterialized venous free flaps in soft-tissue reconstruction of the digits and hand is presented. Neovessel formation induced by an intact venous plexus within the flap proved clinically to be the survival mechanism. Postoperative congestion was present in all flaps and subsided within 14 days; 92 percent of all flaps eventually survived. In 57.5 percent of cases, total flap survival was observed; in 17.5 percent of flaps, a superficial epidermolysis occurred, not requiring further surgery; in 17.5 percent of flaps, a full-thickness skin necrosis developed, requiring grafting (minor complication); in 7.5 percent of reconstructions, total flap necrosis was observed. Thus, in the authors' experience, when conventional local flaps are not available, arterialized venous free flaps proved to be a successful solution for soft-tissue reconstruction in digits and hands. The authors present the main indications and advantages of arterialized venous free flaps, emphasizing the essential technical steps and the most frequent pitfalls in treatment.

Adolescent↗
PubMed2001

Early detection of myocardial ischaemia in the emergency department by rest or exercise (99m)Tc tracer myocardial SPET in patients with chest pain and non-diagnostic ECG.

Chest pain (CP) represents a frequent reason for presentation at the emergency department (ED). A large proportion of patients have non-diagnostic ECG on presentation, and in many cases several hours have elapsed since onset of symptoms. Acute rest myocardial scintigraphy (rest SPET) has been shown to have a relevant role in the detection of patients at risk for coronary events, but its sensitivity and negative predictive value are optimal only within the first 3 h following onset of symptoms. In those with delayed presentation, exercise SPET alone, as a screening approach, appears more promising, but its feasibility and diagnostic role in the ED are still unresolved. A total of 231 consecutive patients with a recent-onset (<24 h) first episode of CP had a negative first-line work-up including ECG, troponins, creatine kinase-MB and echocardiography. These patients were considered at low risk for short-term coronary events. Patients were studied with rest SPET if they presented <3 h after onset of CP and exercise SPET if they presented after > or =3 h. The end-points of the study were detection of significant coronary artery disease (CAD) by angiography and major coronary events or cardiac death at 6 months. Eighty patients (35%) underwent rest SPET, while 151 (65%) underwent exercise SPET. Two of the 159 patients with negative SPET had evidence of critical CAD at 6-month follow-up (one patient in the rest SPET group and one in the exercise SPET group; P=NS). Of the 72 patients (31%) with a positive scan, 34 (15%) had documented CAD (16 patients in the rest SPET group and 18 in the exercise SPET group; P=NS). Sensitivity, specificity, accuracy and predictive value were not statistically different between the two groups. In conclusion, the accuracy of exercise SPET in patients with CP and delayed presentation to the ED is comparable to that of validated rest SPET in patients with early presentation. Owing to the high negative predictive value (99%), exercise SPET is especially valuable as a screening tool for the exclusion of CAD in low-risk patients and implementation of early discharge.

Aged↗
PubMed2001

Parkin immunoreactivity in the brain of human and non-human primates: an immunohistochemical analysis in normal conditions and in Parkinsonian syndromes.

The etiology of Parkinson's disease is unknown, but the gene involved in an autosomic recessive form of the disease with early onset has recently been identified. It codes for a protein with an unknown function called parkin. In the present study we produced a specific polyclonal antiserum against human parkin. Immunohistochemical analysis showed that parkin is expressed in neuronal perikarya and processes but also in glial and blood vessels in the primate brain (human and monkey). Electron microscopy indicated that parkin immunoreactivity is mostly located in large cytoplasmic vesicles and at the level of the endoplasmic reticulum. Parkin was expressed heterogeneously in various structures of the brain. It was detectable in the dopaminergic systems at the level of the perikarya in the mesencephalon but also in the striatum. However, parkin was also expressed by numerous nondopaminergic neurons. The staining intensity of parkin was particularly high in the hippocampal formation, the pallidal complex, the red nucleus, and the cerebellum. Comparison of control subjects with patients with Parkinson's disease and control animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated animals revealed a loss of parkin-immunoreactive neurons only in the substantia nigra pars compacta. Furthermore, the surviving dopaminergic neurons in the parkinsonian state continued to express parkin at a level similar to that observed in the control situation. These data indicate that parkin is a widely expressed protein. Thus, the degeneration of dopaminergic neurons in familial cases of Parkinson's disease with autosomal recessive transmission cannot be explained solely in terms of an alteration of this protein.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

Metabolic activity of excitatory parafascicular and pedunculopontine inputs to the subthalamic nucleus in a rat model of Parkinson's disease.

Using a combination of metabolic measurement and retrograde tracing, we show that the neurons in the pedunculopontine nucleus and parafascicular nucleus of the thalamus that project to the subthalamic nucleus are hyperactive after nigrostriatal dopaminergic denervation in rats. In Parkinson's disease, the loss of dopaminergic neurons induces a cascade of functional changes in the basal ganglia circuitry including a hyperactivity of the subthalamic nucleus. This hyperactivity is thought to be due to a diminution of the inhibitory pallidal influence. However, recent studies have suggested that other cerebral structures are involved in the subthalamic neuronal hyperactivity. This study was undertaken to identify these cerebral structures. Neurons projecting to the subthalamic nucleus were identified by retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase, injected into the subthalamic nucleus of rats with 6-hydroxydopamine unilateral lesion of the substantia nigra pars compacta and sham-lesioned animals. Metabolic activity was determined in the same neurons using in situ hybridization for the first subunit of cytochrome oxidase messenger RNA, a metabolic marker, and image analysis. Horseradish peroxidase-labeled neurons were found in the globus pallidus, parafascicular and pedunculopontine nucleus and sometimes in raphe nuclei and the substantia nigra pars compacta. Measurement of metabolic activity was performed for the globus pallidus, the pedunculopontine and parafascicular nuclei. The expression level of the first subunit of cytochrome oxidase messenger RNA in neurons projecting to the subthalamic nucleus was 62% higher in parafascicular neurons and 123% higher in pedunculopontine neurons in 6-hydroxydopamine-lesioned rats, compared to sham-lesioned animals. An increase was also observed in the globus pallidus, but did not reach significance. Our results suggest that hyperactivity of subthalamic neurons could be due, at least in part, to an increase of excitatory input arising from the pedunculopontine and parafascicular nuclei. These data also suggest that the latter structures may play an important role in the physiopathology of Parkinson's disease.

Animals↗
PubMed2000

Functional mapping of the human globus pallidus: contrasting effect of stimulation in the internal and external pallidum in Parkinson's disease.

Our objective was to elaborate a functional map of the globus pallidus by correlating the intrapallidal localization of quadripolar electrodes implanted in parkinsonian patients with the clinical effect of the stimulation of each contact. Five patients with L-DOPA-responsive Parkinson's disease presenting severe motor fluctuations and L-DOPA-induced dyskinesias were treated by continuous bilateral high-frequency stimulation of the globus pallidus. The effects of stimulation on parkinsonian disability were tested through each of the four stimulating contacts of each electrode. The anatomical localization of each of the stimulating contacts was determined by confronting the pre- and post-operative magnetic resonance imaging with the anatomical atlas of Schaltenbrand and Wharen.(34) The registration procedure comprised digitization of the atlas, the use of deformation tools to fit atlas sections with magnetic resonance imaging sections, and three-dimensional reconstruction of both the atlas and the magnetic resonance imaging sections. Analysis of the 32 stimulating contacts tested did not reveal a somatotopic organization in the pallidal region investigated but demonstrated that high-frequency stimulation had contrasting effects depending on whether it was applied to the external or the internal pallidum. Akinesia was improved by stimulation of the external pallidum but worsened by stimulation of the internal pallidum. In contrast, parkinsonian rigidity was improved by stimulation of either part of the pallidum. The areas in the internal pallidum where stimulation worsened akinesia were those in which stimulation reduced or suppressed L-DOPA-induced dyskinesias. Conversely, stimulation applied to the external pallidum induced dyskinesias. The fact that rigidity was improved by stimulation of the internal and external pallidum suggests that the neuronal bases of parkinsonian rigidity are different from those of akinesia and dyskinesias. The effect on akinesia and dyskinesias is in agreement with the current model of basal ganglia circuitry(10) if high-frequency stimulation activates rather than inhibits pallidal neurons, a possibility which is very likely since there are marked anatomical, biochemical and electrophysiological differences between the globus pallidus and the subthalamic nucleus. This study demonstrates that high-frequency stimulation of the globus pallidus in parkinsonian patients has contrasting effects depending on whether it is applied to the external or the internal part of this nucleus. The effect on akinesia and dyskinesias suggests that stimulation activates pallidal neurons, a result which challenges the generally accepted concept that high-frequency stimulation inactivates neurons in the region stimulated.

Adult↗
PubMed1998

Stavudine plus didanosine and nevirapine in antiretroviral-naive HIV-infected adults: preliminary safety and efficacy results. VIRGO Study Team.

The objective of this open-label trial is to evaluate the virological and immunological effects of triple therapy with stavudine (40 mg twice daily if > or = 60 kg, 30 mg twice daily if < 60 kg)/didanosine (400 mg once daily if > or = 60 kg, 300 mg once daily if < 60 kg)/nevirapine (200 mg daily from day 1 to 14, then 200 mg twice daily) in 60 antiretroviral-naive HIV-infected adults with CD4 cell counts > or = 200 cells/mm3 and plasma HIV RNA > or = 5000 copies/ml. At present, 59 patients have begun receiving the trial regimen. Characteristics of patients at baseline were as follows: 46 men/13 women, CDC stage A, 75%; mean CD4 cell count, 429 cells/mm3; mean HIV RNA, 4.6 log10 copies/ml). Mean decrease of viral load was -1.9 log10 at week 4 (n = 39), -1.9 log10 at week 16 (n = 20), with HIV RNA below the detectable level (< 500 copies/ml) in 62% of patients at week 4 and 85% at week 16. Mean CD4 cell count increase was +118 cells/mm3 at week 4. Cutaneous intolerance occurred within the first 4 weeks in 11/59 (19%) patients after a mean of 14 days (range, 3-24 days) and led to nevirapine discontinuation in 3/11 patients. Preliminary results of this ongoing trial show that combination therapy with stavudine/didanosine/nevirapine is a convenient (seven pills in two daily intakes) triple-therapy regimen with rapid immunological and antiviral effects. Rash, frequent in the first weeks of therapy, usually can be managed without stopping nevirapine. Long-term suppression of plasma HIV RNA with this combination needs to be confirmed but may support use of nevirapine as a component of first-line anti-HIV therapy along with two nucleosides.

Adult↗
PubMed1997

[Coronary embolism and myocardial infarction with heat rupture during infectious endocarditis].

We report a case of transmural myocardial infarction due to coronary embolism complicating infective endocarditis in a 41 year old woman. The infarction, clinically silent, was followed by rupture of left ventricular free wall, leading to hemopericardium and cardiac tamponade. The case is an uncommon complication of infective endocarditis, at the same time an uncommon cause of myocardial infarction.

Adult↗
PubMed1996

Stability study of nanoparticles of poly(epsilon-caprolactone), poly(D,L-lactide) and poly(D,L-lactide-co-glycolide).

The objective was to evaluate the stability of nanoparticles prepared with poly(epsilon-caprolactone), poly(D,L-lactide) and poly(D,L-lactide-co-glycolide) polymers and stored at different temperatures and in different media. The stability parameters studied were molecular weight and crystallinity of the polymer, nanoparticle size and pH. The results show that the stability of polymeric nanoparticles depends on (i) the type of polymers with the following increasing order of polymer stability: PLA25GA50 < PLA37.5GA25 < PLA50 = PCL, (ii) the storage temperature: PCL and PLA50 nanoparticles can be kept at 4 degrees C and RT during one year, while PLA37.5GA25 and PLA25GA50 nanoparticles have to be stored at 4 degrees C, and (iii) the storage conditions: buffering or freeze-drying nanoparticles improves stability.

Biopolymers↗
PubMed1994

Heterodimerization of the IL-2 receptor beta- and gamma-chain cytoplasmic domains is required for signalling.

The interaction of interleukin-2 (IL-2) and IL-2 receptors critically regulates the T-cell immune response following antigen activation. IL-2 can signal through high or intermediate affinity receptors which contain IL-2R alpha (refs 3, 4) +beta (refs 5-8) +gamma (ref. 9) or beta+gamma chains, respectively. IL-2R gamma is a common gamma chain, gamma c, also shared by the IL-7 (ref. 10) and IL-4 (refs 11, 12) receptors, which when mutated results in X-linked severe combined immunodeficiency. Using chimaeric receptor constructs together with monoclonal or bispecific antibodies we demonstrate here that IL-2 signalling requires ligand-induced extracellular-domain-mediated heterodimerization of the beta- and gamma c-chain cytoplasmic domains. Anti-IL-2R alpha monoclonal antibodies trigger proliferation of cells transfected with chimaeric constructs in which the extracellular domains of IL-2R beta and gamma c are replaced by that of IL-2R alpha. Other experiments using chimaeric constructs indicated that IL-2 binds monomerically and monovalently to IL-2R alpha and that the beta-transmembrane domain is not required for receptor chain interactions. Finally, we provide a method for mapping residues in the gamma c cytoplasmic domain even in cells that constitutively express gamma c.

Animals↗
PubMed1993

Construction of a bispecific antibody reacting with the alpha- and beta-chains of the human IL-2 receptor. High affinity cross-linking and high anti-proliferative efficiency.

A bispecific antibody recognizing both the alpha- and beta-chains of the IL-2R was generated by sulfhydryl-directed chemical reassociation of monovalent Fab' fragments prepared from the anti-alpha mAb 33B3.1 (rat IgG2a) and from the anti-beta mAb A41 (mouse IgG1). Whereas the 33B3.1/A41 bispecific mAb (bi-mAb) binds to isolated alpha- and beta-chains with low affinity (Kd = 4 nM), its binding to cells co-expressing the two chains shows both low and high affinity components. The high affinity-binding sites (Kd = 100 pM) most probably correspond to the cross-linking by the bi-mAb of alpha- and beta-chains, whereas the low affinity component corresponds to the excess of alpha-chains. High affinity binding of bi-mAb on activated T cells is observed at 37 degrees C and not at 4 degrees C, suggesting that i) the two chains are dissociated at 4 degrees C in the absence of ligand and ii) the mechanism of bi-mAb catalyzed cross-linking of these two chains is temperature dependent. In contrast to parental 33B3.1 and A41 IgG, which recognize single positive (alpha + and beta +, respectively) and double positive alpha +/beta + cells with similar affinities, the 33B3.1/A41 bi-mAb is specific for activated alpha +/beta + cells with respect to its high affinity binding. In contrast to A41, which does not affect IL-2-induced proliferation of 4AS cells or anti-CD3-activated PBL, and to 33B3.1, which do inhibit proliferation but only partially and at high doses, the bi-mAb showed full blocking efficiencies at low concentrations (IC50 of 300 to 400pM) corresponding to the formation of high affinity alpha/bi-mAb/beta complexes. These half-maximal effects were observed at 10-fold lower concentrations than when using a combination of equimolar concentrations of parental 33B3.1 and A41 IgG. Because of their specificity and high blocking efficiencies, anti-alpha/anti-beta bi-mAb may constitute a better alternative for IL-2R-directed immunosuppression.

Humans↗
PubMed1991

Could non steroidal anti-inflammatory drugs be used to potentiate L.M.W.H activity in thrombosis? (Part I).

Heparin fractions are antithrombotic drugs prescribed for preventive treatment but their efficacy must be optimized to permit curative use without side effects. The present study was performed on 144 rats receiving a low molecular weight heparin (L.M.W.H), Fraxiparine, and a non steroidal anti-inflammatory drug (Phenylbutazone), which were injected simultaneously or separately. Neither Phenylbutazone nor L.M.W.H at their lowest dose (1 mg/kg) reduced thrombus size. However, administered together, they produced a significant limitation of thrombus growth. Variation in anti Xa activity limitation was only observed with the highest dose of Fraxiparine alone or in combination with Phenylbutazone (1 mg/kg) corresponding to its antithrombotic effect.

Animals↗
PubMed1991

Topographic distribution of the neurons of the central complex (centre médian-parafascicular complex) and of other thalamic neurons projecting to the striatum in macaques.

The distribution of the neurons of the central complex (or "centre médian-parafascicular complex") and of other thalamic regions projecting to the striatum was studied using a cartographic technique based on ventricular landmarks. The brain of a macaque was used as a reference for the cytoarchitectonic study of the complex. Three parts were isolated: the pars parafascicularis (or medial part), the pars media (or middle part) and the pars paralateralis (or lateral part). Wheat germ agglutinin conjugated to horseradish peroxidase was stereotaxically injected into either the sensorimotor or the associative territory of the striatum (i.e. the striatal space occupied by the axonal endings coming from either the sensorimotor or the associative cortex) of four macaques. Neurons projecting to the sensorimotor territory of the striatum were found to be located within the pars media (middle part) of the central complex while neurons projecting to the associative territory of the striatum were located within the pars parafascicularis. In all experimental cases, labelled neurons were scarce or absent in the pars paralateralis (or lateral part). Outside the central complex, neurons projecting to the sensorimotor territory of the striatum were scattered within the lateral part of the lateral mass, in the intralaminar nuclei and in the posterior part of the internal lamina. Neurons projecting to the associative territory of the striatum were observed mainly in the paraventricular region, dorsal to the rostral part of the lateral mass, and in the dorsolateral part of the nucleus oralis medialis. Our three-dimensional analysis of the clusters of the central complex cells projecting to the two striatal territories justifies the partitioning of the central complex into three parts. The pars media (or middle part), which projects to the sensorimotor territory of the striatum, receives selectively pallidal afferent axons. It belongs to the Nauta-Mehler loop, a closed loop linking the central complex to the basal ganglia. The pars parafascicularis, which projects to the associative territory of the striatum, seems more related to oculomotor neuronal systems. The pars paralateralis (or lateral part) appears to have very little, if any, relation with the striatum.

Afferent Pathways↗
PubMed1990

Mouse mammary tumor virus (MMTV) infection in SWISS and RIII mice. Correlation between resistance to exogenous infection and anti-MMTV serum response.

Host-virus relationships were examined in mice from the two mouse mammary tumor virus (MMTV)-infected strains SWISS MB+ and RIII, which harbour the same MMTV variant, and from the derived sublines Swiss MB- and RIIIf, which were freed of milk-borne MMTV by foster-nursing. These two strains are not phylogenetically related, the SWISS strain bearing the endogenous Mtv-3 locus in its DNA. In RIII and SWISS MB+ mice, the incidence of early mammary tumors, which was of 96% and 8%, respectively, was correlated to the level of MMTV expression in milk. In the SWISS MB-line, a non-coordinate expression of the provirus associated with the Mtv-3 locus was observed in the mammary glands, the salivary glands and the spleen. This expression was not tumorigenic and was characterized by the presence of the p28 gag antigen and the absence of the gp52 env antigen, except, however, in mammary glands of elder mice where traces of gp52 were found. In the mammary glands of SWISS MB+ mice, the expression of the Mtv-3 locus was masked by large amounts of antigens resulting from exogenous virus expression. RIIIf mice were MMTV-negative. Viral antigens coexisted with anti-MMTV antibodies in the serum of infected and tumor-bearing mice, but not in the form of immune complexes as verified by a method that allowed to detect specific antigen-containing-soluble immune complexes. An anti-MMTV serum reactivity was also detected in SWISS MB- and RIIIf mice. However, the serum response was higher in the two SWISS lines than in the two RIII lines. Except in tumor-bearing mice, the anti-MMTV response was not significantly modified by the presence of exogenous virus and thus resulted essentially from exposure to endogenous MMTV expression. In experimental infection studies, RIII mice were more susceptible to MMTV infection than SWISS mice. The correlation between resistance to MMTV infection and serum response to endogenous MMTV expression, suggests that the non-tumorigenic expression of an endogenous provirus can protect at least partially, against exogenous MMTV infection.

Animals↗
PubMed1985

Natural infection of Swiss mice with mouse mammary tumor virus (MMTV): viral expression in milk and transmission of infection.

Quantitative determinations of gp52, the main envelope glycoprotein, and p28, the main core protein, of MMTV, have been performed in about 1000 individual samples of milk of breeding females from our colony of MMTV-infected Swiss mice, a line characterized by a moderate incidence of mammary tumors. A computer analysis of the results showed: 1-- an important individual variation, ranging from 0 to 120 micrograms per ml of milk for p28, and from 0 to 320 micrograms per ml of milk for gp52; 2-- a variation of the release of both antigens during a single lactation, with a maximum on the 7--8th day of nursing; 3-- an increase of the release of both antigens with parity up to the 6th lactation, followed by a marked decrease during later lactations; 4-- a higher degree of infection in the offspring of 2nd and 3rd litters. The possible dependence of viral expression and transmission of infection upon factors such as cyclic activity of the mammary gland and progressive immunization of mice against MMTV is analyzed. The status of our laboratory line of MMTV infected Swiss mice is discussed in comparison with high and low tumor incidence strains.

Animals↗