Search PubMed⌕ Search

Biomedical subjects

F Rousseau

Publications and source records attributed to F Rousseau.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Spread of Enterobacteriaceae producing broad-spectrum beta-lactamase and the development of their incidence over a 16-month period in a university hospital center].

Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLE) constitute with methicillin-resistant Staphylococcus aureus the main multiresistant bacteria recovered in French hospitals. Our objectives were to evaluate these ESBLE diffusion in our teaching hospital and to follow their incidence during a 16-month period, whereas a control programme (barrier precautions) had been implemented in the beginning of 1999. This study was conducted in a teaching hospital containing 1800 beds, from February 1999 to May 2000. All ESBLE isolated in clinical or screening samples were included. Duplicates (same bacteria in the same patient) were excluded. The detection of the ESBL was performed with the double-disk diffusion test. Incidence densities were determined with their 95% confidence interval (CI95%). Their evolution by four-month period was evaluated with the chi-square test for trend. During the 16-month period, 229 ESBLE were isolated. The incidence was 0.35 per 1000 patient-days (PD) (CI95% = [0.30-0.40]) for the whole hospital. It was 0.47/1000 PD (CI95% = [0.38-0.56]) in medical wards, 0.29/1000 PD (CI95% = [0.20-0.38]) in surgical wards and 1.32/1000 PD (CI95% = [0.90-1.74]) in intensive care units. Enterobacter aerogenes strains represented more than 75% of all ESBLE, whereas Klebsiella pneumoniae stains represented only 8.6%. During the study, the incidence of ESBLE and the proportion of strains acquired in our hospital decreased significantly (p < 0.0001 and p < 0.001 respectively). Indeed, between the first eight-month period and the last one, the incidence of ESBLE acquired in our hospital decreased by 55%, whereas the incidence of imported strains increased slightly. This study shows that the diffusion of ESBLE concerns the entire hospital. The implementation of a control programme of the spread of multiresistant bacteria allowed us to reduce significantly the incidence of ESBLE. This incidence seemed to be stable for several months. The implementation of a policy which restricts antimicrobial use would allow us to complete the the efficacy of barrier precautions.

Academic Medical Centers↗
PubMed2001

A comprehensive phylogeny of the Phaeophyceae based on nrDNA sequences resolves the earliest divergences.

The present study is the first comprehensive phylogeny of the class of the Phaeophyceae. For 67 species representing all orders of the class, the sequences of the 3'-end of the small and the 5'-end of the large subunit nrRNA genes were aligned and analysed. A further analysis based on sequences of the 3'-end of the small and of the complete sequences of the 28S gene of the large subunits was also performed, but for only eight taxa. In both analyses, Tribonema marinum (Xanthophyceae) was used as outgroup. The analyses showed the Dictyotales as diverging first, followed by the Sphacelariales, then the Syringodermatales. Most of the orders currently accepted were confirmed as monophyletic groups but the Laminariales and Tilopteridales remained polyphyletic. The relationships of the remaining orders to each other were not resolved with the present data set. Ascoseira, included for the first time in a molecular study, appeared as a separate lineage without any clear relationship with other algae possessing conceptacles (Splachnidium and Fucales). Algae with stellate plastids, never studied in a global context, were polyphyletic; this result is consistent with their plastid ultrastructure and is discussed in detail. As further result of the present study, the South African genus Bifurcariopsis appeared as the sister taxon of the North Atlantic genus Himanthalia, and Xiphophora appeared as the sister taxon of Hormosira rather than as a member of the Fucaceae; the taxonomic position of these genera is discussed.

DNA, Ribosomal↗
PubMed2001

Observation of signal transduction in three-dimensional domain swapping.

p13suc1 (suc1) has two native states, a monomer and a domain-swapped dimer. The structure of each subunit in the dimer is identical to that of the monomer, except for the hinge loop that connects the exchanging domains. Here we find that single point mutations at sites throughout the protein and ligand binding both shift the position of the equilibrium between monomer and dimer. The hinge loop was shown previously to act as a loaded molecular spring that releases tension present in the monomer by adopting an alternative conformation in the dimer. The results here indicate that the release of strain propagates throughout the entire protein and alters the energetics of regions remote from the hinge. Our data illustrate how the signal conferred by the conformational change of a protein loop, elicited by domain swapping, ligand binding or mutation, can be sensed by a distant active site. This work highlights the potential role of strained loops in proteins: the energy they store can be used for both signal transduction and allostery, and they could steer the evolution of protein function. Finally, a structural mechanism for the role of suc1 as an adapter molecule is proposed.

Ligands↗
PubMed2001

Evaluation of the contribution of isolation precautions in prevention and control of multi-resistant bacteria in a teaching hospital.

From February 1999 to January 2000, a control programme to prevent the spread multi-resistant bacteria (MRB) was implemented in a French teaching hospital. This programme focused on methicillin-resistant Staphylococcus aureus (MRSA) and Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBL), and was based on the application of barrier precautions (washing hands with antiseptic soaps, wearing disposable gloves and gowns, identifying MRB carriers). No changes in antibiotic policy occurred during the year. Our aim was to conduct an evaluation of this programme by measuring incidence rates. Concurrently, the effect of barrier precautions was estimated in an indirect way, by documenting the availability of barrier precautions in MRB carriers' rooms and by analysing the monthly correlation between the supply of such material and the theoretical cumulated length of MRB carriers' isolation in six randomized wards. All MRB isolated in hospitalized patients were recorded, and differentiated between acquisition in our hospital or from elsewhere. For the analysis of trends, the year was divided in three periods of four months. Over the year, the global MRB incidence was 1.26 per 1000 patient-days (PD) [95% confidence interval (95%CI)=1.16-1.36]. The MRSA incidence was 0.89 per 1000 PD (95%CI=0.81- 0.97) and the ESBL incidence was 0.38 per 1000 PD (95% CI=0.33-0.43). The MRB incidence decreased significantly in all types of specialties except for surgical wards. The incidence decreased by 17.9% for MRSA, 54.9% for ESBL and 34.8% for both MRB. Concurrently, the proportion of strains acquired in our hospital decreased for MRSA (P for trend > or = 0.05) and ESBL (P for trend > or = 0.01), whereas the incidence of imported strains increased slightly. The proportion of multiresistant strains in S. aureus (36.8%) and Enterobacter aerogenes (37.0%) remained similar throughout the year. Thus, the decrease of the incidence concerned both resistant and susceptible strains. The availability of antiseptic soaps increased significantly (P for trend > or = 0.01). The amount of antiseptic soap ordered and the theoretical lengths of isolation were correlated on a monthly basis (Spearman coefficient = 0.72; P > or = 0.02). These results shows the efficacy of such a programme of MRB containment in a large hospital, provided barrier nursing is instigated, together with the availability of such material as antiseptic soap, to allow implementation.

Bacterial Infections↗
PubMed2000

Prevalence and detection of delirium in elderly emergency department patients.

BACKGROUND: Delirium is a complex medical disorder associated with high morbidity and mortality among elderly patients. The goals of our study were to determine the prevalence of delirium in emergency department (ED) patients aged 65 years and over and to determine the sensitivity and specificity of a conventional clinical assessment by an ED physician for the detection of delirium in the same population. METHODS: All elderly patients presenting to the ED in a primary acute care, university-affiliated hospital who were triaged to the observation room on a stretcher because of the severity of their illness were screened for delirium by a research psychiatrist using the Mini-Mental State Examination and the Confusion Assessment Method. The diagnosis of "delirium" or an equivalent term by the ED physician was determined by 2 methods: completion of a mental status checklist by the ED physician and chart review. The prevalence of delirium and the sensitivity and specificity of the ED physician's clinical assessment were calculated with their 95% confidence intervals. The demographic and clinical characteristics of patients with detected delirium and those with undetected delirium were compared. RESULTS: A sample of 447 patients was screened. The prevalence of delirium was 9.6% (95% confidence interval 6.9%-12.4%). The sensitivity of the detection of delirium by the ED physician was 35.3% and the specificity, 98.5%. Most patients with delirium had neurologic or pulmonary diseases, and most patients with detected delirium had neurologic diseases. INTERPRETATION: Despite the relatively high prevalence of delirium in elderly ED patients, the sensitivity of a conventional clinical assessment for this condition is low. There is a need to improve the detection of delirium by ED physicians.

Age Factors↗
PubMed2000

Cloning and functional characterization of a cation-Cl- cotransporter-interacting protein.

To date, the cation-Cl(-) cotransporter (CCC) family comprises two branches of homologous membrane proteins. One branch includes the Na(+)-K(+)-Cl(-) cotransporters (NKCCs) and the Na(+)-Cl(-) cotransporter, and the other branch includes the K(+)-Cl(-) cotransporters. Here, we have isolated the first member of a third CCC family branch. This member shares approximately 25% identity in amino acid sequence with each of the other known mammalian CCCs. The corresponding cDNA, obtained from a human heart library and initially termed WO(3.3), encodes a 914-residue polypeptide of 96.2 kDa (calculated mass). Sequence analyses predict a 12-transmembrane domain (tm) region, two N-linked glycosylation sites between tm(5) and tm(6), and a large intracellular carboxyl terminus containing protein kinase C phosphorylation sites. Northern blot analysis uncovers an approximately 3.7-kilobase pair transcript present in muscle, placenta, brain, and kidney. With regard to function, WO(3. 3) expressed either in HEK-293 cells or Xenopus laevis oocytes does not increase Rb(+)-, Na(+)-, and Cl(-)-coupled transport during 5- or 6-h fluxes, respectively. In the oocyte, however, WO(3.3) specifically inhibits human NKCC1-mediated (86)Rb(+) flux. In addition, coimmunoprecipitation studies using lysates from WO(3. 3)-transfected HEK-293 cells suggest a direct interaction of WO(3.3) with endogenous NKCC. Thus, we have cloned and characterized the first putative heterologous CCC-interacting protein (CIP) known at present. CIP1 may be part of a novel family of proteins that modifies the activity or kinetics of CCCs through heterodimer formation.

Amino Acid Sequence↗
PubMed2000

Significant linkage for Tourette syndrome in a large French Canadian family.

Family and twin studies provide strong evidence that genetic factors are involved in the transmission of Gilles de la Tourette syndrome (TS) and related psychiatric disorders. To detect the underlying susceptibility gene(s) for TS, we performed linkage analysis in one large French Canadian family (127 members) from the Charlevoix region, in which 20 family members were definitely affected by TS and 20 others showed related tic disorders. Using model-based linkage analysis, we observed a LOD score of 3.24 on chromosome 11 (11q23). This result was obtained in a multipoint approach involving marker D11S1377, the marker for which significant linkage disequilibrium with TS recently has been detected in an Afrikaner population. Altogether, 25 markers were studied, and, for level of significance, we derived a criterion that took into account the multiple testing arising from the use of three phenotype definitions and three modes of inheritance, a procedure that yielded a LOD score of 3.18. Hence, even after adjustment for multiple testing, the present study shows statistically significant evidence for genetic linkage with TS.

Adult↗
PubMed2000

Sequence conservation provides the best prediction of the role of proline residues in p13suc1.

The unique nature of the proline side-chain imposes severe constraints on the polypeptide backbone, and thus it seems likely that it plays a special structural or functional role in the architecture of proteins. We have investigated the role of proline residues in suc1, a member of the cyclin-dependent kinase (cks) family of proteins, whose known function is to bind to and regulate the activity of the major mitotic cdk. The effect on stability of mutation to alanine of all but two of the eight proline residues is correlated with their conservation within the family. The remaining two proline residues are located in the hinge loop between two beta-strands that mediates a domain-swapping process involving exchange of a beta-strand between two monomers to form a dimer pair. Mutation of these proline residues to alanine stabilises the protein. cdk binding is unaffected by these mutations, but dimerisation is altered. We propose, therefore, that the double-proline motif is conserved for the purpose of domain swapping, which suggests that this phenomenon plays a role in the function of cks proteins. Thus, the conservation of the proline residues is a good indicator of their roles in suc1, either in the stabilisation of the native state or in performing functions that are as yet unknown. In addition, the strain resulting from two of the proline residues was relieved successfully by mutation of the preceeding residue to glycine, suggesting a general method for designing more stable proteins.

Amino Acid Motifs↗
PubMed2000

The folding pathway of the cell-cycle regulatory protein p13suc1: clues for the mechanism of domain swapping.

BACKGROUND: The 113-residue alpha+beta protein suc1 is a member of the cyclin-dependent kinase subunit (cks) family of proteins that are involved in regulation of the eukaryotic cell cycle. In vitro, suc1 undergoes domain swapping to form a dimer by the exchange of a C-terminal beta strand. We have analysed the folding pathway of suc1 in order to determine the atomic details of how strand-exchange occurs in vitro and thereby obtain clues as to the possible mechanism and functional role of dimerisation in vivo. RESULTS: The structures of the rate-determining transition state for the folding/unfolding of suc1 and of the intermediate that is populated during refolding were probed using phi values determined for 57 mutants with substitutions at 43 sites throughout the protein. The majority of phi values are fractional in the intermediate and transition state, indicating that interactions build up in a concerted manner during folding. In the transition state, phi values of greater than 0.5 are clustered around the inner strands beta2 and beta4 of the beta sheet. This part of the structure constitutes the nucleus for folding according to a nucleation-condensation mechanism. Molecular dynamics simulations of unfolding of suc1, performed independently in a blind manner, are in excellent agreement with experiment (proceeding paper). CONCLUSIONS: Strand beta4 is the exchanging strand in the dimer and yet it forms an integral part of the folding nucleus. This suggests that association is an early event in the folding reaction of the dimer. Therefore, interchange between the monomer and dimer must occur via an unfolded state, a process that may be facilitated in vivo by accessory proteins.

Cell Cycle Proteins↗
PubMed2000

The genetics of osteoporosis: 'complexities and difficulties'.

Osteoporosis is characterized by a decrease in bone mass as well as a deterioration of the bone architecture resulting in an increased risk of fracture. Although the disease is multifactorial, twin studies have shown that genetic factors account for up to 80% of the variance in bone mineral density, the best known predictor of the risk of osteoporosis. Some loci, such as the vitamin D and estrogen receptor genes, as well as the collagen type Ialpha1 locus, are promising genetic determinants of bone mass, and possibly other bone phenotypes, but this is controversial and the molecular basis of osteoporosis remains largely undefined. Considering that the effect of each candidate gene is expected to be modest, discrepancies between allelic association studies may have arisen because different populations carry different genetic backgrounds and exposure to environmental factors. Also, we realize the importance of gene-gene as well as gene-environment interactions as significant determinants of bone density and risk of osteoporosis. The use of new tools such as small nucleotide polymorphism maps now allows the possibility to perform allelic association studies in the context of whole-genome search. However, specific study design strategies in large epidemiological studies as well as the best statistical approach will need to be established. We may expect the development of population-specific at-risk profiles for osteoporosis that would include genetic and environmental factors, as well as their interactions. This should eventually lead to better prevention strategies and more adapted therapies against osteoporosis.

Aged↗
PubMed2000

Immune reconstitution in the first year of potent antiretroviral therapy and its relationship to virologic response.

The effects of 1 year of zidovudine, lamivudine, and ritonavir treatment on immune reconstitution were evaluated in 34 human immunodeficiency virus (HIV)-infected individuals. After 48 weeks of therapy, 20 (59%) subjects had <100 copies HIV RNA/mL. CD4+ T cells increased from a median of 192/mm3 at baseline to 362/mm3 at week 48. Lymphocyte proliferative responses to Candida normalized within 12 weeks, but responses to HIV and tetanus remained depressed throughout therapy. Alloantigen responses increased within 12 weeks and then declined to baseline levels. Recovery of delayed-type hypersensitivity responses occurred after 12 weeks for Candida and after 48 weeks for mumps. The magnitude of virologic suppression was correlated with numeric increases in CD4+ T cells, but not with measures of functional immune reconstitution. Plasma virus suppression <100 copies/mL was not significantly correlated with increases in CD4+ T cells or functional immune reconstitution.

Anti-HIV Agents↗
PubMed2000

The association between heel ultrasound and hormone replacement therapy is modulated by a two-locus vitamin D and estrogen receptor genotype.

Evidence supports the role of estrogen deprivation in the process of bone remodeling and increased risk of fracture in postmenopausal women but little is known about the genetic basis of individual differences in response to therapy. In a cross-sectional study, 425 ambulatory postmenopausal French-Canadian women from Quebec (age range, 42-85 years old) were genotyped for a common Bsm I polymorphism at the vitamin D receptor (VDR) gene as well as a Pvu II polymorphism in the estrogen receptor (ESR1) gene. Heel ultrasound was determined by right calcaneal quantitative ultrasound (QUS) and results were expressed as an age-and-weight-adjusted stiffness index (heel SI z score). Our aim was to investigate the interaction between hormone-replacement therapy (HRT) and receptor genotypes in an effect on heel SI. Notably, a two-locus genotype (VDR-bb/ESR-PP) present in 9.5% of women was responsible for over 30% of the total HRT-related heel SI difference in the whole sample. Women bearing this combined VDR/ESR1 genotype who received HRT for more than 5 years had a 21% (1.25 SD) greater heel SI (p = 0.002) than those bearing the same genotype but who received HRT for <5 years. This may translate into a 2- to 3-fold difference in the risk of fracture. Although follow-up studies are needed, our findings suggest that QUS of the heel in postmenopausal women taking HRT is affected by variation in VDR and ESR1 loci, jointly.

Adult↗
PubMed1999

Four tumor suppressor loci on chromosome 9q in bladder cancer: evidence for two novel candidate regions at 9q22.3 and 9q31.

The most common genetic alteration identified in transitional cell carcinoma (TCC) of the bladder is loss of heterozygosity (LOH) on chromosome 9. However, localization of tumor suppressor genes on 9q has been hampered by the low frequency of subchromosomal deletions. We have analysed 139 primary, initial low stage TCC of the bladder using a panel of 28 microsatellite markers spanning chromosome 9 at an average distance of 5 Mb, following a primer-extension preamplification (PEP) technique. Sixty-seven (48%) tumors showed LOH at one or more loci and partial deletions were detected in 62 (45%) tumors; apparent monosomy 9 was detected in only five (4%) tumors. Deletions were more frequent on 9q (44%) than on 9p (23%), the latter being mostly associated with 9q deletion, suggesting that alteration of genes on 9q may be an early event associated with superficial papillary tumors. Combined data from the cases with partial 9q deletions displayed four candidate regions for tumor suppressor loci, based on the frequency of deletion observed and tumors with unique deletions at these sites. In two tumors, the unique partial deletion comprised D9S12 at 9q22.3, a region encompassing loci for the Gorlin syndrome and multiple self-healing squamous epithelioma gene. In two other tumors, the single LOH was identified at the D9S172 locus at 9q31-32 where the dysautonia and Fukuyama-type congenital muscular dystrophy genes have been located. One tumor showed unique LOH at the GSN locus at 9q33, a region frequently deleted in other sporadic tumors while the fourth region of deletion was observed at 9q34 between ASS and ABL-1, in two tumors. This region is frequently deleted in tumors and encompasses the locus for the hereditary hemorrhagic telangiectasia gene. These findings suggest four target regions on 9q within which suppressor genes for TCC may reside.

Chromosomes, Human, Pair 9↗
PubMed1999

FMR1 gene expression in olfactory neuroblasts from two males with fragile X syndrome.

The fragile X mental retardation 1 gene (FMR1) mutation is strongly correlated with specific and marked neurobehavioral and neuroanatomical abnormalities. The protein product, FMRP, is highly expressed in neurons of the normal mammalian brain, and absent or in low levels in leukocytes from individuals with fragile X (FraX)-associated mental impairment. Inferences which arise from these findings are that FMRP has a critical role in the development and functioning of the brain, and that leukocyte-derived molecular assessments provide a good indicator of FMR1 expression in that organ. This latter conclusion appears true in most cases even though the typical FMR1 mutation is an unstable triplet repeat expansion which demonstrates somatic heterogeneity within and across tissues. Blood to brain correspondence in FraX patients has only rarely been confirmed by the direct study of human brain specimens and, to our knowledge, it has never been studied in living individuals with the FMR1 mutation. In this report, we describe the FMR1 patterns in olfactory neuroblasts (ON) from two living brothers with expansion mutations in their leukocytes who are mentally retarded and autistic. ON were chosen for study because they are accessible neurons closely linked to the brain. In both subjects, the ON genotype was highly, but not perfectly, consistent with that observed in leukocytes. Protein phenotypes across tissues were completely consistent showing the absence of FMRP-immunoreactivity (-ir). These results augment the limited amount of direct evidence which indicates that FMR1 mutation patterns in leukocytes are a good, albeit potentially fallible, reflection of such patterns in the brain. This report further demonstrates the feasibility of using ON samples to evaluate the FMR1 mutation in humans in vivo.

Adult↗
PubMed1999

First-line high-dose sequential chemotherapy with rG-CSF and repeated blood stem cell transplantation in untreated inflammatory breast cancer: toxicity and response (PEGASE 02 trial).

Despite the generalization of induction chemotherapy and a better outcome for chemosensitive diseases, the prognosis of inflammatory breast cancer (IBC) is still poor. In this work, we evaluate response and toxicity of high-dose sequential chemotherapy with repeated blood stem cell (BSC) transplantation administered as initial treatment in 100 women with non-metastatic IBC. Ninety-five patients (five patients were evaluated as non-eligible) of median age 46 years (range 26-56) received four cycles of chemotherapy associating: cyclophosphamide (C) 6 g m(-2) - doxorubicin (D) 75 mg m(-2) cycle 1, C: 3 g m(-2) - D: 75 mg m(-2) cycle 2, C: 3 g m(-2) - D: 75 mg m(-2) - 5 FU 2500 mg m(-2) cycle 3 and 4. BSC were collected after cycle 1 or 2 and reinfused after cycle 3 and 4. rG-CSF was administered after the four cycles. Mastectomy and radiotherapy were planned after chemotherapy completion. Pathological response was considered as the first end point of this trial. A total of 366 cycles of chemotherapy were administered. Eighty-seven patients completed the four cycles and relative dose intensity was respectively 0.97 (range 0.4-1.04) and 0.96 (range 0.25-1.05) for C and D. Main toxicity was haematological with febrile neutropenia ranging from 26% to 51% of cycles; one death occurred during aplasia. Clinical response rate was 90% +/- 6%. Eighty-six patients underwent mastectomy in a median of 3.5 months (range 3-9) after the first cycle of chemotherapy; pathological complete response rate in breast was 32% +/- 10%. All patients were eligible to receive additional radiotherapy. High-dose chemotherapy with repeated BSC transplantation is feasible with acceptable toxicity in IBC. Pathological response rate is encouraging but has to be confirmed by final outcome.

Adenocarcinoma↗
PubMed1999

Characterization of viral dynamics in human immunodeficiency virus type 1-infected patients treated with combination antiretroviral therapy: relationships to host factors, cellular restoration, and virologic end points.

Biphasic plasma viral decays were modeled in 48 patients treated with ritonavir, zidovudine, and lamivudine. Estimated first- and second-phase decay rates were d1 as 0.47/day and d2 as 0.04/day. Interpatient differences in both decay rates were significant. The d1 was directly correlated with baseline CD4+, CD4+CD28+, and CD8+CD28+ T lymphocyte counts (P<.05) and inversely correlated with baseline virus load (P=.044) and the magnitude of CD4+ and CD8+ T lymphocyte recovery (P<.01). The d2 was directly correlated with baseline percentage of CD8+ T lymphocytes (P=.023), the CD8+CD38+ cell number (P=.024), and the level of IgG that binds to human immunodeficiency virus (HIV) type 1 gp120 (P=.02). Viral decay rates were not predictive of treatment failure or durability of viral suppression. These exploratory findings are consistent with a model in which immunologic factors contribute to elimination of HIV-infected cells and suggest a dynamic interplay between regulation of HIV expression and lymphocyte activation and recovery.

ADP-ribosyl Cyclase↗