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Biomedical subjects

C Brun

Publications and source records attributed to C Brun.

At least 19 recordsLinked to original sources

Nosocomial infections in the rehabilitation department.

AIM: The patients of a Rehabilitation Department are at high risk of nosocomial infections because they generally have a long term hospitalisation and more and more frequently immune-compromised subjects, like old patients or with chronic illness, are admitted to rehabilitation programs. However, to evaluate the real infectious risk of a Rehabilitation Unit, it is important to consider also that a high number of patients are transferred from other hospitals after a specific therapy of the acute phase of their medical or surgical pathology and so many nosocomial microrganisms previously acquired may spread to a Rehabilitation Unit. METHODS: From January to December 2003 we have performed a screening of the bacteruria among the patients at admittance to the Rehabilitation Unit of S. Orsola Fatebenefratelli Hospital of Brescia (Italy). RESULTS: A significant bacteruria (>100000 cfu/mL) in 28.9% of 114 patients coming from home and in 41.9% of 179 patients transferred from other hospitals without antibacterial treatment has been documented. CONCLUSIONS: These findings confirm the presence of an high number of patients colonized or infected by nosocomial bacteria previously acquired in hospital and underline the need, in addition to specific skill, of wide infectious knowledge among the medical staff of a Rehabilitation Unit. A specific approach to the infectious problem in the Rehabilitation Department in order to reduce the risk of nosocomial infections may be suggested.

Aged↗

U7 snRNAs induce correction of mutated dystrophin pre-mRNA by exon skipping.

Most cases of Duchenne muscular dystrophy are caused by dystrophin gene mutations that disrupt the mRNA reading frame. Artificial exclusion (skipping) of a single exon would often restore the reading frame, giving rise to a shorter, but still functional dystrophin protein. Here, we analyzed the ability of antisense U7 small nuclear (sn)RNA derivatives to alter dystrophin pre-mRNA splicing. As a proof of principle, we first targeted the splice sites flanking exon 23 of dystrophin pre-mRNA in the wild-type muscle cell line C2C12 and showed precise exon 23 skipping. The same strategy was then successfully adapted to dystrophic immortalized mdx muscle cells where exon-23-skipped dystrophin mRNA rescued dystrophin protein synthesis. Moreover, we observed a stimulation of antisense U7 snRNA expression by the murine muscle creatine kinase enhancer. These results demonstrate that alteration of dystrophin pre-mRNA splicing could correct dystrophin gene mutations by expression of specific U7 snRNA constructs.

Animals↗

Trans-complementation of an endonuclease-defective tagged I element as a tool for the study of retrotransposition in Drosophila melanogaster.

I factors are non-LTR retrotransposons of Drosophila melanogaster that transpose at high frequency in the germline of females resulting from appropriate crosses, allowing in vivo studies of the retrotransposition process. Reverse transcription of a full-length RNA intermediate is thought to occur at the site of integration, using a 3' hydroxyl group generated by endonucleolytic cleavage of the genomic DNA to prime synthesis of the first cDNA strand. This target-primed reverse transcription (TPRT) process is mediated by endonuclease and reverse transcriptase activities encoded by the element. We have designed a molecularly tagged, endonuclease-defective I element that can be mobilised with high efficiency by constructs that express the product of the I factor ORF2 in trans. This indicates that the endonuclease activity required for retrotransposition of the I factor can be provided in trans. Using this system, we show that the endonuclease domain of the R1Bm retrotransposon from Bombyx mori cannot functionally replace that of the I factor.

Animals↗

Statistics of Fourier modes in a turbulent flow.

Fourier series are often used to discuss the properties of a homogeneous turbulent field. We investigate the statistics of Fourier modes of the turbulent velocity field and of a passive scalar. The statistics of individual Fourier modes is known to be Gaussian when the size of the system L is much larger that the integral (correlation) size l(0). The case where the integral size is of the order of the system size L approximately l(0), is studied by direct numerical simulations in the range 20 < or approximately = Rlambda < or approximately = 80. At a given Rlambda, we find that the probabilities of large fluctuations become larger when the wave number increases, in qualitative agreement with the notion of intermittency. As the Reynolds number increases, however, the probability density functions become closer to Gaussian, in sharp contrast with the behavior of velocity increments. We also show that in a simple model of cascade, the Fourier series decomposition is not appropriate to capture intermittency effects. Last, we discuss other issues related to our results.

Journal Article↗

Strengths-based case management: individuals' perspectives on strengths and the case manager relationship.

Strengths-based practice in social work has a strong theoretical foundation as an effective helping strategy that builds on a person's successes. Although there is growing empirical evidence informing outcomes associated with strengths-based approaches, missing from the literature is an understanding of how individuals who receive these services view their experiences. Qualitative data collection methods were used to gather individuals' experiences of participating in strengths-based case management implemented in a substance abuse aftercare program. The research questions that guided the study were "What are individuals' perceptions of strengths-based case management?" and "How do those perceptions compare and contrast to the key principles of strengths-based case management?" The emerging themes centered on individuals' responses to a focus on strengths (acceptance of strengths; holding on to strengths and deficits simultaneously; and initial mistrust of the approach) and to the relationship with the case manager (acceptance of the relationship; guilt when success is not achieved; and not needing the relationship). Implications for social work practice are discussed.

Adaptation, Psychological↗

From first base: the sequence of the tip of the X chromosome of Drosophila melanogaster, a comparison of two sequencing strategies.

We present the sequence of a contiguous 2.63 Mb of DNA extending from the tip of the X chromosome of Drosophila melanogaster. Within this sequence, we predict 277 protein coding genes, of which 94 had been sequenced already in the course of studying the biology of their gene products, and examples of 12 different transposable elements. We show that an interval between bands 3A2 and 3C2, believed in the 1970s to show a correlation between the number of bands on the polytene chromosomes and the 20 genes identified by conventional genetics, is predicted to contain 45 genes from its DNA sequence. We have determined the insertion sites of P-elements from 111 mutant lines, about half of which are in a position likely to affect the expression of novel predicted genes, thus representing a resource for subsequent functional genomic analysis. We compare the European Drosophila Genome Project sequence with the corresponding part of the independently assembled and annotated Joint Sequence determined through "shotgun" sequencing. Discounting differences in the distribution of known transposable elements between the strains sequenced in the two projects, we detected three major sequence differences, two of which are probably explained by errors in assembly; the origin of the third major difference is unclear. In addition there are eight sequence gaps within the Joint Sequence. At least six of these eight gaps are likely to be sites of transposable elements; the other two are complex. Of the 275 genes in common to both projects, 60% are identical within 1% of their predicted amino-acid sequence and 31% show minor differences such as in choice of translation initiation or termination codons; the remaining 9% show major differences in interpretation.

Animals↗

From sequence to chromosome: the tip of the X chromosome of D. melanogaster.

One of the rewards of having a Drosophila melanogaster whole-genome sequence will be the potential to understand the molecular bases for structural features of chromosomes that have been a long-standing puzzle. Analysis of 2.6 megabases of sequence from the tip of the X chromosome of Drosophila identifies 273 genes. Cloned DNAs from the characteristic bulbous structure at the tip of the X chromosome in the region of the broad complex display an unusual pattern of in situ hybridization. Sequence analysis revealed that this region comprises 154 kilobases of DNA flanked by 1.2-kilobases of inverted repeats, each composed of a 350-base pair satellite related element. Thus, some aspects of chromosome structure appear to be revealed directly within the DNA sequence itself.

Animals↗

Taz1p and Teb1p, two telobox proteins in Schizosaccharomyces pombe, recognize different telomere-related DNA sequences.

Band shift assays were used to study proteins from the fission yeast that bind double-stranded telomeric repeat sequences. We also examine general DNA binding properties of the telobox domain, which characterizes telomere-binding proteins from a range of species. We demonstrate that Taz1p has a high affinity for the fission yeast telomeric repeat, consistent with genetic results implicating this protein in telomere maintenance. A second Schizosaccharomyces pombe telobox protein, Teb1p, is shown to bind with high affinity to the vertebrate repeat and with low affinity to the fission yeast telomeric DNA. When tested on G-rich single-stranded telomeric DNA, all these proteins bind with very low affinity, much like the human telomere-binding protein TRF1. Recombinant proteins containing just the telobox domains reproduce the specificity of binding demonstrated for the corresponding full-length proteins, indicating that the telobox domain is indeed responsible for specific DNA recognition. The presence of possible Teb1p-binding sites upstream of many genes suggests a role for this protein as a general transcription factor. Finally, band shift experiments with whole cell extracts from wild-type and taz1 (-)strains suggest that in addition to Taz1p, S.pombe has another major telomere-binding activity.

Base Sequence↗

Planar isotropy of passive scalar turbulent mixing with a mean perpendicular gradient.

A recently proposed evolution equation [Vaienti et al., Physica D 85, 405 (1994)] for the probability density functions (PDF's) of turbulent passive scalar increments obtained under the assumptions of fully three-dimensional homogeneity and isotropy is submitted to validation using direct numerical simulation (DNS) results of the mixing of a passive scalar with a nonzero mean gradient by a homogeneous and isotropic turbulent velocity field. It is shown that this approach leads to a quantitatively correct balance between the different terms of the equation, in a plane perpendicular to the mean gradient, at small scales and at large Péclet number. A weaker assumption of homogeneity and isotropy restricted to the plane normal to the mean gradient is then considered to derive an equation describing the evolution of the PDF's as a function of the spatial scale and the scalar increments. A very good agreement between the theory and the DNS data is obtained at all scales. As a particular case of the theory, we derive a generalized form for the well-known Yaglom equation (the isotropic relation between the second-order moments for temperature increments and the third-order velocity-temperature mixed moments). This approach allows us to determine quantitatively how the integral scale properties influence the properties of mixing throughout the whole range of scales. In the simple configuration considered here, the PDF's of the scalar increments perpendicular to the mean gradient can be theoretically described once the sources of inhomogeneity and anisotropy at large scales are correctly taken into account.

Journal Article↗

Effect of treatment on flow-dependent vasodilation of the brachial artery in essential hypertension.

off aim of our study was to evaluate the effect of antihypertensive treatment on flow-mediated dilation (FMD)of a large artery, a noninvasive estimate of endothelial function, in hypertensive patients. In 78 consecutive hypertensive patients (40%men; age range, 42 to 67 years) we measured by a high-resolution ultrasound system the changes of brachial artery diameter during reactive hyperemia and after sublingual glyceryl trinitrate (400 microg); brachial artery flow velocity was measured by pulsed Doppler. The results of 2 studies are reported. In the first study, this procedure was repeated in 58 patients after 6 and 12 months of treatment with a combination of antihypertensive drugs; in a second study, the FMD was assessed in 20 patients after 2 months of monotherapy with either nifedipine or hydrochlorothiazide. In the first study, FMD was significantly increased after treatment compared with baseline (from 3.1+/-3% at baseline to 6.5+/-4.5% at 6 months and to 8.12+/-4. 6% at 12 months; P<0.001 by ANOVA), concomitant with blood pressure reduction (from 162+/-24/102+/-13 mm Hg to 141+/-12/89+/-6 mm Hg and to 141+/-9/89+/-6 mm Hg; P<0.001 by ANOVA); significant changes of endothelium-independent dilation were also observed, but only after 12 months of treatment (from 14.2+/-4.8 at baseline to 15.5+/-4.7 at 6 months and 16.8+/-5.9% at 12 months; P=0.03 by ANOVA). In the second study, FMD was significantly increased during nifedipine treatment as compared with baseline (from 5+/-6.18% at baseline to 9. 45+/-3.94%, P<0.001), while it did not change in patients receiving hydrochlorothiazide (from 5.15+/-5.28% at baseline to 4.69+/-4.34%, NS). No significant changes of endothelium-independent dilation were observed with both drugs (from 17.10+/-2.4% to 18.14+/-3.76% and from 18.73+/-4.07% to 17.46+/-4.27% during nifedipine and hydrochlorothiazide, respectively, NS). Thus, in essential hypertensive patients an improvement of the impaired FMD of the brachial artery, evaluated by noninvasive ultrasound, may be observed after long-term, effective blood pressure reduction, suggesting a beneficial effect of antihypertensive treatment on endothelial function. It seems that beyond blood pressure control, a calcium antagonist may be more effective than a diuretic in this respect.

Adult↗

[Perinatal Campylobacter jejuni infection after Cesarean section].

A 23 year old woman was admitted for delivery after having experienced a few episodes of loose stools. Following an unsuccessful vacuum-extraction, a Caesarean section was performed 12 hours after the membranes had ruptured. Thirty-six hours after the operation, the woman developed fever, and Campylobacter jejuni was isolated from her blood. Subsequently, Campylobacter was also recovered from the faeces of both mother and child. Though it is likely, that the Campylobacter was introduced to the uterus after rupture of the membranes, a transplacental infection can not be ruled out.

Adult↗

Role of the telomeric DNA-binding protein TRF2 in the stability of human chromosome ends.

A major issue in telomere research is to understand how the integrity of chromosome ends is preserved. A recent study shows that expression of a dominant-negative form of the human telomeric protein TRF2 increases the number of chromosome fusions in immortalized cells and decreases the quantity of G-rich telomeric DNA 3' overhang, the G tail. Consequently, TRF2 appears to control the structure of the very end of the chromosomal DNA molecule and to prevent recombination between two telomeres. Remarkably, the same study reveals a potential role of TRF2 in cell division control.

Cell Division↗

[Burn wounds after resuscitation of a newborn girl].

In resuscitation of an asphyctic newborn baby, a chemical hot pack was used for maintaining sufficient body temperature. The child lay for 45 min on the covered hot pack, which had a peak temperature of 54 degrees C. This led to a third degree burn (5% of BSA). The child needed split skin grafting. Control at four months of age showed a well-taken skingraft and the child was developing normally. We conclude that chemical hot packs should not be used for newborn babies unless the peak temperature in the packs is less than 44 degrees C.

Asphyxia Neonatorum↗

Screening for FMR1 and FMR2 mutations in 222 individuals from Spanish special schools: identification of a case of FRAXE-associated mental retardation.

Fragile X syndrome is the most common inherited form of familial mental retardation. It results from a (CGG)n trinucleotide expansion in the FMR1 gene leading to the typical Martin-Bell phenotype. Clinical features vary depending on age and sex. Expansion of a (CCG)n repeat in the FMR2 gene corresponds to the FRAXE fragile site which lies distal to FRAXA and is also associated with mental retardation, but it is less frequent and lacks a consistent phenotype. Analysis of repeat expansions in these two genes allows the molecular diagnosis of these different entities. We report here the screening of the FRAXA and FRAXE mutations in 222 unrelated mentally retarded individuals attending Spanish special schools. PCR and/or Southern blotting methods were used. We detected full mutations in the FMR1 gene in 11 boys (4.9%) and 1 boy (0.5%) with a CCG repeat expansion in the FMR2 gene. The latter shows mild mental retardation with psychotic behaviour and no remarkable physical traits. Molecular studies revealed a mosaicism for methylation in the FMR2 gene. This case supports the observation that expansions greater than 100 repeats can be partially methylated and cause the phenotype.

Adolescent↗

Telomeric localization of TRF2, a novel human telobox protein.

Natural chromosomal ends are stabilized by proteins that bind duplex telomeric DNA repeats. In human cells, the TTAGGG Repeat Factor 1 (TRF1) was identified by two independent studies, one screening for factors that bind duplex telomeric DNA and the other screening for proteins containing a particular Myb motif called the telobox, which is required for telomeric repeat recognition (Fig. 1a; refs 3-5). A second human open reading frame, orf2, contains a telobox sequence and encodes a polypeptide that specifically recognizes mammalian telomeric repeat DNA in vitro. We show that two proteins of 65 and 69 kD, expressed in HeLa cells, contain the orf2 telobox sequence. These proteins are collectively termed TRF2. Affinity-purified antibodies specific for anti-TRF2 label the telomeres of intact human chromosomes, strengthening the correlation between occurrence of telobox and telomere-repeat recognition in vivo.

Amino Acid Sequence↗

An origin of replication and a centromere are both needed to establish a replicative plasmid in the yeast Yarrowia lipolytica.

Two DNA fragments displaying ARS activity on plasmids in the yeast Yarrowia lipolytica have previously been cloned and shown to harbor centromeric sequences (P. Fournier, A. Abbas, M. Chasles, B. Kudla, D. M. Ogrydziak, D. Yaver, J.-W. Xuan, A. Peito, A.-M. Ribet, C. Feynerol, F. He, and C. Gaillardin, Proc. Natl. Acad. Sci. USA 90:4912-4916, 1993; and P. Fournier, L. Guyaneux, M. Chasles, and C. Gaillardin, Yeast 7:25-36, 1991). We have used the integration properties of centromeric sequences to show that all Y. lipolytica ARS elements so far isolated are composed of both a replication origin and a centromere. The sequence and the distance between the origin and centromere do not seem to play a critical role, and many origins can function in association with one given centromere. A centromeric plasmid can therefore be used to clone putative chromosomal origins coming from several genomic locations, which confer the replicative property on the plasmid. The DNA sequences responsible for initiation in plasmids are short (several hundred base pairs) stretches which map close to or at replication initiation sites in the chromosome. Their chromosomal deletion abolishes initiation, but changing their chromosomal environment does not.

Base Sequence↗