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Biomedical subjects

F Bussière

Publications and source records attributed to F Bussière.

At least 19 recordsLinked to original sources

Genetics of lifespan in C. elegans: molecular diversity, physiological complexity, mechanistic simplicity.

The nematode Caenorhabditis elegans is used as a model system for the study of aging. Several mutant strains that have an increased lifespan have been isolated and characterized genetically and molecularly. Molecular analysis reveals that diverse types of gene products can affect worm lifespan, including proteins active in signal transduction, transcription and silencing factors, mitochondrial enzymes, and at least one protein that affects telomere length. Genetic analysis, however, suggests that these activities all converge on a few key mechanisms that impinge on lifespan, namely the production, repair and prevention of molecular damage.

Animals↗

Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans.

Increased protection from reactive oxygen species (ROS) is believed to increase life span. However, it has not been clearly demonstrated that endogenous ROS production actually limits normal life span. We have identified a mutation in the Caenorhabditis elegans iron sulfur protein (isp-1) of mitochondrial complex III, which results in low oxygen consumption, decreased sensitivity to ROS, and increased life span. Furthermore, combining isp-1(qm150) with a mutation (daf-2) that increases resistance to ROS does not result in any significant further increase in adult life span. These findings indicate that both isp-1 and daf-2 mutations increase life span by lowering oxidative stress and result in the maximum life span increase that can be produced in this way.

Amino Acid Sequence↗

Regulation of physiological rates in Caenorhabditis elegans by a tRNA-modifying enzyme in the mitochondria.

We show that the phenotype associated with gro-1(e2400) comprises the whole suite of features that characterize the phenotype of the clk mutants in Caenorhabditis elegans, including deregulated developmental, behavioral, and reproductive rates, as well as increased life span and a maternal effect. We cloned gro-1 and found that it encodes a highly conserved cellular enzyme, isopentenylpyrophosphate:tRNA transferase (IPT), which modifies a subset of tRNAs. In yeast, two forms of the enzyme are produced by alternative translation initiation, one of which is mitochondrial. In the gro-1 transcript there are also two possible initiator ATGs, between which there is a sequence predicted to encode a mitochondrial localization signal. A functional GRO-1::GFP fusion protein is localized diffusely throughout the cytoplasm and nucleus. A GRO-1::GFP initiated from the first methionine is localized exclusively to the mitochondria and rescues the mutant phenotype. In contrast, a protein initiated from the second methionine is localized diffusely throughout the cell and does not rescue the mutant phenotype. As oxygen consumption and ATP concentration have been reported to be unaffected in gro-1 mutants, our observations suggest that GRO-1 acts in mitochondria and regulates global physiology by unknown mechanisms.

Adenosine Triphosphate↗

Mapping in solution shows the peach latent mosaic viroid to possess a new pseudoknot in a complex, branched secondary structure.

We have investigated the secondary structure of peach latent mosaic viroid (PLMVd) in solution, and we present here the first description of the structure of a branched viroid in solution. Different PLMVd transcripts of plus polarity were produced by using the circularly permuted RNA method and the exploitation of RNA internal secondary structure to position the 5' and 3' termini and studied by nuclease mapping and binding shift assays using DNA and RNA oligonucleotides. We show that PLMVd folds into a complex, branched secondary structure. In general, this structure is similar to that reported previously, which was based on sequence comparison and computer modelling. The structural microheterogeneity is apparently limited to only some small domains. More importantly, this structure includes a novel pseudoknot that is conserved in all PLMVd isolates and seems to allow folding into a very compact form. This pseudoknot is also found in chrysanthemum chlorotic mottle viroid, suggesting that it is a unique feature of the viroid members of the PLMVd subgroup.

Base Sequence↗

The viroid and viroid-like RNA database.

This is an online database to facilitate research on viroid, viroid-like RNAs and human hepatitis delta virus (vHDV) by presenting a large number of sequences and related data in a comprehensive and user-friendly format (e.g. position of their self-catalytic domains, open reading frame of the vHDV, prediction of the most stable secondary structures, etc.). Most of these RNA species share a common proposed replication pattern known as a DNA-independent rolling circle mechanism. Together, these species form the 'brotherhood' of the smallest known auto-replicable RNAs. This online database is available on the World Wide Web at http://www.callisto.si.usherb.ca/jpperra

Databases, Factual↗

Subcellular localization and rolling circle replication of peach latent mosaic viroid: hallmarks of group A viroids.

We characterized the peach latent mosaic viroid (PLMVd) replication intermediates that accumulate in infected peach leaves and determined the tissue and subcellular localization of the RNA species. Using in situ hybridization, we showed that PLMVd strands of both plus and minus polarities concentrate in the cells forming the palisade parenchyma. At the cellular level, PLMVd was found to accumulate predominantly in chloroplasts. Northern blot analyses demonstrated that PLMVd replicates via a symmetric mode involving the accumulation of both circular and linear monomeric strands of both polarities. No multimeric conformer was detected, indicating that both strands self-cleave efficiently via their hammerhead sequences. Dot blot hybridizations revealed that PLMVd strands of both polarities accumulate equally but that the relative concentrations vary by more than 50-fold between peach cultivars. Taken together these results establish two hallmarks for the classification of viroids. Group A viroids (e.g., PLMVd), which possess hammerhead structures, replicate in the chloroplasts via the symmetric mode. By contrast, group B viroids, which share a conserved central region, replicate in the nucleus via an asymmetric mechanism. This is an important difference between self-cleaving and non-self-cleaving viroids, and the implications for the evolutionary origin and replication are discussed.

Fruit↗

Impact of attenuation correction by simultaneous emission/transmission tomography on visual assessment of 201Tl myocardial perfusion images.

UNLABELLED: It has been shown in clinical studies that for subjects with a low likelihood of coronary artery disease (CAD), attenuation correction (AC) improves the specificity of defect detection in the inferior wall (right coronary artery [RCA] region). The aim of this study was to investigate the effect of AC on the visual interpretation of the RCA and anteroseptal (corresponding to the left anterior descending artery [LAD]) regions in CAD patients. METHODS: Fifty-six patients with suspected CAD underwent 20Tl stress/4 h-delayed imaging SPECT using a simultaneous 201Tl emission/99mTc transmission imaging protocol. Images were reconstructed using the maximum likelihood-expectation maximum algorithm without and with AC. The stress/4 h-delayed images were interpreted blindly for reversible or fixed defects in the RCA and LAD regions by three experienced physicians. Coronary angiography, electrocardiography and enzyme findings were used to establish diagnoses of ischemia or infarction, and receiver operating characteristic (ROC) analyses were performed. RESULTS: Statistical testing of ROC curve areas showed that defect detection performance improved with AC when compared with performance without AC in the RCA region. This was mainly the result of a systematic increase in specificity of 12% or more (for any observer and any type of defect) for a similar sensitivity (no definite change in sensitivity values). However, defect detection performance significantly decreased in the LAD territory with AC images (P < 0.05) because of a systematic decrease in sensitivity of 20% or more, with no consistent change in specificity. Similar trends were observed when reversible and fixed defects were considered separately. CONCLUSION: AC significantly affects the visual interpretation of 201Tl stress/4 h-delayed SPECT images. This study confirmed the increase in specificity obtained with AC in the RCA territory. However, in the population considered, the studied AC was deleterious for the LAD territory assessment.

Coronary Disease↗

[Role of arthroscopy in the treatment of pyogenic arthritis of the knee in adults. Report of 16 cases].

PURPOSE OF THE STUDY: The goal of this study was to determine the place and the limit of the arthroscopic management of septic knee arthritis. This procedure is an alternative treatment to needle aspiration and to open arthrotomy drainage. MATERIAL AND METHODS: Sixteen adult patients were treated between 1993 and 1997 for pyogenic septic arthritis of the knee. The duration of symptoms prior to arthroscopic debridement was 4.5 days (range, one to 14 days). In 8 patients the infection was hematogenous. 5 patients had post-operative infection, 2 had post-traumatic infection and one infection followed an intraarticular injection. All the patients were treated by arthroscopic debridement and irrigation of the knee. A partial synovectomy of the anterior compartment was carried out in 4 cases in which the infection diagnosis was delayed. In 6 patients with resistant germ or early unfavorable course (clinically or biologically), an early iterative arthroscopy was performed between 2 and 7 days after the first procedure. The medical treatment consisted in a double systemic antibiotherapy for an average duration of 4 weeks, followed by oral treatment for 3 weeks. The patients were encouraged to mobilize their knee as soon as C Reactiv Protein was normal (average 3 weeks, 0 to 12). RESULTS: The average follow up was 20.5 months (2 to 60). Two elderly patients died, one directly related to knee infection. One patient with prior patella osteosynthesis had a recurrent infection 10 months after the arthroscopy. Thirteen out of 14 patients had an excellent or good functional result. DISCUSSION: Arthroscopic drainage is a valuable alternative procedure for the treatment of the septic arthritis. Arthroscopic treatment leads to a more effective infectious result than needle aspiration procedure and the functional result is better than with open drainage. Septic arthritis in the elderly or in patients with multiple organ failure have a poor prognosis. The treatment of pyoarthrosis of the knee must be aggressive and we frequently propose an iterative arthroscopic drainage, specially in case of delayed treatment, early unfavorable course or multiresistant germ.

Adolescent↗

Study of the frequencies of CYP1A1 gene polymorphisms and glutathione S-transferase mu1 gene in primary breast cancers: an update with an additional 114 cases.

We studied the polymorphisms m1 (Msp1 restriction site) and m2 (codon Val substitution) of CYP1A1 gene and the copy number of glutathione S-transferase mu1 (GSTM1) gene on 487 DNA of breast cancer primary tumours from Caucasian group. Tumours of patients aged 55 years and under at diagnosis presented a great proportion of wild m1 (-/-) genotype; 83.6% vs. 69.5% (p < 0.0006), and a higher percentage of copy number of GSTM1 equal or under one copy; 65.2% vs. 53.4% (p < 0.011) for older patients m1 and m2 variants are closely linked (p < 0.0000). Tumour with a low copy number of GSTM1 is correlated with high histological grading (p < 0.01) and high Cathepsin D concentrations (p < 0.02). The combinations of different genotypes showed that association wild m1 (-/-) genotype and copy number of GSTM1 inferior or equal to one copy is correlated with an early onset of breast cancer primary tumour 44% vs. 6.4% for m1 (-/+) or (+/+) genotype and copy number of GSTM1 superior to one (p < 0.0000). The CYP1A1 gene wild form seems to be associated with early cancer development in Caucasian patients.

Adult↗

[Preoperative localization in primary hyperparathyroidism: value of Tc-99m-MIBI scintigraphy].

In order to assess the value of scanning with 99mTc-MIBI before surgery in primary hyperparathyroidism (PHP), we performed this procedure in 30 patients with PHP. MIBI imaging findings were: 24 true positive results, three false positive, three false negative (sensitivity: 89%). The 24 true positive results comprised 21 solitary adenomas (one of which was ectopic), one cancer, and two parathyroid hyperplasias. Thus 99mTc-MIBI scanning seems to be useful for the preoperative localization, and for preparing the surgeon to unusual features that could generate surgical failure.

Adenoma↗

[Glutathione S-transferase mu 1 (GSTM1): susceptibility gene of breast cancer].

Glutathione S-transferases mu (GSTM) are dimeric cytosolic isoenzymes. They catalyze glutathione conjugation upon a large variety of electrophiles as carcinogens, trans-stilbene peroxide or benzo(a)pyrene. The gene GSTM1 is localized on chromosome 1p13, it has drawn attention because it is absent approximately in 50% of the white population. GSTM1 null genotype seems linked with susceptibility to cancers as lung, colon and bladder cancers. We have studied GSTM1 genotype from 373 primary breast tumours. The GSTM1 null genotype was found in 50% of the cases (185/373). The incidence study of GSTM1 copy number on clinical and biological variables displayed a significant difference (p < 0.01) of the GSTM1 genotype, showed by the tumour, according to the patient age at diagnosis. The patients younger than 55 years had a percentage more important of primary tumours (65%) with a copy number of GSTM1 gene, inferior or equal at one, compared to the patients older than 55 years (52%). The tumours, whose cathepsin D level was high, presented few copies of GSTM1 gene (p < 0.03). There was no other relationship, particularly, with tumour size, node status, histological type, hormonal receptors, pS2 cytosolic level GSTM1 gene seems protect the mammary gland from cancerogenesis with its detoxification role. This results had not, pointed out in breast cancer, yet.

Adult↗

Compilation and analysis of viroid and viroid-like RNA sequences.

We have created a catalogue comprising all viroid and viroid-like RNA sequences which to our knowledge have been either published or were available from on-line sequence libraries as of October 1, 1995. In the development of this catalogue nomenclature ambiguities were removed, the likely ancestral sequence of most species was determined and the most stable secondary structures of these sequences were predicted using the MulFold package. Only viroids of PSTVd-type possessed a rod-like secondary structure, while most other viroids adopted branched secondary structures. Several viroids have predicted secondary structures that include either a Y or cruciform structure reminiscent of the tRNA-like end of virus genomes at an extremity. However, it remains unknown whether or not these predicted structures are adopted in solution, and if they serve a particular function in vivo. Additional information such as the position of the self-catalytic domains are included in the catalogue. An analysis of the data compilated in the catalogue is included. The catalogue will be available on the world wide web (http://www.callistro.si.usherb.ca/jpperra), on computer disk and in printed form. It should provide an excellent reference point for further studies.

Base Sequence↗

Effect of pacing rate on regional left ventricular wall motion. Assessment by quantitative analysis of equilibrium radionuclide angiography.

We evaluated the hemodynamic impact of right ventricular pacing at different stimulation frequencies. Fourteen patients with a right ventricular pacemaker (VVI pacing with retrograde P wave) but without clinical and electrocardiographic evidence of coronary artery disease underwent two equilibrium radionuclide angiographies: one under low heart rate (50/60 beats per minute) and the other under fast heart rate (90/100 beats per minute). Left ventricular global and sectorial ejection fractions, amplitude and phase images of first harmonic, and sectorial phases of left ventricle were analyzed. In twelve patients (84.7%), sectorial ejection fraction abnormalities in the left ventricular apicoseptal and inferoapical regions were observed under low heart rate, and worsened under fast heart rate, while new onset sectorial ejection fraction abnormalities under fast heart rate were observed in the other two patients with normal sectorial ejection fraction under low heart rate. Sectorial ejection fractions of left ventricular apicoseptal and inferoapical regions significantly changed between low and high heart rate (- 14.1 +/- 3.8%, p < 0.005; - 7.5 +/- 2.4%, p < 0.01 respectively). Left ventricular sectorial phases were abnormal in only two patients (14.3%) under low heart rate, and in twelve patients (84.7%) under fast heart rate. Our study confirms that left ventricular regional wall motion abnormalities during VVI pacing significantly worsen under fast heart rate in comparison to those under low heart rate.

Aged↗

Evidence for a model ancestral viroid.

The generation of a phylogenetic tree of viroids and viroid-like plant satellite RNAs via computer analysis, coupled with several conspicuous biochemical characteristics of the rolling circle replication of these RNAs -including both self-cleavage and self-ligation- leads us to propose the peach latent mosaic viroid (PLMVd) as a current "living fossil" dating from a precellular world. Incorporated within this proposal is a revised mechanism of PLMVd rolling circle replication which requires a minimal protein involvement.

Evolution, Molecular↗

A radiolabelled iodobenzamide for malignant melanoma staging.

123I-N-(di-ethylamino-2-ethyl) 4 iodobenzamide (I-BZA) has been put forward by the Clermont-Ferrand INSERM U71 group (France) as a tracer for malignant melanoma. We report on the clinical results obtained in 56 studies performed on 48 patients. Whole body scans along with spot views were obtained after injection of 185 MBq of I-BZA. The scans were read by three independent observers and correlated to the clinical findings and the other imaging modalities available, taking into account all lesions larger than 1 cm. Patients were classified into two groups on the basis of a post-treatment survey of patients: group I, in complete remission (24 scans); group II: documented metastases (32 scans). In group 1, 21 studies were truly negative. However, three studies showed positive results. Only one turned out to be a false positive (specificity 95%), the other two revealed unknown lesions and modified the patients' management. In group II, 73% of the known metastases were detected with higher sensitivities (> 80%) for eye and orbit, lung and abdomen. One false positive was reported and four new lesions were detected. I-BZA scintigraphy has the same sensitivity as immunoscintigraphy with higher specificity and without the risk of xenoimmunization. It is a useful tool for staging malignant melanoma which can improve patient management.

Aged↗

[Study of mdm2 gene amplification in primary breast tumors].

mdm2 (mouse double minute) protein seems lead to p53 inactivation and therefore might potentially play a role in carcinogenesis. We have studied mdm2 gene amplification from 239 primary breast cancer tissues. mdm2 gene was amplified in 10% of cases (25/239). mdm2 amplification was associated with c-erbB2 amplification (P < 10(-3)). No other correlation was found. However there was inverse correlation between c-erbB2 gene amplification and hormonal receptors (P < 10(-4)), only from patients without mdm2 gene amplification.

Adult↗

Nitrates improve detection of ischemic but viable myocardium by thallium-201 reinjection SPECT.

Thallium-201 reinjection imaging improves myocardial viability detection when compared to standard 3-4-hr redistribution imaging, however, the extent of ischemic but viable myocardium is still underestimated. We tested whether the sensitivity of reinjection imaging could be increased by giving nitrates postexercise to improve blood flow during the redistribution period. Twenty patients with coronary artery disease were included, 11 of them with a recent myocardial infarction. All patients underwent two exercise/4-hr redistribution 201Tl SPECT protocols: one with reinjection alone and the other with nitrates and reinjection. In the latter case, 20 mg of Isosorbide Dinitrate were given to patients immediately after postexercise imaging. Fifteen patients had reversible defects with reinjection alone, three additional patients were defined as ischemic with nitrates/reinjection protocol. Reinjection alone identified 41 reversible segmental defects, all except one were also evaluated as reversible with nitrates/reinjection. However, among the 54 segments showing fixed defects after reinjection only, 14 (26%) presented as reversible with the nitrates/reinjection protocol. The redistribution extent (segments/patient) was 2.05 +/- 0.41 segments with reinjection alone and 2.75 +/- 0.38 (p < 0.01) with nitrates/reinjection. In 15 patients showing reversible defects with both protocols, the redistribution extent was 2.73 +/- 0.41 segments with reinjection alone and 3.20 +/- 0.40 (p < 0.05) with nitrates/reinjection. Thallium-201 SPECT with nitrates and reinjection improves the detection of ischemic but viable myocardium in comparison to SPECT with reinjection alone.

Coronary Disease↗