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Biomedical subjects

P Boucher

Publications and source records attributed to P Boucher.

At least 19 recordsLinked to original sources

Mediterranean dietary pattern in a randomized trial: prolonged survival and possible reduced cancer rate.

BACKGROUND: The Mediterranean dietary pattern is thought to reduce the risk of cancer in addition to being cardioprotective. However, no trial has been conducted so far to prove this belief. METHODS: We compared overall survival and newly diagnosed cancer rate among 605 patients with coronary heart disease randomized in the Lyon Diet Heart Study and following either a cardioprotective Mediterranean-type diet or a control diet close to the step 1 American Heart Association prudent diet. RESULTS: During a follow-up of 4 years, there were a total of 38 deaths (24 in controls vs 14 in the experimental group), including 25 cardiac deaths (19 vs 6) and 7 cancer deaths (4 vs 3), and 24 cancers (17 vs 7). Exclusion of early cancer diagnoses (within the first 24 months after entry into the trial) left a total of 14 cancers (12 vs 2). After adjustment for age, sex, smoking, leukocyte count, cholesterol level, and aspirin use, the reduction of risk in experimental subjects compared with control subjects was 56% (P=.03) for total deaths, 61% (P=.05) for cancers, and 56% (P=.01) for the combination of deaths and cancers. The intakes of fruits, vegetables, and cereals were significantly higher in experimental subjects, providing larger amounts of fiber and vitamin C (P<.05). The intakes of cholesterol and saturated and polyunsaturated fats were lower and those of oleic acid and omega-3 fatty acids were higher (P<.001) in experimental subjects. Plasma levels of vitamins C and E (P<.05) and omega-3 fatty acids (P<.001), measured 2 months after randomization, were higher and those of omega-6 fatty acids were lower (P<.001) in experimental subjects. CONCLUSIONS: This randomized trial suggests that patients following a cardioprotective Mediterranean diet have a prolonged survival and may also be protected against cancer. Further studies are warranted to confirm the data and to explore the role of the different lipids and fatty acids in this protection.

Diet

Effect of dietary cholesterol on low density lipoprotein-receptor, 3-hydroxy-3-methylglutaryl-CoA reductase, and low density lipoprotein receptor-related protein mRNA expression in healthy humans.

We investigated the possibility that dietary cholesterol downregulates the expression of low density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase genes of circulating mononuclear cells in vivo in healthy humans. We also studied the variations of the LDL receptor-related protein (LRP) gene in the same conditions. Dieters (n = 5) were submitted to a 4-d fat restriction (mean cholesterol intake: 6+/-4 mg/d), followed by a 7-d cholesterol (a mean of 791+/-150 mg/d) supplementation. Controls (n = 3) did not change their diet. During fat restriction, serum total and LDL cholesterol decreased significantly (P < 0.05), and LDL receptor and HMG-CoA reductase mRNA copy numbers in mononuclear cells increased by 57 and 147%, respectively (P < 0.05). After reintroducing cholesterol, serum cholesterol was stable whereas LDL receptor and HMG-CoA reductase mRNA decreased by 46 and 72% (P < 0.05) and LRP mRNA increased by 59% (P < 0.005). The changes in LDL receptor and HMG-CoA reductase mRNA abundance were correlated (r = +0.79, P = 0.02) during cholesterol reintroduction as were LDL receptor and LRP mRNA levels, but negatively (r = -0.70, P = 0.05). Also, 70% of the variability in LRP mRNA (P < 0.005) was explained by dietary cholesterol. Thus, the basic mechanisms regulating cellular cholesterol content, the coordinate feedback repression of genes governing the synthesis and uptake of cholesterol, are operating in vivo in humans. However, serum cholesterol did not increase in response to dietary cholesterol, suggesting that these mechanisms may not play as predominant a role as previously believed in the short-term control of serum cholesterol in vivo in humans. A new finding is that LRP gene is also sensitive to dietary cholesterol, suggesting that it may participate in the control of serum cholesterol. Further in vivo studies in humans are warranted to explore the molecular mechanisms of the physiological response to dietary cholesterol in humans.

Adult

Gait problems in diabetic neuropathic patients.

OBJECTIVE: To examine whether a reduced peripheral sensibility caused by diabetic neuropathy increases the attentional demands necessary for controlling and regulating gait. DESIGN: Nonrandomized control trial. SETTING: University motor performance laboratory. SUBJECTS: Twelve diabetic patients with peripheral neuropathy and 7 control subjects, all volunteers. INTERVENTIONS: All subjects first performed a control seated reaction time task. For the walking task, auditory stimuli were randomly presented in the third, fourth, or fifth walking cycle on left foot toe off on left foot heel contact. The subject's task was to respond verbally as fast as possible to the auditory stimulus, while maintaining progression. MAIN OUTCOME MEASURES: Simple reaction times and kinematics of the gait pattern (cycle amplitude, cycle duration, cycle speed, cadence and percentage of time spent in the single support phase) were evaluated. RESULTS: For the walking task, diabetic neuropathic patients had a smaller cycle amplitude, cycle speed, and percentage of time spent in the single support phase than control subjects. Also, reaction times while walking were higher for diabetic neuropathic patients than for control subjects. CONCLUSIONS: Diabetic neuropathic patients show a less destabilizing and more conservative gait than control subjects. The increased attentional demands in gait for the diabetic neuropathic patients, along with their more conservative gait pattern, suggest that a lack of proprioception from the legs affects the control of gait. Diminished sensory information makes gait control more cognitively dependent in diabetic neuropathic persons than in control subjects.

Aged

Spermoculture: improvement of the bacteriological quality of samples by direct verbal counseling before semen collection.

OBJECTIVE: To compare the bacteriologic quality of samples after direct verbal or written counseling for semen collection. DESIGN: Prospective randomized comparative study. SETTING: Laboratories of biology of reproduction and microbiology in university hospitals. PATIENTS: Male partners of infertile couples on their first attempt to collect semen were assigned randomly into two groups. INTERVENTION: In one group (n = 52) the patients were given direct verbal instruction by one of the investigators on how to avoid bacterial contamination during semen collection. In the other group (n = 52) the patients were asked to follow the usual written instructions. MAIN OUTCOME MEASURE: Bacterial count, number of species, classification of the samples in positive, negative, and noninformative cultures. RESULTS: Direct verbal teaching significantly reduced the bacterial count (2.06 +/- 1.6 versus 3.29 +/- 1.6 log cfu/mL; mean +/- SD) and number of species (1.44 +/- 2.02 versus 3.25 +/- 2.25), increased the percentage of sterile cultures (59.6% versus 23.1%), and decreased the percentage of noninformative cultures (29.9% versus 50%). CONCLUSION: Direct verbal counseling on how to avoid bacterial contamination during semen collection significantly improves the bacteriologic quality of the samples.

Bacteria

Comparison of two HLA-DRB high resolution microtiter plate reverse hybridization typing methods: advantage of a codon-86 valine or glycine PCR segregation.

Two rapid, nonisotopic, high-resolution HLA-DRB typing methods have been developed for DRB1, DRB3, DRB4 and DRB5 alleles. These methods are based on a single procedure consisting of the reverse hybridization of biotinylated amplicons to oligonucleotide probes that are covalently attached to a microtiter plate. Detection is by an enzymatic reaction with a fluorescent substrate. The 1 Generic Amplification (1GA) method amplifies all HLA-DRB alleles in the same reaction mix. The 2 Allelic Subset Amplification (2SA) method uses two distinct amplification reactions that distributes all DRB alleles into two equal-size subsets, according to the codon 86 Gly or Val polymorphism; this adds an extra discrimination level to the typing. 108 samples were typed using the 1GA and the 2SA methods and no discrepancies were found. Typing indeterminations due to overlapping probe combinations were compared; it was found that the 2SA method, with the extra discrimination level at the PCR step, greatly improved resolution.

Alleles

Postural stability in diabetic polyneuropathy.

OBJECTIVE: To examine whether sensory changes in lower limbs associated with diabetic sensory polyneuropathy compromise postural stability in different visual sensory conditions. RESEARCH DESIGN AND METHODS: The presence and severity of sensory neuropathy was evaluated with a clinical scale and measures of nerve conduction velocity in the lower limbs. Balance control was evaluated by testing subjects' postural stability (with a force platform) with vision, without vision, and during a recovery period after being without vision. RESULTS: Neuropathic patients showed larger ranges of sway, a faster sway speed, and a greater dispersion of sway than control subjects in all conditions. They also exhibited similar or less stable postural performance with vision than that of control subjects without vision. There was a strong relationship between the severity of the neuropathy and the postural stability. CONCLUSIONS: This experiment highlights that even with vision, the postural stability of neuropathic patients is impaired and may put them at higher risk of falling when performing more challenging daily tasks.

Aged

Modern war surgery: the experience of Bosnia. 2: The clinical experience.

A Canadian field surgical hospital was deployed in the former Yugoslavia to support the medical needs of Canadian and other United Nations troops. Over a 6-month period, 5661 patients were seen and 50 surgical procedures performed. Gunshot, shrapnel and other blast injuries were responsible for the injury in only 10 patients seen at the hospital. Strict adherence to the concepts of hygiene, safety and trauma prevention is essential for the proper health care of large groups of peacekeepers abroad. Civilian involvement was limited by political restrictions, but a few civilians were helped. The ability to provide modern medicine in the field of battle boosted the morale of the Canadian troops.

Adolescent

Modern war surgery: the experience of Bosnia. 1: Deployment.

In the first of two papers on the experience of a Canadian military surgical team in the former Yugoslavia, the authors describe the deployment of the field surgical hospital, the medical structure that supported the Canadian battle group. The hospital was made up of tent sections erected within an unfinished concrete factory building. The hospital comprised a treatment area for sick parades and reception, a pharmacy, a resuscitation area for nonambulatory casualties, a laboratory, an x-ray section, an operating room and sterilization section and a ward. The hospital could be mobilized if necessary. The setup proved to be functional for the treatment of injured soldiers. Although long delays were expected because of difficulties in transporting the injured, the patients reached the hospital in a reasonable time after injury and could be treated satisfactorily. During the period of its deployment, this hospital was used more than any other Canadian hospital in the United Nations mission. This experience allowed the authors to identify deficiencies and to correct them quickly.

Bosnia and Herzegovina

Neutralizing antibodies and immunoprotection against pertussis and tetanus obtained by use of a recombinant pertussis toxin-tetanus toxin fusion protein.

The currently available diphtheria-tetanus-whole-cell pertussis (DTP) vaccines are associated with a variety of problems, including undesirable side effects and inconsistent efficacy. These problems are probably related to the poor definition of such vaccines, especially with respect to the whole-cell component against pertussis. Ideal vaccines should include only immunoprotective antigens with no toxin activity. As an initial step towards obtaining a well-defined and simplified DTP vaccine, a pertussis toxin-tetanus toxin chimeric protein was constructed. A soluble form of the pertussis toxin S1 subunit was fused to the protective fragment C of tetanus toxin, and the recombinant hybrid protein was produced in Escherichia coli. The 75-kDa fusion protein (p75) was overexpressed as a soluble molecule and purified to near homogeneity by two consecutive chromatographic steps. Purified p75 retained its ability to bind to ganglioside GT1b, the receptor for tetanus toxin, and to be recognized by protective and neutralizing anti-pertussis toxin antibodies specific for conformational epitopes. When administered to mice, the hybrid protein was found to be nontoxic but immunogenic. In addition, it was capable of inducing strong protection against tetanus and some protection against pertussis, as well as eliciting a pertussis toxin-neutralizing antibody response. Although the levels of anti-pertussis toxin antibodies were rather low, neutralizing titers of the immunized mice correlated well with anti-pertussis toxin titers, indicating that protective epitopes are conserved in the recombinant protein.

Animals

Inhibition of proteolysis and cell cycle progression in a multiubiquitination-deficient yeast mutant.

The degradation of many proteins requires their prior attachment to ubiquitin. Proteolytic substrates are characteristically multiubiquitinated through the formation of ubiquitin-ubiquitin linkages. Lys-48 of ubiquitin can serve as a linkage site in the formation of such chains and is required for the degradation of some substrates of this pathway in vitro. We have characterized the recessive and dominant effects of a Lys-48-to-Arg mutant of ubiquitin (UbK48R) in Saccharomyces cerevisiae. Although UbK48R is expected to terminate the growth of Lys-48 multiubiquitin chains and thus to exert a dominant negative effect on protein turnover, overproduction of UbK48R in wild-type cells results in only a weak inhibition of protein turnover, apparently because the mutant ubiquitin can be removed from multiubiquitin chains. Surprisingly, expression of UbK48R complements several phenotypes of polyubiquitin gene (UB14) deletion mutants. However, UbK48R cannot serve as a sole source of ubiquitin in S. cerevisiae, as evidenced by its inability to rescue the growth of ubi1 ubi2 ubi3 ubi4 quadruple mutants. When provided solely with UbK48R, cells undergo cell cycle arrest with a terminal phenotype characterized by replicated DNA, mitotic spindles, and two-lobed nuclei. Under these conditions, degradation of amino acid analog-containing proteins is severely inhibited. Thus, multiubiquitin chains containing Lys-48 linkages play a critical role in protein degradation in vivo.

Cell Cycle

Occurrence of 222Rn and progeny in natural gas processing plants in western Canada.

In Western Canada, there are many plants that process natural gas to remove impurities (CO2, H2S, H2O) and recover natural gas liquids (propane, butane, etc.). Trace quantities of 222Rn present in the inlet stream are concentrated in streams rich with propane. Potential hazards to plant operators include direct inhalation of 222Rn and progeny; exposure to gamma radiation from short-lived progeny deposited inside equipment; or inhalation of 210Pb when contaminated equipment is opened for repair. Twenty-four plants operated by seven companies cooperated to assess these potential hazards. The findings indicate a substantial flux of 222Rn and progeny passing through the plants, but little accumulation of radionuclides. In no case was there evidence of significant exposure of plant operators or maintenance personnel to ionizing radiation. Further investigation of pipeline operations, and chemical operations using natural gas liquids as feed stock, is recommended.

Bismuth

Mapping of functional domains within the v-erb A oncogene protein: the remnants of the hormone binding domain play multiple, vital roles in protein action.

The v-erb A oncogene represents a virally-transduced variant of a thyroid hormone receptor. Biochemical characterization of a series of mutant v-erb A proteins demonstrates that nuclear localization and DNA binding are both necessary for v-erb A function in the neoplastic cell and are mediated by multiple, overlapping domains within the v-erb A polypeptide. Domains of the v-erb A protein necessary for sequence-specific and sequence-independent DNA binding are distinguishable from one another, and encompass sequences projecting beyond the zinc-finger motifs themselves. Although unable to bind T3 thyroid hormone, the remnants of the hormone binding domain continue to play unanticipated essential roles in v-erb A protein function.

Cell Nucleus

Myocardial perfusion imaging with a new radiotracer, technetium-99m-hexamibi (methoxy isobutyl isonitrile): comparison with thallium-201 imaging.

Technetium-99m-hexamibi (methoxy isobutyl isonitrile) is a Tc-99m-hexakis analog that can be used as a myocardial perfusion imaging agent. This is a report of an initial study that was performed in four institutions to assess the feasibility of Tc-99m-hexamibi myocardial imaging for the detection of coronary artery disease in patients undergoing treadmill stress test. Thirty-three patients referred for evaluation of chest pain had two exercise stress tests, one with Tl-201 and at least 24 hours after, and a second one with Tc-99m-hexamibi. Myocardial planar imaging started 60 minutes after injection at stress of 10-20 mCi of Tc-99m-hexamibi. Because this agent does not redistribute in myocardium after a stress injection, a second injection of 10-20 mCi of Tc-99m-hexamibi was performed with the patient at rest a few days later. Qualitative assessment of both Tl-201 and Tc-99m-hexamibi myocardial distribution was performed in 297 left ventricle segments (three segments of each of three views). There was a good correlation for the presence of normality, scar, or ischemia with the two radiopharmaceuticals, both on a segment by segment (259/297, or 87.2%) and patient-by-patient basis (29/33, or 87.9%). The number of segments found ischemic with Tl-201 and with Tc-99m-hexamibi were nearly equal, as were the number that were normal with one radiopharmaceutical and ischemic by the other. This initial study demonstrates that it is possible to detect stress-induced abnormalities of myocardial perfusion with Tc-99m-hexamibi similar to Tl-201 imaging.

Adult

[Lepromatous leprosy: clinical and electrophysiological arguments in favor of axonal multi-neuritis].

UNLABELLED: This work was undertaken because there were only few reports on neurological aspects on lepromatous leprosy. We studied 30 patients suffering from lepromatous leprosy who, at their first visit to the Institute had never been treated. The clinical examination included a quantitative evaluation of the neurological status following the method developed by Pearson. Motor and sensory nerve conduction velocities were measured: values of conduction velocity and distal amplitude were analysed and compared to those of a group of 22 healthy subjects. IN CONCLUSION: (a) There is a high frequency of clinical and especially electrophysiological neurological impairment. This impairment can be extremely precocious and may happen shortly after the first cutaneous signs. (b) Nervous impairment is diffuse, bilateral but not homogeneous. These are characteristics of mononeuritis multiplex. Impairement is predominantly sensitive and tactile sensibility is more involved than thermo-algic sensation. (c) The radial superficial nerve is the most frequently involved clinically and electrophysiologically. (d) The electrophysiological results, showing a normal or slightly reduced conduction velocity and a low amplitude of evoked potentiel are in favour of a predominantly axonal damage.

Axons

The avian erythroblastosis virus erbA oncogene encodes a DNA-binding protein exhibiting distinct nuclear and cytoplasmic subcellular localizations.

The protein product of the v-erbA oncogene of avian erythroblastosis virus was analyzed by use of site-specific antisera. The v-erbA protein was found to exist in distinct nuclear and cytoplasmic forms. Both nuclear and cytoplasmic species of the v-erbA protein were capable of binding to DNA, a property predicted based on the structural relatedness the v-erbA polypeptide shares with the thyroid and steroid hormone receptors. A mutation within the v-erbA coding region which inhibited DNA binding and nuclear localization also inhibited the ability of the v-erbA protein to potentiate erythroid transformation, consistent with a model of the v-erbA protein as a transcriptional regulator.

Alpharetrovirus

Genetic dissection of functional domains within the avian erythroblastosis virus v-erbA oncogene.

The avian erythroblastosis virus v-erbA locus potentiates the oncogenic transformation of erythroid and fibroblast cells and is derived from a host cell gene encoding a thyroid hormone receptor. We report here the use of site-directed mutagenesis to identify and characterize functional domains within the v-erbA protein. Genetic lesions introduced into a putative hinge region or at the extreme C-terminus of the v-erbA coding domain had no significant effect on the biological activity of this polypeptide. In contrast, mutations introduced within the cysteine-lysine-arginine-rich center of the v-erbA coding region, a DNA-binding domain in the thyroid and steroid hormone receptors, abolished or severely compromised the ability of the viral protein to function. Our results suggest that the mechanism of action of the v-erbA protein in establishing the neoplastic phenotype is closely related to its ability to interact with DNA, presumably thereby altering expression of host target genes by either mimicking or interfering with the action of the normal c-erbA gene product.

Alpharetrovirus