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Biomedical subjects

J Mercier

Publications and source records attributed to J Mercier.

At least 91 records · Page 5Linked to original sources

Insulin sensitivity measured with the minimal model is higher in moderately overweight women with predominantly lower body fat.

Lower-body obesity is associated with a lower incidence of diabetes and high values of HDL2 cholesterol and thus seems to have a metabolic profile opposite to upper-body obesity. We measured insulin sensitivity by the minimal model procedure in 20 lower-body overweight women (age 40.3+/-2.3 years, waist-to-hip ratio WHR 0.75+/-0.01, body mass index BMI 29.9+/-0.7 kg/m2), compared to 18 women with a similar degree of upper-body obesity (age 40.4+/-3years, WHR 0.91+/-0.02, BMI 29.4+/-0.7 kg/m2) and 28 control women matched for age and height. Insulin sensitivity and basal insulin effect were higher in lower-body obesity (11.2+/-0.2 min-1/[microU/ml]x 10(-4) and 0.8+/-0.2 min(-1) x 10(-2), respectively) compared to upper-body obesity (2.6+/-0.4, p < 0.001 and 0.3+/-0.05, p < 0.01) and controls (6.1+/-0.7, p < 0.02 and 0.5+/-0.07, p < 0.02). It is suggested that lower-body obesity could be associated with a reduced free fatty acids-induced inhibition of insulin action by the Randle mechanism. This study confirms that body fat distribution is a more relevant determinant than obesity itself in the pathogenesis of insulin resistance. Contrary to upper-body obesity, moderate lower-body overweight seems to be associated with high values on insulin sensitivity.

Adult↗

Location score and haplotype analyses of the locus for autosomal recessive spastic ataxia of Charlevoix-Saguenay, in chromosome region 13q11.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a clinically homogeneous form of early-onset familial spastic ataxia with prominent myelinated retinal nerve fibers. More than 300 patients have been identified, and most of their families originated in the Charlevoix-Saguenay region of northeastern Quebec, where the carrier prevalence has been estimated to be 1/22. Consistent with the hypothesis of a founder effect, we observed excess shared homozygosity at 13q11, among patients in a genomewide scan of 12 families. Analysis of 19 pedigrees demonstrated very tight linkage between the ARSACS locus and an intragenic polymorphism of the gamma-sarcoglycan (SGCG) gene, but genomic DNA sequence analysis of all eight exons of SGCG revealed no disease-causing mutation. On the basis of haplotypes composed of seven marker loci that spanned 11.1 cM, the most likely position of the ARSACS locus was 0.42 cM distal to the SGCG polymorphism. Two groups of ARSACS-associated haplotypes were identified: a large group that carries a common SGCG allele and a small group that carries a rare SGCG allele. The haplotype groups do not appear to be closely related. Therefore, although chromosomes within each haplotype group may harbor a single ARSACS mutation identical by descent, the two mutations could have independent origins.

Alleles↗

Lactate transport activity in rat skeletal muscle sarcolemmal vesicles after acute exhaustive exercise.

The effect of a single bout of exhaustive exercise on muscle lactate transport capacity was studied in rat skeletal muscle sarcolemmal (SL) vesicles. Rats were assigned to a control (C) group (n = 14) or an acutely exercised (E) group (n = 20). Exercise consisted of treadmill running (25 m/min, 10% grade) to exhaustion. SL vesicles purified from C and E rats were sealed because of sensitivity to osmotic forces. The time course of 1 mM lactate uptake in zero-trans conditions showed that the equilibrium level in the E group was significantly lower than in the C group (P < 0.05). The initial rate of 1 mM lactate uptake decreased significantly from 2.44 +/- 0.22 to 1.03 +/- 0.08 nmol. min(-1). mg protein(-1) (P < 0.05) after exercise, whereas that of 50 mM lactate uptake did not differ significantly between the two groups. For 100 mM external lactate concentration ([lactate]), exhaustive exercise increased initial rates of lactate uptake (219.6 +/- 36.3 to 465.4 +/- 80.2 nmol. min(-1). mg protein(-1), P < 0.05). Although saturation kinetics were observed in the C group with a maximal transport velocity of 233 nmol. min(-1). mg protein(-1) and a Michealis-Menten constant of 24.5 mM, saturation properties were not seen after exhaustive exercise in the E group, because initial rates of lactate uptake increased linearly with external [lactate]. We conclude that a single bout of exhaustive exercise significantly modified SL lactate transport activity, resulting in a decrease in 1 mM lactate uptake and was associated with alterations in the saturable properties at [lactate] above 50 mM. These results suggest that changes in sarcolemmal lactate transport activity may alter lactate and proton exchanges after exhaustive exercise.

Animals↗

Early hemorheologic aspects of overtraining in elite athletes.

A standardized questionnaire has been proposed by the French consensus group on overtraining of the Société Française de Médecine du Sport (SFMS) and allows the calculation of a 'score' that may help to quantify the early clinical symptoms of the overtraining syndrome in sportsmen submitted to a heavy training program. We investigated a possible relationship between this score and blood rheology in 36 male elite sportsmen (national level in football, volleyball and karate; age: 17-33 yr) who underwent a standardized check-up including biological measurements and an exercise-test. The overtraining score ranged between 0 and 21 items and was correlated with blood viscosity (r = 0.413, p < 0.02). This correlation was explained by a correlation of this score with plasma viscosity (r = 0.512, p < 0.01) and hematocrit (r = 0.387, p < 0.05). When subjects with a high score (>6) were compared to subjects with a lower score they appeared to have a higher blood viscosity at native (but not corrected) hematocrit (3.18 +/- 0.01 vs. 2.89 +/- 0.05 mPa.s, p < 0.02), explained by higher values in both plasma viscosity (1.39 +/- 0.02 vs. 1.31 +/- 0.02 mPa.s, p < 0.01) and hematocrit (42.8 +/- 0.45 vs. 41.1 +/- 0.44, p < 0.05). By contrast, there was no difference in RBC deformability and aggregation. Overtrained subjects have also lower levels of zinc (0.72 +/- 0.024 vs. 0.84 +/- 0.023 mg/l, p < 0.01), ferritin (55.1 +/- 7.3 vs. 92.3 +/- 9.4 ng/ml), and IGF-binding protein 3 (3.4 +/- 0.22 vs. 4.52 +/- 0.4 ng/ml). Neither zinc nor ferritin status were likely to explain the rheologic alterations since disturbances in zinc or iron are rather associated with abnormalities in erythrocyte deformability or aggregability. Therefore, the early signs of overtraining in elite sportsmen are associated with a hemorheologic pattern that suggests some degree of reversal of the 'autohemodilution' associated with fitness in athletes.

Adult↗

[Vertical development of the face and cervical spine. Diagnostic and therapeutic significance in orthodontics and maxillofacial surgery].

Vertical growth of the cervical spine, of the mandibula and the upper maxilla are normally anatomically and physiologically correlated. At a very early age the relationships are established between the cervical spine and the angle of the mandibula which is normally level with C2's antero-inferior angle. A parallelism can be noticed between the rhythms of the vertical growth of the cervical spine and the changes of the maxillary in relation to the skull. So relationships are gradually established between the palate level, the top of the odontoid, and the foramen magnum. These relationships are well objectivized on a lateral teleradiography by Delaire' analysis. Lateral teleradiography of the situation of the angle of the mandibula, in relation to the basis of the C2 body should be systematic. It provides much information concerning the growth potential of the condylar unit, and makes possible a differential diagnosis between true or false posterior vertical insufficiency (PVI) and true or false posterior vertical excess (PVE) and to recognize clinical types of skeletal class II and class III of vertical origin.

Adolescent↗

[Ewing's sarcoma of the jaw. The value of multidisciplinary management. Apropos of 4 cases].

Ewing's sarcoma is the second most common malignant bone tumor of childhood, yet it is a rare tumor. Primary maxillary localization is unusual and occur in only 1-2% of cases, mostly in the mandible. The prognosis of Ewing's sarcoma has been improving considerably since the introduction of combined modality treatment. The estimated overall survival at 4 years is 75%. It is widely accepted that prompt chemotherapy is necessary to treat occult micrometastasis, present in over 80% of cases at time of diagnosis, and to reduce the tumor size. Prognostic factors correlated with a poor overall survival are large tumor size and poor histologic response to initial chemotherapy. Adequate local control of Ewing's sarcoma can be achieved after chemotherapy, with radical or conservative surgery and radiotherapy. Surgery was recommended whenever possible. Radiation dosage and fields are based upon the quality of surgery and histological response to chemotherapy. Concern has been raised, however, regarding deleterious late effects of radiation in this young population. Conservative surgery and reconstruction are often used to improve functional outcome. We report four cases of Ewing's sarcoma localized to jaw bone and mandible, successfully treated by combined modality treatment.

Adolescent↗

Hemorheology of growth hormone-deficient adults.

Growth hormone deficiency (GHD) in adults results in alterations of body composition and metabolism associated with a lowered insulin sensitivity and an increased cardiovascular risk. Since hemorheologic disturbances (putative factors of vascular risk) are found in the insulin-resistance syndrome, we investigated blood rheology in 9 adults GHDs (5 men, 4 women; age 37.9+/-4.7 years; body mass index 30.23+/-3.2 kg/m2) compared with 23 lean controls and 37 controls matched for sex, age and body mass index. While this sample of GHDs exhibits the typical metabolic picture of this syndrome (upper body overweight with a waist-to-hip ratio at 0.91+/-0.07; low HDL cholesterol at 1.07+/-0.09 mmol x l(-1); low insulin sensitivity with the minimal model technique at 3.3+/-1.29 min(-1)/(microU/ml) x 10(-4)) they have similar values of blood viscosity at either native or corrected hematocrit, similar hematocrit, similar red cell rigidity viscometric index, similar red cell aggregation parameters than overweight matched controls. There is only a nonsignificant tendency for plasma viscosity to be higher in GHDs: this tendency becomes significant when women are considered alone (GHDs: 1.44+/-0.04 mPa.s; controls: 1.31+/-0.04 mPa.s, p<0.05) while it is no longer found in men. This study suggests that GHDs exhibit the classical hemorheological disturbances of non-GHD individuals with the same degree of obesity. There is no evidence for a further impairment of blood rheology associated with the specific metabolic and endocrine pattern of GHDs that may be involved in their increased vascular risk.

Adult↗

Human immunodeficiency virus type 1 vpr protein transactivation function: mechanism and identification of domains involved.

The human immunodeficiency virus type 1 (HIV-1) Vpr protein is a virion-associated protein that localizes in the nucleus of infected cells. Vpr has been shown to facilitate HIV infection of non-dividing cells such as macrophages by contributing to the nuclear translocation of the pre-integration complex. More recently, Vpr expression has been shown to induce an accumulation of cells at the G2 phase of the cell-cycle. We have previously reported that Vpr stimulates reporter gene expression directed from the HIV-1 long terminal repeat (LTR) as well as from heterologous viral promoters. However, the mode of action of Vpr-mediated transactivation remains to be precisely defined. We report here that, for a constant amount of transfected DNA, the level of chloramphenicol acetyltransferase (CAT) mRNA is increased in Vpr-expressing cells using either HIV-1 or a murine leukemia virus (MLV) SL3-3 LTR-CAT reporter construct. Moreover, this Vpr-mediated transactivation requires that promoters direct a minimal level of basal expression. Our mutagenic analysis indicates that the transactivation mediated by Vpr is not dependent on the ability of the protein to localize in the nucleus or to be packaged in the virions. Interestingly, all transactivation-competent Vpr mutants were still able to induce a cell-cycle arrest. Conversely, transactivation-defective mutants lost the ability to mediate cell-cycle arrest, implying a functional relationship between these two functions. Overall, our results indicate that the G2 cell-cycle arrest mediated by Vpr creates a cellular environment where the HIV-1 LTR is transcriptionally more active.

Amino Acid Sequence↗

Noninvasive skeletal muscle lactate detection between periods of intense exercise in humans.

We investigated whether localized 1H nuclear magnetic resonance spectroscopy (NMRS) using stimulated echoes (STEAM) with a long mixing time (t(m)) allowed the suppression of the fat signal and detection of lactate in skeletal muscle. The 1H NMRS sequence was first validated in three isolated and perfused rabbit biceps brachii muscles. Spectra were obtained on a wide-bore spectrometer using a dual-tuned probe (1H and 31P). Death was simulated by ceasing the muscle perfusion, which allowed post-mortem changes to be followed. During and after the simulated death, changes in levels of pH and in content of energy-rich compounds were observed with 31P NMRS. Our results showed an inverse linear relationship between pH and lactate in each of the three rabbits (r = 0.93, P < 0.001; r = 0.92, P < 0.01; r = 0.89, P < 0.01) and a decrease in phosphocreatine and concomitant increase in lactate. We then investigated whether this sequence allowed repeated detection of lactate in human soleus muscle during the recovery between periods of intense exercise (force-velocity test, F-v test). Seven subjects mean age 25.1 (SEM 0.8) years participated in this study. Soleus muscle lactate was detected at rest and for 3 min 30 s of the 5-min recovery between periods using a 2.35-T 40-cm bore magnet spectrometer. Arm venous plasma lactate concentration was measured at rest, during the F-v test when the subject stopped pedalling (S1), and at the end of each 5-min recovery between periods (S2). Results showed that the venous plasma lactate concentration at S1 and S2 increased significantly from the beginning of the F-v test to peak anaerobic power (W(an,peak)) (P < 0.001). The spectra showed that muscle lactate resonance intensity rose markedly when W(an,peak) was achieved. The muscle lactate resonance intensity plotted as a percentage of the resting value increased significantly at W(an,peak) compared with submaximal braking forces (P < 0.05). We concluded from these results that localized 1H NMRS using STEAM with a long t(m) allows suppression of the fat signal and repeated detection of lactate on isolated perfused skeletal muscle in animals and between periods of intense exercise in humans.

Adult↗

Sickle cell trait in Ivory Coast athletic throw and jump champions, 1956-1995.

In order to assess the performance of subjects with sickle cell trait (SCT) during brief and explosive exercise involving mainly alactic anaerobic metabolism, the percentage of athletes with SCT was determined in Ivory Coast track and field throw and jump champions, both men and women, for the period 1956-1995. Thirty-four (27.8%) sickle cell trait carriers (SCTC) were identified among the 122 national champions that we were able to contact. These 34 SCTC had won 78 national titles (24.5%) and established 37 national records (43.5%), distributed among the throw and jump events. These percentages were significantly higher than the prevalence of SCT in the general Ivory Coast population (12.0%). The women's high jump and men's shot put events had the highest percentages of SCTC record holders (90.9% and 87.5%, respectively). Moreover, the two top national record holders and title winners, one man and one woman, were SCTC athletes, and their hemoglobin S percentage (HbS: 39.1% and 39.4%, respectively) and mean corpuscular volume (MCV) excluded an associated alpha-thalassemia. We conclude that the significantly higher percentage of SCTCs among Ivory Coast track and field champions, as compared to the percentage in the general population suggests that SCT may be a determinant factor for success in brief and explosive track and field events involving mainly alactic anaerobic metabolism.

Adult↗

The Professional Transitions Workshop. Cornerstones of practice.

The Professional Transitions Workshop is a new program that integrates the Professional Advancement Program (clinical ladder) and the Professional Model of Practice (primary nursing). Together, these two programs provide the philosophical and structural foundations of professional practice and empower nurses to articulate the defining features of their clinical experiences. Educating staff members about these programs emphasizes critical thinking and storytelling as important skills for the professional nurse. The authors describe the advantages, processes, and outcomes of this change.

Career Mobility↗

Exercise tolerance in heart transplant patients with altered pulmonary diffusion capacity.

To test whether orthotopic heart transplant (OHT) patients with low pulmonary diffusion capacity have a greater limitation to exercise than OHT patients with normal pulmonary diffusion capacity, we investigated cardiorespiratory responses and blood gases in two groups of OHT patients, one with low (LdG) and the other with normal pulmonary diffusion capacity (NdG), during a graded exercise test. The results showed 1) significantly reduced peak power (P < 0.05), peak oxygen uptake (VO2, P < 0.001), peak oxygen pulse (VO2/heart rate, P < 0.01), peak minute ventilation (VE, P < 0.05), and delta PaO2 (peak PaO2 - rest PaO2, P < 0.05) in LdG versus NdG; 2) a nonsignificant decrease in peak heart rate in LdG (P < 0.13, P = 24%); and 3) significant increases in peak respiratory equivalent for oxygen (VE/VO2, P < 0.05) and delta P(A-a)O2 (peak P(A-a)O2 - resting P(A-a)O2, P < 0.05) in LdG versus NdG. No significant difference was found for PaO2 and PaCO2 at rest or at peak exercise between the groups. A strong correlation was found between pulmonary diffusion capacity (TLCO/VA) and peak VO2 (r = 0.81, P < 0.01); that is, TLCO/VA explains 66% of the variance in peak VO2. We conclude that OHT patients with decreased pulmonary diffusion capacity have a lower exercise tolerance than patients with normal pulmonary diffusion capacity. However, because of the lack of exercise-induced hypoxemia, diffusion abnormalities are not the main limiting factor for exercise tolerance in the low diffusion group.

Blood Gas Analysis↗

Blood lactate concentrations during incremental exercise in subjects with sickle cell trait.

The aim of the present study was to assess blood lactate concentrations ([LA], mmol x L(-1)) and oxygen uptake (VO2, L x min(-1), mL x kg(-1) x min(-1)) during incremental exercise in subjects with sickle cell trait (SCT) only, i.e., sedentary subjects with SCT without anemia and/or associated alpha thalassemia. Anemia was ruled out using hemoglobin (Hb) level, and alphathalassemia was ruled out using hemoglobin S (HbS) percentage and concomitant Hb level and mean corpuscular volume (MCV). Comparison was made with control subjects with normal Hb, matched for physical fitness, anthropometric data, and hematological parameters. All subjects underwent an incremental exercise test (IET) using an electromagnetic cycle ergometer. Ventilatory data, i.e., minute ventilation (VE, L x min(-1)), oxygen uptake (VO2, mL x min(-1), mL x Kg(-1) x min(-1)) carbon dioxide production (VO2, mL x min(-1)), ventilatory equivalent for O2(VE x VO2(-1))and for CO2 (VE x VO2(-1)), and respiratory exchange ratio (RER, VO2 x VO2(-1)), were collected every minute during IET and the recovery period using a breath-by-breath automated system. Heart rate (HR, beats x min(-1)) was measured every minute using an EKG. Blood sampling was done every minute during IET and the first 5 min of the recovery period, and then every 5 min until the 20th minute of recovery. [LA] were determined by an enzymatic method with a spectrophotometer. Comparisons of all mean cardioventilatory variables showed no significant differences in subjects with SCT versus controls during IET and recovery. In contrast, analysis of variance revealed significantly lower time courses of [LA] during IET (P < 0.05) and recovery (P < 0.05), whereas time courses of VO2 were similar (P > 0.05). We conclude that the lower [LA] exhibited by subjects with SCT during incremental exercise and the subsequent recovery was not associated with concomitant oxygen uptake impairment.

Adult↗

Skeletal muscle abnormalities in patients with COPD: contribution to exercise intolerance.

Exercise intolerance in COPD patients appears to be in part because of skeletal muscle dysfunction. Studies using biopsy techniques and magnetic resonance spectroscopy have demonstrated changes in enzyme activities and metabolism that indicate reduced oxidative capacity in the peripheral muscles of these patients. Regarding the respiratory muscles, the biochemical characteristics have been studied in only a few works and the results seem to depend on the specific muscle group studied. Several factors, such as hypoxemia, nutritional status, pharmacological treatment, and deconditioning, may be responsible for these skeletal muscle abnormalities. This brief review describes the changes in peripheral and respiratory muscles in COPD patients based on data from the literature. The causes of these muscle abnormalities, their contribution to exercise intolerance, and the effects of training are then discussed. We conclude with suggested directions for future investigation using contemporary noninvasive technologies.

Energy Metabolism↗

Virion-targeted viral inactivation of human immunodeficiency virus type 1 by using Vpr fusion proteins.

Inactivation of progeny virions with chimeric virion-associated proteins represents a novel therapeutic approach against human immunodeficiency virus (HIV) replication. The HIV type 1 (HIV-1) Vpr gene product, which is packaged into virions, is an attractive candidate for such a strategy. In this study, we developed Vpr-based fusion proteins that could be specifically targeted into mature HIV-1 virions to affect their structural organization and/or functional integrity. Two Vpr fusion proteins were constructed by fusing to the first 88 amino acids of HIV-1 Vpr the chloramphenicol acetyltransferase enzyme (VprCAT) or the last 18 C-terminal amino acids of the HIV-1 Vpu protein (VprIE). These Vpr fusion proteins were initially designed to quantify their efficiency of incorporation into HIV-1 virions when produced in cis from the provirus. Subsequently, CD4+ Jurkat T-cell lines constitutively expressing the VprCAT or the VprIE fusion protein were generated with retroviral vectors. Expression of the VprCAT or the VprIE fusion protein in CD4+ Jurkat T cells did not interfere with cellular viability or growth but conferred substantial resistance to HIV replication. The resistance to HIV replication was more pronounced in Jurkat-VprIE cells than in Jurkat-VprCAT cells. Moreover, the antiviral effect mediated by VprIE was dependent on an intact p6(gag) domain, indicating that the impairment of HIV-1 replication required the specific incorporation of Vpr fusion protein into virions. Gene expression, assembly, or release was not affected upon expression of these Vpr fusion proteins. Indeed, the VprIE and VprCAT fusion proteins were shown to affect the infectivity of progeny virus, since HIV virions containing the VprCAT or the VprIE fusion proteins were, respectively, 2 to 3 times and 10 to 30 times less infectious than the wild-type virus. Overall, this study demonstrated the successful transfer of resistance to HIV replication in tissue cultures by use of Vpr-based antiviral genes.

Gene Products, vpr↗