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Biomedical subjects

C Simard

Publications and source records attributed to C Simard.

At least 55 records · Page 3Linked to original sources

Oxidative capacity of the skeletal muscle and lactic acid kinetics during exercise in normal subjects and in patients with COPD.

Early lactic acidosis during exercise and abnormal skeletal muscle function have been reported in chronic obstructive pulmonary disease (COPD) but a possible relationship between these two abnormalities has not been evaluated. The purpose of this study was to compare and correlate the increase in arterial lactic acid (La) during exercise and the oxidative capacity of the skeletal muscle in nine COPD patients (age = 62 +/- 5 yr, mean +/- SD, FEV1 40 +/- 9% of predicted) and in nine normal subjects of similar age (54 +/- 3 yr). Following a transcutaneous biopsy of the vastus laterialis, each subject performed a stepwise exercise test on an ergocycle up to his or her maximal capacity during which 5-breath averages of oxygen consumption (Vo2), and serial La concentration measurements were obtained. From the muscle biopsy specimen, the activity of two oxidative enzymes, citrate synthase (CS) and 3-hydroxyacyl CoA dehydrogenase (HADH), and of three glycolytic enzymes, lactate dehydrogenase, hexokinase, and phosphofructokinase were determined. The La/Vo2 relationship during exercise was fitted by an exponential function in the form La = a + bvo2, where be represents the shape of the relationship. The activity of the oxidative enzymes was significantly lower in COPD than in control subjects (22.8 +/- 3.3 versus 36.8 +/- 8.6 mumol/min/g muscle for CS, and 3.1 +/- 1.1 versus 5.5 +/- 1.4 mumol/min/g for HADH, p < 0.0005) and the increase in lactic acid was steeper in COPD (b = 4.3 +/- 2.0 versus 2.1 +/- 0.2 for normal subjects, p = 0.0005). A significant inverse relationship was found between CS, HADH, and b. No difference was found between the two groups for the glycolytic enzymes. We conclude that in COPD the increase in arterial La during exercise is excessive, the oxidative capacity of the skeletal muscle is reduced, and that these two results are interrelated.

3-Hydroxyacyl CoA Dehydrogenases↗

Skeletal muscle adaptation to endurance training in patients with chronic obstructive pulmonary disease.

The purpose of this study was to evaluate the physiologic responses to endurance training in patients with moderate to severe airflow obstruction by specifically looking at changes in skeletal muscle enzymatic activities. Eleven patients (age = 65 +/- 7 yr, mean +/- SD, FEV1 = 36 +/- 11% of predicted value, range = 24 to 54%) were evaluated before and after an endurance training program. Each evaluation included a percutaneous biopsy of the vastus lateralis and a stepwise exercise test on an ergocycle up to his/her maximal capacity. VE, VO2, VcO2, and serial arterial lactic acid concentration were measured during the exercise test. The activity of two oxidative enzymes, citrate synthase (CS) and 3-hydroxyacyl-CoA dehydrogenase (HADH), and of three glycolytic enzymes, lactate dehydrogenase, hexokinase, and phosphofructokinase was determined. The training consisted of 30-min exercise sessions on a calibrated ergocycle, 3 times a week for 12 wk. The aerobic capacity was severely reduced at baseline (VO2max = 54 +/- 12% of predicted) and increased by 14% after training (p < 0.05). For an identical exercise workload, there was a significant reduction in VE (34.5 +/- 10.0 versus 31.9 +/- 9.0 L/min, p < 0.05) and in arterial lactic acid concentration (3.4 +/- 1.3 versus 2.8 +/- 0.9 mmol/L, p < 0.01) after training. The lactate threshold also increased after training (p < 0.01) while the activity of the three glycolytic enzymes was similar at the two evaluations. In contrast, the activity of CS and HADH increased significantly after training (22.3 +/- 3.5 versus 25.8 +/- 3.8 mumol/min/g muscle for CS, p < 0.05, and 5.5 +/- 2.9 versus 7.7 +/- 2.5 mumol/min/g for HADH, p < 0.01). A significant inverse relationship was found between the percent changes in the activity of CS and HADH, and the percent changes in arterial lactic acid during exercise (p = 0.01). We conclude that endurance training can reduce exercise-induced lactic acidosis and improve skeletal muscle oxidative capacity in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

3-Hydroxyacyl CoA Dehydrogenases↗

Leisure activities and service knowledge and use among the rural elderly.

This exploratory study uses Andersen's service utilization model to examine the relationship between the leisure activity patterns of older people and their knowledge and use of health and social services. Hierarchical stepwise multiple regression analyses of data from 418 people ages 65 and older in rural Qu/ebec revealed that leisure activity patterns may explain a greater amount of variation in service knowledge and use than conventional need characteristics such as physical and psychological health. Various activity patterns were significantly related to knowledge and use of services even after controlling for variables such as age and health status. Although some types of leisure activities appeared to augment knowledge and use of services, others seemed to deter it. Future explanatory models of service utilization among the elderly should be expanded to include leisure activity patterns.

Aged↗

Linkage results on 11Q21-22 in Eastern Quebec pedigrees densely affected by schizophrenia.

The 11q21-22 region is of interest for schizophrenia because several candidate genes are located in this section of the genome. The 11q21-22 region, including DRD2, was surveyed by linkage analysis in a sample (N = 242) made of four large multigenerational pedigrees densely affected by schizophrenia (SZ) and eight others by bipolar disorder (BP). These pedigrees were ascertained in a large area of Eastern Quebec and Northern New Brunswick and are still being extended. Family members were administered a "consensus best-estimate diagnosis procedure" (DSM-III-R criteria) blind to probands and relatives' diagnosis and to pedigree assignment (SZ or BP). For linkage analysis, 11 microsatellite polymorphism (CA repeat) markers, located at 11q21-22, and comprising DRD2, were genotyped. Results show no evidence of a major gene for schizophrenia. However, a maximum lod score of 3.41 at the D11S35 locus was observed in an affected-only analysis of one large SZ family, pedigree 255. Whether or not the positive linkage trend in pedigree 255 reflects a true linkage for a small proportion of SZ needs to be confirmed through the extension of this kindred and through replication.

Base Sequence↗

Sequence analysis of the UL39, UL38, and UL37 homologues of bovine herpesvirus 1 and expression studies of UL40 and UL39, the subunits of ribonucleotide reductase.

We sequenced the region of the bovine herpesvirus type 1 (BHV-1) genome corresponding to map units 0.172-0.230 (7964 bp), representing the UL39, UL38, and UL37 homologues of herpes simplex virus which encode the large subunit of ribonucleotide reductase (RR) and components of the viral capsid and the tegument, respectively. To discriminate between two potential initiator AUGs of the UL39 gene, the 5' end of the mRNA was mapped by S1 nuclease protection assays. Comparison of the amino acid sequences of the three BHV-1 proteins with analogous polypeptides from several other herpesviruses revealed significant levels of homology. We also compared the expression kinetics of the large (R1, UL39) versus the small (R2, UL40) RR subunits during the course of in vitro BHV-1 infection by Western blotting using specifically developed and calibrated antisera. Our results show that the R1 protein was synthesized earlier than its R2 counterpart. Moreover, the R1 protein accumulated to a higher level than the R2 protein even though the R2 transcript was in greater abundance than the R1 mRNA. This is discussed with regard to the translational efficiency of their transcripts.

Amino Acid Sequence↗

Establishment of leukemic T-cell lines from mice inoculated with the MAIDS defective virus.

Mice inoculated with replication-competent stocks of the murine acquired immunodeficiency syndrome (MAIDS) virus are severely immunocompromised and proned to the development of T- and B-cell lymphomas. We have studied the development of T-cell lymphomas in C57BL/6 and RF/J mice inoculated with helper-free stocks of the MAIDS defective virus. We observed the expansion of T cell clones (detected by TCR gene rearrangements and by transplantation) only rarely in diseased C57BL/6 mice and slightly more frequently in RF/J mice. We succeeded in establishing four transplantable T cell tumors and malignant cell lines. The three cell lines from RF/J mice were immature T-cells (Thy-1+, CD3-, CD4+, CD8+, Mac-1+), while the line from the C57BL/6 mouse had the phenotype of mature T-cells (Thy-1+, CD3+, CD4+, CD8-). All lines were virus-producers despite the fact that helper-free stocks of the virus were inoculated. These helper MuLVs most likely originated from endogenous MuLV sequences. Also, the defective viral genome was clearly detectable in one cell line and was rearranged in two other lines. These established cell lines may be useful to determine whether they share some of the characteristics of the anergic T-cells in vivo and to study the role of the MAIDS defective virus in T cell transformation.

Animals↗

Evidence that the amino acid region 124-203 of glycoprotein G from the respiratory syncytial virus (RSV) constitutes a major part of the polypeptide domain that is involved in the protection against RSV infection.

The first 230 residues of the 298-amino acid glycoprotein G of respiratory syncytial virus (RSV) are sufficient to confer complete resistance to challenge with live RSV, whereas the first 180 residues completely failed (Olmsted et al. (1989) J. Virol. 63, 411-420). The characterization of a protective epitope corresponding to the amino acid region 174-187 of the G protein (Trudel et al. (1991) Virology 185, 749-757) suggests that interruption of this region in the 180 residue truncated polypeptide may be responsible for its inability to confer protection and consequently that the 174-187 region may play a major role in the protection effected by the protein G. To support these hypotheses, we examined the ability of the amino acid region 124-203 of glycoprotein G to confer protection. The corresponding peptide was expressed as a non-fusion protein in a recombinant vaccinia virus designated VG27. Immunization of BALB/c mice with this recombinant efficiently induced the production of antibodies capable of recognizing both the parental glycoprotein G and peptide 174-187. Furthermore, upon challenge with RSV, a significant decrease of infectious particles was found in the lungs of mice immunized with VG27 as compared with non-immunized mice. Our results suggest that the 124-203 amino acid region of the RSV G protein constitutes a major part of the domain involved in protection.

Animals↗

A vibrational spectroscopic study of the self-association of polyinosinic acid and polyguanylic acid in aqueous solution.

We have studied by Raman and ir spectroscopy the structure of self-associated polyinosinic acid and polyguanylic acid in aqueous solution. The results are consistent with the formation of a four-stranded complex, which melts cooperatively near 60 degrees C in the case of poly(I) in the presence of K+ ions. The conformation of the ribose in both systems is mixed C2'-endo/C3'-endo, giving a structure that is intermediate between the extremes proposed previously from x-ray diffraction studies. Characteristic Raman bands for the C2'-endo ribose conformation in polyribonucleotides are identified. The four-stranded structure of poly(I) appears to be very flexible, with approximately 15% of the tetrameric segments being disrupted and approximately 30% of the ribose units adopting a disordered conformation prior to melting. This disordering process increases to approximately 75% above the melting transition, with the remaining approximately 25% of the ribose units keeping an ordered C2'-endo or C3'-endo conformation.

Nucleic Acid Conformation↗

Murine AIDS is initiated in the lymph nodes draining the site of inoculation, and the infected B cells influence T cells located at distance, in noninfected organs.

The infection of cells which belong to the B-cell lineage is thought to be the primary event leading to the phenotypic and functional alterations seen in the murine AIDS (M. Huang, C. Simard, D. Kay, and P. Jolicoeur, J. Virol. 65:6562-6571, 1991). Using in situ hybridization, we studied the time course of the anatomic distribution of the murine AIDS-infected B cells in C57BL/6 mice inoculated intraperitoneally or in the foot pad with helper-free stocks of the defective murine AIDS virus. The local lymph nodes draining the injection site (the mediastinal or popliteal lymph nodes) were the primary organs in which infected B cells could be detected. From this initial site, the proliferating infected B cells were found to migrate progressively to most of the other lymph nodes and to the spleen. The bone marrow cells (containing the precursor B cells) were not found to be infected by the virus. These results suggest that the defective murine AIDS virus infects mature Ly-1- B cells present in lymph nodes. We compared the concanavalin A response of the T cells at an early time postinoculation, before all lymphoid organs are infiltrated with infected B cells. In lymphoid organs free of infected B cells, T cells were found to be hyperresponsive. In lymphoid organs in which infected B cells were present, T cells were hyporesponsive. These data suggest that infected B cells influence distant T cells, maybe by the release of a circulating factor or through another uninfected cell population activated by the infected B cells.

Animals↗

Specific expression of the human CD4 gene in mature CD4+ CD8- and immature CD4+ CD8+ T cells and in macrophages of transgenic mice.

The CD4 protein plays a critical role in the development and function of the immune system. To gain more insight into the mechanism of expression of the human CD4 gene, we cloned 42.2 kbp of genomic sequences comprising the CD4 gene and its surrounding sequences. Studies with transgenic mice revealed that a 12.6-kbp fragment of the human CD4 gene (comprising 2.6 kbp of 5' sequences upstream of the transcription initiation site, the first two exons and introns, and part of exon 3) contains the sequences required to support the appropriate expression in murine mature CD4+ CD8- T cells and macrophages but not in immature double-positive CD4+ CD8+ T cells. Expression in CD4+ CD8+ T cells was found to require additional regulatory elements present in a T-cell enhancer fragment recently identified for the murine CD4 gene (S. Sawada and D. R. Littman, Mol. Cell. Biol. 11:5506-5515, 1991). These results suggest that expression of CD4 in mature and immature T-cell subsets may be controlled by distinct and independent regulatory elements. Alternatively, specific regulatory elements may control the expression of CD4 at different levels in mature and immature T-cell subsets. Our data also indicate that mouse macrophages contain the regulatory factors necessary to transcribe the human CD4 gene.

Animals↗

Influence of electrical stimulation on enzymatic activity of old rat muscles during hindlimb suspension.

1. The purpose of this study was to determine the effects of electrical stimulation on the muscles of older rats (21-24 months old) during suspension hypokinesia/hypodynamia. The rats' hindlimbs were suspended for three weeks, after which the activities of three enzymes were measured in the extensor digitorum longus, the medial gastrocnemius and the soleus muscles. 2. The activity of phosphofructokinase decreased in the soleus muscle and in the white part of the medial gastrocnemius muscle. Malate dehydrogenase and beta-hydroxyacyl-CoA-dehydrogenase showed decreased activity in the red part of the medial gastrocnemius muscle. 3. When electrical stimulation was applied, the activity of the glycolytic enzyme phosphofructokinase increased substantially in all studied muscles. The activity of the malate dehydrogenase and beta-hydroxyacyl-CoA-dehydrogenase enzymes was not influenced by electrical stimulation in the majority of the studied muscles. 4. These results suggest that our electrical stimulation model not only prevents loss of phosphofructokinase activity of aged muscles but increases the activity of anaerobic glycolysis metabolism without affecting the oxidative and fatty acid pathways.

Aging↗

Prediction of maximal aerobic power from a submaximal exercise test performed by paraplegics on a wheelchair ergometer.

The aim of the present study was to verify the basic principles underlying the prediction of VO2 peak from a submaximal exercise test performed by paraplegics on a wheelchair ergometer and thus to propose regression equations of VO2 peak prediction. Forty-six paraplegic subjects (mean age = 33.2 +/- 8.7 years) with a traumatic lesion (T1-L3) performed a graded exercise test on a wheelchair ergometer until exhaustion. The test started with an initial workload of 0 watts, with an increment of 6 watts per 2 minutes. Measurements included power output (W), heart rate (HR) and oxygen consumption (VO2) throughout the test. Linear relationships were observed between VO2 and W (VO2 = 0.79 + 0.02 W, r = 0.80, SEE = 0.22 l min-1) as well as between %VO2 max and % maximal heart rate (% VO2 max = 8.7 + 0.83 %HR, r = 0.83 SEE = 10.5%). Combination of the two equations for estimating VO2 peak led to a linear relationship between the estimated and measured VO2 peak. Nonetheless, the strength and accuracy of the prediction were low (r = 0.49, SEE = 0.29 l min-1). Participation in aerobic exercise, body mass and lean body mass, introduced as correction factors in the regression equation, significantly improved the strength and the accuracy of the prediction (r = 0.85, SEE = 0.29 l min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Relationship of impairment and functional ability to habitual activity and fitness following spinal cord injury.

Associations between a physically active leisure, physical fitness, impairment and disability have been tested in 123 volunteers (73 with paraplegia and 50 with quadriplegia). Active physical leisure was assessed by the questionnaire of Godin and Shephard (Canadian Journal of Sports Sciences 10, 141-6 1985). Fitness measures included body mass index, peak oxygen intake on a wheelchair ergometer, and tests of muscle strength and endurance (peak isokinetic torque, average muscle power and total muscle work for shoulder flexion, shoulder adduction and elbow flexion at movement speeds of 60 degrees and 180 degrees s-1). Primary impairment was assessed by the ISMGF scale, and secondary impairment was judged from reported pressure scores, spasticity, and urinary infections over the previous 12 months. Scores for self-care and mobility were obtained using a modified Barthel Index. Physically active leisure and fitness were unrelated to secondary impairment. However, functional ability for a given primary impairment was significantly correlated with peak oxygen intake and the three indices of muscle strength, particularly in individuals with high level lesions. Associations between physical activity and functional ability were weaker, but tended in the same direction. Although longitudinal studies are needed to prove the causality of these relationships, the findings point towards a significant influence of fitness status upon functional ability. Rehabilitation teams should thus give a stronger emphasis to systematic exercise conditioning programmes when planning overall treatment following SCI.

Activities of Daily Living↗

[Maximal physiological response during exertion in quadriplegic subjects].

Devices used for the assessment of physical working capacity in quadriplegics may be determinant in terms of efficiency during maximal exercise testing. The aim of this study was to compare the physiological responses of a group of quadriplegics during graded exercise tests on arm cranking ergometer (ACE) and wheelchair ergometer (WE). Fifty subjects, age 34.1 (+/- 9.5) years, participated in the study. Measurements comprised heart rate, ventilation, oxygen consumption, and power output. Unlike other studies suggesting a higher physical working capacity on ACE compared with WE, no significant differences were observed in physiological measurements between the two ergometers. However, power output on ACE was 65% higher than that of WE (p < or = 0.001). These results suggest that power output of quadriplegics on ACE is higher due to differences in mechanical patterns required to induce movements of propelling (arm cranking vs. rolling movements). The need to link the assessment results to the type of locomotion used by the spinal cord injured persons may suggest the use of WE for testing and training in such individuals.

Adaptation, Physiological↗

Sequencing and 5'- and 3'-end transcript mapping of the gene encoding the small subunit of ribonucleotide reductase from bovine herpesvirus type-1.

The complete nucleotide sequence of the gene encoding the small subunit of ribonucleotide reductase (RNR) from bovine herpesvirus type-1 (BHV-1) was determined. The genomic DNA fragment sequenced also represented regions corresponding to the carboxy termini of RNR large subunit and of a virion protein causing host shut-off. The small subunit polypeptide was constituted of 314 amino acid residues totalling 35.25 kDa. The major transcription initiation and termination sites of the small subunit mRNA were located 95 bases upstream and 88 nucleotides downstream from the coding region, respectively. These findings indicate that the mRNA was 1128 bases long which correlated well with the size of the polyadenylated transcript detected in Northern blot analysis (1.3 kb). Within the RNR large subunit coding region, a TATA box and two CAAT box motifs were found 26, 104, and 190 nucleotides, respectively, upstream from the transcription initiation site of the small subunit mRNA. In contrast to previous studies (Slabaugh et al., J. Virol. 1988, 62, 519-527; Boursnell et al., Virology 1991, 184, 411-416), our comparative analysis of five herpesviruses, one iridovirus, and one poxvirus small subunit protein sequences suggested that the seven viruses arose from a common lineage.

Amino Acid Sequence↗

Characterization and transcript mapping of a bovine herpesvirus type 1 gene encoding a polypeptide homologous to the herpes simplex virus type 1 major tegument proteins VP13/14.

Using in vitro translation of hybrid-selected mRNA, we have previously shown that bovine herpesvirus type 1 HindIII fragment M encodes an abundant 94K polypeptide. Using immunoprecipitation and sequencing analyses, it has now been shown that the polypeptide is related to the major tegument protein VP8 and is homologous to the herpes simplex virus type 1 major tegument proteins VP13/14. The sequence of the VP8 gene (field isolate 34) is reported and compared to published data. Several differences between the sequences were detected, resulting particularly from base insertions/deletions generating three major frameshifts affecting an area of 87 amino acid residues of the encoded protein. In addition, sequence comparison revealed 29 single base alterations, excluding frameshift regions, producing 17 amino acid substitutions. Overall, 14.1% of the deduced amino acid sequences were divergent. We have also established that the last 152 nucleotides of the previously reported sequence correspond to the sequence of the minus not the sense strand. Finally, we report that the 4.4 kb transcript of the VP8 gene is initiated 39 nucleotides upstream from the translation start codon.

Amino Acid Sequence↗

Susceptibility of inbred strains of mice to murine AIDS (MAIDS) correlates with target cell expansion and high expression of defective MAIDS virus.

Murine AIDS (MAIDS) is readily induced by the Duplan strain of defective murine leukemia virus in susceptible C57BL/6 mice. To identify mouse strains resistant to MAIDS, and to understand the genetic factors controlling susceptibility to the disease, we screened more than 20 inbred strains of mice for their susceptibility to MAIDS. For this study, mice of the Fv-1n/n, Fv-1b/b, or Fv-1n/b genotype were inoculated with stocks of defective MAIDS virus pseudotyped with N-tropic, B-tropic, or NB-tropic helper murine leukemia virus, respectively. Strains could be classified as susceptible, resistant, or moderately resistant. None of the individual H-2 haplotypes examined appears to explain resistance to MAIDS by itself. However, a very good correlation between the susceptibility or resistance phenotype and the presence or absence of defective proviral DNA and RNA in the spleen of these animals was found. Since the presence of defective proviral DNA and RNA reflects the oligoclonal proliferation of the cells infected by the defective MAIDS virus, our results strongly suggest that this target cell expansion is genetically controlled and is necessary and perhaps even sufficient for the development of the disease.

3T3 Cells↗