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Biomedical subjects

F Landry

Publications and source records attributed to F Landry.

At least 19 recordsLinked to original sources

Estradiol activates p60src, p53/56lyn and renatured p50/55 protein tyrosine kinases in the dog prostate.

Protein tyrosine kinases (PTKs) are key enzymes implicated in signal transduction pathways regulated by growth factors (GFs). We have previously shown by immunohistochemistry that the level of phosphotyrosine (pY) proteins is increased in prostatic basal epithelial cells following estrogen treatment in castrated dogs. In this study, we investigated if this treatment increases the level and distribution of prostatic PTK activity, and more specifically, if it alters the expression and/or activity of the Src family members p60src and p53/56lyn. Prostates from normal and hyperplastic dog prostates, as well as those from castrated dogs treated with androgens, were also examined. Only the glands obtained from estrogen-treated dogs had a significantly increased total and specific PTK activity, observed uniquely in the particulate extract, as compared to the other types of prostates studied. In addition, this increased activity was correlated upon gel filtration chromatography with the presence of an additional peak of activity with an apparent molecular weight of 130 kDa, which was absent in other prostate fractions presenting only 50 kDa peaks. Using antibodies, we demonstrate that active p60src and pp53/56lyn kinases accounted for 81% of the activity in this 130 kDa peak. On the other hand, in situ renaturation also revealed the presence of still uncharacterized 50/55 kDa PTKs in the 130 kDa peak. Altogether, these findings raise the possibility that these PTKs contribute to the transmission of mitogenic signals originating directly or indirectly from estrogen stimulation of the basal cell layer of the prostate.

Animals

Regulation and activation of focal adhesion kinase and paxillin during the adhesion, proliferation, and differentiation of prostatic epithelial cells in vitro and in vivo.

Focal adhesion kinase (pp125FAK) is a nonreceptor protein tyrosine kinase transducing signals initiated through integrin activation triggered by cell/extracellular matrix (ECM) interactions. To examine its role in epithelial cell adhesion, proliferation, and differentiation, we have studied pp125FAK expression, activity, and association with paxillin in two canine prostate models in which these functions can be selectively regulated: in vitro by vitronectin (VN) and serum factors, and in vivo by sex steroids. Kinetic studies revealed that the adhesion and spreading of prostatic epithelial cells in primary culture was regulated by serum VN and a natural ECM containing VN produced by prostate cells. While barely detectable in freshly isolated prostate cells, proliferating cells, after 72 h in culture, expressed higher levels of FAK mRNA (8-fold), pp125FAK (50-fold), and paxillin (50-fold). In prostate cells with a reduced growth rate after 2 weeks in culture, we observed a decrease in pp125FAK (4-fold) and its transcript (3-fold), but no change in paxillin. In vivo, both proteins were undetectable in normal and hyperplastic glands composed of a well differentiated epithelium, and in prostates restored by androgen supplementation. In contrast, pp125FAK and paxillin were up-regulated by androgen deprivation (castration) and further increased by estrogen treatment, which yielded metaplastic prostates mostly composed of proliferating basal epithelial cells. Moreover, both proteins were constitutively phosphorylated on tyrosine in the metaplastic prostate, as well as in proliferating cultured cells. Together, these results demonstrate that pp125FAK expression is regulated at the protein and mRNA levels and forms active signaling complexes with paxillin when epithelial cells in contact with ECM proteins are induced to proliferate in vivo and in vitro.

Amino Acid Sequence

Phosphotyrosine antibodies preferentially react with basal epithelial cells in the dog prostate.

PURPOSE: Considering the hypothesis that androgen-independent but growth factor dependent epithelial cell division may be important in the development and progression of prostate cancer and that protein tyrosine kinases and phosphotyrosine protein phosphatases are key enzymes modulating the levels of specific phosphotyrosylated proteins implicated in several growth factor regulated signal transduction pathways, our aim was to study the cellular distribution of phosphotyrosine proteins in normal and hyperplastic dog prostates as well as in those of castrated dogs supplemented with either androgens or estrogens in order to modify the relative proportion of basal versus secretory epithelial cells. MATERIALS AND METHODS: Following the determination of optimal conditions to specifically detect phosphotyrosine proteins by a rabbit polyclonal antibody directed against phosphotyrosine, immunohistochemistry was performed on prostate tissue sections from these experimental animals. In addition to morphological criteria, an antibody to high molecular weight cytokeratins and antisera against arginine esterase were used to selectively identify basal and secretory cells. Since prostatic acid phosphatase may be involved in the local regulation of phosphotyrosine proteins, its distribution was also evaluated with a human prostatic acid phosphatase antiserum. RESULTS: In all prostatic tissues examined, basal epithelial cells were preferentially and specifically stained with antiphosphotyrosine. The staining intensity per basal cell was highest in the estrogen-supplemented dogs. In addition, basal cells were numerically increased and all were highly immunoreactive for high molecular weight cytokeratins. In prostates displaying a well-differentiated glandular epithelium, the number of positive basal cells and their staining intensity varied in the following order: normal < hyperplastic < androgen-supplemented dogs. At all times, the levels of phosphotyrosine proteins in prostatic acid phosphatase and arginine esterase positive cells (secretory) remained low. Fibroblasts and smooth muscle cells were unreactive to antiphosphotyrosine, even though estrogen supplementation increased the prostatic stromal volume. CONCLUSIONS: The preferential localization of phosphotyrosine proteins in basal cells, their increased level per cell and the number of positive cells in the different experimental animals support the concept that basal cells represent the stem cells of the prostate. The sex steroid-mediated up-regulation of protein phosphorylation on tyrosine residues in these cells suggests that their proliferation is likely to involve growth factor regulated signal transduction pathways. In this respect, the lack of maturation of basal cells and the differentiation of secretory cells induced by androgen deprivation, combined with estrogen stimulation, favors the activation of these pathways and cell growth. On the other hand, the activation of glandular cell differentiation and the increase of stromal volume do not alter the threshold level of protein tyrosine kinase and phosphatase activities in secretory cells, fibroblasts and smooth muscle cells.

Androgens

Comparison of novel synthetic peptide-based DETECT-RUBELLA enzyme immunoassays with Enzygnost and IMx for detection of rubella-specific immunoglobulin G.

Enzyme immunoassays (EIAs) using synthetic peptides SP-E1 and SP-E1E2 (DETECT-RUBELLA [Bio-Chem]) were compared with two viral lysate-based EIAs (Enzygnost [Behring] and IMx [Abbott]) for the detection of rubella virus-specific immunoglobulin G antibodies. Sensitivities of 94.7, 100, 98.6, and 100% and specificities of 100, 97.4, 100, and 73.7% were found for the SP-E1, SP-E1E2, Enzygnost, and IMx EIAs, respectively.

Antibodies, Viral

Blood pressure responses to a progressive step test in normotensive males and females.

This study documents the blood pressure responses to a progressive step test adapted from the Canadian Aerobic Fitness Test (CAFT). Subjects were administered the first five stages of the CAFT in a progressive and discontinuous manner. Mean heart rate, SBP, and delta SBP increased linearly with exercise intensity, while mean diastolic blood pressure remained stable. The variables that contributed most to delta SBP (Stage 3) in males were age and degree of participation in physical activity, and in females the variables were body weight and degree of participation. Criteria for the detection of an exaggerated (mean delta SBP + 1 SD) and highly exaggerated (mean delta SBP + 2 SD) SBP response were defined. Resting normotensive individuals who demonstrate an excessive exercise blood pressure response seem to do so at the lowest levels of stepping intensities. This step test protocol appears to be a useful and practical procedure for assessing the exercise blood pressure response in higher risk individuals.

Adult

Electrocardiographic responses to jogging in middle-aged and older men and women.

Recent jogging-related sudden deaths rekindled the concern among health professionals as to the hazards of strenuous exercise. The purpose of this study was to evaluate the extent of rhythm disturbances and myocardial ischemia in older men and women during a typical strenuous jogging session. Twenty-two members of a local jogging club (11 men and 11 women) between the ages of 50 and 66 years participated in the study. The CardioData PR3/ST monitor was employed to record heart rate, rhythm disturbances, J point and ST slope during the course of the run. The men ran a 10 km run and the women a 6 km run at a competitive pace. The mean maximal heart rate during the run was 170 +/- 15 beats/min for the males and 176 +/- 14 beats/min for the females. The mean J point during the run was -3.39 +/- 1.21 mV for the males and -2.97 +/- 0.96 mV for the females. Females showed a significantly lower mean ST slope (3.95 +/- 0.91 mV) during the run than the males (5.56 +/- 1.37 mV, p < 0.05). A number of episodes of premature ventricular beats, both uni- and multifocal, were observed. Exercise testing of sufficient intensity is recommended to detect those persons susceptible to developing serious arrhythmias during strenuous exercise.

Aged

Relation between cardiorespiratory fitness and selected risk factors for coronary heart disease in a population of Canadian men and women.

OBJECTIVE: To determine the relation between cardiorespiratory fitness, as determined with the Canadian Aerobic Fitness Test (CAFT), and selected risk factors for coronary heart disease (CHD) in a Canadian population. DESIGN: Cross-sectional study. On the basis of age-specific and sex-specific national percentile scores, subjects were classified as being in the low-fitness, moderate-fitness or high-fitness category according to maximum oxygen consumption (VO2 max) predicted from performance on the CAFT. PARTICIPANTS: A total of 4082 male and 1205 female Canadian federal public servants aged 30 to 59 years who participated in a voluntary fitness testing program between 1984 and 1991. OUTCOME MEASURES: Body composition (body mass index, triceps skinfold thickness, sum of four skinfold measurements, predicted percentage of body fat and waist-hip ratio), blood lipid levels (total cholesterol, triglycerides, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol and ratio of total cholesterol to HDL-C) and hemodynamic measurements (heart rate and blood pressure at rest and during exercise and predicted VO2 max). MAIN RESULTS: For both men and women the mean anthropometric measurements, blood lipid levels and blood pressure measurements at rest and after exercise were significantly associated with fitness category (p less than 0.05). CONCLUSIONS: In both men and women a higher level of aerobic fitness, as defined by VO2 max predicted from performance on the CAFT, is associated with a more favourable CHD risk profile. The results support the use of VO2 max predicted from performance on the CAFT as a valid procedure for classifying people according to fitness level.

Adult

Reactive hypoglycemic coma due to insulin autoimmune syndrome: case report and literature review.

Recurrent episodes of postprandial hypoglycemic symptoms culminated in hypoglycemic coma in a hypertensive but otherwise healthy man while he was taking hydralazine. The patient was found to have an extreme elevation in the immunoreactive insulin level, leading to the discovery of insulin antibodies in the absence of prior exposure to exogenous insulin. Negative results of an anatomic study of the pancreas and an inability to reproduce hypoglycemia during a prolonged fast helped to exclude insulinoma. In contrast, symptomatic hypoglycemia developed in response to oral glucose loading and was associated with an elevation in total and free insulin as well as C-peptide levels. The patient was diagnosed with insulin autoimmune syndrome, which, although a common source of hypoglycemia in Japan, has been well documented in only 15 cases from other countries. HLA typing revealed the patient to be positive for groups Cw4 and DR4, a combination that has been preliminarily associated with insulin autoimmune syndrome in Japan. Unlike the majority of cases previously reported, this patient had no clinical or serologic evidence of an underlying autoimmune disorder and had not been exposed to drugs containing sulfhydryl groups. This case adds to the world literature on insulin autoimmune syndrome, lends support to a postulated HLA association, and documents the presence of insulin autoantibodies in the absence of another underlying autoimmune disorder.

Adult

Randomized 4-week exercise program in patients with impaired left ventricular function.

BACKGROUND: This study was designed to determine the controlled effects of a short-term exercise rehabilitation program on patients with moderate-to-severe left ventricular dysfunction after a recent myocardial infarction. METHODS AND RESULTS: Thirty-nine male patients 51 +/- 8 years old with a large anterior myocardial infarction less than 10 weeks old were recruited for the study. The patients were randomly assigned to either one of two training or control groups on the basis of their resting ejection fraction: training, less than 30%; control, less than 30%; training, 31-50%; or control, 31-50%. Patients were evaluated for filling pressures, radionuclide ventriculography, heart volume, echocardiography, and work capacity. Patients who underwent training participated in an intensive 4-week in-hospital exercise program, whereas the control patients were restricted to a minimal activity program. Results indicated that there were no significant improvements in resting, submaximal, and maximal hemodynamic measurements as a result of the program. Mean work capacity and peak oxygen consumption improved significantly in the less-than-30% training group but was accompanied by a significant increase in mean pulmonary wedge pressure. Resting ejection fraction improved markedly in both less-than-30% training and control patients, but ejection fraction measures were not associated with work capacity. Training did not cause further deterioration in ventricular function. CONCLUSIONS: It was concluded that in the present study, exercise training had little or no effect on hemodynamic measurements and that the training effects achieved in patients with left ventricular dysfunction are most likely due to corrected impaired vasodilation, not necessarily to cardiac function. The importance of using a control group in this type of study and the wide interindividual variations in training responses are emphasized.

Exercise Therapy

Ambulatory blood pressure and Holter monitoring during tennis play.

The effect of tennis play on blood pressure, heart rate response, and rhythm disturbances was evaluated in 21 men 39 to 61 years of age (M = 49.5 +/- 6.7 yrs). A Holter monitor was utilized for continuous ECG recording during tennis play and a portable ambulatory blood pressure recorder (Spacelabs) was used to measure blood pressures and heart rates periodically during tennis matches. The results indicated that blood pressure response to tennis (singles), although an activity of moderate aerobic intensity, can exert significant increases in systolic and diastolic blood pressure even in those persons who are normotensive at rest. Excessive body weight, and particularly abdominal deposition, appears associated with an increase in diastolic blood pressure to exercise. Few heart rhythm disturbances of consequence were uncovered. A simple submaximal step test such as the Canadian Aerobic Fitness Test, with ECG monitoring, could assist in detecting those individuals susceptible to an exaggerated blood pressure response and to heart rhythm disturbances at exercise.

Adult

Body mass index as a discriminant function among health-related variables and risk factors.

A group of 206 subjects (30-55 years) were studied with the objective of quantifying the relationships between fitness indicators (relative body weight (BMI), aerobic power, muscular endurance), health indicators and risk factors, (appraised age, cost of health services consumed, blood pressure (SBP and DBP), blood lipids (CHO and HDL), cigarette smoking). BMI was significantly correlated with the risk indicators in the male sample (.302 less than or equal to r less than or equal to .364) and in the female sample (.217 less than or equal to r less than or equal to .521). All coefficients were in the direction of the established biological assumption as concerns hazards to health. The discriminant analysis revealed that in the total group of men, 77% (p less than or equal to .001) of the subjects could be classified either in high or low BMI (greater than Q75 or less than or equal to Q25) on the basis of the scores in SBP, HDL, HDL/CHO. In the subgroup of women greater than or equal to 40 years, statistically significant classification occurred in 100% of the cases (p less than or equal to .001) on the basis of DBP, CHO, HDL/CHO, NCIG. The results indicate that BMI is a fitness determinant which is valid, convenient and easy to use in the detection of unfavorable health indices and when clinical intervention is justified.

Adult

Accuracy of ambulatory blood pressure monitoring in four exercise situations.

Although ambulatory blood pressure monitoring (ABPM) is still considered in its investigational stage, the technique has become increasingly popular in recent years. The rationale for its utilization is its ability to continuously monitor blood pressure (BP) response to situational stressors occurring over the course of a 24-hour period which cannot be detected by casual measurements. In addition, ABPM eliminates the so-called white-coat auscultatory BP response. However, the accuracy of ABPM under situations which are at the measurement limits of the technical characteristics and/or capabilities of the ABPM equipment, such as in exercise situations commensurate with daily life activities, has not been fully documented. The purpose of this study was to evaluate the accuracy of the Spacelabs ABPM monitor against auscultatory (AUS) determinations in four exercise situations: walking, stair climbing, cycling and a progressive step test (modified Canadian Aerobic Fitness Test). Analyses of variance (ANOVA) were computed to determine if significant differences occurred between ABPM and AUS measurements for systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) over the resting and four exercise conditions. Results indicate that, particularly at low to moderate levels of exercise intensity, there is no statistically significant difference between ABPM and AUS measurements for SBP and HR. In 20 of the 26 resting and exercise determinations, the difference in SBP was less than 6 mmHg. For HR the variation was no greater than 4 bpm. However, there was no such agreement between ABPM and AUS measurements for DBP. As the intensity of the exercise situations increased, there was a tendency for SBP ABPM measurements to register higher readings than those obtained by AUS. The major drawback in ABPM is its sensitivity to artifacts due to arm movement. It was concluded that ABPM, such as provided by the Spacelabs instrument, can provide reasonably accurate readings of SBP and HR, particularly at low to moderate intensities of exercise while at higher exercise intensities ABPM has a tendency to provide consistently lower SBP values than the AUS measurements. DBP ABPM was totally ineffective under any of the exercise conditions chosen for this study.

Adult

Endurance vs. strength training: comparison of cardiac structures using normal predicted values.

There are still disagreements concerning the adaptation of cardiac structures in relation to different training stimuli. To eliminate some of the variance due to individual differences in body surface area, we utilized a new approach based on the calculation of the percentages of each individual's normal predicted values (%NPV). We studied 46 strength (S, bodybuilders) and 57 endurance (E, runners) athletes. Left ventricular (LV) mass was 143.8 +/- 21.9 %NPV (mean +/- SD) in E vs. 134.3 +/- 23.4 %NPV in S (P less than 0.05), and LV volume was 131.0 +/- 24.0 %NPV in E vs. 120.0 +/- 25.5 %NPV in S (P less than 0.05). Moreover, the LV wall thickness-to-radius ratio did not differ from normal values in either group. From these data we conclude that 1) cardiac modifications are greater in E than S, 2) the predominant stimulus is a volume overload type in both groups, and 3) concentric LV hypertrophy may not be as prevalent in S as previously suggested.

Adult

[Physical fitness improves after mitral valve replacement].

To determine whether women with mitral valve prostheses can improve their physical fitness without suffering cardiac dysfunction or hemolysis, 10 women (mean age 47 years) who had undergone mitral valve replacement (an average of 3.7 years earlier) were enrolled in an 8-week program of exercise on a bicycle ergometer. They exercised three times a week, starting at 60% and increasing to 80% of their maximal heart rate achieved during stress testing. Nine other women with similar clinical characteristics (mean age 48 years) constituted a control group. Exercise produced significant cardiovascular improvement, as evidenced by a mean decrease of 12 beats/min in the heart rate at steady-state work load (p less than or equal to 0.01), a mean increase of 121 kpm in the maximal tolerated work load (p less than or equal to 0.01), and a mean increase of 4 ml/kg X min-1 in the peak oxygen consumption (p less than or equal to 0.01). There was a small increase in the mean plasma hemoglobin level (15 to 29 mg/dl) and the mean reticulocyte count (1.8% to 2.4%) after the program (p less than or equal to 0.05). There were no significant changes in any of the variables studied in the control group. There were no changes in the clinical, electrocardiographic or echocardiographic findings in the experimental group. Although slightly increased hemolysis may occur, women with mitral valve replacement can improve their cardiovascular condition by exercising.

Erythrocyte Count

Familial aggregation in physical fitness, coronary heart disease risk factors, and pulmonary function measurements.

In order to test for the presence of familial aggregation in physical fitness and coronary heart disease risk factors, body fat, submaximal power output, muscular strength, muscular endurance, blood pressure, pulmonary functions, and several blood biochemical variables were measured in 304 nuclear families living in the Quebec city area. Analysis of variance indicated a larger between-family than within-family variation for all the variables. When all members of nuclear families were considered, intraclass correlations ranged from 0.21 to 0.34 (P less than or equal to 0.01). Interclass correlations computed for various pairs of relatives revealed significant parent-child and sibling correlations for all the variables (0.14 less than or equal to r less than or equal to 0.55; P less than or equal to 0.01). On the other hand, spousal correlations tended to be lower but significant (0.10 less than or equal to r less than or equal to 0.30; P less than or equal to 0.05) for all variables except subcutaneous fat and hemoglobin concentration. These results suggest that heredity and common lifestyle shared by members of nuclear families are responsible for the familial aggregation of physical fitness, coronary heart disease risk factors, and pulmonary functions. The findings also support the notion of considering the nuclear family as a unit of intervention in the application of preventive measures aimed at the reduction of several risk factors.

Adolescent

Silent ischaemia in post-infarction patients: a 21-month follow-up study.

The purpose of this study was to determine the prevalence of silent myocardial ischaemia (SMI) in post-infarction patients and to follow its clinical evolution in the course of a 21-month follow-up period. Of the 12,500 patients treated at the Klinik Roderbirken between Jan 1980 and Jun 1983 40% had angina. Three-vessel disease was documented in 61% of the 3150 subjects who had a coronary angiography. SMI identifiable on the exercise ECG was observed in 680 patients (5.4%). Sixth-three subjects (mean age 52 +/- 5.5 years) were selected and followed on the basis of stringent criteria. Prevalence of SMI at an average of 6 weeks after MI was 1/200 or 0.5% in that sample. Prognosis was good with a low mortality rate of 3.2% during the 21-month follow-up period. Factors weighing negatively on the observed SMI prognosis are the prevalence of 3-vessel disease (74%) and of pathological ejection fractions (52%) as well as the presence of ischaemia itself. Conversely, factors weighing positively on the observed SMI prognosis are the reasonably high exercise tolerance level (102 +/- 32 W), the low arrhythmogenic potential (73% less than or equal to Lown II), and the normal chest X-ray in more than 80% of the patients. In this study, 43% of the patients were felt to require angiography and only 10% were considered for bypass surgery. Good prognosis may be seen as a contra-indication for revascularization surgery. Yet, the prevalence of 3-vessel disease and the fact that 2/3 of the SMI subjects became symptomatic during the follow-up period are arguments in favour of early angiography.

Adult

Filling pressures in post-myocardial infarction patients: comparison between isometric and dynamic exercise.

The purpose of this study was to determine if isometric exercise (handgrip) using a substantial muscle mass and intensity could be substituted for dynamic exercise in the assessment of left ventricular function in myocardial infarct (MI) patients. Forty patients with documented MI were assigned, on the basis of their previous exercise ECG responses, to either an exercise-induced ischaemic group (Group 1) or to a non-exercise ischaemic group (Group 2). Eight apparently healthy males served as controls. Pulmonary capillary pressure (PCP) was measured at rest, during volume loading and during isometric and dynamic exercise. Mean PCP in Group 1 increased progressively from 7.5 +/- 2.9 mmHg at rest, to 11.6 +/- 3.8 mmHg during volume loading, to 18.8 +/- 10.2 mmHg during the isometric exercise and to 25.2 +/- 10.1 mmHg during the dynamic exercises. For Group 2, the respective values were 9.6 +/- 6.3, 13.1 +/- 6.4, 18.7 +/- 13.7 and 18.4 +/- 9.8 and for the controls 8.9 +/- 1.9, 11.3 +/- 1.2, 13.3 +/- 3.3 and 11.8 +/- 3.6 mmHg. The results of this study indicate that isometric exercise of 50% MVC using both hands can adequately replace dynamic exercise in the diagnosis of left ventricular function in post MI patients.

Adult