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Biomedical subjects

F Landry

Publications and source records attributed to F Landry.

At least 19 recordsLinked to original sources

Insights into a plasma membrane signature.

The plasma membrane (PM) is an organized biological system that serves as a structural barrier and communication interface with the extracellular environment. Many basic questions regarding the PM as a system remain unanswered. In particular, we do not understand the scope of similarity and differences in protein expression at the PM. This study takes an initial step toward addressing these questions by comparing the PM proteomes of fibroblasts and mammary carcinoma cells. Three sets of proteins were revealed by the study. The first set comprises between 9 and 23% of all proteins at the PM and appears to be common to both fibroblasts and mammary carcinoma. A second group of proteins, comprising approximately 40% of the proteins at the PM, is tightly linked to cell lineage. The third set of proteins is unique to each cell line and is independent of cell lineage. It is reasonable to hypothesize then, that this third group of proteins is responsible for unique aspects of cell behavior. In an effort to find proteins linked to the metastatic phenotype, we identified several proteins that are uniquely expressed at the PM of the metastatic MDA-MB-435 cells. These proteins have functions ranging from cell adhesion to the regulation of translation and the control of oxidant stress.

Breast Neoplasms↗

A direct effect of competition on food choice by pigeons.

Previous research on food choice of pigeons foraging alone and in competition showed an indirect response to the competitor, mediated by the resource depletion associated with the competitor. This experiment showed, in addition, that pigeons can adjust their food choice in direct response to the competitor itself. Pigeons foraged for large, preferred grains of maize and smaller, unpreferred grains of wheat presented in bowls covered with sawdust. In a within-subject design, pigeons were tested alone or in competition with another pigeon. In competition, a higher choice proportion of the wheat grains was observed on the first two choices out of 48 items, and this effect increased with time in the experiment. This result underscores the role of learning in group foraging behaviour. It also suggests a possible ecological implication: that individuals that learn faster may enjoy a competitive advantage in terms of reduced delay in responding to the presence of a conspecific.

Journal Article↗

A method for application of samples to matrix-assisted laser desorption ionization time-of-flight targets that enhances peptide detection.

Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry has become a fundamental tool for the identification and analysis of peptides and proteins. MALDI-TOF is well suited for the analysis of complex biological mixtures because samples are crystallized onto a solid support that can be washed to remove contaminants and salts prior to laser desorption. A number of approaches for immobilizing samples onto MALDI targets have been put forth. These include the use of different chemical matrices and the immobilization of samples onto different solid supports. In large part though, the preparation of MALDI targets has been an empirical exercise that often requires a unique series of conditions for every sample. Here, a simple method for the application of peptide mixtures onto MALDI targets is put forth. This method differs because peptides are added directly to a sample of nitrocellulose dissolved in acetone, allowing them to interact in solution-phase organic solvent. This solution-phase mixture is then spotted to the MALDI target and evaporated, forming a homogenous solid surface for laser desorption. This procedure is robust, highly sensitive, tolerant to detergents, and easily learned. In our hands, the method provides as much as a 10-fold enhancement to the detection of tryptic peptide fragments derived from in-gel digests.

Animals↗

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↗

The effect of infused fat emulsions on reticuloendothelial function in the rabbit.

The effect of the infusion of different fat emulsions (Intralipid and MCT/LCT mixtures) on the reticuloendothelial function of the rabbit has been investigated. Emulsions containing 20% dispersed triglyceride were administered over 6 h to a total of 3 g/kg body weight. The extent of blockade of the reticuloendothelial system was measured using a labelled probe in the form of technetium-99m labelled albumin microspheres. Scintigraphic and blood and organ level determinations demonstrated that all emulsions caused an impairment of reticuloendoethlial function, but this was small.

Journal Article↗

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↗