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Biomedical subjects

L A Wolfe

Publications and source records attributed to L A Wolfe.

52 records · Page 3Linked to original sources

Acute effects of exercise intensity on appetite in young men.

This study investigated the acute effects of two exercise intensities on three measures of appetite. Fifteen, 12-h-fasted, college-age males completed three experimental sessions in counterbalanced orders: no-exercise control; cycle exercise performed at 35% VO2max; and cycle exercise performed at 68% VO2max. Both exercise conditions involved a total energy expenditure of 4.1 kcal.kg-1 body weight. Dependent measures were intermittent hunger and sucrose palatability ratings, and food intake at a test meal given approximately 1 h post-exercise. Hunger was briefly suppressed in the high-intensity exercise condition compared to low-intensity exercise and control, while intake of liquid-source kilocalories and carbohydrates was higher after the exercise sessions. Total caloric intake remained stable. Sucrose palatability did not vary across sessions. Intensity is inferred to be an important variable mediating exercise effects on appetite. Relations between appetite measures are discussed, and validity of sucrose palatability ratings and common methods of measuring food intake questioned. Exercise, while not decreasing food intake, does not appear to increase it, and the benefits of exercise for body fat reduction are not immediately offset by compensatory caloric intake.

Adult↗

"Flipped" patterns of lactate dehydrogenase isoenzymes in serum of elite college basketball players.

We kinetically measured total lactate dehydrogenase (LD, EC 1.1.1.27), total creatine kinase (CK, EC 2.7.3.2), and aspartate aminotransferase (AST, EC 2.6.1.1.) in 16 elite college basketball players, before the competition season and not in close temporal relation to near-maximal exercise, and in 17 healthy non-athlete controls. LD isoenzymes were determined by both electrophoretic and immunoprecipitation methods. CK-MB isoenzyme was measured electrophoretically. We found significantly higher mean LD-1 values and LD-1/LD-2 ratios in the players than the controls: 31.6 (SD 3.7)% vs 25.8 (SD 3.2)% (P less than 0.005) and 1.1 (SD 0.13) vs 0.87 (SD 0.16) (P less than 0.001), respectively. A "flipped" LD pattern (LD-1 greater than LD-2) was found in half the players and in six of the eight black athletes, but in only two of the control group and in none of the black controls. Mean CK activity in serum exceeded normal values in the serum of the athletes and was higher in comparison with the control group [274 (SD 156) vs 103 (SD 82) U/L]. Mean CK was significantly higher in the eight athletes with the flipped LD pattern than in those with LD-1 less than LD-2 [322 (SD 163) vs 180 (SD 98) U/L; P = 0.05], and also in comparison with CK in the two controls with flipped LD pattern. We saw no significant difference in mean CK between the nine players with normal immunochemical LD-1/LD ratios and the seven players with above-normal ratios. CK-MB was not detected in either athletes or controls. None of the players had any clinical or electrocardiographic evidence for myocardial ischemia or infarction. Evidently the flipped LD pattern usually found in patients with acute myocardial infarction and reported in some athletes after extreme exercise such as ultra-marathon running may also be found in athletes who are in their "basal fitness shape" but who are not involved in competitive physical activity.

Adult↗

Cardiovascular responses to acute exercise in patients with cerebrovascular accidents.

Blood pressure (BP) and heart rate (HR) responses to isometric hand grip, exercise with the cybex arm ergometer, and cybex fitron cycle ergometer were recorded for 19 stroke subjects and 19 control subjects matched by age and gender. Mean age in both groups was 66 years. There was no significant difference in the resting HR (controls: 69 +/- 10, patients: 70 +/- 11 beats per minute) and BP measurements (systolic--controls: 140 +/- 17, patients: 135 +/- 21; diastolic--controls 80 +/- 8, patients: 75 +/- 11mmHg). There was also no significant difference in either the mean HR (controls: 79 +/- 10, patients: 81 +/- 12 beats per minute) or BP (systolic--controls: 174 +/- 23, patients: 165 +/- 27; diastolic--controls: 98 +/- 15, patients: 92 +/- 14) response to exercise. With the arm ergometer test, the control group attained a significantly higher maximum systolic (190 +/- 23 mmHg) and diastolic blood pressure (102 +/- 15mmHg) than the stroke group (systolic 165 +/- 23; diastolic 91 +/- 10mmHg). During the leg ergometer exercise test, results were similar in both groups except that work completed was significantly higher for the control group (3592 +/- 1162kg) than for patients (2512 +/- 1348kg). None of the patients reported symptoms of dizziness, fainting, or chest pain. Prescribed exercise in stroke patients under supervision and within patient tolerance was found to be safe.

Activities of Daily Living↗

Physical conditioning effects on cardiac dimensions: a review of echocardiographic studies.

Echocardiographic studies related to chronic exercise effects on cardiac dimensions were reviewed. Sources of error in M-mode echocardiography include its resolving power, changes in transmission velocity in a nonhomogeneous medium, subjective analysis of records, and assumptions to predict ventricular volume and mass from one-dimensional data. Existing studies document larger values for left ventricular internal diastolic dimension (LVIDd) in endurance athletes, and for septal and posterior wall thicknesses (ST, PWT) in endurance, strength-type and anaerobic-type athletes compared to nonathletes. Values for the athletes were lower than in cardiac disease states. Short-term conditioning studies generally reported unimpressive changes in ventricular dimensions. Existing literature also does not clearly support a relationship between training intensity and the degree of cardiac enlargement, or changes in the heart's trainability with age. Hereditary and/or familial factors appear to influence heart size to some degree and a correlation with anthropometric variables may exist. Further study concerning hereditary and long-term conditioning effects is recommended.

Adolescent↗

Chronic exercise and left ventricular structure and function in healthy human subjects.

Twelve healthy well-trained participants in a supervised exercise program (mean age, 41.3 yr) were compared with 12 sedentary control subjects (mean age, 38.9 yr) with physical characteristics similar to the exercised group (EG) before training. Resting echocardiograms revealed significantly lower heart rates (HR) in the EG compared with control group (CG) but no evidence for cardiac structural differences between groups. Radionuclide angiograms performed at rest and during two levels of supine cycling (HR targets: 120 and 140 beats X min-1) resulted in increases in background-corrected end-diastolic counts [EDC(bc)] and confirmed use of the Frank-Starling mechanism in the majority of subjects. Mean values (+/- SD) for ejection fraction (EF) and normalized peak systolic ejection rate (PSER) (P greater than 0.05 between groups) were the following. (Formula: see text) The results suggested that fitness training does not induce significant cardiac enlargement as apparent from measurements at rest or important changes in contractile state during exercise. Increases in exercise stroke volume with such training may be the result of an increased end-diastolic volume.

Adult↗

Absence of left ventricular hypertrophy in elite college basketball players.

Left ventricular dimensions of 11 successful male college basketball players engaged in pre-season conditioning (mean age, 20.3 years) and 13 tall healthy male controls (mean age, 21.6 years) were studied by echocardiography. Left ventricular internal dimension (LVIDd, mm), posterior wall thickness (PWT, mm), septal thickness (ST, mm), and calculated left ventricular mass (LV mass, g) in the athletes were within or only slightly in excess of echocardiographic normal limits and mean values were not significantly different from the control group. LVIDd (mm/m2 body surface area) was significantly lower in the athletes. However, five guard-type players displayed significantly greater mean values for PWT and LV mass compared to six taller forwards/centers with linear body builds. It was concluded that left ventricular hypertrophy is not a common characteristic of college basketball players. It was hypothesized that cardiac dimensions of young men may vary independently of gross body size in relation to somatotype or other anthropometric variables.

Adult↗

Effects of chronic exercise on cardiac output and its determinants.

A protocol which combines the noninvasive measurement of cardiac output (Q), systolic time intervals (STIs), and blood pressure was used to evaluate the effects of jogging on cardiac function. Studies were conducted during levels of steady-state cycle ergometer exercise which represented approximately 35, 55, and 75% of aerobic capacity. Subjects were 15 healthy men (mean age = 37.2 years) and 13 healthy controls. Predicted aerobic capacity (pred VO2max) increased 15 and 17% in the training group after 3 and 6 months of training; the control group displayed a small detraining effect. Changes in the training group versus control group included significant increases in exercise Q, stroke volume (SV), mean systolic ejection rate (MSER), and systolic blood pressure (SBP). Changes in STIs were small and usually nonsignificant. The findings, considered in relation to echocardiographic measurements from the same subjects (L. A. Wolfe, D. A. Cunningham, P. A. Rechnitzer, and P. M. Nichol. 1979 J. Appl. Physiol. 47: 207-212.), suggested that changes in cardiac output were due to an increased preload, rather than a change in exercise heart rate, reduced afterload, enhanced contractile state, or myocardial enlargement.

Adult↗

The value of combining noninvasive techniques in exercise testing.

A 3-stage cycle ergometer exercise test which combines the noninvasive measurement of systolic time intervals (STI's), stroke volume (SV), mean systolic ejection rate (MSER) and blood pressure was administered to 2 groups of middle-aged men. Group 1 included 15 healthy men. Group 2 consisted of 20 men with coronary artery disease (CAD), confirmed by a proven myocardial infarction. The groups were matched for age, weight and height. Over the range of heart rates (HR's) encountered (70--173 beats min-1) the STI's described an inversely linear relationship with HT. At all exercise HR's, group 2 displayed higher values for total electromechanical systole (QS2), left ventricular ejection time (LVET) and the pre-ejection period (PEP), and lower values for SV and MSER. Statistical comparison of all variables at a common HR of 100 beats min-1 indicated that QS2 and MSER best discriminated between the groups. It was concluded that this test is sufficiently sensitive to detect differences in cardiac performance in groups of subjects, but not for the diagnosis of CAD in individual patients.

Adult↗

Effects of endurance training on left ventricular dimensions in healthy men.

Echocardiography was employed to measure the serial effects of jogging on resting left ventricular dimensions and function. Twelve men were exercised (mean age 36.8 yr) and 10 served as controls (mean age 34.8 yr). Increases of 14 and 18% were observed for predicted aerobic capacity in the training group (TG) after 3 and 6 mo of training, respectively; the control group (CG) displayed a small detraining effect. Echocardiographic findings included a significant (P less than 0.05) reduction in resting heart rate and a moderate increase in stroke volume (SV) in the TG compared to the CG. The increased SV appeared to be due to increased end-diastolic dimensions (LVIDd, LVEDV), secondary to greater ventricular filling rather than a more vigorous ventricular contraction. Posterior wall thickness, septal thickness, and calculated left ventricular muscle mass were not significantly increased in the TG compared to CG after either 3 or 6 mo training. It was concluded that left ventricular structure and resting contractile status are not altered by 6 mo of jogging training in healthy, previously sedentary men.

Heart↗

Relationship between maximal oxygen uptake and left ventricular function in exercise.

Left ventricular systolic time intervals (STI's), cardiac output, and arterial blood pressures were measured during bicycle ergometer work in three groups of 10 young men (aged 20-33 yr) who represented average (VO2max = 42-45 ml.kg-1.min-1), moderate (VO2max = 50-56 ml.kg-1.min-1), and high (VO2max = 59-72 ml.kg-1.min-1) levels of cardiovascular fitness. The subjects were studied using noninvasive procedures at steady-state heart rate of approximately 110, 130, and 150 beats.min-1. At all exercise levels, the fitter subjects displayed slightly shorter values for the preejection period (PEP) compared with less fit groups. Significantly (P less than 0.05) larger stroke volumes, longer left ventricular ejection times (LVET), faster mean systolic ejection rates and lower PEP/LVET ratios were found in the group with the highest aerobic capacity. Although these observations appear to indicate a superior mean level of left ventricular performance in groups who represent high levels of cardiovascular fitness, it was concluded that the use of STI values by themselves to describe the cardiovascular fitness of an individual would not be warranted.

Adult↗

Reliability of noninvlasive methods for measuring cardiac function in exercise.

Externally recorded systolic time intervals (STI's), indirect (CO2 re-breathing) cardiac output, and auscultatory blood pressures were measured during upright bicycle ergometer work in 20 healthy men, aged 24-56 yr. The subjects were studied on 2 separate days at steady-state work loads chosen to represent light (mean heart rate (HR) = 96 beats.min-1), moderate (HR = 118 beats.min-1) and heavy (HR = 147 beats.min-1) exercise. In addition to determinations of cardiac output, systolic time intervals, and blood pressure, the individual's mean systolic ejection rate (stroke volume/left ventricular ejection time) was calculated as a measure of left ventricular function. In general, heart-rate-corrected STI's were found to be reliable and reproducible. Reliability coefficients for total electromechanical systole and left ventricular ejection time ranged from 0.93 to 0.96 while those for the preejection period and its subcomponents were between 0.63 and 0.88. The reliability of cardiac output, stroke volume, mean systolic ejection rate, and systolic blood pressure was also considered to be acceptable but tended to be higher during moderate and heavy work (r = 0.85-0.95) compared to light exercise (r = 0.60-0.83).

Blood Pressure Determination↗

Vital confocal microscopy in bone.

We wished to exploit confocal microscopy for high spatial and temporal resolution vital microscopy in bone. To this end, we evolved implants with glass windows supported in titanium, which were placed in the medial proximal tibial plateau of the rabbit, and special small, self-focussing objectives (dry 10/0.25, water immersion 20/0.45, and oil immersion 45/0.65 and 120/1.0) which mated and matched to the conical window entrance section of the metal components. At intervals of up to 21 months after implant healing, these lenses were used to study live tissue using two genera of confocal microscope: multiple aperture disc, tandem scanning, microscopes for observation in reflection, and video rate confocal laser scanning microscopes for recording, mainly in the fluorescence mode. The latter allowed the study of a variety of intravenously administered substances, including fluorescein, fluorescein-dextrans, fluorescent microspheres, acridine orange, DASPMI, calcein, and tetracycline. We were able to remove blood, stain cells with fluorescent markers, and replace them into the circulation. Calcein and tetracycline bind to the mineral front in bone: this labelling was studied in progress. We observed that both substances partition and remain for long periods (at least days) in adipocytes. Further characterisation of the system used both confocal fluorescence and scanning electron microscopy methods in the study of retrieved implants. These studies showed that the subimplant cortical bone remodelled to a less compact structure with a rich microvasculature extremely close to bone. The points of attachment of bone to glass were found to involve coarse fibres, with the matrix containing large numbers of large cells: some of this tissue was cartilage and some immature bone. An amorphous, mineralised matrix was in immediate contact with glass. The results provide further confirmation of the general utility of high-scan speed confocal methodology in physiology.

Adipocytes↗

Antibody-directed enzyme prodrug therapy with the T268G mutant of human carboxypeptidase A1: in vitro and in vivo studies with prodrugs of methotrexate and the thymidylate synthase inhibitors GW1031 and GW1843.

Antibody-directed enzyme prodrug therapy (ADEPT) is a technique to increase antitumor selectivity in cancer chemotherapy. Our approach to this technology has been to design a mutant of human carboxypeptidase A (hCPA1-T268G) which is capable of hydrolyzing in vivo stable prodrugs of MTX and targeting this enzyme to tumors on an Ep-CAM1-specific antibody, ING1. Through the use of this >99% human enzyme which is capable of catalyzing a completely nonhuman reaction, we hope to increase ADEPT selectivity while decreasing overall immunogenicity of the enzyme-antibody conjugate. In the current report, prodrugs of the thymidylate synthase inhibitors GW1031 and GW1843 and the dihydrofolate reductase inhibitor methotrexate were studied for their wild-type and mutant hCPA enzyme hydrolysis, their in vivo stability, and their use in therapy. Prodrugs with high kcat/Km ratios for mutated versus wild-type hCPA1 were examined in vitro for their stability in human pancreatic juice, and in vivo for their stability in mouse plasma and tissues. In addition, targeting and in vivo enzyme activity studies were performed with an ING1 antibody conjugate of the mutant enzyme (ING1-hCPA1-T268G). Finally, in vivo therapy studies were performed with LS174T tumors to demonstrate proof of principle. Results indicate that prodrugs can be synthesized that are selective and efficient substrates of hCPA1-T268G and not substrates of the endogenous CPA activities; this leads to excellent in vivo stability for these compounds. In vivo conjugate targeting studies showed that the antibody-enzyme conjugate was targeted to the tumor and enzyme was initially active in vivo at the site. Unfortunately therapeutic studies did not demonstrate tumor reduction. Experiments to determine reasons for the lack of antitumor activity showed that the enzyme activity decreased as a result of enzyme instability. The results offer encouragement for additional novel mutant enzyme improvements and additional in vivo studies on this unique approach to ADEPT.

Adenocarcinoma↗

A radiometric method for objectively screening large numbers of compounds against Pneumocystis carinii in vitro.

A relatively simple method is reported for accurately quantitating the incorporation of [3H]para aminobenzoic acid (pABA) into the folates of Pneumocystis carinii cultured in vitro, and the subsequent development of a highly sensitive and reproducible 96-well microtitre plate drug screening system. Incorporation of [3H]pABA under optimized conditions has been utilized as a selective indicator of the in vitro viability of P. carinii against which the inhibitory effects of potential drugs were quantified. The anti-Pneumocystis agents pentamidine, sulfamethoxazole, 566C80 and piritrexim gave median inhibitory concentration values of 7.3, 0.1, 1.4 and approximately 100 microM, respectively in this assay. The results suggest that this 96-well plate P. carinii [3H]pABA-incorporation system is suitable as a rapid high throughput primary in vitro screen for detecting compounds with anti-Pneumocystis activity.

4-Aminobenzoic Acid↗