Biomorphometric analysis of human prostatic carcinoma by using three-dimensional computer models

Advances in the detection of carcinoma of the prostate during the last 15 years have accounted for a sharp increase and then an abrupt decrease in the incidence of the disease. A more recent decline in its mortality rates has been variously interpreted as either the success of early detection and improved treatment or lead-time bias. The recently reported Prostate Cancer Prevention Trial had an overall detection rate that approached the 30%-40% prevalence rates reported in autopsy series in which men died of other causes. However, the prognostic information that can be obtained from prostate cancer found on biopsy is limited. Three-dimensional computer modeling is one technique that allows multiple studies on "immortal" prostates to test methods of biopsy sampling accuracy and to assist in the determination of the disease's severity. Computer modeling can assess detection rates and assesses tumor multifocality and heterogeneity. It can provide a more accurate representation of tumor volume, aiding in therapeutic decision making, and can assess sampling errors of various biopsy methods. It has been shown to be superior to wire-frame technique by immortalizing the original shape and dimensions of the surgically excised prostate gland. Moreover, our 3-dimensional computer modeling system improves upon other systems: It is more than a simple extension of the planimetric technique, and it is able to demarcate clearly the boundaries of Gleason grades just 1 grade apart.     

Extracellular detection of K+ release during migration of transformed Madin-Darby canine kidney cells

 Madin Darby canine kidney cells transformed by alkaline stress (MDCK-F cells) constitutively migrate at a rate of about 1 μm·min^–1. Migration depends on the intermittent activity of a Ca²⁺-stimulated, 53-pS K⁺ channel (K_Ca channel) that is inhibitable by charybdotoxin. In the present study we examined whether this intermittent K_Ca channel activity results in a significant K⁺ loss across the plasma membrane. K⁺ efflux from MDCK-F cells should result in a transient increase of extracellular K⁺ ([K⁺]_e) in the close vicinity of a migrating cell. However, due to the rapid diffusion of K⁺ ions into the virtually infinite extracellular space, such a transient increase in [K⁺]_e was too small to be detected by conventional K⁺-selective electrodes. Therefore, we developed a ”shielded ion-sensitive microelectrode” (SIM) that limited diffusion to a small compartment, formed by a shielding pipette which surrounded the tip of the K⁺-sensitive microelectrode. The SIM improved the signal to noise ratio by a factor of at least three, thus transient increases of [K⁺]_e in the vicinity of MDCK-F cells became detectable. They occurred at a rate of 1.3 min^–1. The cell releases 40 fmol K⁺ during each burst of intermittent K_Ca channel activity, which corresponds to about 15% of the total cellular K⁺ content. Since transmembrane K⁺ loss must be accompanied by anion loss and therefore leads to a decrease of cell volume, these findings support the hypothesis that intermittent volume changes are a prerequisite for the migration of MDCK-F cells. Received: 15 April 1996 / Received after revision: 18 June 1996 / Accepted: 23 July 1996     

Hemodynamic and hormonal responses to lower body negative pressure in men with varying profiles of strength and aerobic power

Hemodynamic, cardiac, and hormonal responses to lower-body negative pressure (LBNP) were examined in 24 healthy men to test the hypothesis that responsiveness of reflex control of blood pressure during orthostatic challenge is associated with interactions between strength and aerobic power. Subjects underwent treadmill tests to determine peak oxygen uptake ( O_2max) and isokinetic dynamometer tests to determine knee extensor strength. Based on predetermined criteria, subjects were classified into one of four fitness profiles of six subjects each, matched for age, height, and body mass: (a) low strength/average aerobic fitness, (b) low strength/high aerobic fitness, (c) high strength/average aerobic fitness, and (d) high strength/high aerobic fitness. Following 90 min of 0.11 rad (6°) head-down tilt (HDT), each subject underwent graded LBNP to –6.7 kPa or presyncope, with maximal duration 15 min, while hemodynamic, cardiac, and hormonal responses were measured. All groups exhibited typical hemodynamic, hormonal, and fluid shift responses during LBNP, with no intergroup differences between high and low strength characteristics. Subjects with high aerobic power exhibited greater (P < 0.05) stroke volume and lower (P < 0.05) heart rate, vascular peripheral resistance, and mean arterial pressure during rest, HDT, and LBNP. Seven subjects, distributed among the four fitness profiles, became presyncopal. These subjects showed greatest reduction in mean arterial pressure during LBNP, had greater elevations in vasopressin, and lesser increases in heart rate and peripheral resistance. Neither O_2max nor leg strength were associated with fall in arterial pressure or with syncopal episodes. We conclude that interactions between aerobic and strength fitness characteristics do not influence responses to LBNP challenge.     

Effect of age on cardiac index,stroke index and left ventricular ejection fraction at rest and during exercise as studied by radiocardiography

Radiocardiography was used to measure cardiac output, stroke volume and left ventricular ejection fraction at rest and during muscular exercise in relation with age in 148 healthy subjects (age range: 6–78 years). A clear dependence of these parameters on age was found. The mean annual decrease at rest was 22±9 ml/min/m² for cardiac index, 0.22±0.04 ml/m² for stroke index and 0.0017±0.0003 for left ventricular ejection fraction. Male subjects had significantly (p < 0.001) greater cardiac (9±4%) and stroke indices (11±23%) than females. During submaximal exercise cardiac index increased from 3.5±0.7 l/min/m' to 8.1±1.6 l/min/m² in male subjects (mean age: 32 years) and from 3.1±0.4 l/min/m² to 7.2±1.2 l/min/ m² in female subjects (mean age: 29 years). The corresponding increases in stroke index and left ventricular ejection fraction were: from 52±7 ml/m² to 62±9 ml/m². from 46±7 ml/m² to 51±9 ml/m² and from 0.66±0.08 to 0.79±0.05 and from 0.64±0.10 to 0.72±0.10. In subjects who were 60 years and older the increases of these parameters during exercise were considerably smaller.     

Cell shrinkage stimulates bradykinin-induced cell membrane potential oscillations in NIH 3T3 fibroblasts expressing the ras-oncogene

In NIH 3T3 fibroblasts expressing the Ha-ras oncogene (+ras) bradykinin leads to sustained oscillations of cell membrane potential due to oscillations of intracellular Ca²⁺ with subsequent activation of Ca²⁺-sensitive K⁺ channels. In cells not expressing the oncogene (-ras), bradykinin leads only to a single transient hyperpolarization of the cell membrane. The present study has been performed to elucidate the possible interaction of cell volume, intracellular pH and bradykinin-induced oscillations of the cell membrane potential. Bradykinin leads to cell shrinkage and intracellular alkalinization of both +ras cells and –ras cells. Inhibition of Na⁺/H⁺ exchanger by HOE 694 abolishes the bradykinin-induced alkalinization but does not significantly interfere with the bradykinin-induced oscillations of cell membrane potential. In contrast, prevention of bradykinin-induced cell shrinkage by simultaneous reduction of extracellular osmolarity blunts the oscillations. Thus, cell shrinkage stimulates bradykinin-induced oscillations of cell membrane potential. On the other hand, cell shrinkage alone does not elicit oscillations unless, in addition, Ca²⁺ entry is stimulated by ionomycin.     

ACE Genotype May Have an Effect on Single versus Multiple Set Preferences in Strength Training

A polymorphic variant of the human angiotensin converting enzyme (ACE) gene was identified. The 'D' (rather than 'I') variant was associated with improvements in strength related to physical training. We set out to determine whether the response to different patterns of strength training might also differ. Ninty-nine Caucasian male non-elite athletes were randomly allocated into one of three groups: 31 non-training/control (CG: 31), single-set (SSG: 35) and multiple-set (MSG: 33). SSG and MSG trained three times a week for 6 weeks. Both training groups were underwent a strength-training program with two mesocycles (12-15 repetition maximum (RM) and 8-12 RM mesocycles). One RM loads in half squat and bench press were assessed before training and after the first and second mesocycles. ACE polymorphisms analysed by polymerase chain reaction (PCR) methods. Subjects with ACE II genotype in the MST group had improved strength development in 12-15 RM, while SST and MST groups had similar gains in 8-12 RM. Subjects with ACE DD genotype in both the SSG and the MSG had similar benefits from both 12-15 RM and 8-12 RM. Strength gains for subjects with ACE ID genotype in the SSG were similar to MSG gains in response to 8-12 RM loads but not with 12-15 RM loads. Additionally, subjects with DD genotype had superior strength gains in both strength training groups. Tailoring strength training programmes (single-set vs. multiple set) according to the athlete's ACE genotype may be advantageous.     

Kinetics of cardiorespiratory response to dynamic and rhythmic — static exercise in men

Summary Kinetics of cardiorespiratory response to dynamic (DE) and then to rhythmic-static exercise (RSE) was compared in nine male subjects exercising in an upright position on a cycle ergometer at an intensity of about 50 % O_2max and a mean pedalling frequency of 60 rpm over 5 min. Respiratory frequency (f _R), tidal volume (V _T), minute ventilation ( _E), heart rate (f _c), stroke volume (SV), and cardiac output (Q _t) were measured continuously. The RSE caused a greater increase in f _R than DE, whereas V _T increased more during DE. The effect of reciprocal changes in f _R and V _T was that _E and its kinetics, expressed as a time constant (), did not differ between experimental situations. The ventilatory equivalent for O₂ ( _E: O₂) was greater for RSE (31.3) than for DE (23.0, P<0.01). Elevation of f _c was similar for both types of exercise. The SV increased suddenly at the beginning of DE from 54 ml to 74 ml and then decreased to the end of exercise. At the onset of RSE only a moderate increase in SV was observed, from 56 ml to 62 ml, and then SV remained stable. The DE caused a greater and faster increase in Q _t (4.20 l · min^–1, for equal to 16.1s) than RSE (3.25 l · min^–1, for equal to 57.0s, P<0.05 and P<0.002, respectively). Total peripheral resistance was almost 40% greater for RSE than for DE. No relationship was found between Q _t and V_E at the first 15 s of both types of exercise. It is concluded that the kinetics of _E did not depend on to kinetics of Q _t in the exercising subjects. This finding contradicts the hypothesis of cardiodynamic hyperpnoea indicating an importance of neurogenic factors, mediated either centrally or peripherally, in fast cardiorespiratory responses to exercise.     

Evaluation of encephalic ventricular volume from the magnetic resonance imaging scans of thirty-eight human subjects

Summary Accurate volume determination of the encephalic ventricles is of importance in several clinical conditions, including Alzheimer's presenile dementia, schizophrenia, and benign intracranial hypertension. Previous studies have investigated the accuracy with which magnetic resonance imaging (MRI) can be used in clinical practice to evaluate the encephalic ventricles. However, adequate evaluation of pathological conditions depends on a sufficient amount of morphometric data from normal subjects. To begin establishing this data base for normal subjects, we evaluated the MRI scans of 38 subjects found to have no apparent pathology and calculated the ventricular volume in each case by using methods previously developed in our laboratory. The results were then compared with published volumes determined from studies that used either ventricular casts or computerized tomographic scans. The average total ventricular volume for all 38 subjects was 17.4 cm³, while that for males was 16.3 cm³ and that for females was 18.0 cm³. A small but significant correlation was found between age of subject and ventricular volume, with ventricular size increasing with age.

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Evaluation du volume des ventricules cérébraux à partir des images obtenues en résonance magnétique nucléaire chez 38 sujets humains

Résumé La détermination exacte du volume des ventricules cérébraux est importante en clinique comme par exemple dans la démence présénile d'Alzheimer, la schizophrénie et l'hypertension intracrânienne bénigne. Des études antérieures ont étudié la fiabilité de la résonance magnétique nucléaire en pratique clinique pour évaluer le volume des ventricules cérébraux. Toutefois une évaluation correcte dans les conditions pathologiques implique une bonne connaissance des données morphométriques du sujet normal. Pour établir ces données sur « le sujet normal », nous avons étudié les coupes obtenues en IRM chez 38 sujets apparemment indemnes de toute pathologie; nous avons calculé le volume ventriculaire dans chaque cas en utilisant des méthodes mises au point auparavant dans notre laboratoire. Les résultats ont été ensuite comparés avec ceux obtenus par d'autres études utilisant soit des moules ventriculaires, soit des coupes tomographiques computérisées. Le volume ventriculaire total moyen chez 38 sujets est de 17,4 cm³, mais il est chez les sujets masculins de 16,3 cm³ et chez les sujets de sexe féminin de 18 cm³. Une corrélation faible mais significative a été trouvée entre l'âge du sujet et le volume ventriculaire, étant entendu que la taille du ventricule augmente avec l'âge.

     

The influence of the initial state of hydration on endocrine responses to exercise in the heat

Summary This study examines the effect of the initial state of hydration on hormone responses to prolonged exercise in the heat. Five subjects at two initial hydration levels (hypohydrated and hyperhydrated) were exposed to a 36°C environment for 3 h of intermittent exercise. During exercise, the subjects were either fluid-deprived, or rehydrated with water or an isotonic electrolyte sucrose solution (ISO). Both the stress hormones, adrenocorticotropic hormone and cortisol, and the main fluid regulatory hormones, aldosterone, renin activity (PRA) and arginine vasopressin (AVP), were measured in blood samples taken every hour. Prior hyperhydration significantly reduced initial AVP, aldosterone and PRA levels. However, except for AVP, which responded to exercise significantly less in previously hyperhydrated subjects (p<0.05), the initial hydration state did not influence the subsequent vascular and hormonal responses when the subjects were fluid-deprived while exercising. Concurrent rehydration, either with water or with ISO, reduced or even abolished the hormonal responses. There were no significant differences according to the initial hydration state, except for PRA responses, which were significantly lower (p<0.01) in previously hyperhydrated subjects who also received water during exercise. These results indicate that prior hydration levels influence only slightly the hormonal responses to prolonged exercise in the heat. Progressive rehydration during exercise, especially when extra electrolytes are given, is more efficient in maintaining plasma volume and osmolarity and in reducing the hormonal responses.