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Biomedical subjects

G Mall

Publications and source records attributed to G Mall.

At least 145 records · Page 8Linked to original sources
PubMed1987

Influence of hypertension on serum concentration of type IV collagen antigens in streptozotocin-diabetic and non-diabetic rats.

The serum concentration of 7S collagen was measured radioimmunologically as a marker of basement membrane type IV collagen synthesis in diabetic and nondiabetic rats with Goldblatt hypertension. In non-diabetic rats the 7S collagen level was significantly raised after induction of hypertension (51%; p less than 0.001), and showed a positive correlation with relative heart weight as an integral parameter of hypertension (r = 0.63; p less than 0.01). In diabetic rats, which displayed a 7S collagen concentration roughly 2.5 times as high as the metabolically normal animals, the 7S collagen level was 27% higher in the hypertensive animals (p less than 0.01). There was no correlation with blood pressure or heart weight, but only a positive correlation with blood glucose (r = 0.51; p less than 0.05). The results indicate that haemodynamic alterations may alter basement membrane collagen metabolism. However, type IV collagen metabolism in diabetes is influenced to a greater extent by metabolic than by haemodynamic factors.

Animals↗
PubMed1987

Synergistic effects of diabetes mellitus and renovascular hypertension on the rat heart--stereological investigations on papillary muscles.

The effects of combined renovascular hypertension and diabetes mellitus on the rat heart were investigated in order to detect possible synergistic effects of the two conditions. Hypertensive diabetic and hypertensive nondiabetic young male Wistar rats were compared with diabetic and non-diabetic controls. Since the normal body weight increase of the diabetic animals was markedly suppressed a weight-matched nondiabetic control group was introduced in addition. Hypertension was established for eight weeks by a surgical stenosis of the left renal artery, diabetes mellitus was maintained for four weeks after a single intraperitoneal injection of 75 mg/kg streptozotocin. Light and electron microscopic stereological parameters were obtained for the left ventricular papillary muscles. The whole hearts were also investigated histologically. Qualitative morphology failed to substantiate synergistic effects in the hypertensive diabetic rats. Vascular abnormalities were not observed. The stereological parameters, however, revealed microstructural reactions which were observed exclusively in the hypertensive diabetic group: the volume ratio of mitochondria-to-myofibrils was decreased, the surface-to-volume ratio of mitochondria was increased (reduction of mitochondrial size) and the mean cross sectional area of capillaries was decreased. Similar quantitative mitochondrial changes have been frequently described in long-standing hypertension, but in the present investigation, they were not found in the nondiabetic hypertensive group. It is therefore concluded that diabetes mellitus potentiates the effects of chronic pressure overload on myocardial cells. However, the myocardial fibrosis which has been found by other groups at later stages of hypertension and/or diabetes mellitus was not detected in the present study. The reduced mean cross sectional area of capillaries in hypertensive-diabetic rats may be correlated with early molecular changes of the myocardial interstitium or with early abnormalities of small arteries. Thus our stereological results support the hypothesis that a non-coronary hypertensive diabetic cardiomyopathy occurs in mammalian hearts.

Animals↗
PubMed1987

Growth of capillaries and myocardial cells in the normal rat heart.

The normal growth process of myocardial cells and capillaries in the late postnatal period (after weaning) was studied in 33 normal male Wistar rats (group I: 5 weeks, n = 9; group II: 7 weeks, n = 7; group III: 13 weeks, n = 8; group IV: 52 weeks, n = 9). The rats were fixed by retrograde vascular perfusion via the abdominal aorta. Two transverse and 2 longitudinal sections per animal were selected at random from the left ventricular papillary muscles for light and electron microscopic stereological investigation. Length density and surface density of myocardial cells and capillaries were estimated with correction for partial anisotropy and curvature by means of the mathematical model of a Dimroth-Watson orientation distribution. The results were analyzed by allometric techniques. Relative left and right ventricular weight decreased continuously throughout the growth process; in terms of allometry, ventricular weight was proportional to (body weight). The capillaries showed predominantly longitudinal growth with nearly constant cross-sectional area, whereas the myocardial cells grew by nearly harmonic enlargement into all three directions of space. The relation between total capillary length and left ventricular weight could be described in close approximation by the allometric model (r = 0.98, P less than 0.001). Corresponding to the result that total capillary length was proportional to (left ventricular weight)0.71, the myocardial capillarization (length, surface area, and volume of capillaries per unit tissue volume) decreased with increasing heart size. As allometry makes possible the quantitation of the intensity of growth processes by a single dimensionless number (the allometric exponent), this method permits a convenient interlaboratory comparison of growth studies, and it allows a comparison of capillary reactions during maturation and in experimental cardiac hypertrophy.

Animals↗
PubMed1987

Diminished parathyroid 1,25(OH)2D3 receptors in experimental uremia.

In Sprague Dawley rats, six days after subtotal nephrectomy, serum 1,25(OH)2D3 concentration was diminished (59.8 +/- 17.5 pg/ml vs. 121 +/- 48; P less than 0.01). Despite low circulating 1,25(OH)2D3 levels, maximal specific binding capacity for 1,25(OH)2D3 in parathyroid glands was diminished (Nmax 87.5 fmol/mg protein and 3.52 fmol/mg DNA vs. 143 fmol/mg protein and 4.75 fmol/mg DNA, respectively). There was no change of KD, apparent molecular size (sucrose density gradient) and DNA binding affinity (DNA cellulose chromatography) pointing to intactness of the receptor. Since 1,25(OH)2D3 is a potent negative feedback signal for parathyroids, the data are potentially relevant for the genesis of secondary renal hyperparathyroidism.

Animals↗
PubMed1987

Dipyridamole-induced neoformation of capillaries in the rat heart. Quantitative stereological study on papillary muscles.

Eighteen young male Wistar rats were randomly divided into two groups of equal size. Each experimental animal was treated with the powerful vasodilating drug dipyridamole (4 mg kg-1 intraperitoneally twice daily) for a period of 6 weeks. The control animals received sham injections with saline. The rats were fixed by retrograde vascular perfusion. Seven transverse and two longitudinal sections per animal were randomly selected from the left ventricular papillary muscles for stereological investigation. Length density of capillaries (length of capillaries per unit of tissue volume), surface density of capillaries (surface area of capillaries per unit of tissue volume) and the "true" three-dimensional capillary-fiber ratio (length of capillaries per unit length of myocardial fibers) were estimated by means of the Dimroth-Watson distribution, a mathematical model of directional statistics which assumes that the capillary directions scatter around the longitudinal axis of the muscle. This model was recently introduced into the stereology of myocardial capillaries and leads to a more accurate quantitation of the capillary network than parameters used hitherto, such as the "capillary density" (number of capillary profiles per mm2 of cross sectional area) and the "capillary-fiber ratio" (number of capillary profiles per number of myofiber profiles in cross sections). After chronic dipyridamole treatment, the length density of myocardial capillaries (+5%; p less than 0.02), the surface density of capillaries (+8%, p less than 0.01) and the three-dimensional capillary-fiber ratio (+6%, p less than 0.05) were increased. It is therefore concluded that the vasodilating drug dipyridamole evokes capillary growth in the heart which may be induced by mechanical factors via the enhanced myocardial blood flow. Investigation of the frequency distribution of capillary directions in space in both groups provided evidence that the capillary growth resulted from neoformation of capillaries.

Animals↗
PubMed1987

Statistical methods for growth allometric studies.

Simple least square regression analysis, major axis regression, and reduced major axis regression have been advocated for straight line fitting to the logarithmically transformed data pairs in bivariate allometric studies. As all these techniques are based on rigid a priori assumptions on the error structure, their application may lead to considerable biases in slope estimation if these requirements are not met. A different mathematical model, the linear functional relationship, allows to remove the bias by estimating the error structure from grouped empirical data. The model is applicable to interspecific and cross-sectional growth allometric studies where natural grouping criteria are available (species, age). The technique is illustrated by growth allometry of myocardial cells and capillaries in the late postnatal period (after weaning) in 33 normal male Wistar rats (group 1: 5 weeks, group 2: 7 weeks, group 3: 13 weeks, group 4: 52 weeks). In left ventricular myocardium fixed by vascular perfusion, length and volume densities of myocardial cells and capillaries were estimated by stereological techniques at the light and electron microscopic level. Total capillary length and total myocardial cell volume were scaled to total myocardial cell length. A comparison of the scaling methods showed an underestimation of the slope and its confidence interval by all regression techniques, which would have led to the erroneous conclusion that the myocardial cell does not remain geometrically similar throughout the normal growth process. Linear functional relationship and the technique of instrumental variables led to nearly identical results and were both compatible with geometric similarity of the myocardial cell during growth. Positive allometry of total capillary length to total myocardial cell length (b = 1.674) demonstrates continuous neoformation of capillaries. The intensity of capillary proliferative activity during growth was intermediate between the reactions observed in myocardial hypertrophy due to pressure overload and that due to physical training. This agrees with the fact that both systemic arterial pressure and cardiac output increase during maturation. The study is designed as a worked example which should enable the practicing researcher to treat data from cross-sectional growth allometric studies with a simple and unbiased statistical method.

Animals↗
PubMed1987

[Protective reaction of the myocardium in poisoning].

Intensive synthesis of collagen-like substance was revealed in the rabbit myocardium during experimental diphtheria intoxication. It was more marked in the right ventricle 24 hours after the injection of diphtheria toxin. Since similar changes (the substance was mainly formed around blood vessels) have been observed in other cases of toxic myocardial alterations (i.e. ethanol intoxication, injection of pharmacological agents, etc.), it can be assumed that it is a standard protective reaction of the altered heart to the penetration of toxic agents from the blood into the myocardial tissue.

Animals↗
PubMed1986

Morphological reaction patterns in experimental cardiac hypertrophy--a quantitative stereological study.

Four experimental models of myocardial hypertrophy were investigated in rats: 1. Mild hypertrophy induced by physical exercise, 2. mild hypertrophy induced by chronic pressure overload (24 weeks), 3. moderate hypertrophy induced by chronic pressure overload (8 weeks), 4. moderate hypertrophy in diabetes induced by chronic pressure overload (8 weeks). Stereological investigations on left ventricular papillary muscles disclosed different morphological reaction patterns: 1. The capillary bed of the myocardium responded differently in mild hypertrophy:physical training, but not mild chronic pressure overload, evoked neoformation of capillaries. 2. Mild hypertrophy and moderate hypertrophy induced by chronic pressure overload were not associated with quantitative structural reactions of myofibrils and mitochondria. Those alterations appeared, however, in hypertensive-diabetic rats with moderate hypertrophy. Our data provide further experimental evidence for the existence of a hypertensive-diabetic cardiomyopathy.

Animals↗
PubMed1986

Stereology of myocardial hypertrophy induced by physical exercise.

Twenty young female Sprague-Dawley rats were randomly assigned to 2 groups. Ten animals served as sedentary controls, the 10 experimental animals were subjected to a training program with gradually increasing intensity of 18 weeks duration on a motor-driven treadmill. The rats were fixed by retrograde vascular perfusion via the abdominal aorta under anesthesia. Two transverse and 2 longitudinal sections per animal were selected at random from the left ventricular papillary muscles for light and electron microscopic stereological investigation. Length density and surface density of myocardial cells and capillaries were estimated with correction for partial anisotropy and curvature by means of the mathematical model of a Dimroth Watson orientation distribution. Left and right ventricular weight increased by 20% in the exercise group (P less than 0.001), whereas body weight remained unchanged. Physical training led to a significant increase of heart muscle fiber cross-sectional area by 17% (P less than 0.01). The ultrastructural volumetric composition of the myocardial cell cytoplasm by myofibrils, mitochondria, and sarcoplasmic matrix remained unchanged. Volume density, length density and surface density of capillaries, as well as capillary cross-sectional area and capillary anisotropy parameters were not significantly altered by training. From the data one concludes an increase of the 3-dimensional capillary-fiber ratio by 19% (P less than 0.001). Thus physical training induces mild absolute biventricular cardiac hypertrophy in young female rats, in which capillary proliferation compensates for the increase of mean oxygen diffusion distance resulting from fiber thickening, by supplying each unit of fiber length by more units of capillary length.

Animals↗
PubMed1986

Stereological study on the rat heart in chronic alimentary thiamine deficiency--absence of myocardial changes despite starvation.

Young male Wistar rats were fed with a thiamine-free diet for 35 days. The growth of the thiamine-deficient animals was considerably suppressed, as compared to a pair-fed control group (body weights: 140.4 +/- 4.3 g v. 243.1 +/- 4.3 g). A weight-matched control group was therefore evaluated in addition. Histological and ultrastructural investigations of the hearts did not reveal any morphological abnormalities. Stereological analysis was performed on left ventricular papillary muscles. One-way analysis of variance showed significant differences of stereological parameters between the three groups which were not associated with significant linear contrasts between the thiamine-deficient group and the weight-matched control group. Thus, the changes are not to be related to direct effects of thiamine depletion on the myocardium. Conclusively, the data indicate that stereological parameters (ratios) of the myocardium depend on heart weight and body weight, respectively, and are changed during normal growth. Our stereological estimates disclosed alterations of the following parameters: numerical density of myocardial cell nuclei, length density and volume density of capillaries, surface density of outer mitochondrial membranes and surface-to-volume ratio of mitochondria, and volume density of myofibrils. Furthermore, relative heart weights decrease in normal growth. It is concluded that our experimental model of chronic alimentary thiamine deficiency was associated with a normal structure of the myocardium. All significant differences between the thiamine-deficient group and the control group are explained by body weight changes following starvation in chronic thiamine deficiency.

Animals↗
PubMed1985

Myocardial hypertrophy in rats with renal insufficiency.

Increased defatted dry wt of the heart and increased heart calcium content were observed in subtotally nephrectomized male Sprague-Dawley rats compared with sham-operated pairfed controls. Increased heart wt contrasted with no change of the weight of viscera (liver, spleen) and markedly decreased weight of striated muscle. Heart wt was unchanged after 5 days of renal insufficiency, but significantly increased after 14 or 21 days. Increased heart wt persisted despite effective beta adrenoreceptor blockade (2 X 10 mg metroprolol/kg/day i.p.) or effective alpha-1-adrenoreceptor blockade (2 X 2 mg prazosin/kg/day i.p.). Increased heart wt was also demonstrable despite normalization of basal blood pressure (intraarterial blood pressure measurement in conscious animals): blood pressure was lowered in one series with hydralazine/nadolol in drinking water (calculated to deliver 20 and 2 mg/kg/day, respectively) and in another series with furosemide in drinking water (15 mg/kg/day) combined with metoprolol (2 X 10 mg/kg/day i.p.). Increased heart wt was also noted despite correction of anemia by blood transfusion (Hct greater than 40%) and after parathyroidectomy in animals kept eucalcemic with high dietary calcium. Micromorphometry of left ventricular myocardium in perfusion-fixed tissue showed no significant change of the relative proportion of connective tissue and myocardial fibers. Myocardial isomyosin pattern was changed with an increase of fast-migrating V1 isomyosin in animals with renal insufficiency compared to sham-operated pairfed controls.

Adenosine Triphosphatases↗
PubMed1985

Orthogonal triplet probes: an efficient method for unbiased estimation of length and surface of objects with unknown orientation in space.

If the axis of anisotropy of oriented, tubular or lamellar objects is unknown, the unbiased stereological estimation of length density and surface density (Lv and Sv) requires counts on sections with isotropic uniform random (IUR) orientation. It is shown theoretically that in homogeneous, anisotropic specimens the precision of Lv and Sv estimation is considerably augmented if IUR-oriented sets of three mutually perpendicular sections (orthogonal triplet probes = ortrips) are used instead of three directionally independent IUR sections. The mechanism of variance reduction results from a negative covariance between sections within 'ortrips' and corresponds to the antithetic variate principle of Monte Carlo work. Heterogeneity decreases the efficiency of the ortrip method, but this effect can often be counteracted by systematic sampling of ortrips within specimens. Practical estimation of length and surface area of the highly anisotropic, tubular myocardial capillaries per tissue volume in the left ventricles of eight normal, adult, male perfusion-fixed Wistar rats provided estimates of excellent precision with CEs of 3.3% (Lv) and 2.1% (Sv) of the group mean. The method will hopefully allow stereologists dealing with arbitrary anisotropic structures to apply the same simple, efficient, and unbiased sampling designs that have long been used in the study of liver, lung, and kidney tissue.

Animals↗
PubMed1985

Kinetics of 13N-ammonia uptake in myocardial single cells indicating potential limitations in its applicability as a marker of myocardial blood flow.

To study kinetics and principles of cellular uptake of 13N-ammonia, a marker of coronary perfusion in myocardial scintigraphy, heart muscle cells of adult rats were isolated by perfusion with collagenase and hyaluronidase. Net uptake of 13N, measured by flow dialysis, reached equilibrium within 20 sec in the presence of sodium bicarbonate and carbon dioxide (pH 7.4, 37 degrees C). Total extraction, 80 sec after the reaction start, was 786 +/- 159 mumol/ml cell volume. Cells destroyed by calcium overload were unable to extract 13N-ammonia. Omission of bicarbonate and carbon dioxide reduced total extraction to 36% of control. 13N-Ammonia uptake could also be reduced by 50 muM 4,4' diisothiocyanostilbene 2,2' disulfonic acid, by 100 micrograms/ml 1-methionine sulfoximine, and by preincubation with 5 muM free oleic acid. These results indicate that in addition to metabolic trapping by glutamine synthetase, the extraction of 13N-ammonia by myocardial cells is influenced by cell membrane integrity, intracellular-extracellular pH gradient, and possibly an anion exchange system for bicarbonate. For this reason, the uptake of 13N-ammonia may not always provide a valid measurement of myocardial perfusion.

Ammonia↗
PubMed1985

[Neuroendocrine larynx cancer of the small cell (oat cell) type. Morphologic and immunohistochemical findings and their significance for therapy].

By combining immunohistochemical, biochemical, and light and electron microscopy techniques, the following original observations concerning the rare and highly malignant small cell ("oat cell") carcinoma of the larynx were made: The typical electron microscopic feature was the presence of neurosecretory granules in some cells. This indicates that this tumour was a carcinoma with endocrinal differentiation. The demonstration of cytokeratins as major cytoskeletal components, as well as the presence of desmosomes, confirmed the epithelial origin of the tumour cells. The detection of neuroendocrinal markers such as calcitonin and neuronspecific enolase (NSE) in some of the tumour cells, as well as the presence of neurosecretory granules allow us to classify this tumour as a neuroendocrinal carcinoma of the small-cell type. This is in accordance with the latest classification of neuroendocrine carcinomas of the lung. The rapid clinical evolution of the disease is typical for patients with anaplastic carcinomas. Laryngectomy followed by adjuvant chemotherapy and radiotherapy is indicated only in cases without metastases. The detection of regional metastases suggests haematogenous spread with distinct metastases, restricting treatment to chemotherapy and radiotherapy.

APUD Cells↗
PubMed1984

Estimation of length and surface of anisotropic capillaries.

Surface density (SV) and length density (LV) of myocardial capillaries have hitherto been estimated from their profile boundary length (BA) and their numerical density (QA) on transverse sections by the simplifying assumptions of the Krogh model (perfectly anisotropic, straight, unbranched capillaries with constant cross-sectional area). As the capillaries actually are partially anisotropic, curved, branching cylinders with variable cross-sectional area, a geometrical bias arises from the model-reality discrepancies. We have applied and compared two methods to overcome these inconsistencies: (1) estimation of LV and SV by a more realistic model (the Dimroth-Watson distribution); (2) estimation of LV and SV from isotropic uniform random (IUR) sections. Twelve male Wistar rats were fixed by retrograde vascular perfusion. One pair of longitudinal and transverse sections, and six IUR sections per animal were selected at random from the left ventricular papillary muscles. Ultrathin sections were silver-impregnated and studied by light microscopic morphometry. Nearly identical estimates of LV and SV were found by both methods. The model-based estimation provides biologically meaningful anisotropy constants, but it presupposes knowledge of the anisotropy axis. The IUR method provides no measure of anisotropy, but it can be applied in tissues where the anisotropy axis is not known. Both methods are equally efficient and practically unbiased in SV estimation, but the model-based estimation is far more efficient in LV estimation.

Animals↗
PubMed1984

Reduction of coronary reserve: a mechanism for angina pectoris in patients with arterial hypertension and normal coronary arteries.

The pathogenesis of angina pectoris in patients with left ventricular hypertrophy secondary to arterial hypertension and with normal coronary arteries remains uncertain. We measured coronary blood flow (argon method) in 12 control subjects and in 16 patients with arterial hypertension at rest and after intravenous administration of dipyridamole (0.5 mg/kg). In the patients with arterial hypertension, coronary blood flow response to dipyridamole was markedly reduced (p less than .001 as compared with control values). During coronary vasodilation there was a linear correlation between coronary resistance and left ventricular end-diastolic pressure (r = .67, p less than .001). Left ventricular catheter biopsy specimens did not reveal alterations in myocardial microvasculature. These findings suggest that reduction of coronary reserve may be an important contributor to the pathogenesis of angina pectoris in these patients.

Adult↗