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T Mattfeldt

Publications and source records attributed to T Mattfeldt.

90 records · Page 5Linked to original sources
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

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

Stereologic correlates of steroid receptor concentration in invasive ductal breast cancer.

The hypothesis was tested that morphometric parameters of tumor cell nuclei correlate with the steroid receptor concentration in mammary carcinoma. In 50 consecutive mastectomy specimens with a diagnosis of invasive ductal cancer in which estrogen receptor (ER) and progesterone receptor (PR) concentrations had been assayed quantitatively, morphometric measurements were performed on four visual fields of two sections per case. The fields were sampled from the most cellular regions of the tumor. The number of tumor cell nuclear profiles per tissue area, the nuclear profile area and the long and short nuclear profile axes and their ratios were measured with a semiautomatic image analysis system. Estimates of the number of tumor cell nuclei per tissue volume (Nv) and of the mean tumor cell nuclear volume (V) were obtained by standard stereologic techniques. Association between the morphometric and biochemical parameters was tested by Spearman's rank correlation coefficient. Nv correlated positively with the steroid receptor concentration whereas V correlated negatively with both ER and PR concentrations. A correlation of the receptor concentrations to the standard deviation of the nuclear area or the mean ratio of the nuclear axes could not be demonstrated. These results suggest that receptor-rich tumors have a large number of small tumor cell nuclei whereas receptor-poor tumors have a small number of large tumor cell nuclei per tissue volume in the actively proliferating, highly cellular regions. These differences are not accompanied by significant changes in nuclear size variability or nuclear shape.

Breast Neoplasms↗
PubMed1984

Necropsy evaluation in seven patients with evolving acute myocardial infarction treated with thrombolytic therapy.

Systemic and intracoronary streptokinase application may recanalize a coronary artery occluded by a thrombus in patients with acute myocardial infarction (MI). However, thrombolysis fails in a number of patients for unknown reasons. The coronary and myocardial histologic characteristics were studied in 3 patients in whom recanalization was successful without subsequent reocclusion, and in 4 patients in whom recanalization was unsuccessful. All patients died within 4 weeks after the acute intervention. Serial sections from the angiographically localized occlusive site of the infarct vessel, and transverse slices of the heart stained with nitroblue tetrazolium for delineation of MI, were examined by light microscopy. Successfully recanalized arteries were patent at necropsy and showed obstructive fibrous atherosclerotic plaques. Among patients in whom recanalization was unsuccessful, 1 patient had occlusions from nonatherosclerotic intramural hemorrhage and 1 from persisting long, mixed old and fresh thrombus, and 2 patients had high-grade obstructions from ruptured atherosclerotic plaques with intimal hemorrhage and residual clot. Reperfused infarct tissue consisted predominantly of contraction band necroses, whereas MIs without reperfusion showed coagulation necroses of the muscle fibers. The results suggest that the success of recanalization depends, in part, on the morphologic features of the coronary occlusion, and that reperfusion after successful thrombolysis may lead to a different pattern of muscle fiber necrosis in the irreversibly injured infarct areas.

Adult↗
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↗
PubMed1983

Dipyridamole-induced capillary endothelial cell proliferation in the rat heart--a morphometric investigation.

20 male Wistar rats were randomly divided into two equal groups. Each experimental rat was injected with 4 mg . kg-1 dipyridamole ip twice daily for 4 weeks, the control rats received sham injections of an equal volume of saline. The rats were fixed by retrograde vascular perfusion. Left ventricular papillary muscles were sampled for light and electron microscopic morphometry. By means of a combination of serial section reconstruction and morphometry we could demonstrate that the number of capillary endothelial cell nuclei per tissue volume had increased by 37% (P less than 0.01), whereas the average nuclear volume remained constant. All other morphometric parameters (volume densities of myocardial cells, capillaries, cellular and non-cellular interstitial tissue, and myocardial cell nuclei; surface area, diameter, and density of capillaries; volume densities of myofibrils, mitochondria, and sarcoplasmic matrix; surface areas of the inner and outer mitochondrial membranes; dimensions of average mitochondrial section profiles) were unchanged. We conclude that chronic dipyridamole application induces proliferation of capillary endothelial cells in the rat myocardium, possibly by an increase of myocardial blood flow.

Animals↗
PubMedDate not supplied

Capillary neoformation in the rat heart--stereological studies on papillary muscles in hypertrophy and physiologic growth.

Stereological investigations on myocardial capillaries provided evidence that the common estimator of capillarity, the capillary density (i.e., number of capillary profiles per unit transverse sectional area), underestimates the true capillary supply since the capillary axes are not oriented perfectly in parallel to the myofiber axes. Recently, we studied the "true" capillarity, i.e., the length density of capillaries (LV = capillary length per capillary volume), in some experimental models of cardiac hypertrophy which have been published elsewhere. It has been shown that LV decreases in renovascular hypertension, but is maintained in physical exercise and after chronic thyroxin application. However, the growth pattern of capillaries in hypertrophic hearts has not yet been analyzed. In the present paper it is demonstrated that important information on the capillary network can be derived from the two-dimensional capillary-to-fiber ratios (2D CFR: capillary profiles per myofiber profiles in transverse sections) and from the three-dimensional capillary-to-fiber ratios (3D CFR: capillary length per unit myofiber length). Increase in both suggests neoformation of additional capillary branches in parallel connection. Retrospective analysis of the quantitative data indicates that in hypertrophy induced by physical exercise or by chronic thyroxin application capillary neoformation in parallel connection counterbalances increase of oxygen diffusion distance due to myofiber enlargement. In renovascular hypertension, capillary neoformation in parallel connection does not occur. Studies on normal growth indicated both a slight decrease of LV of capillaries, as well as a continuous neoformation of additional capillary branches.

Animals↗
PubMedDate not supplied

Morphometric analysis of the rabbit myocardium after chronic ethanol feeding - early capillary changes.

Male rabbits were fed with ethanol for 3 weeks. 10 ml of a 20% ethanol solution were applied daily with a stomach tube. The macroscopic, histologic and ultrastructural investigation of the hearts did not reveal and structural alterations. Morphometrically, the endothelial cells of the capillaries were changed, whereas the muscle cells did not show any abnormalities. The quantitative data indicate that the numerical density of endothelial cells is increased, whereas the volume density is not changed. This type of quantitative reaction pattern may be characterized as "proliferation" of endothelial cells. The proliferation is possibly related to ethanol-induced metabolic changes similar to chronic hypoxia. On the other hand, there is some evidence that the alteration is part of a general activation of mesenchymal cells in various organs after ethanol ingestion. The alteration is probably an early stage of the proliferation of capillaries.

Animals↗
PubMedDate not supplied

High-dose diltiazem prevents migration and proliferation of vascular smooth muscle cells in various in-vitro models of human coronary restenosis.

BACKGROUND: Restenosis after coronary angioplasty is considered to be caused mainly by increased migration and proliferation of smooth muscle cells (SMC). The concept of local, site-specific delivery of pharmacologic therapies has opened the door for new, high-dose drug regimes. METHODS AND RESULTS: SMC were isolated by enzymatic disaggregation with collagenase/elastase from human coronary plaque tissue of 29 patients (pSMC) and post mortem from the coronary media of 33 corpses (mSMC). Endothelial cells were isolated from human umbilical veins by enzymatic disaggregation with collagenase/dispase. By positive reaction with antibodies against smooth muscle alpha-actin and von Willebrand factor cells were identified as SMC or endothelial cells. In proliferation studies 5-150 micrograms/ml diltiazem was added to the culture media of pSMC, mSMC and endothelial cells. After 5 days there was a significant dose-dependent inhibition of cell proliferation (for pSMC with > 50 micrograms/ml, for mSMC with > 25 micrograms/ml, and for endothelial cells with > 5 micrograms/ml). In migration studies the effect of 5-150 micrograms/ml diltiazem on the velocity of migration of pSMC was investigated over a period of 48 h. Administration of diltiazem at concentrations of 100 and 150 micrograms/ml caused a significant inhibition of the migration of pSMC. The cytoskeletal components smooth muscle alpha-actin, vimentin, and alpha-tubulin of pSMC and the expression of von Willebrand factor of endothelial cells were investigated after an incubation period of 5 days with 50 and 150 micrograms/ml diltiazem. In the transfilter coculture model the effect of 50 micrograms/ml diltiazem on mSMC was investigated after mechanical injury of cocultured endothelial cells. Administration of diltiazem at a concentration of 50 micrograms/ml inhibited the development of a neointimal proliferate in the transfilter coculture model significantly (P < 0.001). CONCLUSIONS: A high dose of diltiazem inhibited the migratory and proliferative activities of coronary SMC significantly. In further experimental studies the effect of locally applied high doses of diltiazem on postangioplasty restenosis should be elucidated.

Actins↗
PubMedDate not supplied

[Classification of cytological smears of the cervix with neuronal methods].

BACKGROUND: Cytological smears obtained from the cervix are routinely examined under the microscope as part of screening programs for the early detection of cervical cancer. The aim of the present study was to investigate whether a simple feature extraction approach using only standard image processing techniques combined with a neural classifier would lead to acceptable results that might serve as a starting point for the development of a fully automated screening system. MATERIALS AND METHODS: Gray-value images of 106 cervical smears (512 x 512 pixels) divided into two groups--inconspicuous (57) and atypical (49)--by an experienced pathologist on the basis of the original smears were employed to evaluate the method. From these images, 31 features quantifying properties of either the cell nucleus or the cytoplasm were extracted. These features were categorized with three different architectures of a neural classifier: learning vector quantization (LVQ), multilayer perceptron (MLP) and a single perceptron. CONCLUSIONS: The results show a reclassification accuracy of about 91% for all three algorithms. Sensitivity was uniform at approximately 78%, and specificity varied between 75% and 91% in the leave-one-out evaluation. These very good results provide strong encouragement for further studies involving PAP scores and colour images.

Artificial Intelligence↗
PubMedDate not supplied

P53 mutation but not p16/MTS1 mutation occurs in intraductal papillary mucinous tumors of the pancreas.

BACKGROUND/AIMS: Intraductal papillary mucinous tumors of the pancreas are rare lesions, which typically show a benign clinical course. However, some of these tumors have a malignant nature and grow in an invasive manner. The purpose of the study was to determine the prevalence of p53-, p16/MTS1- and K-ras mutations in benign and malignant intraductal papillary mucinous tumors with intent to value their importance for tumor progression. METHODOLOGY: Thirteen different archival tumor specimens were obtained at the Department of Pathology, University of Ulm. Three cases showed an invasive component of the tumor. Genomic DNA was extracted after laser capture microdissection of tumor cells from paraffin-embedded tissue sections. The corresponding sequences of p53 (exon 5, 6, 7, 8) and p16/MTS1 (exon 2) were amplified by polymerase chain reaction and subjected to single strand conformation polymorphism analysis. Codon 12 of K-ras was analyzed by the enrichment polymerase chain reaction-restriction fragment length polymorphism method. Positive samples were further investigated by sequencing. RESULTS: K-ras mutations occurred in benign and malignant intraductal papillary mucinous tumors (4/13), whereas an alteration of the coding p53 gene sequence could only be detected in the intraductal and invasive component of one malignant tumor. None of the tissue specimens revealed mutations in exon 2 of p16/MTS1. CONCLUSIONS: In contrast to K-ras mutations, alterations in the p53 gene may characterize ductal papillary mucinous carcinomas, which could be of major interest for their early diagnosis. The lack of mutations in the p16/MTS1 gene suggests that other genes may be involved in the formation of intraductal papillary mucinous neoplasias.

Biomarkers, Tumor↗