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Biomedical subjects

B Speiser

Publications and source records attributed to B Speiser.

13 recordsLinked to original sources

Expression of platelet-derived growth factor and its receptor in AIDS-related Kaposi sarcoma in vivo suggests paracrine and autocrine mechanisms of tumor maintenance.

As previously described, proliferation of Kaposi sarcoma (KS)-derived cells in vitro is dependent on the presence of platelet-derived growth factor (PDGF). To test the hypothesis that PDGF may also be a major growth factor for KS cells in vivo, we performed in situ hybridization and immunohistochemical staining for PDGF and PDGF receptors in tissue sections of AIDS-related KS. The data suggest that KS consists of two types of tumor cells. (i) The main population are spindle-shaped cells with elongated nuclei (KS-s cells). They reveal a strong expression of PDGF beta receptors but do not express the PDGF-A and PDGF-B isoforms. (ii) A minor population of KS cells express PDGF beta receptor as well as PDGF-A and PDGF-B (KS-p cells). These cells are often grouped in whorls and surrounding vascular slits. They reveal spherical nuclei with evenly distributed chromatin and inconspicuous nucleoli. PDGF alpha receptor is not expressed in either form of KS cells. The results suggest that the isoforms of PDGF and the PDGF beta receptor are differentially expressed in two different cell types in KS and that PDGF isoforms may contribute to the pathogenesis of KS.

Acquired Immunodeficiency Syndrome

The extracellular matrix in the failing human heart.

The composition of the extracellular matrix was investigated in eight human hearts explanted at the time of transplantation surgery because of endstage cardiomyopathy. All patients showed clinical signs of heart failure. The tissue was investigated by electron microscopy and immunofluorescence microscopy using monoclonal antibodies against collagen I, III, VI, and IV, fibronectin, laminin, and vimentin. All matrix proteins occurred in increased amounts in the extracellular space separating the myocardial cells by septa of enlarged thickness. Laminin and collagen IV surrounded myocardial and endothelial cells as layers of increased thickness. Vimentin localization was normal in individual cells, but occurred more often and corresponded to the numerous fibroblasts as observed by electron microscopy. It is concluded that an excessive deposition of extracellular matrix material in addition to myocyte degeneration (as reported previously (9)) are the structural correlates of cardiac failure.

Cardiomyopathy, Dilated

Ultrastructural quantitation of mitochondria and myofilaments in cardiac muscle from 10 different animal species including man.

The ultrastructural quantitative composition of normal myocardial cells has been studied in 10 different species: man, dog, pig, cat, rabbit, ferret, guinea-pig, rat, mouse, and bat. Volume densities of mitochondria, myofibrils, and cytoplasm were determined using morphometry. It was found that the content of mitochondria differs in various species ranging between 22.0-37.0%. It is a very specific and constant value for any particular species, the smallest having the highest content. A close correlation exists between the mitochondrial volume density, heart rate and the rate of basal oxygen consumption in any group of animals. The myofibrillar volume density shows no species variability. It was about 60.0% in all species. It is concluded that the mitochondrial volume density is a good indicator of the oxidative capacity of cardiac muscle and that the species specific normal ultrastructural myocyte composition should be a useful baseline in pathophysiological studies of the heart in various animals.

Actin Cytoskeleton

The extracellular matrix in human cardiac tissue. Part II: Vimentin, laminin, and fibronectin.

In continuation of our previous work describing the localization of the collagens type I, III, VI, and IV the present study describes the localization of vimentin, laminin, and fibronectin in human myocardium obtained as left ventricular needle biopsies during cardiac surgery. Myocardium from normal pigs served for comparison. Monoclonal antibodies against the various proteins were used on frozen sections, labeled with fluorescein and viewed in the fluorescence microscope. Vimentin, the intermediate filament of mesenchymal cells, is present in fibroblasts, fibrocytes, and endothelial cells. Laminin is observed in the basal membrane of myocytes, smooth muscle and endothelial cells. The staining intensity for the B1-chain is higher in and around myocytes as compared with the B2-chain antibody, but more blood vessels were stained with the latter. The antibody against the A-chain only stained the basal lamina of vascular cells but not that of myocytes. Fibronectin was localized homogeneously throughout the extracellular space as matrix material in which the cellular elements and the various other proteins such as collagens are embedded. Intracellular staining in myocytes (T-tubules) was commonly observed. Both parts of this study show the distribution of extracellular proteins in normal human cardiac tissue and are intended to be the basis for investigations of pathological changes in diseased human myocardium.

Animals

Impairment of the myocardial ultrastructure and changes of the cytoskeleton in dilated cardiomyopathy.

This study was designed to determine the morphological correlate of chronic heart failure. Myocardial tissue from eight patients undergoing transplantation surgery because of end-stage dilated cardiomyopathy was investigated by electron microscopy and immunocytochemistry using monoclonal antibodies against elements of the cytoskeleton: desmin, tubulin, vinculin, and vimentin. The tissue showed hypertrophy, atrophy of myocytes, and an increased amount of fibrosis. Ultrastructural changes consisted of enlargement and varying shape of nuclei, numerous very small mitochondria, proliferation of T tubules, and accumulation of lipid droplets and glycogen. The most obvious ultrastructural alteration was the decrease of myofilaments, ranging from rarefication to complete absence of sarcomeres in cells filled with unspecified cytoplasm. Immunocytochemistry showed that desmin was localized at the Z lines. In diseased myocardium, the amount of desmin was increased, but it was disorderly arranged. Tubulin formed a fine network throughout the myocytes and was significantly increased in cardiomyopathic hearts. Vinculin, a protein closely associated with the cytoskeleton, occurred not only at the sarcolemma and the intercalated disc but also within the myocardial cells. Ultrastructural changes and alterations of the cytoskeleton were severe in about one third of all cells. About one third of all cells showed moderately severe changes, and the remaining cells were normal. Vimentin was present in the interstitial cells and was increased in relation to the increase of fibrosis. We conclude that the increase of fibrosis, the degeneration of hypertrophied myocardial cells, and the alterations of the cytoskeleton are the morphological correlates of reduced myocardial function in chronic heart failure.

Antibodies, Monoclonal

[Morphologic HIV demonstration in formalin embedded material--techniques, problems, results].

Formalin-fixed, paraffin-embedded material of archival specimens is suitable for a morphological HIV-detection: Infected cells with HIV in the proliferative phase can be demonstrated with reliable results on tissue sections by immunohistological technics using new antibodies. In situ nucleic acid hybridisation technics can also show HIV in the expression phase on paraffin-embedded material, but often fail in demonstrating latently HIV-infected cells. The DNA-Polymerase chain reaction can detect latent Provirus in morphologically defined areas of paraffin sections even in autopsy material, i.e. lymphnodes and even eyes of patients with HIV-Infection, but requires precaution and control with respect to contamination.

Acquired Immunodeficiency Syndrome

The extracellular matrix in human myocardium: Part I: Collagens I, III, IV, and VI.

The composition of the extracellular matrix in normal human myocardium obtained at open-heart surgery was investigated using monoclonal antibodies against the collagens I, III, IV, and VI, and fluorescence microscopy. The aim of the study was to provide information on normal myocardium that could be used in the evaluation of pathological changes. Porcine myocardium was used for comparison, and both tissues showed a perfect agreement of the results, apart from collagen IV. This was negative in pig myocardium, due to the species specificity of the antibody. Collagens I and III were localized in the extracellular space as either coarse or fine fibrillar structures; the cellular elements of the interstitium, except for the endothelial cells, were also stained. Labeling for collagen VI was much finer than for the other collagens, and was present throughout the interstitium. Collagen IV stained the basement membranes of myocytes and capillary endothelial cells, and also labeled the T-tubular system in the myocytes. The second part of this communication will describe the localization of fibronectin, laminin and vimentin in normal human myocardium.

Animals

Intermediate dose rate remote afterloading brachytherapy for intraluminal control of bronchogenic carcinoma.

Forty-five patients with symptomatic proximal malignant airway disease received 128 intraluminal intermediate dose rate (IDR) brachytherapy treatments by remote afterloading technique. Multiple small catheters were bronchoscopically placed. Iridium-192 sources delivering an intermediate dose rate (200-1000 rads/hr) were guided under remote computer control. Treatment times were 1-4 hr. Fourteen of these patients also received YAG laser photoresection. External beam radiation was also given (6000 rads) to 16 patients for curative intent and (3000 rads) to 9 patients for palliative intent. Twenty recurrent disease patients were also treated, but they did not receive external irradiation. An obstruction score (OS) was developed in an attempt to quantitate the improvement in intraluminal narrowing. Patients treated with curative intent showed 66% improvement after initial therapy. Initial therapy for palliative patients showed an 84% improvement and for recurrent disease patients, 64% of luminal narrowing was seen. Patients who received laser in addition to brachytherapy showed a 70% reduction. A 67% improvement was seen in those who did not receive laser therapy. The entire group averaged a 69% improvement of narrowing. Four complications, three minor, (1 bronchospasm, and 2 episodes of transient intratreatment increased ventricular irritability) and one major (pneumothorax) were noted. The relatively short treatment times allowed most of the treatments to be performed on an outpatient basis and were well-tolerated by the patients. Forty-four of the 45 patients experienced significant symptomatic improvement. The remote afterloading technique allowed improved radiation protection for personnel.

Adult