Biomedical subjects

M Kasper

Publications and source records attributed to M Kasper.

At least 37 records · Page 2Linked to original sources

PubMed1997

Cytoskeletal characterization of arteriovenous epithelioid cells.

Data on the cytoskeleton of epithelioid cells in arteriovenous anastomosis (AVA) are sparse, but there is evidence that the (myo)-epithelioid cells of the AVAs represent a specialized smooth muscle cell type with less contractile properties. We demonstrated the expression of alpha-smooth muscle actin, smooth muscle myosin, calponin, caldesmon, and caveolin in epithelioid cells of rabbit ear and in human toes, finger tips, and glomus tumors by means of indirect immunofluorescence techniques and immunoelectron microscopy. Epithelioid cells in rabbit ear did not express vimentin, but it was present in human toes, finger tips, and glomus tumors. Epithelioid cells in human toes, finger tips, and glomus tumors did not express desmin, but it was present in rabbit ear. Epithelioid cells did not express cytokeratins. The epithelioid cells examined showed only a weak expression of the protein smoothelin, which occurs exclusively in contractile smooth muscle cells. Immunoelectron microscopical demonstration of (alpha-smooth muscle actin revealed a striking difference in the arrangement of actin filaments in the epithelioid cells as compared to that in the smooth muscle cells of blood vessels. The epithelioid cells contained a loose array of actin filaments, whereas the smooth muscle cells contained tightly packed parallel actin bundles. In the present study we observed a correlation between the lack of contractile marker protein expression in epithelioid cells and the presence of only a few filaments, although the epithelioid cells are alpha-smooth muscle actin positive. The reduced number of contractile elements in the epithelioid cells of rabbit and human anastomoses suggests a lower contractility of epithelioid cells compared to that of the surrounding smooth muscle cells in anastomoses. A second interesting difference between both cell types is the high number of caveolae in epithelioid cells. Immunoelectron microscopy showed a compact distribution of caveolae at the epithelioid cell border, but a more dispersed distribution of caveolae in the cytoplasm of the blood vessel endothelium. The benign glomus tumor was characterized by an expression pattern of cytoskeletal proteins similar to that of epithelioid cells, confirming its description as a benign tumor.

Animals↗

PubMed1997

[Gasless video-endoscopic implantation of aortobifemoral vascular prostheses via extraperitoneal approach in the animal experiment].

The gasless videoendoscopic implantation of GELSOFT aortobifemoral vascular prostheses times 6 x 6 mm in diameter using an extraperitoneal approach was tested in ten porcine experimental models at the Surgical Department of the University of Cologne, Germany. Gasless videoendoscopic surgery is performed with a laparolift-laparofan system. Aortobifemoral GELSOFT prostheses were successfully implanted in nine of ten animals, whereby one animal died during preparations for surgery of massive coronary infarctions. Average surgical durations using the extraperitoneal approach were 270 min. Dissection of the infrarenal aorta until occlusion took 45 min, average aortic occlusion 75 min, and iliacofemoral occlusion 45 min for the left side and 75 min for the right side. After successful videoendoscopic implantation of aortobifemoral GELSOFT prostheses all nine animals underwent laparotomy and resection of the aortobifemoral prosthetic segment. The quality of the endoscopically sutured aortic end-to-side anastomoses was examined in vitro under artificial circulation of glycerol/Ringer's lactate solution for evaluation of possible leakage and bursting pressures and then compared to conventionally sutured end-to-side anastomoses of 6-h-old porcine abdominal aorta and GELSOFT prostheses 6 mm in diameter. The maximum bursting pressure of all endoscopically sutured anastomoses was 480 mmHg mean pressure: the minimum was 140 mmHg mean pressure. The minimum leakage per minute was less than 10 ml/min for systolic pressure values between 120 and 350 mmHg. All endoscopically sutured aortic end-to-side anastomoses were comparable to conventionally sutured anastomoses concerning in vitro evaluation of bursting pressure and leakage per minute.

Anastomosis, Surgical↗

PubMed1997

Cellular distribution of c-Jun and c-Fos in rat lung before and after bleomycin induced injury.

C-Jun and c-Fos transcription factors have been associated with enhanced cellular proliferation. We studied their cellular distribution in normal and fibrotic rat lung. Pulmonary fibrosis was induced by intratracheal administration of bleomycin. In normal rat lung, c-Jun and c-Fos are present in alveolar macrophages and type II pneumocytes, in the bronchiolar epithelium and in smooth muscle cells of bronchioli and blood vessels. Subcellular fractionation of proteins revealed a predominant presence of both c-Jun and c-Fos in the heavy membrane fraction containing mitochondria and secretory granules. This was confirmed by immunoelectron microscopy, which also revealed a different localization of c-Jun and c-Fos in different cell types. Whereas in type II pneumocytes and in macrophages cytoplasmic c-Jun and c-Fos is associated with mitochondria, in Clara cells of the bronchial epithelium only secretory granules contain c-Jun and c-Fos. In addition, c-Jun is strongly present in the nuclear fraction. In the fibrotic rat lung c-Jun and c-Fos are located in the same cell types as in control lungs. In addition, fibroblasts contain c-Jun and c-Fos in areas of proliferation whereas in areas of complete fibrosis there is only a very weak expression of c-Jun and c-Fos.

Animals↗

PubMed1997

Comparative studies on mammalian Müller (retinal glial) cells.

Müller cells from 22 mammalian species were subjected to morphological and electrophysiological studies. In the 'midperiphery' of retinae immunocytochemically labeled for vimentin, estimates of Müller cell densities per unit retinal surface area, and of neuron-to-(Müller) glia indices were performed. Müller cell densities were strikingly similar among the species studied (around 8000-11,000 mm-2) with the extremes of the horse (< or = 5000 mm-2) and the tree shrew (> or = 20,000 mm-2). By contrast, the number of neurons per Müller cell varied widely, being clustered at 6-8 (in retinae with many cones), at about 16, and at up to more than 30 (in strongly rod-dominated retinae). Isolated Müller cell volumes were estimated morphometrically, and cell surface areas were calculated from membrane capacities. Müller cells isolated from thick vascularized retinae (carnivores, rats, mice, ungulates) were longer and thinner, and had smaller volumes but higher surface-to-volume ratios than cells from thin paurangiotic (i.e. with blood vessels only near the optic disc) or avascular retinae (rabbits, guinea pigs, horses, zebras). In whole-cell voltage-clamp studies, Müller cells from all mammals studied displayed two dominant K+ conductances, inwardly rectifying currents and delayed rectifier currents. TTX-sensitive Na+ currents were recorded only in some species. Based on these data, the following hypotheses are presented, (a) neuron-to-(Müller) glia indices are determined by precursor cell proliferation rather than by metabolic demands; (b) Müller cell volumes depend on available space rather than on the number of supported neurons; and (c) it follows that, the specific metabolic activities of Müller cells must differ greatly between species, a difference that may contribute to distinct patterns of retinal vascularization.

Animals↗

PubMed1997

Detection and distribution of the carbohydrate binding protein galectin-3 in human notochord, intervertebral disc and chordoma.

Galectin-3 is an endogenous carbohydrate-binding protein which plays a role in cell differentiation, morphogenesis and cancer biology. We investigated the occurrence and distribution of galectin-3 in the embryonic and fetal human notochord, the developing human vertebral column, adult intervertebral discs and in six chordomas, which are tumors thought to originate from notochordal remnants. By means of Western blots, the expression of galectin-3 was confirmed in tissue probes from the vertebral column region beginning with the 8th gestational week. These results were supported by immunohistochemical data which revealed the presence of galectin-3 in the cytoplasm of cells of the notochord also from the 8th gestational week onwards. Notochordal immunostaining became stronger with increasing gestational age. A persisting notochordal remnant in an adult intervertebral disc and various cells of the nucleus pulposus also contained galectin-3. All chordomas showed moderate or strong immunoreactivity irrespective of their cellular composition. Subcellularly, galectin-3 was localized mostly in the cytoplasm, while a subset of tumor cells also showed nuclear distribution. Differences in staining patterns of chordoma cells could not, in general, be correlated to any histological features of these tumors.

Adolescent↗

PubMed1997

[Acute respiratory insufficiency after inhaling concrete dust--a case report].

UNLABELLED: Inhalation of inorganic, inert dusts, like concrete dust, has generally not been considered dangerous. Very rarely alterations following chronic exposures can be observed, such as airflow obstruction and increased mucous secretion. Acute reactions in terms of acute respiratory failure have not been described so far. CASE REPORT: The present case report introduces a 54-year old male patient who developed acute respiratory failure after sawing a concrete block for several hours without wearing a face mask. Save for a chronic obstructive pulmonary disease he was unremarkable for his past medical history. When the emergency physician arrived, oxyhaemoglobin saturation was only 54%. Severely obstructed breathing sounds and coarse bubbling rales over both lungs were audible. After endotracheal intubation, a great deal of white viscous mucus could be aspirated via the tubus. The chest radiograph after admission demonstrated cloudy, shadowed areas with emphasis on both lower lung fields. As pulmonary function did not improve inspite of drug therapy with prednisolone, theophylline, fenoterol, n-acetylcysteine and respiration therapy with 100% oxygen concentration, the patient was treated daily with bronchoscopic aspiration of the mucus. Only on the fourth day, after an additional ten hours in prone position, the lung function improved. The patient could be extubated on the fifth day. The final chest radiograph indicated no residuum apart from a very small shadowed area on the right angle between heart and diaphragm. CONCLUSION: The inhalation of dusts, which have long been considered inert, can cause acute pulmonary reactions. We suggest that the massive, mechanical covering on the alveolar layer with still alkaline concrete dust in conjunction with a history of chronic bronchitis was responsible for the acute inflammation and oedematous swelling of the bronchial mucosa, bronchospasm, secretion of a highly viscid mucus, atelectasis, and thus for the ARDS.

Acetylcysteine↗

PubMed1997

Connexin 43 expression in normal and irradiated mouse skin.

The expression of connexin 43 (Cx43) in normal and irradiated mouse skin was evaluated using immunofluorescence with polyclonal antisera to Cx43 on cryostat sections. One week after the start of daily irradiation with 3 Gy, enhanced immunoreactivity in basal cells and in the lower part of the spinous layer of the epidermis was detected. In hypertrophic and hyperplastic skin, about 3 weeks after irradiation, a further increase in the expression of Cx43 was found in the epidermis as well as in the dermis. Western blot analysis of normal and irradiated skin homogenates confirmed the increased Cx43 protein concentration in the skin. In nuclear extracts of the same preparations, increased AP-1-binding activity was found. These data suggest that the gap-junction protein is expressed in response to irradiation of the skin and may be related to the subsequent hyperproliferative response which is associated with accelerated repopulation.

Animals↗

PubMed1997

Epitope-mapped monoclonal antibodies as tools for functional and morphological analyses of the human urokinase receptor in tumor tissue.

uPAR (CD87), the receptor for the urokinase-type plasminogen activator (uPA) facilitates tumor cell invasion and metastasis by focusing uPA proteolytic activity to the cell surface. As uPAR exists in various molecular forms, it is desirable to use well defined antibodies for analyses of uPAR antigen expression in human malignant tumors by immunological methods. Therefore, twelve monoclonal antibodies (MAbs) directed against uPAR were generated by using nonglycosylated, recombinant human uPAR (spanning amino acids 1 to 284), expressed in Escherichia coli, as the immunogen. The reaction pattern of these MAbs with the immunogen and a series of carboxyl-terminally truncated versions of uPAR demonstrated that at least six different epitopes of uPAR are recognized. All MAbs reacted under reducing conditions in immunoblot analyses with E. coli-expressed uPA and also with highly glycosylated, functionally intact, recombinant human uPAR expressed in Chinese hamster ovary (CHO) cells. Seven of the MAbs recognized CHO uPAR under nonreducing conditions as well. By flow cytofluorometric analyses, three of these MAbs were shown to bind to native human uPAR present on the cell surface of monocytoid U937 cells with MAb IIIF10 being the best. Saturation of uPAR with uPA on U937 cells completely blocked interaction of MAb IIIF10 with uPAR (mapped epitope, amino acids 52 to 60 of domain I of uPAR). In turn, preincubation of U937 cells with MAb IIIF10 efficiently reduced binding of uPA to uPAR, indicating that the epitope detected by MAb IIIF10 is located within or closely to the uPA-binding site of uPAR, and thus, this site may be a target to influence uPA/uPAR-mediated proteolysis in tumors. Binding of MAbs IID7 or IIIB11 (mapped epitope, amino acids 125 to 132 of domain II of uPAR) to uPAR is not affected when uPAR is occupied by uPA. As these MAbs reacted strongly with cellular uPAR antigen in formalin-fixed paraffin-embedded tumor sections, the domain-II-specific antibodies IID7 and IIIB11 may be useful for immunohistochemical studies of uPAR expression in tissue remodeling processes in tumor invasion. In conclusion, we have devised well defined and epitope-mapped MAbs to uPAR that are highly specific tools for detection and targeting of uPAR in tumor tissue.

Animals↗

PubMed1997

Gasless videoendoscopic implantation of aortobifemoral vascular prostheses via a transperitoneal approach--an animal experiment.

BACKGROUND: Standard approach for aortobifemoral vascular approach prostheses is the transperitoneal approach, following median laparotomy and bilateral inguinal incision. The goal of this animal experiment was the development of a new minimal-invasive surgical technique utilizing a less-traumatic approach for aortobifemoral bypass. METHODS: The gasless videoendoscopic implantation of 6 x 6 mm diameter aortobifemoral-bifurcation prostheses in transperitoneal approach was tested at the Surgical Department of the University of Cologne in 10 domestic pigs. Gasless videoendoscopic surgery is performed with a laparolift-laparfan-system. After videoendoscopic implantation of aortobifemoral prostheses, all 9 animals underwent laparotomy and resection of the aortobifemoral prosthetic segment. The quality of the endoscopically sutured aortic end-to-side anastomoses was examined under artificial in-vitro circulation of glycerol/ringer-lactate solution for evaluation of possible leakage and bursting pressures. Moreover, the anastomoses were compared to conventionally sutured end-to-side anastomoses of six-hour old porcine abdominal aortas and 6 mm diameter prostheses. The maximum bursting pressure of all endoscopically sutured anastomoses averaged 450 mmHg, whereby the minimum bursting pressure amounted to 100 mmHg mean pressure. RESULTS: Aortobifemoral prostheses were successfully implanted in 9 out of 10 animals, one animal dying during preparation for the surgery, succumbing to massive coronary infarctions. Surgical durations for the transperitoneal approach averaged four hours, whereby surgical durations were reduced with increasing experience to a minimum of 3 hours 30 minutes. Dissection of the infrarenal aorta until occlusion required 35 minutes. Average aortic occlusion duration amounted to 1 hour; iliacofemoral occlusion duration amounted to 1 hour for each side. The leakage per minute at the beginning achieved a maximum of 80 ml/min and systolic pressure values of 350 mmHg in consideration of all flow levels, 60 ml/min for systolic pressure values of 200 mmHg and 20 ml/min for systolic pressure values of 120 mmHg. The minimum level leakage per minute was less than 10 ml/min for systolic pressure values between 120-350 mmHg. CONCLUSION: Gasless videoendoscopic implantation of aortobifemoral vascular prostheses in transperitoneal approach is practicable in animal experiments. All endoscopically sutured aortic endo-side anastomoses were comparable to conventionally sutured anastomoses in in-vitro evaluation of bursting pressure and leakage per minute.

Animals↗

PubMed1997

Changes in CD44 and ApoE immunoreactivities due to retinal pathology of man and rat.

In cases of retinal light damage, glaucoma, or senile macula degeneration, the loss of retinal neurons is thought to cause alterations of glial cells. We performed immunocytochemical studies on retinae of (i) healthy rats and human donors, (ii) rats exposed to enhanced illumination for 24 months, a procedure which leads to complete loss of photoreceptor cells, (iii) a human donor who had suffered from senile macula (photoreceptor cell) degeneration, and (iv) human donors who had suffered from glaucoma, known to be accompanied by a loss of ganglion cells and other retinal neurons. Furthermore, Müller cells were enzymatically isolated from human glaucomatous retinae. All preparations were subjected to immunocytochemistry for CD44 antigen and Apolipoprotein E (ApoE). In normal rat and human retinae, CD44 immunoreactivity was observed in the microvillous sclerad processes of Müller cells: in human retinae, perivascular (astro-)glial cell processes were also CD44 immunopositive. ApoE immunoreactivity was only found in some perivascular (astro-)glial cell processes of human retinae. Both rat and human Müller cells respond to photoreceptor cell damage by increased, and ectopic, expression of the CD44 antigen. Increased ApoE immunoreactivity was found in Müller cells from degenerative human retinae, but rarely in light-damaged rat retinae. It is concluded that degeneration-related reorganization involves enhanced expression of the glial cell adhesion molecule CD44 as well as elevated activity of the glial lipid transport molecule ApoE.

Aged↗

PubMed1996

Role of tissue factor in embryonic blood vessel development.

Tissue factor, a member of the cytokine-receptor superfamily and high-affinity receptor and cofactor for plasma factor VII/VIIa (ref. 1), is the primary cellular initiator of blood coagulation. It is involved in thrombosis and inflammation associated with sepsis, atherosclerosis and cancer, and can participate in other cellular processes including intracellular signalling, metastasis, tumor-associated angiogenesis, and embryogenesis. Here we report that inactivation of the tissue factor gene (TF) results in abnormal circulation from yolk sac to embryo beyond embryonic day 8.5, leading to embryo wasting and death. Vitelline vessels from null mice were deficient in smooth-muscle alpha-actin-expressing mesenchymal cells, which participate in organization of the vessel wall. This implies that tissue factor has a role in blood vessel development.

Animals↗

PubMed1996

Immunocytochemical evidence for a modulation of galectin 3 (Mac-2), a carbohydrate binding protein, in pulmonary fibrosis.

Galectin 3 is endogenous mammalian carbohydrate-binding protein with affinity for terminal beta-galactose residues, polylactosamine glycans, and ABH-blood group carbohydrate epitopes. To determine the distribution and regulation of galectin 3 during pulmonary injury, which is known to be accompanied by profound changes in the carbohydrate moieties of cell surface glycoproteins of alveolar cells, a rat model of irradiation-induced lung inflammation and repair was used. Immunocytochemistry showed that in normal rat lungs, galectin 3 was localized to alveolar macrophages, with weaker staining of bronchial epithelial cells. Shortly after irradiation-induced lung injury, when there is active proliferation of type II alveolar epithelial cells and re-epithelialization of alveolar basement membranes by type I cells, the total galectin concentration in the lung increased dramatically. This increase was due in part to an increased population of galectin 3-positive interstitial and alveolar macrophages. In addition, galectin 3 was expressed prominently at the surface of the newly formed type I alveolar epithelium and to lesser extent at the apical surface of type II cells. These findings suggest that the increased synthesis and secretion of galectin 3 during irradiation-induced lung injury, together with ligation of secreted lectin at the surface of alveolar epithelial cells, may play roles in pulmonary alveolar epithelial expansion and differentiation during injury and repair.

Animals↗

PubMed1996

Immunolocalization of cathepsin D in pneumocytes of normal human lung and in pulmonary fibrosis.

Cathepsin D expression has been assessed by immunohistochemistry and immunoelectron microscopy in fetal, normal adult and injured lungs of human beings. In addition to the well known positivity of alveolar macrophages and the bronchial epithelial cells, normal type I and to a lesser extent type II pneumocytes showed a granular, cytoplasmic staining pattern. Using immunogold labelling of lowicryl embedded human lung, cathepsin D was present in lysosomes of epithelial cells. Double immunofluorescence labelling employing type I and type II specific antibodies or lectins confirmed the epithelial staining for cathepsin D. At the terminal sac period during lung development cathepsin D appears in the alveolar epithelium. In fibrotic specimens, enhanced immunoreactivity was found in epithelial and non-epithelial cells. Proliferative epithelial formations were strongly stained with cathepsin D antibodies, whereas detached, desquamated epithelial cells were weakly positive or negative. We suggest that cathepsin D plays a role in the remodelling process during fibrogenesis.

Adult↗

PubMed1996

Expression of CD44 isoforms during bleomycin-or radiation-induced pulmonary fibrosis in rats and mini-pigs.

The distribution of CD44s and CD44v molecules in normal and injured lung tissue of rats and mini-pigs was studied by examining the immunohistochemical binding of monoclonal antibodies against CD44 isoforms. We showed that the expression of CD44v and CD44s varies greatly among different pulmonary fibrosis samples and that some tissues express either enhanced expression of CD44s, particularly in the interstitium and on alveolar macrophages, or very low levels of CD44v in the alveolar epithelium. Normal type II pneumocytes expressed the CD44s and CD44v molecules at the basolateral aspect of the cell. Such localisation favours a role for CD44 in epithelial cell-fibroblast interaction during lung development and repair.

Animals↗

PubMed1996

Upregulation of gap junction protein connexin43 in alveolar epithelial cells of rats with radiation-induced pulmonary fibrosis.

The degree of immunoreactive connexin43 (C x 43) in rat lung was evaluated during the development of radiation-induced pulmonary fibrosis in rat by a double immunofluorescence technique using polyclonal antisera to Cx43 and monoclonal antibodies to cytokeratins on cryostat sections. In normal rat lungs, Cx43 was detected in pneumocytes type II and I, in large blood vessel endothelia, in peribronchial smooth muscle cells, and in some peribronchial and perivascular interstitial cells. As early as 1 week after irradiation, enhanced immunoreactivity for Cx43 in the epithelial cells was detected. In severely injured lungs (about 3 months after irradiation), Cx43 was found also in the cytoplasm of type II pneumocytes. These findings were confirmed by western blot data. Western blot analysis also revealed increased phosphorylation of Cx43. It remains to be investigated whether the increased content of Cx43 in irradiated rat lung may be due to an enhanced number of gap junctions between type I and II alveolar epithelial cells.

Actins↗

PubMed1996

[Prognostic significance of micrometastases in axillary lymph nodes in breast carcinoma].

We looked for micrometastases in the axillary lymph nodes of 163 women with breast carcinoma, using monoclonal anticytokeratin antibodies. We found 26 micrometastases (2.1%) in node-negative patients (n = 17). Life-table analysis after 3 years detected the conformity of this group with the N1 group with regard to overall survival and distant-metastasis-free survival.

Adult↗

PubMed1996

Distribution of von Willebrand factor in capillary endothelial cells of rat lungs with pulmonary fibrosis.

To determine the value of von Willebrand factor (vWF) antigen as a marker of endothelial injury in radiation-induced fibrosis of rat lungs, we studied endothelial immunoreactivity to antibodies against vWF using the indirect immunoperoxidase technique combined with morphometric analysis. Using immunoelectron microscopy of LR White embedded lung samples to detect vWF, immunogold-labelled Weibel Palade bodies were found in endothelial cells of capillary endothelium. The irradiated lungs showed a statistically significant elevation of vWF expression, ie, vWF positive endothelia per unit area, and a significant increase of vWF expression per unit of parenchyma as well. The results suggest that vWF antigen expression and the number of vWF positive structures is modulated under condition of injury in radiation-induced fibrosis.

Animals↗

PubMed1996

Changes in keratinocyte differentiation during accelerated repopulation of the irradiated mouse epidermis.

Epidermal stem cells accelerate their repopulation rate during fractionated irradiation. To study the changes in keratinocyte differentiation associated with radiation-induced repopulation, we investigated the expression of a panel of 14 monoclonal or polyclonal antibodies against keratins, involucrin and others, as well as the expression of 15 lectins in the irradiated mouse leg skin. Tissue samples were collected after 1, 2, and 3 weeks of daily irradiation with 3 Gy per fraction. Abnormal morphological appearance of the irradiated epidermis suggested disturbed terminal differentiation. Keratin 16 (K16) was negative in normal epidermis but intense staining was observed in the irradiated epidermis. Involucrin was expressed in the outmost suprabasal layers only in the normal epidermis but extended to the lower layers in the irradiated epidermis. The lectin binding patterns for agglutinins from Soybean, Dolichos biflorus, and Helix pomatia showed differences between the normal and the irradiated epidermis. From these characteristic changes in staining patterns we concluded that accelerated repopulation of the epidermis during fractionated irradiation is associated with a deficiency in terminal squamous differentiation.

Animals↗