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K Kayser

Publications and source records attributed to K Kayser.

At least 19 recordsLinked to original sources

Distinct expression patterns of CD44 isoforms during human lung development and in pulmonary fibrosis.

The transmembrane glycoprotein CD44 represents a family of molecules, all encoded by one gene. The variability of the isoforms is generated by alternative splicing of the nuclear RNA. Apart from the abundant standard form (CD44s), the variant isoforms (CD44v) are mostly restricted to epithelia. The present study demonstrates the expression of CD44s and CD44v isoforms in embryonic and fetal lungs and in normal and pathologically altered (pulmonary fibrosis after radio- or chemotherapy) human adult pulmonary tissues. Using double immunofluorescence and avidin biotin complex (ABC) techniques on paraffin sections, presence of CD44s and CD44v isoforms (CD44v4, CD44v6, CD44v9) has been analyzed. In normal lung tissue, CD44s is present at the cell surface of alveolar macrophages, in some interstitial cells and in epithelial cells. It is also present in epithelial and non-epithelial cells during lung development. CD44v isoforms containing exon v6 and v9 encoded epitopes are selectively detectable in normal epithelial cells with a strong basolateral distribution pattern in the entire population of type II pneumocytes and in basal cells of the bronchial epithelium. During development exon v9 encoded isoforms appear at the pseudoglandular stage, whereas CD44v6 has only been found at the saccular stage. Examination of 12 fibrotic lung samples has revealed major alterations in the CD44 expression in comparison to normal lung tissue. These changes include cytoplasmic deposits of CD44s in alveolar epithelial cells and reduced expression of the CD44v6 and CD44v9 isoforms in alveolar epithelial and bronchial epithelial cells. The results suggest that CD44v isoforms may be utilized by type II pneumocytes in epithelial-mesenchymal interactions and in the maintenance of the pulmonary histoarchitecture.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Expression of lectin, interleukin-2 and histopathologic blood group binding sites in prostate cancer and its correlation with integrated optical density and syntactic structure analysis.

The binding of several biotinylated biologic probes was determined in sections of 20 surgical specimens of prostate cancer and of 21 biopsy specimens of hyperplastic prostate. Whereas neither the immunomodulatory, galactoside-specific lectin from Viscum album nor the human beta-galactoside-specific lectin (M(r) 14 kd) or its specific antibody discerned any remarkable differences, the lectin from Urtica dioica (UDA) and interleukin-2, the in vitro production of which is enhanced by this lectin, exhibited obvious preference for hyperplastic cells. In addition, the presence of binding sites for chemically synthesized blood group determinants was tested. Carcinoma cases revealed a higher percentage of binding of synthetic blood group trisaccharide H than hyperplasia cases. Due to these differences, diverse parameters, derived from measurement of integrated optical density (IOD) and from syntactic structure analysis, were correlated with the extent of binding of these biologic probes for the tumor cases. Primarily, parameters that are related to computation of a minimum spanning tree were significantly different in positive and negative cases for both UDA and interleukin-2. For the binding of blood group trisaccharide H the 5C exceeding rate, the 2CV deviation index and the distance of neighboring tumor cells with an IOD > 5 were clearly dissimilar. Our results thus suggest an extension of the panel of biologic probes for prostate cancer and substantiate the usefulness of correlations of binding of selected biologic probes to features derived from the assessment of IOD and syntactic structure analysis.

Adenocarcinoma

Expert consultation by use of telepathology--the Heidelberg experiences.

The benefits and constraint using visual telecommunication in pathology (telepathology) are described based upon the experiences of the authors for more than 4 years. The experiences include first trials in visual telecommunication to analyze image quality, transfer rates, handling of commercially available equipment, and need for routinely diagnostic work followed by routinely expert consultations in frozen sections. A quality control study on diagnostic reliability of bronchial carcinomas was performed later, and the diagnosticly different cases were reclassified by a panel of pathologists using visual telecommunication. The latest experiences are based upon routinely expert consultations in morphologically difficult cases by ISDN-based telecommunication. As a result, image quality and transfer rates are sufficient to permit efficient expert contribution to diagnostically difficult cases in 30-50% of transmitted cases in both common telephone lines and ISDN connections. No influence of various staining procedures, immunohistology, or in situ hybridization on image quality or transfer rates were observed. The area of transmitted images is still too small, and the reliability of ISDN lines is still not sufficient for remote control service in Germany. The handling of commercially available equipment needs to be improved; however, as a general result, telepathology will probably improve the diagnostic quality and access in histopathology within the coming years.

Clinical Laboratory Techniques

Paraganglioma of the lung--developed after exposure to nuclear radiation by the Tschernobyl atomic reactor accident?

A 36-year-old Russian patient had been exposed to severe nuclear radiation during the Tschernobyl accident and developed Cushing's syndrome in September 1991. After bilateral adrenalectomy a small centrally localized lung tumor in the left segment S6 was diagnosed, and the syndrome was correlated to primary lung cancer. Thoracotomy and resection of the segments S6 revealed a primary ACTH-producing lung tumor of the cell type of a paraganglioma. The patient lost his symptoms after curative tumor resection. The case is discussed under the aspects of tumor etiology, its clinical course and immunohistochemical findings.

Adrenocorticotropic Hormone

[DNA and MST entropy and current of entropy. New parameters of tumor biological characterization].

The clinical significance of the entropy of the integrated optical density E (IOD) and the corresponding entropiefluss EF (IOD) is discussed as well as the structural entropy E (MST) and its entropiefluss EF (MST). The E (IOD) is based upon the formula given by Stenkvist and Strande. It describes the statistical entropy of the DNA distribution of tumor cell nuclei; the E (MST) is based upon differences in IOD and distance between neighboring tumor cell nuclei and describes the deviation of tumor structure from a "biological constant" structure. The entropiefluss measures the current of entropy or irreversibly created heat which has to be removed through the surface of the tumor. It is a universally valid description of a thermodynamically open system and measures the distance of such a system from its equilibrium stage. The clinical significance of these parameters is tested on 241 specimens of human lung carcinomas and intrapulmonary metastases of extrapulmonary malignancies. The surgical specimens were fixed with buffered formalin. Histological sections cut from paraffin-embedded tissue were FEULGEN stained. The nuclei of the histomorphological images were segmented using an automated image analyzing system, and the attributed minimum spanning trees (MST) were calculated. The following results were obtained: The measured E (IOD) and E (MST) showed significant differences in the primary carcinomas compared to those measured in intrapulmonary lymph node metastases or intrapulmonary metastases. The survival of patients was remarkably improved if the carcinomas displayed a low E (MST), EF (IOD), and EF (MST).

Adenocarcinoma

[Detection of tenascin in stomach cancer. An immunohistochemical study].

Tenascin, a glycoprotein of the extracellular matrix, is involved in epithelial proliferation, differentiation and cell migration during embryonic development. Later on, it is important in proliferative processes like tumor growth and wound healing. We examined the distribution of tenascin, especially in the stroma near basement membranes, in paraffin sections from 25 patients with gastric cancer by immunohistological staining with regard to tumor staging, grading and Lauren classification. In two series we used a monoclonal and a polyclonal antibody against human tenascin. In most of the sections there was a more intensive staining of the surrounding stroma in areas close to the tumor, which could indicate the direction of tumor growth. In highly differentiated tumors we found a positive, yet discontinuous staining close to the basement membrane. In contrast to this, we saw a more diffuse reaction of the stroma with network-like staining of the collagen fibres in undifferentiated tumors. In lymph nodes we also detected a small number of tumor cells by staining of the surrounding stroma.

Adenocarcinoma

Analysis of tumour necrosis factor alpha-specific, lactose-specific and mistletoe lectin-specific binding sites in human lung carcinomas by labelled ligands.

Receptor sites can be visualized by labelled ligands as an alternative to receptor-specific antibodies, as substantiated for two different receptor classes. Recombinant tumour necrosis factor alpha (TNF) was biotinylated via amino-groups and the resultant probe was applied to formalin-fixed, paraffin-embedded tissue sections of 94 primary bronchial carcinomas and to normal peripheral lung parenchyma. In addition, monoclonal antibodies specific for neuron-specific enolase (NSE) and TNF itself were used. The biotinylated beta-galactoside-specific mistletoe lectin, which exhibits dose-dependent immunomodulatory and toxic potency, and two probes that specifically detect certain types of sugar receptors were employed to illustrate further the feasibility of using ligands for receptor localisation. The tumours comprised 62 small cell lung carcinomas, 10 epidermoid carcinomas, 11 adenocarcinomas and 11 large cell anaplastic carcinomas. Expression of TNF-binding sites was found in 39 of the small cell lung carcinomas and in 13 of the non-small cell lung carcinomas. Binding capacity for the TNF-specific antibody was seen in similar proportions of small cell lung carcinomas and of non-small cell lung carcinomas. None of the normal lung parenchymas revealed significant staining. Binding capacities to mistletoe lectin were seen in all normal lung parenchymas and in nearly all cases of adenocarcinoma (10/11). A correlation between the expression of NSE and the binding capacities to TNF was detected. Endogenous lectins, specific for lactose or beta-GalNAc, were displayed in nearly one half of the small cell lung carcinoma cases (44% or 45% respectively) and in about 25% of the non-small cell lung carcinoma cases.

Acetylgalactosamine

An approach based on two-dimensional graph theory for structural cluster detection and its histopathological application.

An approach based on graph theory is described for detecting clusters of cells in tissue specimens (two-dimensional space). With a set of discrete basic elements (cell nuclei) having several measurable features (area, surface, main and minor axis of best-fitting ellipses) a graph is defined as having attributes associated with edges. Different minimum spanning trees (MSTs) can be constructed using different weight functions on the attributes (attributed MST). Analysis of the MST and of an attributed MST by use of a decomposition function allows detection of image areas with similar local properties. These clusters, which are then clusters of the tree, describe, for example, partial growth in different directions in a case of a human fibrosarcoma assuming that tumour cell nuclei are homogeneous with respect to their configuration and size. The model allows the separation of clusters of tumour cells growing in different directions and the approximation of the different growth angles. This decomposition also allows us to create new (higher) orders of structure (cluster tree).

Algorithms

Aspects of standardization in telepathology.

Effective telepathology is only possible, if the partners are supplied by a broad variety of equipment connected by far-spread communication lines. These prerequisites can only be fulfilled if technical and medical standards are available obligate for all participants. The technical and medical aspects of those standards are described in general and include procedures and notations in pathology, standards of the image source, image sampling, clinical information, classification of diagnosis, communication channels, hard- and software equipment. New standards should only be developed for those not existing, or if the already existing ones are not appropriate. The standardization classes should allow flexible formats and be developed as "open modules" allowing "individual" peripheral work stations and progressive development in the future.

Computers

Visual telecommunication for expert consultation of intraoperative sections.

Histopathological images of intraoperative sections were transferred by use of normal telephone line between the Department of Pathology, Thoraxklinik, Heidelberg, and the Institute of Pathology, Hospital Baumgartnerhöhe, Vienna. The images were digitized using a colour TV camera and stored in a specific image transmission system (VP2000). The transfer of one image lasted 1.4-2 min at average; normally two different areas of the section were transmitted. The expert discussion including the clinical history usually started a few minutes prior to the image transfer, and was finished 3 min after the transfer of the last image. A substantial assistance in the intraoperative classification of the disease was achieved in 37% of the 35 submitted cases. The images transfer was only useful for medium to high magnifications of the microscope, i.e., an objective x 25 or higher. The trail allows the following conclusions: a) Visual transfer of microscopic images is a useful technique for expert consultation of intraoperative sections, and can give additional information in 20-40% of the analyzed cases; b) it is useful only for medium or high microscopic magnifications and limited by the spatial resolution of the TV cameras.

Consultants

Analysis of expression of erythropoietin-binding sites in human lung carcinoma by the biotinylated ligand.

Recombinant glycosylated erythropoietin (EPO) was biotinylated with biotin-aminocaproyl hydrazide via periodate-treated sialic acid moieties and applied to sections of 64 tumors of the lower respiratory tract, comprising 19 primary adenocarcinomas, 19 epidermoid carcinomas, 13 large cell anaplastic carcinomas, 11 small cell lung carcinomas, 11 intrapulmonary metastases, 1 mesothelioma and 1 lymphocytic interstitial pneumonia. The formalin-fixed, paraffin-embedded specimens were incubated with labelled EPO at room temperature and a concentration of 10 micrograms/ml for 60 min. The expression of the EPO-binding sites was visualized by the ABC technique. All of the analyzed large cell anaplastic carcinomas and the majority of the epidermoid carcinoma (89%), adenocarcinoma (79%), and metastases (82%) displayed binding capacities for EPO. Five out of the eleven small cell lung carcinomas, the analyzed mesothelioma and lymphocytic interstitial pneumonia revealed definite staining, too. Binding sites could, in addition, be seen in air dried, non-fixed, acetone-fixed, and ether-ethanol-fixed cytological specimens. The data indicate that the expression of binding sites with specificity for EPO can be frequently seen in human bronchial malignancies.

Binding Sites

Alteration of the lung parenchyma associated with autoimmune hepatitis.

The clinical history, radiological and histomorphological alterations of the lung parenchyma associated with chronic active autoimmune hepatitis are described. A 6-month-old female infant developed chronic active autoimmune hepatitis associated with autoimmune haemolytic anaemia. She was treated with immunosuppressive drugs, including steroids, for more than 6 years and developed symptoms and radiological signs of interstitial pneumonitis 4 years after onset of the autoimmune hepatitis. Associated bronchiectasis was detected 1 year later. No abnormalities of lung defence mechanisms could be demonstrated. Resection of the sixth left segment and of the basal parts of the left lower lobe revealed honeycombing with changes in the lung parenchyma which included chronic interstitial pneumonitis with multinucleate giant cells, seen predominantly in the distal airways, marked diffuse interstitial mononuclear infiltrates and mild diffuse interstitial fibrosis as well as bronchiectasis and organizing pneumonia. Granulomatous lesions, angiitis and necrotic areas were absent. Immunohistochemistry for immunoglobulins was negative for IgA, IgG and IgM and positive for IgD in the multinucleate giant cells. A strong positive reaction to HLA-DR-specific monoclonal antibody was noted, whereas no specific sugar receptors (endogenous lectins) could be detected by use of biotinylated glyconeoproteins.

Autoimmune Diseases

Expression of transferrin- and interleukin-2-receptors, and HLA-DR in human lung carcinoma.

The expression of HLA-DR and of the receptors for transferrin and interleukin-2 was histochemically analyzed for 27 human lung carcinomas, 3 mesotheliomas, and 3 thymomas by use of the monoclonal antibodies CLONAB Tf-R, Il-2R, and LN3. In addition, a pan B-cell antibody (CD-19) and a pan T-cell antibody (CD3) were applied. The transferrin receptor was found to be expressed in all cases of adenocarcinoma, in 12/17 cases of epidermoid carcinoma, and in a similar percentage of the thymoma cases (2/3). The interleukin-2 receptor specific antibody stained positively only for 3 cases (1 mesothelioma, 1 adenocarcinoma, and 1 epidermoid carcinoma). The expression of HLA-DR could be demonstrated in a similar small percentage of adenocarcinoma and of epidermoid carcinoma, however in 2/3 cases of mesothelioma and thymoma, respectively. The CD-19 antibody stained negatively for all tumor cases, the pan T-antibody positive in 2/10 adenocarcinoma and in 1/3 thymoma. The data suggest that the transferrin receptor may play an important role in human lung tumor growth. In addition, it may be used as diagnostic aid for distinguishing mesothelioma from metastatic adenocarcinoma of lung into the pleura.

Adenocarcinoma

Long distance image transfer: first results of its use in histopathological diagnosis.

Histopathological images were transferred by use of normal telephone lines between three pathology institutes located in three different cities in the FRG. Images were digitized using a colour TV camera and stored in a special computerized image transmission system. The stored image was transferred and visualized on a (receiver) colour TV screen after dialing the telephone number connected to the receiver image transmission system. An additional telephone dialogue was activated by use of a normal acoustic telephone, and the diagnostic difficulties of the underlying image were discussed. Diagnostic assistance was possible in all transferred cases as well as histopathological diagnosis. Resolution of the images was set at 512 x 512 pixel x 8 bit. Image transfer time was 3.2 min on average. The differences between the original and transferred image were measured by "retransfer" of the original image and by subtracting the two images from each other. No major transfer errors could be measured.

Breast Neoplasms

Alterations in human lung parenchyma after cytostatic therapy.

Chemotherapy does not only affect the viability of the tumor cell. It may also cause alterations in normal organs. Thus, tumor-free areas within human lung parenchyma of 63 surgical specimens of intrapulmonary metastases were analyzed to assess the extent of morphologic changes in response to previous cytostatic therapy. The material included 34 cases of sarcoma, 20 cases of germ cell tumors, 6 cases of hypernephroid carcinoma, two cases of mammary carcinoma and one case of metastatic melanoma. All patients had received cytostatic therapy in generally applied regimens for more than two years. Morphologic analysis was carried out by routine procedures. In addition to conventional staining procedures including HE, PAS, and Sirius stain, further tools were employed to extend the array of determined characteristics. To evaluate any changes in the tissue in order to specifically recognized carbohydrate structures, labeled neoglycoproteins or proteoglycans with specificity for endogenous receptors that bind to mannose, maltose, L-fucose, lactose, N-acetyl-D-glucosamine, and heparin were used. A monoclonal antibody binding the HLA-DR receptor was also included in the study. As a control, sections of 20 cases with intrapulmonary metastases without exposure to previous cytostatic therapy were included. To address the further question whether cytostatic therapy may induces changes in tumor-free lung that show similarities to the organ in question, sections from 18 cases with tuberculosis and from 37 cases suffering from sarcoidosis were similarly examined. Focal interstitial fibrosis was seen in 28/63 (44%) of the patients receiving chemotherapy. In contrast, only 2/20 (10%) patients of the untreated group exhibited this alteration. An active fibrosis with proliferating smooth muscle cells was found in two cases, dysplastic pneumocytes in 10 cases (16%) in the group with cytostatic therapy, but in no cases in the untreated group. Expression of the HLA-DR receptor in the pneumocytes was observed in 27/63 cases (43%) of the cytostatic cohort, in 21/37 (57%) patients of the sarcoidosis cohort, in 15/18 (83%) patients of the tuberculosis cohort, and in 1/20 (5%) of the untreated patients. In contrast to sections from treated patients, binding of neoglycoproteins was low in the untreated cohort. Interestingly, similarities between the tuberculosis cohort and the cytostatic cohort were seen for receptors that are specific for fucose and lactose, respectively. The results suggest that long-lasting cytostatic therapy induces focal fibrosis in 40%-50% of the patients, mainly via unspecific interstitial inflammatory infiltrates. A hypersensitivity reaction or direct toxicity may less frequently lead to pathologic alterations.

Adult

Analysis of soft tissue tumors by an attributed minimum spanning tree.

Histologic slides of 22 soft tissue tumors (9 malignant fibrous histiocytoma, 8 fibrosarcoma, 2 rhabdomyosarcoma, 2 osteosarcoma, 1 Askin tumor) were Feulgen stained. Using an automated image analyzing system (Cambridge 570) at low magnification (25x), the tumor cell nuclei were segmented. The geometrical center of the nuclei was considered the vertex. A basic graph was constructed according to the neighborhood condition of O'Callaghan. Neighboring tumor cell nuclei were visualized by connecting edges. Several features of tumor cell nuclei were measured, including area, surface, major and minor axis of best fitting ellipsis and extinction (DNA content). Nuclear features are attributed to the vertices. The differences, or "distances," between features of connected vertices are attributed to the corresponding edges, which are dependent on the attributes. Thus, different minimum spanning trees (MST) result. Each MST can be decomposed into clusters using a suitable decomposition function on the edges, which rejects an edge if its attributes differ from the mean of the attributed values of surrounding edges more than a neighbor dependent bound (lower limit). Taking into account the length and other attributes of edges (e.g., differences in orientation of the major axis), clusters of different nuclear orientation can be detected. A cluster tree can be constructed by defining the geometric center of a cluster as a new vertex, and by computing the neighborhood of the cluster vertices. The result is an attributed MST containing characteristic structural properties of the image (in cases of sarcomatous tumors, local orientation of tumor cell nuclei and local DNA abnormalities).

Cell Nucleus

Morphologic lesions in non-neoplastic bronchial mucosa associated with bronchial carcinomas.

The histomorphologic alterations of bronchial mucosa were analyzed in 332 cases with primary bronchial carcinomas and 48 cases with intrapulmonary metastases. The surgical specimens (lobes and lungs) were cut into serial sections after expansion and fixation, and the bronchial mucosa was analyzed in relation to its distance from the tumor boundary. Samples of the bronchial mucosa were taken at distances 10 mm, 20 mm, 30 mm and 40 mm. The following results were obtained: In primary bronchial carcinomas 18% of cases revealed a normal mucosa at 10 mm distance and 45% at 40 mm distance. The histomorphological alterations included hyperplasia of basal cells and goblet cells and less frequent squamous metaplasia. They were seen twice as frequent in primary bronchial carcinomas as in intrapulmonary metastases and were found to be distance-related only in small-sized primary bronchial carcinomas (maximum diameter less than 30 mm). Epidermoid carcinomas and small cell carcinomas displayed hyperplasia of basal cells in 40-60% of cases, adenocarcinomas only in 20-40%. Squamous metaplasia was seen in 10-15% of epidermoid carcinomas and small cell carcinomas, and only rarely in adenocarcinomas and metastases. The histomorphologic changes of bronchial mucosa associated with primary bronchial carcinomas can clearly be separated from those seen in intrapulmonary metastases in respect to their frequency and distance-relation. The findings indicate that the analyzed morphological alterations are probably associated with the histogenesis of the bronchial carcinomas.

Adenocarcinoma