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K Kayser

Publications and source records attributed to K Kayser.

At least 91 records · Page 5Linked to original sources
PubMed1995

[Protein-carbohydrate recognition. Foundation and medical application with illustrations of tumor lectin studies].

Protein-carbohydrate interactions are involved in multifarious physiological processes. Together with antibodies and enzymes, lectins constitute the family of carbohydrate-binding proteins. The current research activities of tumor lectinology comprise the design of custom-made carrier-immobilized carbohydrate ligands (neoglycoconjugates), their application for the detection of specific binding sites and the evaluation of potential therapeutical approaches by blocking access or by directing drug conjugates to cell surface lectins, correlation of their expression to clinical parameters such as prognosis and their biochemical characterization. Thereby, mammalian lectins are made available to serve as tools. These experimental approaches are evaluated as regards their potential for improving cancer diagnosis and therapy.

Animals↗
PubMed1995

Syntactic structure analysis.

Syntactic structure analysis is a relatively new technique in diagnostic quantitative pathology that, based on the graph theory, can provide quantitative information on tissue architecture. This article gives an introduction to syntactic structure analysis and discusses the potential of syntactic structure analysis in diagnostic quantitative pathology. In addition, some examples of its application in histo- and cytopathology are presented and it is speculated which other applications the user of syntactic structure may find for quantitation of architecture in diagnostic quantitative pathology.

Algorithms↗
PubMed1994

Cell type-dependent alterations of binding of synthetic blood group antigen-related oligosaccharides in lung cancer.

Blood group antigen-related oligosaccharides have been implicated in growth regulation, cell mobility control and adhesion; we are therefore interested in the localization of receptors for these oligosaccharides in tumour cells. Labelled neoglycoconjugates that carry synthetic sugar structures are suitable tools to determine: whether such binding sites are present in human lung cancer; whether structural alterations of the glycoligand part will affect extent of binding; and whether cell type-associated alterations can be detected. Sections from 121 cases of lung cancer, representing small cell and non-small cell lung carcinoma, mesothelioma and metastases from extrapulmonary primary carcinomas were used to study the binding of nine synthetic AH- and Le-related oligosaccharides. Probes with fucose-alpha 1-3/4-N-acetylglucosamine-beta 1-R, an A-like disaccharide and 3'-sulfated galactose as ligand appear to bind less well to small cell than to non-small cell lung cancer cases, whereas Lec-disaccharide distinguishes mesothelioma from metastatic carcinoma. The latter ligand, A-like disaccharide and H (type III)-like trisaccharide exhibit evident cell type-associated differences in extent of binding. Thus, tailor-made neoglycoconjugates constitute a promising class of histopathological tools that warrants further study.

Antigens, Neoplasm↗
PubMed1994

Correlation of expression of binding sites for synthetic blood group A-, B- and H-trisaccharides and for sarcolectin with survival of patients with bronchial carcinoma.

Carrier-immobilised carbohydrates were used to monitor the presence of specific carbohydrate-binding sites in tissue sections. Sarcolectin, an interferon-alpha/beta antagonist and growth regulator, had been shown to bind the lymphokine macrophage migration inhibitory factor (MIF). The lectin is thus a MIF-specific probe. Biotinylated sarcolectin, neoglycoproteins with lactose or N-acetylglucosamine residues, and polyacrylamide-attached trisaccharides, that represent the ABH histo-blood group antigens, were applied to sections of 187 primary lung carcinomas. The panel of cases consisted of 57 epidermoid carcinomas, 55 adenocarcinomas, 43 large cell anaplastic carcinomas and 32 small cell anaplastic carcinomas. 47 cases with intrapulmonary metastatic tumours were also included. Expression of binding sites of both sarcolectin and trisaccharides of histo-blood group antigens A and H correlated with patient survival in lung cancer. In view of the widely performed analysis of the presence of histo-blood group antigens, concomitant profiling of binding sites for these sugar components is suggested to be of potential benefit.

ABO Blood-Group System↗
PubMed1994

Integrated optical density (IOD), syntactic structure analysis, and survival in operated lung carcinoma patients.

Histological sections of formalin fixed, paraffin-embedded tissue comprising 195 specimens of human lung carcinomas 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. Features related to the DNA-content of the nuclei (integrated optical density (IOD), IOD-entropy, S-phase related fraction, percentage > 5C, etc.), and structural parameters (minimum distance between tumor cell nuclei, minimum distance between tumor cells and neighboring lymphocytes, MST-entropy, MST-current of entropy (entropiefluss), distance between neighboring proliferating tumor cells, etc.) were measured. The following results were obtained: the measured IOD and MST features showed significant differences between the primary carcinomas and metastatic carcinomas in the intrapulmonary lymph nodes. The survival of patients was remarkably improved if the carcinomas displayed a low S-phase related fraction, a low percentage of tumor cells > 5C, a low number of stem lines, and a low MST-current of entropy.

Carcinoma, Bronchogenic↗
PubMed1994

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↗
PubMed1994

[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↗
PubMed1994

[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↗
PubMed1994

Alteration of integrated optical density and intercellular structure after induction chemotherapy and survival in lung carcinoma patients treated surgically.

Histologic sections of formalin-fixed, paraffin-embedded tissue consisting of 53 surgical specimens, 48 biopsy specimens and 29 intrapulmonary lymph nodes of human non-small cell lung carcinoma were Feulgen stained. The biopsy specimens were obtained before and the surgical specimens after induction chemotherapy (down staging). The integrated optical density (IOD) of tumor cell nuclei was measured using an automated image analysis system, and the attributed minimum spanning trees (MSTs) were computed. The measured features included IOD (DNA content of the nuclei), IOD entropy, S-phase-related fraction (SRF), percentage of tumor cells with an IOD > 5C (P5C), standard deviation of IOD and structural parameters (minimum distance between neighboring tumor cell nuclei, minimum distance between tumor cell nuclei and neighboring lymphocytes, MST entropy, minimum distance between neighboring proliferating tumor cell nuclei, etc.). The measured IOD and MST features showed significant differences in the biopsy specimens as compared to those measured in the surgically excised carcinomas and those growing in the intrapulmonary lymph nodes (lymph node metastases). After down staging, the SRF was significantly diminished, and the percentage of cells with an IOD > 5C increased (P < .05). The survival of patients was remarkably improved if both the carcinomas before and after induction chemotherapy displayed a low SRF, a low number of stemlines and low MST entropy.

Adenocarcinoma↗
PubMed1993

Detection of the lymphokine migration inhibitory factor in normal and disease-affected lung by antibody and by its major binding protein, the interferon antagonist sarcolectin.

Human migration inhibitory factor (MIF) is suggested to play a notable role in regulation of macrophage functions in host defense. A major binding component for the lymphokine in human tissue is the interferon antagonist sarcolectin. This high-affinity interaction gives access to MIF by affinity chromatography on immobilized sarcolectin and may be of significance for in situ activity of MIF. Localization of MIF is one step towards answering this question. Labelled sarcolectin and MIF-specific antibodies can be employed to analyze the expression of the factor. Surgical specimens of 74 patients, who underwent lobe/lung resection or diagnostic biopsy, were fixed with buffered formalin and embedded in paraffin. The material consisted of 36 cases of morphologically normal lung parenchyma of patients, suffering from bronchial carcinoma, of 16 cases with sarcoidosis, of 15 cases with tuberculosis and of 7 cases with idiopathic interstitial pneumonitis. The two types of probe to visualize presence of MIF invariably showed the same level of reactivity, underscoring the potential physiological significance of sarcolectin-MIF interaction. In detail, all cases with pneumonitis, most tuberculosis-affected as well as normal cases and 44% of the cases with sarcoidosis were positive. All positive cases with sarcoidosis and some cases from the other groups revealed accessible binding sites for biotinylated MIF.

Binding Sites↗
PubMed1993

Tumor presence at resection boundaries and lymph-node metastasis in bronchial carcinoma patients.

A prospective study was performed analyzing the bronchial resection boundaries of 120 patients operated on for lung carcinoma. The resection boundary, maximum tumor diameter, distance between tumor and resection boundary, and lymph-node stage were analyzed by serial sections of the surgical specimens (lobes and lungs). The following results were obtained: 20/120 cases (17%) displayed microscopic tumor invasion of the resection boundary (R1 status), most frequently adenocarcinoma (21%). The R1 status was closely associated with the distance between tumor and resection boundary and postsurgical lymph-node state (pN stage): all 8 tumors excised at distance 1 mm or less from the bronchial resection boundary revealed bronchial submucous tumor growth, whereas none of the tumors located more than 20 mm from the resection boundary was found to display tumor invasion of the bronchial boundary. Curative resection was noted in all 40 tumors operated at pNO stage and in only 11 cases (69%) of tumors with distant lymph-node metastases (pN3 stage). No relationship between tumor infiltration of the resection boundary and type of resection was seen. The data indicate that a) intra-operative control of bronchial resection boundaries is necessary in all lung-carcinoma patients with central tumor localization less than 20 mm from the proposed resection boundary; b) a "safety distance" between resection boundary and tumor boundary is of specific importance in bronchial carcinoma with lymph-node metastases.

Adenocarcinoma↗
PubMed1993

Atherosclerosis-associated changes in the carbohydrate-binding capacities of smooth muscle cells of various human arteries.

A set of labelled neoglycoproteins and sulfated polysaccharides, recognizing carbohydrate receptors specific for glucose (glu), mannose (man), lactose (lac), fucose (fuc), fucoidan (fud), dextran sulfate (dex), and heparin (hep), as well as polyclonal antibodies specific for an endogenous beta-galactoside-specific lectin of molecular weight 14kD (A14kD) and a heparin-binding lectin (AHL) have been applied to the main arteries of 10 autopsy cases. Slides of the following types of vessels were incubated with solutions of the biotinylated probes or antibodies at room temperature for 60 min: right and left coronary artery, carotid artery, abdominal and thoracic aorta, pulmonal artery, and the left femoral artery. Atherosclerotic lesions and non-atherosclerotic areas were analyzed for each individual type of vessel. The percentage of the determined expression of the presence of specific binding sites for the various probes was the lowest in the carotid and cardiac arteries, and the highest in the pulmonal artery. Pronounced quantitative differences between the normal and atherosclerotic arterial walls were noted for binding of fuc-, man-, and lac-exposing neoglyco-proteins of the right coronary artery and the carotid artery. Pulmonal and femoral arteries differed with respect to fucoidan or dextran sulfate binding. The heparin-specific lectin and the 14kD-lectin were found to be present in nearly all arterial walls, independent from the localization and the presence of an atherosclerotic lesion. The findings suggest that the expression of sugar receptors, as assessed by labelled neoglycoproteins or sulfated polysaccharides, may be of importance in the development of atherosclerotic lesions in the coronary and carotid arteries.

Aged↗
PubMed1993

Alteration of human lung parenchyma associated with primary biliary cirrhosis.

The clinical history, radiological and histomorphological alterations of the lung parenchyma in a patient suffering from primary biliary cirrhosis are described. The 70-year-old woman had developed a primary biliary cirrhosis, verified by serological abnormalities (AMA positivity, elevated IgM levels) and by liver biopsy. The lung parenchyma displayed immature epithelioid granulomas and characteristics of a chronic organizing pneumonia. Lung function revealed moderate restrictive changes; chest radiographs revealed bilateral, diffuse, patchy infiltrates in the basal lobes. Application of immunohistology detected antigens in liver cells reactive with anti-IgD and anti-IgG, in pneumocytes those reactive with anti-IgD. Presence of macrophage migration inhibitory factor (MIF) by application of its antibody and of the ligand sarcolectin as well as expression of binding capacities to MIF could not be demonstrated in the liver and lung parenchyma. Neoglycoproteins exposing fucose, N-acetyl-D-glucosamine, lactose and mannose residues did not bind to both the liver and lung tissue. The data indicate that at least some patients with primary biliary cirrhosis may develop or suffer from immunological abnormalities, affecting the lung.

Aged↗
PubMed1993

Malignant teratoma of the lung with lymph node metastasis of the ectodermal compartment: a case report.

A rare case with a metastasizing teratocarcinoma of the lung is presented. The 51-year-old man developed a central tumour mass in the left lung. Bronchoscopy and intraoperative sections of an involved lymph node supplied histomorphologic findings that are indicative for an epidermoid carcinoma. Further detailed analysis resulted in the final classification as a malignant teratoma. This rare tumour was further analyzed for the expression of various cellular characteristics, namely binding sites for various carbohydrates including sequences such as saccharides of the ganglioside GM1, for erythropoietin, tumour necrosis factor-alpha, and epidermal growth factor. Immunohistochemistry was used to determine the expression of neuron-specific enolase, carcino-embryonic antigen, calcyclin, epidermal growth factor, beta-HCG, AFP, p53 protein, and heparin-specific lectin. The results revealed similarities to a case with a pulmonary blastoma, and remarkable differences to that of epidermoid carcinoma cases. Similar results were seen in the DNA- and syntactic-structure analysis. The tumour reported on here should, therefore, be considered as a rare, specific entity of primary lung malignancies.

Carcinoma, Squamous Cell↗
PubMed1993

Glutathione reductase in human and murine lung tumors: high levels of mRNA and enzymatic activity.

The enzyme glutathione reductase (GR) (GSSG+NADPH+H+-->2 GSH+NADP+) plays a key role in the cellular defense against oxidative stress. High levels of GR activity are often associated with tumor growth and/or resistance mechanisms against drug and radiation therapy. In order to investigate the molecular basis of elevated glutathione reductase activities we studied the enzyme at the DNA, mRNA and protein levels in murine experimental tumor cell lines and in human lung tumors. A modified ultracentrifugation procedure was developed which allowed the simultaneous isolation of DNA and total cellular RNA. Out of 11 human bronchial carcinomas obtained from patients without prior chemotherapy, five tumors showed a GR activity which was 2.4 to 3.8 times higher than in the respective control tissues. In each case the elevated enzyme activity was accompanied by an elevated GRmRNA levels. For none of the tumors, GR gene rearrangement or amplification was observed by Southern blot analyses. The mouse tumor cell lines ASB XIV, Lewis lung carcinoma and EAT cells, also showed high levels of GRmRNA whereas this mRNA was hardly detectable in normal mouse lung tissue.

Animals↗
PubMed1993

Minimum spanning tree, integrated optical density and lymph node metastasis in bronchial carcinoma.

Surgical specimens comprising 80 primary lung carcinoma (lobes and lungs) were expanded by insufflation of air into the main bronchi, and fixed with buffered formalin for 24 h. After the usual tissue procedures, 3-4 microns thick histological sections of the tumour mass were Feulgen stained and various nuclear features such as integrated optical density (IOD), area, form factor, etc. were measured using an automated image analysing system (VISIAC). The geometrical centres of the nuclei were defined as vertices and the corresponding minimum spanning tree (MST) was calculated according to the distance between the vertices. The tumour mass was measured by serial sections of the surgical specimens; the lymph node stage was defined according to the rules of the UICC. Non-tumour infiltrated lymph nodes of the same case served as controls for the IOD and MST. The results revealed a DNA index of 1.1-3.0, a malignancy index (Böcking) 0.90-1.08 and a percentage of S-phases 10-23% (confidence limits). Only 19% of the bronchial carcinoma were found to be not aneuploid. Based upon the weighted MST, the distance of neighbouring cells, the IOD of the centre cells and IOD/area of neighbouring cells revealed statistically significant differences between tumours with and without lymph node metastases. The more advanced the lymph node stage, the 'closer' was the 'packing' of the tumour cells.

Aged↗
PubMed1993

Reverse lectin histochemistry: design and application of glycoligands for detection of cell and tissue lectins.

Plant and invertebrate lectins are valuable cyto- and histological tools for the localization of defined carbohydrate determinants. The well-documented ubiquitous occurrence of sugar receptors encourages functional considerations. Undoubtedly, analysis of the presence of vertebrate lectins in tissues and cells is required to answer the pertinent and tempting question on the physiological relevance of protein (lectin)-carbohydrate recognition in situ. Carrier-immobilized glycoligands, derived from custom-made chemical synthesis, enable the visualization of respective binding sites. Histochemically inert proteins or synthetic polymers with appropriate functional groups are suitable carrier molecules for essential incorporation of ligand and label. The resulting neoglycoconjugates can track down tissue receptors that are neither impaired by fixation procedures nor blocked by endogenous high-affinity ligands. Lectins, especially the receptors of the tissue under investigation (endogenous lectins), and appropriately tailored immobilized glycoligands or lectin-specific antibodies (when available) are complementary tools to test the attractive hypothesis that diverse, functionally relevant glycobiological processes within or between cells are operative. Concomitant evaluation of both sides of lectin histochemistry, namely lectins as tools and lectins as functionally important molecules in situ, will indubitably render desired progress amenable in our often still fragmentary understanding of the importance of tissue lectin and glycoconjugate expression and its regulation.

Animals↗