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Biomedical subjects

K Kayser

Publications and source records attributed to K Kayser.

At least 127 records · Page 7Linked to original sources
PubMed1990

Biotinylated epidermal growth factor: a useful tool for the histochemical analysis of specific binding sites.

Epidermal growth factor (EGF) was labelled with biotin via modification of either the amino or carboxyl groups, using suitable reagents, namely biotinyl-N-hydroxysuccinimide ester or biotinamidocaproyl hydrazide. To assure that the specific binding capacity of EGF is retained despite its chemical modification, displacement of the EGF by biotinylated derivatives in a routine binding assay was performed. The inhibitory potency compared to unmodified EGF was only slightly reduced. This result is the prerequisite for testing the usefulness of biotinylated EGF in histochemistry. The biotinylated probes were applied to sections of human tumour tissue and of monkey organs (liver, kidney, uterus of Cynomolgus and Rhesus monkey) to localize the specific binding sites for EGF. Formalin-fixed, paraffin-embedded tissue sections were deparaffinized and incubated with the probes at a concentration of 10 micrograms ml-1 at room temperature for 60 min. Specific binding of the EGF was visualized by the avidin-biotin techniques (ABC). A positive reaction in conjunction with appropriate controls by competitive inhibition was seen for all monkey tissue sections and for the following number of cancer cases: breast carcinoma: 7/10; mesothelioma: 2/4; lung carcinoma: 1/3; colon carcinoma: 1/3. The staining properties were similar for both types of probes that differed in the functional group that is involved in modification by biotin attachment. However, the batches with modification of the amino groups stained more intensely and more distinctly than the carboxyl modified EGF. Overall, the data indicate that the ligand properties of the EGF are not impaired by biotinylation of the two types of functional groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Are there characteristic alterations in lung tissue associated with Crohn's disease?

Two male patients aged 12 and 31 years suffered from Crohn's disease for more than six years and were treated with Cortison for more than four years. Surgical excision of parts of the terminal ileum was performed in both patients. They suffered from pulmonary symptoms as dyspnoea, shortness of breath and ventilation disturbances two years after operation. Wedge biopsies of the lungs revealed the following histomorphological findings: 1. Granulomatous interstitial lymphocyte infiltrates 2. Acute alveolitis with severe dysplasia of pneumocytes 3. Moderate interstitial fibrosis. Immunohistology performed in one case showed predominantly lambda chains expressed by lymphocytes associated with IgA and IgM. IgG was missing, furthermore kappa chains could not be detected. Macrophages contained endogenous lectins (sugar receptors) for fucose, maltose, and N-acetyl-D-glucosamine (glcNAc). No receptors specific for mannose, lactose, and heparin could be found. Pneumocytes did not bind the neoglycoproteins but were found to express HLA-DR receptors detectable by the monoclonal antibody LN 3 in dysplastic pneumocytes only. The histomorphological and immunohistochemical findings suggest that the analyzed alterations of lung tissue are related to the underlying disease of enteritis regionalis.

Adolescent↗
PubMed1990

Combined morphometrical and syntactic structure analysis as tools for histomorphological insight into human lung carcinoma growth.

Histological sections of formalin-fixed, paraffin-embedded tissue comprising 60 surgical specimens of human lung carcinoma were Feulgen stained. The histomorphological images were transferred to an automated image analysing system (VISIAC) and analysed as follows. The geometrical centers of tumor cell nuclei were defined as vertices, and the minimum spanning tree (MST) was calculated based on the two-dimensional distance between the vertices. Segmentation of the images was performed semiautomatically by interactive definition of nuclei of interest and automated detection of nuclear boundaries. Several morphometric features of tumor cell nuclei were measured including size, DNA-content (extinction), and form factor, and were set in relation to parameters of the MST. The following results were obtained: DNA-content and tumor cell nucleus size ('center cell') of different microscopic tumor growth patterns are related to the number of nearest neighboring cells. No relation was found in the neighboring (surrounding) cells. The different cell types of lung carcinoma, i.e., the different microscopic tumor textures expressed the relation of center cell features to the parameters of MST. A high amount of DNA content in branching points of the MST for epidermoid carcinoma may be interpreted as carcinoma growing in epidermoid textures tend to proliferate from tumor cell nuclei related to at least one neighboring cell. The opposite was found for large cell anaplastic carcinoma (no perceptible microscopic textures of the tumors) which showed the highest DNA content in tumor cell nuclei but which was not related to any neighboring cells. This technique allows analysis of growth centers and microenvironment conditions in human lung cancer in relation to tumor texture at the light microscopy level.

Adenocarcinoma↗
PubMed1990

Differentiation-related expression of epidermal growth factor receptors in human lung carcinoma demonstrated histochemically by biotinylated epidermal growth factor.

Biotin-labeled epidermal growth factor (EGF) was applied to routinely processed sections of 64 cases of human lung carcinoma as a histochemical tool for demonstrating EGF-specific receptors. Formalin-fixed, paraffin-embedded tissue sections were deparaffinized and incubated with the labeled EGF (10 micrograms/ml) for 60 min at room temperature. The specific binding of the growth factor to its receptor was visualized by the avidin-biotin complex (ABC) technique. Positive binding capacities were obtained for the following cases: 15/16 epidermoid carcinoma; 13/15 adenocarcinoma; 2/11 large cell anaplastic carcinoma; 12/20 small cell anaplastic carcinoma; 0/11 normal lung tissue; 0/6 main bronchi; 0/1 hamartoma; 0/1 primary fibrosarcoma of lung. In addition, a strong positive reaction was seen for neutrophilic granulocytes present within the tumorous tissue. Data indicate that EGF receptors are frequently expressed in more differentiated carcinoma in comparison with anaplastic carcinoma of lung.

Aged↗
PubMed1989

MDR1 gene expression in lung cancer.

The MDR1 gene (also known as PGY1) is frequently overexpressed in multidrug-resistant cell lines. We investigated the role of MDR1 gene expression in lung cancer by performing RNA slot blot analysis in samples from a panel of 24 lung cancers, 10 corresponding nontumorous lung tissues, and 67 tumor cell lines of several histologic types. Almost all of the tumors, nontumorous lung tissues, and cell lines expressed low levels of MDR1 RNA. Relatively higher levels were found in only one type of lung cancer, a subgroup of non-small cell lung cancers expressing neuroendocrine markers. No evidence of MDR1 gene amplification or rearrangements was detected. We found no correlation between MDR1 gene expression in cell lines and (a) in vitro chemosensitivity of the cells, (b) prior therapy status of the patients, or (c) clinical response to therapy. We conclude that the clinical multidrug resistance of many lung cancers cannot be explained solely on the basis of expression of the MDR1 gene.

Drug Resistance↗
PubMed1989

Histopathologic evaluation of application of labeled neoglycoproteins in primary bronchus carcinoma.

Neoglycoproteins are readily available conjugates of a histochemically inert carrier protein and histochemically crucial carbohydrate moieties which are covalently attached to the carrier protein by chemical synthesis. Biotinylation renders these conjugates detectable in formalin-fixed, paraffin-embedded tissue sections of human lung cancer by standard staining protocols, thereby localizing endogenous receptors for carbohydrate moieties. Examination of 30 cases of main types of human lung cancer revealed the presence of alpha-fucosyl-, alpha-mannosyl-, and alpha-glucosyl-specific receptors in adenocarcinomas or epidermoid carcinomas with high positivity rates. The extent of the expression of receptors for alpha- and beta-galactosides appeared to be comparatively lower. Within the standard protocol, using a concentration of the biotinylated probes of 10 micrograms/mL, this panel of probes consistently failed to detect endogenous sugar receptors in ten cases of small cell anaplastic carcinoma of the lung. Whereas none of the sections from the tumor cases bound the sulfated fucan fucoidan, the accompanying inflammatory cells, especially the granulocytes, expressed receptors for the sulfated fucan. Pronounced labeling for macrophages was observed for the alpha-galactoside-specific probe, whereas no binding to inflammatory cells and pneumocytes was detectable for the beta-galactoside-specific probe. The results indicate that expression of endogenous receptors for neoglycoproteins may be useful in discriminating between small cell and non-small cell lung carcinoma and carcinomatous cells from accompanying inflammatory cells.

Carbohydrate Metabolism↗
PubMed1989

Is the profile of binding of a panel of neoglycoproteins useful as a diagnostic marker in human lung cancer?

Histomorphological evaluation of the profile of carbohydrate-binding proteins with specificities to alpha- and beta-glucosides (maltose, cellobiose), alpha-L-fucosides (L-fucose), alpha-D-mannosides (D-mannose), a N-acetylated sugar, present in natural glycoconjugates (N-acetyl-D-glucosamine), two negatively charged sugars (glucuronic acid and sialic acid), rhamnose (6-deoxy-L-mannose) or to heparin has been assessed. 133 cases of formalin fixed, paraffin embedded human lung carcinoma specimens (45 cases of epidermoid carcinoma, 24 cases of small cell anaplastic carcinoma, 48 cases of adenocarcinoma, and 16 cases of large cell anaplastic carcinoma) as well as 14 cases with epithelial or biphasic mesothelioma and 7 cases of pleuritis carcinomatosa were incubated with biotinylated, suitably modified neoglycoproteins or heparin for detecting the corresponding endogenous sugar receptors (lectins). Histochemical reaction was demonstrated by use of the avidin-biotin-method. Significant differences were obtained between the different markers used for each cell type as well as between the different cell types. For separating small cell anaplastic carcinoma from non small cell anaplastic carcinoma the markers carrying the histochemically crucial maltose, fucose, and mannose residues are useful, showing a positive reaction to only 4-8% of the small cell anaplastic carcinoma cases compared to 60-80% of the non small cell carcinoma cases. For separation of mesothelioma from pleuritis carcinomatosa a carrier, modified by attachment of N-acetylglucosamine moieties is the most useful marker being negative in all cases of the analyzed mesothelioma cases and being positive in 62-80% of the adenocarcinoma cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗
PubMed1989

DNA-content, inflammatory tissue response and tumour size in human lung carcinoma.

Tumour imprints of 75 resection specimens with human lung carcinoma (lobe and lungs) were fixed with alcohol and Feulgen-stained. Resection specimens were cut into serial sections 6 mm thick and tumour mass, tumour involvement into intrapulmonary and extrapulmonary lymph nodes, detailed pTN-stage were determined. DNA-content, DNA-index, percentage of diploid/hyperploid tumour cells, and morphometric nuclear features were measured using an automated image analyzing system (VISIAC). Only 10% of the measured carcinomas were diploid. The DNA-index showed the broadest variance in large cell anaplastic carcinoma (1.2-3.3). Carcinomas growing predominantly within the alveolar space, i.e. without destroying the interstitial tissue showed a lower DNA-content above 3c and above 5c compared to carcinomas destroying the interstitial tissue. Carcinomas with severe stroma reaction were found to have 33%-48% of DNA above the 3c value whereas carcinomas without stromal reaction had a percentage above 3c ranging 46%-64% (confidence limits, p less than 0.05). DNA-index increases with increasing tumour volume and decreases for large tumours (greater than 100 ccm). Hyperploid and polyploid tumours were found more frequently in case of pT2 and pT3-stages compared to pT1-stages. No relation of DNA-content or ploidy was found to lymph node involvement and inflammatory response of host tissue.

Carcinoma, Bronchogenic↗
PubMed1989

Minimum spanning tree, Voronoi's tesselation and Johnson-Mehl diagrams in human lung carcinoma.

A program written in Amba was developed for the automated construction of minimum spanning trees, Voronoi's tesselation and Johnson-Mehl diagrams, combined with quantitative measurements of nuclear parameters in histopathological specimens. Sections, 4 microns thick obtained from paraffin-embedded surgical lung specimens, were Feulgen-stained. The boundaries of the nuclei were calculated automatically after interactive identification of the relevant cells. The geometric centres of the nuclei were computed. They were used for constructing the minimum spanning tree, Voronoi's tesselation and the Diriclet cells. The direction of the main axis to the best fitting ellipsis according to the nuclear size was used for construction of the Johnson-Mehl diagrams. The following textural parameters were measured: 1) Minimum spanning tree: Distribution of neighbouring cells; minimum distance between neighbouring cells according to number of neighbours. 2) Voronoi's tesselation: Area and surface of obtained cells; Ratio of nuclear area/cell area. 3) Johnson-Mehl diagram: Area and surface of obtained cells; Ratio of nuclear area/cell area. The following nuclear parameters were measured: 1) Area, surface, absolute extinction (DNA-content); Similarity of quantitative nuclear parameters between neighbouring cells and in relation to number of neighbouring cells was analyzed. Twenty cases of primary lung carcinoma (five cases of each of epidermoid, adeno, large cell anaplastic, and small cell anaplastic carcinoma) were measured. Analysis of texture parameters in combination with morphometric nuclear parameters offers new possibilities in quantitative histopathology.

Adenocarcinoma↗
PubMed1989

[Computed tomographic findings in bronchial adenoma].

The diagnostic value of CT was studied in 36 patients with histologically proved bronchial adenomas. Peripheral masses were found in 16% of the patients. Mediastinal metastases were detected at operation in 8 (22%) of these patients. Two patients showed distant metastases. We were not able to find reliable CT criteria for bronchial adenomas.

Adenoma↗
PubMed1989

[SPECT-3-D reconstructions of lung perfusion in patients with thoracic space-occupying lesions].

The present study deals with 3-dimensional reconstruction of lung perfusion examinations in 20 patients with thoracic masses. The images were obtained by single photon emission tomography (SPECT) and were compared with conventional scintigraphic images and with the CT findings. 3-D reconstructions proved superior to 2-dimensional images for the topographic demonstration of the affected lung segments. No additional information could be obtained concerning the extent of the mass. Use of this method is valuable for the preoperative estimation of pulmonary perfusion.

Adult↗
PubMed1989

[The liquefactive behavior of bronchial carcinomas and their metastases from the radiological viewpoint].

Necrosis in bronchial carcinomas and in their soft tissue metastases was studied in 368 patients by means of CT and ultrasound. In primary bronchial carcinomas (59 cases) there was clear correlation between tumour necrosis and the histology. There was a significant preponderance amongst squamous carcinomas, whereas small cell carcinomas rarely show radiologically visible necrosis (p less than 0.01). Amongst metastases in the liver (128 cases), central nervous system (164 cases) and suprarenals (23 cases) there was no correlation between histology and the recurrence of necrosis. Necrosis in deposits in suprarenals and in the brain depends on the size of the lesion and could be demonstrated in more than 50% of cases. Liver metastases show necrosis in less than 5% of the cases by the imaging methods used.

Abdomen↗
PubMed1989

Expression of cortical and medullary thymic epithelial antigens in thymomas. An immunohistological study of 14 cases including a characterization of the lymphocytic compartment.

Four monoclonal antibodies against antigens expressed differentially by the normal thymus epithelium, which define the cortical, medullary and subcapsular compartments, were used for immunohistological characterization of the epithelial cells in 14 thymomas. Furthermore, thymoma-associated lymphocytes were studied with monoclonal antibodies directed against T-lymphocyte differentiation antigens (CD1a, CD3, T-cell antigen receptor). Only four of the 14 thymomas could be classified into either medullary or cortical type thymoma based on the immunophenotype of epithelial cells. Ten cases escaped immunophenotypical classification due to co-expression of medullary and cortical antigens by the tumour cells. This aberration from the normal phenotype might indicate the failure of differentiation of such tumours. The immunophenotype of the associated lymphocytes, on the other hand, made it possible to classify the tumours as cortical (5 cases), mixed (2) and medullary (3) thymomas. Four thymomas escaped this classification scheme due to the absence of lymphocytes (2) or to a hybrid immunophenotype (2). Nevertheless, thymocytes of cortical type clearly predominated and were seen in all thymomas with associated lymphocytes. This feature may constitute a good diagnostic tool in differential diagnosis since, in 28 mediastinal or extramediastinal metastasis of tumours not derived from thymic epithelium and associated with various numbers of lymphocytes, none of them were found to contain CD1a positive lymphocytes.

Antibodies, Monoclonal↗
PubMed1989

[The simulation of histopathological diagnosis with the help of an automated image analysis system (VISIAC)].

Simulation of the diagnostic algorithm in histopathology at 2 different light microscopical magnifications (x4, x40) for separating 7 diagnostic groups in lung pathology (healthy lung, healthy bronchus, lymphocytic inflammation, epidermoid-, adeno-, small cell, and large cell carcinoma) is presented. 140 cases were tested as a teaching set, 105 cases as learning set. Gray value distribution discriminates between healthy parenchyma and the diseases in all cases tested; minimum spanning tree discriminates between inflammation and carcinoma in all cases, and in between the carcinoma with 70% to 80% accuracy. The measurements may be used as additional aid in difficult diagnostic cases.

Algorithms↗
PubMed1989

[Demonstration of independent cellular prognostic factors in squamous cell carcinoma of the lung].

The aim of this investigation was to find out whether a histopathologically homogeneous group of patients (similar in histology, grade, operation, and therapy) could be divided with respect to survival by determining cellular tumor factors. Therefore out a group of 100 patients 46 patients with previously untreated epidermoid lung carcinomas were selected. From these patients fresh surgical specimens of tumors were investigated by means of flow cytometry and the obtained data were correlated with five years survival. Patients with aneuploid tumors had significantly shorter survival times than did those with diploid tumors (p = 0.02). Seven of eleven patients with diploid tumors survived five years or more, whereas 25 of 35 patients with aneuploid tumors died within this period. Patients having tumors with a high proportion of G0/G1-phase cells survived significantly longer (p = 0.04) than patients having tumors with a lower proportion of G0/G1-phase cells. Within five years half of the patients with a high proportion of G0/G1-phase cells survived in contrast to 10% of patients in the other group. These data demonstrate that in addition to the well known clinical and histological factors independent cytometric prognostic factors in epidermoid carcinoma of the lung exist.

Aneuploidy↗
PubMed1988

Expression of neuroendocrine markers (neuronspecific enolase, synaptophysin and bombesin) in carcinoma of the lung.

The value of immunoreactivity of antibodies against neuronspecific enolase (NSE), bombesin (GRP), and synaptophysin (SY 38) as markers for various human lung carcinoma has been assessed. One hundred-forty-two primary bronchus carcinomas (small cell anaplastic carcinoma, epidermoid carcinoma, adeno carcinoma, and large cell anaplastic carcinoma) were studied by the indirect immunoperoxidase method (PAP). SY 38 was found to react positively in 49/68 (79%) of the small cell anaplastic carcinoma (SCCL) and in 6/74 (8%) of the non-small cell carcinoma of the lung (NSCCL). Positive immunohistochemical data with antibody SY 38 showed in some cases an immunoreactive polypeptide of Mr = 40.000 obtained by immunoblotting similar in molecular weight as described for synaptophysin in other tumours. Reactivity of NSE was observed in 41/68 (61%) of the SCCL and in 8/74 (10%) of the NSCCL. Positive reactivity to GRP was similar to NSE in 42/68 (62%) of SCCL and in 7/74 (10%) of NSCCL. All cases of NSCCL reacting positively to SY 38 were found to react positively to NSE, and to GRP. Prognostic value of SY 38 was calculated vp = 0.71 for positive prediction and vn = 0.91 for negative prediction. The data indicate that SY 38 represents the broadest marker for neuroendocrine carcinoma of the lung since in addition to the majority of SCCL about 10% of NSCCL are recognized by the antibody SY 38.

Antibodies, Monoclonal↗
PubMed1988

Histomorphological aspects of TNM-classification of carcinoma of the lung.

This prospective study evaluates the histopathological findings on 613 patients undergoing curative resection of a bronchus carcinoma and operated on between January 1982 and September 1984. The WHO rules for tumor classification and grading, and the 1979 pTN classification rules of the UICC were followed. Taking into account the biological properties of the tumors and the patient survival times, the prognostic value of histopathological data is discussed. Apart from the clear general dependence of the average survival time on the tumor cell type, it was found that tumor volume is of greater prognostic value with respect to patient survival than tumor diameter.

Adenocarcinoma↗