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Biomedical subjects

K Kayser

Publications and source records attributed to K Kayser.

At least 55 records · Page 3Linked to original sources

Immunochemical analysis of cathepsin B in lung tumours: an independent prognostic factor for squamous cell carcinoma patients.

In order to evaluate the possible role of the proteolytic enzyme cathepsin B (cath B) in human non-small cell lung cancer (NSCLC) we examined cath B concentrations (cath B(C)) and activities (cath B(A)) in homogenates of 127 pairs of lung tumour tissues and corresponding non-tumourous lung parenchyma. Total cath B activity (cath B(AT)) and enzymatic activity of the fraction of cath B, which is stable and active at pH 7.5 (cath B(A7.5)) were determined by a fluorogenic assay using synthetic substrate Z-Arg-Arg-AMC. The immunostaining pattern of cath B was determined in 239 lung tumour tissue sections, showing the presence of the enzyme in tumour cells (cath B(T-I)) and in tumour-associated histiocytes (cath B(H-I)). The median levels of cath B(AT), cath B(A7.5) and cath B(C) were 5.6-, 3.2- and 9.1-fold higher (P < 0.001), respectively, in tumour tissue than in non-tumourous lung parenchyma. Out of 131 tissue sections from patients with squamous cell carcinoma (SCC), 59.5% immunostained positively for cath B, while among the 108 adenocarcinoma (AC) patients 48.2% of tumours showed a positive reaction. There was a strong relationship between the levels of cath B(AT), cath B(A7.5), cath B(C) and cath B(T-I) in the primary tumours and the presence of lymph node metastases. Significant correlation with overall survival was observed for cath B(T-I) and cath B(A7.5) (P < 0.01 and P < 0.05, respectively) in patients suffering from SCC. In these patients positive cath B in tumour cells (cath B(T-I)) and negative cath B in histiocytes (cath B(H-I)) indicated significantly shorter survival rate compared with patients with negative cath B(T-I) and positive cath B(H-I) (P < 0.0001). In contrast, in AC patients, both, positive cath B(T-I) and positive cath B(H-I), indicated poor survival probability (P < 0.014). From these results we conclude that the proteolytic enzyme cath B is an independent prognostic factor for overall survival of patients suffering from SCC of the lung.

Adenocarcinoma↗

Use of a concurrent operants paradigm to evaluate positive reinforcers during treatment of food refusal.

The authors evaluated the responsiveness of 4 preschool-aged children to positive reinforcers within a concurrent operants paradigm during mealtimes. The children were presented with two identical, concurrently available sets of food. Each set differed in quantity and quality of positive reinforcement paired with acceptance of each bite of food or in the number of bites of food required to obtain positive reinforcement. Experiment 1 evaluated 1 child's responsiveness to positive reinforcement while permitting escape from bite offers. Experiment 2 evaluated 2 children's responsiveness to positive reinforcement when escape extinction occurred. Results from these experiments suggested that the children were responsive to positive reinforcers and chose more often the bites paired with the greater quantity and/or quality of reinforcement. Experiment 3 evaluated 1 child's responsiveness to positive reinforcement both without and with escape extinction. Results suggested that positive reinforcement affected choice behavior and that escape extinction affected amount of food consumed.

Behavior Therapy↗

Basic aspects of and recent developments in telepathology in Europe, with specific emphasis on quality assurance.

Telepathology is the diagnostic work of a pathologist from a distance and includes all specific fields of diagnostic pathology, such as frozen section services, expert consultation, cytometric and histometric measurement, and continuous education. For about 15 years experience has been collected at several universities in the United States and Europe based upon analog telephone lines (9.2 kbaud), digitized lines (ISDN, 64 kbaud), broad band connections (1.5 Mbaud) and the World Wide Web (28 kbaud). Potential use can be expected in the application of telepresentation, remote slide preparation, remote central diagnostics and telediscussion. The transfer of still images is well developed; that of live images is used in only a few institutions for frozen section services. The image quality and spatial resolution as well as the transfer speed are sufficient for expert consultations, morphometric measurements, quality assurance and education. All applications focus on discontinuous work flow. Although the European Community focuses on user needs and standardization aspects of telepathology by sponsoring a widespread telepathology project (Europath), implementation of telepathology into routine application in the continuous work flow has still to be developed. The technical equipment has still to be adjusted to the labor flow charts in routine pathologic diagnostic procedures. Telepathology seems to be the appropriate technique to offer both improvement in diagnostic quality and inclusion of the "control institution" into diagnostic responsibility.

Critical Pathways↗

Pulmonary metastases of breast carcinomas: ligandohistochemical, nuclear, and structural analysis of primary and metastatic tumors with emphasis on period of occurrence of metastases and survival.

BACKGROUND AND OBJECTIVES: Pulmonary metastases of breast carcinomas have a high frequency and are often subject to surgical intervention. To contribute to advances in the knowledge about morphometric and biochemical parameters of primary tumors and their metastatic lesions, analysis of syntactic structure and thermodynamic aspects as well as of expression of distinct glycohistochemical features with respect to period of metastasis occurrence and patient survival is desirable. METHODS: Clinical history, surgical findings, histopathological reports, survival of the patients with a maximum follow-up of 15 years, and paraffin blocks of 32 breast carcinoma specimens and their pulmonary metastases were examined. Only potentially curative resections of both the breast carcinoma and their metastases have been included for analysis. The following markers were applied: neoglycoconjugates with histoblood group A- and H-trisaccharides, lactose, alpha-N-acetyl-D-galactosamine and the Forssman disaccharide, a polyclonal immunoglobulin G fraction from human serum with specificity for 9-0-acetylated sialic acid, which is a tumor marker for melanomas, the serum lectins serum amyloid P component and mannan-binding lectin, the mannose-specific plant lectin concanavalin A, and monoclonal antibodies specific for estrogen and progesterone receptors, respectively. In addition, measurements of the integrated optical density (IOD) and tissue structure were performed. RESULTS: The frequency of expression of hormone receptors and expression of binding capacities to most of the applied probes was similar between the primary and metastatic tumors; however, it varied markedly between different patients. For the IOD parameters, a close association between the primary tumors and their metastases was seen, especially a rather low S-phase-related tumor cell fraction and a high percentage of tumor cells with an IOD >5C. The mean time for the development of intrapulmonary metastases measured 43 months. It was considerably longer in progesterone receptor-negative tumors (49.7 months) and those with a lack of expression of sites with specificity for the Forssman disaccharide (48.7 months). The survival was positively correlated with the presence of binding capacity of histoblood group A-trisaccharide and certain structural parameters, especially the structural entropy and its current. The presence of estrogen and progesterone receptors was not associated with the total survival at a statistically significant level. CONCLUSIONS: Histochemical features between the primary breast carcinoma and their intrapulmonary metastases can evidently vary. Analysis of the hormone receptor status in metastatic lesions seems to be useful for diagnostic purposes only in rare cases, i.e., distinguishing metastases from primary lung carcinoma. Nonetheless, the survival of patients with metastasizing breast carcinoma is associated with features of the primary tumors, especially the detection of binding capacities for the Forssman disaccharide and the histoblood group A-trisaccharide. Extent of lymph node involvement of the breast carcinoma is not prognostic for later pulmonary involvement.

Adult↗

Diffuse pulmonary hemosiderosis after exposure to pesticides. A case report.

This report describes the clinical, radiological, microscopical and ligandohistochemical findings in a 17-year-old woman who suffered from an acute onset of pulmonary hemosiderosis after inhalation of pesticides used for the cultivation of strawberries. She complained of headache, dyspnea, rhinitis, weakness and recurrent severe hemoptysis. Chest radiographs revealed bilateral patchy infiltrates, predominantly in the lower parts of both lungs. The consecutive severe anemia was treated by multiple blood transfusions which were repeated every 4-5 days. Open lung biopsies displayed signs of diffuse hemorrhage with hemosiderin-loaded macrophages, some hyaline membranes, focal fibroid deposits with intermingled histiocytes, mild interstitial fibrosis and focal intra-alveolar calcified bodies surrounded by foreign body giant cells. Analysis of endogenous lectins failed to demonstrate expression of binding capacities for maltose, fucose, mannose, lactose and sialic acid, Neither binding capacities for the macrophage-migration-inhibitory factor nor its presence, as analyzed by labeled sarcolectin, could be detected histochemically. The light microscopical findings are consistent with a longer-lasting diffuse pulmonary hemosiderosis; the presence of calcified bodies and foreign body giant cells (including the ligandohistochemical data) argues for a causal role of inhaled substances. The patient's clinical course improved after cyclophosphamide treatment, which restored her ability to work and released her from the need for recurrent blood transfusions.

Adolescent↗

Family conferences as forums for decision making in hospital settings.

Social workers in hospitals are often involved in family conferences where patient, family members and hospital personnel meet together to exchange information about the patient's condition and to plan for the future. In this paper the complexities of these meetings as decision making arenas are discussed and an outline of the three phases of family conferences--preparation, the conference meeting and follow up--is presented. The final section reports on an exploratory review of recent conferences as perceived by social workers from an acute and rehabilitation teaching hospital. The social workers' comments indicate that the conferences achieve the desired outcomes, especially for hospital staff. In this hospital the conferences are more often used for providing family members with information, and for collective decision making about the patient's future care, than for providing information to the patients about their illness and treatment.

Attitude of Health Personnel↗

Beyond plant lectin histochemistry: preparation and application of markers to visualize the cellular capacity for protein-carbohydrate recognition.

Oligosaccharides can store biological information. In this respect, their capacity even outmatches that of oligo- and polymeric structures of nucleotides and amino acids. Protein-carbohydrate interactions are thus considered to be involved in the regulation of diverse cellular activities. Over decades, plant lectins have proven valuable for assessing structural aspects of the enormous variety of carbohydrate epitopes and for monitoring spatially and/or temporally restricted patterns of expression. If the presence of these epitopes and the alterations in their occurrence bear physiological relevance, one reasonable possibility is that the visualized saccharides serve as ligands in an operative protein-carbohydrate recognition system. To support the validity of this hypothesis, receptor sites for a sugar compound must be localized. Carrier-immobilized carbohydrates (neoglycoconjugates) are adequate for this purpose. Chemical synthesis gains access to such probes. In the first stage, the presence of binding sites such as lectins in the tissue is ascertained. The next step toward proving the outlined hypothesis is the application of the first localized then purified endogenous receptors as glycohistochemical markers. It is essential to point out that the fine specificities of plant and animal lectins can differ, although they share an identical monosaccharide specificity. Thus, neoglycoconjugates for localizing sugar ligand-binding proteins and endogenous lectins to detect suitable binding partners are promising probes to enhance our knowledge about the capacities of cells to be engaged in protein-carbohydrate recognition in situ.

Biomarkers↗

Glycohistochemical properties of malignancies of lung and pleura.

Based upon the reasoning that protein-carbohydrate recognition is involved in diverse intercellular activities including growth control and cell motility 14 probes have been employed to characterize epitope presence in sections of 80 cases with operated lung carcinomas, 20 patients with mesothelioma, and 20 cases with non-malignant lung diseases. As parts of the innate immune system with supposed relevance for host defense the mannan-binding lectin (MBL) and serum amyloid P component (SAP) were employed. The naturally occurring immunoglobulin G fractions with selectivity for alphaa-galactosides (alpha+) and beta-galactosides (beta+) and their subfractions with enhanced target selectivity (alpha+beta-,alpha-beta+) allowed the monitoring of expression of reactive sites for these autoantibodies as a step to elucidate potential anti-tumor activity. Due to the diversity of cellular galactoside-containing glycoconjugates two galectins and a plant lectin were included. As a measure of receptor activities for carbohydrates, neoglycoconjugates with alpha-galactose, the B-disaccharide, the Forssman-disaccharide, and alpha-glucose as histochemically crucial ligand part were tested in addition to an antibody against heparin-binding lectin. Quantitative image analysis revealed significant differences between cases with small cell and non-small cell lung cancer for the plant lectin and one galectin, cases with non-tumorous lung disease and lung carcinoma for serum amyloid P component and the beta-galactoside-selective autoantibody fraction. Prognostic relevance was observed for the presence of glucose-specific sites in small cell lung cancer and meso-thelioma cases, and of galectin- and alpha-galactoside-selective immunoglobulin G fraction-binding sites in non-small cell lung cancer patients.

Adenocarcinoma↗

Association of prognosis in surgically treated lung cancer patients with cytometric, histometric and ligand histochemical properties: with an emphasis on structural entropy.

OBJECTIVE: To explore new tumor features for refined category formation that permits the tailoring of individualized treatment schemes in lung cancer. STUDY DESIGN: Survival data on patients from six independent studies on cases with surgically treated lung cancer, primary lung carcinoids or metastasizing breast carcinoma (including data on primary breast carcinoma) were analyzed by nonhierarchic multivariant discriminant analysis with respect to a set of cytometric/histometric and immunohistochemical/ligand histochemical parameters. The number of stem lines, S-phase-related tumor cell fraction and the extent of structural entropy and its current were measured. In addition, the expression of binding capacities for histo-blood group trisacharides, galectins, the alpha/beta-interferon antagonist sarcolectin, the lymphokine macrophage migration inhibitory factor and a monoclonal antibody to the Le(y) epitope was monitored for insight into aspects of immunologic and biologic behavior. RESULTS: In all studies, a correlation between tumor parameters, according to TNM stage and survival, was seen. In order to refine this category formation, at least certain selected features should provide an even more stringent association than TNM stages. Indeed, statistical correlation of the cytometric and histometric parameters as well as the expression of receptors for the two histo-blood group trisaccharides, ligands for the galectins (CL-16, CL-14) and macrophage migration inhibitory factor was stronger than that of TNM stage. A large amount of the current of structural entropy was especially highly significantly associated with poor survival. This observation could be verified in each of the different studies. CONCLUSION: The obtained data strongly support the notion that thermodynamic evaluation of tumor growth focusing on the "entropy distance" of the tumor from its environment is a promising perspective warranting extended studies. Additionally, glycohistochemical features, including binding capacities for histo-blood group trisaccharides, have the potential to aid in establishment of a biologic marker set for tumor staging.

Biomarkers, Tumor↗

[Incomplete resections in bronchial carcinoma: morbidity and prognosis].

Residual tumor (R1) was proven at the proximal bronchial resection margin in 88 (3.6%) of 2464 cases of lung cancer following lung resection and standard lymph node dissection. Postoperative complications (8%) were: fistula of the bronchial suture line (n = 7), bleeding (n = 2) and heart luxation (n = 1). The in-hospital mortality was 16.6%. Causes of death were: bronchial fistula (n = 7), erosion of the pulmonary artery (n = 4), respiratory failure (n = 1), and empyema (n = 1). Forty-three patients received postoperative radiation therapy. Median survival of all patients following incomplete resection was 16 months, compared to 37 months following complete resection (P < 0.001). Length of survival was independent of tumor stage, histology, site of infiltration and postoperative radiation. In conclusion, in resection for lung cancer clear margins should be verified by intraoperative frozen section. In the case of residual tumor at the bronchial resection margin, wider resection is mandatory in stage I and II if the patient meets the functional criteria. Even in stage III a and III b prognosis is significantly better after complete resection than R1-resection; the difference, however, is smaller than in lower stages.

Adult↗

Changes during the last decade in clinical parameters of operated lung carcinoma patients of a center for thoracic surgery and the prognostic significance of TNM, morphometric, cytometric, and glycohistochemical properties.

Two sets of patients with potentially curative resection of primary carcinomas operated in the Department of Thoracic Surgery, Thoraxklinik, Heidelberg during the period 1983-1984 (cohort I), and in 1994 (cohort II) were analyzed. The survival of patients, postsurgical TNM-stages, cell types, and exposure to potentially harmful substances were evaluated. In addition, cytometric and morphometric techniques, and various biotinylated markers have been applied to the tissue sections of the 1994 cohort. Cohort I comprised 282 patients (253 men and 29 women), cohort II all in all 171 patients (121 men and 49 women). In cohort I there were 262 heavy smokers, and 28 patients had a history of exposure to harmful environmental substances (asbestos, polycyclic aromates, etc.) compared to 145 smokers and 68 patients who inhaled potentially harmful substances in cohort II. Major changes were also seen in early lung cancer stages (pT1, pN0) which increased in cohort II, and in a decrease in the relative frequency of epidermoid carcinomas in both men and women with corresponding increase in the frequency of adenocarcinoma in both sexes. The median survival of patients operated with advanced tumor stages had remained unchanged, that of early stages (pT1, pN0, pN1) seems to have improved. Within the cytometric features syntactic structure analysis revealed that the current of structural entropy is closely associated with the survival of patients. Of prognostic significance are, in addition, the expression of binding capacities to histoblood group trisaccharides A and H, the presence and the binding of macrophage migration inhibitory factor, and the presence of ligands for the chicken liver galectin CL-16 and the LewisY antigen. Multivariant statistical analysis gave preferential prognostic importance to the glycohistochemical and morphometric parameters relative to the clinical pT and pN stages in survival analysis.

Adenocarcinoma↗

[Bipolar radiofrequency energy in arteries--the experimental results with a new catheter system].

PURPOSE: To evaluate the effects of radiofrequency heated bipolar probes on the human arterial wall. METHODS: Under standardised conditions, lesions were set on the inner layer of a piece of human cadaver arterial wall, using a radiofrequency-heated bipolar catheter. These lesions were measured and described both macroscopically and microscopically. Lesion size, applied energy levels and application conditions were correlated. RESULTS: The size of a lesion depended significantly on the size of the catheter, angle and pressure of catheter application (p < 0.05) and length of impulse (p = 0.002). There was no influence from the energy level employed. It proved impossible to treat calcified plaques. The depth of a lesion depended on the angle of catheter application only. No perforations were seen. CONCLUSIONS: Radiofrequency-heated bipolar catheters ablate the tissue of the arterial wall. Increasing tissue resistance resulting from higher energy levels prevents perforation in the experimental set-up. Calcified plaques cannot be treated by this method.

Aorta, Abdominal↗

Application of computer-assisted morphometry to the analysis of prenatal development of human lung.

Morphometry is well-established in tumour pathology. To evaluate is potential usefulness for description of developmental processes, histological slides from paraffin-embedded specimens of 67 human fetal lungs were Feulgen-stained, and morphometric characteristics of nuclei of epithelial pulmonary cells were analysed with an automated image analysis system. The measured cytometric features comprised of integrated optical density (IOD), S-phase-related IOD fraction, IOD entropy and nuclear area. Histometric features of the specimens were based upon the minimum spanning tree (MST) and included distances between neighboring epithelial cells, between epithelial cells and neighboring lymphocytes, and assessment of MST entropy. Notably, certain parameters revealed a non-uniform level during prenatal development S-phase-related IOD fraction increased from 5% to 8% between 14 and 16 weeks of gestation, then declined to 6% until birth. The IOD entropy steadily increased during development, whereas the extent of nuclear area remained constant. In accordance with an increase of the S-phase-related fraction the MST entropy displayed a singular peak between 14 and 16 weeks of gestation, which is probably associated with development of glandular structures in the lung. Correlation of expression of binding sites for markers, presumably involved in functional aspects of development, with such alterations, is shown for binding capacities of biotinylated fucoidan and the S-phase-related fraction. This may be helpful to infer immuno- or ligando histochemically defined tissue sites with potential physiological significance in morphometrically distinguished periods of development.

Cell Differentiation↗

Parameters derived from integrated nuclear fluorescence, syntactic structure analysis, and vascularization in human lung carcinomas.

Combined measurements of integrated nuclear fluorescence (INF) and vascularization were performed on surgical specimens of human lung carcinomas. Histological slides of formalin-fixed, paraffin-embedded tissue samples were treated with Texas Red-labeled antibody to factor VIII and the fluorochrome DAPI. The resulting images were analyzed with an epi-illumination fluorescence microscope and two different filter blocks. The first image displayed the vessels, and the second the DAPI-stained nuclei of surrounding cells. The extent of vascularization was assessed by calculating the volume fraction (Vv), the surface fraction (Sv), the area, and the minimum diameter of the vessels. The INF was measured in tumour cells and lymphocytes, and was grouped according to the distance from the nearest vascular boundary into the intervals of 0-20, 21-40, 41-60, 61-80, and > 80 mu. The numerical densities (Nv) as well as the percentages of S-phase-related tumour cell fraction (SPRF) and of tumour cells with an INF > 5C were computed. A minimum of 50 vessels and 300 tumour cells were examined. The material included 100 cases with primary lung carcinoma (39 epidermoid carcinomas, 39 adenocarcinomas, 13 large cell carcinomas, three small cell anaplastic carcinomas, and 6 carcinoid tumours). On the average, the volume density of the stroma amounts to 16.7%, and that of the vessels (Vv) to 12.8%. The minimum diameter of the intratumoral vessels is 13 mu and the measured circumference 138 mu. The numerical densities of tumour cells (lymphocytes) decrease with increasing distance from the vascular boundary from 6.3 (1.7) to 1.0 (0.1). A reduction is also seen in the percentage of the SPRF from 10.7 to 8.1%. The percentage of tumour cells with an INF > 5C, however, is positively correlated to the distance from the vascular surfaces from 34.2 to 38.2%. The measurements reveal that tumour cells are densely positioned and have an increased proportion of proliferation in the populations close to perivascular spaces, whereas chromosome abnormalities are seen more frequently, when tumour cells are located at a distance > 20 mu from the vascular surfaces.

Aneuploidy↗