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G Kayser

Publications and source records attributed to G Kayser.

At least 19 recordsLinked to original sources
PubMed2007

Surgery for cystic lymphangioma in Gorlin-Goltz syndrome.

INTRODUCTION: We present a case of three major lymphomesenteric cysts in a female patient with known basal cell nevus syndrome (BCNS or Gorlin-Goltz syndrome). DISCUSSION: Although those cysts have been reported to appear in this syndrome, the exact prevalence is not known. In this case, the patient suffered from severe and recurrent abdominal pain due to bowel obstruction. CONCLUSION: By causing severe symptoms, cystic lymphangiomas are an important complication of the BCNS despite of their seldom occurrence. Surgeons confronted with intraabdominal masses in a patient with BCNS should always be aware of this manifestation of the disorder and plan interdisciplinary operations.

Abdominal Pain↗
PubMed2006

Digitized pathology: theory and experiences in automated tissue-based virtual diagnosis.

AIMS: To describe the theory and develop an automated virtual slide screening system. Theoretical considerations. Tissue-based diagnosis separates into (a) sampling procedure to allocate the slide area containing diagnostic information, and (b) evaluation of diagnosis from the selected area. Nyquist's theorem broadly applied in acoustics, serves to presetting the sampling accuracy. Tissue-based diagnosis relies on two different information systems: (a) texture, and (b) object information. Texture information can be derived by recursive formulas without image segmentation. Object information requires image segmentation and feature extraction. Both algorithms complete another to a "self-learning" classification system. METHODS: Non-overlapping compartments of the original virtual slide (image) are chosen at random with predefined error-rate (Nyquist's theorem). The standardized image compartments are subject for texture and object analysis. The recursive formula of texture analysis computes median gray values and local noise distribution. Object analysis includes automated measurements of immunohistochemically stained slides. The computations performed at different magnifications (x 2, x 4.5, x 10, x 20, x 40) are subject to multivariate statistically analysis and diagnosis classification. RESULTS: A total of 808 lung cancer cases of diagnoses groups: cohort (1) normal lung (318 cases) - cancer (490 cases); cancer subdivided: cohort (2) small cell lung cancer (10 cases) - non-small cell lung cancer (480 cases); non-small cell lung cancer subdivided: cohort (3) squamous cell carcinoma (318 cases) - adenocarcinoma (194 cases) - large cell carcinoma (70 cases) was analyzed. Cohorts (1) and (2) were classified correctly in 100%, cohort (3) in more than 95%. The selected area can be limited to 10% of the original image without increased error rate. A second approach included 233 breast tissue cases (105 normal, 128 breast carcinomas) and 88 lung tissue cases (58 normal, 38 cancer). Texture analysis revealed a correct classification with only 10 training set cases in >92% for both, breast and lung tissue. CONCLUSIONS: The developed system is a fast and reliable procedure to fulfill all requirements for an automated "pre-screening" of virtual slides in tissue-based diagnosis.

Algorithms↗
PubMed2005

Phenotype and genotype associations of lung carcinoma with atypical adenomatoid hyperplasia, squamous cell dysplasia, and chromosome alterations in non-neoplastic bronchial mucosa.

The frequency of preneoplastic lesions of the lung and bronchial mucosa as well as potential genotype alterations in spatial relationship to pulmonary malignancies still need intensive investigations in order to understand the occurrence and manifestation of lung cancer in detail. To investigate the contemporary manifestation of lung cancer precursor lesions, peripheral (non-neoplastic) lung parenchyma and bronchial mucosa of operated lung carcinomas were analyzed at distinct distances (1, 2, 3, and 4 cm) from the tumor boundary for pre-neoplastic lesions--atypical adenomatoid hyperplasia (AAH) and squamous cell dysplasia (SCD), in 150 surgical specimens. Short-term tissue cultures of additional 55 primary and secondary lung tumors and their surrounding non-neoplastic bronchial mucosa were performed at the same distances in order to search for chromosome alterations, i.e. genotype aberrations. In phenotype observations, atypical adenomatoid hyperplasia was noted in 19/150 (13%) cases, and squamous cell dysplasia in 46/150 (31%) cases. The degree of cellular atypia decreased with increasing distance from the tumor boundary in both AAH and SCM. AAH was observed more frequently in adenocarcinomas, SCQ more frequently in squamous cell carcinomas. In genotype observations, the average number of abnormal metaphases measured 4.5/10 high power fields (HPF) in primary lung carcinomas, and only 2/10 in metastases. Data indicate that the so-called preneoplastic lesions in the lung are not completely tumor-precursor lesions, but, in addition, induced by the tumor itself.

Bronchi↗
PubMed2001

Small pulmonary lesions--a challenge for thoracic surgery?

We analyzed the diagnosis, the potentially associated external and clinical features, and the surgical procedures of small pulmonary lesions, especially hamartomas (in relation to peripheral T1 lung carcinomas and lymphoid hyperplasia) in 103 patients who experienced enucleation or resection of pulmonary hamartomas between March 1, 1995 and December 31, 2000. The causes of surgical intervention, presurgical diagnoses, surgical procedures, location, size, and histological compartments were analyzed, as well as clinical features potentially associated with the tumors (alcohol, asbestos, smoking, and chronic lung diseases). Follow up of patients lasted for 5.5 years at maximum. For comparison, 36 patients with peripheral T1 lung carcinomas are included as well as 50 patients with lymphoid hyperplasia. The sex and age distribution of the patients with hamartomas was comparable to that of patients with lymphoid hyperplasia. About 75% of men and 55% of women were heavy smokers, with an average history of 30 and 17 pack years, respectively. In 84% of patients, the lesions were incidentally detected in chest radiographs, whereas 12% of patients underwent thoracic surgery suspicious for intrapulmonary metastases of known extrapulmonary malignancies. Enucleation was performed in 21%, and wedge resection in 77% of patients. At average, hamartomas were smaller than T1 lung carcinomas, but considerably larger in comparison to lymphoid hyperplasia. No recurrent tumors or additionally detected hamartomas were noted during the follow up, and both surgical procedures (enucleation or wedge resection) were identical in curative treatment. All patients with peripherally localized T1 tumors underwent lobectomy. The 3/5 year survival rate was calculated to 69/52%. Lymphoid hyperplasia is of clinical importance for the estimation of prognosis in patients with metastatic disease, as the number of radiologically suggestive metastatic nodules can often be significantly changed due to this entity. Pulmonary hamartomas are benign lesions that display certain clinical associations with malignant lung carcinomas in respect to external risk factors, and to lymphoid hyperplasia. Both surgical procedures (enucleation or wedge resection) can be performed, giving identical results in respect to treatment.

Adolescent↗
PubMed2001

[Proliferation rate of small cell lung carcinoma. A cytomorphometric parameter with prognostic significance].

AIM: Evaluation of prognosis-associated parameters in patients with small cell lung carcinoma. MATERIAL AND METHODS: Biopsies of 46 patients suffering from a non-treated small cell lung carcinoma were stained with Feulgen and immunohistochemically with Ki-67 antibody. The integrated optical density (IOD) and proliferation rate was measured by syntactic structure analysis and correlated with survival. RESULTS: About 85% of patients had a smoking history (46 pack years on average). The median survival time was 13.5 months, the proliferation rate (Ki-67 positive tumor cell nuclei) 68.2% and S-phase percentage 9.2%. Ot average, 25 proliferating tumor cell nuclei formed clusters (mean diameter 95 microns). The prognosis was associated with the proliferation rate (p < 0.04), tumor stage (stage I versus lib, p < 0.05), at threshold limits with S-phase rate (p < 0.07) and serum levels of LDH and NSE (p < 0.06 and p < 0.07 respectively). CONCLUSIONS: Immune histochemical determination of the Ki-67 protein is a useful method to estimate the prognosis of patients with small cell lung carcinoma.

Antigens, Neoplasm↗
PubMed2001

Survival, disease-free interval, and associated tumor features in patients with colon/rectal carcinomas and their resected intra-pulmonary metastases.

OBJECTIVE: Colon/rectum cancer often presents with intrapulmonary metastases. Surgical resection can be performed in a selected group of patients. In this study, the search for possible prognostic factors of patients with primary colon/rectum cancer and lung metastases was performed. METHODS: Medical records of 110 patients operated on pulmonary metastases of primary colon/rectum cancer were reviewed. The clinical parameters include age, sex, pTNM/UICC stage, grading, localization, surgical and adjuvant therapy of the primary cancer. The number, maximum diameter and total intra-thoracic resected tumor-mass ('load'), the pre-thoracotomy serum carcinoembryonic antigen (CEA) levels, localization of the metastases (uni- vs. bilateral), the presence of hilar/mediastinal tumor-infiltrated lymph nodes, the surgical procedure and performed therapy schemes of lung metastases were recorded. RESULTS: The cumulated 5- and 10-year total survival after diagnosis of the primary carcinomas was estimated to 71 and 33.7%, respectively. After resection of the pulmonary metastases, the 3- and 5-year post-thoracotomy survival measured 57 and 32.6%, respectively. The median time interval between diagnosis of the primary cancer and thoracotomy (disease free interval (DFI)) was found to be 35 months. A non-negligible percentage of patients (15.4%) displayed limited tumor stages of the primary cancer (pT1/2, pN0). The median diameter of the largest metastasis measured 28 mm, and the median resected intrathoracic tumor-load was calculated to 11.4 cm(3). In only 8 patients hilar or mediastinal tumor-involved lymph nodes were found. A potentially curative resection of lung metastases was recorded in 96 patients. The overall survival was significantly correlated with the DFI and the number of intrapulmonary metastases. The DFI correlated significantly with the tumor load and the number of metastases; the post-thoracotomy survival with the number of metastases, tumor-load and pre-thoracotomy serum CEA level. Treatment, stage and grade of the primary cancer, occurrence of liver metastases and local recurrences, mode of treatment of metastases and postoperative residual stage had no significant correlation with either total nor post-thoracotomy survival. CONCLUSIONS: Pulmonary metastases occur even in patients with limited tumor-stages of primary colon/rectum cancer. DFI is the major parameter to estimate the total survival of patients with lung metastases. The survival after thoracotomy depends on the number of metastases, the intrapulmonary tumor load and the presence of elevated serum CEA level prior to thoracotomy.

Adult↗
PubMed2000

Telediagnosis of transbronchial fine needle aspirations--a feasibility study.

AIM: To analyze the diagnostic accuracy of telediagnostic procedures for transbronchial fine needle aspirations. MATERIAL AND METHODS: A double blind study was performed on cytological slides of 54 randomly selected cases with transbronchial fine needle aspirations. The slides were digitized using a Leica digital camera DC100 mounted on a microscope Leica Laborlux S, and analyzed by an experienced pathologist without knowing the definite diagnosis or any additional clinical data. The diagnoses stated by analyzing the digital images were compared to the final conventional diagnoses. In addition, the duration of the digital diagnosis, used magnifications, and difficulties for correct sampling were documented. RESULTS: The "digital" diagnoses of the 54 cases were all in general agreement with the definite diagnoses. No wrong positive or wrong negative case in respect to malignant/non-malignant (31/23) or to small cell/non-small cell (9/22) occurred. The performance of a digital diagnosis lasted for 115 s at average (15-260 s), and is significantly longer compared to that of conventional fine needle aspiration judgement (20 s). The screening magnification was commonly set to x2.5, that for definite diagnostic analysis x40. Benign diseases (2 tuberculosis and 3 sarcoidosis cases) were correctly classified. CONCLUSIONS: Telepathology systems can probably be used for fine needle aspiration analysis without major diagnostic errors. Their use can improve the endoscopic sampling and avoid second anesthesia when missing the lesion of request during the first examination.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2000

Recent developments and present status of telepathology.

Telepathology which is the diagnostic work of a pathologist at a distance has been developed to routine application within the last ten years. It can be classified in relation to application, technical solutions, or performance conditions. Diagnostic pathology performance distinguishes primary diagnosis (for example, frozen section statement) from secondary diagnosis (for example, expert consultation) and quality assurance (diagnostic accuracy, continuous education and training). Applications comprise (a) frozen section service; (b) expert consultations; (c) remote control measurements; and (d) education and training. The technical solutions distinguish active (remote control, live imaging) systems from passive (conventional microscope handling, static imaging), and the performance systems with interactive (on-line, live imaging) use from those with passive (offline, static imaging) practice. Intra-operative frozen section service is mainly performed with remote control systems; whereas expert consultations and education/training are commonly based upon Internet connections with static imaging in an off-line mode. The image quality, transfer rates, and screen resolution of active and passive telepathology systems are sufficient for an additional or primary judgment of histological slides and cytological smears. From the technical point of view, remote control telepathology requires a fast transfer and at least near on-line judgement of images, i.e., image acquisition, transfer and presentation can be considered one performance function. Thus, image size, line transfer rate and screen resolution define the practicability of the system. In expert consultation, the pixel resolution of images and natural color presentation are the main factors for diagnostic support, whereas the line transfer rate is of minor importance. These conditions define the technical compartments, especially size and resolution of camera and screen. The performance of commercially available systems has reached a high quality standard. Pathologists can be trained in a short time and use the systems in a routine manner. Several telepathology systems have been implemented in large Institutes of Pathology which serve for frozen section diagnosis in small hospitals located in the local area. In contrast, expert consultation is mainly performed with international connections. There is a remarkable increase of expert consultations by telepathology according to the experiences of the Armed Forces Institute of Pathology or the Department of Pathology, Thoraxklinik, Heidelberg. In expansion of these experiences, a "globalization" of telepathology can be expected. Telepathology can be used to shrink the period necessary for final diagnosis by request for diagnostic assistance to colleagues working in appropriate related time zones. Telepathology is, therefore, not a substitute of conventional diagnostic procedures but a real improvement in the world of pathology.

Europe↗
PubMed2000

Telecommunication--a new tool for quality assurance and control in diagnostic pathology.

Telepathology is the diagnostic work of a pathologist at a distance. It includes specific application fields which require specific system solutions. These comprise: a. frozen section service; b. expert consultations; c. remote control measurements, and d. education and training. Applications but, in addition, all aspects of diagnosis, especially those involved in the daily work flow of a pathologist. The image quality, transfer rates, and screen resolution of telepathology systems are sufficient for an additional or primary judgment of histological slides and cytological smears. It is, therefore, possible to include this technique into intralaboratory quality control of all steps of diagnostic procedures and to use this technique for quality assurance and control. Diagnostic quality is not a well defined term, and depends, in addition to external circumstances, on the diagnosis itself. The diagnostic quality can be maintained or even improved by use of telepathology systems. They can serve for control of image quality, access to various information sources, simultaneous transfer of images and diagnosis, and continuous education of the involved pathologists. For example, in continuous education and training, as a first step the pathologist should have access to an image data bank storing images related to the specific case, for example images taken from the same organ and from patients of similar age. The final stage would be an intra-diagnostic learning from the specific case; i.e. the time difference between questionnaires for a difficult diagnosis and the final diagnosis will become a minimum. Automated storing of the specific and diagnosis-associated images of the case will permit an open diagnostic system which will itself adjust to the micro-environment of the department of pathology. Although this future scenario has not been implemented to our knowledge, there is little doubt the development in telepathology will promote the technical procedures in the environment of a diagnostic pathologist. Telepathology is, therefore, not a substitute of conventional diagnostic procedures but a real improvement in the world of pathology.

Education, Medical, Continuing↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

Lectin ligands: new insights into their conformations and their dynamic behavior and the discovery of conformer selection by lectins.

The mysteries of the functions of complex glycoconjugates have enthralled scientists over decades. Theoretical considerations have ascribed an enormous capacity to store information to oligosaccharides. In the interplay with lectins sugar-code words of complex carbohydrate structures can be deciphered. To capitalize on knowledge about this type of molecular recognition for rational marker/drug design, the intimate details of the recognition process must be delineated. To this aim the required approach is garnered from several fields, profiting from advances primarily in X-ray crystallography, nuclear magnetic resonance spectroscopy and computational calculations encompassing molecular mechanics, molecular dynamics and homology modeling. Collectively considered, the results force us to jettison the preconception of a rigid ligand structure. On the contrary, a carbohydrate ligand may move rather freely between two or even more low-energy positions, affording the basis for conformer selection by a lectin. By an exemplary illustration of the interdisciplinary approach including up-to-date refinements in carbohydrate modeling it is underscored why this combination is considered to show promise of fostering innovative strategies in rational marker/drug design.

Crystallography↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

Involvement of laser photo-CIDNP (chemically induced dynamic nuclear polarization)-reactive amino acid side chains in ligand binding by galactoside-specific lectins in solution.

For proteins in solution the validity of certain crystallographic parameters can be ascertained by a combination of molecular-dynamics (MD) simulations and NMR spectroscopy. Using the laser photo-CIDNP (chemically induced dynamic nuclear polarization) technique as a measure for surface accessibility of histidine, tyrosine and tryptophan, the spectra of bovine galectin-1 and Erythrina corallodendron lectin (EcorL) are readily reconcilable with the crystallographic data for these two proteins. The results emphasise the role of Trp68/Trp69 for carbohydrate binding in bovine galectin-1/chicken galectins and of Trp194 in murine galectin-3. This feature derived from the crystal structure of bovine galectin-1 is maintained in solution for the prototype human homologue, two avian galectins and the chimera-type murine galectin-3, as the spectra corroborate the CIDNP-inferable spatial parameters of the four calculated models for binding-site architecture. In EcorL, Tyr106/Tyr108 are constituents of the extended combining pocket, which can be shielded in solution by ligand presence. Discrepancies between results from modelling and CIDNP measurements concern primarily the lack of reactivity of histidine residues for human and avian prototype galectins and of Tyr82/Tyr229 of the plant lectin. Site-directed mutagenesis of EcorL is assumed to provide information on the role of a certain residue for functional aspects. When single-site mutants of EcorL ([Ala106]EcorL, [Ala108]EcorL, [Ala229]EcorL) were subjected to molecular-dynamics (MD) simulations, the apparent surface accessibilities even of spatially separated amino acid side chains could non-uniformly be affected. This conclusion is supported by the assessment of the spectra for the mutant proteins. On the basis of these CIDNP-results modelling of the binding-site architecture of the lectin indicates the occurrence of notable alterations in the orientation of Tyr106/Tyr108 phenyl rings. The implied potential effect of single-site mutations on conformational features of a protein will deserve attention for the interpretation of studies comparing wild-type and mutant proteins.

Amino Acid Sequence↗
PubMed1995

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↗
PubMed1992

Inhibition of cyclooxygenase attenuates baroreceptor function and increases the pressor response to norepinephrine in man.

The possible influence of prostaglandins on baroreceptor function in man has been investigated. Baroreceptor reflex was activated by intravenous infusion of norepinephrine and the pressor response was measured, both before and after administration of indomethacin. Resting blood pressure remained unchanged after indomethacin while resting heart rate was significantly decreased as compared to placebo and the norepinephrine-induced rise in mean arterial blood pressure was significantly more pronounced. The baroreceptor-mediated decrease in heart rate tended to be smaller. Baroreceptor sensitivity (delta heart rate/delta blood pressure) was significantly reduced by indomethacin to about half of the control value. In addition to attenuation of sensitivity, the findings represent resetting of the baroreceptor setpoint and a more pronounced pressor response to norepinephrine after cyclooxygenase inhibition. Thus, eicosanoids originating via the cyclooxygenase pathway of arachidonate metabolism may modulate the vascular response to adrenergic stimulation and may participate in the regulation of baroreceptor reflex setpoint and sensitivity.

Adult↗