PubMed Health⌕ Search

Biomedical subjects

K Münch

Publications and source records attributed to K Münch.

18 recordsLinked to original sources
PubMed2001

[Measurement of the diameter of segments of retinal branch vessels in digital fundus images - An experimental study of the method and reproducibility].

PURPOSE: The aim of this study was the evaluation of new algorithms to measure diameter of segments of retinal branch vessels offline in local dependence and independent by observer. Methods 360 flashed fundus images (camera FF 450 ZEISS Germany, Visualis IMEDOS GmbH Weimar/Germany) of 12 eyes of healthy volunteers (10 independent sessions containing 3 images for every eye) were analysed. Algorithms detect the vessel diameter along the vessel course automatically. Corresponding segments of a retinal artery and vein were examined (mean length of the segment 2.5 mm) in every image of one eye. Results The marked arterial segment was detected automatically in 359 pictures and the venous segment in all pictures. The mean vessel diameter was detected in single pictures with a mean coefficient of variation (CV) for arteries of 3.4 % and for veins of 2.7 %. The differences of arterial and venous diameter between images were not significant. Analyzing sessions the CV of the mean vessel diameter were reduced for arteries to 2.7 % and for veins to 2.5 %. The standard deviation of the mean vessel diameter was independent of the vessel diameter (branch vessels with diameter of 120 to 200 micrometer). The mean CV of the vessel diameter at single locations were 5.7 % for arteries and 3.8 % for veins. Conclusions The new algorithms are useful for retinal vessel analysis, if there are no questions concerning the dynamic of vessel behaviour.

Adult↗
PubMed2000

Use of simple and complex in vitro models for multiparameter characterization of human blood-material/device interactions.

Medical devices, intended for blood contacting applications, undergo extensive in vitro testing followed by animal and clinical feasibility studies. Besides the use of materials known to be intrinsically blood-compatible, the surface of such devices is often modified with a coating in order to improve the performance characteristics during blood exposure. In vitro evaluation of blood-device interactions accompanies the product development cycle from the early design phase using basic material geometries until final finished-product testing. Specific test strategies can vary significantly depending on the end application, the particular study objectives and variables of interest, and cost. To examine the degree to which findings derived from two different in vitro approaches complement one another, this report contrasts findings from a simple multipass loop model with findings from a simulated cardiopulmonary bypass (CPB) model. The loop model consists of tubular test materials, with and without surface modification, formed into valved Chandler loops. The CPB model has an oxygenator with and without surface modification connected to a reservoir and a blood pump. The surface modifications studied in this report are the Carmeda BioActive Surface and Duraflo II heparin coatings. Common blood parameters in the categories of coagulation, platelets, hematology, and immunology were monitored in each model. Ideal models employ the optimal level of complexity to study the design variables of interest and to meet practical cost considerations. In the case of medical device design studies, such models should also be predictive of performance. In the more complex and realistic simulated CPB model, experimental design and cost factors prevented easy/optimum manipulation of critical variables such as blood donor (use of paired samples) and heparin level. Testing in the simpler loop model, on the other hand, readily offered manipulation of these variables, and produced findings which overlapped with observations from the more complex CPB model. Thus, the models described here complimented one another. Moreover, conclusions from consistent findings, such as favorable responses associated with the heparin coatings, between the two models were considered to be more robust.

Biocompatible Materials↗
PubMed1998

[Germline mutations in the MEN1 gene: basis for predictive genetic screening and clinical management of multiple endocrine neoplasia type 1 (MEN1) families].

BACKGROUND AND OBJECTIVE: Mutations in the MEN 1 gene were recently discovered as the causative genetic defect of the autosomal dominantly inherited multiple endocrine neoplasia type 1. It was the aim of this study to evaluate the spectrum of MEN 1 mutations in our own series of patients in order to obtain a basis for predictive family screening. PATIENTS AND METHODS: Genomic DNA from peripheral blood of 21 patients with MEN 1, members of 14 non-related MEN 1 families, was examined for MEN 1 germ-line mutations by means of single-strand conformation variant analysis (SSCP) and direct DNA sequencing. In addition, blood from 20 asymptomatic family members of five families was tested for its predictive value. RESULTS: Eleven different heterozygotic germ-line mutations, among them eight frameshift, two missense and one nonsense mutations, were identified. In four of the 20 asymptomatic members from five MEN 1 families who had been tested after appropriate genetic counselling, the MEN 1 mutation characteristic for the particular family was found. Clinical screening programme in three mutation carriers revealed abnormal findings in all three: one primary hyperparathyroidism, one prolactinoma and one nonfunctioning pancreatic tumour each. The 16 family members without MEN 1 mutation were spared further unnecessary screening investigations. CONCLUSION: Although the function of the MEN 1 gene is not yet known, molecular genetic tests provide a basis for genetic counselling, predictive genetic screening and clinical management of MEN 1 families.

Adult↗
PubMed1998

Frequent abnormalities of the putative tumor suppressor gene FHIT at 3p14.2 in pancreatic carcinoma cell lines.

The FHIT gene is localized on chromosome 3p14, a region including a tumor cell-specific, commonly deleted region. To determine the role of the FHIT gene in pancreatic carcinogenesis, 14 pancreatic carcinoma cell lines were analyzed by reverse transcription-PCR and exon-specific PCR amplification of genomic DNA. The full-length FHIT transcript was lost in 70% of the pancreatic carcinoma cell lines analyzed, while 66% also revealed intragenic homozygous deletions of exons 3, 4, and 5. Truncated FHIT transcripts lacking a variable number of exons most likely represented alternative splicing products. Fhit protein expression was dependent on a full-length FHIT transcript. The results suggest that the FHIT gene may be a target tumor suppressor gene involved in pancreatic carcinogenesis.

Acid Anhydride Hydrolases↗
PubMed1998

MEN1 gene mutations in 12 MEN1 families and their associated tumors.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited tumor syndrome characterized by the development of multiple endocrine tumors. The gene responsible for the disease, termed MEN1 gene. has recently been isolated and germline mutations have been described in affected MEN1 individuals. Twelve unrelated (German MEN1 families and their associated tumors (5 parathyroid tumors, 1 vipoma, 1 gastrinoma, 1 insulinoma) were characterized for MEN1 gene mutations by single-strand conformational variant (SSCV) analysis and DNA sequence analysis as well as for loss of heterozygosity on chromosome 11q13. We identified nine different heterozygous germline mutations (6 frameshift, 2 missense, 1 nonsense), eight of them were novel. Four of five informative MEN1-associated tumors revealed deletion of the second MEN1 allele, supporting the concept of a tumor suppressor gene. Furthermore. SSCV analysis proved an effective and sensitive method for the detection of menin mutations providing a reliable genetic screening approach supporting genetic counseling and clinical management of MEN1 family members.

Adenoma↗
PubMed1997

RAP1-like binding activity in islet cells corresponds to members of the Sp1 family of transcription factors.

Deletion and mutational analyses of the gastrin promoter have identified a binding site for the yeast transcription factor RAP1 relevant for transcriptional activation in islet cells. We here report that the mammalian transcription factors binding to this site in islet cells are the Sp transcription factor members Sp1 and Sp3. Furthermore, functional analyses revealed Sp1- and Sp3-mediated transcriptional activation of gastrin. These data reveal that the zinc finger proteins Sp1 and Sp3 do have similar binding specificities as the multifunctional yeast RAP1 protein.

Animals↗
PubMed1995

[Adaptive algorithm for automatic measurement of retinal vascular diameter].

A new adaptive computer-aided method for the measurement of blood vessel diameters has been developed. Within areas of interest in the image, the algorithm detects, line-wise, the edges of the vessels, which are then used for image-wise approximation and noise filtration. A high level of adaptivity with respect to numerous measuring parameters ensures its use in a wide range of applications. Thus, it has been shown to significantly improve clinically relevant reproducibility in the area of follow-up observations. The standard deviation for vessel diameter was (2.2 +/- 0.7)% in the case of arteries and (1.8 +/- 0.5)% in the case of veins. Testing the algorithm in images of poor quality revealed its high level of reliability and sensitivity.

Algorithms↗
PubMed1995

[Adaptive procedures for measuring arterial blood flow velocity in retinal vessels using indicator technique].

There are highly significant differences in the measuring results of arterial blood velocity between the indicator and laser-Doppler techniques (up to 800%). A new measuring procedure for the analysis of indicator dilution curves was developed based on indicator model and experimental results. The use of this new measuring procedure results in reduced mean systematic error between the indicator and laser-Doppler techniques to values around 10%. With the introduction of adaptive measuring arrays for the creation of indicator dilution curves and the application of adaptive algorithms for centering and spectral normalizing of the dilution curves, improved reproducibility can be expected.

Blood Flow Velocity↗
PubMed1992

An acidic region of the 89K murine cytomegalovirus immediate early protein interacts with DNA.

The product of the ie1 gene, the regulatory immediate early protein pp89 of murine cytomegalovirus (MCMV), interacts with core histones, which can mediate the association of pp89 with DNA. We report the capacity of pp89 to interact directly with DNA in the absence of cellular proteins. After separation of proteins by SDS-PAGE, pp89 bound ds- and ssDNA, with a preference for ssDNA. Binding to specific DNA sequences in the MCMV genome was not detected. The DNA-binding region of pp89 was located to amino acids 438 to 534 by analysis of deletion mutants expressed as beta-galactosidase or TrpE fusion proteins. This region is identical to the highly acidic C-terminal region spanning amino acids 424 to 532. The human cytomegalovirus IE1 protein, which contains a similar extended C-terminal acidic region, does not react with DNA under the same experimental conditions.

Animals↗
PubMed1991

The core histone-binding region of the murine cytomegalovirus 89K immediate early protein.

The gene regulatory immediate early protein, pp89, of murine cytomegalovirus interacts with both DNA-associated and isolated histones in vitro. We characterized the histone-binding region of pp89 and its cellular localization during cell division to examine the possible interaction between pp89 and chromatin. pp89 expressed constitutively in cell line BALB/c 3T3 IE1 does not interact with condensed chromatin. As observed in infected cells, pp89 is localized within the nucleus of cells during interphase but spreads throughout the cell plasma following degradation of the nuclear membrane during early mitosis. In late telophase, pp89 is reorganized within the nucleus. Analysis of pp89 deletion mutants and of fragments generated by cleavage at pH 2.5 revealed that the regions responsible for association with histone are located between amino acids 71 and 415, and are not identical with the domain that shows homology to histone H2B or the highly acidic carboxy-terminal region. A potential gene-activating role of the high affinity of pp89 for isolated histones and the low affinity for DNA-associated histones is discussed.

Animals↗
PubMed1989

Presentation of CMV immediate-early antigen to cytolytic T lymphocytes is selectively prevented by viral genes expressed in the early phase.

The regulation of antigen processing and presentation to MHC class I-restricted cytolytic T lymphocytes was studied in cells infected with murine cytomegalovirus. Recognition by cytolytic T lymphocytes of the phosphoprotein pp89, the immunodominant viral antigen expressed in the immediate-early phase of infection, was selectively prevented during the subsequent expression of viral early genes. The surface expression of MHC class I glycoproteins and their capacity to present externally added pp89-derived antigenic peptides were not affected. Because recognition of several other antigens occurred during the early phase, a general failure in processing and presentation was excluded. Since neither rate of synthesis, amount, stability, nor nuclear transport of pp89 was modified, the failure in recognition indicates a selective interference with pp89 antigen processing and presentation.

Animals↗
PubMed1988

Interaction of the 89K murine cytomegalovirus immediate-early protein with core histones.

The conditions that permit the interaction of immediate-early proteins of murine cytomegalovirus (MCMV) with DNA were studied. Chromatography of extracts from infected cells on MCMV DNA cellulose and calf thymus DNA cellulose showed that pp89, the regulatory major immediate-early protein, interacts with DNA and dissociates at salt concentrations between 0.3 and 0.6 M NaCl. pp76, a cleavage product of pp89, and additional minor ie 1 proteins eluted already at low ionic strength. Cellular DNA-binding factors were required for association of pp89 with DNA. These factors were identified as core histones. Chromatography of IE proteins on histone-Sepharose in the absence of DNA revealed a high-binding affinity that was resistant to 2 M NaCl. These results suggest that pp89 has no direct DNA-binding activity. A role for an amino acid sequence homology in the N-terminal region of pp89 with histone H2B in the pp89-histone-DNA interaction is discussed.

Cytomegalovirus↗
PubMed1987

Molecular analysis of herpesviral gene products recognized by protective cytolytic T lymphocytes.

The infection of the mouse with murine cytomegalovirus (MCMV) served as a model system to understand the biology of human CMV infection. The contribution of cytolytic T lymphocytes (CTL) to the recovery from infection was studied. Protection against lethal MCMV disease could be conferred on immunodepleted hosts by adoptive transfer of lymphocytes. The antiviral effect was mediated by specifically sensitized T lymphocytes of the CD8+ subset. These cells limited viral spread, prevented tissue destruction by viral cytopathic effects, and protected from lethal disease. Transferred cells have protective therapeutic function even when the virus has already colonized host tissues. CD8+ cells do not require the contribution of CD4+ cells for in vivo function. Selective expression of immediate-early (IE) phase genes in target cells allowed the detection of the immunodominant IE antigen recognized by CTL. The major IE gene ieI encodes a non-structural viral phosphoprotein, pp89, which resides in the nucleus of infected cells where it acts as transcriptional regulator. Expression of gene ieI is under temporal control, and membrane presentation of the protein domain detected by CTL is down-regulated by MCMV early-phase products. A recombinant vaccinia virus expressing gene ieI induced immunity that protected mice against a subsequent challenge with a lethal dose of MCMV. The protective effect was entirely mediated by CD8+ T lymphocytes. Thus, an experimental vaccine expressing a single nonstructural herpesvirus protein can induce a protective cellular immune response.

Animals↗
PubMed1987

CD8-positive T lymphocytes specific for murine cytomegalovirus immediate-early antigens mediate protective immunity.

We have shown in a murine model system for acute, lethal cytomegalovirus (CMV) disease in the immunocompromised natural host that control of virus multiplication in tissues, protection from virus-caused tissue destruction, and survival are mediated by virus-specific CD8+ CD4-T lymphocytes. Protection from a lethal course of disease did not result in a rapid establishment of virus latency, but led to a long-lasting, persistent state of infection. The CD8- CD4+ subset of T lymphocytes was not effective by itself in controlling murine CMV (MCMV) multiplication in tissue or essential for the protective function of the CD8+ CD4- effector cells. The antiviral efficacy of the purified CD8+ CD4- subset was not impaired by preincubation with fibroblasts that presented viral structural antigens, but was significantly reduced after depletion of effector cells specific for the nonstructural immediate-early antigens of MCMV, which are specified by the first among a multitude of viral genes expressed during MCMV replication in permissive cells. Thus, MCMV disease provides the first example of a role for nonstructural herpesvirus immediate-early antigens in protective immunity.

Animals↗
PubMed1986

The 89,000-Mr murine cytomegalovirus immediate-early protein activates gene transcription.

To study trans-activation of gene expression by murine cytomegalovirus (MCMV) immediate-early (IE) proteins, the IE coding region 1 (ie1), which encodes the 89,000-Mr IE phosphoprotein (pp89), was stably introduced into L cells. A cell line was selected and characterized that efficiently expressed the authentic viral protein. The pp89 that was constitutively expressed in L cells stimulated the expression of transfected recombinant constructs containing the bacterial chloramphenicol acetyltransferase (CAT) gene under the control of viral promoters. The regulatory function of the ie1 product was confirmed by transient expression assays in which MCMV IE genes were cotransfected into L cells together with recombinant constructs of the CAT gene. For CAT activation by the ie1 product, a promoter region was required, but there was no preferential activation of a herpes simplex virus type 1 delayed-early promoter. All plasmid constructs that contained the intact coding sequences for pp89 induced gene expression in trans. The MCMV enhancer region was not essential for the expression of a functional IE gene product, and testing of the cis-regulatory activity of the MCMV enhancer revealed a low activity in L cells. Another region transcribed at IE times of infection, IE coding region 2, was unable to induce CAT expression and also did not augment the functional activity of ie1 after cotransfection.

Animals↗
PubMed1985

Interstitial murine cytomegalovirus pneumonia after irradiation: characterization of cells that limit viral replication during established infection of the lungs.

Interstitial pneumonia associated with viral replication in lung tissue was observed after cytomegalovirus infection of total-body gamma-irradiated mice, whereas in noncompromised hosts the lungs were not affected and virus multiplication was restricted to the salivary glands. The radiation damage could either predispose normally nonpermissive cell types for productive infection or abrogate an immune control of the tissue manifestation of infection by elimination of lymphocytes. Adoptive transfer of lymphoid cells into irradiated, infected recipients supported the second alternative. Even when infection was established in the lungs, as manifested by the presence of infected lung tissue cells in the alveolar septa, an antiviral effect could be assigned to the Lyt-2+, L3T4- subset of T lymphocytes specifically sensitized in the immunocompetent donor. These cells did not require in vitro propagation to perform effector cell functions in vivo and were operative under physiological conditions in comparatively low numbers. Hence, there is reason to assume that T lymphocytes are responsible for the tissue distribution of cytomegalovirus replication during infection.

Animals↗
PubMedDate not supplied

Servoregulation of centrifugal pumps. A new technical approach to improve patient safety during long-term extracorporeal life support.

The objective of this study was to evaluate the principle technical requirements to servoregulate a centrifugal pump (Bio-Pump) and to discuss the potential risks and benefits of the potential use of such a device during long-term extra-corporeal support in an experimental laboratory study. A pressure control module (PCM) for the Bio-Pump was developed and a pressure measurement chamber to indirectly measure pressure in the venous limb of an extracorporeal circuit was constructed. The performance of the PCM combined with the pressure measurement chamber was evaluated in an experimental test circuit by recording pressure changes after sudden clamping of the venous line with and without servoregulation. Without the PCM pressure dropped from baseline to approximately -200 mm Hg after clamping and remained at that level. With the PCM active the pump speed was automatically and immediately reduced and the preclamping pressure level (+/- 10 percent) was restored within 500 msec. In this laboratory setting the Bio-Pump could effectively and rapidly be servoregulated with a conventional controller and an indirect pressure monitoring system. A potential clinical use of this system could help to improve the safety without imposing additional risks such as air embolism or backflow.

Centrifugation↗