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Biomedical subjects

B D Bültmann

Publications and source records attributed to B D Bültmann.

11 recordsLinked to original sources
PubMed2006

Simplified detection of microsatellite instability in colorectal cancer without the need for corresponding germline DNA analysis.

A panel of five quasimonomorphic mononucleotide repeats that dispenses with the need to analyse corresponding germline DNA was proposed by Suraweera et al for the detection of high-frequency microsatellite instability (MSI) in colorectal cancer. Using this panel, a simplified and a more sensitive (compared with the original) algorithm (p<0.05) was developed to define the instability of each repeat by assessing the morphological shape of its plot and not its absolute length. 103 cases of colorectal tumours were investigated and the results compared with those obtained by the analysis of five consensus microsatellites (Bethesda reference panel). By the proposed method, a higher specificity, but no loss of sensitivity, was found. Thus, the use of the five mononucleotide repeats in combination with the modified assessment technique simplifies the assessment of MSI, while retaining the sensitivity of the Bethesda panel for the detection of high-frequency MSI.

Algorithms↗
PubMed2004

[The overexpression of NCAM (CD56) in human hearts is specific for ischemic damage].

The main reason for myocardial dysfunction is chronical myocardial ischemia. Recently we could show, that NCAM (CD56), a neural cell adhesion molecule and member of the immunoglobuline superfamily, and the transcription factor AML1 (RUNX1) are overexpressed in chronic ischemic human heart failure compaired to normal hearts. Here we demonstrate, that the overexpression of NCAM (CD56) is specific for ischemic damage as compaired to other heart diseases including congestive cardiomyopathy, hypertrophic obstrutive cardiomyopathy, myocarditis and sarcoidosis. Concerning the transcriptional regulation of NCAM (CD56) by AML1 (RUNX1) we isolated 3 novel isoforms of AML 1 (RUNX1) with different transactivating function, that might be a regulatory element of the NCAM (CD56) overexpression in chronical myocardial ischemia.

Adult↗
PubMed1985

Interaction between enteroviruses and human endothelial cells in vitro. Alterations in the physical properties of endothelial cell plasma membrane and adhesion of human granulocytes.

Fluorescent molecular probes were used for study of the interaction between enteroviruses (Echo 9, Echo 12, and Coxsackie B3 virus) and human endothelial cells in monolayer culture. With the use of the monomer-excimer method with pyrene decanoic acid it was shown that a marked dose-dependent restructuring of the plasma membrane occurred following addition of virus to the endothelial cells. This took the form of an increase in the lipid surface available to the lipophil reporter molecules, probably due to an alteration in the domain structure of the plasma membrane caused by insertion of virus capsid proteins. Experiments with diphenylhexatriene indicated that the enteroviruses had only a slight tendency to make the plasma membrane of the endothelial cell more fluid. Concomitant with these alterations in the biophysical properties of the membrane, a virus-induced increase in granulocyte adherence to the endothelial cells was observed for all three enteroviruses studied. Possible mechanisms for this elevated adherence are discussed, as well as the significance of the results for the phenomenon of virus-induced granulocytopenia.

Cell Adhesion↗
PubMed1984

Analysis of cell movement.

The methods of statistical physics have been applied to the analysis of cell movement. Human leukocytes (granulocytes) were observed using time-lapse photography. The center of gravity of a cell, variations of cell shape, and cell orientation were investigated. This analytical description leads to a better understanding of cell movement. Stationary motion of a cell is described by the anisotropy of the cell shape. The cell displacement can be characterized by three different types of movement: The persistent mode where the cell moves away from an arbitrary chosen origin with its track velocity. The diffusion mode where the cells become dispersed in space by a random walk process. The drift mode where the cell moves with a drift velocity, v parallel, in a concentration gradient of chemoattractant molecules. The chemokinetic response is described by the diffusion constant D (= 240 microns2/min) and the track velocity vc (= 30 microns/min). The chemotactic response is described by the degree of orientation P1 (= 0.8), which is identical with the McCutcheon index and the chemotropism index. Cell movement can be described by elementary moving states, and the life time of such a moving state is 0.5 min. The survival probability of the moving state is determined by an internal program. It is not described by a stochastic process. The angular change in moving direction is also programmed, as the square root of the mean square angular change is +/- 50 degrees. The plus and minus direction are equally probable in a chemokinetic response. However, in a chemotactic assay the plus and minus directions are not equally probably. We found that the information transfer from the chemotactic gradient to the migrating cell is 1 bit per change in moving direction. A disturbance in this information transfer leads to an order-disorder transition. Furthermore, we found that the migrating cell exhibits a directional memory of 75 s.

Biophysical Phenomena↗
PubMed1984

Echo 9 virus-induced order-disorder transition of chemotactic response of human polymorphonuclear leucocytes: phenomenology and molecular biology.

By means of functional, morphological, and biophysical methods the in vitro interaction of Echo virus, type 9, strain A. Barty with human polymorphonuclear leucocytes (PMNs) was investigated and analyzed by statistical methods. Control cells and virus-treated PMNs (15 min, 37 degrees C; PMN: virus (pfu)-ratio ranging from 1:1 to 1:50) were exposed to a chemotactic gradient (N-formylmethionyl-leucylphenylalanine = f-Met-Leu-Phe, 10(-8) M/mm) in a Zigmond chamber. Whereas the track velocity of the moving PMNs was not affected by the virus, the degree of orientation of virus-treated PMNs declined in a way dependent on the viral dose and on the time of PMN:virus interaction, resulting in a shift from chemotactic to chemokinetic response. This virus-induced order-disorder transition of chemotactic response can be described by a logarithmic law in analogy to the Weber-Fechner law. Parallel to the functional disturbances, virus-induced changes of cell shape, which could be confirmed by additional light and electron microscopy techniques, were also detected using statistical analysis of cytological data (median cell size, anisotropy of cell shape) by means of two-dimensional histograms. To investigate f-Met-Leu-Phe- or/and Echo 9 virus-induced PMN-cell membrane changes, the monomer-excimer technique with pyrenedecanoic acid as fluorescent probe was applied, which gives information about structural changes of the cell membrane. Addition of the chemotactic peptide (10(-8) M) to control PMNs resulted in a higher rate of excimer formation obviously due to the formation of new functional (receptor) units (= activated cell membrane). Echo 9 virus exhibited an opposite effect. Quantitative analysis of these results revealed that the f-Met-Leu-Phe-induced cell membrane changes were extinguished by the addition of 2 pfu Echo 9 virus. So far, we have additional indicators of a virus-induced order-disorder transition of chemotactic response of human PMNs on a molecular biological level.

Biophysical Phenomena↗
PubMed1984

F-Met-Leu-Phe and echo 9 virus interaction with human granulocytes. Changes of cell membrane structure.

Biophysical and biochemical methods were applied for investigation of cell membrane properties of human polymorphonuclear leukocytes (PMNs) exposed to the chemotactic peptide N-formylmethionyl-leucylphenylalanine (f-Met-Leu-Phe) and echovirus type 9, strain A, Barty. Steady-state fluorescence depolarization with diphenylhexatriene demonstrated no gross changes of the total membrane fluidity under the different experimental conditions. However, by means of the monomer-excimer technique with pyrenedecanoic acid (PDA), significant changes of the local membrane structure were detected for both agents. As demonstrated by a higher excimer ratio, the membrane area available for the PDA molecules was restricted by f-Met-Leu-Phe. This effect was dependent on the dose and on the time of interaction of the chemotactic peptide. These experimental findings were explained by the formation of functional receptor units ("activated membrane"). Echo 9 virus exhibited the opposite effect, characterized by a higher ratio of monomers, which also depended on the viral dose and the time of virus-PMN interaction. These virus-induced findings were explained by the dissolution of functional receptor units. Consecutive exposure of the PMNs to f-Met-Leu-Phe and echovirus, or vice versa, demonstrated a virus-predominant effect on the membrane structures.

Cell Membrane↗
PubMed1983

Analysis of the directed and nondirected movement of human granulocytes: influence of temperature and ECHO 9 virus on N-formylmethionylleucylphenylalanine-induced chemokinesis and chemotaxis.

The directed movement of human polymorphonuclear leukocytes (PMN) in a plane (Zigmond chamber assay) is described by a statistical model. We demonstrate that (a) the movement of a single cell is a superposition of a directed and a random movement, and (b) the degree of orientation, P1, of moving cells in a chemotactic gradient can be determined either by the time average of a single cell or by the average of movement of multiple cells at a fixed time (Ergoden hypothesis). However, an homogeneous cell population is a necessary condition. P1, which is identical with the McCutcheon index, is derived from the measured angular distribution function of moving cells. The statistical model allows one to distinguish between chemotaxis and chemokinesis. Applying this model to the temperature-dependent changes of cell movement, we found that P1 = 0.82 (37 degrees C) decreased to P1 = 0.4 (22 degrees C). The average speed of moving cells exhibits a very strong temperature-dependent variation from 30 microns/min (37 degrees C) to 5 microns/min (22 degrees C), indicating a different temperature dependence of chemotaxis and chemokinesis. At a fixed temperature (37 degrees C) the stability of the chemotactic gradient can also be checked by the angular distribution function. In addition, this model was applied to investigate the enteric cytopathogenic human orphan, strain 9 (ECHO 9) virus-induced disturbances of cell movement. We found: (a) The average speed of cell movement is not affected by the virus. (b) The degree of orientation is not affected for virus doses below a critical virus dose, ao (virus/PMN = 0.8:1). (c) The degree of orientation above this critical value exhibits a time- and virus-dose-dependence. (d) At a fixed viral dose, the time-dependent decrease of P1 is described by an exponential law (virus/PMN = 5:1, the characteristic time is 110 min). (e) This characteristic time investigated as a function of viral dose results in a logarithmic law analogous with the Weber-Fechner law. These findings indicate that only chemotactic and not chemokinetic response is disturbed by ECHO 9 virus.

Cell Movement↗
PubMed1983

Age dependence of paralysis induced by echovirus type 9 in infant mice.

Newborn mice of different strains (including NMRI) infected with 2-5 x 10(6) pfu of echovirus type 9 strain A. Barty developed progressive flaccid paralysis five days after inoculation, followed by death. Suckling mice injected with the same infective dose two, four, or six days after birth disclosed at most transient paresis and survived. Infectivity titrations revealed in all groups a similar rate of virus multiplication exceeding 10(8) 50% tissue culture infective doses per mouse four days after virus inoculation. Histologically, polymyositis resulting in muscle fiber necrosis was seen. The percentage of damaged muscle tissue declined with increasing age of the experimental groups. It is concluded that in order for paralysis to occur, at least 50% of skeletal muscle tissue must be destroyed by virus-induced lesions before the sixth day of life. Electron microscopy demonstrated additional age-dependent, virus-mediated disturbances of postnatal muscle growth. Reparative events in destroyed muscle fibers seemed to be unaffected in all age groups.

Age Factors↗
PubMed1983

[Changes in the membrane fluidity of human neutrophilic granulocytes under the effect of a chemoattractant (FMLP) and of echo virus, type 9, A. Barty strain].

Preincubation of human polymorphonuclear leucocytes (PMNs) with different concentrations of Echo virus, type 9, strain A. Barty results in viral dose- and time-dependent inhibition of chemotactic cellular response to chemoattractant (N-formylmethionylleucylphenylalanine = FMLP). In the present experiments, by means of biophysical methods using excimer forming lipids (pyrendecanoic acid) the influence of FMLP and Echo 9 virus on membrane fluidity of PMNs was investigated. It is shown that the increase of membrane fluidity elicited by FMLP is reduced by the virus in a dose dependent manner. These results indicate virus-induced disturbance of molecular architecture and failure of natural signal processing of PMN-membranes. This biophysical method, therefore, can be used as a functional histochemical method to demonstrate functional defects in membranes of living cells.

Chemotaxis, Leukocyte↗
PubMed1982

Disseminated mycobacterial histiocytosis due to M. Fortuitum associated with helper T-lymphocyte immune deficiency.

Mycobacterial histiocytosis is a rare disease usually associated with haematological or immunological disorders. We report a fatal case caused by M. fortuitum infection showing the typical disseminated histiocytosis. Immunological investigations revealed impaired cellular immunity demonstrated by negative skin tests with different "recall-antigens", and in vitro an isolated defect of helper T-lymphocytes in the peripheral blood which in combination with hypergammaglobulinemia suggests a "lymphocyte and distribution syndrome".

Adult↗