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Biomedical subjects

U Gebhardt

Publications and source records attributed to U Gebhardt.

At least 19 recordsLinked to original sources

The low affinity Fc gamma RIIa and Fc gamma RIIIb on polymorphonuclear neutrophils are differentially regulated by CD45 phosphatase.

Stimulation of human polymorphonuclear neutrophils through ligation and cross-linking of the low affinity Fc gamma RIIa and Fc gamma RIIIb using mAb Fab and F(ab')2 fragments led to transient intracellular calcium mobilization and activation of the respiratory burst. Fc gamma RIIIb engagement resulted in a different pattern of intracellular calcium flux, and induction of the respiratory burst was significantly more effective than in the case of Fc gamma RIIa. These data demonstrate that the capacity of Fc gamma RIIIb to transduce transmembrane signals itself contributes to full cell activation. Treatment with a mAb F(ab')2 fragment recognizing CD45 phosphatase suppressed Fc gamma R-induced calcium mobilization in a dose-dependent manner. An ongoing intracellular calcium mobilization was immediately terminated when activation was followed by co-cross-linking Fc gamma R and CD45. This suggests that the initial steps of Fc gamma R signal transduction pathways are influenced by the state of tyrosine phosphorylation. Combined cross-linking of both receptors, however, was hardly susceptible to CD45. Also, inhibition of respiratory burst by CD45 in the case of Fc gamma RIIIb was minimal compared with that for Fc gamma RIIa. Signal transduction pathways of low affinity Fc gamma RIIa and Fc gamma RIIIb are differentially regulated by CD45, underlining the essential function of Fc gamma R-mediated tyrosine phosphorylation in polymorphonuclear neutrophil activation.

Adult

Introduction of an automatic QT interval driven rate responsive pacemaker.

QT driven rate responsive pacemakers have been implanted since 1981. The more than 6 years experience and additional knowledge gained during several clinical studies have culminated in the design of an automatic rate responsive pacemaker. The adjustment of the rate responsive function to each individual patient is carried out automatically by the pacemaker, which therefore performs several measurements both at rest and during exercise. The results of these measurements are used to adapt the rate responsive parameters in order to optimize the rate response, even under changing circumstances.

Algorithms

DSA--control of implanted devices for arterial hepatic perfusion.

In contrast to conventional film angiography, the perfusion pattern of hepatic arterial chemotherapy was consistently visualized by DSA in 40 patients with implanted Infusaid pump or Port-A devices. Incomplete perfusion of a liver region by the cytotoxic agent was recognized by DSA as accurately as by nuclide scintigraphy. Furthermore, DSA appeared to be more sensitive in determining aberrantly perfused extrahepatic regions; this was especially true when there was a nonligated right hepatic artery. Specific details of vascular lesions and associated complicating events also could be satisfactorily analyzed by DSA only.

Adult

Hemodynamic response to LBNP following 2 hours HDT (-6 degrees).

Central hemodynamics have been determined during stepwise decreasing LBP in head-down tilt (HDT) of -6 degrees. Measurements were performed on eight healthy volunteers using right heart catheterization. During LBNP, pressures in the right atrium, pulmonary artery, and pulmonary capillary (preload) decreased in parallel with the increase of negative pressure applied to the lower part of the body. Similarly, stroke volume and cardiac output decreased with increasing negative pressure. Heart rate moderately increased (30%) as well as total peripheral resistance. The left ventricular function curve was shifted downward and to the left during LBNP indicating hypovolemia with no evidence of decreased contractility. Cardiac dimensions determined by echocardiography changed in a similar way as those obtained by invasive measurements. There was a very close correlation between stroke volume determined by thermodilution and by echocardiography. Plasma norepinephrine and dopamine tended to increase at the end of LBNP. Echocardiography proved a useful and reliable approach to hemodynamic measurement during LBNP and is recommended for analysis of hemodynamic parameters during zero G and Gz simulation.

Adult

Central hemodynamics during zero gravity simulated by head-down bedrest.

Central hemodynamics during head-down tilt of -6 degrees lasting for 2 h were studied using catheterization of the pulmonary artery. M-mode echocardiography was performed simultaneously. Significant increases occurred for pressures in the right atrium, pulmonary artery in pulmonary wedge position, and for pulmonary vascular resistance. Cardiac and stroke volume index, heart rate, mean arterial pressure, and total systemic resistance remained constant throughout the exposure time. Constancy was also observed for echocardiographic measures of cardiac dimensions. It is concluded that head-down tilt leads to an increase of preload without any evidence of disturbed left ventricular function. No distinct time course of hemodynamic variables could be seen. Echocardiography proved a useful method to study cardiovascular adaptations during head-down tilting.

Adaptation, Physiological

Cardiovascular and biochemical response to simulated space flight entry.

Twelve men and 12 women were exposed to two types of short-duration (6 h) space flight entry simulation: bedrest (no head-down tilt) and water immersion (to the neck). Preceding and following the simulation, orthostatic tolerance testing using LBNP (Lower Body Negative Pressure) was performed. Male LBNP tolerance was greater than female LBNP tolerance at all four comparison points (pre- and post-bedrest, pre- and post-water immersion); whereas the short-duration bedrest reduces female LBNP tolerance about as effectively as water immersion, only water immersion leads to marked LBNP intolerance in the male subjects. If the water immersion model simulates zero G, loss of male and female orthostatic tolerance will be about equal after short-duration space flight. On the other hand, the bedrest simulation would indicate a greater loss of orthostatic tolerance for females.

Blood Pressure

Development of an electrocatalytic glucose sensor.

For the determination of glucose in body fluids, the electrocatalytic sensor, besides the enzyme sensor, is quite suitable, particularly for long-term intracorporeal operation. The measuring response is disturbed by the fluctuating concentrations of the interfering substances that are simultaneously present in body fluids. However, the disturbance can essentially be controlled, as is shown in the case of amino acids. Their marked influence on glucose oxidation is suppressed at a membrane-covered sensor electrode by the use of a potential step method.

Artificial Organs

[In vitro and in vivo investigations with different nitrofurantoin formulations (author's transl)].

In vitro dissolution tests and biopharmaceutical investigations on healthy test persons were carried out with 4 different galenic tablet formulations. Three of these formulations were prepared by a special galenic process, the fourth corresponded to the usual tablet formulations. It was shown that the dissolution behaviour of the formulations in vitro, in accordance with the specifications of the American Pharmacopoeia (USP XIX), does not correlate with the parameters found in vivo. However, if the formulations in vitro are checked with the Sartorius model according to Stricker, correlations can be found with the in vivo behaviour of nitrofurantoin. A linear relationship was achieved by the special galenic formulation directly regulating the pharmacokinetic behaviour of nitrofurantoin. The known biological scatter of nitrofurantoin was strongly reduced by this process. The amount of the substance still present and circulating in the body creating the side effects could be reduced to a minimum. All facts considered, the therapeutic safety is also ensured.

Adult

Computer assistance in multiparameter flow microphotometry of mammalian cells.

Flow system technology enables the biological and medical experimenter to investigate the distribution spectra of various cellular characteristics separately or in parameter combination on the basis of ultrarapid single cell measurements. A typical rate of recognition is about 1000 to 5000 cells per second and the precision of measurements and their statistical relevance has been previously unobtainable. According to the approach of the multiparameter analysis and high data rate, computer assistance in flow system technology is given primary consideration. In this study three different kinds of software controlled modes in data acquisition are demonstrated: normal acquisition and linear accumulation of single parameters, spectra accumulation of two correlated parameters of each single cell and documentation as linear, two- or three-dimensional distribution pattern, and linear accumulation of two correlated parameters simultaneously with their actual signal-to-signal ratio. A first attempt to analyze distribution spectra was the application of the entropy of the structure routinely used in cybernetics. This function seems to be a measure for determining the degree of synchrony in an appropriate pretreated cell population. A special mathematical strategy has been applied to the linear spectra cellular DNA content, whose advantage is the quantitative extraction of the fractions concerning the various phases of the life cycle cells. The validity of this special curve fitting procedure has been proven on various experimental cell populations.

Animals