Biomedical subjects

G Pfister

Publications and source records attributed to G Pfister.

At least 19 recordsLinked to original sources

PubMed2006

The impact of boreal forest fire on climate warming.

We report measurements and analysis of a boreal forest fire, integrating the effects of greenhouse gases, aerosols, black carbon deposition on snow and sea ice, and postfire changes in surface albedo. The net effect of all agents was to increase radiative forcing during the first year (34 +/- 31 Watts per square meter of burned area), but to decrease radiative forcing when averaged over an 80-year fire cycle (-2.3 +/- 2.2 Watts per square meter) because multidecadal increases in surface albedo had a larger impact than fire-emitted greenhouse gases. This result implies that future increases in boreal fire may not accelerate climate warming.

Ecosystem↗

PubMed2006

[Results from biomedical aging research. Trends and current examples from immunology].

The public health of our society is challenged by a continuous increase in life expectancy. Hence, biomedical aging research is enjoying a steadily increasing popularity but also enlightens our understanding of age-related diseases by a number of striking results from basic research. One of the most striking changes that occurs during normal human aging is an overall diminution of immune functions, a phenomenon often termed immunosenescence. Starting from some highly exciting examples from basic immunological research, this article sheds light on which impact normal human aging has on several immune defence mechanisms. In addition, clinical consequences in view of Alzheimer's disease, immunogenicity of vaccines and autoimmune diseases are discussed.

Adult↗

PubMed2004

Chaos from Hopf bifurcation in a fluid flow experiment.

Results of an experimental study of a Hopf bifurcation with broken translation symmetry that organizes chaotic homoclinic dynamics from a T2 torus in a fluid flow as a direct consequence of physical boundaries are presented. It is shown that the central features of the theory of Hopf bifurcation in O(2)-symmetric systems where the translation symmetry is broken are robust and are appropriate to describe the appearance of modulated waves, homoclinic bifurcation, Takens-Bogdanov point, and chaotic dynamics in a fluid flow experiment.

Journal Article↗

PubMed2003

Standing waves in flow between finite counterrotating cylinders.

Experimental evidence for standing waves resulting from a supercritical Hopf bifurcation that appears as the first pattern-forming instability in counterrotating Taylor-Couette flow is presented. Depending on the aspect ratio two different types of standing waves, denoted as SW0 and SW(pi), could be observed. Both modes have an azimuthal wave number m=1 but differ in symmetry. While for SW(pi), a spatiotemporal glide-reflection symmetry could be found, SW0 is purely spatial reflection symmetric. The transition between the two modes is found to be organized in a cusp bifurcation unfolded by variations of the aspect ratio. The "classical" spiral vortex flow appears in this control parameter regime only as a result of a secondary steady bifurcation from SW0. This transition is found to be either subcritical or supercritical. The experimentally observed bifurcation structure has been predicted by theory of Hopf bifurcation to spiral vortex flow in finite counterrotating Taylor-Couette systems.

Journal Article↗

PubMed2003

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: evaluation of active electrode contacts.

BACKGROUND: The subthalamic nucleus is the preferred target for deep brain stimulation in patients with advanced Parkinson's disease. The site of permanent stimulation is the subject of ongoing debate, as stimulation both within and adjacent to the subthalamic nucleus may be effective. OBJECTIVE: To assess the position of active electrode contacts in relation to the dorsal margin of the subthalamic nucleus as determined by intraoperative microrecordings and magnetic resonance imaging (MRI). METHODS: In 25 patients suffering from severe levodopa sensitive parkinsonism, deep brain stimulating electrodes (n = 49) were implanted following mapping of the subthalamic nucleus by microrecording and microstimulation along five parallel tracks. Postoperative stereotactic radiography and fusion of pre- and postoperative MRI studies were used to determine the stereotactic position relative to the midcommissural point of the most effective electrode contacts selected for permanent stimulation (n = 49). Intraoperative microrecordings were analysed retrospectively to define the dorsal margin of the subthalamic nucleus. In cases where the dorsal margin could be defined in at least three microrecording tracks (n = 37) it was correlated with the position of the active contact using an algorithm developed for direct three dimensional comparisons. RESULTS: Stimulation of the subthalamic nucleus resulted in marked improvement in levodopa sensitive parkinsonian symptoms and levodopa induced dyskinesias, with significant improvement in UPDRS III scores. In several instances, projection of the electrode artefacts onto the T2 weighted MRI visualised subthalamic nucleus of individual patients suggested that the electrodes had passed through the subthalamic nucleus. When the actual position of active electrode contacts (n = 35) was correlated with the dorsal margin of the subthalamic nucleus as defined neurophysiologically, most contacts were located either in proximity (+/- 1.0 mm) to the dorsal border of the subthalamic nucleus (32.4%) or further dorsal within the subthalamic region (37.8%). The other active contacts (29.7%) were detected within the dorsal (sensorimotor) subthalamic nucleus. The average position of all active contacts (n = 49) was 12.8 mm (+/- 1.0) lateral, 1.9 mm (+/- 1.4) posterior, and 1.6 mm (+/- 2.1) ventral to the midcommissural point. CONCLUSIONS: Subthalamic nucleus stimulation appears to be most effective in the border area between the upper subthalamic nucleus (sensorimotor part) and the subthalamic area containing the zona incerta, fields of Forel, and subthalamic nucleus projections.

Aged↗

PubMed2003

Expression levels of heat shock protein 60 in human endothelial cells in vitro are unaffected by exposure to 50 Hz magnetic fields.

Magnetic fields (MFs) from domestic power sources have been implicated as being a potential risk to human health. A number of epidemiological studies have found a significant link between exposure to MFs and increased rates of cancers. There have also been a number of in vivo and in vitro studies reporting effects of MFs in animal disease models and on the expression or activity of a range of proteins. In the past decade, our group proposed that atherosclerosis may have an autoimmune component, with heat shock protein 60 (Hsp60) expressed in endothelial cells as the dominant autoantigen. A number of stressors have been shown to induce the expression of Hsp60, including the classical risk factors for atherosclerosis. We were interested to see if the exposure of endothelial cells to an MF elicited increased expression of Hsp60, as has been reported previously for Hsp70. The present work describes the exposure of endothelial cells to domestic power supply (50 Hz) MFs at an intensity of 700 microT. The results from our system indicate that cultured endothelial cells exposed to a high intensity of MF either alone or in combination with classical heat stress show no effects on the expression of Hsp60 at either the messenger ribonucleic acid or the protein level. As such, there is no evidence that exposure to extremely low-frequency MF would be expected to increase the expression of Hsp60 and therefore the initiation or progression of atherosclerosis.

Chaperonin 60↗

PubMed2002

Influence of nonylphenol on the microbial community of lake sediments in microcosms.

In this study the impact of nonylphenol, an estrogenic degradation product of alkylphenol polyethoxylates, on the microbial community structure in contaminated sediments of aquatic microcosms using in situ hybridization with fluorescently labeled oligonucleotides probes was investigated. A positive correlation between nonylphenol concentration and cell numbers of bacteria and microfungi as well as an increase in the numbers of active bacteria was found. However, the ratio between total microorganisms and active bacteria remained unchanged. A large fraction of the cells could be identified using group specific oligonucleotide probes. A slight change in the composition of the microbial community structure was observed, with Gram-positive bacteria with high DNA G + C-content becoming more abundant at higher concentrations of nonylphenol.

Bacteria↗

PubMed2001

Gluing bifurcations in a dynamically complicated extended flow.

We report the results of the first experimental study of imperfect gluing bifurcations in an extended fluid flow. It is shown that the central features of the theory are robust and are appropriate to describe the dynamics of a nontrivial physical system. The results include the first experimental evidence for a route to chaos which is an essential part of the theory of imperfect gluing bifurcations.

Journal Article↗

PubMed2001

Delay estimation for cortico-peripheral relations.

In neurophysiology, time delays between concurrently measured time series are usually estimated from the slope of a straight line fitted to the phase spectrum. We point out that this estimate is valid only in the case in which, one signal is a mere time-delayed copy of the other one. We present a procedure for delay estimation that applies to a much wider class of systems with nontrivial phase spectrum like for example lowpass filters. The procedure is based on the Hilbert transform relation between the phase of a linear system and its log gain. The Hilbert transform relation is nonlocal in frequency space, a fact that limits its applicability to experimental data. We explore these limits, and demonstrate that the method is applicable to neurophysiological time series. We present the successful application of the Hilbert transform behavior method to concurrently recorded epicortical brain activity and peripheral tremor. We point out and explain physiologically unreasonable delay estimates given by the traditional method. Finally, we discuss the assumptions underlying the applicability of the Hilbert transform method in the neuroscience context.

Cerebral Cortex↗

PubMed2001

Control of chaotic Taylor-Couette flow with time-delayed feedback.

We demonstrate that unstable periodic orbits embedded in the experimental chaotic attractor determined by the Taylor-Couette flow can be stabilized with a time-delay autosynchronization algorithm. The optimal parameters of the feedback and their dependence on the control parameter are shown as experimental results.

Journal Article↗

PubMed2001

Metabolic stabilization of p27 in senescent fibroblasts correlates with reduced expression of the F-box protein Skp2.

When mortal human cells reach their finite lifespan, they enter an irreversible G1 growth arrest status referred to as senescence. Growth suppression of senescent cells can be explained by the accumulation of several growth-suppressive proteins, acting on mitogenic signal transduction and cell cycle regulation, respectively. We show here that the cdk inhibitor p27(KIP1), which is involved in several forms of G1 checkpoint control, accumulates in senescent cells. Whereas, the rate of p27 synthesis is reduced, accumulation of p27 is accompanied by an increase of the metabolic stability in senescent cells. p27 is a substrate for ubiquitin-mediated proteolysis, and its stabilization in senescent cells correlates with a deregulation of the p27-specific E3 ubiquitin ligase referred to as the SCF complex. Whereas, the Skp1 component of the SCF complex is overexpressed in senescent fibroblasts, the abundance of the F-box protein Skp2 is strongly reduced. In contrast to our findings with p27, the synthesis of the cell cycle regulators p21 and cyclin D1 is increased in senescent cells; however, both proteins are also highly unstable in these cells.

Cell Cycle Proteins↗

PubMed2001

Exacerbated vein graft arteriosclerosis in protein kinase Cdelta-null mice.

Smooth muscle cell (SMC) accumulation is a key event in the development of atherosclerosis, including vein bypass graft arteriosclerosis. Because members of the protein kinase C (PKC) family signal cells to undergo proliferation, differentiation, or apoptosis, we generated PKCdelta knockout mice and performed vein bypass grafts on these animals. PKCdelta(-/-) mice developed normally and were fertile. Vein segments from PKCdelta(-/-) mice isografted to carotid arteries of recipient mice of either genotype led to a more severe arteriosclerosis than was seen with PKCdelta(+/+) vein grafts. Arteriosclerotic lesions in PKCdelta(-/-) mice showed a significantly higher number of SMCs than were found in wild-type animals; this was correlated with decreased SMC death in lesions of PKCdelta(-/-) mice. SMCs derived from PKCdelta(-/-) aortae were resistant to cell death induced by any of several stimuli, but they were similar to wild-type SMCs with respect to mitogen-stimulated cell proliferation in vitro. Furthermore, pro-apoptotic treatments led to diminished caspase-3 activation, poly(ADP-ribose) polymerase cleavage, and cytochrome c release in PKCdelta(-/-) relative to wild-type SMCs, suggesting that their apoptotic resistance involves the loss of free radical generation and mitochondrial dysfunction in response to stress stimuli. Our data indicate that PKCdelta maintains SMC homeostasis and that its function in the vessel wall per se is crucial in the development of vein graft arteriosclerosis.

Animals↗

PubMed2000

High levels of zinc ions induce loss of mitochondrial potential and degradation of antiapoptotic Bcl-2 protein in in vitro cultivated human prostate epithelial cells.

Prostate epithelial cells contain the highest levels of zinc among all organs and tissues in the human body. Zinc is accumulated primarily in the mitochondria, where it is responsible for inhibition of mitochondrial aconitase activity, thereby increasing citrate production. The present study was designed to clarify the role of zinc for human prostate epithelial cell growth and apoptosis. Apoptosis of in vitro cultivated human prostate epithelial cells exposed to ZnCl(2) was analyzed by determination of phospholipid membrane asymmetry, nuclear fragmentation, DNA strand breaks, changes of mitochondrial potential and cellular pro/antiapoptotic proteins. Zinc induced apoptosis without involvement of p53 by decreasing mitochondrial transmembrane potential (DeltaPsi(m)) and Bcl-2 protein levels in proliferating epithelial cells. Thus, the high local concentrations of zinc ions in the prostatic lumen seem to be necessary to regulate proliferative activities and to enforce epithelial differentiation processes.

Actins↗

PubMed2000

An unusual member of the human growth hormone/placental lactogen (GH/PL) family, the testicular alternative splicing variant hPL-A2: recombinant expression revealed a membrane-associated growth factor molecule.

The human growth hormone/placental lactogen (GH/PL) gene cluster consists of five highly-related genes (GH-N, GH-V, PL-L, PL-A, PL-B). This evolutionarily young gene cluster codes for an array of mRNAs and proteins, such as the major 22 k forms (hGH-N/V, identical PL-A and B), 20 k and 17.5 k hGH-N and the recently described 25 k hGH-Delta4, a presumably chimeric molecule. In addition, two longer alternatively spliced, (intron D retaining) mRNAs isoforms, termed PL-A2 and GH-V2, have been described in placenta and testis. To elucidate the role of hPL-A2 in male reproduction and pregnancy, testicular PL-A2 cDNA was cloned in a complementary overlapping 2-way RT-PCR approach to analyze translation, localization and structure/function of this unusual member of the GH/PL growth factor family. Analysis of insect mRNA revealed that intron D-retaining PL-A2 cDNA was expressed without splicing in the baculovirus expression system. Thus, PL-A2 mRNA does not represent a nuclear intermediate splicing product simply co-isolated with the mature RNA, but is a stable mRNA isoform generated by placental/testis-specific splicing factors. Recombinant protein was present in whole cell extracts, and no secreted protein was detected in the supernatant. Immunologically, the N-terminus of the 230 amino acid protein is similar to 22 k hPL-A/B, as determined by hPL-specific monoclonal antibodies. In contrast, the C-terminus shares a hydrophobic region presumably responsible for membrane insertion. By the use of confocal microscopy recombinant hPL-A2 was localized in the cell membrane. Thus, hPL-A2 might exert its function by modulating GH/PL actions or act as an independent growth-regulatory molecule itself and its functions in male reproduction and embryonic development remain to be investigated.

Aged↗

PubMed2000

Multiple oscillators are causing parkinsonian and essential tremor.

The tremors of Parkinson's disease (PD) and essential tremor (ET) are traditionally considered to depend on a central oscillator producing rhythmic activation of the motoneurones of all extremities. To test this hypothesis, we have compared electromyographic tremor activity in different muscles of the affected limbs using cross spectral analysis, including coherence and phase. Surface electromyographic recordings from both arms, legs, and the neck were analyzed in 22 patients with PD and 28 patients with ET. Volume conduction between neighboring muscles producing artificial "coherence" has been found to be an important methodologic problem. We have developed a mathematical test to exclude data that could distort the results. According to this test, 10% or 25% of muscle combinations from the same limb had to be excluded from further analysis in PD or ET, respectively. In both, patients with PD and ET, we found a considerable number of muscle combinations oscillating at virtually the same frequency (delta frequency <0.4 Hz) without showing a significant coherence. Thus, the frequency difference between different muscles is not sufficient to measure the correlation between two muscles. Significant coherencies between muscles within the same arm or leg were found in 70% or 90% of patients with PD or ET, respectively, whereas only one patient with PD and not a single patient with ET showed significant coherencies between muscles from different limbs. The phase between coherent muscles of the same arm of patients with PD showed a preference of either a reciprocal alternating pattern for antagonistic muscles in forearm flexor and upper arm extensor as opposed to a co-contraction pattern between the hand flexors and the triceps brachii. In patients with ET such clear differences were lacking. We conclude that multiple oscillators are responsible for the tremor in different extremities of patients with PD and ET. Differences between PD and ET concerning the phase relation within the arm may either be related to the topography within the basal ganglia or to differently involved-spinal pathways.

Arm↗

PubMed1999

Addition of a small curvature reduces power losses across total cavopulmonary connections.

BACKGROUND: In the Fontan circulation the vis a tergo for lung perfusion is limited. The hypothesis of this in vitro study was that energy dissipation at the common cavopulmonary connection can be reduced by the addition of caval curvature. METHODS: Two Perspex models were analyzed, the commonly used crosslike cavopulmonary connection (model 1) and a modified curved configuration (model 2). Pressures and flows across the connections were measured simultaneously at various caval and pulmonary artery flow splits and resistances. Mixing of inferior and superior caval fluid was evaluated. RESULTS: Caval pressure oscillations occurred in model 1 only. Curvature reduced power losses in all settings significantly (alpha = 0.05), most successfully at adult caval flow ratios and at high flow rates. At equal pulmonary resistances pulmonary flow was balanced in both models. The inferior caval fluid is preferably directed to the right lung in model 2 predominantly for caval flow conditions in younger patients. CONCLUSIONS: Our data show that the modified curved cavopulmonary connection is hydrodynamically advantageous but might impair caval fluid mixing in younger children.

Age Factors↗

PubMed1999

An in-vitro evaluation of aortic arch vessel perfusion characteristics comparing single versus multiple stream aortic cannulae.

OBJECTIVE: During extracorporeal circulation design and orientation of aortic cannulae tips mainly determine flow pattern in the aortic arch and arch vessels which is the objective of this in vitro study, comparing single versus multiple stream cannulae. METHODS: In an aortic arch glass model, jet streams of 21-24 French aortic cannulae which were inserted in the ascending aorta were directed alternatively at the different arch vessels. Flows and pressures in the arch vessels were measured at pump flows of 3-6 l/min. RESULTS: With optimal orientation of the jet stream in the aortic arch, no preferential flow in the arch vessels was seen. In the single jet stream aortic cannulae group a significant parallel increase in flow and pressure in the jet streamed arch vessels compared to the non-jet streamed arch vessels occurred (P < 0.05). With the jet stream directed on vessel 2 (left carotid vessel) there was a significant pressure and flow difference comparing the two non-jet streamed vessels with each other (P < 0.03). In the single stream 24 French cannulae the highest vessel pressure of 168 mmHg and an increase in flow of 186 ml/min was measured in the jet streamed left carotid artery at 6 l/min pump flow. The multiple stream cannulae provoked the highest vessel pressure of 106 mmHg in the corresponding jet streamed vessel and an increase in flow of 20 ml/min. CONCLUSION: Tip design of aortic cannulae and the orientation of its jet stream are potential sources of remarkable imbalance of arch vessel perfusion especially with single jet stream cannulae. These effects are more pronounced with single jet stream cannulae. These results may have important clinical implications regarding perfusion of arch vessels during extracorporeal circulation.

Aorta, Thoracic↗

PubMed1998

Superior hydrodynamics of a modified cavopulmonary connection for the Norwood operation.

BACKGROUND: In the Fontan circulation, energy consumption at the cavopulmonary connection is crucial. Our hypothesis was that a modification of the standard Norwood variant of cavopulmonary connection with an extended anastomosis would improve hydrodynamics. METHODS: The in vitro hydrodynamics of two different Perspex glass models resembling the Norwood variant of cavopulmonary connection (model I) and the modification (model II) were analyzed in a mock circulation at nonpulsatile flows of 2 to 5 L/min to simulate rest and exercise. The pulmonary flow split was varied to imitate varying lung resistances. Inferior-to-superior caval flow ratio and size of models were increased to simulate growth. RESULTS: The pulmonary flow was preferentially directed to the left lung in model I and was better balanced in model II. Power losses increased exponentially with total flow in both models and were markedly higher in model I. These differences were attenuated in the larger models. Anastomotic turbulences were larger in model I. Power losses in both models were relatively insensitive to changes in pulmonary flow split. CONCLUSIONS: The proposed modification of the Norwood variant of cavopulmonary connection seems to be hydrodynamically advantageous and warrants further evaluation.

Anastomosis, Surgical↗