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Biomedical subjects

G Schmid

Publications and source records attributed to G Schmid.

At least 19 recordsLinked to original sources
PubMed2006

Capacitance fluctuations causing channel noise reduction in stochastic Hodgkin-Huxley systems.

Voltage-dependent ion channels determine the electric properties of axonal cell membranes. They not only allow the passage of ions through the cell membrane, but also contribute to an additional charging of the cell membrane resulting in the so-called capacitance loading. The switching of the channel gates between an open and a closed configuration is intrinsically related to the movement of gating charge within the cell membrane. At the beginning of an action potential, the transient gating current is opposite to the direction of the current of sodium ions through the membrane. Therefore, the excitability is expected to become reduced due to the influence of a gating current. Our stochastic Hodgkin-Huxley-like modeling takes into account both the channel noise-i.e. the fluctuations of the number of open ion channels-and the capacitance fluctuations that result from the dynamics of the gating charge. We investigate the spiking dynamics of membrane patches of a variable size and analyze the statistics of the spontaneous spiking. As a main result, we find that the gating currents yield a drastic reduction of the spontaneous spiking rate for sufficiently large ion channel clusters. Consequently, this demonstrates a prominent mechanism for channel noise reduction.

Action Potentials↗
PubMed2006

Schooling mediates brain reserve in Alzheimer's disease: findings of fluoro-deoxy-glucose-positron emission tomography.

BACKGROUND: Functional imaging studies report that higher education is associated with more severe pathology in patients with Alzheimer's disease, controlling for disease severity. Therefore, schooling seems to provide brain reserve against neurodegeneration. OBJECTIVE: To provide further evidence for brain reserve in a large sample, using a sensitive technique for the indirect assessment of brain abnormality (18F-fluoro-deoxy-glucose-positron emission tomography (FDG-PET)), a comprehensive measure of global cognitive impairment to control for disease severity (total score of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery) and an approach unbiased by predefined regions of interest for the statistical analysis (statistical parametric mapping (SPM)). METHODS: 93 patients with mild Alzheimer's disease and 16 healthy controls underwent 18F-FDG-PET imaging of the brain. A linear regression analysis with education as independent and glucose utilisation as dependent variables, adjusted for global cognitive status and demographic variables, was conducted in SPM2. RESULTS: The regression analysis showed a marked inverse association between years of schooling and glucose metabolism in the posterior temporo-occipital association cortex and the precuneus in the left hemisphere. CONCLUSIONS: In line with previous reports, the findings suggest that education is associated with brain reserve and that people with higher education can cope with brain damage for a longer time.

Aged↗
PubMed2006

Fractional Fokker-Planck dynamics: Numerical algorithm and simulations.

Anomalous transport in a tilted periodic potential is investigated numerically within the framework of the fractional Fokker-Planck dynamics via the underlying continuous-time random walk. An efficient numerical algorithm is developed which is applicable for an arbitrary potential. This algorithm is then applied to investigate the fractional current and the corresponding nonlinear mobility in different washboard potentials. Normal and fractional diffusion are compared through their time evolution of the probability density in state space. Moreover, we discuss the stationary probability density of the fractional current values.

Journal Article↗
PubMed2006

Entropic transport: kinetics, scaling, and control mechanisms.

We show that transport in the presence of entropic barriers exhibits peculiar characteristics which makes it distinctly different from that occurring through energy barriers. The constrained dynamics yields a scaling regime for the particle current and the diffusion coefficient in terms of the ratio between the work done to the particles and available thermal energy. This interesting property, genuine to the entropic nature of the barriers, can be utilized to effectively control transport through quasi-one-dimensional structures in which irregularities or tortuosity of the boundaries cause entropic effects. The accuracy of the kinetic description has been corroborated by simulations. Applications to different dynamic situations involving entropic barriers are outlined.

Journal Article↗
PubMed2006

Current and universal scaling in anomalous transport.

Anomalous transport in tilted periodic potentials is investigated within the framework of the fractional Fokker-Planck dynamics and the underlying continuous time random walk. The analytical solution for the stationary, anomalous current is obtained in closed form. We derive a universal scaling law for anomalous diffusion occurring in tilted periodic potentials. This scaling relation is corroborated with precise numerical studies covering wide parameter regimes and different shapes for the periodic potential, being either symmetric or ratchetlike.

Journal Article↗
PubMed2006

[Distribution of MRI signal alterations of the cartilage endplate in pre-operated patients with special focus on recurrent lumbar disc herniation].

PURPOSE: To study the location of (Modic) MR signal alterations (SA) of the cartilage endplate (CEP) in pre- and non-operated segments L3-S1 with special focus on the presence of recurrent lumbar disc herniation (RLDH). MATERIALS AND METHODS: In a retrospective study the MR images of vertebrae L3-S1 of 65 consecutive patients with a history of microdiscectomy were evaluated. Of the 190 segments studied, 67 were pre-operated. These were divided into a group with recurrent lumbar disc herniation (RLDH) (n = 19) and a group without evidence of RLDH (n = 48). Non-operated segments (n = 123) were also considered as a separate group. In these three groups the prevalence of different Modic types was determined using the sag. T1- and T2-weighted images, and, in particular, the distribution of SA at the upper and lower CEP was examined by evaluating the sag. T2-weighted images. In order to achieve this, each CEP was divided into nine regions. RESULTS: Pre-operated segments showed significantly more frequent (p < 0.001) and more expansive (p < 0.001) SA than non-operated segments. Non-operated segments showed SA less frequently in the central region of both upper and lower CEP (p = 0.056 and p = 0.015, respectively). In operated segments without RLDH, the upper CEP had significantly more SA on the operation side than in the mid-sagittal and contra-lateral regions (p = 0.016, p = 0.037) and significantly more on the operation side of the lower CEP than in the contra-lateral region (p = 0.027). Operated segments with RLDH did not show an emphasis of SA on the operation side. In this group SA occurred significantly more often in the central and ventral mid-sagittal regions of the upper CEP than in the pre-operated segments without RLDH. CONCLUSION: 1. There are different patterns of signal alterations in the three groups. 2. The importance of the central region of the CEP for the integrity of the disc is strongly supported by the low incidence of signal alterations in this location in non-operated segments. 3. There are clear indications for the influence of the operation on the development and distribution of signal alterations. 4. In pre-operated segments signal alterations occurring in the central and ventral mid-sagittal regions of the upper CEP can be indicative of the development of RLDH.

Adult↗
PubMed2006

[(Modic) signal alterations of vertebral endplates and their correlation to a minimally invasive treatment of lumbar disc herniation using epidural injections].

PURPOSE: To study the influence of (Modic) signal alterations (SA) of the cartilage endplate (CEP) of vertebrae L3-S1 on the outcome of an in-patient minimally invasive treatment (MIT) using epidural injections on patients with lumbar disc herniation (LDH). MATERIALS AND METHODS: The MR images of 59 consecutive patients with LDH within segments L3/L4 - L5/S1 undergoing in-patient minimally invasive treatment with epidural injections were evaluated in a clinical study. The (Modic) signal alterations of the CEP were recorded using T1- and T2-weighted sagittal images. On the basis of the T2-weighted sagittal images, the extension and distribution of the SA were measured by dividing each CEP into 9 areas. The outcome of the MIT was recorded using the Oswestry Disability Index (ODI) before and after therapy and in a 3-month follow-up. Within a subgroup of patients (n = 35), the distribution and extension of the signal alterations were correlated with the development of the ODI. RESULTS: Segments with LDH showed significantly more (p < 0.001) SA of the CEP than segments without LDH. Although the extension of the SA was not dependent on sex, it did increase significantly with age (p = 0.017). The outcome after MIT did not depend on the sex and age of the patients nor on the type of LDH. The SA extension tended to have a negative correlation with the outcome after MIT after 3 months (p = 0.071). A significant negative correlation could be established between the SA extension in the central section of the upper endplate and the outcome after 3 months (p = 0.019). CONCLUSION: 1. Lumbar disc herniation is clearly associated with the prevalence of (Modic) signal alterations. 2. Extensive signal alterations tend to correlate with a negative outcome of an MIT using epidural injections. 3. Such SA in the central portion of the upper CEP correlate significantly with a negative treatment result. 4. The central portion of the upper CEP being extensively affected by (Modic) SA is a negative predictor for the success of a minimally invasive pain therapy.

Adolescent↗
PubMed2005

Alloy formation of supported gold nanoparticles at their transition from clusters to solids: does size matter?

Gold nanoclusters of a size approaching the molecular limit (<3 nm) were prepared on Si substrates in order to study alloy formation on the nanometer scale. For this purpose, indium atoms are deposited on top of the gold particles at room temperature and the formation of AuIn(2) is studied by x-ray photoelectron spectroscopy in situ. It is observed that the alloy formation takes place independent of whether the particles electronically are in an insulating molecular or in a metallic state. Most important, however, closed packed full-shell clusters containing 55 Au atoms are found to exhibit an outstanding stability against alloying despite a large negative heat of formation of the bulk Au-In system. Thus, Au(55) clusters may play a significant role in the design of nanoscaled devices where chemical inertness is of crucial importance.

Journal Article↗
PubMed2005

Role of p53 tumor suppressor in ageing: regulation of transient cell cycle arrest and terminal senescence.

In this study we investigated the function of p53 as a regulator of cell cycle progression in cycling and senescent cells. Using the conditional temperature-sensitive (ts) mutant we could prevent the detrimental effect of constitutive expression of high levels of wt p53 protein. High levels of wt p53 inhibited cell proliferation by blocking the cells to progress from G1 to S phase of the cell cycle. Flow cytometric analysis revelaed a maintenance of G1 cell population for a longer time depending on the prolonged expression of wt p53 protein. The p53 mediated inhibition of cell proliferation and of the cycle was reversible. However, a spontaneous increase of wt p53 occurring in ageing normal human MRC-5 fibroblasts was associated with irreversible reduction of proliferative potential. The accumulation of G1 cells was detected by flow cytometry. By the measurement of DNA content it is not possible to discriminate between cells arrested in G1 and G0 phase, therefore, the expression of G1 markers was determined. Analysis of the expression of distinct cell cycle regulators revealed that quiescent MRC-5 cells were in G0 phase. Our results indicate that cell cycle arrest occurring in senescent cells is associated with the G0 transition.

Animals↗
PubMed2005

Physiological ageing: role of p53 and PARP-1 tumor suppressors in the regulation of terminal senescence.

Ageing of organisms is among the most complex processes currently known. Understanding the molecular mechanism of physiological ageing is one of the most essential issues in biology and medicine because it is not possible to predict when and how a certain individual will start ageing. In the past centuries human life expectancies increased. Extension of life span is associated with increased susceptibility to a number of chronic diseases. Insight into the cellular and molecular targets of the ageing process would offer the opportunity to prevent at least some of the destructive processes. In the present paper the involvement of two tumor suppressor proteins: wild-type p53 and poly(ADP-ribose)polymerase-1 (PARP-1) in the regulation of cellular senescence and physiological ageing was reviewed. Moreover, the interaction and cross-talk between p53 and PARP1-1 was discussed.

Aging↗
PubMed2004

Gold nanoparticles: assembly and electrical properties in 1-3 dimensions.

Ligand stabilized gold nanoparticles have attracted much attention in the search for new chemically designed compounds for a future information technology, based on single-electron devices. This article gives an overview about the strategies used to synthesize and to assemble uniform gold nanoparticles in different dimensions as well as about the present status of the electrical properties of these. Examples are given for three-dimensional organisations, for the formation of self-assembled monolayers as well as for one-dimensional assemblies.

Journal Article↗
PubMed2004

Therapeutic strategies in Friedreich's ataxia.

Friedreich's ataxia is caused by a pronounced lack of frataxin, a mitochondrial protein of not fully understood function. Lack of frataxin homologues in yeast and mice leads to increased sensitivity to oxidative stress, depletion of proteins with iron-sulfur clusters like respiratory chain complexes I-III and aconitase, and to iron accumulation in mitochondria. Similar effects have been demonstrated in human disease with increased markers of oxidative DNA damage in urine and impaired oxidative phosphorylation in in vivo exercise studies using 31 Phosphorus magnetic resonance spectroscopy (31P-MRS). Therapeutical trials mainly focus on antioxidative treatment with coenzyme Q10 or its short-chain variant idebenone. Promising effects on cardiac hypertrophy in uncontrolled preliminary studies contrast with minor effects in controlled trials and no effect of antioxidants on neurological deficits has been established. Preliminary encouraging 31P-MRS data exist for the treatment with L-carnitine but not with creatine. However, all these interventions may take effect too late in the pathogenic process. Alternative strategies aiming at an enhancement of frataxin by stem cell transplantation, gene transfer or frataxin supplementation are desirable. Additionally, more efficient biomarkers are needed to monitor treatment effects.

Animals↗
PubMed2004

Impact of apomorphine on BOLD signal during movement in normals.

Our group investigated modulatory effects of apomorphine on cerebral activation patterns during finger tapping movements in six healthy right-handed volunteers using an established fMRI protocol. Apomorphine application disclosed a reduction of cerebral activation to the contralateral precentral and postcentral gyrus and ipsilateral cerebellum, with a prominent net reduction of BOLD signal in cerebellar areas. These findings contradict those of similar studies performed on dopaminergic function and Parkinson's disease (PD), which predominantly found augmentation of cerebral activation patterns in normal volunteers and PD patients after dopaminergic stimulation. One conceivable explanation for our singular results would be preferred binding of apomorphine to presynaptic dopaminergic receptors, leading to inhibition of endogenous dopamine release and resultant diminished dopaminergic stimulation, reflected in diminished cerebral activation patterns. These findings warrant future consideration and further investigation of possible central inhibitory effects of dopaminergic therapy in functional imaging studies of the dopaminergic system in general and PD in particular.

Adult↗
PubMed2004

[Gallstone ileus].

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Cholecystectomy↗
PubMed2004

[Direct MR-arthrography of the shoulder with maximum capsular distension for surgical planning].

PURPOSE: To evaluate the effectiveness of direct MR arthrography of the glenohumeral joint with maximum distension of the joint capsule in patients with glenohumeral instability for preoperative diagnosis and for determining the method of surgical intervention. MATERIALS AND METHODS: MR arthrography of the shoulder joint was performed on a 1.5 T system in 38 patients. All patients suffered from anterior or bidirectional instability. Using a fluoroscopically guided posterior approach, a 1 % dilution of dimeglumine gadopentetate (5 mmol Gd-DTPA/l) was injected until full capsular stretching was achieved. MR imaging protocol included fat-saturated transversal, oblique-coronal and oblique-sagittal T1-weighted spin-echo, T1-weighted 3-D and transversal T2-weighted Flash-2D. RESULTS: MR imaging revealed significant capsule distention in 22 patients and ventral capsule defects in 9 patients. Labral lesions were depicted in 25 patients, bicipital tendon lesions in 4 patients and partial ruptures of the rotator cuff in 3 patients. 15 of the 38 patients underwent surgery. Areas of pathologic laxity of the glenohumeral capsule were correctly described in all cases. In 12 of 15 patients, the best method of intervention could be determined prospectively. In 3 of 15 patients, the necessary operation was overestimated. Regarding labral ruptures, MRI had a sensitivity of 88 %, a specificity of 86 %, and a diagnostic accuracy of 87 %. CONCLUSION: Direct glenohumeral MR arthrography allows accurate preoperative evaluation of labral and tendinous structures. Judging the capsular laxity allows the determination of the optimal method of surgical intervention. The maximum extent of a stabilizing operation can be predicted preoperatively.

Adult↗
PubMed2004

Effect of channel block on the spiking activity of excitable membranes in a stochastic Hodgkin-Huxley model.

The influence of intrinsic channel noise on the spontaneous spiking activity of poisoned excitable membrane patches is studied by use of a stochastic generalization of the Hodgkin-Huxley model. Internal noise stemming from the stochastic dynamics of individual ion channels is known to affect the collective properties of the whole ion channel cluster. For example, there exists an optimal size of the membrane patch for which the internal noise alone causes a regular spontaneous generation of action potentials. In addition to varying the size of ion channel clusters, living organisms may adapt the densities of ion channels in order to optimally regulate the spontaneous spiking activity. The influence of a channel block on the excitability of a membrane patch of a certain size is twofold: first, a variation of ion channel densities primarily yields a change of the conductance level; second, a down-regulation of working ion channels always increases the channel noise. While the former effect dominates in the case of sodium channel block resulting in a reduced spiking activity, the latter enhances the generation of spontaneous action potentials in the case of a tailored potassium channel blocking. Moreover, by blocking some portion of either potassium or sodium ion channels, it is possible to either increase or decrease the regularity of the spike train.

Action Potentials↗
PubMed2002

Oxidation-resistant gold-55 clusters.

Gold nanoparticles ranging in diameter from 1 to 8 nanometers were prepared on top of silicon wafers in order to study the size dependence of their oxidation behavior when exposed to atomic oxygen. X-ray photoelectron spectroscopy showed a maximum oxidation resistance for "magic-number" clusters containing 55 gold atoms. This inertness is not related to electron confinement leading to a size-induced metal-to-insulator transition, but rather seems to be linked to the closed-shell structure of such magic clusters. The result additionally suggests that gold-55 clusters may act as especially effective oxidation catalysts, such as for oxidizing carbon monoxide.

Journal Article↗