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Biomedical subjects

T Wilhelm

Publications and source records attributed to T Wilhelm.

At least 19 recordsLinked to original sources

Boolean networks with biologically relevant rules show ordered behavior.

It was found recently that natural gene regulatory systems are governed by hierarchically canalyzing functions (HCFs), a special subclass of Boolean functions. Here we study the HCF class in detail. We present a new minimal logical expression for all HCFs. Based on this formula, we calculate the cardinality of the HCF class. Moreover, we define HCF subclasses and calculate their cardinality as well. Using the well-known critical connectivity condition 2K(c)p(1-p)=1, we discuss order-chaos transitions of Boolean networks (BNs) regulated by functions of given HCF subclasses. Finally, analysing real gene regulatory rules we show that nearly all of the biologically relevant functions belong to the simplest HCF subclasses. This restriction is important for reverse engineering of transcription regulatory networks and for ensemble approach studies in systems biology. It is shown that Boolean networks with functions belonging to the biologically realized HCF subclasses show ordered behavior.

Algorithms↗

Dynamic simulation of protein complex formation on a genomic scale.

MOTIVATION: One of the central questions in the post-genomic era is the understanding of protein-protein interactions and of protein complex formation. It has been observed that protein complex size distributions of the yeast Saccharomyces cerevisiae decay exponentially. The shape of these size distributions reflects mechanisms of protein complex association and dissociation. RESULTS: We present the most simple dynamic model that is able to reproduce the observed protein complex size distribution for yeast. This protein association-dissociation model (PAD-model) simulates the dynamics of protein complex formation on a genomic scale for about 50 million protein molecules. By ruling out different model variants it is possible to elucidate fundamental features of the protein complex dynamics, e.g. complex association is independent of complex size. In addition, the PAD-model provides information about the complexity of the yeast proteome and it gives an idea of how many complexes could not be identified during the measurements. AVAILABILITY: All programs used for this publication are available on request from the authors. CONTACT: beyer@imb-jena.de SUPPLEMENTARY INFORMATION: Supplementary information about the model and its interpretation can be downloaded from http://www.imb-jena.de/tsb/pad.

Computer Simulation↗

Analysis of structural robustness of metabolic networks.

We study the structural robustness of metabolic networks on the basis of the concept of elementary flux modes. It is shown that the number of elementary modes itself is not an appropriate measure of structural robustness. Instead, we introduce three new robustness measures. These are based on the relative number of elementary modes remaining after the knockout of enzymes. We discuss the relevance of these measures with the help of simple examples, as well as with larger, realistic metabolic networks. Thereby we demonstrate quantitatively that the metabolism of Escherichia coli, which must be able to adapt to varying conditions, is more robust than the metabolism of the human erythrocyte, which lives under much more homeostatic conditions.

Adaptation, Physiological↗

Atraumatic intracutaneous skin closure with self-made fishing line suture compared to commercial thread.

OBJECTIVE: The aim of this study was to prove, whether the intracutaneous skin closure with self made fishing line suture is equivalent to commercial sutures. DESIGN: It was a randomised blinded animal study. SETTING: The study was performed in December 2002 at the Muhimbili University College of Health Sciences in Dar-es-salaam. SUBJECTS: Both German surgeons from Mannheim, and Tanzanian surgeons from Dar es salaam operated on nine one year old Tanzanian domestic sheep. INTERVENTIONS: 108 standardised cutaneous wounds on the backs of the animals were closed by intracutaneous sutures either with self produced fishing line suture or a commercial nylon suture (Ethilon). MAIN OUTCOME MEASURES: The clinical and histological outcomes, as well as the costs of this self-made fishing line suture, with a commercial nylon thread were evaluated and compared. RESULTS: There are no significant differences between the two sutures in histological or clinical findings, or in the reported ease of use by the surgeons. The cost of a self-produced atraumatic thread is US$ 0.12, less than one-twentieth of the cost of the commercial thread. CONCLUSION: Self-made fishing nylon suture has characteristics and properties in sheep skin wounds comparable to commercial nylon suture. The advantage of the commercial thread is the guaranteed quality assurance. It is discussed whether this quality assurance justifies the large price difference, and whether the self-produced thread should be recommended to surgeons in countries where the costs of surgical material often remains an obstacle for life saving operations.

Animals↗

In vivo 31P echo-planar spectroscopic imaging of human calf muscle.

Localized phosphorus-31 NMR spectra of human calf muscle in vivo were obtained by means of echo-planar spectroscopic imaging (EPSI) with a 1.5-T whole-body scanner. The technique permits the measurement of two-dimensional 31P SI data at a minimum acquisition time of 2.4 s (8x8 voxels, TR=300 ms). With 9.4 min measurement time (TR=1100 ms, 64 averages) and 25x25x40 mm spatial resolution in vivo the 31P NMR signal-to-noise ratio (S/N) of the phosphocreatine (PCr) resonance was about 45; the multiplets of nucleoside 5'-triphosphates were resolved. Spectral quality permits quantitative assessment of the PCr signal in a measurement time that is shorter by a factor of 2 or more than the minimum measurement time feasible with chemical-shift imaging. In a functional EPSI study with a time resolution of 20.5 s on the calf muscle of volunteers, spectra showed a 40% decrease of the PCr signal intensity (at rest: S/N congruent with12) upon exertion of the muscle.

Echo-Planar Imaging↗

[Rheologic infusion therapy, neurotransmitter administration and lidocaine injection in tinnitus. A staged therapeutic concept].

BACKGROUND AND OBJECTIVE: Cochlear dysfunction and tinnitus are treated by means of hemorrheological infusions in order to increase the cochlear oxygen supply and restore function of hair cells, neurotransmission and central processing of auditory information. PATIENTS/METHODS: In a retrospective analysis of the charts of 123 patients treated between February 1993 and May 1994, we analyzed effectiveness and safety of a gradual therapeutic regimen, consisting of dextrane/procaine infusions, lidocaine i.v. injection and infusion therapy with the neurotransmitter glutamic acid. RESULTS: Tinnitus decreased in 83.7% of patients with acute tinnitus (AT) and 16.1% of patients with chronic tinnitus (CT) during dextrane/procaine infusion. The majority (89%) experienced their tinnitus relief during the first 5 days. Treatment with glutamic diethylester and glutamic acid resulted in a 26.5% overall improvement. Application of lidocaine intravenously over a period of 10 min diminished tinnitus loudness or frequency in 16.7% (AT) and 38.9% (CT) of cases respectively. The long-term effects of therapy were investigated by a follow-up mailing action: 66.7% of the AT and 15.6% of the CT sufferers stated a clear therapy effect over time. Nonserious side effects were noted in 4% of the treated patients. Therefore safety was excellent. CONCLUSIONS: For acute and chronic tinnitus a gradual therapeutic regimen is recommended: (1) infusions with dextrane and procaine over 5 days; (2) intravenous application of 100 mg lidocaine over 10 min; and if necessary (3) administration of glutamic diethylester and glutamic acid for 3 days. This resulted in overall tinnitus relief in 95.3% of the acute and 26.7% of the chronic tinnitus sufferers.

Adolescent↗

[Brain stem and cerebellar atrophy in neurosyphilis].

A 54-year-old man suffered from serologically proven neurosyphilis with tetraspastic syndrome and bladder dysfunction. He showed a pronounced psychopathy with cognitive decline and attention/concentration deficits. MRI showed slowly progressive cerebellar and brainstem atrophy, which has rarely been described over the past decades. During times of higher incidence and prevalence of neurosyphilis, infratentorial atrophy had been described occasionally, but today this clinical manifestation has been all but forgotten.

Atrophy↗

Stereotactic guided laser-induced interstitial thermotherapy (SLITT) in gliomas with intraoperative morphologic monitoring in an open MR-unit.

Stereotactic guided laser-induced interstitial thermotherapy (SLITT) represents a minimal invasive method to produce necrosis in cerebral tumor tissue by local heating. The dose/response relationship relies on experimental studies and few clinical data performed in high field MR systems. A better understanding of the energy-dose/tissue response in human brain tumors is important to optimize this treatment modality. Twenty-four patients with gliomas were treated with SLITT, with a total of 30 laser procedures performed. Under local anesthesia 600 microns laser-fibers were inserted by stereotactic-guided technique into the center of the tumor. In a low field open MR system (0.2 T) the denaturation of the tumor using a neodymium YAG laser (1064 nm) was monitored by 3D-turbo FLASH T1-weighted sequences. Laser energy was applied in steps of 400 to 1200 Joules. Development of necrosis at a mean total energy dose of 2979 Joules could be monitored in all procedures. Two different thermal lesion architectures were observed. First signal changes were monitored after a mean of 1108 Joules and 1393 Joules, respectively. Mean max. total lesion size was 21.2 mm. The higher the total energy the larger was the thermolesion, but no linear relationship could be seen. Tumor tissue response showed no dependency on tumor grading. Monitoring of stereotactic guided laser-induced thermolesions in the low-power MR OPEN is feasible and safe. Although lesion size basically is energy dependent, it should be applied individually, since the thermal response in brain tumors varies due to different optical properties, even in the same tumor gradings.

Brain Neoplasms↗

[The radiological diagnosis of an intraorbital bullet projectile].

Beside conventional X-ray examination, ultrasound and computer tomographic examination are accepted radiologic techniques to assess the extend of damage of intraorbital injuries. With the exception of a few reports in the literature there is agreement that intraorbital metallic foreign bodies and gun-shot bullets represent a contraindication for magnetic resonance (MR) imaging examination because of artificial imaging side effects and the potential of secondary dislocation of the metallic foreign body due to ferromagnetism. By means of the case reported here it is shown that this general opinion is not universally valid. Depending on the elemental metallic composition of foreign bodies and gun-shot bullets it is demonstrated that MR examination allows high-resolution illustration and in some cases is advantageous compared with other radiologic imaging techniques.

Adult↗

Investigation of ion-bombarded conducting polymer films by scanning electrochemical microscopy (SECM).

Scanning electrochemical microscopy (SECM) was used to investigate the effect of ion bombardment on thin films of the conducting polymers poly[3-ethoxy-thiophene] (PEOT) and poly[ethylenedioxy-thiophene] (PEDT). Bombardment with Ar+-ions converts the topmost 30 nm thick layer to an essentially insulating material. SECM approach curves as well as two dimensional scans prove the existence of regions of different conductivity within the irradiated regions that did not show a significant dependence on ion dosage. PEDT layers patterned by ion bombardment through microscopic masks are investigated as prototypes of miniaturized printed circuit boards that can be formed by galvanic copper deposition onto conducting PEDT. Defects in conducting polymer patterns were analyzed by SECM imaging before any deposition of copper. Appropriate representations of SECM images for the evaluation of this technologically important question are discussed.

Journal Article↗

Model reduction by extended quasi-steady-state approximation.

We extend the quasi-steady-state approximation (QSSA) with respect to the class of differential systems as well as with respect to the order of approximation. We illustrate the first extension by an example which cannot be treated in the frame of the classical approach. As an application of the second extension we prove that the trimolecular autocatalator can be approximated by a fast bimolecular reaction system. Finally we describe a class of singularly perturbed systems for which a higher order QSSA can easily be obtained.

Enzymes↗

[The "heme"-sequence (T2*-weighted gradient echo magnetic resonance tomography). Value in differential spontaneous intracerebral hemorrhage diagnosis].

In four patients presenting with acute non-traumatic intracerebral or intraspinal hemorrhage, T2*-weighted gradient-echo MRI showed numerous residual hemosiderin deposits due to old intracerebral hemorrhages that were missed on initial CT and spin-echo MRI. The demonstration of additional chronic bleedings and their anatomical distribution provided important diagnostic information. In a hypertensive patient, the hemosiderin deposits were most pronounced within deep brain structures suggesting hypertensive cerebral microangiopathy. In a second patient, the cortico-subcortical distribution of the hemorrhages was typical of cerebral amyloid angiopathy. In a third patient, the diffuse distribution including spinal bleeding, the marked calcification, and the characteristic appearance on spin-echo MRI were consistent with multiple cavernomas. In another patient with cerebral and spinal hemorrhage, T2*-weighted gradient-echo MRI revealed new subclinical hemorrhages during follow-up. Based on these findings, we recommend that T2*-weighted gradient-echo MRI of the brain should be performed in all patients with acute intracranial and spinal bleedings.

Aged↗

Prevention of type I diabetes in the non-obese diabetic (NOD) mouse with 15-deoxyspergualin (15-DS) or 15-DS + cyclosporin A (CyA).

By selectively inbreeding diabetic individuals, we have been able to establish an NOD mouse population with a genetic predisposition towards insulin-dependent diabetes mellitus (IDDM) in approximately 100% of cases. We examined the preventive effect of 15-DS or 15DS + CyA on developing IDDM in these animals. Whereas 15-DS has been proved to be effective in preventing diabetes (significant decrease of the diabetic risk ratio to 0.368 and a reduction of the incidence of the disease to 46.7%), combined treatment with CyA did not produce any additional benefit.

Animals↗