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Biomedical subjects

A Bauer

Publications and source records attributed to A Bauer.

At least 19 recordsLinked to original sources

Transforming growth factor-beta-mediated autocrine growth regulation of gliomas as detected with phosphorothioate antisense oligonucleotides.

Transforming growth factors-beta 1 and -beta 2 (TGF-beta 1 and -beta 2) are important growth-regulatory proteins for astroglial neoplasms. We analyzed their role in tumor-cell proliferation in 12 glioma cell lines, employing phosphorothioate antisense oligodeoxynucleotides (S-ODNs, 14 mer), specifically targeted against the coding sequences of TGF-beta 1-mRNA and TGF-beta 2-mRNA. TGF-beta 1-S-ODNs inhibited cell proliferation in 5 of 12 gliomas, whereas TGF-beta 2-S-ODNs reduced the cell proliferation in all glioma cell lines, compared to nonsense-S-ODN-treated and S-ODN-untreated cells as controls. The efficacy and specificity of antisense effects was validated by Northern-blot analysis and determination of protein concentrations in culture supernatants (ELISA). Exogenous hrTGF-beta 1 either stimulated or inhibited the cell lines, whereas pnTGF-beta 2 stimulated the proliferation of most glioma cells. Blocking the extracellular pathway of TGF-beta by neutralizing antibodies only slightly inhibited those cell lines, which were markedly stimulated by TGF-betas. As the effects of TGF-beta 2-S-ODNs were much stronger than those of TGF-beta neutralizing antibodies, we postulate that the endogenously produced TGF-beta 2 control glioma-cell proliferation, in part by an intracellular loop.

Base Sequence

[Cotard syndrome].

We describe a schizophrenic paranoid patient, who developed a unique clinical state that fits the Cotard syndrome. The article deals with the course of the disease, the clinical characteristics, the difficulties of treatment. The process of diagnosis and its difficulties, and the rareness of the symptoms are emphasized. Various etiological causes of the syndrome are discussed.

Adult

Characterization of the SAC3 gene of Saccharomyces cerevisiae.

A temperature-sensitive mutation (act1-1) in the essential actin gene of Saccharomyces cerevisiae can be suppressed by mutations in the SAC3 gene. A DNA fragment containing the SAC3 gene was sequenced. SAC3 codes for a 150 kDa hydrophillic protein which does not show any significant similarities with other proteins in the databases. Sac3 therefore is a novel yeast protein. A nuclear localization of Sac3 is suggested by the presence of a putative nuclear localization signal in the Sac3 sequence. A SAC3 disruption mutation was constructed. SAC3 disruption mutants were viable but grew more slowly and were larger than wild-type cells. In contrast to the sac3-1 mutation, the SAC3 disruption was not able to suppress the temperature sensitivity and the osmosensitivity of the act1-1 mutant. This demonstrates that act1-1 suppression by sac3-1 is not the result of a simple loss of SAC3 function. Furthermore, we examined the act1-1 and the sac3 mutants for defects in polarized cell growth by FITC-Concanavalin A (Con A)-labelling. The sac3 mutants showed a normal ConA-labelling pattern. In the act1-1 mutant, however, upon shift to non-permissive temperature, newly synthesized cell wall material, instead of being directed towards the bud, was deposited at discrete spots in the mother cell.

Actins

[Ultrasound contrast media. New perspectives in ultrasound diagnosis].

Ultrasound contrast agents have recently proven to be clinically useful in many different areas and with many different ultrasound modalities. B-mode contrast echocardiography and delineation of cavities with ultrasound contrast agents are already accepted. Based on the contrast agent Echovist, assessment of tubal patency is possible with hysterosalpingo contrast sonography (HyCoSy). A new generation of transpulmonary, stable ultrasound contrast agents such as Levovist offer potential for various Doppler applications. Ultrasound contrast agents act as signal enhancers in Doppler examinations and therefore help to overcome the limitations of insufficient Doppler signal intensity. Recently, clinical studies have shown [correction of shown.] Doppler examinations to have many clinical benefits. Contrast agents are useful in the assessment of high-grade stenosis or the delineation of small vessels and under difficult conditions. Ultrasound contrast agents also create new applications: analysis of tumor vascularization and delineation of the transcranial venous system are possible with contrast enhancement. Future developments in contrast-specific scanning ("harmonic imaging") and new contrast agents, including organ-specific contrast agents, are expected to make a significant impact in the years to come.

Contrast Media

The SAC3 gene encodes a nuclear protein required for normal progression of mitosis.

The SAC3 gene of Saccharomyces serevisiae has been implicated in actin function by genetic experiments showing that a temperature sensitive mutation in the essential actin gene (actl-1) can be suppressed by mutations in SAC3. An involvement of SAC3 in actin function is further suggested by the observation that the actin cytoskeleton is altered in SAC3 mutants. Our fractionation experiments, however, point to a nuclear localization of Sac3p. On sucrose density gradients Sac3p co-fractionated with the nuclear organelle markers examined. Furthermore, Sac3p was enriched 10-fold in a nuclei preparation along with the nuclear protein Nop1p. In this report we further show that SAC3 function is required for normal progression of mitosis. SAC3 mutants showed a higher fraction of large-budded cells in culture, indicative of a cell cycle delay. The predominant population among the large-budded sac3 cells were cells with a single nucleus at the bud-neck and a short intranuclear spindle. This suggests that a cell cycle delay occurs in mitosis prior to anaphase. The observation that SAC3 mutants lose chromosomes with higher frequency than wild-type is another indication for a mitotic defect in SAC3 mutants. We further noticed that SAC3 mutants are more resistant against the microtubule destabilizing drug benomyl. This finding suggests that SAC3 is involved, directly or indirectly, in microtubule function. In summary, our data indicate that SAC3 is involved in a process which affects both the actin cytoskeleton and mitosis.

Actins

Pyrrolidino enaminones structural related to gyrase inhibitors: synthesis, cyclization and pharmacological activity.

The synthesis and stereochemical characteristics of pyrrolidino enaminones with structural analogy to quinolone antibacterial agents are reported. Retro-aldol reaction of the esters 7 is observed under all conditions of hydrolysis, the enzyme catalyzed reaction also does not yield the corresponding acids. In contrast to clinically used quinolones exemplary tests with monocyclic esters of type 7 and the tricyclic derivative 10 indicate low or no antibacterial activity. Additionally to the lack of the carboxylic acid function the enaminones 7 differ from quinolones in stereochemical demands and the electronic situation of the phenyl substituents of 10, respectively possibly preventing the formation of a co-operative tetrametric system between compounds and DNA bases.

Anti-Bacterial Agents

[New aspects of defibrillator therapy].

The implantable cardioverter defibrillator is currently a therapy of first choice in patients with malignant therapy refractory ventricular arrhythmias. The occurrence of malignant ventricular tachycardia cannot be suppressed by the defibrillator but is treated using antitachycardia pacing, cardioversion or defibrillation. During recent years, electrodes, defibrillation shockforms and device size were continuously optimized. The development of transvenous lead systems resulted in significant reduction of perioperative mortality and morbidity. With the availability of biphasic shockforms and single-lead unipolar devices marked reduction of defibrillation thresholds were achieved and transvenous lead systems without subcutaneous could be implanted. Improvements in device technology lead to smaller devices which can be implanted subpectorally even using local anaesthesia. But there is still enormous potential to develop an ideal antiarrhythmic device. One of the most significant problems of the defibrillator therapy represents the delivery of inappropriate shocks due to supraventricular tachyarrhythmias and sinustachycardia. To solve this problem different approaches are currently developed. Extension in memory allows to store several data logs and intracardiac electrograms for individual adapted adjustment of the therapy. Intracardiac electrogram width measurement for discrimination between ventricular and supraventricular arrhythmias is currently evaluated. Dual-chamber arrhythmia discrimination algorithms of an integrated dual-chamber pacemaker and defibrillator are clinically studied. Hemodynamic sensors for determining the severity of the arrhythmia are currently under experimental evaluation. The combination of latissimus dorsi dynamic cardiomyoplasty and ICD therapy may improve survival in patients with severely depressed left ventricular function and malignant ventricular arrhythmias. Several randomized prospective trials are currently in progress potentially expanding the use of the ICD in patients at risk for sudden cardiac death. The high costs of defibrillator therapy is still a limitation for its use, but higher production figures and advancing technology could reduce the system prize.

Anti-Arrhythmia Agents

Nerve terminals of mucous gland electroreceptors in the platypus (Ornithorhynchus anatinus).

Platypus mucous gland electroreceptors differ from electroreceptors described for fish in that they lack an associated specialized sensory cell. Thus a bare nerve terminal is used to detect electrical stimuli, and also to generate local and action potentials. Previous studies have identified these terminals (an average of 16 per mucous gland), but had not shown whether the terminals have direct contact with the duct of the mucous gland. This poses the problem of how the electrical stimulus reaches the nerve terminals. This study demonstrates the portions of the nerve terminals responsible for electroreception, and shows how these portions use the surrounding epidermal tissue to overcome the combined problems of lacking a sensory cell and making physical contact with the conducting medium in the duct of the gland. A terminal axonal filament is described which accommodates for these problems, the terminal filament provides a low-resistance pathway for the electrical stimuli, and is embedded with its proximal and distal portions in high and low resistance epidermis, respectively. Lateral interactions occur between adjacent terminal filaments via a plexus that is directed circumferentially around the duct from the proximal portion of the terminal filament. These circumferential arbors form an interconnecting ring between all 16 terminal filaments, and may be used to lower the signal-to-noise ratio of the electroreceptor and thus enhance overall sensitivity.

Animals

Virtual reality in surgical arthroscopic training.

Arthroscopy has become an irreplaceble method in diagnostics. The arthroscope, with optics and light source, and the exploratory probe are inserted into the knee joint through two small incisions underneath the patella. Currently, the skills required for arthroscopy are taught through hands-on clinical experience. Therefore, the Fraunhofer-Institut fuer Graphische Datenverarbeitung in Darmstadt, in cooperation with the Berufsgenossenschaftliche Unfallklinik Frankfurt am Main, developed a highly interactive medical training system for arthroscopy through computer graphics and virtual reality (VR) techniques. Two main issues are addressed: the three-dimensional (3-D) reconstruction process and the 3-D interaction. The goal of the reconstruction process is to obtain a realistic representation of the knee joint derived from a magnetic resonance image sequence suitable for computer simulation. Moreover, the 3-D interaction of the training system must stimulate real arthroscopy, providing an intuitive handling of the instruments.

Arthroscopy

Mechanical perturbation of jaw movements during speech: effects on articulation and phonation.

12 subjects uttered the testword/papapas/repeatedly with three different speech rates and two stress patterns. On 17% randomly chosen trials, a mechanical load was applied unpredictably to the jaw in the direction of the opening movement. Load onset was triggered by the start of the first phonation. Analysis showed that the opening and closing displacements of the jaw movement in the first syllable were not influenced significantly by the perturbation. The load application prolonged the duration of the jaw movement in unstressed syllables but not in stressed syllables. Further, the mechanical perturbation of the jaw led to increased duration of phonation in unstressed syllables only, the effect for duration of phonation being greater at higher speech rates. These results demonstrate a coupling between articulation and phonation.

Adult

SPECT imaging of ischemic myocardium using a technetium-99m-nitroimidazole ligand.

UNLABELLED: This investigation evaluates the efficacy of a 99mTc-labeled nitroimidazole (BMS-181321) in identifying oxygen-deprived tissue in two canine models of myocardial ischemia. METHODS: For both models (A and B), epicardial microvascular oxygen pressure (mPO2) was monitored by measuring the oxygen-dependent quenching of phosphorescence lifetime of Palladium mesotetra (4-carboxyphenyl) porphine. In Model A (beagles, n = 5), BMS-181321 was administered intravenously and a distal branch of the left anterior descending coronary artery (LAD) was ligated completely 40 sec later. Ten minutes later, the ligature was released establishing tissue reoxygenation. In Model B, flow through the LAD was reduced until the mPO2 was about 2 Torr. After bolus administration of BMS-181321 (50-60 mCi), coronary ischemia was continued for a residence period of up to 4 hr. RESULTS: With Model A, SPECT reconstructions revealed a small ischemic area in three of five dogs, however, a transmural accumulation of the compound was evident in the autoradiograms from all dogs. In the two animals in which the defect was not observed by SPECT, the ischemic episode had nominal effects on the ratio of +/- dp/dt (< 4% change as compared to baseline values). In Model B, SPECT reconstructions showed positive images of the oxygen-deprived area within the mid- to apical regions of the left ventricle (n = 5). Autoradiographic analysis showed a transmural association with cells resulting in an ischemic-to-nonischemic ratio of 3.5 +/- 0.4 (n = 4) for animals with similar residence times. CONCLUSION: The results from both models suggest that BMS-181321 provides a noninvasive marker of regional ischemia in the heart and that this compound may have clinical utility for detection of coronary artery disease.

Animals

[Internal medicine in German-speaking countries and in the USA. Mutual influences and changes in relations 1870 to 1990].

Scientific relations in Internal Medicine between German-speaking countries and the United States were characterized by various stages during the last hundred and twenty years. From 1870 to the First World War German medical research and teaching as well as the competitive German university system were regarded as a model for US Medical Schools. After World War I, however, things changed as a result of American Medical Schools' reforms which had been implemented. On the other hand, financial equipment of German universities was decreasing due to inflation and unemployment. Furthermore, between 1933 and 1945, many excellent scientists and clinicians were forced to emigrate from Germany and Austria to the US because of persecution by the Nazis for political or "racial" reasons. After the end of World War II, scientific and technical leadership of American Internal Medicine remained unchallenged; today many European physicians complete their training in the biomedical sciences in the United States. Beginning in the 1980s, German-speaking internists increasingly publish the results of their research in American scientific journals.

Austria

High-resolution one- and two-dimensional 1H MRS of human brain tumor and normal glial cells.

Astrocytoma (WHO grade II, III), glioblastoma, malignant melanoma, and normal glial cell cultures, established from biopsies, were investigated by 1H MRS. At a 1H resonance frequency of 500 MHz (11.75 T) a high spectral resolution was achieved in 1D 1H spectra; in conjunction with 2D shift-correlated (COSY) MRS, resonances of alanine, aspartate, choline, creatine, glutamate, glutamine, hypotaurine, myo-inositol, phosphocreatine, phosphoryl-ethanolamine, phosphoryl-choline, lactate, lysine, N-acetylaspartate, taurine, threonine and valine could be identified. T1 relaxation times for the most prominent compounds are presented. T1 values of lactate ranged between 450 ms and 850 ms. The intensity of the lactate signal revealed differences between individual spectra, but exhibited no correlation between different tumor specimens or degree of malignancy. It was shown that the lactate signal at 1.3 ppm is covered by peaks arising from threonine and fatty acids. The choline signal level varied among spectra of different tumors, among tumors with similar degree of malignancy, and within the same tumor. Further preliminary differences due to aspartate, inositol and glutamine/glutamate were found in 1D and 2D COSY spectra between normal glial cells as well as different tumors. These results indicate that some differences observed in in vivo spectra may be attributable to secondary macroscopic structural changes (hypoxia, necrosis) and not to tumor inherent characteristics. Further correlation between in vivo and in vitro spectroscopy is therefore required.

Astrocytoma

An improved pair potential to recognize native protein folds.

We present a novel method to improve a simple pair potential of mean force, derived from experimentally determined protein structures, in such a way that it recognizes native protein folds with high reliability. This improvement is based on the use of mutation data matrices to overcome difficulties arising from the poor statistics of small sample sizes. A set of 167 protein chains taken from the Brookhaven Protein Structure Data Base, selected from high-resolution structures and avoiding homologous proteins, is used for generation of the potential set. The potential describes interresidue pair energies depending on distance and sequential separation, and is calculated using the Boltzmann equation. Its performance is evaluated by jackknife tests that try to identify the native fold for a given sequence among a large number of possible threadings on all structures in the set without allowing for gaps. Up to 94% of the protein chains are correctly assigned to their native folds, so that all proper single-chain domains are recognized.

Computer Simulation