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Biomedical subjects

F Neumann

Publications and source records attributed to F Neumann.

At least 37 records · Page 2Linked to original sources
PubMed1997

Anatomical variability and functional ability of vascular trees modeled by constrained constructive optimization.

The aim of this study was to investigate the extent that functional capability of vascular trees is related to anatomical variability. To these ends we used the method of Constrained Constructive Optimization (CCO) to generate optimized computer models of coronary arterial trees. All these model trees were optimized according to the same principle under equal boundary conditions of pressures and flows. However, by stochastically casting the locations of the terminal segments, different tree structures were generated, each of which conformed to the same boundary conditions. The structural variability of these models was interpreted as the correlate of the anatomical variability found in real arterial trees. The advantage that computer model trees are known in numerical detail was exploited to perform comprehensive and exact classifications of all segments into bifurcation levels, STRAHLER orders and composite vessels, and to compute the area expansion ratio. The unexpected result was that, despite striking visual differences in anatomical structure, the model trees were almost identical with regard to functional performance. We conclude that models optimized on the computer for a given perfusion task show little differences in their morphometric parameters even if they differ considerably regarding the course of the large vessels.

Computer Simulation↗
PubMed1997

Constitutive expression of human ribosomal protein L7 arrests the cell cycle in G1 and induces apoptosis in Jurkat T-lymphoma cells.

Protein L7 is involved in translational control in eucaryotic cells as indicated by its association with ribosomes, its capability to inhibit specifically the cell-free translation of distinct mRNAs, and its interference with the synthesis of two major nucleus-associated proteins in L7 cDNA-transfected Jurkat T-lymphoma cells [F. Neumann et al. (1995) Nucleic Acids Res. 23, 195]. In this report we show that the constitutive expression of protein L7 in Jurkat cells leads to an arrest in G1 of the cell cycle and induces apoptosis as a consequence of cell-to-cell contact. Treatment of the L7 transfectants with the inhibitor of translation cycloheximide, at doses which do not affect untransfected cells, enhances their sensitivity to the induction of apoptosis. These results suggest that L7 can interfere with the translation of proteins which control cell cycle progression and/or the initiation of the apoptotic pathways.

Apoptosis↗
PubMed1997

Distribution and structure of vagal afferent intraganglionic laminar endings (IGLEs) in the rat gastrointestinal tract.

Intraganglionic laminar endings (IGLEs) are special terminal structures of vagal afferent fibers and have been demonstrated in the myenteric plexus of esophagus and stomach. In order to quantitatively map their presence and distribution over the entire gastrointestinal tract, including the small and large intestines, vagal afferents were anterogradely labeled in vivo by microinjections of the fluorescent carbocyanine dye DiI into the left or right nodose ganglion of adult male rats. In the most successfully labeled cases the highest density of IGLEs was found in the stomach, with about half to one-third of the myenteric ganglia receiving at least one IGLE. The proportion of myenteric ganglia innervated by IGLEs decreased in the small intestine; however, because of its large surface area this gut segment was estimated to contain the highest total number of IGLEs. Both the cecum and colon also contained significant numbers of IGLEs. In the stomach, this vagal afferent innervation by IGLEs was more or less lateralized, with less than 20% of labeled IGLEs found on the contralateral side with respect to the injection. The left/ventral vagus contributed a larger proportion of IGLEs to the proximal duodenum, while the right/dorsal vagus contributed a larger proportion of IGLEs to the distal duodenum and jejunum. Laser scanning confocal microscopy on select specimens revealed further structural details. The parent axon typically formed two or more branches that flanked the ganglia laterally, and in turn produced numerous highly arborizing laminar terminal branches that covered one or both flat sides of the ganglion in a dome-like fashion. The similar distribution patterns and structural details suggest a uniform function for the IGLEs throughout the gastrointestinal tract, but there is as yet no clear proof for any of the hypothesized roles as specialized mechanosensors or local effector terminals.

Animals↗
PubMed1997

Limited bifurcation asymmetry in coronary arterial tree models generated by constrained constructive optimization.

Models of coronary arterial trees are generated by the algorithm of constrained constructive optimization (CCO). In a given perfusion area a binary branching network of straight cylindrical tubes is generated by successively adding terminal segments to the growing structure. In each step the site of connection is chosen according to an optimization target function (total intravascular volume), and in any stage of development the tree fulfills physiologic boundary conditions (constraints involving pressures, flows and bifurcation rules). CCO generates structures which in many aspects resemble real coronary arterial trees, except for very asymmetric bifurcations, occurring when a large branch gives off a tiny terminal segment. In the present work we evaluate an additional constraint within CCO, namely imposing a limit on the asymmetry of bifurcations during the construction process. Model trees are grown with different limits imposed, and the effects on structure are studied both phenomenologically and via statistical descriptors. As the limit to asymmetry is tightened, blood is conveyed to the perfusion sites via detours rather than directly and the comparison with measured data shows that the structure to change from a conveying to a delivering type of function. Simultaneously total intravascular volume, surface and sum of segments' lengths increase. It is shown why and how local bifurcation asymmetry is able to determine the global structure of the optimized arterial tree model. Surprisingly, the pressure profile from inlet to terminals, being a functional characteristic, remains unaffected.

Algorithms↗
PubMed1996

Mass spectrometric identification of leucine zipper-like homodimer complexes of the autoantigen L7.

The eucaryotic protein L7 has been shown to associate in the cytoplasm with the large subunit of ribosomes and to interact specifically with as yet unknown cognate sites of mRNA, thereby inhibiting cell-free translation (Neumann, F., Hemmerich, P., von Mikecz, A., Peter, H. H., and Krawinkel, U.(1995) Nucleic Acids Res. 23, 195-202). The N-terminal region of protein L7 contains a sequence motif similar to the leucine zipper domain of eucaryotic transcription factors, which promotes dimerization through alpha-helical coiled coil formation. Using electrospray-ionization mass spectrometry as a method of molecular specificity, we have directly identified the dimeric complexes comprising the leucine zipper-like region of protein L7 and have determined the dissociation constant of L7 homodimers in an affinity binding assay. We also demonstrate the high content of alpha-helicity of the dimer by circular dichroism spectra and computer-based structure simulation and show that the leucine zipper region of protein L7 is fully sufficient to mediate the inhibition of cell-free mRNA translation. A structural basis for the function of L7 to regulate translation is discussed. From the present results we conclude that L7 interacts with double stranded mRNA in a similar fashion as leucine zipper proteins with specific cognate sites on double stranded DNA.

Amino Acid Sequence↗
PubMed1996

Structural quantification and bifurcation symmetry in arterial tree models generated by constrained constructive optimization.

Arterial tree models are generated by Constrained Constructive Optimization according to minimum intravascular volume. These models, which have been shown to adequately reproduce pressure profiles and branching angles, are analysed topologically and geometrically in order to investigate how structure influences the functional capabilities. Therefore, the number of bifurcation levels and STRAHLER orders was evaluated for the complete trees as well as for subtrees of all possible sizes. Bifurcation symmetry, being a particular aspect of structure, was found to be higher in the smaller than in the larger subtrees. This confirms a more delivering type of function for the small subtrees, as expected from intuitive arguments. Conversely, lower symmetry in larger subtrees relates to their conveying type of function. Moreover, different shapes of the tissue to be perfused lead to different symmetry properties of optimized tree models.

Algorithms↗
PubMed1996

Perioperative myocardial injury with different modes of antegrade and retrograde cardioplegic delivery.

The effect of three cardioplegic protocols on perioperative myocardial injury was studied in 62 coronary artery bypass grafting (CABG) patients randomized into three groups with either antegrade or retrograde cold blood cardioplegia, or coronary sinus occlusion during antegrade supply. During the aortic cross-clamp time anterior and posterior septal temperatures were recorded, indicating the distribution of cardioplegic solution within the myocardium. Serum creatine kinase (CK), CK-isoenzyme MB and myoglobin as well as 12-lead electrocardiograms (ECG) were analyzed. Statistical analysis showed no effect of the cardioplegic protocol, whereas the patient's preoperative status, aortic cross-clamp time and intraoperative myocardial temperature had significant (P < 0.05) effects on immediate postoperative CK and CK-MB enzyme release. Creatine kinase-MB peak values were significantly increased in patients with major vessel disease and reduced left ventricular function (92 +/- 53 U/l versus 67 +/- 25 U/l). Both CK and CK-MB values were significantly higher in patients with aortic cross-clamp times of more than 1 h than in patients with shorter clamping times (661 +/- 188 and 78 +/- 40 U/l versus 500 +/- 200 and 57 +/- 24 U/l). Patients with 22 +/- 3 degrees C myocardial temperature before terminal cardioplegia had significantly elevated CK as compared to patients with temperatures of 15 +/- 2 degrees C (665 +/- 185 U/l versus 510 +/- 211 U/l). However, enzyme peak values had only poor predictive power for postoperative ECG changes, suggesting that enzyme peaks were not necessarily a sign of perioperative ischemia. Patients with major vessel disease and reduced myocardial function, with aortic cross-clamp time of more than 1 h and/or inadequate intraoperative myocardial cooling may be highly susceptible to global ischemia and operative procedures, and therefore show elevated peak enzyme levels shortly after surgery. In contrast, elevated myoglobin peaks within 1 h after aortic declamping were significantly correlated to perioperative signs of transient ischemia (P < 0.02).

Aged↗
PubMed1996

[Acute renal failure--differential diagnosis and therapeutic procedure].

Acute renal failure accompanied by an increase in retention parameters and oligo-anuria is a common medical problem. The most important medical task in nephrology is a fast diagnostic differentiation between prerenal-, renal- and postrenal failure. Using simple techniques such as case history, medical examination, ultrasound and specific analysis of serum and urine, it is possible to obtain a relatively certain diagnosis. Radiographic techniques with radiocontrast agents are contraindicated because of nephrotoxic side effects. The treatment of acute renal failure is based on the underlying disease. Apart from symptomatic treatment, there are only very few medications available to improve the excretory kidney function and diuresis. Complications like hyperkalemia, hyperhydration, metabolic acidosis and uremia require early renal replacement therapy. Especially in cases of extreme hyperkalemia, an immediate beginning of therapy is important. In the medical practice, emphasis should be placed upon the prevention of renal failure.

Acute Kidney Injury↗
PubMed1995

Human ribosomal protein L7 inhibits cell-free translation in reticulocyte lysates and affects the expression of nuclear proteins upon stable transfection into Jurkat T-lymphoma cells.

Eucaryotic ribosomal protein L7 carries a 'Basic-Region-Leucine-Zipper (BZIP)'-like region which mediates high-affinity binding to mRNA and 28S rRNA and formation of homodimers [P. Hemmerich et al. (1993) Nucleic Acids Res. 21, 223-231). Its biological function is unknown as yet and no direct L7-equivalent in procaryotes has been found. In this report we show that eucaryotic L7 specifically inhibits the cell-free translation of reporter mRNAs. The interaction of L7 with mRNA is an essential step in this reaction which is inhibitable by antibodies directed against the BZIP-like region of L7, and by competitors of mRNA binding. L7-mediated inhibition of cell-free translation of polyA+ RNA from Jurkat T-lymphoma cells is selective in that the synthesis of a major 46 kD protein is suppressed. Upon stable transfection of L7 cDNA into Jurkat lymphoma cells two major proteins disappear, namely one nuclear protein and one which associates with the nucleus. Our data suggest a regulatory role of protein L7 in the eucaryotic translation apparatus.

Amino Acid Sequence↗
PubMed1995

The influence of optimization target selection on the structure of arterial tree models generated by constrained constructive optimization.

The computational method of constrained constructive optimization was used to generate complex arterial model trees by optimization with respect to a target function. Changing the target function also changes the tree structure obtained. For a parameterized family of target functions a series of trees was created, showing visually striking differences in structure that can also be quantified by appropriately chosen numerical indexes. Blood transport path length, pressure profile, and an index for relative segment orientation show clear dependencies on the optimization target, and the nature of changes can be explained on theoretical grounds. The main goal was to display, quantify, and explain the structural changes induced by different optimization target functions.

Animals↗
PubMed1994

The branching angles in computer-generated optimized models of arterial trees.

The structure of a complex arterial tree model is generated on the computer using the newly developed method of "constrained constructive optimization." The model tree is grown step by step, at each stage of development fulfilling invariant boundary conditions for pressures and flows. The development of structure is governed by adopting minimum volume inside the vessels as target function. The resulting model tree is analyzed regarding the relations between branching angles and segment radii. Results show good agreement with morphometric measurements on corrosion casts of human coronary arteries reported in the literature.

Animals↗
PubMed1993

Structural and functional properties of ribosomal protein L7 from humans and rodents.

By subtractive screening of a library made from mRNA of lipopolysaccharide (LPS)-stimulated mouse B lymphocytes we isolated cDNA-clones encoding the ribosomal protein L7. Human L7 mRNA was cloned from activated T-lymphocytes. Although no specific function of L7 in the translation apparatus is known as yet, it should be a critical one as indicated by its high degree of structural conservation during evolution and its regulated expression in lymphoid cells. Human and rodent L7 proteins carry sequences similar to the basic-region-leucine-zipper(BZIP)-motif of DNA-binding eucaryotic transcription factors. We show here that the region of L7 carrying the latter motif mediates L7-dimerization and stable binding to DNA and RNA. A preferential binding to RNA-structures is demonstrated.

Amino Acid Sequence↗