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M Neumann

Publications and source records attributed to M Neumann.

At least 109 records · Page 6Linked 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

Preferential binding of poly(A)-binding protein 1 to an inhibitory RNA element in the human immunodeficiency virus type 1 gag mRNA.

Human immunodeficiency virus type 1 (HIV-1) mRNAs encoding structural proteins contain multiple inhibitory/instability elements (INS), which decrease the efficiency of viral protein expression. We have previously identified a strong INS element (INS-1) within the p17(gag) coding region. Here we show that poly(A)-binding protein 1 (PABP1) binds preferentially to INS-1 within the p17(gag) mRNA, but not to a mutated mRNA in which INS-1 function is eliminated. Competition experiments performed in the presence of different nucleic acids and homoribopolymers demonstrated preferential binding of PABP1 to the INS-1-containing RNA. In contrast to HeLa cells and several lymphoid cell lines, certain human glioma cell lines exhibit high levels of gag expression in the absence of Rev upon transient transfection with wild type gag expression vectors. We analyzed extracts of different cell lines and found that the binding of PABP1 to INS-1 RNA is significantly diminished in glial cell extracts. The expression levels of gag correlate with the absence of binding of PABP1 to the INS-1 RNA in cellular extracts. These results suggest a role for PABP1 in the inhibition of gag expression mediated through INS-1.

Blotting, Western↗
PubMed1997

Cyclosporin A interferes with the inducible degradation of NF-kappa B inhibitors, but not with the processing of p105/NF-kappa B1 in T cells.

The transcription factor NF-kappa B controls the induction of numerous cytokine promoters during the activation of T lymphocytes. Inhibition of T cell activation by the immunosuppressants cyclosporin A (CsA) and FK506 exerts a suppressive effect on the induction of these NF-kappa B-controlled cytokine promoters. We show for human Jurkat T leukemia cells, as well as human and mouse primary T lymphocytes, that this inhibitory effect is accompanied by an impaired nuclear translocation of the Rel proteins c-Rel, RelA/p65 and NF-kappa B1/p50, whereas the nuclear appearance of RelB remains unaffected. CsA does not interfere with the synthesis of Rel proteins, but prevents the inducible degradation of cytosolic NF-kappa B inhibitors I kappa B alpha and I kappa B beta upon T cell activation. CsA neither inhibits the processing of the NF-kappa B1 precursor p105 to p50, nor does it "stabilize" the C-terminal portion of p105, I kappa B gamma, which is degraded during p105 processing to mature p50. These results indicate that CsA interferes with a specific event in the signal-induced degradation of I kappa B alpha and I kappa B beta, but does not affect the processing of NF-kappa B1/p105 to p50.

Animals↗
PubMed1997

Three dimensional variability in patient positioning using bite block immobilization in 3D-conformal radiation treatment for ENT-tumors.

BACKGROUND AND PURPOSE: The aim of this prospective study was to analyze the three-dimensional (3D) reproducibility of the isocenter position and of patient positioning with the use of bite block immobilization by means of a simple verification procedure for a complex beam arrangement applied for ENT-tumors. MATERIALS AND METHODS: We analyzed the positioning data of 29 consecutive patients treated for ENT-tumors at the Department of Radiotherapy and Oncology of the University of Wurzburg. A total of 136 treatment sessions were analyzed. Patients were positioned and immobilized using an individualized bite block system and a head and neck support. A complex beam arrangement was applied combining two offset rotational and two oblique wedge fields on a 5 MV linear accelerator. Orthogonal verification films were taken once weekly. Four to six film pairs per patient were obtained (during 4-6 weeks) with a mean number of 4.7 film pairs per patient. These were compared to the corresponding orthogonal simulator films taken during primary simulation. Deviations of the verified isocenter from the isocenter on the simulator film were measured and analyzed in three dimensions in terms of overall, systematic and random categories. A 3D-deviation vector was calculated from these 3D data as well as a 2D-deviation vector (for comparison with literature data) from the lateral verification films. RESULTS: The overall setup deviation showed standard deviations (SD) of 2.5, 2.7 and 3.1 mm along the cranio-caudal, anterior-posterior and medio-lateral axes, respectively. The random component ranged from SD 1.9 to 2.1 mm and the systematic component ranged from SD 1.8 to 2.2 mm. The mean length of the 3D-vector was 3.1 mm for the systematic as well as the random component. Ninety percent of 3D systematic and random deviations were less than 5 mm. The mean length of the 2D-vector was 2.4 mm for the random component and 2.2 mm for the systematic component. Ninety percent of 2D-random and systematic variations were less than 4 mm. CONCLUSIONS: The presented individualized bite block immobilization device provides an accurate and reproducible patient positioning for 3D-conformal radiation therapy in the head and neck. Random and systematic deviations in each of the three directions are in the range of +/-4 mm (2 SD, comprising 95% of the deviations) and are within the range or even less than deviations described for most thermoplastic or PVC-mask fixation devices. These deviations should be taken into account during definition of planning target volume in head and neck tumors.

Head and Neck Neoplasms↗
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↗
PubMed1997

Meso-tetraphenylporphyrin dimer derivative as a potential photosensitizer in photodynamic therapy.

Studies on the synthesis, preliminary in vivo biological activity, singlet oxygen and fluorescence yields of a dimeric porphyrin (D1) are described. The pharmacokinetic behavior and photodynamic properties of the dimer D1 were examined in Balb/c mice bearing an MS-2 fibrosarcoma. Compound D1 shows a high selectivity for tumor localization (tumor/peritumoral tissue ratios of dye concentration ranging between ca 100 and 140 at 24 h after drug administration of 5.0-1.0 mg kg-1 into DL-alpha-dipalmitoylphosphatidylcholine liposomes). The phototherapeutic efficiency of dimer D1 was evaluated by following the growth curves of fibrosarcoma irradiated with red light (600-700 nm) with a total dose of 400 J cm-2, at 24 h after intravenous injection. Photodynamic therapy-treated tumors showed a significant delay in growth as compared to untreated control mice. The results obtained suggest that the porphyrin dimer D1 may be a promising candidate for further use in PDT experiments.

Animals↗
PubMed1997

Comparison of methods for isolation of mycobacteria from water.

Twelve methods for the isolation of mycobacteria were compared by applying them in parallel to 26 samples of surface water and 109 samples of treated water. Each method was defined by a particular combination of decontamination method, growth medium, and incubation temperature. For the decontamination of surface water, we used cetylpyridinium chloride (CPC) (30 min, 0.05%), as well as sample preincubation in tryptic soy broth (TSB) followed by decontamination with a cocktail of NaOH, cycloheximide, and malachite green. Treated water was decontaminated with 0.005 and 0.05% CPC (30 min). After enrichment by filtration, all samples were incubated on Lowenstein-Jensen medium (LJ), Ogawa egg yolk medium (OEY), and Ogawa whole-egg medium containing ofloxacin and ethambutol (OEOE) at temperatures of 30 and 37(deg)C. The efficacy of each method was determined by calculating the positivity rate, negativity rate, contamination rate, mean number of mycobacterial colonies grown, and mean number of different mycobacterial strains isolated. The last value was determined by subjecting the isolates to PCR restriction analysis and mycolic acid thin-layer chromatography. Statistical analysis demonstrated that both the TSB method and 0.05% CPC were appropriate for the decontamination of surface water. Decontamination with 0.005% CPC was best for treated water. The results for incubation on LJ were at least equal to those for incubation on OEY and always superior to the results with OEOE. At an incubation temperature of 30(deg)C, all methods achieved higher yields than at 37(deg)C.

Journal Article↗
PubMed1997

RNA aptamers specifically interact with the prion protein PrP.

We have isolated RNA aptamers which are directed against the recombinant Syrian golden hamster prion protein rPrP23-231 (rPrPc) fused to glutathione S-transferase (GST). The aptamers did not recognize the fusion partner GST or the fusion protein GST::rPrP90-231 (rPrP27-30), which lacks 67 amino acids from the PrP N terminus. The aptamer-interacting region of PrPc was mapped to the N-terminal amino acids 23 to 52. Sequence analyses suggest that the RNA aptamers may fold into G-quartet-containing structural elements. Replacement of the G residues in the G quartet scaffold with uridine residues destroyed binding to PrP completely, strongly suggesting that the G quartet motif is essential for PrP recognition. Individual RNA aptamers interact specifically with prion protein in brain homogenates from wild-type mice (C57BL/6), hamsters (Syrian golden), and cattle as shown by supershifts obtained in the presence of anti-PrP antibodies. No interaction was observed with brain homogenates from PrP knockout mice (prn-p(0/0)). Specificity of the aptamer-PrP interaction was further confirmed by binding assays with antisense aptamer RNA or a mutant aptamer in which the guanosine residues in the G tetrad scaffold were replaced by uridine residues. The aptamers did not recognize PrP27-30 in brain homogenates from scrapie-infected mice. RNA aptamers may provide a first milestone in the development of a diagnostic assay for the detection of transmissible spongiform encephalopathies.

Animals↗
PubMed1997

Traffic-related NO2 and the prevalence of asthma and respiratory symptoms in seven year olds.

The aim of this study was to determine whether outdoor nitrogen dioxide (NO2) was associated with the prevalence of asthma and respiratory symptoms. In eight nonurban communities, 843 children resident for a minimum of 2 yrs were studied. Since industrial sources of air pollution were at least 20 km away from the study communities, NO2 was considered to primarily indicate traffic-related air pollution. NO2 was recorded at central monitors, and the 3 yr mean exposure was calculated. Asthma and respiratory symptoms were assessed according to the International Study on Asthma and Allergy in Childhood. Prevalence of asthma at some time ("ever asthma") was associated with long-term NO2. In parallel with increasing levels of NO2 (community specific 3 yr mean 6.0-17.0 parts per billion (ppb)), asthma prevalence was 2.5, 1.4, 1.6, 2.3, 3.4, 3.6, 7.6 and 8.5%, respectively (p=0.002 for trend). The prevalence odds ratios (PORs) for "ever asthma", following adjustment for gender, age, parental education, passive smoke exposure, type of indoor heating, and parental asthma, were 1.28 (95% confidence interval (95% CI) 0.20-7.98), 2.14 (95% CI 0.40-11.3) and 5.81 (95% CI 1.27-26.5), when each of two communities with low, regular and high NO2, respectively, were compared with the two communities with very low NO2. For symptoms "wheeze" (adjusted PORs for increased NO2: 1.47, 1.23 and 2.27) and "cough apart from colds" (adjusted PORs for increased NO2: 1.49, 1.93 and 2.07), a similar trend was seen. In this study a significant relationship was observed between traffic-related nitrogen dioxide and the prevalence of asthma and symptoms. Whether this association is causal has to be tested in longitudinal studies.

Asthma↗
PubMed1997

Congenital lymphocytic choriomeningitis virus syndrome: a disease that mimics congenital toxoplasmosis or Cytomegalovirus infection.

OBJECTIVE: To describe the clinical characteristics of intrauterine infection with lymphocytic choriomeningitis (LCM) virus, an uncommonly recognized cause of congenital viral infection. PATIENTS: Three infants born in the midwestern United States in 1994 and 1995 with clinical features and serologic studies consistent with congenital LCM virus infection and cases of congenital infection identified by review of the medical literature between 1955 and 1996. RESULTS: Twenty-six infants with serologically confirmed congenital LCM virus infection were identified. Twenty-two infants were products of term gestations, and birth weights ranged from 2384 to 4400 g (median, 3520 g). Ocular abnormalities, macrocephaly, or microcephaly were the most commonly identified neonatal features. Twenty-one infants (88%) had chorioretinopathy, 10 (43%) had macrocephaly (head circumference >90th percentile) at birth, and 3 (13%) were microcephalic (head circumference <10th percentile). Macrocephaly and hydrocephalus developed postnatally in one of the latter infants. Hydrocephalus or intracranial calcifications were documented in five infants by computed tomography or magnetic resonance imaging. Nine infants (35%) died, and 10 (63%) of the 16 reported survivors had severe neurologic sequelae, consisting of spastic quadriparesis, seizures, visual loss, or mental retardation. One-half of the mothers reported illnesses compatible with LCM virus infection, and 25% reported exposures to rodents during their pregnancies. CONCLUSIONS: These cases suggest that congenital LCM virus infection could be an underrecognized cause of congenital infection among infants born in the United States. Because of the clinical similarities of these congenital infections, cases of congenital LCM virus infection can be confused with infections with cytomegalovirus or Toxoplasma gondii.

Apgar Score↗
PubMed1997

Evaluation of the pediatric renal transplant recipient.

Renal transplantation is the preferred therapy for children with end stage renal disease. A functioning renal allograft can dramatically improve a child's quality of life. Advances in immunosuppressive therapy and clinical practice approaches have significantly improved graft survival rates allowing children to attain near normal growth and development. Accurate assessment and appropriate nursing care enhances long-term survival of these young patients.

Child↗
PubMed1996

CD40, but not lipopolysaccharide and anti-IgM stimulation of primary B lymphocytes, leads to a persistent nuclear accumulation of RelB.

In this study we analyzed the effect of CD40 stimulation on the activity and nuclear appearance of Rel/nuclear factor kappaB (NF-kappaB) factors in primary murine B lymphocytes. We show that triggering of CD40 signaling pathway(s) by CD40 ligands expressed on L cells led to strong activation of an NF-kappaB-controlled beta-globin reporter gene in primary B lymphocytes from transgenic mice. Analyses of nuclear translocation of individual members of Rel proteins after CD40 induction of primary B cells showed a strong and long-lasting accumulation of RelB and, less pronounced, of c-Rel. LPS stimulation did not give rise to a persistent nuclear accumulation of RelB and c-Rel, whereas nuclear c-Rel, but not RelB, accumulated after B cell receptor stimulation. CD40 induced not only nuclear translocation but also de novo synthesis of RelB RNA and protein. S107 plasmacytoma cells, which express CD40 but are defective for the nuclear appearance of p50/p65-NF-kappaB, do not express RelB after CD40 stimulation. In S107 cells stably transfected with relB genes, stimulation of nuclear RelB translocation by CD40 was observed. These results indicate that stimulation of CD40 signaling pathways exerts a long-lasting stimulatory effect on both the transcription and nuclear translocation of RelB. Since LPS and anti-IgM were unable to activate RelB, CD40 appears to trigger a special program of gene expression involved in the proliferation and/or differentiation of B lymphocytes.

Animals↗
PubMed1996

[Serum levels of sialic acid in patients with type 1 diabetes mellitus in relation to the incidence of late complications].

BACKGROUND: Sialic acid is released from terminal oligosaccharide chain of some proteins of the acute phase (fibrinogen, orosomucoid, haptoglobin, etc.). Its serum concentrations have been commonly increased during acute inflammation. Its relation diabetes mellitus or late complications of the disease have been recently studied as well. The aim of our investigation was to determine serum concentrations of sialic acid in patients with diabetes mellitus Type 1 in relation to presence or absence of late diabetic complications. METHODS AND RESULTS: The authors examined a group of 62 patients treated for diabetes mellitus Type 1, mean age 28.7 +/- 9.8 years, having been treated for this disease for 11.8 +/- 8.7 years on the average. The mean level of glycated hemoglobin HbAlc was 9.08 +/- 1.84%. In 21 patients there were signs of diabetic nephropathy, seven of them already suffering from proteinuria. Retinopathy already developed in 12 patients. The mean concentration of sialic acid in the whole cohort was 1.916 +/- 0.292 mmol/litre. The correlation of serum sialic acid with age, duration of diabetes and glycated hemoglobin was not statistically significant. There was no significant difference between the serum concentration of sialic acid in patients without apparent nephropathy and those who were affected by nephropathy, or the subgroup with proteinuria (1.945 +/- 0.328 against 1.914 +/- 0.302 mmol/litre and 1.943 +/- 0.328 mmol/litre, respectively). Statistically significantly higher concentrations of serum sialic acid were found in the subgroup of patients with present retinopathy (2.085 +/- 0.244 mmol/litre against 1.890 +/- 0.270 mmol/litre, P < 0.018). CONCLUSIONS: Our findings are in agreement with the previously proved increased concentration of proteins of the acute phase in diabetic patients and correspond well to the previously proved finding of elevated serum concentration of sialic acid in diabetic patients of Type 2 with retinopathy against other patients. It may not be excluded that the serum sialic acid could be used as a marked of the risk of late complications of diabetes mellitus.

Adult↗
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

Mutations in a subgroup of patients with mild haemophilia A and a familial discrepancy between the one-stage and two-stage factor VIII:C methods.

A subgroup of patients with haemophilia A who have a familial discrepancy between the one-stage and two-stage factor VIII:C results has previously been described. These patients show factor VIII:C levels by one-stage assay that are 2-7-fold higher than their two-stage results. We have studied 10 such families and identified six different mutations in the factor VIII gene in this group. The chemical cleavage method and DNA sequencing was used to identify mutations in factor VIII gene fragments generated by reverse transcription and PCR. All available family members were tested to confirm the presence of the mutation in affected individuals. These patients were found to have one of six single point substitutions causing a missense mutation and alteration to one codon in exons 7, 11, 14 or 18. The mutations comprise three that have not previously been described (Ala284Glu. Arg698Leu. Leu1932Phe) and three that have been previously described (Ser289Leu, Arg531His, Arg698Trp). Alterations to the amino acid composition of the A1, A2 and A3 domains of factor VIII are predicted by these molecular studies. In contrast, a control group of 23 mild haemophilia families with equivalent factor VIII:C results by one-stage and two-stage assays did not have any of the above mutations. Detailed studies in seven of these latter families identified four mutations affecting the A3, C1 and C2 domains of factor VIII. These findings suggest a genetic basis to the unusual factor VIII phenotype but do not explain the mechanism of the discrepant factor VIII activity.

Exons↗