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Biomedical subjects

M Neumann

Publications and source records attributed to M Neumann.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Analysis of mortality trends in the West Bohemian Region in comparison with the entire Czech Republic 1988-1995].

BACKGROUND: Unfavourable trends in Czech republic (CR) started in the sixties and peaked in the late eighties i.e. in years when a dramatic mortality fall was observed in most western european countries. So, CR belonged among those Eastern European countries in that total and cardiovascular mortality showed increasing and alarming trends. West Bohemia Region (WB) was characterised by the concentration of heavy industry and high environmental pollution. Because of its geographical position on the western frontier, it was generally restricted in capital investment in the past. We wondered whether these phenomenon were reflected in higher mortality rates than in the rest of CR and which changes occurred after the year 1989. METHODS AND RESULTS: We compared the age standardized mortality data from 1988, 91, 93 and 95 in CR and WB for total mortality, cardiovascular mortality, coronary heart disease, strokes, malignancies and respiratory diseases. Data were age-adjusted for "World Population Standards" and rates were given for 100,000 inhabitants. In the whole CR a significant decrease of total, cardiovascular and cancer mortality was observed from 1988 to 1995. In WB these trends were similar, however in comparison to the whole CR the mortality rates remained in each respective period higher for total, cancer (mainly lung cancer) mortality and for non specific respiratory disease. In contrast, the coronary mortality rates in CR and WB were similar, however in WB after a temporary decrease in 1993 a significant increase in 1995 was observed. On the other hand the stroke mortality rates which were until 1993 in WB higher, significantly decreased in 1995 below the rates for CR. The cause of higher mortality rates in WB are far from being clear. To elucidate this observation epidemiologic studies of environmental pollution, life style of the population and socioeconomic factors are necessary, even as a further monitoring of regional mortality rates and trends.

Cause of Death↗
PubMed1998

Induction of nuclear factor-kappa B during primary B cell differentiation.

We have investigated activation of nuclear factor-kappa B (NF-kappa B) in the process of primary B cell differentiation in vitro. In this system, NF-kappa B is strongly induced when B cells develop from the pre-B cell to the immature B cell stage. Unlike the typical NF-kappa B activation in response to exogenous stimuli, induction proceeds with a slow time course. NF-kappa B induction is only observed in B cells that undergo differentiation, not in Rag2-deficient cells. Nuclear DNA binding complexes predominantly comprise p50/RelA heterodimers and, to a lesser extent, c-Rel-containing dimers. The increase in NF-kappa B binding activity is accompanied by a slow and steady decrease in I kappa B beta protein levels. Interestingly, absolute RelA protein levels remain unaffected, whereas RelB and c-Rel synthesis is induced. The reason for preferential nuclear translocation of RelA complexes appears to be selective inhibition by the I kappa B beta protein. I kappa B beta can efficiently inhibit p50/RelA complexes, but has a much reduced ability to interfere with p50/c-Rel DNA binding both in vitro and in vivo. Interestingly, p50/RelB complexes are not at all targeted by I kappa B beta, and coimmunoprecipitation experiments show no evidence for an association of I kappa B beta and RelB in vivo. Consistent with these observations, I kappa B beta cotransfection can inhibit p50/RelA-mediated trans-activation, but barely affects p50/RelB mediated trans-activation.

3T3 Cells↗
PubMed1998

Determinants of reproducibility of lung function tests in children aged 7 to 10 years.

Lung function (LF) tests are part of many investigations in childhood lung disease. However, individual reproducibility of LF will confound between-subject differences. At the same time, increased LF variability has been linked to respiratory disease. In a sample of 598 children, two LF tests, separated by a 5-min interval, were recorded, and reliability (Rel) of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and maximal expiratory flow at 50% of FVC (MEF50) was determined. Rel was also assessed in children trained and untrained in the performance of LF. To investigate determinants of reproducibility for FEV1, the absolute difference between two repeated tests was calculated. Whenever this difference was > 120 ml, a child was considered to demonstrate excessive variability (poor reproducibility) in FEV1. For volume parameters coefficients of reliability (Crel) were found to be better than for MEF50 (FEV1: 0.96; FVC: 0.94, MEF50: 0.91). In untrained children Crel for FEV1 was only 0.91, but it was increased in subsequent visits (0.98, 0.97, and 0.97 at the second, third, and fourth tests, respectively). Excessive variability in FEV1 was observed in 10% of children and was related to the presence of wheeze [odds ratio (OR) 6.31; 95% confidence interval (CI) 1.78-22.4), shortness of breath (OR 3.14; 95% CI 1.00-9.93), a diagnosis of asthma (OR 6.25; 95% CI 1.76-22.1), and bronchial hyperresponsiveness (OR 4.30; 95% CI 2.07-8.94). We conclude that increased variability of LF is likely to be present in young children not accustomed to the testing procedure and in children with respiratory symptoms. Therefore, before guidelines for LF testing are applied, children should be trained to perform the tests and we should be cautious in the interpretation of test results in children who present with symptoms.

Child↗
PubMed1998

Evaluation of the vasoconstrictive effects of topical steroids by laser-Doppler-perfusion-imaging.

Corticosteroids are one of the most frequently prescribed local therapeutic treatments. Their potency and bioavailability are tested with different methods. One of the most accepted methods is the skin-blanching test designed by McKenzie. In this study we investigated whether the skin-blanching test designed by McKenzie for screening topically active corticosteroids, producing vasoconstriction, is sufficiently detectable by a laser-Doppler-perfusion-imager (LDPI). Eight sites in two rows on the right forearm of 10 healthy volunteers were treated with a topical glucocorticosteroid (clobetasol-17-propionate 0.05% (Dermovate), and the bloodflow at each site was measured by the LDPI at different timesteps. Four sites per row were chosen to evaluate the dependency of bioavailability according to anatomical differences due to skin changes within the forearm. Furthermore, half of the sites were occluded to demonstrate the difference between occluded and non-occluded sites in bioavailability. The results show that the LDPI can easily detect changes in bloodflow due to the vasoconstriction caused by topical corticosteroid. The results showed significant changes during the different measurements, with a maximum reaction 30 h after the application of the corticosteroid. The sites under occlusion showed a slower decrease of laser values than those without occlusion, so that it can be pointed out that occlusion prolongs the bioavailability of corticosteroids but does not influence the speed of onset. So far we conclude that this technique is a simple and non-traumatic method for assessing steroid potency. Blanching, as a result of vasoconstriction, can be quantified by LDPI measurement. However, LDPI measurements have to be compared with other techniques, such as the non-traumatic 133Xe washout technique, to find out if the two technologies respond in a similar way.

Administration, Topical↗
PubMed1998

Linking injection drug users to medical services: role of street outreach referrals.

Street outreach workers in HIV prevention have expanded their role to include referring injection drug users to medical services. However, little is known about whether drug users act on these referrals. The study discussed in this article examined the level of exposure to street outreach reported by injection drug users, the most common medical referrals acted on as a result of such contacts, and the predictors of acting on these referrals. Findings indicate that injection drug users with four or more contacts with street outreach workers during the preceding six months were more likely to report acting on referrals. To maximize the relevance of outreach for encouraging medical treatment, both street outreach workers and social workers in health care could benefit from cross training that focuses on strengthening the referral process.

Adult↗
PubMed1998

Antimicrobial peptides melittin and cecropin inhibit replication of human immunodeficiency virus 1 by suppressing viral gene expression.

Antimicrobial peptides are effectors of innate immunity, providing their hosts with rapid non-specific defence against parasitic invaders. In this report, the effects are assessed of two well-characterized antimicrobial amphipathic peptides (melittin and cecropin) on human immunodeficiency virus 1 (HIV-1) replication and gene expression in acutely infected cells at subtoxic concentrations. Production of infectious, cell-free virus was inhibited in a dose-dependent manner, with ID50 values in the range 0.9-1.5 microM for melittin and 2-3 microM for cecropin. Analysis of the effect of melittin on cell-associated virus production revealed decreased levels of Gag antigen and HIV-1 mRNAs. Transient transfection assays with HIV long terminal repeat (LTR)-driven reporter gene plasmids indicated that melittin has a direct suppressive effect on activity of the HIV LTR. HIV LTR activity was also reduced in human cells stably transfected with retroviral expression plasmids for the melittin or cecropin gene. It is concluded that antimicrobial peptides such as melittin and cecropin are capable of inhibiting cell-associated production of HIV-1 by suppressing HIV-1 gene expression.

Anti-Infective Agents↗
PubMed1998

Outer radius-wall thickness ratio, a postmortem quantitative histology in human coronary arteries.

Although the anatomy, histology and pathology of human coronary arteries have been studied extensively, little is known about the functional relationship between vessel radius and wall thickness. It is the purpose of this study to present detailed measurements and to describe this relationship covering the range from the feeding coronary artery to the arterioles. Human hearts of 10 adults less than 36 +/- 3 years old were investigated immediately postmortem. Ten cubic tissue blocks, measuring about 10 mm in length on each side, were dissected from the left ventricular wall. After fixation by immersion, 15-microm sections were prepared and outer and inner perimeters of 52 arterial segments were digitalized. Vessel radius and wall thickness were calculated and plotted to show their relationship over the whole range of vessel calibers. Outer vessel radii ranged from 100 to 3,000 microm and wall thickness from 80 to 800 microm. Plotting the outer vessel radius against the wall thickness, the data points were found to cluster around a straight line. A significant correlation between the two parameters was found (R2 = 0.79). This mathematical correlation and the good agreement of the presented results with data from other species indicate a common physiologic concept.

Adult↗
PubMed1998

Longitudinal predictors of airway responsiveness to distilled water: the role of atopy and maternal smoke exposure.

Airway responsiveness is an objectively measurable clinical trait related to the presence of asthma. Although risk factors for this trait have been evaluated cross-sectionally, little is known about its longitudinal predictors. A population cohort of 539 children, aged 8 yrs at the start of follow-up, underwent 3-7 bronchial challenge tests spaced at 3-9 month intervals. Airway responsiveness was assessed by a single-step distilled water challenge. To investigate responsiveness as a continuous trait, the ratio of the postchallenge to prechallenge forced expiratory volume in one second was calculated. A child's repeated ratios were then regressed on the time of follow-up. The resulting child-specific regression coefficient was the outcome variable to assess longitudinal predictors of airway responsiveness (AR). Results were based on 2,267 repeated challenge tests, and indicated an overall decrease in responsiveness. Children with a diagnosis of asthma (mean+/-SD, longitudinal change in AR + yr(-1): -0.060+/-0.149), those with a positive skin-prick test (-0.018+/-0.106) and those with reported exposure to maternal smoking (-0.004+/-0.083) demonstrated increased airway responsiveness over time. All of these changes in airway responsiveness were found to be significant in multiple linear regression analysis (p<0.05). Stratified analysis further indicated that the effect of maternal smoking was observed primarily in nonatopic children and was greatest at an exposure level of > or =10 cigarettes x day(-1). In conclusion, atopy and exposure to maternal smoking can predict longitudinal change in childhood airway responsiveness.

Air Pollutants↗
PubMed1998

Adhesion molecule expression in basal cell carcinoma.

Basal cell carcinomas (BCCs) are frequently associated with a peritumoral mononuclear infiltrate. Until now, the function of this inflammatory infiltrate and its possible role in the control of tumor growth is unclear. Mechanisms controlling endothelial and target cell adhesiveness for leukocytes are important features in the development of a specific local immune response. The expression and distribution of the adhesion molecules ICAM-1, VCAM-1 and E-selectin by microvascular endothelial cells and tumor cells, together with their leukocyte receptors LFA-1, VLA-4 and CLA respectively, were studied in 33 BCCs of different histological subtypes. In normal skin, ICAM-1 is expressed by resting endothelial cells, whereas VCAM-1 and E-selectin expression correlates with endothelial activation. The epidermis in normal conditions displays no ICAM-1, VCAM-1, or E-selectin expression. In BCC, endothelial ICAM-1 expression was only slightly increased compared to normal skin, whereas expression of endothelial VCAM-1 and E-selectin was low or absent in all BCCs examined. Peritumoral infiltrates contained mostly LFA-1-expressing lymphocytes, with minimal VLA-4 and CLA positivity. In none of the cases studied was adhesion molecule expression by BCC tumor cells identified. The lack of significant expression of adhesion molecules on peritumoral vascular endothelial cells and BCC tumor cells does not support the idea of specific, cell-mediated immunity being an important mechanism in limiting BCC tumor spread.

Biomarkers, Tumor↗
PubMed1997

Co-localization of HIV-1 Nef with the AP-2 adaptor protein complex correlates with Nef-induced CD4 down-regulation.

The nef gene of human and simian immunodeficiency viruses is critical for AIDS pathogenesis. Its function in vivo is unknown, but in vitro natural isolates of Nef down-regulate expression of the cell surface CD4 molecule, a component of the T cell antigen receptor and the viral receptor, by accelerating its endocytosis. We have used chimeric proteins comprised of the natural HIV-1 NA7 Nef fused to a strongly fluorescing mutant of green fluorescent protein (GFP) to correlate Nef function with intracellular localization in human CD4-positive Jurkat T cells. The NA7-GFP fusion protein co-localizes with components of the clathrin coat, including clathrin and the beta-subunit of the AP-2 adaptor protein complex, at discrete locations that are consistent with the normal cellular distribution of clathrin coats at the plasma membrane. The NA7-GFP protein is also found in the perinuclear region of the cell, which is likely to reflect the Golgi apparatus. Evidence from a CD4-negative fibroblast cell line indicates that co-localization of NA7-GFP with components of the clathrin coat does not require expression of the CD4 molecule. Analysis of a large panel of chimeric molecules containing mutant Nef moieties demonstrated that the N-terminal membrane targeting signal cooperates with additional element(s) in the disordered loops in the Nef molecule to co-localize the Nef protein with AP-2 adaptor complexes at the cell margin. This localization of NA7-GFP correlates with, but is not sufficient for, down-regulation of surface CD4 and at least one additional function of Nef is required. In T cells co-expressing CD4 and NA7-GFP, CD4 at the cell surface is redistributed into a discrete pattern that co-localizes with that of NA7-GFP. Our observations place NA7-GFP in physical proximity to AP-2-containing clathrin coat at the plasma membrane and imply that Nef interacts, either directly or indirectly, with a component of the AP-2-containing coat at this location. This evidence supports a model whereby Nef recruits CD4 to the endocytic machinery via AP-2-containing clathrin coats at the plasma membrane.

Adaptor Protein Complex alpha Subunits↗
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

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↗