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Biomedical subjects

M Neumann

Publications and source records attributed to M Neumann.

At least 91 records · Page 5Linked to original sources
PubMed1999

An artificial neural net and error backpropagation to reconstruct single photon emission computerized tomography data.

At present, algorithms used in nuclear medicine to reconstruct single photon emission computerized tomography (SPECT) data are usually based on one of two principles: filtered backprojection and iterative methods. In this paper a different algorithm, applying an artificial neural network (multilayer perception) and error backpropagation as training method are used to reconstruct transaxial slices from SPECT data. The algorithm was implemented on an Elscint XPERT workstation (i486, 50 MHz), used as a routine digital image processing tool in our departments. Reconstruction time for a 64 x 64 matrix is approximately 45 s/transaxial slice. The algorithm has been validated by a mathematical model and tested on heart and Jaszczak phantoms. Phantom studies and very first clinical results ((111)In octreotide SPECT, 99mTc MDP bone SPECT) show in comparison with filtered backprojection an enhancement in image quality.

Algorithms↗
PubMed1999

Diminished rev-mediated stimulation of human immunodeficiency virus type 1 protein synthesis is a hallmark of human astrocytes.

Astrocytes are target cells for human immunodeficiency virus type 1 (HIV-1) in the central nervous system with attenuated virus replication in vivo and in vitro. In infected astrocytes, viral gene expression is restricted mainly to nonstructural (early) viral components like Nef, suggesting inhibition of Rev-dependent posttranscriptional processes in these cells. Because of the heterogeneity of astrocytic cells, the objective of this study was to determine whether restriction of HIV-1 Rev-associated activities is a common property of human astrocytes. To this end, we compared the trans activation capacity and intracellular distribution of Rev in four astrocytoma cell lines previously shown to be infectible by HIV-1 and in primary human fetal astrocytes from different sources with Rev-permissive nonglial control cell lines. In all astrocytic cell cultures, the Rev response was reduced to about 10% of that of Rev-permissive control cells. Rev was apparent both in cytoplasmic and in nuclear compartments of living astrocytes, in contrast to the typical nuclear and/or nucleolar localization of Rev in permissive control cells. Nuclear accumulation of Rev in astrocytes was restored by blocking export of Rev. The trans activation capacity and nuclear localization of Tat were not affected in astrocytes. These results demonstrate that inhibition of Rev-dependent posttranscriptional regulation of HIV-1 is a hallmark of human astrocytes and may contribute to suppression of HIV-1 production in these HIV-1 reservoirs. Astrocytes constitute the first example of a human cell type showing an impaired Rev response, indicating that posttranscriptional control of HIV-1 gene expression can be modulated in a cell-dependent manner.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Transcription-dependent nuclear-cytoplasmic trafficking is required for the function of the von Hippel-Lindau tumor suppressor protein.

Mutation of the von Hippel-Lindau tumor suppressor gene (vhl) causes the von Hippel-Lindau cancer syndrome as well as sporadic renal clear cell carcinoma. To pursue our study of the intracellular localization of VHL protein in relation to its function, we fused VHL to the green fluorescent protein (GFP) to produce the VHL-GFP fusion protein. Like VHL, VHL-GFP binds to elongins B and C and Cullin-2 and regulates target gene product levels, including levels of vascular endothelial growth factor and glucose transporter 1. VHL-GFP localizes predominantly to the cytoplasm, with some detectable nuclear signal. Inhibition of transcription by actinomycin D or 5,6-dichlorobenzimidazole riboside (DRB) causes VHL to be redistributed to the nucleus. A cellular fusion assay was used to demonstrate that inhibition of transcription induces a decrease in the nuclear export rate of VHL. The dependence of transcription for trafficking is lost with a deletion of exon 2, a region with a mutation causing a splice defect in the VHL gene in sporadic renal clear cell carcinoma. Addition of a strong nuclear export signal (NES) derived from the Rev protein results in complete nuclear exclusion and abrogates the redistribution of VHL-GFP-NES into the nucleus upon inhibition of transcription. Leptomycin B, which inhibits NES-mediated nuclear export, reverts the distribution of VHL-GFP-NES to that of VHL-GFP and restores sensitivity to actinomycin D and DRB. Uncoupling of VHL-GFP trafficking to transcription either by an exon 2 deletion or fusion to NES abolishes VHL function. We suggest that VHL function requires not only nuclear or cytoplasmic localization, but also exon 2-mediated transcription-dependent trafficking between these two cellular compartments.

Animals↗
PubMed1999

[The police in psychiatric daily routine].

PURPOSE: The following is a description of those patients brought by the police to the emergency room of a general hospital of Berlin for a psychiatric exploration. METHOD: The medical records of those patients brought in to the emergency room during one year were analyzed retrospectively. RESULTS: Within one year, 317 (10.8%) out of 2903 patients were brought by the police to have an emergency psychiatric exploration. The ratio of men to women was 2:1, and the median age was 41. Most illnesses diagnosed were schizophrenia, disorders caused by psychotropic substances, alcoholism, alcohol intoxication, and adjustment disorders/stress disorders. One third of the 317 patients were under influence of alcohol. 21.8% of the 317 patients were suicidal. Over two thirds of the patients were admitted to the psychiatric ward. Only 31 patients were not admitted to the ward for lack of indication. The most frequent reason for intervention of police was suicidal behaviour (35%), "strange behaviour" (28.7%) or aggressive behaviour (23%). CONCLUSION: The results show that those patients brought in by the police are in acute crisis situations often involving suicidal tendencies and suffer from more severe psychiatric illnesses. The psychiatric emergency exploration initiated by the police was generally justifiable.

Adult↗
PubMed1998

Multiplex dye DNA sequencing in capillary gel electrophoresis by diode laser-based time-resolved fluorescence detection.

A new one-lane, four-dye DNA sequencing method was developed which is based on time-resolved detection and identification of fluorescently labeled primers. For fluorescent labels, we used two newly synthesized rhodamine derivatives (MR200-1, JA169), a new oxazine derivative (JA242), and a commercially available cyanine dye (CY5). The dye fluorescence was excited by a pulsed diode laser emitting at 630 nm. The fluorescence decay was detected by an avalanche photodiode using a single-filter system. The dyes used here, so-called multiplex dyes, can be distinguished and identified via their fluorescence decay patterns. The DNA fragments were labeled at the primer using linkers of various lengths and positions. For separation of the enzymatically generated DNA fragments, capillary gel electrophoresis (CGE) with a 5% linear polyacrylamide gel was employed. On covalent attachment to oligonucleotides, the dyes exhibit fluorescence decay times of 3.7 (MR200-1), 2.9 (JA169), 2.4 (JA242), and 1.6 ns (CY5) measured during CGE. The CGE mobility of the labeled DNA fragments could be controlled and nearly equalized by the coupling position and the linker length. First, time-resolved, one-lane, four-dye DNA sequencing runs in CGE are presented. The sequence information of 660 bp was determined with a probability of correct classification of > 90%. This result was obtained directly from the raw data without any of the mobility corrections that are necessary with other methods.

DNA↗
PubMed1998

Interphase cytogenetic study of preoperative core biopsies for the prediction of early serum prostate specific antigen recurrence after radical prostatectomy of clinically localized prostate carcinoma.

BACKGROUND: Current clinical and pathologic methods are imprecise in predicting the extent of prostate carcinoma progression. This study was conducted to evaluate the role of interphase cytogenetics (ICG) with chromosome enumeration probes relative to the role of conventional pathologic characteristics in the preoperative prediction of postoperative tumor classification and recurrence of elevated serum concentrations of prostate specific antigen (PSA). METHODS: The authors performed ICG with enumeration probes for chromosomes 7, 17, and X on 6-microm sections of core biopsies from 75 patients with clinically localized adenocarcinoma of the prostate. Results were compared with pathologic findings (tumor classification, volume, and status of surgical margins) of the corresponding radical prostatectomy specimens and data on serum PSA measurements taken for 72 patients during a follow-up period of up to 42 months (mean, 19.8 months). In addition to ICG, biopsies were reviewed for primary, secondary, highest, and combined Gleason grades, number and bilaterality of positive biopsies, amount of carcinoma (percentage and core length of infiltration), amount of high grade carcinoma, and perineural invasion. RESULTS: Chromosome categories were unevenly distributed among pathologic tumor classification groups (P = 0.0008) and between groups with positive and negative surgical margins (P = 0.0116). Tumors with aneusomic chromosome numbers had larger volumes than those with eusomy and tetrasomy (P = 0.0022). Kaplan-Meier analysis demonstrated that PSA recurrences (> or = 0.4 ng/mL) were more frequent and observed earlier in patients with detected chromosomal aneusomies than in those with eusomic and tetrasomic chromosome numbers (P < 0.0001). Cox regression analysis indicated that ICG was the most valuable independent factor in predicting PSA recurrences. CONCLUSIONS: The detection of numeric chromosomal aberrations in preoperative core biopsies is an adverse prognostic sign. Grading based on the quantification of genetic changes might prove useful in the prognostic stratification of patients with clinically localized prostate carcinoma.

Adenocarcinoma↗
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↗