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G Schumann

Publications and source records attributed to G Schumann.

At least 37 records · Page 2Linked to original sources
PubMed2000

Combined semantic dementia and apraxia in a patient with frontotemporal lobar degeneration.

In this study we report neuropsychological and brain-imaging findings in a patient with frontotemporal lobar degeneration. Brain imaging using registration of (18)fluorodeoxyglucose (FDG)-PET data to three-dimensional (3-D) magnetic resonance imaging showed atrophy and highly significant hypometabolism of the left temporal lobe and both frontal lobes. Volumetric measurements of the hippocampi/amygdala showed a reduction in volume of 25% on the left compared to right within cortical areas. Neuropsychological testing revealed semantic dementia with severe anomia as well as apraxia with impairment of both recognition and production of motor acts. The implications of this case of early manifestation of frontotemporal lobar degeneration for our knowledge of dementia are discussed.

Anomia↗
PubMed2000

Estimation of the uncertainty of CRMs in accordance with GUM: application to the certification of four enzyme CRMs.

Uncertainties of four enzyme-CRMs that have recently been certified in a co-operation between the IRMM and the International Federation for Clinical Chemistry were estimated. Estimation was based on the sum of the uncertainties of characterization, homogeneity and stability. Data from the certification collaborative study were used to estimate laboratory uncertainties, which form the basis for the uncertainty of characterization. Estimations for the uncertainty of homogeneity were derived from classical homogeneity studies. The estimations of uncertainty of stability caused the most difficulties. Realistic uncertainties fitting the needs of customers while being derived from measurement data based on theoretical considerations were obtained.

Algorithms↗
PubMed1999

The effect of lethal electrical shock on postmortem serum myoglobin concentrations.

Postmortem serum myoglobin concentrations in blood from the femoral vein (peripheral withdrawal) and the heart (central withdrawal) of nine electrical fatalities were compared with those of 74 individuals who had died of other causes. Independent of the cause of death or topographical site, serum myoglobin concentrations rose dramatically with the passage of postmortem time (maximum concentrations in the control group: 975,100 micrograms/l). In 59% of the total sample (electrical fatalities plus controls), serum myoglobin concentrations were higher in the central blood, in the other 41% the concentrations were higher in the peripheral blood. The differences in concentrations between the peripheral and the central withdrawal area correlated with neither the postmortem interval nor the cause of death. Up to the second day postmortem there was a statistically significant difference in serum myoglobin concentrations between electrical fatalities and controls. The individual values within each group, however, varied widely and overlapped between groups. Controls who had also suffered muscle injury (polytrauma, myocardial infarction) did not have significantly higher serum myoglobin concentrations than controls without muscle injury. Myoglobin concentrations appear to be greatly influenced by the extent and duration of the muscle cramps induced by the electrical current. Correct interpretation of serum myoglobin concentrations depends on the knowledge of events surrounding the lethal electrical shock. Postmortem determination of serum myoglobin concentrations alone is, therefore, not sufficient to establish intravital exposure to electrical current and can aid the diagnosis only in special cases.

Adolescent↗
PubMed1999

The non-steroidal anti-inflammatory drug tepoxalin inhibits interleukin-6 and alpha1-anti-chymotrypsin synthesis in astrocytes by preventing degradation of IkappaB-alpha.

Tepoxalin is a structurally and functionally novel non-steroidal anti-inflammatory drug (NSAID) with potent anti-inflammatory and analgesic properties. Apart from its inhibitory effect on cyclooxygenase activity, tepoxalin is able to inhibit production of cytokines in peripheral cells outside the CNS. No data, however, are available concerning the effects of this drug in the CNS. Since cytokines such as interleukin-1 (IL-1) or interleukin-6 (IL-6) as well as acute-phase proteins such as alpha1-anti-chymotrypsin (ACT) participate in the etiopathology of Alzheimer's disease (AD), we were interested whether tepoxalin is able to inhibit the synthesis of these immunomodulators in primary rat microglia and astrocytes as well as in the human astrocytoma cell line U373 MG. We found that tepoxalin markedly inhibits IL-1beta-induced IL-6 and ACT synthesis in astrocytes and the synthesis of IL-1beta and IL-6 in lipopolysaccharide (LPS)-stimulated microglial cells. Electrophoretic mobility shift and reporter gene assays revealed that tepoxalin exerts its inhibitory effect through the inhibition of nuclear factor kappaB (NF-kappaB), a transcription factor involved in the induction of IL-1, IL-6 and ACT gene expression. We show that inhibition of NF-kappaB activation by tepoxalin is mediated by preventing IkappaB-alpha degradation. Based on this inhibitory effect of tepoxalin on cytokine and ACT synthesis and the documented therapeutic efficacy of NSAIDs in AD, we conclude that tepoxalin may be of therapeutic benefit for the treatment of AD patients and should therefore be tested in clinical trials.

Alzheimer Disease↗
PubMed1999

Anti-inflammatory substances - a new therapeutic option in Alzheimer's disease.

Among several pathogenetic elements underlying Alzheimer's disease (AD), a brain-specific inflammatory response has recently attracted attention as a cause of neurodegeneration and progressive cognitive decline. Markers of inflammation in AD are activated microglial cells, synthesis of cytokines, acute-phase proteins and complement proteins in areas of brain destruction. Epidemiological studies point to a reduced risk of AD among users of anti-inflammatory drugs. Influencing inflammatory parameters has become the focus of several new treatment strategies and a clinical trial with indomethacin shows promising results. The results from current clinical trials with steroidal and non-steroidal anti-inflammatory drugs will be available in the near future.

Journal Article↗
PubMed1999

Transport and utilization of rhizoferrin bound iron in Mycobacterium smegmatis.

Transport and metabolization of iron bound to the fungal siderophore rhizoferrin was analyzed by transport kinetics, Mössbauer and EPR spectroscopy. Saturation kinetics (vmax = 24.4 pmol/(mg min), K(m) = 64.4 microM) and energy dependence excluded diffusion and provided evidence for a rhizoferrin transport system in M. smegmatis. Based on the spectroscopic techniques indications for intracellular presence of the ferric rhizoferrin complex were found. This feature could be of practical importance in the search of novel drugs for the treatment of mycobacterial infections. EPR and Mössbauer spectroscopy revealed different ferritin mineral cores depending on the siderophore iron source. This finding was interpreted in terms of different protein shells, i.e. two types of ferritins.

Electron Spin Resonance Spectroscopy↗
PubMed1999

Health effects of sulfur-related environmental air pollution. II. Cellular and molecular parameters of injury.

Recently, concern has been raised about effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on nonrespiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to a neutral sulfite aerosol at a sulfur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to an acidic sulfate aerosol providing a hydrogen concentration of 15.2 micromol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each animal. A second group of eight dogs (control) was kept for the entire study under clean air conditions. No clinical symptoms were identified that could be related to the combined exposure. Biochemical and cellular parameters were analyzed in sequential bronchoalveolar lavage (BAL) fluids. The permeability of the alveolo-capillary membrane and diethylenetriaminepentaacetic acid (DTPA) clearance was not affected. Similarly, oxidant burden of the epithelial lining fluid evaluated by levels of oxidation products in the BAL fluid protein fraction remained unchanged. Both the lysosomal enzyme beta-N-acetylglucosaminidase and the alpha-1-AT were increased (p <.05). In contrast, the cytoplasmic marker lactate dehydrogenase remained unchanged, indicating the absence of severe damages to epithelial cells or phagocytes. Various surfactant functions were not altered during exposure. Three animals showed elevated levels of the type II cell-associated alkaline phosphatase (AP), indicating a nonuniform response of type II cells. Significant correlations were found between AP and total BAL protein, but not between AP and lactate dehydrogenase, suggesting proliferation of alveolar type II cells. Absolute and relative cell counts in the BAL fluid were not influenced by exposure. Alveolar macrophages showed no alterations with regard to their respiratory burst upon stimulation with opsonized zymosan. The percentage of alveolar macrophages capable of phagocytozing latex particles was significantly decreased (p<.05), while the phagocytosis index was not altered. In view of the results of this and previous studies, we conclude that there is no synergism of effects of these two air pollutants on nonrespiratory lung functions. It is hypothesized that antagonistic effects of these air pollutants on phospholipase A2-dependent pathways account for compensatory physiological mechanisms. The results emphasize the complexity of health effects on lung functions in response to the complex mixture of air pollutants and disclose the precariousness in the risk assessment of air pollutants for humans.

Aerosols↗
PubMed1999

Health effects of sulfur-related environmental air pollution. III. Nonspecific respiratory defense capacities.

Recently concern has been raised about health effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on respiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to 1.0 microm neutral sulfite aerosol with a particle associated sulfur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to 1.1 microm acidic sulfate aerosol providing an hydrogen ion concentration of 15.2 micromol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each dog. A second group of eight dogs (control) was kept for the entire study under clean air conditions. Nonspecific defense mechanisms in the airways and in the peripheral lung were studied during chronic exposure of the combination of neutral sulfur(IV) and acidic sulfur(VI) aerosols. No functional changes of tracheal mucus velocity were found, in agreement with unchanged morphometry of the airways. However, the exposure resulted in changes of several alveolar macrophage (AM) mediated particle clearance mechanisms: (1) Based on in vivo clearance analysis and cultured AM studies using moderately soluble cobalt oxide particles, intracellular particle dissolution was significantly reduced since phagolysosomal proton concentration was decreased. We deduce exposure-related malfunction of proton pumps bound to the phagolysosomal membrane as a result of an increase of cytosolic proton concentration. (2) Based on in vivo clearance analysis using insoluble polystyrene particles, AM-mediated particle transport from the lung periphery toward ciliated terminal bronchioli and further to the larynx was significantly reduced. Activation of epithelial type II cells at the entrance of alveoli was inferred from observed type II cell proliferation at those alveolar ridges and enhanced secretion of alkaline phosphatase in the fluid of bronchoalveolar lavages. As a result, hypersecretion of chemotactic mediators by activated type II cells at these loci led to the observed decrease of particle transport toward ciliated bronchioli. (3) Based on in vivo clearance analysis using insoluble polystyrene particles, particle transport from the alveolar epithelium into interstitial tissues was increased and (4) particle transport to the tracheobronchial lymph nodes was significantly enhanced. Particle transport into interstitial tissues is the most prominent clearance pathway from the canine alveolar epithelium. We conclude that the deteriorated particle transport toward ciliated terminal bronchioli resulted in an enhanced particle transport across the epithelial membrane into interstitial tissues and the lymphatic drainage. The observed alterations in alveolar macrophage-mediated clearance mechanisms during chronic exposure of these air pollutants indicate an increased risk of health.

Aerosols↗
PubMed1999

Interleukin-6 activates signal transducer and activator of transcription and mitogen-activated protein kinase signal transduction pathways and induces de novo protein synthesis in human neuronal cells.

Interleukin-6 (IL-6) is involved in the pathophysiology of various diseases of the CNS. Because the molecular mechanism of action of this cytokine in human neurons is not well understood, we were interested in characterizing and defining a model system for IL-6-induced activation of signal transduction cascades, transcriptional activation, and protein synthesis in human neuronal cells. We show that IL-6 leads to transcriptional activation of signal transducer and activator of transcription 3 (STAT3) in human SH-SY5Y neuroblastoma cells. IL-6-induced activation and translocation of STAT3 and to a lesser degree STAT1 but not STAT5 are demonstrated. STAT3 is phosphorylated on Tyr705 and Ser727 residues on stimulation with IL-6, suggesting maximal activation of transcription. We also show IL-6-induced phosphorylation of p42/44 mitogen-activated protein (MAP) kinase, providing evidence for MAP kinase pathway activation. The physiological relevance of our results is confirmed by IL-6-induced phosphorylation of key signaling proteins of both STAT and MAP kinase pathway in rat primary hippocampal neurons. Furthermore, de novo protein synthesis on IL-6 activation is demonstrated.

Animals↗
PubMed1999

Cystatin C and creatinine after successful kidney transplantation in children.

BACKGROUND: Serum creatinine is commonly used for the monitoring of allograft function following renal transplantation (RTX). Due to lower muscle mass, creatinine production rate is reduced in children, thus decreasing its sensitivity for the detection of allograft dysfunction. In children, the serum concentration of cystatin C, a low molecular weight protein of 13.3 kDa, reflects glomerular filtration rate independent of age, height and body composition. We, therefore, sought to assess the potential of cystatin C as a marker of allograft function in children. METHODS: Cystatin C and creatinine were measured in parallel at least daily in 24 children (14 boys, 10 girls; mean age 10.5+/-5.1 years) during hospitalization after successful RTX. Cystatin was determined immunoturbidimetrically, creatinine enzymatically. RESULTS: Within one hour after RTX, cystatin C (mean+/-SE) almost halved from 6.69+/-0.45 mg/l to 3.69+/-0.38 mg/l while creatinine declined from 862 +/-65.4 to 633+/-62.9 micromol/l. Following a nadir of 1.82+/-0.18 mg/l on day 2, there was a secondary increase in cystatin C concentrations to 2.69+/-0.35 mg/l on day 10. Creatinine concentrations continued to decline until day 9 reaching 80.5+/-13.1 micromol/l. Day-to-day variation at steady-state was comparable. In the course of 9 acute rejection episodes, both parameters rose in parallel, the increase in creatinine concentration being much greater. CONCLUSION: Cystatin C was an early indicator of allograft function following successful RTX in children. It did not prove superior to creatinine for the recognition of acute allograft dysfunction, however.

Biomarkers↗
PubMed1998

Cytokine-induced transcription of protein-tyrosine-phosphatases in human astrocytoma cells.

Interleukin-1 (IL-1) and Tumor Necrosis Factor-a (TNFalpha) are potent mediators of inflammatory reactions in the brain. Although much is known about the effects of IL-1 on expression of secretory proteins, few studies have addressed the question of a selective, IL-1-dependent expression of genes involved in neuromodulatory effects of inflammation. Protein-tyrosine-phosphatases (PTP's) have been shown to regulate signal transduction and adhesion processes in the developing nervous system. They are candidates for inflammation-induced neuromodulation. Therefore, we investigated if IL-1 regulates expression of PTP's. We applied a DNA-fingerprinting method based on the PCR-amplification of conserved domains of gene families and observed IL-1-dependent induction of two PTP's, cytoplasmic PTPvarepsilon and receptor-PTPgamma, RPTPgamma, in human U373-MG astrocytoma cells. Using Northern blot analysis, we confirmed this result and also show that in addition to IL-1, TNFalpha but not IL-6 induces the transcription of cytoplasmic PTPvarepsilon and RPTPgamma in human astrocytoma cells. Given the important role for PTP's in neuromodulatory aspects such as axonal guidance and neurite outgrowth, cytokine-induced induction of PTP's may play an important pathenogenic role in the development of chronic inflammatory diseases in the brain.

Astrocytoma↗
PubMed1998

Skipper, an LTR retrotransposon of Dictyostelium.

The complete sequence of a retrotransposon from Dictyostelium discoideum , named skipper , was obtained from cDNA and genomic clones. The sequence of a nearly full-length skipper cDNA was similar to that of three other partially sequenced cDNAs. The corresponding retrotransposon is represented in approximately 15-20 copies and is abundantly transcribed. Skipper contains three open reading frames (ORFs) with an unusual sequence organization, aspects of which resemble certain mammalian retroviruses. ORFs 1 and 3 correspond to gag and pol genes; the second ORF, pro, corresponding to protease, was separated from gag by a single stop codon followed shortly thereafter by a potential pseudoknot. ORF3 (pol) was separated from pro by a +1 frameshift. ORFs 2 and 3 overlapped by 32 bp. The computed amino acid sequences of the skipper ORFs contain regions resembling retrotransposon polyprotein domains, including a nucleic acid binding protein, aspartyl protease, reverse transcriptase and integrase. Skipper is the first example of a retrotransposon with a separate pro gene. Skipper is also novel in that it appears to use stop codon suppression rather than frameshifting to modulate pro expression. Finally, skipper and its components may provide useful tools for the genetic characterization of Dictyostelium.

Amino Acid Sequence↗
PubMed1998

Retrotransposon R1Bm endonuclease cleaves the target sequence.

The R1Bm element, found in the silkworm Bombyx mori, is a member of a group of widely distributed retrotransposons that lack long terminal repeats. Some of these elements are highly sequence-specific and others, like the human L1 sequence, are less so. The majority of R1Bm elements are associated with ribosomal DNA (rDNA). R1Bm inserts into 28S rDNA at a specific sequence; after insertion it is flanked by a specific 14-bp target site duplication of the 28S rDNA. The basis for this sequence specificity is unknown. We show that R1Bm encodes an enzyme related to the endonuclease found in the human L1 retrotransposon and also to the apurinic/apyrimidinic endonucleases. We expressed and purified the enzyme from bacteria and showed that it cleaves in vitro precisely at the positions in rDNA corresponding to the boundaries of the 14-bp target site duplication. We conclude that the function of the retrotransposon endonucleases is to define and cleave target site DNA.

Amino Acid Sequence↗
PubMed1998

Reference values for cystatin C serum concentrations in children.

Cystatin C, a low molecular weight protein, is a new endogenous marker of renal function whose serum concentration correlates better with glomerular filtration rate than creatinine. The aim of the present study was to define a reference interval for cystatin C concentrations in children. Cystatin C was measured by an immunoturbidimetric assay in sera obtained from 258 children (93 girls, 165 boys, median age 6.29 years, range 1 day to 18 years) without evidence of kidney disease. The reference interval was calculated non-parametrically using the 2.5th and 97.5th percentiles. For comparison, creatinine was measured in the same samples. The cystatin C concentration was highest on the first days of life (range 1.64-2.59 mg/l) with a rapid decrease during the first 4 months. Beyond the 1st year, the cystatin C concentration was constant, with a reference interval of 0.7-1.38 mg/l. In contrast, serum creatinine concentrations steadily increased with age until adulthood. Compared with creatinine, cystatin C facilitates the recognition of abnormal renal function in children as its reference range is constant beyond the 1st year of life. The higher levels of cystatin C in the 1st year of life probably reflect the low glomerular filtration rate of neonates and infants.

Adolescent↗
PubMed1998

Moloney murine leukemia virus protease expressed in bacteria is enzymatically active.

Replication of Moloney murine leukemia virus requires a readthrough translation mechanism to generate the Gag-Pol polyprotein. One of the final products of this polyprotein is the protease (PR), which is required to generate the mature virion proteins. The assembly of Gag and Gag-Pol polyprotein into a virion followed by activation of the viral protease is necessary to produce a mature, infectious particle. These events are believed to occur near the cell membrane just prior to the budding of the virion. We report here the autoproteolytic activity of the viral PR when a Gag-PR fusion protein is expressed in E. coli. Efficient cleavage at the p12/CA, CA/NC and NC/PR junctions was observed. Thus the Moloney murine leukemia virus PR is capable of cleaving its substrates in the absence of specific host factors.

Endopeptidases↗
PubMed1998

Cystatin C--a new marker of glomerular filtration rate in children independent of age and height.

OBJECTIVES: Serum creatinine is the most common endogenous marker of renal function. The proportionality between creatinine production and muscle mass requires adjustment for height and body composition. The low molecular weight protein cystatin C is produced by all nucleated cells and eliminated by glomerular filtration. Therefore, cystatin C was studied as an alternative marker of glomerular filtration rate (GFR) in children. METHODS: Cystatin C and creatinine were measured in sera from inulin clearance (CIn) examinations performed in 184 children aged 0.24 to 17.96 years. CIn ranged from 7 to 209 mL/min/1.73 m (median, 77). RESULTS: The reciprocal of cystatin C correlated better with CIn (r = 0.88) than the reciprocal of creatinine (r = 0.72). Stepwise regression analysis identified no covariates for the correlation between cystatin C and CIn, whereas height was a covariate for creatinine. Using an estimate of GFR from serum creatinine and height, correlation with CIn was similar to cystatin C, but female gender and dystrophy were associated with an overestimation of GFR. Diagnostic accuracy in the identification of reduced GFR measured as area under the receiver-operating characteristic plot was 0.970 +/- 0.135 (mean +/- SE) for cystatin C and 0.894 +/- 0.131 for creatinine (NS). A cutoff cystatin C concentration of 1.39 mg/L had 90% sensitivity and 86% specificity for detecting abnormal GFR. CONCLUSION: Unlike creatinine, serum cystatin C reflects renal function in children independent of age, gender, height, and body composition.

Adolescent↗