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M Prinz

Publications and source records attributed to M Prinz.

At least 37 records · Page 2Linked to original sources
PubMed2001

Interventional strategies against prion diseases.

Only a few years ago, the idea that transmissible spongiform encephalopathies could be treated pharmacologically would have met with considerable scepticism. Even now, there is no way to cure a patient or animal suffering from a manifest prion disease. But recent, exciting developments seem to indicate that immunological and pharmacological interventions could have some potential for the pre-exposure and post-exposure prophylaxis of prion diseases. Although it is unlikely that we will be able to cure the clinically overt stages of prion diseases in the foreseeable future, palliative and even life-prolonging interventions might no longer be confined to the realm of science fiction.

Animals↗
PubMed2001

Targeting gene-modified hematopoietic cells to the central nervous system: use of green fluorescent protein uncovers microglial engraftment.

Gene therapy in the central nervous system (CNS) is hindered by the presence of the blood-brain barrier, which restricts access of serum constituents and peripheral cells to the brain parenchyma. Expression of exogenously administered genes in the CNS has been achieved in vivo using highly invasive routes, or ex vivo relying on the direct implantation of genetically modified cells into the brain. Here we provide evidence for a novel, noninvasive approach for targeting potential therapeutic factors to the CNS. Genetically-modified hematopoietic cells enter the CNS and differentiate into microglia after bone-marrow transplantation. Up to a quarter of the regional microglial population is donor-derived by four months after transplantation. Microglial engraftment is enhanced by neuropathology, and gene-modified myeloid cells are specifically attracted to the sites of neuronal damage. Thus, microglia may serve as vehicles for gene delivery to the nervous system.

Animals↗
PubMed2001

Similar effects of atorvastatin, simvastatin and pravastatin on thrombogenic and inflammatory parameters in patients with hypercholesterolemia.

BACKGROUND: Previous studies have suggested that statins exert beneficial effects beyond their favorable lipid lowering effect. Particularly, the modification of thrombus formation and degradation, alteration in inflammatory response, plaque stabilization and improved endothelial function are thought to be responsible for additional reduction of morbidity and mortality due to cardiovascular events. To date, however, it is still unclear whether these effects are elicited by all statins. METHODS AND RESULTS: We set out to compare in a controlled, randomized, double-blind study design the effects of almost equieffective cholesterol lowering doses of three chemically and pharmacokinetically different statins (atorvastatin, simvastatin, pravastatin) on hemostatic and inflammatory markers in 99 hypercholesterolemic patients. At entry and 3 months after onset of statin therapy plasma cholesterol and von Willebrand factor antigen (vWf-Ag), fibrinogen, d-dimer, prothrombin fragment 1+2 (F1.2) and C-reactive protein (CRP) were measured. The effect on plasma values of F1.2, vWf-Ag, d-dimer and CRP was not significantly different between the three treatment groups. The effect of simvastatin on fibrinogen (p = 0.005) was more pronounced than the effects of atorvastatin (p = 0.48 n.s.) and pravastatin (p = 0.15 n.s.). Plasma levels of F1.2 and vWf-Ag (when data of all statins were pooled) were significantly reduced by 7% and 10% versus baseline, respectively. No significant reduction was observed for d-dimer (p = 0.26) and CRP (p = 0.5). Total plasma cholesterol levels decreased significantly (p < 0.0001 in all groups) between 22% and 29% compared to baseline. CONCLUSION: The present study shows similar short-term (3 months) effects of atorvastatin, simvastatin and pravastatin on selected hemostatic and inflammatory parameters in plasma in patients with hypercholesterolemia. Thus, chemical and pharmacological differences between statins appear to exert no major influence on these parameters.

Adult↗
PubMed2001

Y chromosome-specific short tandem repeats in forensic casework.

Several case examples are presented to illustrate the usefulness of Y chromosome specific human DNA markers in a forensic setting. The markers used are the tetrameric short tandem repeats (STR's) DYS19, DYS389I, DYS389II, and DYS390. The main advantage of the Y-STR approach is the ability to detect the male component in a mixture of male and female DNA. It is also useful for the determination of the number of semen donors for mixtures of two or more male individuals.

DNA Fingerprinting↗
PubMed2000

Mice trisomic for a bacterial artificial chromosome with the single-minded 2 gene (Sim2) show phenotypes similar to some of those present in the partial trisomy 16 mouse models of Down syndrome.

The Drosophila single-minded (sim) transcription factor, is a master regulator of fruitfly neurogenesis. Recently, we have cloned and mapped a human homolog of sim, SIM2, to chromosome 21 in the so-called 'Down syndrome chromosomal region'. Three copies of SIM2 may contribute to some Down syndrome (DS) phenotypes because of the mapping position function as transcriptional repressor, temporal and spatial expression pattern of mouse Sim2, and the potentially analogous role of human SIM2 to that of Drosophila sim during neurogenesis. In order to validate this hypothesis in vivo, we have created the first bacterial artificial chromosome transgenic mice overexpressing a gene possibly involved in DS with only one or two additional copies of mouse Sim2. The transgene was shown to be expressed in the same spatial pattern as the endogenous gene. The mice develop normally, are fertile and do not show detectable histopathological abnormalities. However, detailed analysis of their behavior revealed anxiety-related/reduced exploratory behaviour and sensitivity to pain, phenotypes similar to those also present in other partial trisomy 16 mouse models of DS. Our data therefore suggest that overexpression of SIM2 contributes to some of the complex DS phenotypes.

Animals↗
PubMed2000

Voltage- and gamma-aminobutyric acid-activated membrane currents in the human medulloblastoma cell line MHH-MED-3.

The whole-cell patch clamp technique was used to characterize voltage- and neurotransmitter-activated currents in the medulloblastoma cell line MHH-MED-3 and cells from tissue slices and primary cultures of two medulloblastoma biopsies. These preparations revealed similar electrophysiological properties. All tested cells displayed 4-aminopyridine-sensitive delayed rectifying K(+) currents, gamma-aminobutyric acid(A) receptor-mediated Cl(-) currents and most of them inward rectifier K(+) currents. Transient inward currents were mainly carried by low-voltage activated T-type Ca(2+) channels in MHH-MED-3 cells, and tetrodotoxin-sensitive Na(+) channels in cells from the primary culture. From these characteristics we conclude that medulloblastoma cells share physiological features with developing cerebellar granule cells at an immature stage.

Adolescent↗
PubMed2000

[Genetic polymorphisms of eight STR loci in a Chinese Han population].

OBJECTIVE: To understand the allele structure and genetic polymorphism at eight STR loci in Chinese Han population and construct a preliminary database. METHODS: EDTA-blood specimens were collected from the unrelated individuals in Chengdu, China. The DNA samples were extracted with Chelex method and were amplified by PCR technique. The PCR products were analyzed by the PAG horizontal electrophoresis with discontinuous buffer system and by the approach of the automated fluorescence detection. RESULTS: Five STR loci consist of simple repeat motifs, while three STR loci contain complex repeat structures. The STR polymorphisms at all of the eight loci have been observed in Chinese Han population. According to the obtained data, the combined exclusion probability and the combined discrimination power for these STR markers in Chinese population are 0.9978 and 0.999 999 992, respectively. CONCLUSION: The obtained data are beneficial to understanding the population genetics of the eight STR loci in Chinese Han population. For forensic genetics, the obtained data can be used to calculate the probabilities dealing with the paternity test and the individual identification.

China↗
PubMed1999

[A preliminary study of human Y chromosome specific short tandem repeat loci]

OBJECTIVE: To understand the allele structure and reveal genetic polymorphism of Y chromosome specific short tandem repeat (Y-specific STR) loci in Chinese Han population. METHODS: The authors used a set of five Y-specific STR loci which were tetrameric tandem repeat loci chosen from the Genome Database. EDTA-blood specimens were collected from the unrelated individuals. DNA was extracted by Chelex method and amplified by the polymerase chain reaction (PCR). The PCR products were analyzed using both the PAGE horizontal electrophoresis with discontinuous buffer system and the automated fluorescence detection approach. RESULTS: The authors observed that the alleles at the five Y-specific STR loci were composed of some complex repeat structures. They successfully prepared a set of human allele ladders for the typing of the five Y-specific STRs and demonstrated the polymorphisms at the five Y-specific STR loci in Chinese Han population. CONCLUSION: Y-specific STRs are good genetic markers for the purpose of analysis of genetic relationship between populations. This preliminary study not only reveals allele frequencies and haplotype distribution of Y-specific STR in Chinese Han population, but also indicates a reference population for detecting male migration events and for reconstructing paternal history.

Journal Article↗
PubMed1999

D20S161 data for three ethnic populations and forensic validation.

In order to evaluate the forensic applicability of the STR locus D20S161 and construct a preliminary database, the genotype distributions and allele frequencies in five populations from three main ethnic groups were investigated, including Germans, Slovakians, African Americans, Japanese and Chinese. A total of 512 samples from unrelated individuals and 85 confirmed father/mother/ child triplets were analyzed by PCR and allele determination was carried out by comparison with a sequenced human allelic ladder. The results showed that D20S161 typing was both precise and reliable. A total of 7 alleles was found in these populations and no evidence of deviation from Hardy-Weinberg equilibrium was observed. Pairwise comparisons between populations showed that there were significant differences in the distributions of the allele frequencies among the three main ethnic groups. No mutation events were observed from the confirmed father/mother/child triplets. With a maximum likelihood method, the mutation rate was indirectly estimated as 2.5 x 10(-5). These results suggest that D20S161 is a useful marker for forensic casework and paternity analysis.

Asian People↗
PubMed1999

Induction of potassium channels in mouse brain microglia: cells acquire responsiveness to pneumococcal cell wall components during late development.

Lipopolysaccharides derived from cell walls of Gram-negative bacteria have proven a useful tool to simulate bacterial infection of the central nervous system. Rapid activation of microglia within the brain parenchyma as well as in vitro has thereby been shown to be an early event upon bacterial or lipopolysaccharide challenges. Less is known about microglial responses to a contact with Gram-positive bacteria, such as Streptococcus pneumoniae, a lethal pathogen causing meningitis with a 30% mortality rate. In the present study, we compared lipopolysaccharide-induced microglial activation in vitro with that induced by preparations of pneumococcal cell walls. As a readout of microglial activation, we studied by patch-clamp recording the expression of outward rectifying potassium currents (IK+OR), which are known to be induced by lipopolysaccharide. We found that pneumococcal cell walls and lipopolysaccharide induced a similar type of IK+OR. Stimulation of IK+OR by pneumococcal cell walls and lipopolysaccharide involved protein synthesis since it was not induced in the presence of cycloheximide. Pharmacological characterization of the pneumococcal cell wall- and lipopolysaccharide-induced currents with specific ion channel blockers indicated for both cases expression of the charybdotoxin/margatoxin-sensitive Kv1.3 subtype of the Shaker family of voltage-dependent potassium channels. Activation of the outward currents by pneumococcal cell walls depended on the developmental stage: while lipopolysaccharide triggered IK+OR in both embryonal and postnatal microglial cells, pneumococcal cell walls had only a marginal effect on embryonal cells. This, however, does not imply that embryonic microglial cells are unresponsive to pneumococcal cell walls. In both embryonic and postnatal cells, (i) the amplitude of the constitutively expressed inward rectifying potassium current was significantly reduced, (ii) tumor necrosis factor-a was released and (iii) the cells changed their morphology, similarly as it was induced by lipopolysaccharide treatment. Thus, embryonic microglial cells are sensitive to pneumococcal cell wall challenges, but respond with a distinctly different pattern of physiological reactions. The expression of IK+OR could thus be a suitable tool to study signalling cascades selectively involved in the activation of microglia by Gram-negative and -positive cell wall components and to functionally distinguish between populations of microglial cells.

Animals↗
PubMed1999

Murine microglial cells produce and respond to interleukin-18.

Interleukin (IL)-18 (interferon-gamma-inducing factor or IL-1gamma) belongs structurally to the IL-1 cytokine family and shares biological properties with IL-12. Expression, intracellular signaling, and functional relevance of IL-18 within the CNS are mostly unknown. We show that IL-18 protein is synthesized within mouse brain, preferentially during early postnatal stages, and that microglial cells but not astrocytes are a potential source. IL-18 is produced by cultured microglia on exposure to lipopolysaccharide (LPS). Microglia also express major components of the IL-1/IL-18 receptor system. On IL-18 stimulation, microglial IL-1 receptor-associated kinase (IRAK) can be coprecipitated with tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) but not with IL-1 receptor type I, indicating that IRAK recruits TRAF6 during IL-18 signaling. IL-18 inhibits the LPS-induced release of IL-12 and attenuates that of TNF-alpha, whereas the production of IL-6 and macrophage inflammatory protein-1alpha is only marginally affected. IL-18 may play a role during CNS development and can be produced by activated microglia, thus probably contributing to immune and inflammatory processes in the brain.

Aging↗
PubMed1999

Microglial activation by components of gram-positive and -negative bacteria: distinct and common routes to the induction of ion channels and cytokines.

Gram-positive Streptococcus pneumoniae is the major pathogen causing lethal meningitis in adults. We used pneumococcal cell walls (PCW) to investigate microglial consequences of a bacterial challenge and to determine the role of serum in the activation process. PCW caused the characteristic induction of an outwardly rectifying K+ channel (IK+(OR)), together with a concomitant suppression of the constitutively expressed inward rectifier K+ current, and evoked the release of tumor necrosis factor-alpha (TNF alpha), interleukin-6 (IL-6), IL-12, KC, macrophage inflammatory protein (MIP) 1alpha and MIP-2. Serum presence strongly facilitated the PCW effects, similarly as observed for lipopolysaccharide (LPS) from gram-negative Escherichia coli. The inflammatory cytokine, interferon-gamma (IFNgamma) induced the same electrophysiological changes, but independent of serum. Recombinant LPS binding protein (LBP) could partially replace serum activity in LPS stimulations. In contrast, neither LBP nor an antibody-mediated blockade of the LPS receptor, CD14 had significant influences on PCW-inducible changes. Cell surface interactions and cofactor involvement in microglial activation by gram-positive bacteria are thus distinct from the mechanisms employed by LPS. Moreover, tyrphostin AG126, a protein kinase inhibitor that prevents activation of the mitogen-activated protein kinase, p42MAPK (ERK2), potently blocked the PCW-stimulated cytokine release while having only a limited effect on LPS-inducible cytokines. In contrast, AG126 did not influence IK+(OR) inductions. This indicates that PCW recruits more than 1 intracellular signaling pathway to trigger the various responses and that different bacterial agents signal through both common and individual routes during microglial activation.

Acute-Phase Proteins↗
PubMed1999

[Genetic polymorphism at FES locus in Chinese and German populations].

OBJECTIVE: The aim of this study on the genetic polymorphism at FES locus was to know whether there is genetic relationship between Chinese and German populations. METHODS: EDTA-blood specimens were collected from 311 healthy unrelated Han individuals in Jilin, Chengdu and Guangzhou in China and from 123 healthy unrelated individuals in Germany. The DNA samples were extracted using Chelex method and amplified by PCR technique. The PAGE horizontal electrophoresis was used for typing the PCR product.DNA sequences were analyzed by ALF. RESULTS: There were nine alleles at FES locus in the Chinese population. The allele frequencies were FES*6,0-0. 0051; FES *8,0-0.0042; FES*9,0.0083-0.0202; FES*10,0.0202-0.0604; FES*11,0.4066-0.5101; FES*12,0.2424-0.3099;FES*13, 0.1860-0.2198; FES*14,0.0041-0.0165; and FES*15,0-0.0050, respectively. In the German population, a variation in 5 flanking region and nine alleles at FES locus were noted. The allele frequencies were FES*8,0.0120; FES*10a,0.02317; FES*10,0.0407; FES*11a,0.0122; FES*11,0.4146; FES*12a, 0.0041; FES*12, 0.2357; FES*13, 0.0447; and FES*14, 0.0041, respectively. The results of test for Hardy-Weinberg equilibrium showed that the genotype distributions observed in the populations were correspondent with the expected. CONCLUSION: There is a remarkable difference in the distribution of allele frequencies at FES locus between Chinese and German populations.

Alleles↗
PubMed1999

[Genetic polymorphisms of five STR loci in a Chinese Han population].

OBJECTIVE: To understand the allele structure and genetic polymorphism at five STR loci in Chinese Han population, and construct a preliminary database. METHODS: EDTA-blood specimens were collected from the unrelated individuals. The DNA samples were extracted with Chelex method and were amplified by PCR technique. The PCR products were analyzed using both the PAGE horizontal electrophoresis with discontinuous buffer system and the automated fluorescence detection approach. RESULTS: Four STRs consist of simple repeat motifs, while one STR contains a complex repeat structure. The STR polymorphisms at all of the five loci have been observed in Chinese Han population. CONCLUSION: The obtained data are beneficial to understanding the population genetics of the five STR loci in Chinese Han population. As a simple approach, the PAGE horizontal electrophoresis can be employed for typing the five STR markers.

Alleles↗
PubMed1999

Frequencies of D8S384 alleles and genotypes in European, African-American, Chinese, and Japanese populations.

D8S384 is a tetranucleotide tandem repeat locus. In order to evaluate the forensic validation of D8S384, the genotype distributions and allele frequencies in ten populations from three main ethnic groups were investigated, including Germans, Slovakians, African Americans, Japanese, and Chinese (Jilin, Guangzhou, Nanning, Hailaer, Dali, and Chengdu). A total of 1011 unrelated individuals, 41 pedigrees, 30 disputed paternity trios and three personal identification cases were analyzed for D8S384 by Amp-FLP technique. Many kinds of tissues, body fluids, secreta and stains have been tested. The alleles were determined by comparison with a human allele ladder. The results showed that D8S384 typing was both precise and reliable. There were eight alleles in these populations. The genotype distributions conformed to Hardy-Weinberg equilibrium predictions. No mutation events were observed. With a maximum likelihood method, the mutation rate was indirectly estimated as 2.14 x 10(-5). The heterozygosity was 0.704 +/- 0.014 at D8S384 locus. All these results suggest that D8S384 locus is a useful marker for forensic identification and paternity analysis.

Adult↗
PubMed1998

Alternative splicing of mouse IL-15 is due to the use of an internal splice site in exon 5.

IL-15 is a pleiotropic cytokine modulating growth and differentiation of several hematopoietic cell types. Recently, we have demonstrated that mouse microglial cells, the brain macrophages, express both IL-15 and IL-15/IL-2 receptors. Based on single-cell RT-PCR data, we describe here an alternatively spliced IL-15 mRNA variant found in a small subpopulation of mouse microglia (5%, 3 out of 60 cells expressing IL-15 transcripts). PCR cycle sequencing of this larger transcript revealed the mouse homologue of the alternatively spliced exon A as it is known from the human IL-15 gene. Analysis of the corresponding mouse IL-15 gene region shows that the larger IL-15 transcript contains an yet unidentified 5' sequence of exon 5 while the shorter transcript uses an internal splice acceptor site. The mouse exon 5A segment has a length of 136 nt (17 nt longer than the human exon A). It contains five in-frame stop codons at its 5' end and a new translation initiation site at its 3' end. This new start site is surrounded by a favourable Kozak consensus sequence suggesting a more efficient translation rate. Further translational control by stem-loop binding factors is inferred by a predicted RNA stem-loop structure around the start site. Insertion of exon 5A would lead to an IL-15 polypeptide with a shortened leader sequence of 26 amino acids, as compared to the 48 amino acid leader sequence encoded by the transcript lacking exon 5A. Thus, the final IL-15 protein of the two splice variants is identical; different leader sequences could, however, lead to differences in the intracellular sorting, processing and/or secretion of IL-15.

Alternative Splicing↗
PubMed1998

The university training programs in Austria.

A description is given of Austria's currently operational framework of training opportunities and post-doctoral courses in Medical Informatics. The description includes a brief outline of the currently valid curriculum in informatics and the methods on how to specialise in medical informatics within this framework.

Austria↗