Search Results - (Author, Cooperation:C. Epstein)

2018-04-20

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Geosciences

Computer Science

Medicine

Natural Sciences in General

Physics

Physics

2014-12-24

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Binding Sites ; Cell Differentiation/*genetics ; Cell Lineage/genetics ; Embryonic Stem Cells/*cytology/metabolism ; Epigenesis, Genetic/*genetics ; Epigenomics/*methods ; Humans ; Neural Stem Cells/*cytology/*metabolism ; RNA, Small Interfering/analysis/genetics ; Reproducibility of Results ; Transcription Factors/metabolism ; Transcription, Genetic/genetics

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract: Copper/zinc-superoxide dismutase (CuZn-SOD) transgenic mice overexpress the gene for human CuZn-SOD. To assess the effects of the overexpression of CuZn-SOD on the brain scavenging systems, we have measured the activities of manganese-SOD (Mn-SOD), catalase, and glutathione peroxidase (GSH-Px) in various regions of the mouse brain. In nontransgenic mice, cytosolic CuZn-SOD activity was highest in the caudate–putamen complex; this was followed by the brainstem and the hippocampus. The lowest activity was observed in the cerebellum. In transgenic mice, there were significant increases of cytosolic CuZn-SOD activity in all of these regions, with ratios varying from a twofold increase in the brainstem to 3.42-fold in the cerebellum in comparison with nontransgenic mice. Particulate Mn-SOD was similarly distributed in all brain regions, and its levels also were significantly increased in superoxide dismutase (SOD)-transgenic mice. In the brains of nontransgenic mice, cytosolic catalase activity was similar in all brain regions except the cortex, which showed 〈50% of the activity observed in the other regions. In transgenic mice, cytosolic catalase activity was significantly increased, with the cortex showing the greatest changes (133%) in comparison with nontransgenic mice. The smallest increases were observed in the hippocampus (34%). In contrast to what was observed for SOD and catalase, there were no significant changes in cytosolic GSH-Px activity in any of the brain regions examined. The present results indicate that, in addition to displaying marked increases in the levels of brain CuZn-SOD activity, SOD-transgenic mice also exhibit increases in other enzymes that scavenge oxygen-based radicals. We also found that aminotriazole caused significantly greater inhibition of brain catalase activity in SOD-transgenic mice (67.6%) than in nontransgenic littermates (43.6%). The latter finding provides evidence for a higher production of H2O2 in the brains of SOD-transgenic mice. When taken together, these results further support the use of these animals to assess the role of free radicals in ischemia/reperfusion and in the aging process.

Electronic Resource

1749-6632

Blackwell Publishing Journal Backfiles 1879-2005

Natural Sciences in General

Electronic Resource

1440-1681

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

1. Inhibitors of nitric oxide (NO) formation or ADP-ribosylation attenuate methamphetamine (METH)- and methyl-enedioxymetamphetamine (MDMA)-induced neurotoxicity on dopaminergic and serotonergic cells in primary cultures.2. They also prevent METH-induced reactive gliosis in dopaminergic cultures.3. Overexpression of superoxide dismutase (SOD) in cells obtained from SOD-transgenic mice also attenuates drug-induced toxicity.4. These data indicate a role for oxygen-based and NO free radicals in the mechanisms of cell death associated with drugs of abuse in vitro.

Electronic Resource

1476-4687

Nature Archives 1869 - 2009

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

[Auszug] Fig. 1 Metaphase spreads from membranes of trisomic mouse embryos prepared as described by Evans et a.15, a, Trisomy 1; b, trisomy 12. The two metacentric chromosomes indicative of the trisomic state are indicated by arrows in each spread. Males doubly heterozygous for two different metacentric ...

Electronic Resource

1420-9071

Developmental genes ; developmental disorders ; chromosome abnormalities ; animal models

Springer Online Journal Archives 1860-2000

Biology

Medicine

Summary Of particular concern to the human geneticist are the effects of genetic abnormalities on development. To gain an understanding of these effects it is necessary to engage in a reciprocal process of using knowledge of normal developmental events to elucidate the mechanisms operative in abnormal situations and then of using what is learned about these abnormal situations to expand our understanding of the normal. True developmental genes have not been described in man, although it is likely that they exist, but many developmental abnormalities are ascribable to mutations in genes coding for enzymes and structural proteins. Some of these even produce multiple malformation syndromes with dysmorphic features. These situations provide a precedent for asserting that not only monogenic developmental abnormalities, but also abnormalities resulting from chromosome imbalance must ultimately be explicable in molecular terms. However, the major problem confronted by the investigator interested in the pathogenesis of any of the chromosome anomaly syndromes is to understand how the presence of an extra set of normal genes or the loss of one of two sets of genes has an adverse effect on development. Several molecular mechanisms for which limited precedents exist may be considered on theoretical grounds. Because of the difficulties in studying developmental disorders in man, a variety of experimental systems have been employed. Particularly useful has been the mouse, which provides models for both monogenic and aneuploidy produced abnormalities of development. An example of the former is the mutation oligosyndactylism which in the heterozygous state causes oligosyndactyly and in the homozygous state causes early embryonic mitotic arrest. All whole arm trisomies and monosomies of the mouse can be produced experimentally, and of special interest is mouse trisomy 16 which has been developed as an animal model of human trisomy 21 (Down syndrome). In the long run, the most direct approach to elucidating the genetic problems of human development will involve not only the study of man himself but also of the appropriate experimental models in other species.

Electronic Resource

0037-7996

History

1432-0584

Akute Leukämien ; Plasma-Gerinnsel-Kultur ; Acute leukemia ; Plasma clot culture

Springer Online Journal Archives 1860-2000

Medicine

Summary Human normal and granulocytic leukemic progenitor cells produce colonies and clusters when cultured in the plasma clot system in vitro. The number of colonies formed and their cellular composition was comparable to that reported for the system (soft agar) usually used for these studies. The plasma clot system has the advantage of permitting in situ morphologic and cytochemical characterization of the cells within the colonies. A comparison was also made of the growth of leukemic cells in suspension cultures placed within conventional and modified Marbrook flasks. These studies demonstrated no advantage for the Marbrook system in cultures incubated for up to 7 days.

Zusammenfassung In einem Plasma-Gerinnselsystem bilden normale menschliche Vorläuferzellen der Hämatopoese und leukämische Zellen bei myeloischer Leukämie Kolonien und Cluster. Anzahl und Zusammensetzung der gebildeten Kolonien sind den Verhältnissen vergleichbar, die von anderen Systemen her bekannt sind (Agar), welche gewöhnlich für diese Untersuchungen verwendet werden. Das hier vorgestellte Plasma-Gerinnselsystem hat den Vorteil, daß die Zellen der gebildeten Kolonien in situ morphologisch und zytochemisch charakterisiert werden können. Diese Ergebnisse werden ebenfalls verglichen mit dem Wachstum leukämischer Zellen in Suspensionskulturen innerhalb konventioneller und modifizierter Marbrook-Flaschen. Die hier vorgelegten Studien belegen, daß das Marbrook-System für Kulturen, die bis zu 7 Tage inkubiert werden, keine Vorteile besitzt.

Electronic Resource

1432-1203

Springer Online Journal Archives 1860-2000

Biology

Medicine

Summary Trisomy 21 human fibroblasts are more sensitive to human interferon-α (IFN-α) than are diploid controls, consistent with the location of the gene (IFRC) which codes for the IFN-α receptor on chromosome 21. When compared in the antiviral assay, the difference in sensitivity is five-to tenfold, much greater then the 50% difference in IFRC gene dosage. An understanding of the mechanism by which this amplification of gene dosage occurs is relevant to the specific pathology of Down's syndrome and as a model system for studying the pathogenic effects of chromosomal aneuploidy. The enzyme (2′–5′) oligoisoadenylate synthetase (2–5A synthetase), which is believed to be central to the interferon-induced antiviral response, is induced 50% more in trisomy 21 fibroblasts than in diploid controls. Thus the amplification in response occurs subsequent to the binding of IFN-α to its receptor and the triggering of the first set of intracellular events, the latter exemplified by the induction of 2–5A synthetase. Similar results were obtained with IFN-γ, consistent with other evidence which indicates that a gene coding for a separate IFN-γ receptor is also located on chromosome 21.

Electronic Resource

1432-0738

Springer Online Journal Archives 1860-2000

Medicine

Electronic Resource

1432-1203

Springer Online Journal Archives 1860-2000

Biology

Medicine

Summary A technique for isolating DNA sequences that are likely to be transcriptionally active in both humans and mice has been developed. This method is based on the screening of a human genomic DNA library with single stranded cDNA prepared from late gestation mouse fetal RNA. Using a human chromosome 21 DNA library, we have isolated and characterized two clones which are entirely composed of single copy human DNA sequences and are 2.7 and 6.7 kilobases in length. The 2.7 kilobase clone is homologous to a transcript found predominantly in nonpolyadenylated human fibroblast RNA. It also shows homology to mouse genomic DNA and recognises several polyadenylated RNAs in mouse testis. This cloned sequence has been mapped by in situ hybridization to the distal third of chromosome 21, the region involved in the causation of Down syndrome.

Electronic Resource

1432-1297

Springer Online Journal Archives 1860-2000

Mathematics

Electronic Resource

1871-2509

Springer Online Journal Archives 1860-2000

Mathematics

Electronic Resource

1871-2509

Springer Online Journal Archives 1860-2000

Mathematics

Electronic Resource

1432-1777

Springer Online Journal Archives 1860-2000

Biology

Medicine

Abstract A highly sensitive method for the mapping of transgenes and other genes in the mouse genome is described. This technique combines high-resolution G-banding and fluorescence in situ hybridization (FISH) with either biotin/avidin-FITC or digoxigenin-anti-digoxigenin-FITC, the latter being the more sensitive. Banding patterns are obtained with trypsin/Geimsa-treated slides, and sensitivity is greatly increased by the use of mouse Cot-1 DNA. With this protocol, four different 14.5-kb human Cu/Zn-superoxide dismutase transgene insertions ranging in copy number from 2 to 8 have been localized to four different mouse chromosomes. The utility and sensitivity of this procedure were verified with a Chromosome (Chr) 16-specific cosmid probe, H22, as well as with the mapping of a high-copy-number human β-amyloid/A4 transgene.

Electronic Resource