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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Human genetics 〈Berlin〉 101 (1997), S. 190-197 
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Gene amplification, which occurs in more than 50% of malignant gliomas, is considered to play a pivotal role in tumorigenesis. There are, however, few studies aimed toward the isolation of novel genes from amplified sequences. Previously, we reported amplification of the protooncogene MET (hepatocyte growth factor receptor; 7q31) in more than 20% of glioblastomas. For an approximate size estimation of the amplification unit we analyzed three glioblastomas all of which carried an amplified MET gene, by Southern blot analysis and/or competitive polymerase chain reaction using eight DNA markers. Although the extent of the amplified domain varied, the close vicinity of the MET gene was the only region consistently amplified in these glioblastomas. A yeast artificial chromosome (YAC) contig of 900 kb was refined spanning the amplified region flanking the MET gene. The YAC inserts were subcloned into 59 cosmids, which were used for exon trapping. Eight sequences were identical to parts of the genes MET and CAPZA2 (human actin capping protein α-subunit). Two newly identified exons and the CAPZA2 exons were amplified in tumor TX3095, which retains an amplified MET gene. The new exons were localized close to MET and CAPZA2. Characterization of the clones, which were termed glioma-amplified sequence (GAS)7-1 and GAS7-2, showed an open reading frame and a different expression pattern in multiple human tissues. This study reports the identification of a cluster of amplified genes including two novel genes in a region amplified in more than 20% of glioblastomas.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Human genetics 〈Berlin〉 100 (1997), S. 172-181 
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Holoprosencephaly (HPE) is a genetically heterogeneous disorder that affects the midline development of the forebrain and midface in humans. As a step toward identifying one of the HPE genes, we have set out to refine the HPE3 critical region on human chromosome 7q36 by analyzing 34 cell lines from families with cytogenetic abnormalities involving 7q, 24 of which are associated with HPE. Genomic clones surrounding the DNA marker D7S104, which has previously been shown to be in the HPE3 critical region, have been examined by fluorescent in situ hybridization and microsatellite analysis of our panel of patient cell lines. We report the analysis of a cluster of four translocation breakpoints within a 300-kb region of 7q36 that serves to define the minimal critical region for HPE3 and that has directed the search for candidate genes. The human Sonic Hedgehog (hSHH) gene maps to this region and has been shown to be HPE3 on the basis of mutations within the coding region of the gene. We present evidence that cytogenetic deletions and/or rearrangements of this region of chromosome 7q containing Sonic Hedgehog, and translocations that may suppress Sonic Hedgehog gene expression through a position effect are common mechanisms leading to HPE.
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  • 3
    Electronic Resource
    Electronic Resource
    [s.l.] : Macmillian Magazines Ltd.
    Nature 434 (2005), S. 325-337 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise ...
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  • 4
    Electronic Resource
    Electronic Resource
    [s.l.] : Macmillian Magazines Ltd.
    Nature 428 (2004), S. 493-521 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality ‘draft’ ...
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  • 5
    Electronic Resource
    Electronic Resource
    [s.l.] : Macmillian Magazines Ltd.
    Nature 409 (2001), S. 945-946 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Our sequence-tagged site-content map of chromosome 12 is now integrated with the whole-genome fingerprinting effort. It provides accurate and nearly complete bacterial clone coverage of chromosome 12. We propose that this integrated mapping protocol serves as a model for constructing physical ...
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neurocytology 28 (1999), S. 333-347 
    ISSN: 1573-7381
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the localization of Caspr and the K+ channels Kv1.1 and Kv1.2, all of which are intrinsic membrane proteins of myelinated axons in the PNS. Caspr is localized to the paranode; Kv1.1, Kv1.2 and their β2 subunit are localized to the juxtaparanode. Throughout the internodal region, a strand of Caspr staining is flanked by a double strand of Kv1.1/Kv1.2/Kvβ2 staining. This tripartite strand apposes the inner mesaxon of the myelin sheath, and forms a circumferential ring that apposes the innermost aspect of Schmidt-Lanterman incisures. The localization of Caspr and Kv1.2 are not disrupted in mice with null mutations of the myelin associated glycoprotein, connexin32, or Kv1.1 genes. At all of these locations, Caspr and Kv1.1/Kv1.2/Kvβ2 define distinct but interrelated domains of the axonal membrane that appear to be organized by the myelin sheath.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neurocytology 13 (1984), S. 519-565 
    ISSN: 1573-7381
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The features of unlesioned and lesioned trochlear nerves of goldfish have been examined electron microscopically. Lesioned nerves were studied between 1 and 107 days after cutting or crushing the nerve. 1. Unlesioned nerves contained, on average, 77 myelinated axons and 19 unmyelinated axons. The latter were found in 1–2 fascicles per nerve. A basal lamina surrounded each myelinated axon and fascicle of unmyelinated axons. The numbers of myelinated axons, fascicles of unmyelinated axons and basal laminae varied by less than 5% over the intraorbital extramuscular segment of the nerve. 2. Following interruption of the nerve, by either cutting or crushing, all of the axons and their myelin sheaths began to degenerate by 4 days in the distal nerve-stump. Both abnormally electron-dense and electron-lucent axons were observed. Both Schwann cells and macrophages appeared to phagocytose the myelin sheaths. 3. Following a lesion, the Schwann cells and their basal laminae persisted in the distal nerve-stump. In crushed nerves, the basal laminae surrounding myelinated axons formed 97%, on average, of the Schwann tubes in the distal stump. The perimeters of the basal laminae were of similar size to those in the proximal stump, at least for the first 8 days after crush. 4. In crushed nerves, single myelinated axons in the proximal nerve-stump gave rise to multiple sprouts, some of which reached the site of crush by 2 days, the distal stump by 4 days and the superior oblique muscle by 8 days. The regeneration of the unmyelinated axons was not examined. 5. In both crushed and transected nerves, nearly all of the sprouts in the proximal and distal stumps were found within the basal laminae of Schwann cells, even though the sprouts were disorganized in the transected region where there were no basal laminae. The growth cones of the regenerating axons were always found apposed to the inner surface of the basal laminae, which may have provided an adhesive substrate that directed their growth. 6. Terminal sprouts from the ends of myelinated axons in the proximal stump accounted for the majority of the regenerating axons in the distal stump, as only a few collateral sprouts were found in the proximal stump, and only a small amount of axonal branching was found within the distal stump itself. 7. The largest axons in the distal stump were remyelinated first, and the number of remyelinated axons increased progressively between 8 and 31 days after crush, at which time there were about twice as many as in unlesioned nerves. The number of remyelinated axons remained constant at least until 107 days, the longest time considered, and none was observed to degenerate, whereas some axons that were not remyelinated appeared to degenerate. 8. Although each basal lamina in the distal stump often surrounded several regenerating axons during the first 2 weeks post-lesion, each remyelinated axon became individually surrounded by a basal lamina, collagen fibres and extracellular space between 13 and 107 days, thereby increasing the number of basal laminae in the distal stump. 9. Regenerated axonal terminals in the superior oblique were first observed 8 days after crush. The number of synapses increased progressively between 8 and 107 days, at which time they were as numerous as in unlesioned animals.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Mammalian genome 9 (1998), S. 136-143 
    ISSN: 1432-1777
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. We have cloned and characterized the Na,K-ATPase β3 subunit gene (ATP1B3), and a β3 subunit pseudogene (ATP1B3P1), from a human PAC genomic library. The β3 subunit gene is 〉50 kb in size and is split into 7 exons. The exon/intron organization of the β3 subunit gene is identical to that of the Na,K-ATPase β3 subunit gene, indicating that these two genes evolved from a common evolutionary ancestor. Comparison of the promoter region of the human and mouse β3 subunit gene reveals a high degree of homology within a 300-bp segment located immediately upstream of the translation start site, suggesting that control elements that serve to regulate the cell-specific expression of the β3 subunit gene are likely to be located within this conserved region. Dot blot analysis of β3 subunit transcripts revealed expression within virtually all human tissues, while in situ hybridization showed expression of β3 mRNA in both neurons and glia of rat brain. Fluorescence in situ hybridization with PAC DNA clones localized ATP1B3 to the q22 → 23 region of Chromosome (Chr) 3, and the β3 pseudogene to the p13 → 15 region of Chr 2.
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  • 9
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature genetics 11 (1995), S. 226-228 
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] While inherited peripheral neuropathies have been recognized for more than a century1, the molecular basis of forms with demyelina-tion has only been established within the past three years2. A variety of genetic alterations affecting one of three genes, myelin protein zero (P0), peripheral myelin ...
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