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  • 1
    Electronic Resource
    Electronic Resource
    Overexpression of mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase does not correct glucose-stimulated insulin secretion from diabetic GK rat pancreatic islets (1998)
    Springer
    Diabetologia 41 (1998), S. 649-653 
    Details
    ISSN: 1432-0428
    Keywords: Keywords FAD-linked glycerol-3-phosphate dehydrogenase ; GK rat ; non-insulin-dependent diabetes mellitus ; insulin secretion ; adenovirus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glucose-stimulated insulin secretion is impaired in GK (Goto-Kakizaki) rats, perhaps because of abnormalities in glucose metabolism in pancreatic islet beta cells. The glycerol phosphate shuttle plays a major role in glucose metabolism by reoxidizing cytosolic NADH generated by glycolysis. In the pancreatic islets of GK rats, the activity of mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase (mGPDH), the key enzyme of the glycerol phosphate shuttle, is decreased and this abnormality may be responsible, at least in part, for impaired glucose-stimulated insulin secretion. To investigate this possibility, we overexpressed mGPDH in islets isolated from GK rats via recombinant adenovirus-mediated gene transduction, and examined glucose-stimulated insulin secretion. In islets isolated from diabetic GK rats at 8 to 10 weeks of age, glucose-stimulated insulin secretion was severely impaired, and mGPDH activity was decreased to 79 % of that in non-diabetic Wistar rats. When mGPDH was overexpressed in islets from GK rats, enzyme activity and protein content increased 2- and 6-fold, respectively. Basal (3 mmol/l glucose) and glucose-stimulated (20 mmol/l) insulin secretion from the Adex1CAlacZ-infected GK rat islets were, respectively, 4.4 ± 0.7 and 8.1 ± 0.7 ng · islet−1· 30 min−1, and those from mGPDH-overexpressed GK rat islets 4.7 ± 0.3 and 9.1 ± 0.8 ng · islet−1· 30 min−1, in contrast to those from the Adex1CAlacZ-infected non-diabetic Wistar rat islets (4.7 ± 1.6 and 47.6 ± 11.9 ng · islet−1· 30 min−1). Thus, glucose-stimulated insulin secretion is severely impaired in GK rats even in the stage when mGPDH activity is modestly decreased, and at this stage, overexpression of mGPDH cannot restore glucose-stimulated insulin secretion. We conclude that decreased mGPDH activity in GK rat islets is not the defect primarily responsible for impaired glucose-stimulated insulin secretion. [Diabetologia (1998) 41: 649–653]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050963
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  • 2
    Electronic Resource
    Electronic Resource
    Protection of islet allografts transplanted together with Fas ligand expressing testicular allografts (1998)
    Springer
    Diabetologia 41 (1998), S. 315-321 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Fas ; Fas ligand ; islet transplantation ; testicular tissue ; apoptosis ; composite graft.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fas ligand (FasL) is highly expressed in testicular tissues and thought to be responsible for protection from allograft rejection by inducing apoptosis of anti-graft activated T cells. FasL-expressing islets have been shown to induce a granulocyte-mediated inflammatory reaction. We investigated whether a graft can be protected from alloimmune responses by manipulating the Fas/FasL-system. We transplanted allogeneic islets under the kidney capsule of streptozotocin-induced diabetic mice together with testicular tissue. Significant prolongation of survival of C3H islet allograft was observed in C57BL/6 (B6) recipients transplanted with C3H testicular tissue, but not in those transplanted with C3H-gld testicular tissue expressing non-functional FasL. No significant prolongation was observed in B6-lpr recipients expressing non-functional Fas. Immunohistochemical staining of C3H testicular tissue in the composite graft showed a high expression of FasL, but not that of the C3H-gld testicular tissue. In situ terminal deoxynucleotidyl transferase-mediated dUDP-biotin catalysed DNA nick-end labelling (TUNEL) staining of a composite graft of C3H islet and testicular tissue in B6 recipients demonstrated extensive apoptosis of infiltrating mononuclear cells around the graft. The protective effect of C3H testicular tissue was abrogated when anti-FasL monoclonal antibody was administered i. p. postoperatively. Our results suggest that FasL-positive testicular allografts protect composite islet allografts and indicate that manipulation of Fas/FasL mediated apoptosis is a suitable strategy for controlling rejection of islet allografts. [Diabetologia (1998) 41: 315–321]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050909
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  • 3
    Electronic Resource
    Electronic Resource
    Overexpression of dominant negative mutant hepatocyte nuclear factor (HNF)-1α inhibits arginine-induced insulin secretion in MIN6 cells (1999)
    Springer
    Diabetologia 42 (1999), S. 887-891 
    Details
    ISSN: 1432-0428
    Keywords: Keywords MODY ; hepatocyte nuclear factor-1α ; recombinant adenovirus ; MIN6 cells ; dominant negative effect ; arginine.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. To explain the mechanisms whereby mutations in the HNF-1α gene cause insulin secretory defects. Methods. A truncated mutant HNF-1α (HNF-1α288 t) was overexpressed in hepatoma cells (HepG2) and murine insulinoma cells (MIN6) using a recombinant adenovirus system and expression of the HNF-1α target genes and insulin secretion were examined. Results. Expression of phenylalanine hydroxylase and α1-antitrypsin genes, the target genes of HNF-1α, was suppressed in HepG2 cells by overexpression of HNF-1α288 t. In MIN6 cells, overexpression of HNF-1α288 t did not change insulin secretion stimulated by glucose (5 mmol/l and 25 mmol/l) or leucine (20 mmol/l). Potentiation of insulin secretion by arginine (20 mmol/l, in the presence of 5 mmol/l or 25 mmol/l glucose) was, however, reduced (p 〈 0.0001 and p = 0.027, respectively). Similarly reduced responses were observed when stimulated with homoarginine. Expression of the cationic amino acid transporter-2 was not reduced and insulin secretory response to membrane depolarization by 50 mmol/l KCl was intact. Conclusion/interpretation. The HNF-1α288 t, which is structurally similar to the mutant HNF-1α expressed from the common MODY3 allele, P291fsinsC, exerts a dominant negative effect. Suppression of HNF-1α in MIN6 cells severely impaired potentiation of insulin secretion by arginine, whereas glucose-stimulated and leucine-stimulated insulin secretion was intact. Our findings delineate the complex nature of beta-cell failure in patients with MODY3. This cell model will be useful for further investigation of the mechanism of insulin secretory defects in these patients. [Diabetologia (1999) 42: 887–891]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051242
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  • 4
    Electronic Resource
    Electronic Resource
    Identification and genetic mapping of Xenopus TAP2 genes (1999)
    Springer
    Immunogenetics 49 (1999), S. 171-182 
    Details
    ISSN: 1432-1211
    Keywords: Key words MHC ; Transporter ; Evolution ; PCR cloning ; Allelic lineage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The amphibian Xenopus laevis is one non-mammalian vertebrate in which the major histocompatibility complex (MHC) has been analyzed extensively. Class IIβ, class Ia, LMP2, LMP7, HSP70, C4, Factor B, and Ring3 genes have been identified and mapped to the MHC. Here, we report the isolation of a transporter associated with antigen processing (TAP) gene, TAP2, and demonstrate its linkage to the MHC. While the ATP-binding region of Xenopus TAP2 is highly conserved in evolution, amino acid identity to other vertebrate TAP proteins was not detected in the N-terminal region. Segregation analysis of 34 individuals from two families showed exact restriction fragment length polymorphism matching between the MHC class Ia gene and the one TAP2 gene demonstrating linkage conservation since the mammalian/amphibian divergence ∼350 million years ago. In addition, one non-MHC-linked TAP2–hybridizing fragment was detected in approximately half of the individuals tested. Interestingly, TAP2 allelic lineages appear to match those of LMP7 and classical class I, which previously were categorized into two highly divergent groups that emerged at least 60 million years ago. Similar to LMP7 and class Ia,TAP2 is expressed ubiquitously with highest levels in intestine and spleen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050478
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  • 5
    Electronic Resource
    Electronic Resource
    Isolation of transporter associated with antigen processing genes, TAP1 and TAP2, from the horned shark Heterodontus francisci (1999)
    Springer
    Immunogenetics 49 (1999), S. 981-986 
    Details
    ISSN: 1432-1211
    Keywords: Key words Transporter ; Shark ; MHC ; cDNA sequence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050582
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  • 6
    Electronic Resource
    Electronic Resource
    Picard–Fuchs equations and Whitham hierarchy in N=2 supersymmetric SU(r+1) Yang–Mills theory (1999)
    College Park, Md. : American Institute of Physics (AIP)
    Journal of Mathematical Physics 40 (1999), S. 6292-6301 
    Details
    ISSN: 1089-7658
    Source: AIP Digital Archive
    Topics: Mathematics , Physics
    Notes: In general, Whitham dynamics involves infinitely many parameters called Whitham times, but in the context of N=2 supersymmetric Yang–Mills theory it can be regarded as a finite system by restricting the number of Whitham times appropriately. For example, in the case of SU(r+1) gauge theory without hypermultiplets, there are r Whitham times and they play an essential role in the theory. In this situation, the generating meromorphic one-form of the Whitham hierarchy on the Seiberg–Witten curve is represented by a finite linear combination of meromorphic one-forms associated with these Whitham times, but it turns out that there are various differential relations among these differentials. Since these relations can be written only in terms of the Seiberg–Witten one-form, their consistency conditions are found to give the Picard–Fuchs equations for the Seiberg–Witten periods. © 1999 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.533093
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  • 7
    Electronic Resource
    Electronic Resource
    Surface magnetic anomaly study on the eastern part of the Forlandsundet Graben (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Polar research 14 (1995), S. 0 
    Details
    ISSN: 1751-8369
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geography , Geosciences
    Notes: A surface magnetic survey was carried out by use of a proton magnetometer over wide strandflats along the eastern coast of Forlandsundet, western Spitsbergen, to decipher subsurface structures and lithologies. Distinctive linear high-anomaly segments and zones were recognised on the magnetic anomaly maps. These zones coincide well with the eastern marginal fault of the Tertiary Forlandsundet Graben and associated faults north of St Jonsfjorden, while they reflect bedrock lithologies in the south. The high-anomaly segments, which constitute the zones, are locally aligned in a left-stepping, en echelon arrangement within the zones, indicating a dextral transpressional stress regime on the eastern marginal fault of the graben during a certain time. Sudden termination and bends of the segments define a later transverse fault system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1751-8369.1995.tb00710.x
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  • 8
    Electronic Resource
    Electronic Resource
    Additional Rb-Sr and single-grain zircon datings of Caledonian granitoid rocks from Albert I Land, northwest Spitsbergen (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Polar research 15 (1996), S. 0 
    Details
    ISSN: 1751-8369
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geography , Geosciences
    Notes: Previous K-Ar and Rb-Sr datings of the metamorphic and granitic rocks from the northwestern basement region of Spitsbergen mainly show the cooling time of the rocks, except for a Rb-Sr isochron age of the Hornemantoppen granitoid. New samples were collected during several years of geological mapping in the area and the Rb-Sr whole rock isochron and single-grain zircon evaporation methods were applied to the Hornemantoppen granitoids and the grey granites. A dioritic dyke was also dated by the latter method. The bulk rock chemistry study shows that most of both granitic rocks are of the S-type and probably post orogenic, with distinctive incorporation of crustal materials. The isotopic data also support this interpretation. The results of the Rb-Sr isotope analyses, 412 ± 4.8 Ma and the zircon Pb evaporation age of 424 ± 56 Ma, confirm the previous age of the Hornemantoppen granitoid, 414 ± 10 Ma. An older zircon age of 547 ± 19 Ma is considered to be the minimum age of inherited zircon. Zircons from the grey granites suggest an age of ca. 420 Ma with a large error. Field relations demonstrate that the grey granites are older than the Hornemantoppen granitoids. A minimum inherited zircon age, 952 ± 20 Ma, has been obtained from the grey granites. Three multi-grain Pb ages, 423 ± 22 Ma (2 grains), 461 ± 42 Ma and 561 ± 93 Ma (the last two 3 grains) were considered to be mixed ages. Although no definitive evidence for the presence of Grenvillian granites in this area has been obtained in the present study, preliminary results from the multi-grain zircon evaporation method, carried out in the Russian laboratory at Apatity, infer Paleo- and Mesoproterozoic protoliths for the metamorphic rocks of northwestern Spitsbergen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1751-8369.1996.tb00466.x
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  • 9
    Electronic Resource
    Electronic Resource
    Newtontoppen granitoid rocks, their geology, chemistry and Rb-Sr age (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Polar research 15 (1996), S. 0 
    Details
    ISSN: 1751-8369
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geography , Geosciences
    Notes: A post-tectonic Caledonian granite in southern Ny Friesland has been fully mapped and the following new names are proposed: the Chydeniusbreen granitoid suite, consisting of the Raudberget granitoid body in the north; the Newtontoppen granitoid body in the middle; and the Ekkoknausane granitoid body in the southThe contact relationships, internal structures and distribution of various rock types infer an asymmetric lopolith or a harpolith-like body, a large sickle-shaped intrusion stretched in the direction of general tectonic transport, for the Newtontoppen granitoid body.Seven rock types are described in the Newtontoppen granitoid and four emplacement stages are recognised. The major rock types seem to have an alkali-calcic to alkalic bulk rock chemistry and show a transition between I- and S-type granite derived from anatectic melting of various protoliths under relatively high temperature conditions. Possible later K20 introduction modified the earlier formed rock types.A Rb-Sr whole rock age of 432 ± 10 Ma has been obtained by a seven point isochron with MSDW = 2.59 and an initial Sr isotope ratio = 0.715. This age is approximately 30 Ma older than the previously obtained K-Ar whole rock and Rb-Sr biotite ages, ca. 400 Ma, which represents the period of cooling. The high initial Sr isotope ratio supports the interpretation of an anatectic origin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1751-8369.1996.tb00459.x
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  • 10
    Electronic Resource
    Electronic Resource
    Grenvillian U-Pb zircon ages of quartz porphyry and rhyolite clasts in a metaconglomerate at Vimsodden, southwestern Spitsbergen (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Polar research 14 (1995), S. 0 
    Details
    ISSN: 1751-8369
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geography , Geosciences
    Notes: Proterozoic metasupracrustal rocks form a NNW-SSE trending basement zone along the western coast of Spitsbergen. The rocks show complex structures as a result of both Caledonian and Tertiary deformation, and most of the subordinate metaigneous rocks are not suitable for isotopic age determination. Some zircon-bearing rocks were found in the southwestern part of Spitsbergen and an attempt of U-Pb dating was performed.U-Pb dating was carried out on zircon fractions from quartz porphyry and rhyolite clasts in a metaconglomerate unit of the Pyttholmen Formation northwest of Hornsund, southwestern Spitsbergen. The Pyttholmen Formation is considered to be a lateral equivalent of the upper part of the Gulliksenfjellet quartzite and in the same time as the upper part of the Skålfjellet metavolcanites. Therefore, the obtained ages are applicable to the age of the Skålfjellet igneous activities. Some of the dated samples are strongly schistose and their magmatic origin is difficult to confirm; the interpretation of the isotopic results is not well constrained; however, some explanations are possible which refer to the known geological conditions; an igneous age of siliceous volcanic rocks of ca. 1200 Ma, inherited zircon ages of ca. 2500 Ma and a regional metamorphic age of ca. 930 Ma. The last age belongs to the Grenvillian period and is conformable with the Rb/Sr whole rock age obtained from the garnet-biotite schists of the Isbjernhamna Group underlying the Skålfjellet metavolcanites.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1751-8369.1995.tb00716.x
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