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  • 1
    Electronic Resource
    Electronic Resource
    Molecular scanning of the insulin receptor substrate-1 (IRS-1) gene in Japanese patients with NIDDM: identification of five novel polymorphisms (1996)
    Springer
    Diabetologia 39 (1996), S. 600-608 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin receptor substrate-1 (IRS-1) ; non-insulin-dependent diabetes mellitus ; genetics ; single-stranded conformation polymorphisms ; insulin resistance ; polymorphism.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Since the insulin receptor substrate-1 (IRS-1) is the major substrate of the insulin receptor tyrosine kinase and has been shown to activate phosphatidylinositol (PI) 3-kinase and promote GLUT4 translocation, the IRS-1 gene is a potential candidate for development of non-insulin-dependent diabetes mellitus (NIDDM). In this study, we have identified IRS-1 gene polymorphisms, evaluated their frequencies in Japanese subjects, and analysed the contribution of these polymorphisms to the development of NIDDM. The entire coding region of the IRS-1 gene of 94 subjects (47 NIDDM and 47 control subjects) was screened by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) analysis. Seven SSCP polymorphisms were identified. These corresponded to two previously identified polymorphisms [Gly971→Arg (GGG→AGG) and Ala804 (GCA→GCG)] as well as five novel polymorphisms [Pro190→Arg (CCC→CGC), Met209→Thr (ATG→ACG), Ser809→Phe (TCT→TTT), Leu142 (CTT→CTC), and Gly625 (GGC→GGT)]. Although the prevalence of each of these polymorphisms was not statistically different between NIDDM and control subjects, the prevalence of the four IRS-1 polymorphisms with an amino acid substitution together was significantly higher in NIDDM than in control subjects (23.4 vs 8.5 %, p 〈 0.05), and two substitutions (Met209→Thr and Ser809→Phe) were found only in NIDDM patients. Equilibrium glucose infusion rates during a euglycaemic clamp in NIDDM and control subjects with the IRS-1 polymorphisms decreased by 29.5 and 22.0 %, respectively on the average when compared to those in comparable groups without polymorphisms, although they were not statistically significant. Thus, IRS-1 polymorphisms may contribute in part to the insulin resistance and development of NIDDM in Japanese subjects; however, they do not account for the major part of the decrease in insulin-stimulated glucose uptake which is observed in subjects with clinically apparent NIDDM. [Diabetologia (1996) 39: 600–608]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403308
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  • 2
    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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  • 3
    Electronic Resource
    Electronic Resource
    Molecular scanning of the insulin receptor substrate-1 (IRS-1) gene in Japanese patients with NIDDM: identification of five novel polymorphisms (1996)
    Springer
    Diabetologia 39 (1996), S. 600-608 
    Details
    ISSN: 1432-0428
    Keywords: Insulin receptor substrate-1 (IRS-1) ; non-insulin-dependent diabetes mellitus ; genetics ; single-stranded conformation polymorphisms ; insulin resistance ; polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Since the insulin receptor substrate-1 (IRS-1) is the major substrate of the insulin receptor tyrosine kinase and has been shown to activate phosphatidylinositol (PI) 3-kinase and promote GLUT4 translocation, the IRS-1 gene is a potential candidate for development of non-insulin-dependent diabetes mellitus (NIDDM). In this study, we have identified IRS-1 gene polymorphisms, evaluated their frequencies in Japanese subjects, and analysed the contribution of these polymorphisms to the development of NIDDM. The entire coding region of the IRS-1 gene of 94 subjects (47 NIDDM and 47 control subjects) was screened by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) analysis. Seven SSCP polymorphisms were identified. These corresponded to two previously identified polymorphisms [Gly971→Arg (GGG→AGG) and Ala804 (GCA→GCG)] as well as five novel polymorphisms [Pro190→Arg (CCC→CGC), Met209→Thr (ATG→ACG), Ser809→Phe (TCT→TTT), Leu142 (CTT→CTC), and Gly625 (GGC→GGT)]. Although the prevalence of each of these polymorphisms was not statistically different between NIDDM and control subjects, the prevalence of the four IRS-1 polymorphisms with an amino acid substitution together was significantly higher in NIDDM than in control subjects (23.4 vs 8.5%, p〈0.05), and two substitutions (Met209→Thr and Ser809→Phe) were found only in NIDDM patients. Equilibrium glucose infusion rates during a euglycaemic clamp in NIDDM and control subjects with the IRS-1 polymorphisms decreased by 29.5 and 22.0%, respectively on the average when compared to those in comparable groups without polymorphisms, although they were not statistically significant. Thus, IRS-1 polymorphisms may contribute in part to the insulin resistance and development of NIDDM in Japanese subjects; however, they do not account for the major part of the decrease in insulin-stimulated glucose uptake which is observed in subjects with clinically apparent NIDDM.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403308
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Probing bulk states of correlated electron systems by high-resolution resonance photoemission (2000)
    [s.l.] : Macmillian Magazines Ltd.
    Nature 403 (2000), S. 396-398 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Electron correlations are known to play an important role in determining the unusual physical properties of a variety of compounds. Such properties include high-temperature superconductivity, heavy fermion behaviour and metal-to-insulator transitions. High-resolution photoelectron spectroscopy ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/35000140
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  • 5
    Electronic Resource
    Electronic Resource
    ALTERATION IN THE RELEASE OF ENDOTHELIUM-DERIVED RELAXING FACTORS BY α-ADRENOCEPTOR STIMULATION IN THE AORTA OF STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 22 (1995), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Endothelium-dependent relaxation by a-adrenoceptor agonists was examined in the thoracic aorta from normoten-sive Wistar-Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP).2. In ring preparations from both strains, noradrenaline-induced contraction was increased by L-nitro arginine (L-NNA), a NO synthesis inhibitor.3. L-NNA increased the contraction induced by phenyl-ephrine, an α1-adrenoceptor agonist. UK-14304 and clonidine, α2-adrenoceptor agonists, did not contract the preparations with intact endothelium. However, these agents contracted preparations when NO synthesis was inhibited.4. In a precontracted preparation, clonidine and UK-14304 induced relaxations. The relaxations in SHRSP aorta were smaller than those in WKY aorta.5. These results indicate that a-agonists release NO from endothelium in WKY and SHRSP aorta. The mechanism related to NO release by α2-adrenoceptor agonist is impaired in SHRSP aorta.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1995.tb02856.x
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  • 6
    Electronic Resource
    Electronic Resource
    Low resistance magnetic tunnel junctions and their interface structures (2001)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 89 (2001), S. 7558-7560 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Effects of interface structure and oxidation state were studied in stacked magnetic tunnel junction (MTJ) structures with top and bottom antiferromagnetic layers to obtain optimum resistance and high tunneling magnetoresistance (TMR) ratios for read heads. The roughness of the NiFe surface and the Al coverage were significantly improved by introduction of O2 surfactant gas on the Ta-seed-layer surface, which increased TMR ratios of the MTJ with low resistance area (RA) products of less than 10 Ω μm2. Furthermore, it was found that avoidance of Ni oxidation and Co oxidation at the tunnel barrier interface is essential to obtaining high TMR ratios, and that a good Al coverage and Fe–oxide formation may enhance TMR ratios when Fe-rich magnetic materials are used. For the top-type and bottom-type structures, a TMR ratio of 12%–17% with RA products of 6–7 Ω μm2 was obtained, which provides sufficient performance for read heads. © 2001 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.1361054
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  • 7
    Electronic Resource
    Electronic Resource
    Exchange-biased magnetic tunnel junctions fabricated with in situ natural oxidation (1999)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 85 (1999), S. 5261-5263 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Exchange-biased magnetic tunnel junctions with a Ta/NiFe/FeMn/NiFe/Al–oxide/NiFe/Ta structure have been fabricated. The tunnel barrier was formed by the in situ natural oxidation of an Al metal layer under controlled oxygen pressure. Photolithography and ion milling were used to pattern the multilayer into junction structures of 2×2 μm2–20×20 μm2 dimensions. Magnetoresistance (MR) curves show spin-valve-like characteristics, in which an antiparallel configuration of magnetizations in both ferromagnetic layers is observed between 50 and 240 Oe, and the hysteresis loops for both the free and pinned layers exhibit sufficient separation. An evaluation of the MR curves shows the exchange-bias field to be 340 Oe and coercivity levels in the free layer to become as low as 13 Oe. At room temperature normalized junction resistance is 2×10−5 Ω cm2, with MR ratios still being maintained at 13%. This resistance value is much lower than previously reported values for junctions produced either with plasma oxidation or thermal oxidation in air. Maximum variation in junction resistance is only ±5% for 10×10 μm2 junctions over a 2 in. wafer. The MR ratio decreases by half when the bias voltage is raised from 0 to 440 mV, approximately the same ratio of decrease as has been previously reported for other successful junctions. © 1999 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.369960
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  • 8
    Electronic Resource
    Electronic Resource
    Interface structures and magnetoresistance in magnetic tunnel junctions (1999)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 85 (1999), S. 5807-5809 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The interface structures of magnetic tunnel junctions were studied using x-ray photoelectron spectroscopy (XPS). The structures were correlated with magnetoresistance (MR) characteristics. For MR measurements, Fe(50 nm)/AlOx/CoFe(30 nm) junctions with an in situ naturally oxidized Al tunnel barrier were fabricated. The thickness of the Al layer, an important parameter in MR characteristics, was varied from 0 to 5 nm. MR curves showed that the largest MR ratio occurred when the Al layers were 2–3 nm in thickness. XPS analysis showed that an Al layer greater than 1 nm thick covers the entire surface of the Fe underlayer. However, if the Al layer is more than 1 nm thick, the unoxidized Al remaining after the oxidation process increases as the thickness is increased. For Al layers that are greater than 3 nm thick, the MR ratio is strongly affected by unoxidized Al, probably due to the decrease in spin polarization at the surface of an Fe/Al electrode. On the other hand, the hysteresis loops indicate that the difference in coercive force between Fe and CoFe layers reduces with decreasing Al thickness for Al layers less than 2.5 nm thick. This means that the antiparallel direction of magnetization in the two layers becomes incomplete due to the gradual increase of the ferromagnetic coupling between them. As a result, the MR ratio decreases, although a 1-nm-thick Al layer seems to be enough to cover the Fe surface. © 1999 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.369926
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  • 9
    Electronic Resource
    Electronic Resource
    Formation of MnSb during the growth of MnSi layers in the presence of an Sb flux (2002)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 91 (2002), S. 4932-4935 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Structural and compositional analyses of a MnSi layer have been performed to elucidate the growth mechanism. The MnSi layer was grown by reactive deposition epitaxy in the presence of an Sb flux. The existence of Sb was found at the MnSi/Si interface and on the surface of MnSi layer by secondary ion mass spectrometry. In addition, x-ray photoelectron spectroscopy measurement shows that MnSb is formed on the surface of the grown MnSi layer. On the atomic scale, scanning transmission electron microscopy observations reveal the existence of an Sb–Mn–Sb structure at the interface between the MnSi layer and the Si substrate. The formation of the MnSb plays an important role for the improvement of crystalline quality of the silicide layer, acting both as a surfactant and as a compliant substrate for stress relief. © 2002 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.1461063
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  • 10
    Electronic Resource
    Electronic Resource
    Near-field optical fiber probe optimized for illumination–collection hybrid mode operation (1999)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 74 (1999), S. 2773-2775 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The structure of a near-field probe was optimized for illumination-collection hybrid mode (I–C mode) operation. We developed a highly sensitive probe with a sharp-edged aperture and a double-tapered structure fabricated by a chemical etching technique. Through measurement of the photoluminescence (PL, λ=1 μm) image of single quantum dots, the performance of many versions of the probe with different aperture diameters, ranging from 80 to 500 nm, was systematically evaluated. In addition to the throughput and spatial resolution, the absolute value of the PL collection efficiency of the probe in (I–C mode) was also estimated for the first time. A collection efficiency several times greater than that of an objective lens with a numerical aperture of 0.8 was achieved with high spatial resolution in the 130–200 nm (λ/8–λ/5) range. © 1999 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.123307
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