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  • 1
    ISSN: 1432-0428
    Keywords: Keywords Calcium-activated potassium channels ; islets of Langerhans ; diabetes mellitus ; radiation hybrids ; physical map ; chromosome 10
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin secretion from pancreatic beta cells is dependent on membrane potential changes that result from the concerted regulation of multiple ion channels. Among the distinct K + channels known to be expressed in beta cells, large conductance Ca2 + -activated K + channels have been suggested to play an important role in stimulus-secretion coupling. In the course of a strategy to identify transcripts that are enriched in human pancreatic islet cells, we isolated a partial cDNA encoding a human large conductance Ca2 + -activated K + channel mRNA (hSlo). Northern analysis of mRNA showed that among a panel of human tissues hSlo is expressed at its highest levels in pancreatic islets. Screening of human insulinoma and islet cDNA libraries with the partial cDNA resulted in the isolation of 19 hSlo cDNAs. These comprised three splice variants: one shared the common underlying structure of previously reported Slo cDNAs, another variant encoded a novel 60-amino acid insertion in the putative Ca2 + -sensing domain of hSlo, while the third group of clones had an alternate exon encoding eight amino acids in the predicted COOH-terminal end. Analysis of somatic-cell hybrids containing different portions of chromosome 10 indicated that hSlo maps to chromosome 10q22.2–q23.1. Furthermore, high resolution localization was obtained by analysis of genome-wide radiation hybrids and the CEPH “B” mega-YAC library, both of which identified for the first time a highly polymorphic genetic marker (D10S195) linked to hSlo. These studies provide tools with which to explore the physiological role of Ca2 + -activated K + channel proteins in pancreatic islets, and also to investigate the contribution of this locus to the inherited susceptibility to non-insulin-dependent diabetes mellitus. [Diabetologia (1996) 39: 891–898]
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Potassium channel ; inward rectifier ; non-insulin-dependent diabetes mellitus ; genetics ; single strand conformation polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ligand gated potassium channels, such as the ATP-regulated potassium channel, play crucial roles in coupling of stimuli to insulin secretion in pancreatic beta cells. Mutations in the genes might lead to the insulin secretory defects observed in patients with non-insulin-dependent diabetes mellitus (NIDDM). We isolated a cDNA encoding a putative subunit of a ligand gated potassium channel from a human islet cDNA library. The channel, which we designated hiGIRK2, appeared to be an alternative spliced variant and a human homologue of recently reported mbGIRK2, KATP-2/BIR1. Transcripts were detected in human brain and pancreas, but not in other tissues including cardiac muscle. The sizes of transcripts in the pancreas differed from those in the brain, suggesting tissue-specific alternative splicing and possible isoforms. We then isolated human genomic clones, determined the complete genomic structure and localized the gene to chromosome 21 (21q22). The gene was comprised of four exons and the protein was encoded by three exons. The entire coding region of the hiGIRK2 gene was scanned by polymerase chain reaction-single strand conformation polymorphism analysis in 80 Japanese NIDDM patients. We found five nucleotide substitutions; three were silent mutations of the third base of codons, one in the first intron, 9 bases upstream of exon 2, and one in the 3′-untranslated region. We conclude that mutations in the gene encoding MGIRK2, a (subunit of) ligand gated potassium channel, is not a major determinant of the susceptibility to NIDDM in Japanese.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Human islets ; islet function ; onset of Type 1 (insulin-dependent) diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Viable human pancreatic islets isolated from a recent-onset Type 1 (insulin-dependent) diabetic patient were used to perform in vitro studies. Pre-proinsulin mRNA and insulin content, as well as insulin response were analysed. Insulin response to glucose and forskolin was completely absent in diabetic islets, as compared to control islets. Insulin content was reduced to only one-third of control values (395.0±3.5 vs 989.0±46.3 μU/islet) and 20.7±3.9% of islets from the diabetic pancreas contained insulin-positive cells in immunofluorescence studies. Northern blot analysis revealed a severe reduction in the content of pre-proinsulin mRNA in diabetic pancreatic tissue. Our results indicate that although markedly decreased, beta cells in human pancreatic islets at the onset of Type 1 diabetes are still present. Never-theless, pancreatic islet function is disproportionately impaired with a complete absence of an insulin response.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Calcium-activated potassium channels ; islets of Langerhans ; diabetes mellitus ; radiation hybrids ; physical map ; chromosome 10
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin secretion from pancreatic beta cells is dependent on membrane potential changes that result from the concerted regulation of multiple ion channels. Among the distinct K+ channels known to be expressed in beta cells, large conductance Ca2+-activated K+ channels have been suggested to play an important role in stimulus-secretion coupling. In the course of a strategy to identify transcripts that are enriched in human pancreatic islet cells, we isolated a partial cDNA encoding a human large conductance Ca2+-activated K+ channel mRNA (hSlo). Northern analysis of mRNA showed that among a panel of human tissues hSlo is expressed at its highest levels in pancreatic islets. Screening of human insulinoma and islet cDNA libraries with the partial cDNA resulted in the isolation of 19 hSlo cDNAs. These comprised three splice variants: one shared the common underlying structure of previously reported Slo cDNAs, another variant encoded a novel 60-amino acid insertion in the putative Ca2+-sensing domain of hSlo, while the third group of clones had an alternate exon encoding eight amino acids in the predicted COOH-terminal end. Analysis of somatic-cell hybrids containing different portions of chromosome 10 indicated that hSlo maps to chromosome 10q22.2–q23.1. Furthermore, high resolution localization was obtained by analysis of genome-wide radiation hybrids and the CEPH “B” mega-YAC library, both of which identified for the first time a highly polymorphic genetic marker (D10S195) linked to hSlo. These studies provide tools with which to explore the physiological role of Ca2+-activated K+ channel proteins in pancreatic islets, and also to investigate the contribution of this locus to the inherited susceptibility to non-insulin-dependent diabetes mellitus.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Keywords Potassium channel ; inward rectifier ; non-insulin-dependent diabetes mellitus ; genetics ; single strand conformation polymorphism.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ligand gated potassium channels, such as the ATP-regulated potassium channel, play crucial roles in coupling of stimuli to insulin secretion in pancreatic beta cells. Mutations in the genes might lead to the insulin secretory defects observed in patients with non-insulin-dependent diabetes mellitus (NIDDM). We isolated a cDNA encoding a putative subunit of a ligand gated potassium channel from a human islet cDNA library. The channel, which we designated hiGIRK2, appeared to be an alternative spliced variant and a human homologue of recently reported mbGIRK2, KATP-2/BIR1. Transcripts were detected in human brain and pancreas, but not in other tissues including cardiac muscle. The sizes of transcripts in the pancreas differed from those in the brain, suggesting tissue-specific alternative splicing and possible isoforms. We then isolated human genomic clones, determined the complete genomic structure and localized the gene to chromosome 21 (21q22). The gene was comprised of four exons and the protein was encoded by three exons. The entire coding region of the hiGIRK2 gene was scanned by polymerase chain reaction-single strand conformation polymorphism analysis in 80 Japanese NIDDM patients. We found five nucleotide substitutions; three were silent mutations of the third base of codons, one in the first intron, 9 bases upstream of exon 2, and one in the 3 ′-untranslated region. We conclude that mutations in the gene encoding hiGIRK2, a (subunit of) ligand gated potassium channel, is not a major determinant of the susceptibility to NIDDM in Japanese. [Diabetologia (1996) 39: 447–452]
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We present the genotype/phenotype correlation analysis for 16 cystic fibrosis (CF) patients who carry mutation R334W. Current age and age of diagnosis was significantly higher in the R334W/any-mutation group (P 〈 0.05 and P 〈 0.01), compared with the Δ508/Δ508 group. A slightly, but not significantly, worse lung function was found in the R334W/any-mutation group, when compared with the Δ508/Δ508 patients. The proportion of patients with lung colonization with bacterial pathogens was slightly, but not significantly, higher in the R334W/any-mutation group (71.4%), compared with the Δ508/Δ508 or R334W/Δ508 groups (55.5%). None of the R334W patients had meconium ileus but 60% were pancreatic insufficient (PI), a significantly lower proportion (P ≪ 0.001) than Δ508/Δ508 patients. Two R334W/N1303K compound heterozygous sisters were PI but discrepant for lung function. Two groups of three sibs with genotype R334W/Δ508 showed interfamilial discordant clinical data for lung and pancreatic function. The data provided here for mutation R334W demonstrate that this mutation is responsible for a less severe form of CF than Δ508. Interfamilial differences for PI and lung function suggest that other factors, viz. genetic, environmental and medical, contribute to the wide spectrum of clinical differences observed in CF patients with the same CF transmembrane conductance regulator genotypes.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    s.l. ; Stafa-Zurich, Switzerland
    Materials science forum Vol. 228-231 (July 1996), p. 223-226 
    ISSN: 1662-9752
    Source: Scientific.Net: Materials Science & Technology / Trans Tech Publications Archiv 1984-2008
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1248-9204
    Keywords: Lichtenstein technique ; Groin hernia recurrence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We report a 3.4% incidence of hernial recurrence (all recurrences were reoperated) after inguinal hernia repair by the Lichtenstein technique: 14 reoperated recurrences (in 13 patients) in a series of 440 inguinal hernias (375 primary and 65 recurrent) in 379 patients (62 bilateral) over 5 years (1994–1998). Some 2/3 of all recurrences appeared within a year of surgery. Eleven of these patients were operated on for bilateral and/or recurrent groin hernia, and eleven also showed at least one risk factor for recurrence, such as obesity and other general diseases (specially pulmonary and hepatic). The incidence of recurrence was 0.7% (2 in 272) for primary unilateral hernia, 3.8% for primary bilateral hernia (2 in 52), 11.1% for recurrent unilateral hernia (5 in 45) and 40% for recurrent bilateral hernia (4 in 10). Recurrences were 5 indirect hernias, 4 direct hernias and 5 femoral hernias. Indirect recurrence was attributed to technical errors, but femoral and direct hernias seem to be the consequence of a poor indication for the Lichtenstein technique. Log-rank tests showed very significant statistical differences (p〈0.01) in the risk of hernial recurrence between recurrent and primary hernias. We suggest that certain conditions should be contraindications for the standard Lichtenstein technique (bilateral groin hernia, recurrent hernia, obesity, chronic pulmonary and liver disease), and propose for these either a preperitoneal repair or some modifications of the Lichtenstein technique (an extremely floppy mesh and simultaneous femoral repair with the mesh).
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Il nuovo cimento della Società Italiana di Fisica 12 (1990), S. 53-59 
    ISSN: 0392-6737
    Keywords: General theory and models of magnetic ordering
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Description / Table of Contents: Riassunto Si ottengono formule generali per la valenza, la carica e suscettibilità di spin e per il calore specifico a temperatura bassa e campo magnetico zero per il modello di Anderson di un'impurità con l'uso del metodo dell'ansatz di Bethe seguendo il lavoro di Tsvelick e Wiegmann.
    Abstract: Резюме Получаются общие формулы для валентности, заряда, спиновой восприимчивости и удельной теплоемкости при низкой температуре и нулевом магнитном поле для модели Андерсона для описания примеси с использованием подхода Бете.
    Notes: Summary General formulae for the valence, charge and spin susceptibility, and specific heat at low temperature and zero magnetic field are obtained for the Anderson model of an impurity with the use of the Betheansatz method, following the work of Tsvelick and Wiegmann.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Copenhagen : International Union of Crystallography (IUCr)
    Acta crystallographica 57 (2001), S. 1752-1753 
    ISSN: 1399-0047
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: Automation of protein crystallography synchrotron beamlines is becoming necessary to face challenging structural genomics projects. In this context, a program has been developed that processes diffraction frames using popular software but analyzes statistics and makes choices the way crystallographers usually do. This program includes the classical peak search, indexing, integration, scaling and anomalous signal analysis. The result, comparable with that obtained by standard users, is rapidly available, providing the required information for a more efficient use of the beam time.
    Type of Medium: Electronic Resource
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