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  • 1
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    German Medical Science; Düsseldorf, Köln
    In:  67. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 89. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie und 44. Tagung des Berufsverbandes der Fachärzte für Orthopädie; 20031111-20031116; Berlin; DOC03dguK4-3 /20031111/
    Publication Date: 2003-11-11
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 2
    ISSN: 1432-1211
    Keywords: Key words Molecular convergence ; New World monkeys ; HLA-DRB ; Major histocompatibility complex evolution ; Gene conversion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract   In both Old World and New World monkeys Mhc-DRB sequences have been found which resemble human DRB1*03 and DRB3 genes in their second exon. The resemblance is shared sequence motifs and clustering of the genes or the encoded proteins in phylogenetic trees. This similarity could be due to common ancestry, convergence at the molecular level, or chance. To test which of these three explanations applies, we sequenced segments of New World monkey and macaque genes which encompass the entire second exon and large parts of both flanking introns. The test strongly supports the monophyly of New World monkey DRB intron sequences. The phylogenies of introns 1 and 2 from DRB1*03-like and DRB3-like genes are congruent, but both are incongruent with the exon 2-based phylogeny. The matching of intron 1- and intron 2-based phylogenies with each other suggests that reciprocal recombination has not played a major role in exon 2 evolution. Statistical comparisons of exon 2 from different DRB1*03 and DRB3 lineages indicate that it was neither gene conversion (descent), nor chance, but molecular convergence that has shaped their characteristic motifs. The demonstration of convergence in anthropoid Mhc-DRB genes has implications for the classification, age, and mechanism of generation of DRB allelic lineages.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Keywords HIV protease inhibitors ; lipodystrophy syndrome ; diabetes mellitus ; insulin resistance ; insulin signalling.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Patients treated with human immunodeficiency virus-1 protease inhibitors often develop impaired glucose tolerance or diabetes, most likely due to an induction of insulin resistance. We therefore investigated whether the protease inhibitor indinavir alters insulin signalling. Methods. We incubated HepG2 cells for 48 h without or with indinavir (100 μmol/l). Subsequently 125I-insulin binding to the cells and the effects of insulin stimulation on insulin-receptor substrate-1-phosphorylation, association of phosphatidylinositol 3-kinase with insulin-receptor substrate-1 and Akt-Thr308-phosphorylation were measured. Results. In cells not exposed to indinavir, insulin (100 nmol/l) led to rapid increases of insulin-receptor substrate-1-phosphorylation, association of phosphatidylinositol 3-kinase with insulin-receptor substrate-1 and Akt-phosphorylation during the first 75 s, followed by subsequent decreases. In indinavir-treated cells, these insulin-stimulated increases during the first 75 s were reduced by 30–60 % and this was not associated with alterations in cell number or viability, insulin binding to the cells or cellular insulin-receptor substrate-1-content. Conclusion/interpretation. Effects of indinavir on initial insulin signalling could cause, or contribute to, the metabolic effects of human immunodeficiency virus-1 protease inhibitors. [Diabetologia (2000) 43: 1145–1148]
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  • 4
    ISSN: 1435-1285
    Keywords: Key words Lyme disease – borreliosis – cardiomyopathy – myocarditis – heart failure ; Schlüsselwörter Lyme-Karditis – Borreliose – Kardiomyopathie – Myokarditis – Herzinsuffizienz
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Eine kardiale Beteiligung wird bei der Lyme-Borreliose in ca. 4–10% beobachtet. Zu den häufigsten Frühmanifestationen der akuten Lyme-Karditis zählen Reizleitungsstörungen sowie eine Perimyokarditis. Aufgrund der eingeschränkten Sensitivität und Spezifität sowie mangelnder Standardisierung der laborchemischen Testverfahren (ELISA, Westernblot, PCR) muss die Diagnose durch eine synoptische Wertung von Anamnese, Serologie und klinischen Befunden gestellt werden. Seit wenigen Jahren mehren sich Hinweise, dass ein kausaler Zusammenhang zwischen der Entstehung einer inflammatorischen dilatativen Kardiomyopathie und einer chronischen Borrelieninfektion besteht. Nach dem erfolgreichen Nachweis von Spirochäten aus dem Endomyokardgewebe bei Patienten mit dilatativer Kardiomyopathie konnte in Seroprävalenzstudien signifikant häufiger eine positive Immunserologie nachgewiesen werden (26% gegenüber 8% in der Referenzpopulation). In mehreren Therapiestudien zeigte sich eine Besserung bzw. Normalisierung der linksventrikulären Funktion unter antimikrobieller Therapie. Voraussetzung hierfür scheint allerdings ein entsprechend frühzeitiger Therapiebeginn vor Eintritt struktureller Myokardveränderungen zu sein.
    Notes: Summary Heart involvement of Lyme disease occurs in about 4–10% of patients with Lyme borreliosis. The most common manifestation is acute, self-limiting Lyme carditis, which manifests mostly as transient conduction disorders of the heart, pericarditis and myocarditis. Laboratory tests (ELISA, immunoblotting and PCR) usually have limited sensitivity and specifity, and criteria of performance and interpretation have not yet been fully evaluated. Therefore the laboratory evidence should only be interpreted in conjunction with other clinical and diagnostic features. Recently there has been convincing evidence published that long standing dilated cardiomyopathy in many cases is associated with a chronic Borrelia burgdorferi (BB) infection. Several studies showed a higher prevalence of BB antibodies in patients with severe heart failure in endemic areas (e.g., 26% versus 8% in healthy individuals). The isolation of spirochetes from the myocardium gave further evidence that BB may cause chronic heart muscle disease. In several studies antimicrobial treatment showed an improvement of the left ventricular function in patients with dilated cardiomyopathy associated with BB. However the duration of dilated cardiomyopathy before treatment plays an important part in the clinical outcome of BB-associated chronic myocarditis.
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  • 5
    ISSN: 1435-1463
    Keywords: Keywords: Membrane breakdown ; phospholipids ; phospholipase A2 ; phosphatidylcholine ; glycerophosphocholine ; choline.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Breakdown of cellular membranes is a characteristic feature of neuronal degeneration in acute (stroke) and chronic (senile dementia) neurological disorders. The present review summarizes recent experimental and clinical work which concentrated on changes of choline-containing phospholipids as indicators of neuronal membrane breakdown. Experimental studies identified glutamate release, calcium influx, and activation of cellular phospholipase A2 (PLA2) as important steps initiating membrane breakdown in cultured neurons or brain slices under hypoxic or ischemic conditions. Proton NMR studies have shown an elevation of choline-containing compounds in the brain of Alzheimer patients while neurochemical studies in post mortem-brain demonstrated increases of the catabolic metabolite, glycerophosphocholine, an indicator of PLA2 activation. In contrast, studies of cerebrospinal fluid, phosphorus NMR studies, and measurements of phospholipases in post mortem Alzheimer brain gave ambiguous results which may be explained by methodical limitations. The finding that, in experimental studies, choline was a rate-limiting factor for phospholipid biosynthesis has stimulated clinical studies aimed at counteracting phospholipid breakdown, e.g. by combinations of choline and cytidine. Future experimental approaches should clarify whether loss of membrane phospholipids is cause or consequence of the neurodegenerative disease process.
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  • 6
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The genome of the cichlid (teleost) fish Oreochromis niloticus contains a set of genes which encode group V C-type lectin proteins homologous to the mammalian NKG2/CD94 family of natural killer (NK) cell receptors. To determine the genomic organization of these killer cell-like receptor (KLR) genes, an O. niloticus BAC library was screened with a cDNA probe derived previously from an expressed sequence tag of the related cichlid species Paralabidochromis chilotes. Four distinct KLR-bearing BAC clones were analysed, three of which could be assembled into a contig. One of the clones was sequenced in its entirety, whereas the others were partially sequenced to identify the KLR loci borne by them. Altogether, 28 distinct KLR loci were identified, of which at least 26 occupy a single chromosomal region, the KLR complex. One half of the loci appear to be occupied by pseudogenes. Compared to the human NK cell receptor complex, the Oreochromis KLR complex is more compact and, apart from transposons, appears to contain only KLR loci. The gene density of the complex is one KLR locus per 18 kb of sequence. All the KLR loci constituting the complex are derived from a single most recent common ancestor, which is estimated to have existed 7.7 million years ago. The 180 kb of the determined sequence is a mosaic of blocks of similar segments reflecting a complex history of duplications, deletions and rearrangements. The transposons found in the sequenced part belong to the TC1, Xena, CR1 and TX1 families.
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  • 7
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The α2-macroglobulin (A2M) and the complement components C3 and C4 are related proteins derived from a common ancestor. Theoretically, this derivation could have occurred either by tandem duplications of their encoding genes or by polyploidization involving chromosomal segments, a chromosome or the whole genome. In tetrapods the A2M-, C3- and C4-encoding genes are generally each located on a different chromosome. This observation has been interpreted as supporting their origin by polyploidization. We identified and mapped (with the help of a radiation hybrid panel of cell lines) the A2M, C3 and C4 loci in the zebrafish, Danio rerio. Each of the three types of loci is present in the zebrafish in multiple copies, but all of the identified copies of a given type map to the same region in linkage groups 1 (C3) and 15 (A2M, C4). The A2M and C4 loci are mapped in the same region not linked to any of the class I or class II major histocompatibility complex (Mhc) loci. These observations are interpreted as supporting the origin of the A2M family of genes by tandem duplications, followed by the dispersal of the copies to different chromosomes. It is also argued that the association of C4 with the class I/II loci in tetrapods is accidental and without functional significance.
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  • 8
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary.  Outlined is our experience with couples in whom the male was both human immunodeficiency virus (HIV) seropositive and a haemophiliac who underwent assisted reproductive technologies (ART) in order to attain family goals while minimizing the risk of HIV transmission. We report their demographics, attitudes towards assisted reproduction, and ART performance and outcomes. The study included HIV serodiscordant couples (n = 11) who underwent ART at a university-based infertility practice from August 1997 to May 2002. Prior to treatment, couples prospectively completed a survey regarding their demographics and attitudes towards assisted reproduction. All couples underwent ART and pregnancy outcomes were analysed. The majority of the patients were fully employed, college-educated, in good health, married and motivated to have a child while minimizing the risk of HIV transmission. Eleven couples underwent 25 cycles of ART [19 in vitro fertilization (IVF) cycles; five frozen embryo transfer cycles; and one oocyte donation cycle] resulting in nine successful pregnancies. The ongoing/delivered pregnancy rate per initiated IVF cycle was 42.1% per embryo transfer. Eight of 11 (72.7%) couples achieved a successful pregnancy. More than half (six of 11; 54.5%) the couples conceived during their initial attempt. Four of nine (44.4%) pregnancies were multiple gestations, including three sets of triplets. All female recipients tested seronegative for HIV at 3 and 6 months post-embryo transfer. All delivered babies (n = 8) tested seronegative for HIV at birth and 3 months postpartum. Four pregnancies are currently ongoing. ART should be considered for HIV serodiscordant couples with haemophilia who desire to have children in order to minimize the risk of viral infection.
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  • 9
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Cathepsins are enzymes that have been cleaving peptide bonds of lysosomal proteins probably since lysosomes appeared in early eucaryotes. When the adaptive system emerged in gnathostomes, cathepsins were recruited to produce peptides for loading onto the major histocompatibility complex class II molecules and for degrading the class II-associated invariant chain just before the loading. The circumstances under which this recruitment took place are unclear because the knowledge about vertebrate cathepsins is limited largely to mammals. To shed light on the recruitment, 10 amphioxus, one lamprey and one cichlid fish cathepsin cDNA clone were characterized and analysed phylogenetically. Disregarding cathepsin O, whose phylogenetic position is uncertain, the analysis confirms the existence of two old lines of descent, the B and the L lineages of cathepsins, which diverged from each other early in the evolution of eucaryotes. The B lineage encompasses cathepsins B, C and Z (X). The L lineage splits off sublineages encompassing cathepsins F and W before the plant–animal separation and cathepsin H early in the evolution of the metazoa. The remaining cathepsins belonging to the L lineage diverged from one another during the evolution of vertebrates: S, K and L before the emergence of bony fishes, and the group of rodent placentally expressed cathepsins [J (P), M, Q, R, 3, 6, 7 and 8] as well as the testis/ova-expressed cathepsins (testins) probably after the divergence of rodents from primates. The part possibly played by the adaptive immune system in some of these divergences is discussed.
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  • 10
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We report the pre-operative preparation and anaesthetic management for resection of an intracerebral tumour during awake craniotomy in a 9-year-old boy. We believe this is the youngest patient reported to have undergone this procedure. The challenges of sedation and psychological care throughout the procedure are discussed. We conclude that the procedure can be performed safely and that it seems unacceptable to uphold an age restriction. We believe that it is the individual level of development of the child that determines suitability for this type of surgery.
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