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  • 1
    ISSN: 1432-0428
    Keywords: Islet cell autoantibodies ; Type 1 (insulin-dependent) diabetes mellitus ; first degree relatives ; prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Factors associated with diabetes onset were analysed for their predictive value in 708 first-degree relatives of Type 1 (insulin-dependent) diabetic patients including 374 parents and 308 siblings of Type 1 diabetic patients. Relatives were prospectively followed for 2 304 subject years with blood samples for specific autoantibody evaluation. Islet cell cytoplasmic autoantibody titres were quantified in Juvenile Diabetes Foundation units with a threshold of positivity of 5 units. Insulin autoantibodies were determined using Tyr-A14 iodinated human insulin. HLA typing was performed in 92% of the relatives. During the time of study, 17 of 646 (2.6%) relatives showed islet cell antibodies. During follow-up, eight relatives developed diabetes, including six with high islet cell antibody titre. Taking titres above 20 units increased the positive predictive value from 35% to 75% whereas the presence of insulin autoantibodies did not increase the positive predictive value for the disease. Analysis of metabolic profiles months before the onset of diabetes by either oral or intravenous glucose loads, indicated a considerable level of heterogeneity with relatives with a high islet cell antibody titre who rapidly developed insulin-dependent diabetes, whereas others remained insulin-independent during the same observation period despite comparable titres. This study clearly indicates that initial islet cell antibody titre is not sufficient to predict individual outcome. Follow-up samples are clearly needed to monitor progression of the disease. Few relatives with persistent immunologic positivity progress to clinical Type 1 diabetes, suggesting that non-progressive and sub-clinical Beta-cell dysfunction is common. Despite current knowledge and available genetic and immune markers, early identification of the relatives progressing to clinical diabetes is still difficult and does not allow at the present time aggressive immunointervention at the prediabetic stage.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Keywords Linomide ; Type I diabetes.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The quinoline-3-carboxamide, linomide, protects non-obese diabetic mice from diabetes. The effects of linomide on insulin needs and beta cell function were studied in recent juvenile Type I diabetes in a double-blind trial. Patients with recent onset diabetes were randomly assigned to treatment with a fixed dose of 2.5 mg linomide (42 patients) or placebo (21 patients) for 1 year, in addition to insulin and diet. Glycated haemoglobin was 10–15 % lower at 9 months (p = 0.003) and 12 months (p 〈 0.05) in the linomide group. The insulin dose was 32–40 % smaller in the linomide group at 3 (p 〈 0.03), 6 (p 〈 0.02), 9 (p 〈 0.001) and 12 months (p = 0.01). Insulin doses correlated negatively with C peptide values (p = 0.001–0.002). The trend for higher C peptide values in the linomide group did not reach significance. In a post hoc subgroup analysis performed in 40 patients (25 from the linomide group and 15 from the placebo group) who still had detectable residual beta cell function at entry, linomide was associated with 45–59 % higher C peptide value at 6 months (p 〈 0.05), 9 months (p 〈 0.05) and 12 months (p 〈 0.05). The main adverse effects of linomide were mild transitory anaemia (45 vs 10 % in the linomide and placebo groups), thrombocytopenia (24 vs 10 %), and mild joint discomfort (45 vs 5 %) with no clinical signs. In conclusion, low-dose linomide reduced the insulin needs in patients with juvenile Type I diabetes of recent onset and improved beta cell function in patients who still had detectable beta cell function at entry. These results support further clinical and experimental studies to define the effects of linomide in Type I diabetes provided the safety of linomide is reliably established. [Diabetologia (1998) 41: 1040–1046]
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Glutamate decarboxylase ; Type 1 (insulin-dependent) diabetes mellitus ; islet cell autoantibody ; prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prevalence of glutamic acid decarboxylase autoantibodies was determined with an immunotrapping enzyme activity assay in newly-diagnosed Type 1 (insulin-dependent) diabetic patients as well as in first-degree relatives using rat brain homogenate as a source of glutamate decarboxylase. Twenty-six out of 86 islet-cell cytoplasmic autoantibody positive and one out of 24 islet cell autoantibody negative patients of recent onset, had autoantibodies to glutamate decarboxylase above the upper 99% confidence limit obtained from 89 control sera. Among 27 islet cell autoantibody positive relatives including 19 siblings and 8 parents, antibodies to glutamate decarboxylase were found in 8 of 9 (89%) relatives and 7 of 8 (87.5%) siblings with islet cell autoantibody titres above 20 JDF units, in 1 of 19 (5.2%) relatives with islet cell autoantibody titres between 2 and 5 JDF units, in 2 of 263 (0.7%) siblings and 1 of 139 parents without islet cell autoantibodies. In first-degree relatives, high titre islet cell autoantibodies and autoantibodies to glutamate decarboxylase were tightly associated (X2=182, p=0.0001). None of the relatives with low genetic risk (n=64), i.e. HLA-different to the diabetic proband, was found to be antibody positive. Antibodies to glutamate decarboxylase were present only in those relatives sharing at least one haplotype with the diabetic proband, including two islet cell autoantibody negative but HLA-identical siblings. Autoantibodies to glutamate decarboxylase were present in 7 of 9 (77%) relatives who developed the disease, including one islet cell autoantibody negative sibling. Altogether, the simultaneous presence of autoantibodies to glutamate decarboxylase and high titre islet cell autoantibody increases the positive predictive value for the disease from 66% to 75%. This study indicates therefore that autoantibodies to glutamate decarboxylase detected by an immunotrapping enzyme activity assay are additional predictive markers for future development of Type 1 diabetes and should be now prospectively studied in high risk individuals as well as other autoantibodies to Beta-cell autoantigens.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 93 (1986), S. 23-32 
    ISSN: 1432-1424
    Keywords: n-alkanols ; adenylate cyclase ; partition coefficient ; rat heart
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary n-Alkanols (from methanol to decanol) have a biphasic effect on rat cardiac adenylate cyclase either basal or stimulated by GTP, GppNHp, NaF or hormones (isoproterenol, glucagon, secretin) in the presence of GTP. At high concentration, all the enzyme activities are inhibited. At low concentration, adenylate cyclase activity is either unchanged or potentiated depending on both the stimulus and the alkanols involved. Potentiation is due to an increase of maximum velocity with no change in the activation constant of the enzyme. Basal activity is unchanged as well as the isoproterenol-and glucagon-stimulated enzyme. The secretin-stimulated enzyme is potentiated. It is the guanyl nucleotide regulatory protein-mediated stimulation of adenylate cyclase which is mainly affected. An attempt was made to relate these effects on adenylate cyclase with physical parameters of the alkanols (partition coefficient). From the data obtained as a function of the alkanol chain-length and of temperature on the adenylate cyclase stimulated by GTP, GppNHp, NaF and permanently activated, it is concluded that the increase in efficacy observed in the presence of alkanol is due to an interaction with the protein moeity particularly with the guanyl nucleotide regulatory protein.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 279 (1987), S. 241-246 
    ISSN: 1432-069X
    Keywords: Cultures ; Epidermal cells ; Extracellular matrices ; Keratinocytes ; Pemphigus ; Pemphigoid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Extracellular matrices (ECM) have been reported to enhance epithelial cell attachment and proliferation as well as to induce differentiation in vitro. Since ECM components are physiological constituents of the dermoepidermal basement membrane, we studied the growth and differentiation of human keratinocytes on ECM in order to determine the benefits of culturing epidermal epithelial cells (keratinocytes) on reconstituted basement membranes. Dissaggregated epidermal cells were grown in primary and subcultures in liquid medium; the attachment of the cells was greatly enhanced by ECM and noted within the first few hours after seeding; cells formed small islets that reached confluence within 2–12 days depending upon the plating density and the type of culture (primary or passages). Histological and ultrastructural crosssections of the cultures clearly indicated that a multilayered epithelium can be obtained including a basal cell layer, several intermediate cell layers with cytoplasmic organelles, intermediate size filaments, desmosomes, and keratohyaline granules, and an upper layer of anucleated cells. Using immunofluorescence, both pemphigus and pemphigoid (basal membrane zone) antigens were expressed. The keratin pattern noted indicated that these epithelia differentiate and keratinize but do not express a complete program of keratinization, a finding usually noted when cells are grown submersed. These data show that ECM favor epidermal cell proliferation and differentiation and suggest that they may be used to obtain large amounts of epidermal equivalent suitable for grafting and/or in vitro studies.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 152 (1993), S. 559-563 
    ISSN: 1432-1076
    Keywords: Neonates ; Cardiac murmur ; Peripheral pulmonary branch stenosis ; Echocardiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Transient systolic murmurs in neonates and premature infants due to mild left (LPA) and right (RPA) pulmonary branch stenosis is recognized but follow up studies are lacking. We studied echocardiographically 21 neonates with murmur and 10 controls. Diameters of the main pulmonary artery (MPA), LPA and RPA were smaller in patients with murmur. Colour-coded Doppler showed turbulent flow in LPA and RPA in 20/21 (95%) patients and flow velocities of both pulmonary branches were significantly higher than in controls. The follow up study at 3 months in 14/21 (67%) patients showed absent or decreased murmur in 9 (64%). Echographically, absolute and relative diameters of LPA and RPA increased whereas the ratio of MPA/aorta did not change suggesting accelerated growth or dilatation of the pulmonary branches. Flow velocities decreased significantly in the branches. Thus, transient systolic murmurs in neonates are associated with temporary relative hypoplasia of the pulmonary branches which showed increased growth leading to disappearance of the murmur in most cases within 3 months of life.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European biophysics journal 6 (1980), S. 97-97 
    ISSN: 1432-1017
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 564 (1989), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Biomembranes 419 (1976), S. 540-546 
    ISSN: 0005-2736
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Biomembranes 597 (1980), S. 1-14 
    ISSN: 0005-2736
    Keywords: (Monolayer, Small unilamellar vesicle) ; Adriamycin ; Cardiolipin ; Phospholipid
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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