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  • 1
    ISSN: 0888-7543
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2307
    Keywords: Glomerular structure ; Morphometry ; Monocomponent insulin ; Antibody formation ; Mesangium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Weak nonspecific immunological stimuli can irritate the glomerular mesangium as observed following administration of insulin preparations of varying degrees of purity. In the present study further substances were investigated with regard to this effect. We wished to examine which substances obtained during purification of insulin are mainly responsible for the antigenicity, and whether porcine and bovine MC insulin have the same antigenic properties. Rabbits were treated for up to 90 days with bovine MC insulin, bovine proinsulin, bovine a + b-component, porcine a-component and porcine b-component. The kidneys were analysed morphometrically and antibody titers to bovine insulin, a-component, porcine PP and proinsulin were determined in the various test groups. It was found that bovine MC insulin and porcine MC insulin possess the same immunological activity, i.e. no antibody formation to either of the two insulins was demonstrable. Similarly, there were no differences in the morphometric findings; slight transient mesangial changes were demonstrable after both insulins. However a-component and b-component showed a pronounced immunogenic potency with antibody formation. Marked and partly persisting mesangial alterations were demonstrable, with the antigenicity of the a-component being particularly marked. The implication of the study is that a “pure” or optimally purified insulin should be used in the therapy of diabetes mellitus.
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  • 3
    ISSN: 1432-0533
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die retrograden Zellveränderungen im Facialiskern der Maus wurden nach intracerebraler Injektion von Actinomycin D untersucht. Normalerweise zeigen diese Neurone erhöhte Basophilie des Cytoplasmas und abnehmende Größe der Nissl-Schollen während der ersten Tage nach Durchtrennung des Nerven. Der Nervenzelldurchmesser nimmt während des 2.–4. Tages nach der Nervendurchtrennung zu. Nach intracerebraler Injektion von Actinomycin D kommt es zur raschen Desintegration der Nucleoli sämtlicher Neurone, während das Cytoplasma nur geringe Veränderungen aufweist. Die Nissl-Substanz der normalen Neurone erscheint 2 Tage nach der Behandlung gut erhalten. Wird Actinomycin zum Zeitpunkt der Durchtrennung des N. facialis verabreicht, so sind alle Veränderungen der retrograden Zellveränderung während der folgenden 48 Std blockiert. Diese Befunde weisen darauf hin, daß die Auflösung der Nissl-Substanz im Rahmen der retrograden Zellreaktion durch eine induzierte Enzymsynthese vermittelt wird. Wird die erste Actinomycin-Injektion 2 Tage nach der Nervendurchtrennung verabreicht, so zeigen die Neurone der durchtrennten Seite nach 2 Tagen extreme Chromatolyse. Das könnte auf eine raschere Übertragungsrate von RNS auf die fein verteilten basophilen Partikeln des Cytoplasmas als auf die großen Nissl-Granula der normalen Neurone hinweisen.
    Notes: Summary The retrograde reaction in the facial nucleus of mice has been studied after intracerebral injection of actinomycin D. Normally these neurons show increasing cytoplasmic basophilia and decreasing size of the Nissl granules during the first days after section of the facial nerve. The nerve cell diameter increases between the 2nd and 4th day after section of the nerve. After intracerebral injection of actinomycin D the nucleolus of all neurons disintegrates rapidly while the cytoplasm shows only slight changes. The Nissl substance of normal neurons appears well preserved after 2 days' treatment. When actinomycin is given at the time of section of the facial nerve, all aspects of retrograde reaction is blocked during the next 48 hours. The findings suggest that the dispersion of the Nissl substance during retrograde reaction is mediated through induced enzyme synthesis. When the first injection of actinomycin is given 2 days after section of the nerve the neurons on the operated side show extreme chromatolysis 2 days later. This may indicate a more rapid turnover rate of the RNA of the finely dispersed cytoplasmic basophilic particles than of the large Nissl granules of normal neurons.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1432-0614
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary Streptomyces griseus DTH-2 was grown in 5 1 fermentors on complex media containing calcium carbonate as a buffering agent. It was shown that automatic pH control (4N KOH) could substitute the calcium carbonate giving higher yields of streptomycin. The yield was further increased by omitting inorganic phosphate from the medium and by differential addition of glucose/ammonium sulphate during the fermentation. The maximal yield obtained was 8.5 g of streptomycin per liter.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 11 (1975), S. 541-548 
    ISSN: 1432-0428
    Keywords: Radioimmunoassay ; human C-peptide ; human pro-insulin ; insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A routine radioimmunoassay for human C-peptide in serum is described. Antibodies against human C-peptide were raised by immunizing guinea pigs with human b-component. Nine out of 12 animals produced useful antibodies within 6 months. Insulin antibodies coupled to Sepharose were used to bind human proinsulin and insulin in the serum and after centrifugation C-peptide was determined in the supernatant. The detection limit of the assay (calculated as 2 SD from zero) was about 0.003 pmole of C-peptide (in 100 μl). The main sources of error were: (1) Normal and diabetic sera devoid of C-peptide gave a displacement of125I-Tyr-C-peptide varying from 0 to 0.16 nM (6 different antisera). Only one antiserum (M 1181) showed no displacement, and the values of C-peptide determined with this antiserum in normal and diabetic sera were lower than the values determined with another antiserum, which gave a value of 0.07 nM in the sera free of C-peptide. It is suggested that displacement found with most antisera is due to substances in serum that are not related to C-peptide or proinsulin. (2) Serial dilutions of pancreatic extracts and sera may yield dilution curves slightly different to those of the synthetic standard. Possible explanations are discussed. These sources of error can be eliminated or reduced by the proper selection of antisera. Fasting sera from 15 normals, 8 maturity-onset diabetics and 10 insulin-requiring diabetics showed the following concentrations of C-peptide: (M 1181) 0.35±0.09, 0.74+0.51 and 0.21±0.14 (nM, mean±SD). One hour after 1.75 g/kg oral glucose the values increased to 2.24±0.71, 2.34±1.18 and 0.42 ± 0.24 nM.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 12 (1976), S. 627-630 
    ISSN: 1432-0428
    Keywords: Juvenile diabetes ; C-peptide ; remission ; ketonuria ; insulin antibodies ; total IRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Serum C-peptide, insulin-binding IgG and total insulin (IRI) were determined in 96 juvenile diabetics aged 4–21 years, with onset of diabetes at the age of 1–16 years and with 2–17 years' duration of diabetes. Thirty-four patients (35.4%) had detectable levels of C-peptide (≥ 0.04 pmol/ml). Compared to non-diabetic adults, 19 had values below the normal range, 12 showed values within the normal range (0.18–0.63 pmol/ml) and 3 rated above normal. There was a negative correlation between the fasting C-peptide concentration and the degree of ketonuria at the onset of diabetes and a positive correlation between C-peptide levels and the incidence of postinitial remission periods. Patients without detectable C-peptide had significantly higher levels of insulin antibodies than those who had detectable levels of C-peptide. The possibility of a relationship between the intensity of the initial treatment of diabetes and the preservation of the B-cell function is discussed, as well as the possibility of insulin antibodies being a cause of B-cell exhaustion.
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  • 7
    ISSN: 1432-0428
    Keywords: Insulin antibodies ; proinsulin antibodies ; pancreatic polypeptide antibodies ; a-component antibodies ; total serum immunoreactive insulin ; insulin immunogenicity ; insulin-dependent diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ninety-two insulin-dependent diabetics (aged 4–20 years, mean±SD: 13±4) with a duration of diabetes from 2 to 17 years (7±3) were transferred from Lente or NPH (5 × crystallised insulin) to Monotard insulin (highly purified insulin). Total serum immunoreactive insulin levels and concentrations of antibodies against insulin, porcine proinsulin, a-component and pancreatic polypeptide were determined prior to [I] and at a mean of 220 [II], 460 [III], 830 [IV], and 1170 [V] days after the change. All but two subjects had insulin antibodies (IgG) at the start, with a mean value of 2864 μU/ml. There was a significant fall in the mean insulin antibody level between [I] and [II] to 2165 μU/ml (p〈10-7), followed by an increase between [II] and [III] whereafter a slight decrease was observed being significant between [III] and [IV], as well as between [IV] and [V] (p〈0.05); some patients showed a constant fall over the entire period, while others showed fluctuations. Total serum insulin showed a similar pattern, with a mean value of 1141 μU/ml at [I] declining to 522 μU/ml at [V]. The percentage fall between [I] and [V] was greater (54%) than that in the insulin antibodies (30%). Antibodies against acomponent, proinsulin and pancreatic polypeptide were present in 96%, 72% and 41% of the patients respectively before the change in therapy. There was a decline in these antibodies between each sampling (p values between 〈10-3 and 10-8) and, at the end of the investigation antibodies against a-component were above the detection limit in only 4 patients, and none of the patients showed antibodies against proinsulin or pancreatic polypeptide. Thus, removal of the impurities, including the hormonal contaminants of insulin, leads to a slow fall in antibodies to insulin and a much faster disappearance of antibodies against acomponent, proinsulin and pancreatic polypeptide.
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  • 8
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Acanthosis nigricans ; insulin resistance ; C-peptide ; proinsulin ; diabetes mellitus ; glucagon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 16-year-old boy with persistent hyperglycaemia (approximately 16 mmol/l in the fasting state) and acanthosis nigricans had insulin resistance and received daily up to 2 800 U of short-acting, soluble, highly purified porcine insulin. The number and affinity of insulin receptors were markedly decreased. No significant insulin binding to IgG could be detected. Immunoreactive insulin varied between 1344 and 2400 mU/l. Endogenous insulin secretion and proinsulin levels were grossly elevated in the fasting state (C-peptide 2.2–3.5 pmol/ml; proinsulin approximately 1 pmol/ml). After an oral glucose tolerance test and intravenous arginine infusion, B cell hypersecretion was confirmed. The molar ratio of C-peptide to immunoreactive insulin, normally approximately 7, was about 0.3, clearly indicating that most of the immunoreactive insulin was exogenous. The molar ratio of proinsulin to C-peptide, which is about 0.05 in fasting control subjects, was 0.23–0.45, clearly showing that too high a proportion of proinsulin was being secreted. This may indicate that the constant hyperstimulation of the B cell leads to reduced conversion of proinsulin to insulin. Immunoreactive glucagon levels were within normal limits fasting but were above normal after intravenous arginine infusion. Thus, in this case of diabetes with acanthosis nigricans, the severe insulin resistance, probably caused by a receptor defect, was associated with markedly increased B cell function.
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  • 10
    ISSN: 1432-0428
    Keywords: C-peptide ; Type 1 diabetes ; B cell reserve ; children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary C-peptide was determined in 24-h urine collections and in fasting plasma of 27 Type 1 (insulin-dependent) diabetic children (duration of disease 0–6 years) and in 11 matched normal children. Grouping the patients according to duration of disease from onset to 6 years, it was found that in the first year of disease the B cell reserve was a mean of 4.89±1.95 pmol · mg creatinine-1. 24 h-1 compared with a mean of 24.51±2.91 pmol · mg-1 · 24 h-1 in the control group. A further diminution was seen with increase in the duration of disease, until after 6 years when only traces of C-peptide could be detected. There was a good correlation between the levels of plasma C-peptide and urinary C-peptide values as related to creatinine (r = 0.89; p = 〈 0.001). In view of this, and since it is simpler and less traumatic to obtain frequent urine samples from children than it is to obtain blood samples, it was felt that the determination of urinary C-peptide constitutes a valuable tool in the evaluation of the diabetic child.
    Type of Medium: Electronic Resource
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