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  • 1
    Electronic Resource
    Electronic Resource
    Measurement of human proinsulin by an indirect two-site immunoradiometric assay (1979)
    Springer
    Diabetologia 17 (1979), S. 229-234 
    Details
    ISSN: 1432-0428
    Keywords: Indirect two-site immunoradiometric assay ; human proinsulin ; insulin ; C-peptide ; diabetes ; insulinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An indirect two-site immunoradiometric assay is described for the measurement of human proinsulin in plasma. Polyethylene tubes coated with purified guinea-pig antibodies to insulin were used to extract proinsulin and insulin from plasma. Rabbit antibody to human C peptide was then added to react with the C-peptide moiety of the bound proinsulin. The uptake of this antibody was measured by the subsequent binding of125I-sheep antibody to rabbit IgG. The binding of radioactivity to the tubes was a function of the proinsulin concentration in the sample. The sensitivity of the assay was 0.006 pmol/ml. Only 200 μl of plasma was required in the assay and the125I-labelled antibody was produced from readily available reagents. The polyethylene tubes remained stable for at least 5 months after coating. The mean fasting proinsulin level was 0.009 pmol/ml in sixteen normal subjects and 0.025 pmol/ml in twelve maturity onset diabetics. Oral glucose produced an 8 fold increase in proinsulin concentration but a decline in the plasma proinsulin/insulin molar ratio. Four patients with insulinoma had extremely elevated proinsulin levels and proinsulin/insulin ratios.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01235859
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  • 2
    Electronic Resource
    Electronic Resource
    Indirect two-site immunoradiometric assay of rat and mouse proinsulin (1979)
    Springer
    Diabetologia 17 (1979), S. 235-242 
    Details
    ISSN: 1432-0428
    Keywords: Indirect two-site immunoradiometric assay ; rat proinsulin ; mouse proinsulin ; islets ; proinsulin/insulin ratio
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An indirect two-site immunoradiometric assay for rat and mouse proinsulin using a rabbit antibody to synthetic rat C-peptide has been developed. The sensitivity of the assay is 0.006 pmol/ml. Proinsulin was 4.95% of the total proinsulin and insulin in extracts of rat pancreas and 5.45% in extracts of isolated rat islets. The mean fasting rat insulin and proinsulin concentrations were 0.13±0.09 pmol/ml (n=5) and 0.008±0.002 pmol/ml (n=5) respectively. The mean fasting mouse proinsulin concentration was 0.019±0.006 pmol/ml (n=8). In rats intravenous glucose produced a biphasic insulin response but proinsulin rose progressively to 0.021±0.011 pmol/ml at 45 min. In mouse oral glucose increased the proinsulin concentration to 0.13 pmol/ ml at 30 min. Proinsulin release from isolated rat islets was studied during intermittent or continuous high glucose (20 mmol/l) stimulation in static incubation. Significant increases in proinsulin release were only observed 90 min after initial exposure to high glucose whether glucose stimulation was continuous or intermittent. Both in vivo and in vitro glucose stimulation led initially to a fall in the proinsulin/ insulin molar ratio but later upon prolonged stimulation this progessively increased to above the basal value.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01235860
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  • 3
    Electronic Resource
    Electronic Resource
    Functional and structural abnormalities in the nerves of Type I diabetic baboons: aminoguanidine treatment does not improve nerve function (2000)
    Springer
    Diabetologia 43 (2000), S. 110-116 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Diabetic complications, neuropathy, autonomic, nerve conduction velocity, aminoguanidine, monkey, morphometry, myelin, advanced glycation end products.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. To improve understanding of the pathophysiology of diabetic neuropathy and to establish a primate model for experimental studies, we examined nerve changes in baboons with Type I (insulin-dependent) diabetes mellitus. We also examined the effect of aminoguanidine (an inhibitor of the formation of advanced glycation end products) on nerve function.¶Methods. Male baboons (Papio hamadryas) were assigned to four groups; control, diabetic, control and diabetic treated with aminoguanidine. Diabetes was induced with streptozotocin (60 mg/kg, intravenous). Insulin and aminoguanidine (10 mg/kg) were injected subcutaneously daily. Motor and sensory nerve conduction velocity was measured using standard techniques. Autonomic function was examined by measuring heart rate response to positional change. Sural nerve morphometry was analysed in the diabetic group (mean duration 5.5 years) along with their age-matched controls.¶Results. The diabetic groups were smaller in size with a mean HbA1 c of 8.9 ± 1.2 %. The nerve conduction velocity and heart rate response was reduced in the diabetic groups. Morphometric analysis of the diabetic sural nerve showed smaller axon diameter (2.99 ± 0.06 μm vs 3.29 ± 0.06 μm; p 〈 0.01) accompanied by thinner myelin (1.02 ± 0.02 μm vs 1.15 ± 0.02 μm, p 〈 0.01) with no change in the axon density. Treatment with aminoguanidine for 3 years had no effect on glycaemic control and did not restore conduction velocity or autonomic dysfunction in the diabetic animals, contrary to the studies in rats.¶Conclusions/interpretation. These results show that the primate is a good model to study diabetic neuropathy and suggest that the accumulation of advanced glycation end products are not an early mechanism of nerve damage in this disorder. [Diabetologia (2000) 43: 110–116]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050014
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  • 4
    Electronic Resource
    Electronic Resource
    High glucose concentration inhibits the expression of membrane type metalloproteinase by mesangial cells: possible role in mesangium accumulation (2000)
    Springer
    Diabetologia 43 (2000), S. 642-648 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Matrix metalloproteinase ; nephropathy ; extracellular matrix ; degradation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. High glucose concentration decreases the degradation of mesangium matrix, an action substantially mediated by a reduction in the activities of the matrix metalloproteinases (MMPs). Metalloproteinase-2 is unique in that it is activated on the cell surface by one of the membrane type metalloproteinases (MT1-MMP), a process involving complex interactions with tissue inhibitor of metalloproteinase-2. The aim of this study was investigate the effects of glucose concentration on mesangial cell gene expression of MT1-MMP and its ability to modulate the activation of metalloproteinase-2. Methods. Gene expression was determined using competitive RT-PCR, protein expression of MMP-2 was measured by western blot and its activation by zymography. Concanavalin A, known to increase MT1-MMP expression was added in some experiments. Results. High glucose concentration decreased MT1-MMP gene expression (11.52 ± 1.63 and 4.84 ± 0.72 amol/μg RNA, 5 vs 25 mmol/l glucose, respectively) and decreased activation of MMP-2 by 30 % despite a twofold increase in gene expression of MMP-2. Concanavalin A increased expression of MT1-MMP and activation of MMP-2. Irrespective of whether MMP-2 was from endogenous or exogenous source there was an excellent correlation between the MT1-MMP expression and degree of MMP-2 activation, whereas the gene expression of TIMP-2 was not significantly altered by high glucose concentration or concanavalin A. Conclusions/interpretation. Our results indicate that in a high glucose milieu, suppression of MT1-MMP expression could explain the low MMP-2 activity in the presence of high MMP-2 expression. This process could contribute to the mesangium matrix accumulation in diabetic nephropathy. [Diabetologia (2000) 43: 642–648]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051353
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  • 5
    Electronic Resource
    Electronic Resource
    Response of Charcot's arthropathy to contact casting: assessment by quantitative techniques (2000)
    Springer
    Diabetologia 43 (2000), S. 481-484 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Complications, neuropathy, foot, radionuclide scan, podiatry.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. This study used two different methods of quantitative bone scanning to study the relation between activity of Charcot's arthropathy and clinical variables over 12 months.¶Methods. Skin temperature of affected and unaffected feet was measured at baseline and every 3 months for 12 months in 17 subjects. Eight subjects underwent a three-phase quantitative bone scan at baseline and 3 monthly for 12 months. Bone isotope uptake in a standard rectangular area over the foot and tibia was analysed by the bilateral scan method (the ratio of isotope uptake of affected and unaffected feet) and the unilateral scan method (the ratio of isotope uptake of affected foot and ipsilateral tibia). The affected foot was placed in a contact cast for an average of 8 months.¶Results. At presentation the affected foot was hotter than the unaffected foot but the temperature became progressively cooler over 12 months. Median isotope uptake in the affected foot was 2.1 % of the injected dose (interquartile range, IQR 1.9–3.0). In both scanning methods the ratio of uptake decreased after casting but at 12 months the affected foot still had more isotope uptake. There was a strong correlation between temperature difference and the ratio of uptake in the bilateral scan method (r = 0.90; p 〈 0.0001) but when using the unilateral scan method this relation was not significant (r = 0.1; p = 0.6). A strong relation existed between perfusion of the affected foot in the dynamic phase and isotope uptake in the delayed phase of the scans (r = 0.92; p 〈 0.0001).¶Conclusion/interpretation. Bone activity and skin temperature of Charcot's arthropathy can be measured quantitatively and both improve over 12 months with contact casting. There is a strong relation between perfusion and disease activity in this condition. [Diabetologia (2000) 43:481–484]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051332
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  • 6
    Electronic Resource
    Electronic Resource
    The Thermal stability of collagen in diabetic rats: correlation with severity of diabetes and non-enzymatic glycosylation (1983)
    Springer
    Diabetologia 24 (1983), S. 282-285 
    Details
    ISSN: 1432-0428
    Keywords: Diabetes ; rat collagen ; thermal stability ; glycosylated haemoglobin ; ageing ; non-enzymatic glycosylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The thermal stability of collagen fibres from rat tail tendon was studied in both normal and diabetic rats. Results were correlated with the age of the animals, glycosylated haemoglobin level and the degree of non-enzymatic glycosylation of the collagen. Age was found to be the most important single determinant of the thermal rupture time of collagen fibres (r=0.87, p 〈 0.005). Thermal rupture time was also increased in diabetes and showed good correlation with glycosylated haemoglobin (r=0.69, p 〈 0.005) and non-enzymatic glycosylation of collagen (r=0.51, p 〈 0.005). The correlation of glycosylated haemoglobin level and thermal rupture time was significant, independent of age and non-enzymatic glycosylation of collagen. Experiments in vitro showed that incubation of collagen fibres with glucose increased the thermal stability of collagen. These results demonstrated an independent effect of severity of diabetes on the physical properties of collagen. The role of non-enzymatic glycosylation in causing the changes in collagen properties in diabetes remains to be fully elucidated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00282714
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  • 7
    Electronic Resource
    Electronic Resource
    Non-enzymatic glycosylation of tissue protein in diabetes in the rat (1983)
    Springer
    Diabetologia 24 (1983), S. 377-381 
    Details
    ISSN: 1432-0428
    Keywords: Non-enzymatic glycosylation ; diabetes ; glycosylated haemoglobin ; complications ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Non-enzymatic glycosylation of tissue and haemolysate proteins has been studied in normal and diabetic rats by reduction with tritiated sodium borohydride (NaB3H4) alone or in combination with chromatography on m-aminophenyl-boronic acid coupled to Biogel P-6. With NaB3H4 reduction alone, there was a linear relationship between plasma glucose and tritium incorporation into haemolysate protein. However, increased non-enzymatic glycosylation of tissue protein could not be demonstrated with NaB3H4 reduction alone. Tritiated glycosylated amino acids could be selectively removed by maminophenylboronic acid immobilized on Biogel P-6, then eluted by acidification and the radioactivity in the acidic peak used to estimate non-enzymatic glycosylation. Using the combined techniques, an increase in non-enzymatic glycosylation was observed in heart, kidney and liver obtained from rats with diabetes of 18 weeks duration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00251828
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  • 8
    Electronic Resource
    Electronic Resource
    Computation of Nonlinear Free-Surface Flows (1996)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 28 (1996), S. 249-278 
    Details
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.fl.28.010196.001341
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  • 9
    Electronic Resource
    Electronic Resource
    Hydrodynamics of Fishlike Swimming (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 32 (2000), S. 33-53 
    Details
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Interest in novel forms of marine propulsion and maneuvering has sparked a number of studies on unsteadily operating propulsors. We review recent experimental and theoretical work identifying the principal mechanism for producing propulsive and transient forces in oscillating flexible bodies and fins in water, the formation and control of large-scale vortices. Connection with studies on live fish is made, explaining the observed outstanding fish agility.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.fluid.32.1.33
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  • 10
    Electronic Resource
    Electronic Resource
    Some properties of a hybrid element method for water waves (1979)
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 14 (1979), S. 1627-1641 
    Details
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: Two properties of hybrid element method for diffraction and radiation of water waves are examined. For long waves in shallow water the method is shown to give a unique solution for all frequencies. Thus, unlike several other known methods, there are no irregular frequencies for which the approximating matrix equation is singluar. For a sea of arbitrary depth, it is shown that all known global identities such as reciprocity and energy theorems are preserved by the discrete solution. Thus, satisfaction of these identities by the numerical solution is only a necessary but by no means sufficient condition for accuracy.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/nme.1620141105
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