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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Inorganic chemistry 29 (1990), S. 4483-4486 
    ISSN: 1520-510X
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1520-510X
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 35 (1992), S. 1170-1172 
    ISSN: 1432-0428
    Keywords: Myotonic dystrophy ; proinsulin ; insulin resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hyperinsulinaemia is a reported feature of the inherited multisystem disorder myotonic dystrophy. This phenomenon has been attributed to a compensatory beta cell response to tissue insulin resistance. In this study, circulating concentrations of insulin, proinsulin, and split proinsulin molecules were determined after an overnight fast in ten patients with myotonic dystrophy using two-site monoclonal antibody-based immunoradiometric assays. Results were compared with ten healthy control subjects matched for age, gender, and body mass index. Oral glucose tolerance (75 g), as defined by World Health Organization criteria, was normal in all subjects. Fasting plasma immunoreactive insulin concentration, as determined using a conventional radioimmunoassay, was almost three times higher (p〈0.005) in the myotonic dystrophy patients than the healthy control subjects. By contrast, fasting concentrations (mean±SEM) of C-peptide (0.75±0.09 vs 0.52±0.03 nmol/l, p=0.07) and immunoradiometrically-determined insulin (60±12 vs 38±4 pmol/l, p=0.09) were not significantly different between the groups. Fasting concentrations of proinsulin (10.3±2.9 vs 1.6±0.3 pmol/l, p〈0.01), and 32–33 split proinsulin (7.8±2.5 vs 2.9±0.4 pmol/l, p〈0.05) were significantly elevated in the patients with myotonic dystrophy. Accordingly, the mean fasting proinsulin∶insulin ratio, expressed as a percentage, was significantly increased in the myotonic patients (20±5 vs 4±1%, p〈0.01). The overall C-peptide response to the oral glucose challenge was significantly greater in the myotonic patients compared with the healthy control subjects (p〈0.001). These results provide corroborative evidence of increased beta-cell secretion in myotonic dystrophy. In addition, myotonic dystrophy is characterised by elevated plasma concentrations of proinsulin-like molecules which may cross-react in insulin radioimmunoassays.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; islet-cell antibodies ; insulin secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Basal insulin secretion was compared in nine islet-cell antibody positive, non-diabetic first-degree relatives of children with Type 1 (insulin-dependent) diabetes mellitus and nine normal control subjects matched for age, sex and weight. Acute insulin responses to a 25 g intravenous glucose tolerance test were similar in the two groups (243 (198–229) vs 329 (285–380) mU·l−1·10min−1, mean (±SE), p=0.25). Fasting plasma insulin was assayed in venous samples taken at one min intervals for 2 h. Time series analysis was used to demonstrate oscillatory patterns in plasma insulin. Autocorrelation showed that regular oscillatory activity was generally absent in the islet-cell antibody positive group, whereas a regular 13 min cycle was shown in control subjects (p〈 0.0001). Fourier transformation did, however, show a 13 min spectral peak in the islet-cell antibody positive group, consistent with intermittent pulsatility. We conclude that overall oscillatory patters of basal insulin secretion are altered in islet-cell antibody positive subjects even when the acute insulin response is within the normal range.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; environmental temperature ; non-obese diabetic (NOD) mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An association between the incidence of childhood Type 1 (insulin-dependent) diabetes mellitus and the average yearly temperature in different countries has been reported, the incidence being higher in countries with a lower mean temperature. We have studied the effect of environmental temperature on the incidence of diabetes in an animal model of Type 1 diabetes, the non-obese diabetic (NOD) mouse. Female NOD mice were divided at weaning, with one group placed at a higher temperature (mean 23.7±1.7° C) and the other at a lower temperature (21.0±1.8° C). At 20 weeks of age 6 of 16 mice at lower temperature and 1 of 17 mice at higher temperature had developed diabetes (p 〈 0.02); at 30 weeks 10 of 16 and 5 of 17 mice had developed diabetes (p 〈 0.05). Non-diabetic animals in the low temperature group had a higher food intake than those in the high temperature group between 13–15 weeks of age (28.0±1.2 g/week vs 24.8± 0.7 g/week, P 〈 0.05). In a parallel experiment, histological examination showed that there were similar degrees of insulitis in the high and low temperature groups at seven weeks of age. We conclude that environmental temperature can affect the incidence of diabetes in the NOD mouse and that this may be related to alterations in food intake.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0533
    Keywords: Neuronal autophagy ; Bovine spongiform encephalopathy ; Lysosomes ; Ultrastructure ; Vactiolation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructural neuropathology of mice experimentally inoculated with brain tissue of nyala (Tragelaphus angasi; subfamily Bovinae), or kudu (Tragelaphus strepsiceros; subfamily Bovinae) affected with spongiform encephalopathy was compared with that of mice inoculated with brain tissue from cows (Bos taurus: subfamily Bovinae) with bovine spongiform encephalopathy (BSE). As fresh brain tissue was not available for nyala or kudu, formalin-fixed tissues were used for transmission from these species. The effect of formalin fixation was compared with that of fresh brain in mice inoculated with fixed and unfixed brain tissue from cows with BSE. The nature and distribution of the pathological changes were similar irrespective of the source of inoculum or whether the inoculum was from fresh or previously fixed tissue. Vacuolation caused by loss of organelles and swelling was present in dendrites and axon terminals. Vacuoles were also seen as double-membrane-bound and single-membrane-bound structures within myelinated fibres, axon terminals and dendrites. Vacuoles are considered to have more than one morphogenesis but the structure of vacuoles in this study was nevertheless similar to previous descriptions of spongiform change in naturally occurring and experimental scrapie, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome and kuru. Other features of the ultrastural pathology of the transmissible spongiform encephalopathies including dystrophic neurites and scrapie-associated particles or tubulovesicular bodies were also found in this study. Neuronal autophagy was a conspicuous finding. It is suggested that excess prion protein (PrP) accumulation, or accumulation of the scrapie-associated protease-resistant isoform of PrP, may lead to localised sequestration and phagocytosis of neuronal cytoplasm and ultimately to neuronal loss.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1793
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The marine amphipodAllorchestes compressa Dana, fed on the seagrassHeterozostera tasmanica, was exposed to sublethal concentrations of Cd, Cr, Cu and Zn for 4 wk in flowing sea water, and the concentrations producing the minimum detectable decreases (the minimum effect concentrations, MECs) in average weight, survival and biomass (average weight × survival proportion) were estimated by interpolation from regression models. Survival and biomass were more sensitive than average weight as indicators of sublethal effects. The lowest values of MEC for Cd, Cr, Cu and Zn were 11, 〉250, 3.7 and 99µg 1−1, respectively. For Cu, this value fell below the minimum risk concentration (MRC) calculated from acute toxicity tests (LC50) and application factors (AF); for Cd, the MEC was similar to the MRC; for Cr and Zn, the MECs were well above the MRCs. The metal concentrations in the amphipods at the MECs were 46, 〉46, 364 and 139µg g−1 dry wt for Cd, Cr, Cu and Zn, respectively. Accumulation of the nutrient metals (Cr, Cu and Zn) showed some evidence of metabolic regulation, but the non-nutrient Cd was accumulated without regulation until the amphipods died. In general, those metals that were more highly accumulated by the amphipods were the more toxic.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1424
    Keywords: Adenosine ; Sarcoplasmic reticulum ; Cardiac Ca2+-release channel ; Caffeine ; Adenine nucleotides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Calcium-release channels of sheep cardiac sarcoplasmic reticulum were incorporated into phosphatidylethanolamine bilayers and single channel currents were recorded under voltage-clamp conditions. The effect of adenosine on single channel conductance and gating was investigated, as were the interactions between adenosine and caffeine and adenosine and α,β-methylene ATP. Addition of adenosine (0.5–5 mm) to the cytosolic but not the luminal side of the membrane increased the open probability of single calcium-activated calcium-release channels by increasing the frequency and duration of open events, yielding an EC50 of 0.75 mm at 10 μm activating Ca2+. Addition of 1 mm caffeine potentiated the effects of adenosine at 10 or 100 μm-activating cytosolic calcium, but had no effect on the inability of adenosine to activate the channel at 80 pmcalcium, suggesting discrete sites of action on the calcium-release channel for adenosine and caffeine. In contrast, addition of 100 μm α,β-methylene-ATP decreased single channel open probability in the presence of adenosine, suggesting that these compounds act on the same site on the channel. Activation of single channel opening by adenosine, or by adenosine together with caffeine, had no effect on single channel conductance or the Ca2+/Tris+ permeability ratio. Channels activated by adenosine were characteristically modified by ryanodine and blocked by μm ruthenium red or mm magnesium. These results show that adenosine activates the sheep cardiac sarcoplasmic reticulum Ca2+-release channel by increasing the frequency and duration of open events in a Ca2+-dependent manner. The receptor site on the channel for adenosine is distinct from that for caffeine but probably the same as that for adenine nucleotides.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 137 (1994), S. 215-226 
    ISSN: 1432-1424
    Keywords: Ca2+-release channels ; Sarcoplasmic reticulum ; Cardiac ; Sulmazole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract We investigated the effects of changes in luminal [Ca2+] on the gating of native andpurified sheep cardiac sarcoplasmic reticulum (SR) Ca2+-release channels reconstituted intoplanar phospholipid bilayers. The open probability (P o )of channels activated solely by cytosolic Ca2+ was greater at positive than negative holding potentials. Channels activatedsolely by 10 μm cytosolic Ca2+ exhibited no change in steady-stateP o or in the relationship betweenP o and voltage when the luminal[Ca2+] was increased from nanomolar to millimolar concentrations. In the absence of activating concentrationsof cytosolic Ca2+, the channel can be activated by the phosphodiesterase inhibitor sulmazole (AR-L 115BS). However, cytosolicCa2+-independent activation of the channel by sulmazole requires luminal Ca2+. In the presence ofsulmazole, at picomolar luminal [Ca2+] the channel remains completely closed. Increasing the luminal [Ca2+]to millimolar levels markedly increases the P o via an increase in theduration of open events. The P o and duration of the sulmazole-activated, luminalCa2+-dependent channel openings are voltage dependent. In the presence of micromolar luminal Ca2+, theP o and duration of sulmazole-activated openings are greater atnegative voltages. However, at millimolar luminal [Ca2+], long openings are also observed at positive voltages and theP o appears to be similar at positive and negative voltages. Our findings indicate thatthe regulation of channel gating by luminal Ca2+ depends on the mechanism of channel activation.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1238
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Conclusions Considerable time and energy has been invested in the conception, modelling and evaluation of sophisticated severity scoring systems for ICU patients. These systems are created to enhance the precise estimation of hospital mortality for large ICU patient populations. Their current low sensitivity precludes their use for predicting out-come for individual ICU patients. However, severity scores can already be valuable for predicting mortality in groups of general ICU patients, and are very useful in the clinical trial setting. Outcome of ICU therapy, however, should incorporate more than mortality. Morbidity, disability and quality of life should also be taken into account; these factors were not taken into consideration in the design of the currently available severity scoring systems. At present, the severity scores have a very limited or no role in clinical decision-making for an individual patient, because they are based on a number of physiological and disease-oriented variables collected during the first 24 h after ICU admission. Future developments and subsequent validation of the dynamic process of clinical, physiological and organ-specific variables could improve the sensitivity and the value of severity scoring. Further collaborative developmental work in this field should be encouraged and supported across Europe and North America.
    Type of Medium: Electronic Resource
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