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  • 1
    ISSN: 0303-7207
    Keywords: Catecholamine ; Glucagon ; Glucose ; Insulin ; Pyruvate kinase ; Thyroid
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0533
    Keywords: Primary cerebral lymphoma ; AIDS ; Epstein-Barr virus ; In situ hybridization ; SouthernBlot
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Three cases of primary cerebral lymphoma in acquired immunodeficiency syndrome were studied. Tumoral fragments taken at autopsy were frozen and studied by the Southern blot technique (SBT). Other tumoral fragments were fixed in formalin, embedded in paraffin and used for in situ hybridization (ISH) with biotinylated probes for DNA of Epstein-Barr virus (EBV). ISH was positive in each case with a spotty nuclear labelling of certain tumoral cells. SBT evidenced a clonal rearrangement of the immunoglobulin heavy chain gene in each case. In addition, EBV DNA was detected in each frozen fragment with only one restriction pattern, indicating that the EBV-infected cell population was a clonal expansion of a progenitor cell.
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  • 3
    ISSN: 1432-0533
    Keywords: Peripheral nerve biopsy ; HIV infection ; Ultrastructure ; in situ hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A peripheral nerve biopsy was performed in 15 patients with human immunodeficiency virus (HIV) infection and polyneuropathy. Two cases [1 asymptomatic, 1 AIDS-related complex (ARC)] presented with chronic inflammatory demyelinating polyneuropathy; there was 1 case (asymptomatic) of mononeuropathy multiplex and 12 cases (1 asymptomatic, 1 ARC, 10 AIDS) with distal symmetrical polyneuropathy. Epi- or endoneurial microvasculitis was observed in 6 cases. Electron microscopy showed that nerve fiber lesions were mainly axonal. Severe segmental demyelination was also present in both cases of chronic inflammatory demyelinating polyneuropathy, with characteristic features of active demyelination in one. Numerous plasmacytoid cells were found in the endoneurium in 4 patients. Tubuloreticular inclusions were present in endothelial cells in the 10 cases with AIDS but absent in the other patients. Direct immunopathological examination with anti-immunoglobulin sera was negative in all cases. HIV was evidenced by in situ hybridization in 2 AIDS patients; no Epstein-Barr virus or cytomegalovirus was detected.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 19 (1980), S. 505-510 
    ISSN: 1432-0428
    Keywords: Hyperthyroidism ; blood ketone bodies ; glycerol ; catecholamines ; starvation ; β-blockade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The metabolic status of 16 hyperthyroid patients and 22 control subjects was studied in the post-absorptive state after 3 days on a standard diet (35 kcal/kg body weight/day). In hyperthyroidism the ranges of blood ketone body (19–1159 vs 17–233 μmol/l, p〈0.001) and glycerol (59–285 vs 15–69 μmol/l, p〈0.001) concentrations were increased relative to controls despite slight hyperglycaemia (4.9±0.6 vs 4.6±0.4 mmol/l, mean±SD p〈0.05). Plasma non-esterified fatty acids, immunoreactive insulin and glucagon levels were not significantly different. A positive correlation was found between thyroid hormone and ketone body (p〈0.02) and glycerol (p〈0.05) levels and between glycerol and ketone bodies (p〈0.05). There was no correlation of non-esterified fatty acids with either thyroid hormone or ketone body concentrations. In hyperthyroid patients propranolol administration for 4 days induced a decrease in triiodothyronine (349±140 to 229±107 ng/100ml, p〈0.01) and a dramatic fall in ketone body (18–295 μmol/l, p〈0.001) and glycerol (44–130 μmol/l, p〈0.001) levels. Non esterified fatty acids were unchanged. There was no longer a correlation between thyroid hormones and ketone bodies or glycerol. Placebo administration to 6 other hyperthyroid patients had no significant effect. In euthyroid obese subjects on a 600 kcal/day diet, propranolol administration did not change ketone body or glycerol levels. These data provide evidence for an increase in both lipolysis and ketogenesis in hyperthyroidism which might, at least in part, be dependent upon a catecholamine β-receptor mediated mechanism.
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  • 5
    ISSN: 1432-0428
    Keywords: Keywords Krebs cycle ; stable isotope ; mass spectrometry ; gluconeogenesis ; fatty acid oxidation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To test whether gluconeogenesis is increased in non-insulin-dependent diabetic (NIDDM) patients we infused (post-absorptive state) healthy subjects and NIDDM patients with [6,6-2H2]glucose (150 min) and [3-13C]lactate (6 h). Liver glutamine was sampled with phenylacetate and its labelling pattern determined (mass spectrometry) after purification of the glutamine moiety of urinary phenylacetylglutamine. After correction for 13CO2 re-incorporation (control test with NaH13CO3 infusion) this pattern was used to calculate the dilution factor (F) in the hepatic oxaloacetate pool and fluxes through liver Krebs cycle. NIDDM patients had increased lactate turnover rates (16.18 ± 0.92 vs 12.14 ± 0.60 μmol · kg−1· min−1, p 〈 0.01) and a moderate rise in glucose production (EGP) (15.39 ± 0.87 vs 12.52 ± 0.28 μmol · kg−1· min−1, p = 0.047). Uncorrected contributions of gluconeogenesis to EGP were 31 ± 3 % (control subjects) and 17 ± 2 % (NIDDM patients). F was comparable (1.34 ± 0.02 and 1.39 ± 0.09, respectively) and the corrected percent and absolute contributions of gluconeogenesis were not increased in NIDDM (25 ± 3 % and 3.8 ± 0.5 μmol · kg−1· min−1) compared to control subjects (41 ± 3 % and 5.1 ± 0.4 μmol · kg−1· min−1). The calculated pyruvate carboxylase over pyruvate dehydrogenase activity ratio was comparable (12.1 ± 2.6 vs 11.2 ± 1.4). Lastly hepatic fatty oxidation, as estimated by the model, was not increased in NIDDM (1.8 ± 0.4 vs 1.6 ± 0.1 μmol · kg−1· min−1). In conclusion, in the patients studied we found no evidence of increased hepatic fatty oxidation, or, despite the increased lactate turnover rate, an increased gluconeogenesis. [Diabetologia (1998) 41: 212–220]
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  • 6
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; tubulin ; microtubules ; anti-tubulin antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Antibodies to tubulin, the fundamental protein of microtubules, were studied by radioimmunoassay in patients with Type 1 (insulin-dependent) diabetes of varying duration and in healthy control subjects. Elevated levels of anti-tubulin antibodies were found in 46% of 28 patients with Type 1 diabetes of recent onset (⩽ 6 months) and in only 6.2% of 64 patients with long-standing Type 1 diabetes (duration 6–43 years). None of 34 DR3-positive normal subjects and none of 20 Type 2 (non-insulin-dependent) diabetic patients were positive for anti-tubulin antibodies. Anti-tubulin antibody levels were elevated in two out of 26 first-degree relatives of Type 1 diabetic patients. The specificity of the detection of anti-tubulin antibodies was demonstrated by (1) dilution of the sera, (2) competitive binding experiments between labelled and unlabelled tubulin, (3) immunoblotting. Antibodies to tubulin were elevated in 60% of patients with islet cell surface antibodies and there was a significant association between anti-tubulin antibodies and islet-cell surface antibodies. These antibodies, however, recognize different specificities, since adsorption of islet cell surface antibody by rat islets did riot alter the anti-tubulin antibody activity. Elevated anti-actin antibody responses were found in two out of 17 and one out of 26 patients with recent onset and long-standing Type 1 diabetes, respectively. In conclusion, anti-tubulin antibodies are detected in a high proportion of patients with diabetes of recent onset, are associated with islet cell surface antibodies and like islet cell surface antibodies decrease or disappear during the course of the disease. Therefore, elevation of antitubulin antibodies could represent another ‘marker’ of the immunological features of Type 1 diabetes. However, these findings, together with our previous observation of an elevation of anti-tubulin antibodies in autoimmune thyroid disorders, indicate a wider involvement of autoimmunity with tubulin and suggest that similar autoimmune phenomena could develop in Type 1 diabetes and some other diseases.
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  • 7
    ISSN: 1432-0428
    Keywords: Dawn phenomenon ; Type 1 (insulin-dependent) diabetes ; adolescent ; growth hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to reassess the role of growth hormone in the dawn phenomenon, we studied eight C-peptide negative diabetic adolescents, who are likely to exhibit important nocturnal growth hormone surges. The insulin infusion rate necessary to maintain euglycaemia was predetermined in each patient from 22.00 hours to 01.00 hours, and then kept constant until 08.00 hours resulting in stable free insulin levels. Blood glucose rose from 4.3±0.7 mmol/l at 01.00 hours to 7.1±1.1 mmol/l at 08.00 hours (p〈0.01) secondary to an increased hepatic glucose production. All the subjects presented an important growth hormone secretion, ranging from 20 to 66 ng/ml (peak values) and from 3619 to 8621 ng·min· ml−1 (areas under the curve). The insulin infusion rate selected for each patient was positively correlated with the nocturnal growth hormone secretion (area under the curve) (r=0.87, p〈0.01). On the other hand, there was no relationship between the nocturnal growth hormone secretion and the magnitude of the early morning blood glucose rise (r=−0.48, p〉0.2). We conclude that, in Type 1 (insulin-dependent) diabetic adolescents, the dawn phenomenon exists but is moderate despite important growth hormone surges; the nocturnal growth hormone secretion influences the nocturnal insulin requirements but not the dawn phenomenon itself, if insulinisation is adequate.
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  • 8
    ISSN: 1432-0428
    Keywords: Fructose ; glucose ; stable isotopes ; [13C] ; mass spectrometry ; nutrition ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Among monosaccharides, fructose has a small hyperglycaemic effect. In order to better explain the mechanisms which cause this metabolic property, we used tracers labelled with stable isotopes (deuterated glucose and naturally 13C labelled fructose) to quantify the overall glucose appearance, the rate of appearance in plasma of the 13C glucose synthesized from fructose, and the fructose oxidation in vivo in man during a 6-h period following ingestion of 0.5 and 1 g · kg−1 fructose. Fructose had a very small effect on overall glucose appearance (NS). During the 6 h of the study, it was found that the overall glucose appearance was 0.87±0.06 and 0.89±0.06 g · kg−1 (NS). The amount of glucose synthesized from fructose was 0.27±0.04 and 0.51±0.03 g · kg−1 (p〈0.01) representing 31% and 57% of overall glucose appearance (p〈0.01); the non-fructose glucose production was 0.60±0.02 and 0.38±0.03 g · kg−1 (p〈0.05) after the 0.5 and 1 g · kg−1 load, respectively. Fructose oxidation was 0.28±0.03 and 0.59±0.07 g · kg−1 after the 0.5 and 1 g · kg−1 load respectively (p〈0.01) representing 56% and 59% of the fructose loads (NS). These data show that the low hyperglycaemic effect of fructose is explained by its very small effect on overall glucose appearance and that fructose has a sparing effect on glucose metabolism.
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  • 9
    ISSN: 1432-0428
    Keywords: Acetoacetate ; β-hydroxybutyrate ; ketogenesis ; ketone body kinetics ; stable isotopes ; mass spectrometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to avoid the use of radioactive tracers for the determination of human ketone body turnover, we have developed a method using a primed-continuous infusion of 13C-labelled acetoacetate or D-β-hydroxybutyrate. Determination of the mole percent enrichment of blood acetoacetate and D-β-hydroxybutyrate was performed by gas chromatography/mass spectrometry. In the post-absorptive state, the mean total ketone body appearance rate, determined in four subjects, was 3.74 μmol · kg−1 · min−1 using [3,4-13 C2] acetoacetate and 2.76 μmol · kg−1 · min−1 using [3-13C]D-β-hydroxybutyrate, values in agreement with those reported in studies with 14C-labelled tracers. In order to evaluate the usefulness of the method for determination of ketone body kinetics in non steady-state conditions, we infused four subjects with natural sodium acetoacetate and calculated the isotopically determined total ketone body appearance rate using a single compartment model (volume of distribution 0.201/kg; functional pool fraction: 1). During the tests with [3,4-13C2]-acetoacetate, the actual infusion rates of natural acetoacetate were 7.3±0.3, 14.6±0.8, 21.9±1.2 and 10.9 ± 0.6 μ mol · kg−1 · min−1 whereas the corresponding isotopically determined total ketone body appearance rates were respectively 9.2±1.0, 16.3±0.7, 23.1±1.1 and 10.7±0.8 μmol· kg−1 · min−1. During the tests with [3-13C]D-β-hydroxybutyrate, the actual infusion rates were 8.4 ± 0.5, 16.8 ± 0.9, 25.2 ±1.4 and 12.6±0.8 μmol · kg−1 · min−1, and the isotopically determined appearance rates respectively 11.1±0.7, 16.7±0.7, 25.0±1.1 and 11.1 ± 0.7 μmol · kg−1 · min−1. Thus, using either tracer we found a good agreement between acetoacetate infusion rate and tracer-determined appearance rate of ketone bodies. In conclusion, the present method may be used to determine human ketone body kinetics under steady-state and non steady-state conditions.
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  • 10
    ISSN: 1432-0428
    Keywords: Stable isotope ; [13C] glucose ; mass spectrometry ; human ; oral glucose load ; gas chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The use of 13C labelled glucose in human metabolic studies has been limited by the high cost of the tracer and the problems of measuring low 13C isotopic abundance in plasma glucose. In the present work we describe a new gas chromatograph-isotope ratio mass spectrometer allowing the measurement of a 0.001 atom % increase in 13C abundance over baseline, on a nanomole glucose sample. Studies were performed in rats and in human subjects. The rate of glucose appearance in 24 h fasted rats using D-[1-13C] glucose as tracer and analysed by this new method was found to be 10.4±0.7 mg·kg−1· min−1, a value 21% lower than that found using D-[6,6-2H2] glucose as tracer (13.1±1.1 mg· kg−1· min−1) analysed by classic gas chromatography-mass spectrometry. The new method was also used to trace, in combination with D-[6,6 2H2] glucose, the metabolic fate in human subjects of two oral glucose loads (0.5 g· kg·−1), 1 g· kg ·−1) labelled with 0.1% D-[U-13C] glucose. During the six hours following the glucose load, it was found that total glucose appearance was 0.97±0.04 g· kg·−1 and 1.2±0.04 g· kg·−1, exogenous glucose appearance was 0.51±0.02 g· kg·−1 and 0.84±0.04 g· kg·−1, endogenous glucose production was 0.44±0.04 g· kg·−1 and 0.35±0.06 g·kg·−1 after the 0.5 and 1 g·kg·−1 load respectively. These values are similar to those reported using glucose labelled with radioactive isotopes. These results show that reliable kinetic parameters of glucose metabolism can be determined, without health hazard, in humans, at low cost, using 13C labelled glucose analysed with a new gas chromatograph-isotope ratio mass spectrometer.
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