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| 2. |
- Bosaeus, Ingvar, 1950, et al.
(författare)
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Comparison of methods to estimate body fat in growth hormone deficient adults.
- 1996
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Ingår i: Clinical endocrinology. - 0300-0664. ; 44:4, s. 395-402
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Tidskriftsartikel (refereegranskat)abstract
- All of the presently used methods for in-vivo determination of body composition have inherent methodological errors and depend on various assumptions. We have therefore compared several different methods used to measure body fat in adult GH deficiency during GH treatment.Comparison of body composition data from a two-phase trial with an initial placebo-controlled, double-blind 6-month period, followed by open treatment with GH until all patients had received GH for 12 months.Twenty-five patients with known GH deficiency entered the study. Baseline examinations were complete in 23 patients, and 22 patients (16 males, 6 females) completed all examinations after treatment.Body fat calculated from total body potassium (TBK) by whole-body 40K counting, total body water (TBW) by tritium dilution, total body nitrogen (TBN) by neutron activation, and bioelectric impedance (BIA) measurements were compared to body fat determinations by dual-energy X-ray absorptiometry (DEXA) in two-compartment and multicompartment body composition models.At baseline, DEXA fat mass agreed well at group level with measurements based on TBW or TBK alone, in a four-compartment model based on TBK and TBW, and a multicompartment model based on bone mineral (by DEXA), TBN and TBW. Body fat by BIA agreed less well. After 12 months of GH treatment, body fat decreased by all methods used. This decrease was smaller by DEXA than by the other methods. The four-compartment model based on TBK and TBW, and TBW alone, showed the best agreement with changes in DEXA fat.All methods showed a decrease of body fat with GH treatment, but variation between methods was considerable.
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| 3. |
- Carlsson, Jörgen, et al.
(författare)
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Conjugate chemistry and cellular processing of EGF-dextran
- 1999
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 38:3, s. 313-321
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Tidskriftsartikel (refereegranskat)abstract
- Conjugates with specific binding to the epidermal growth factor receptor, EGFR, of interest for radionuclide based imaging and therapy were prepared using mouse epidermal growth factor, mEGF, and dextran. In one type of conjugate, mEGF was coupled to dextran by reductive amination in which the free amino group on the mEGF N-terminal reacted with the aldehyde group on the reductive end of dextran. The end-end coupled conjugate could be further activated by the cyanopyridinium agent CDAP, thereby introducing tyrosines to the dextran part. In the other type of conjugate, the cyanylating procedure using CDAP was applied, first to activate dextran and then allowing for the amino terminus of mEGF to randomly attach to the dextran. In the latter case, radionuclide-labelled tyrosines or glycines could be added in the same conjugation step. All types of mEGF-dextran conjugates had EGFR-specific binding since the binding could be displaced by an excess of non-radioactive mEGF. The conjugates were to a large extent internalized in the test cells and the associated radioactivity was retained intracellularly for different times depending on both the type of cells and conjugate applied. Different intracellular 'traffic routes' for the radionuclides are discussed as well as applications for both imaging and therapy.
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| 4. |
- Carlsson, Margaretha S.
(författare)
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Pharmacokinetics of 2-mercaptopropionylglycine (Tiopronin) in man
- 1993
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 2-Mercaptopropionylglycine (2-MPG, tiopronin) has been used successfully in the treatment of cystinuria despite the lack of knowledge of its pharmacokinetics. Therefore methods based on high-performance liquid chromatography and fluorometric detection were developed for quantitative analysis. The total, non-protein-bound, and free (thiolic) tiopronin were measured in plasma using this method.The phannacokinetic disposition of tiopronin in plasma after intravenous administration was best described by a three exponential function. Plasma concentration time-curves of total tiopronin exhibited a rapid distribution phase, a B-phase corresponding to renal excretion, and a long terminal elimination phase. The latter was the result of strong disulphide binding of tiopronin to proteins. The non-protein-bound tiopronin was eliminated faster judging by its early appearance in urine. Mean bioavailability was 63 % in healthy volunteers with great interindividual variability (range 33-91%).Multiple dosing studies gave similar pharrnacokinetic parameters as for single dose studies and studies on patients with renal impaitment elucidated the renal clearance of the drug. In vitro studies showed a slow dissolution of the drug dosage form employed. A metabolite, 2-mercaptopropionic acid, was identified and its pharmacokinetics was investigated. The mechanism of action of the drug is discussed based on the results of measuring free tiopronin in plasma.
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| 5. |
- Carvalho, Eugénia, 1967, et al.
(författare)
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Low cellular IRS 1 gene and protein expression predict insulin resistance and NIDDM.
- 1999
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Ingår i: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - 0892-6638 .- 1530-6860. ; 13:15, s. 2173-8
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Tidskriftsartikel (refereegranskat)abstract
- We examined the gene and protein expression of IRS 1 (insulin receptor substrate 1) in adipocytes from two groups of healthy individuals with an increased propensity for non-insulin-dependent diabetes mellitus (NIDDM): those with two first-degree relatives with diabetes and another group with massive obesity. A low expression of IRS 1 (
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| 6. |
- Ekblad, Alf, 1957-, et al.
(författare)
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Day-to-day variation in nitrogenase activity of alnus-incana explained by weather variables : a multivariate time-series analysis
- 1994
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Ingår i: Plant, Cell and Environment. - : Wiley. - 0140-7791 .- 1365-3040. ; 17:3, s. 319-325
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Tidskriftsartikel (refereegranskat)abstract
- A modelling system is described that indicates the extent to which day-to-day variations in nitrogenase activity in young Alnus incana (L.) Moench, grown in defined conditions in the field, may be affected by weather conditions both during and prior to the day of measurement. Nitrogenase activity (acetylene reduction activity, ARA) was measured weekly on intact field-grown grey alder (A. incana) plants, 0.15–0.42 m tall at planting, nodulated with Frankia. The measurements were done at noon on two groups of plants in 1987 and on two other groups in 1988. Each group was made up of five or six plants. Seven weather variables: daily sunshine hours, daily mean, maximum and minimum air temperature, daily mean and 1300 h relative humidity, and daily rainfall were used. The relation between log(ARA/leaf area) and the weather variables were analysed using a PLS model (partial least squares projection to latent structures). The advantage of PLS is that it can handle x-variables that are correlated. Data from 1987 were chosen as a training set. Multivariate PLS time series analysis was made by adding, in a stepwise manner, the weather data up to 5 d before the day of measurement. This procedure gave six models with n * 7 x-variables (n= 1–6). With the models from the time series analysis of 1987 data, true predictions of ARA per leaf area were made from weather data 1988 (test set 1) and from ‘early-season’ weather data from 1987 and 1988 (test set 2). The variation in ARA/leaf area could be predicted from the weather conditions. The predictions of the two test sets improved when the weather conditions one and two days before the day of measurements were added to the model. The further addition of weather data from 3 to 5 d before the day of measurement did not improve the model. The good predictions of ARA/leaf area show that the alders responded to the variable weather conditions in the same way in 1988 as in 1987, despite the ten-fold difference in size (leaf area) at the end of the growing season. Among the weather variables, air temperature and the daily sunshine hours were positively correlated to ARA, while relative air humidity and rainfall were negatively correlated to ARA. The daily minimum temperature and rainfall appeared to have least impact on ARA. By use of PLS, we could extract information out of a data set containing highly correlated x-variables, information that is non-accessible with conventional statistical tools such as multiple regression. When making measurements of nitrogenase activities under field conditions, we propose that attention should be paid to the weather conditions on the days preceding the day of measurement. The day-to-day variation in nitrogenase activity is discussed with reference to known effects of stress factors under controlled conditions.
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| 7. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Growth hormone treatment of abdominally obese men reduces abdominal fat mass, improves glucose and lipoprotein metabolism, and reduces diastolic blood pressure.
- 1997
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X. ; 82:3, s. 727-34
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Tidskriftsartikel (refereegranskat)abstract
- The most central findings in both GH deficiency in adults and the metabolic syndrome are abdominal/visceral obesity and insulin resistance. Abdominal obesity is associated with blunted GH secretion and low serum insulin-like growth factor-I concentrations. GH treatment in GH-deficient adults has demonstrated favorable effects on most of the features of GH deficiency in adults, but it is not known whether GH can improve some of the metabolic aberrations observed in abdominal/visceral obesity. Thirty men, 48-66 yr old, with abdominal/visceral obesity were treated with recombinant human GH (rhGH) in a 9-month randomized, double-blind, placebo-controlled trial. The daily dose of rhGH was 9.5 micrograms/kg. Body fat was assessed from total body potassium, and abdominal sc and visceral adipose tissue was measured using computed tomography. The glucose disposal rate (GDR) was measured during an euglycemic, hyperinsulinemic glucose clamp. In response to the rhGH treatment, total body fat and abdominal sc and visceral adipose tissue decreased by 9.2 +/- 2.4%, 6.1 +/- 3.2%, and 18.1 +/- 7.6%, respectively. After an initial decrease in the GDR at 6 weeks, the GDR increased in the rhGH-treated group as compared with the placebo-treated one (P < 0.05). The mean serum concentrations of total cholesterol (P < 0.01) and triglyceride (P < 0.05) decreased, whereas blood glucose and serum insulin concentrations were unaffected by the rhGH treatment. Furthermore, diastolic blood pressure decreased and systolic blood pressure was unchanged in response to rhGH treatment. This trial has demonstrated that GH can favorably affect some of the multiple perturbations associated with abdominal/visceral obesity. This includes a reduction in abdominal/visceral obesity, an improved insulin sensitivity, and favorable effects on lipoprotein metabolism and diastolic blood pressure.
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| 8. |
- Jönsson, Leif, et al.
(författare)
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Characterization of a laccase gene from the white-rot fungus Trametes versicolor and structural features of basidiomycete laccases
- 1995
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Ingår i: BBA - Protein Structure and Molecular Enzymology. - : Elsevier BV. - 0167-4838. ; 1251:2, s. 210-215
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Tidskriftsartikel (refereegranskat)abstract
- A gene coding for the multi-copper phenol oxidase laccase has been isolated from the white-rot basidiomycete Trametes oersicolor. The gene, which is preceded by a TATA box and a pyrimidine-rich region, is predicted to contain ten introns. The mature translation product, preceded by a 22-residue signal peptide, should consist of 498 residues. Comparisons with Edman degradation data of peptides from T. versicolor laccase strongly suggest that two disulfide bridges are formed by Cys-85/Cys-487 and Cys-117/Cys-205, respectively. The encoded protein contains five Cys, and the sequence surrounding the remaining Cys-452 is consistent with its involvement in the ligation of type-1 copper. Alignment of sequences indicates that T. versicolor laccase displays a Phe at the position corresponding to a residue (Met in ascorbate oxidase and azurin) considered important for the reduction potential of type-1 copper proteins.
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| 9. |
- Karlsson, C, et al.
(författare)
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Effects of growth hormone treatment on the leptin system and on energy expenditure in abdominally obese men.
- 1998
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 0804-4643. ; 138:4, s. 408-14
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Tidskriftsartikel (refereegranskat)abstract
- The present study has examined the short- and long-term effects of growth hormone (GH) treatment on the leptin system and energy expenditure. Thirty male individuals with abdominal obesity were randomised to GH or placebo treatment in a 9-month, double-blind study. The dose of GH was 9.5 microg/kg, administered subcutaneously every evening. Serum leptin concentrations were measured by a human leptin RIA. Total RNA was isolated from adipose tissue biopsies and leptin mRNA levels were determined by a semi-quantitative reverse transcriptase-PCR assay. Body composition was determined by potassium-40 and the basal metabolic rate (BMR) was measured by a computerised, ventilated, open-hood system. As compared with placebo, an overall decrease in serum leptin concentrations as assessed by the area under the curve (AUC) (P < 0.05) and an increase in BMR (AUC, P < 0.05) were observed during GH treatment. The overall GH-induced changes were due to marked changes in serum leptin concentrations and BMR after 6 weeks of treatment. After 9 months of GH treatment there was a significant reduction in body fat (BF) while serum leptin concentrations and BMR did not differ from baseline values. Leptin mRNA levels did not change over the study period. We speculate that long-term GH treatment induces a new energy balance steady state with decreased BF stores. The effects of GH on the leptin system is suggested to be of importance for the maintenance of a lower BF mass.
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| 10. |
- Mårin, P, et al.
(författare)
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The morphology and metabolism of intraabdominal adipose tissue in men.
- 1992
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Ingår i: Metabolism: clinical and experimental. - 0026-0495. ; 41:11, s. 1242-8
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Tidskriftsartikel (refereegranskat)abstract
- Mass, morphology, and metabolism of total adipose tissue and its subcutaneous, visceral, and retroperitoneal subcompartments were examined in 16 men with a wide variation of total body fat. Computerized tomography (CT) scans showed that the intraabdominal fat mass comprised approximately 20% of total fat mass. Visceral and retroperitoneal fat masses were approximately 80% and 20% of total intraabdominal fat mass, respectively. Enlargement of intraabdominal fat depots was due to a parallel adipocyte enlargement only. Direct significant correlations were found between these adipose tissue masses and blood glucose and plasma insulin levels, blood pressure, and liver function tests, while glucose disposal rate during euglycemic glucose clamp measurements at submaximal insulin concentrations (GDR), plasma testosterone, and sex hormone-binding globulin concentrations correlated negatively. The correlations for glucose, insulin, and GDR were strongest with visceral fat mass. Adipose tissue lipid uptake, measured after oral administration of labeled oleic acid in triglyceride, was approximately 50% higher in omental than in subcutaneous adipose tissues. Adipocytes from omental fat also showed a higher lipolytic sensitivity and responsiveness to catecholamines. Furthermore, these adipocytes were less sensitive to the antilipolytic effects of insulin. Both lipid uptake and lipolytic sensitivity and responsiveness showed strong correlations (r = 0.8 to 0.9) to blood glucose and plasma insulin concentrations and also to the GDR (negative), while no such correlations were found with lipid uptake in subcutaneous or retroperitoneal abdominal adipose tissues. Taken together, these results suggest a higher turnover of lipids in visceral than in the other fat depots, which is closely correlated to systemic insulin resistance and glucose metabolism in men.
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