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- Fredlund, J O, et al.
(författare)
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Ornithine decarboxylase and S-adenosylmethionine decarboxylase expression during the cell cycle of Chinese hamster ovary cells
- 1995
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 1090-2422 .- 0014-4827. ; 216:1, s. 86-92
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Tidskriftsartikel (refereegranskat)abstract
- Cells in mitosis were harvested from exponentially growing Chinese hamster ovary cells by the mitotic detachment technique. Immediately after harvesting, the mitotic cells were seeded in tissue culture flasks and incubated at 37 degrees C in a CO2 incubator. Care was taken not to perturb the progression of cells through the cell cycle. At every hour after seeding for 14 h, cells were collected for analysis of cell cycle distribution, cellular polyamine content, ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) activities, and relative mRNA contents. The progression through the cell cycle was monitored by DNA flow cytometry. The putrescine, spermidine, and spermine levels were approximately doubled during the cell cycle: putrescine mainly during late S and G2, spermidine continuously during the entire cell cycle, and spermine mainly during G1 and S. The ODC activity was low in seeded mitotic cells and the enzyme was activated in late G1 and reached a plateau in S phase. A second burst in activity was observed during late S phase and maximal ODC activity was found at the S/G2 transition. The relative ODC mRNA level approximately doubled during the cell cycle and the increase in the relative level mainly took part during mid and late S phase. AdoMetDC activity increased in late G1 and a first maximum was observed during the G1/S transition. A second burst in activity was found in mid S phase. Maximal AdoMetDC activity was found in G2. The relative AdoMetDC mRNA approximately doubled during the cell cycle and the increase in the relative level mainly took place during late G1 and early S phase. Our results indicate that polyamine synthesis was regulated at transcriptional and translational/post-translational levels during the cell cycle of Chinese hamster ovary cells.
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- Johansson, J O, et al.
(författare)
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Long-term treatment with growth hormone decreases plasminogen activator inhibitor-1 and tissue plasminogen activator in growth hormone-deficient adults.
- 1996
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Ingår i: Thrombosis and haemostasis. - 0340-6245. ; 76:3, s. 422-8
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Tidskriftsartikel (refereegranskat)abstract
- The syndrome of growth hormone deficiency (GHD) in adults is associated with premature atherosclerosis, increased cardiovascular mortality, abnormal lipoprotein patterns and abnormal body composition. We have previously shown that GH-deficient adults have increased concentrations of fibrinogen and plasminogen activator inhibitor (PAI-1) activity. The aim of the present investigation was to study coagulation and fibrinolysis in 17 patients with adult-onset GHD during two years of treatment with recombinant human GH (12 micrograms/kg body weight/day). The impact of the contemporary changes in metabolic variables and body composition on coagulation and fibrinolysis was studied. The patients received conventional thyroid, adrenal and gonadal hormone replacement therapy. PAI-1 activity, PAI-1 antigen and tissue plasminogen activator (t-PA) antigen levels decreased during the GH treatment period (p < 0.05). The decrease was more pronounced in patients with high pre-treatment levels of the different variables. alpha 2-antiplasmin decreased (p < 0.05), while plasminogen was unchanged during two years of GH treatment. Fibrinogen concentrations tended to decrease after two years of GH treatment (p = 0.06), while the coagulation factors VII and VIII were unchanged. von Willebrand factor demonstrated a transient decrease after 18 months of GH treatment. The coagulation inhibitor, protein C, decreased (p < 0.05), while antithrombin was unchanged. Fasting plasma insulin increased (p < 0.01), but blood glucose did not differ after two years of GH treatment. Serum high-density lipoprotein cholesterol, total cholesterol and triglycerides were unaltered. Body fat decreased during the initial GH treatment but was unaltered after two years, while lean body mass increased (p < 0.001) and the waist over hip circumference ratio tended to decrease (p = 0.06). In conclusion, PAI-1 activity, PAI-1 antigen and t-PA antigen decreased during long-term GH treatment. These changes may be a direct effect of GH itself or may be secondary to the favourable changes in body composition. It remains to be seen whether changes in these fibrinolytic variables during rhGH treatment reduces the cardiovascular risk in patients with GHD. The present results suggest that GH plays a role in the regulation of fibrinolysis.
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| 4. |
- Johansson, S A, et al.
(författare)
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Dosimeter gel and MR imaging for verification of calculated dose distributions in clinical radiation therapy
- 1997
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Ingår i: Acta Oncologica. - 0284-186X. ; 36:3, s. 90-283
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Tidskriftsartikel (refereegranskat)abstract
- A dosimeter gel, based on an agarose gel infused with a ferrous sulphate solution and evaluated in a magnetic resonance scanner, was used for complete verification of calculated dose distributions. Two standard treatment procedures, treatment of cancer in the urinary bladder and treatment of breast cancer after modified radical mastectomy, were examined using pixel-by-pixel and dose volume histogram comparison. The dose distributions calculated with the dose planning system was in very good agreement with the measured ones. However, in the case of the more complicated breast cancer treatment, some discrepancies were found, mainly at the beam abutment region. This may be explained by field displacements errors and by a small limitation of the dose planning utilising small electron beams in this region. The dosimeter gel system have proven to be a useful tool for dosimetry in clinical radiation therapy applications.
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| 5. |
- Oscarsson, J, et al.
(författare)
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Diurnal variation in serum insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations during daily subcutaneous injections of recombinant human growth hormone in GH-deficient adults.
- 1997
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Ingår i: Clinical endocrinology. - 0300-0664. ; 46:1, s. 63-8
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Tidskriftsartikel (refereegranskat)abstract
- Whereas there seems to be little, if any, circadian variation in circulating concentrations of IGF-I and IGFBP-3 in healthy subjects, there are conflicting reports on this issue in GH-deficient patients treated with GH as a daily subcutaneous injection. We have therefore investigated the 24-hour serum profiles of IGF-I and IGFBP-3 concentrations after one week and more than one year of GH treatment.Eleven subjects, with adult onset GH deficiency mainly caused by pituitary adenomas were included in the study.In an open study, six subjects (three women and three men; age (+/-SEM) 41.2 +/- 3.9 years) were investigated after one week of GH therapy and five subjects (three women and two men; age (+/-SEM) 61.4 +/- 3.3 years) were investigated after 13-40 months of GH therapy. The GH injections were given at 2000 h. The subjects were hospitalized for 24-hour blood sampling at 1-hour intervals and serum concentrations of GH, IGF-I and IGFBP-3 were determined.There was a significant diurnal variation in serum IGF-I and IGFBP-3 concentrations both in the subjects who had received GH for one week and in those who had received GH treatment for more than one year. The serum concentrations of IGF-I and IGFBP-3 were highest in the morning and lowest during night-time and early morning. The molar IGF-I/IGFBP-3 ratio varied significantly with time in both groups of patients in a similar way as IGF-I and IGFBP-3 indicating a more pronounced variation in IGF-I compared with IGFBP-3 in response to the GH therapy.Significant diurnal variations in serum IGF-I and IGFBP-3 concentrations occur after one week and more than one year of GH treatment with daily subcutaneous injections. The results indicate that the free fraction of IGF-I may exhibit a diurnal variation.
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| 6. |
- Rosén, T, et al.
(författare)
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Consequences of growth hormone deficiency in adults and the benefits and risks of recombinant human growth hormone treatment. A review paper.
- 1995
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Ingår i: Hormone research. - 0301-0163. ; 43:1-3, s. 93-9
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Forskningsöversikt (refereegranskat)abstract
- Growth hormone deficiency (GHD) in adults is now recognized as a specific clinical syndrome with characteristic symptoms and signs. Thus, the patients are overweight, have an abnormal body composition (excess body fat and a decrease in the extracellular water volume) and a low bone mineral content compared to normals. Furthermore, the GHD patients have lipid abnormalities, decreased insulin sensitivity and a decreased fibrinolysis. Finally, the 'quality of life' is low in terms of energy and social life. Short- and long-term studies with recombinant human GH (rhGH) treatment have shown normalization of body composition, increase in the lipid pattern and marked improvement of the psychological well-being. The treatment seems safe with no serious side effects reported. In analogy with other hormonal replacement therapies, the rhGH dose should be individualized.
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| 7. |
- Stenlöf, Kaj, 1965, et al.
(författare)
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Diurnal variations in twenty-four-hour energy expenditure during growth hormone treatment of adults with pituitary deficiency.
- 1997
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 82:4, s. 1255-60
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Tidskriftsartikel (refereegranskat)abstract
- The effects of growth hormone (GH) treatment on 24-h energy expenditure (EE) were studied in a open trial over a period of 4 weeks. Five subjects, four men and one woman, with a history of complete GH deficiency were included. All the subjects were examined on 2 consecutive days on baseline and, thereafter, at six occasions during a period of 1 month (days 1, 2, 5, 8, 15, and 30). The dose of GH was 0.25 U/kg.week, administered sc once a day in the evening. EE was determined in a chamber for indirect calorimetry. Body composition was determined with dual-energy x-ray absorptiometry and computed tomography using a four-scan technique. Blood samples were examined using well-established RIAs. During the first 2 weeks, 24-h EE increased by 6 +/- 3% (range 1-8%) from 40.9 +/- 4.8 to 42.9 +/- 4.8 kcal/24 h.kg (P < 0.05), sleeping metabolic rate by 14 +/- 3% (range 10-18%) from 28.4 +/- 1.9 to 32.9 +/- 2.2 kcal/24h.kg (P < 0.001), and basal metabolic rate by 11 +/- 7% (range 0-18%) from 29.6 +/- 2.4 to 33.3 +/- 2.6 kcal/24h.kg (P < 0.05). No change was found in daytime EE. The increase in EE covaried with changes in insulin-like growth factor 1, the free T3/free T4 ratio, insulin-like growth factor-binding protein-3, and the aminoterminal procollagen III peptide but not with changes in body composition. It is suggested that the stimulating effect of GH on EE occurs gradually during a 2-week period and is only detectable during night and morning hours, when significant levels of GH occur.
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