| 1. |
- Andersson, Irene, 1978, et al.
(författare)
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Endothelial dysfunction in growth hormone transgenic mice
- 2006
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 110:2, s. 217-25
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Tidskriftsartikel (refereegranskat)abstract
- Acromegaly [overproduction of GH (growth hormone)] is associated with cardiovascular disease. Transgenic mice overexpressing bGH (bovine GH) develop hypertension and hypercholesterolaemia and could be a model for cardiovascular disease in acromegaly. The aims of the present study were to investigate the effects of excess GH on vascular function and to test whether oxidative stress affects endothelial function in bGH transgenic mice. We studied the ACh (acetylcholine)-induced relaxation response in aortic and carotid rings of young (9-11 weeks) and aged (22-24 weeks) female bGH transgenic mice and littermate control mice, without and with the addition of a free radical scavenger {MnTBAP [Mn(III)tetrakis(4-benzoic acid)porphyrin chloride]}. We also measured mRNA levels of eNOS (endothelial nitric oxide synthase) and EC-SOD (extracellular superoxide dismutase). Intracellular superoxide anion production in the vascular wall was estimated using a dihydroethidium probe. Carotid arteries from bGH transgenic mice had an impaired ACh-induced relaxation response (young, 46 +/- 7% compared with 69 +/- 8%; aged, 52 +/- 5% compared with 80 +/- 3%; P < 0.05), whereas endothelial function in aorta was intact in young but impaired in aged bGH transgenic mice. Endothelial dysfunction was corrected by addition of MnTBAP in carotid arteries from young mice and in aortas from aged mice; however, MnTBAP did not correct endothelial dysfunction in carotid arteries from aged bGH transgenic mice. There was no difference in intracellular superoxide anion production between bGH transgenic mice and control mice, whereas mRNA expression of EC-SOD and eNOS was increased in aortas from young bGH transgenic mice compared with control mice (P < 0.05). We interpret these data to suggest that bGH overexpression is associated with a time- and vessel-specific deterioration in endothelial function, initially caused by increased oxidative stress and later by other alterations in vascular function.
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| 2. |
- Andersson, Irene, 1978, et al.
(författare)
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Increased atherosclerotic lesion area in apoE deficient mice overexpressing bovine growth hormone
- 2006
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 188:2, s. 331-40
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Tidskriftsartikel (refereegranskat)abstract
- Human growth hormone (GH) excess is linked to increased cardiovascular morbidity and mortality. However, little is known about the effect of GH excess on atherosclerosis. We developed a new mouse model to assess the hypothesis that GH overexpression accelerates atherosclerotic lesion formation. apoE(-/-) mice were crossed with bovine GH (bGH) transgenic mice to yield apoE(-/-) mice overexpressing bGH (apoE(-/-)/bGH). The mice were fed either standard or Western diet. At 22 weeks, atherosclerotic lesion area of thoracic aorta was larger in apoE(-/-)/bGH mice compared with littermate apoE(-/-) mice fed either diet (standard: +161+/-50%, Western: +430+/-134%). Aortic sinus lesions were more severe in apoE(-/-)/bGH mice fed standard diet compared with littermate apoE(-/-) mice. apoE(-/-)/bGH mice had lower (VLDL+LDL)/HDL ratios compared with littermate apoE(-/-) mice, while systolic blood pressure was higher in apoE(-/-)/bGH mice, irrespective of diet. The levels of serum amyloid A and hepatic CRP mRNA were higher in apoE(-/-)/bGH mice than in littermate apoE(-/-) mice. In conclusion, this study shows that excess GH augments the development of atherosclerosis in apoE(-/-) mice. The mechanisms could be direct effects of GH on cellular processes in the vessel wall or the result of concomitant processes such as hypertension or a general inflammatory state.
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| 3. |
- Andersson, Irene, 1978, et al.
(författare)
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Reduced sympathetic responsiveness as well as plasma and tissue noradrenaline concentration in growth hormone transgenic mice
- 2004
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Ingår i: Acta Physiol Scand. - 0001-6772. ; 182:4, s. 369-78
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Acromegaly [overproduction of growth hormone (GH)] and GH deficiency have both been associated with alterations in autonomic nervous system function. The aim of this study was to investigate autonomic nervous system influence on heart rate (HR) in transgenic mice overexpressing bovine GH (bGH). METHODS: HR and HR variability (HRV) were measured in conscious young (8-13 weeks) and old (5-6 months) female bGH and control mice using telemetry. HR control was studied using antagonists and an agonist of adrenergic and muscarinic receptors. Noradrenaline was measured in plasma, heart and kidney using high performance liquid chromatography. RESULTS: Average 24 h resting HR did not differ between bGH and control mice. After saline injection and after muscarinic blockade with methylscopolamine HR increase was blunted (in old) or absent (in young) bGH mice compared with control mice (P < 0.05). Phenylephrine caused a baroreflex mediated decrease in HR from around 550 to 300-350 beats min(-1), not different between bGH and control mice. Time- and frequency-domain measures of HRV were reduced in old bGH compared with control mice (P < 0.05). Noradrenaline concentrations were reduced by 25-49% in plasma and tissue of bGH compared with control mice (P < 0.05). CONCLUSION: The current study suggests reduced autonomic modulation of HR in bGH transgenic mice. Thus, GH appears to have marked effects on autonomic tone, reducing sympathetic nervous system function possibly via reduced noradrenaline stores.
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| 4. |
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| 5. |
- Bergström, Göran, 1977-
(författare)
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Från svensk malmexport till utländsk etablering : Grängesbergsbolagets internationalisering 1953-1980
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main purpose of this thesis is to analyze the internationalisation of the Grängesberg Company from 1953 to 1980. The strategies that the company used and the knowledge it gained by participating in international mining projects are studied. The first and largest mining activity abroad was the Lamco project in Liberia. By transferring the company’s competence and knowledge of mining activities to Liberia, the Grängesberg Company used an international strategy of horizontal integration. The company’s contacts were of importance to start the production in 1963. The main ambition was thereafter to negotiate new long-term contracts in order to create stability for the project in the 1960s and the 1970s. Through its involvement in the Lamco project, the Grängesberg Company also acquired shares in a Belgian steel company and became half-owner with the Liberian state in a foreign shipping company. The experience and knowledge that the company gained in the Lamco project was used to increase its internationalisation in the 1970s. Appointing a Mineral Project Group, it investigated existing mineral projects abroad and formulated new internationalisation strategies such as vertical integration and diversification. The main motive for the further expansion abroad in the mining area was a need for resources for its domestic production. The most important outcome was the acquisition of a Canadian copper company, and the company integrated backwards to gain access to copper. The Grängesberg Company also used its competence by doing prospecting work in New Caledonia, Peru and Canada and consultant work in mining projects in Iran and Saudi Arabia in the 1970s. The study has shown that further international expansion became limited because of the downturn of the international economy in the 1970s, but also because of the company’s cautious attitude towards the political risks that were associated with international mining projects.
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| 6. |
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| 7. |
- Bergström, Göran, 1964, et al.
(författare)
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Mechanisms underlying the antihypertensive functions of the renal medulla
- 2004
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Ingår i: Acta Physiol Scand. - 0001-6772. ; 181:4, s. 475-86
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Tidskriftsartikel (refereegranskat)abstract
- There is good evidence that the renal medulla plays a pivotal role in long-term regulation of blood pressure. 'Renal medullary' blood pressure regulating systems have been postulated to involve both exocrine (pressure natriuresis/diuresis) and endocrine [renal medullary depressor hormone (RMDH)] functions. However, recent studies indicate that pressure diuresis/natriuresis dominates the antihypertensive renal response to increased renal perfusion pressure, suggesting little physiological role for a putative RMDH in compensatory responses to acutely increased blood pressure. The medullary circulation appears to play a key role in mediating pressure diuresis, although the precise mechanisms involved remain controversial. Counter-regulatory vasodilator mechanisms (e.g. nitric oxide), at least partly mediated through cross-talk between the vasculature and the tubular epithelium, protect the medullary circulation from the vasoconstrictor effects of hormonal factors such as angiotensin II. These mechanisms also appear to contribute to compensatory responses to increased salt intake in salt-resistant individuals. Failure of these mechanisms predisposes the organism towards the development of hypertension, appears to underlie the development of some forms of experimental hypertension, and may even contribute to the pathogenesis of essential hypertension.
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| 8. |
- Bergström, Jonas, 1970-
(författare)
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The evolution of mating rates in Pieris napi
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the green-veined white butterfly (Pieris napi), females obtain direct fitness benefits from mating multiply and studies have shown that fitness increases seemingly monotonically with number of matings. The reason is that at mating males transfer a large nutritious gift (a so called nuptial gift) to the females that the females use to increase both their fecundity and lifespan. In addition, if exposed to poor food conditions as larvae, females mature at a smaller size compared to males. Accordingly, it was suggested that smaller females could compensate for their size through nuptial feeding by, for instance, mating more frequently. We did not find any support for that hypothesis. On the contrary, larger females remated sooner and had a higher lifetime number of matings. Neither were smaller females able to compensate in any other way, because singly mated females and multiply mated females suffered to the same extent from their smaller size. This thesis also shows that despite the positive relationship between fitness and number of matings, there is a large variation in female mating frequency in wild populations and about every second female mates only once or twice. This variation is not dependent on how often females get courted by males, because female mating frequency was shown not to be affected by male courtship intensity. Hence, the reason for the low mating frequency could either be that males have evolved the ability to manipulate females to mate at a suboptimal rate as a measure of protection against sperm competition, or alternatively, that female mating rate is suppressed by some costs. Using two selection lines, artificially selected for either a high or a low mating rate, we showed that the variation in mating rate was mainly a female trait because which line the females were from affected their mating rate whereas which line the male was from did not. This implies that females mate at a low rate due to hidden costs or due to constraints. The same study also showed that females with a high "intrinsic" mating rate lived shorter, but only when denied remating. This led us to test the hypothesis that the cost females face is to have the ability to mate at a high rate but the cost is only paid when remating opportunities are scarce. However, we found no support for such an idea, because females with a high intrinsic mating rate held in a cold environment where the butterflies were prevented from flying and feeding did not live shorter. Neither was there an effect of a female’s mating rate on her ability to quickly break down and convert male nutrient gifts into egg material. Female mating rate did, on the other hand, affect dispersal tendency, with low mating rate females being more inclined to fly between different habitats. The underlying reason for this is still to be explored.
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| 9. |
- Bergström, Mats, et al.
(författare)
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PET imaging of adrenal cortical tumors with the 11beta-hydroxylase tracer 11C-metomidate
- 2000
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Ingår i: Journal of Nuclear Medicine. - 0161-5505 .- 1535-5667. ; 41:2, s. 275-282
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the study was to evaluate PET with the tracer 11C-metomidate as a method to identify adrenal cortical lesions.METHODS:PET with 11C-metomidate was performed in 15 patients with unilateral adrenal mass confirmed by CT. All patients subsequently underwent surgery, except 2 who underwent biopsy only. The lesions were histopathologically examined and diagnosed as adrenal cortical adenoma (n = 6; 3 nonfunctioning), adrenocortical carcinoma (n = 2), and nodular hyperplasia (n = 1). The remaining were noncortical lesions, including 1 pheochromocytoma, 1 myelolipoma, 2 adrenal cysts, and 2 metastases.RESULTS:All cortical lesions were easily identified because of exceedingly high uptake of 11C-metomidate, whereas the noncortical lesions showed very low uptake. High uptake was also seen in normal adrenal glands and in the stomach. The uptake was intermediate in the liver and low in other abdominal organs. Images obtained immediately after tracer injection displayed high uptake in the renal cortex and spleen. The tracer uptake in the cortical lesions increased throughout the examination. For quantitative evaluation of tracer binding in individual lesions, a model with the splenic radioactivity concentration assigned to represent nonspecific uptake was applied. Values derived with this method, however, did show the same specificity as the simpler standardized uptake value concept, with similar difference observed for cortical versus noncortical lesions.CONCLUSION:PET with 11C-metomidate has the potential to be an attractive method for the characterization of adrenal masses with the ability to discriminate lesions of adrenal cortical origin from noncortical lesions.
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