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Biomedical subjects

J Jensen

Publications and source records attributed to J Jensen.

At least 19 recordsLinked to original sources
PubMed2006

Global myocardial perfusion and diastolic function are impaired to a similar extent in patients with type 2 diabetes mellitus and in patients with coronary artery disease--evaluation by contrast echocardiography and pulsed tissue Doppler.

AIMS/HYPOTHESIS: Using modern echocardiography, we quantified the extent of global myocardial function and perfusion abnormalities in patients with type 2 diabetes and compared this with the hypothetically similar extent of impairments in patients with coronary artery disease (CAD). SUBJECTS AND METHODS: This case-control study (66 patients) compared four age-matched groups: control, type 2 diabetic, CAD, and diabetic subjects with CAD (DCAD) and left ventricular ejection fraction >50%. CAD patients had 1-2 vessel disease. Diastolic and systolic myocardial velocities were assessed with pulsed tissue Doppler. Global myocardial perfusion was assessed with contrast echocardiography as indices of capillary blood volume and myocardial blood flow at maximal vasodilatation. In CAD and DCAD patients, functional and perfusion parameters were additionally assessed in the territory with a normal coronary angiogram reading, providing a model for comparison with the global data from control and diabetic patients. RESULTS: Comparing diabetic with control subjects, myocardial velocity at early diastole was impaired (8.8+/-1.8 vs 10.1+/-1.7 cm/s; p=0.02) and correlated inversely with age, HbA(1c) and pulse pressure (R (2)=0.761). Capillary blood volume (16.6+/-5.0 vs 24.4+/-4.9%) and blood flow (56+/-35 vs 114+/-40) were decreased (p=0.001). In CAD patients, myocardial velocity at early diastole was similarly decreased (p=0.02). CAD and DCAD patients were receiving more cardiovascular preventive therapy for the same extent of impaired global perfusion as in the less extensively treated diabetes group without CAD (p<0.002), but had superior perfusion of the 'normal' coronary territory than that group (p<0.05). CONCLUSIONS/INTERPRETATION: In patients with diabetes, global diastolic function and myocardial capillary blood volume and blood flow are impaired to the same extent as in patients with CAD. These impairments could form the basis of new therapeutic concepts.

Blood Pressure↗
PubMed2006

CD8+ T cell activation correlates with disease activity in clinically isolated syndromes and is regulated by interferon-beta treatment.

An increased percentage of blood CD8+ T cells from patients with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) was found to express CD26 and CD69. The percentage of CD26 or CD69 positive CD8+ T cells was higher in patients with MRI evidence of disease dissemination in space or with active MRI lesions than in the remaining patients. Treatment of MS with interferon (IFN)-beta resulted in a decrease in the percentage of CD26 and CD71 positive CD8+ T cells and an increase in the percentage of CD8+ T cells that expressed interleukin (IL)-10 and IL-13. CD8+ T cell activation in MS may be linked to disease activity already at disease onset, and is regulated by treatment with IFN-beta.

Adult↗
PubMed2006

Leukaemia inhibitory factor stimulates glucose transport in isolated cardiomyocytes and induces insulin resistance after chronic exposure.

AIMS/HYPOTHESIS: Hypertrophic and failing hearts have increased utilisation of glucose, but also develop insulin resistance and reduced ability to produce ATP. Increased levels of the IL-6-related cytokine leukaemia inhibitory factor (LIF) are found in failing hearts, and we have recently shown that LIF reduces ATP production in isolated cardiomyocytes. In the present study we investigated effects of LIF on glucose metabolism, and how LIF-treated cells respond to insulin stimulation. METHODS: Cardiomyocytes were isolated from adult Wistar rats by collagen digestion, maintained in culture for 48 h, and then treated with 1 nmol/l LIF. RESULTS: Acute LIF treatment increased deoxyglucose uptake compared with controls, but no additive effect was observed in cardiomyocytes treated with LIF and insulin. The phosphatidylinositol 3-kinase inhibitor wortmannin did not affect LIF-induced glucose uptake. LIF had no effect on AMP-activated protein kinase phosphorylation. Cardiomyocytes treated with LIF for 48 h did not respond to insulin by increasing deoxyglucose uptake and showed a reduced insulin-mediated uptake of oleic acid and formation of complex lipids compared with control cells. Chronic LIF treatment increased gene expression of the suppressor of cytokine signalling (Socs) 3 and reduced expression of solute carrier family 2, member 4 (Slc2a4, previously known as glucose transporter 4 [Glut4]). In line with these observations, chronic LIF treatment reduced insulin-mediated phosphorylation of both Akt/protein kinase B (PKB) and glycogen synthase kinase (GSK)-3. CONCLUSIONS/INTERPRETATION: Acute LIF treatment increased glucose uptake in isolated cardiomyocytes by a pathway different from that of insulin. Chronic LIF treatment induced insulin resistance, possibly mediated by altered expression of Socs3 and Slc2a4, and impaired insulin-mediated phosphorylation of GSK-3 and Akt/PKB.

Animals↗
PubMed2006

Lifetimes of C60(2-) and C70(2-) dianions in a storage ring.

C60(2-) and C70(2-) dianions have been produced by electrospray of the monoanions and subsequent electron pickup in a Na vapor cell. The dianions were stored in an electrostatic ring and their decay by electron emission was measured up to 1 s after injection. While C70(2-) ions are stable on this time scale, except for a small fraction of the ions which have been excited by gas collisions, most of the C60(2-) ions decay on a millisecond time scale, with a lifetime depending strongly on their internal temperature. The results can be modeled as decay by electron tunneling through a Coulomb barrier, mainly from thermally populated triplet states about 120 meV above a singlet ground state. At times longer than about 100 ms, the absorption of blackbody radiation plays an important role for the decay of initially cold ions. The tunneling rates obtained from the modeling, combined with WKB estimates of the barrier penetration, give a ground-state energy 200+/-30 meV above the energy of the monoanion plus a free electron and a ground-state lifetime of the order of 20 s.

Journal Article↗
PubMed2006

Clinical and angiographic follow-up after coronary drug-eluting and bare metal stent implantation. Do drug-eluting stents hold the promise?

OBJECTIVES: To investigate the influence of drug-eluting stent (DES) implantation on clinical and angiographic restenosis. DESIGN: Registry study of data from the Swedish Coronary Angiography and Angioplasty Registry with a coronary angiographic substudy. SETTING: Multi-centre study. SUBJECTS: During October 2002 to May 2004 a total of 23 590 percutaneous coronary intervention (PCI) procedures were performed at 25 hospitals. After selection, to achieve comparable groups, a total of 5068 patients of whom 4111 had a bare metal stent (BMS) implanted and 957 had a DES implanted, remained. End-point in the registry follow-up was >50% diameter restenosis at clinically driven reangiography within 12 months after index PCI. The primary end-point in the angiographic substudy was late loss in patients' DES at 6-month angiographic follow-up. RESULTS: The rate of clinically driven restenosis, within 12 months, in patients receiving DES was less (3.9%) compared with those who received BMS (7.0%). In multivariate analysis the risk of clinical restenosis was one-third for DES compared with BMS (HR 0.36, 95% CI 0.25-0.52). In the angiographic substudy late loss was 0.07+/-0.53 mm (range -0.88 to 1.62). The amount of late loss was related to the presence of diabetes mellitus or not (0.19+/-0.45 mm vs. -0.12+/-0.58 mm), and lack of postdilatation of the stent or not (0.23+/-0.51 mm vs. -0.09+/-0.50 mm). CONCLUSIONS: The use of DES in the Swedish 'real world' is effective in reducing the clinically driven restenosis rate, when compared with patients with BMS treatment. In the angiographic follow-up the average late loss was as low as observed in recent randomized multi-centre trials.

Aged↗
PubMed2006

Bayesian analysis of the linear reaction norm model with unknown covariates.

The reaction norm model is becoming a popular approach for the analysis of genotype x environment interactions. In a classical reaction norm model, the expression of a genotype in different environments is described as a linear function (a reaction norm) of an environmental gradient or value. An environmental value is typically defined as the mean performance of all genotypes in the environment, which is usually unknown. One approximation is to estimate the mean phenotypic performance in each environment and then treat these estimates as known covariates in the model. However, a more satisfactory alternative is to infer environmental values simultaneously with the other parameters of the model. This study describes a method and its Bayesian Markov Chain Monte Carlo implementation that makes this possible. Frequentist properties of the proposed method are tested in a simulation study. Estimates of parameters of interest agree well with the true values. Further, inferences about genetic parameters from the proposed method are similar to those derived from a reaction norm model using true environmental values. On the other hand, using phenotypic means as proxies for environmental values results in poor inferences.

Bayes Theorem↗
PubMed2005

Glucocorticoid-induced insulin resistance in skeletal muscles: defects in insulin signalling and the effects of a selective glycogen synthase kinase-3 inhibitor.

AIMS/HYPOTHESIS: Treatment with glucocorticoids, especially at high doses, induces insulin resistance. The aims of the present study were to identify the potential defects in insulin signalling that contribute to dexamethasone-induced insulin resistance in skeletal muscles, and to investigate whether the glycogen synthase-3 (GSK-3) inhibitor CHIR-637 could restore insulin-stimulated glucose metabolism. MATERIALS AND METHODS: Skeletal muscles were made insulin-resistant by treating male Wistar rats with dexamethasone, a glucocorticoid analogue, for 12 days. Insulin-stimulated glucose uptake, glycogen synthesis and insulin signalling were studied in skeletal muscles in vitro. RESULTS: Dexamethasone treatment decreased the ability of insulin to stimulate glucose uptake, glycogen synthesis and glycogen synthase fractional activity. In addition, the dephosphorylation of glycogen synthase by insulin was blocked. These defects were paralleled by reduced insulin-stimulated protein kinase B (PKB) and GSK-3 phosphorylation. While expression of PKB, GSK-3 and glycogen synthase was not reduced by dexamethasone treatment, expression of the p85alpha subunit of phosphatidylinositol 3-kinase (PI 3-kinase) was increased. Inhibition of GSK-3 by CHIR-637 increased glycogen synthase fractional activity in soleus muscle from normal and dexamethasone-treated rats, although the effect was more pronounced in control rats. CHIR-637 did not improve insulin-stimulated glucose uptake in muscles from dexamethasone-treated rats. CONCLUSIONS/INTERPRETATION: We demonstrated that chronic dexamethasone treatment impairs insulin-stimulated PKB and GSK-3 phosphorylation, which may contribute to insulin resistance in skeletal muscles. Acute pharmacological inhibition of GSK-3 activated glycogen synthase in muscles from dexamethasone-treated rats, but GSK-3 inhibition did not restore insulin-stimulated glucose uptake.

Animals↗
PubMed2005

Quantum phase transition of a magnet in a spin bath.

The excitation spectrum of a model magnetic system, LiHoF4, was studied with the use of neutron spectroscopy as the system was tuned to its quantum critical point by an applied magnetic field. The electronic mode softening expected for a quantum phase transition was forestalled by hyperfine coupling to the nuclear spins. We found that interactions with the nuclear spin bath controlled the length scale over which the excitations could be entangled. This generic result places a limit on our ability to observe intrinsic electronic quantum criticality.

Journal Article↗
PubMed2005

Consumption of carbohydrate solutions enhances energy intake without increased body weight and impaired insulin action in rat skeletal muscles.

OBJECTIVES: In the present study, we investigated whether replacement of tap water by fructose or sucrose solutions affect rat body weight and insulin action in skeletal muscles. METHODS: Rats were fed standard rodent chow ad libitum with water, or water containing fructose (10.5% or 35%) or sucrose (10.5% or 35%) for 11 weeks. Body weight and energy intake from chow and drinking solutions were measured. Urinary catecholamines secretion was determined after 50-60 days. At the end of the feeding period, soleus and epitrochlearis were removed for in vitro measurements of glucose uptake (with tracer amount of 2-[3H]-deoxy-D-glucose) and PKB Ser473 phosphorylation (assessed by Western Blot) with or without insulin. RESULTS: Fructose and sucrose solutions enhanced daily energy intake by about 15% without increasing rat body weight. Secretion of urinary noradrenaline was higher in rats drinking a 35% sucrose solution than in rats drinking water. In the other groups, urinary noradrenaline secretion was similar to rats consuming water. Urinary adrenaline secretion was similar in all groups. Insulin-stimulated glucose uptake and insulin-stimulated PKB phosphorylation were not reduced by intake of fructose or sucrose solution. CONCLUSIONS: Fructose and sucrose solutions enhanced energy intake but did not increase body weight. Although noradrenaline may regulate body weight in rats drinking 35% sucrose solution, body weight seems to be regulated by other mechanisms. Intake of fructose or sucrose solution did not impair insulin-stimulated glucose uptake or signaling in skeletal muscles.

Administration, Oral↗
PubMed2005

Improved insulin-stimulated glucose uptake and glycogen synthase activation in rat skeletal muscles after adrenaline infusion: role of glycogen content and PKB phosphorylation.

AIM: Effects of in vivo adrenaline infusion on subsequent insulin-stimulated glucose uptake and glycogen synthase activation was investigated in slow-twitch (soleus) and fast-twitch (epitrochlearis) muscles. Furthermore, role of glycogen content and Protein kinase B (PKB) phosphorylation for modulation insulin sensitivity was investigated. METHODS: Male Wistar rats received adrenaline from osmotic mini pumps ( approximately 150 microg kg(-1) h(-1)) for 1 or 12 days before muscles were removed for in vitro studies. RESULTS: Glucose uptake at physiological insulin concentration was elevated in both muscles after 1 and 12 days of adrenaline infusion. Insulin-stimulated glycogen synthase activation was also improved in both muscles. This elevated insulin sensitivity occurred despite the muscles were exposed to hyperglycaemia in vivo. After 1 day of adrenaline infusion, glycogen content was reduced in both muscles; insulin-stimulated PKB ser(473) phosphorylation was increased in both muscles only at the highest insulin concentration. After 12 days of adrenaline infusion, glycogen remained low in epitrochlearis, but returned to normal level in soleus; insulin-stimulated PKB phosphorylation was normal in both muscles. CONCLUSION: Insulin-stimulated glucose uptake and glycogen synthase activation were increased after adrenaline infusion. Increased insulin-stimulated glucose uptake and glycogen synthase activation after adrenaline infusion cannot be explained by a reduction in glycogen content or an increase in PKB phosphorylation. The mechanisms for the improved insulin sensitivity after adrenaline treatment deserve particular attention as they occur in conjunction with hyperglycaemia.

Animals↗
PubMed2005

A Bayesian threshold-normal mixture model for analysis of a continuous mastitis-related trait.

Mastitis is associated with elevated somatic cell count in milk, inducing a positive correlation between milk somatic cell score (SCS) and the absence or presence of the disease. In most countries, selection against mastitis has focused on selecting parents with genetic evaluations that have low SCS. Univariate or multivariate mixed linear models have been used for statistical description of SCS. However, an observation of SCS can be regarded as drawn from a 2- (or more) component mixture defined by the (usually) unknown health status of a cow at the test-day on which SCS is recorded. A hierarchical 2-component mixture model was developed, assuming that the health status affecting the recorded test-day SCS is completely specified by an underlying liability variable. Based on the observed SCS, inferences can be drawn about disease status and parameters of both SCS and liability to mastitis. The prior probability of putative mastitis was allowed to vary between subgroups (e.g., herds, families), by specifying fixed and random effects affecting both SCS and liability. Using simulation, it was found that a Bayesian model fitted to the data yielded parameter estimates close to their true values. The model provides selection criteria that are more appealing than selection for lower SCS. The proposed model can be extended to handle a wide range of problems related to genetic analyses of mixture traits.

Animals↗
PubMed2005

Prior (co)variances can improve multiple-trait across-country evaluations of weakly linked bull populations.

National genetic evaluation results for fore udder attachment from 9 Ayrshire populations were used to assess the impact of different uses of prior genetic correlations in multiple-trait across-country evaluations (MACE) on predicted international genetic merit. These Ayrshire populations were poorly connected; that is, 2% of the bulls had evaluations in 2 or more countries. Genetic correlations from the Holstein populations in the same countries were used as prior information to improve inferences of location parameters and international genetic merits. Fully Bayesian analyses using Gibbs sampling and computationally less demanding traditional MACE assuming a weighted average of prior and estimated Ayrshire genetic correlations were compared for 3 different prior degrees of belief and for different groups of bulls. Posterior means of genetic correlations estimated by Gibbs sampling were on average higher (+0.2) than those estimated by REML. Posterior heritabilities differed up to 0.2 units from those assumed in national genetic evaluations. Predicted genetic merit and international sire rankings of bulls with daughter information in the country of interest were not affected substantially by method of analysis and even less by varying prior degree of belief. Method of analysis had a larger impact on predicted genetic merit for bulls without daughter information in the country of interest. Here the average correlation between predicted genetic merit in different analyses ranged from 0.62 to 0.99. The predictive ability for young and randomly chosen bulls favored Bayesian MACE. The prior degree of belief did not have much impact on sire rankings and predictive ability, but intermediate prior degree of belief tended to perform best. All MACE analyses yielded nearly unbiased predictions. Traditional MACE assuming a simple weighted average of prior and estimated Ayrshire genetic correlations has been implemented by Interbull for routine international genetic evaluations.

Analysis of Variance↗
PubMed2005

Short communication: Difficulties in estimating across-country genetic correlations for weakly linked bull populations.

Genetic correlations across 9 weakly linked bull populations were estimated with various models, methods, and data sets. Estimates of the same genetic correlation differed noticeably depending on estimation strategy (up to 1.03 units) for country-pairs with no or few direct genetic links. Differences in estimated genetic correlations decreased with an increasing number of genetic ties between countries, and, essentially, no differences were found between estimated genetic correlations based on 61 common bulls, regardless of the estimation strategy used.

Analysis of Variance↗
PubMed2004

Chronic hyperglycaemia promotes lipogenesis and triacylglycerol accumulation in human skeletal muscle cells.

AIMS/HYPOTHESIS: The present study was conducted to evaluate the effect of hyperglycaemia in itself on glucose and lipid metabolism in human skeletal muscle cells. METHODS: Satellite cells were isolated from biopsy samples from the vastus lateralis muscle and differentiated into multinucleated myotubes in cultures. Metabolism studies were performed using isotopes ([3H]deoxyglucose, [14C]glucose, [14C]oleic acid and [14C]palmitic acid), and mRNA and protein levels were analysed by real-time RT-PCR and western blotting respectively. RESULTS: Exposure of myotubes to 20 mmol/l glucose for 4 days reduced insulin-stimulated glucose uptake and glycogen synthesis to 57+/-5% (p<0.0001) and 56+/-5% (p<0.0001) of normoglycaemic (5.5 mmol/l glucose) controls respectively. Basal glucose uptake and glycogen synthesis were both reduced, whereas glucose oxidation was unaltered. Total cell content of glycogen and expression of GLUT1 and GLUT4 mRNA were not affected. There was a significant increase in the incorporation of glucose into cellular NEFA (88+/-17% increase, p=0.006), triacylglycerol (44+/-21% increase, p=0.04) and cholesterol ester (89+/-36% increase, p=0.02) in hyperglycaemic myotubes compared with controls. Diacylglycerol tended to be increased though not significantly, and phospholipid formation were unchanged. Relative to controls, total cell content of triacylglycerol was increased by 25+/-7% (p=0.02) and acyl-CoA:1,2-diacylglycerol acyltransferase 1 activity was increased by 34+/-4% (p=0.004), whereas acyl-CoA:1,2-diacylglycerol acyltransferase 1 mRNA expression was unchanged. Total cellular uptake of palmitic acid was reduced by 18+/-3% (p=0.006) in hyperglycaemic cells compared with controls, while uptake of oleic acid was unchanged. Oxidation of palmitic acid or oleic acid was not affected by hyperglycaemia. CONCLUSIONS/INTERPRETATION: Chronic hyperglycaemia increased triacylglycerol accumulation and the incorporation of carbohydrate into triacylglycerol (i.e. de novo lipogenesis) concomitantly with a reduced insulin-stimulated glucose uptake and glycogen synthesis. Enhanced acyl-CoA:1,2-diacylglycerol acyltransferase 1 activity supported the increased triacylglycerol synthesis during hyperglycaemia.

Base Sequence↗
PubMed2004

Le Fort I miniplate osteosynthesis: a randomized, prospective study comparing resorbable PLLA/PGA with titanium.

The aim of this study was to compare the use of resorbable osteosynthesis material (LactoSorb) with titanium osteosynthesis for the fixation of Le Fort I osteotomies with respect to long-term stability and morbidity. To achieve exact cephalometric measures, five tantalum micro implants were inserted in the maxilla during surgery. A total of 60 patients undergoing a non-segmented Le Fort I osteotomy were randomized to one of the treatments and were followed for 1 year postoperatively. For the osteotomies fixated with LactoSorb, the lateral cephalometric analysis demonstrated a statistically significant difference in the vertical position of the maxilla after 6 weeks as the position became more superior compared with the postoperative situation (mean change of 0.6 mm). In the titanium group no significant changes in position were observed. There were no statistically significant changes in the position of the maxilla from 6 weeks to 12 months in either of the treatment groups. The changes in maxillary postion were not clinically noticeable in either of the treatment groups, and all treatments were completed with satisfactory results. There were two cases of infection and wound dehiscence in the LactoSorb group, whereas titanium osteosynthesis was more often palpable after 6-12 months and required surgical removal in three cases.

Absorbable Implants↗
PubMed2004

CD4 T cell activation and disease activity at onset of multiple sclerosis.

We studied CD4 T cell activation in patients with clinically isolated syndromes (CIS) suggesting an initial attack of multiple sclerosis. The percentage of blood CD26+ CD4 T cells was increased in these patients, and correlated with magnetic resonance imaging disease activity and clinical disease severity. In contrast, the percentage of CD25+ CD4 T cells in cerebrospinal fluid correlated negatively with the cerebrospinal fluid concentration of myelin basic protein and the presence of IgG oligoclonal bands. These results suggest that distinct systemic and intrathecal T cell activation states correlate with disease activity and risk of subsequently developing MS in CIS patients.

Adult↗
PubMed2003

Highly charged clusters of fullerenes: charge mobility and appearance sizes.

Clusters of fullerenes (C60,C70)(n) are produced in a gas aggregation source and are multiply ionized in collisions with highly charged Xe(20+,30+) ions. Their stabilities and decay processes are analyzed with high-resolution time-of-flight mass spectrometry. Fullerene clusters in charge states up to q=5 have been observed and appearance sizes are found to be as small as n(app)=5, 10, 21, and 33 for q=2, 3, 4, and 5, respectively. The analysis of the multicoincident fragmentation spectra indicates a high charge mobility. This is in contrast to charge localization effects which have been reported for Ar(q+)(n) rare gas clusters. Clusters of fullerenes are found to be conducting when multiply charged.

Journal Article↗