| 1. |
- Moberg, Christina, et al.
(författare)
-
De unga gör helt rätt när de stämmer staten
- 2022
-
Ingår i: Aftonbladet. - 1103-9000.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
|
|
| 2. |
- Mårtensson, Ulrika, et al.
(författare)
-
Deletion of the G protein-coupled receptor 30 impairs glucose tolerance, reduces bone growth, increases blood pressure, and eliminates estradiol-stimulated insulin release in female mice.
- 2009
-
Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 150:2, s. 687-98
-
Tidskriftsartikel (refereegranskat)abstract
- In vitro studies suggest that the G protein-coupled receptor (GPR) 30 is a functional estrogen receptor. However, the physiological role of GPR30 in vivo is unknown, and it remains to be determined whether GPR30 is an estrogen receptor also in vivo. To this end, we studied the effects of disrupting the GPR30 gene in female and male mice. Female GPR30((-/-)) mice had hyperglycemia and impaired glucose tolerance, reduced body growth, increased blood pressure, and reduced serum IGF-I levels. The reduced growth correlated with a proportional decrease in skeletal development. The elevated blood pressure was associated with an increased vascular resistance manifested as an increased media to lumen ratio of the resistance arteries. The hyperglycemia and impaired glucose tolerance in vivo were associated with decreased insulin expression and release in vivo and in vitro in isolated pancreatic islets. GPR30 is expressed in islets, and GPR30 deletion abolished estradiol-stimulated insulin release both in vivo in ovariectomized adult mice and in vitro in isolated islets. Our findings show that GPR30 is important for several metabolic functions in female mice, including estradiol-stimulated insulin release.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Adler, Jan-Olof, et al.
(författare)
-
A broad range tagging spectrometer for the MAX-laboratory
- 1997
-
Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 388:1-2, s. 17-26
-
Tidskriftsartikel (refereegranskat)abstract
- A broad range tagging spectrometer together with a new beam transport system for photonuclear experiments at the MAX-laboratory in Lund is described. The spectrometer consists of a quadrupole followed by an Elbek-type dipole and has a large momentum acceptance. It can produce both polarized and unpolarized tagged photons in the energy range 10–80 MeV with an energy resolution of about 300 keV.
|
|
| 6. |
- Rask, Olof, et al.
(författare)
-
Oestrogen treatment of constitutional tall stature in girls: is there a risk of thrombosis or bleeding?
- 2008
-
Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 97:3, s. 342-347
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: To evaluate haemostatic effects and clinical outcome of oestrogen treatment of constitutionally tall stature in girls. Methods: We conducted a single-centre cohort study, 63 girls referred over a period of 15 years were investigated. The girls were given oestrogen treatment for constitutional tall stature at a median initial dose of 300 ug ethinyl estradiol/day and were consecutively examined for changes in coagulation. Medical records were retrospectively reviewed, additional data were collected at follow-up by blood sampling and interviews. Results: After 1 year of treatment, levels of antithrombin and von Willebrand factor (VWF) were significantly decreased (p < 0.001 and p = 0.015, respectively), whereas there was no significant change in levels of plasminogen inhibitor type 1. No venous thromboembolism (VTE) or major side effects were observed. Genetic risk factors for thrombosis were present, as was expected. The mean height reduction was 5.5 cm. The height-reducing effect was inversely correlated with chronological age (r =-0.44, p < 0.01) and bone age (r =-0.61, p < 0.01). Conclusions: Changes in coagulation parameters occurred both towards pro- and anticoagulation. Treatment with high-dose ethinyl estradiol can successfully limit final height, and it is most effective when started at a younger bone age.
|
|
| 7. |
- Santillo, Alexander Frizell, et al.
(författare)
-
Grey and white matter clinico-anatomical correlates of disinhibition in neurodegenerative disease
- 2016
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:10
-
Tidskriftsartikel (refereegranskat)abstract
- Disinhibition is an important symptom in neurodegenerative diseases. However, the clinico- anatomical underpinnings remain controversial. We explored the anatomical correlates of disinhibition in neurodegenerative disease using the perspective of grey and white matter imaging. Disinhibition was assessed with a neuropsychological test and a caregiver information- based clinical rating scale in 21 patients with prefrontal syndromes due to behavioural variant frontotemporal dementia (n = 12) or progressive supranuclear palsy (n = 9), and healthy controls (n = 25). Cortical thickness was assessed using the Freesurfer software on 3T MRI data. The integrity of selected white matter tracts was determined by the fractional anisotropy (FA) from Diffusion Tensor Imaging. Disinhibition correlated with the cortical thickness of the right parahippocampal gyrus, right orbitofrontal cortex and right insula and the FA of the right uncinate fasciculus and right anterior cingulum. Notably, no relationship was seen with the thickness of ventromedial prefrontal cortex. Our results support an associative model of inhibitory control, distributed in a medial temporal lobe-insularorbitofrontal network, connected by the intercommunicating white matter tracts. This reconciles some of the divergences among previous studies, but also questions the current conceptualisation of the prefrontal syndrome and the central role attributed to the ventromedial prefrontal cortex in inhibitory control.
|
|
| 8. |
- Aad, G., et al.
(författare)
-
- 2012
-
Ingår i: Nuclear Physics, Section B. - : Elsevier BV. - 0550-3213 .- 1873-1562. ; 864:3, s. 341-381
-
Tidskriftsartikel (refereegranskat)
|
|
| 9. |
- Aad, G., et al.
(författare)
-
- 2013
-
Tidskriftsartikel (refereegranskat)
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Abdallah, J., et al.
(författare)
-
The Laser calibration of the ATLAS Tile Calorimeter during the LHC run 1
- 2016
-
Ingår i: Journal of Instrumentation. - 1748-0221. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- This article describes the Laser calibration system of the ATLAS hadronic Tile Calorimeter that has been used during the run 1 of the LHC. First, the stability of the system associated readout electronics is studied. It is found to be stable with variations smaller than 0.6 %. Then, the method developed to compute the calibration constants, to correct for the variations of the gain of the calorimeter photomultipliers, is described. These constants were determined with a statistical uncertainty of 0.3 % and a systematic uncertainty of 0.2 % for the central part of the calorimeter and 0.5 % for the end-caps. Finally, the detection and correction of timing mis-configuration of the Tile Calorimeter using the Laser system are also presented.
|
|
| 26. |
- Abu Al-Soud, Waleed, et al.
(författare)
-
DNA of Helicobacter spp. and common gut bacteria in primary liver carcinoma.
- 2008
-
Ingår i: Digestive and Liver Disease. - : Elsevier BV. - 1590-8658. ; 40:2, s. 126-131
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIM: Gastric and enteric Helicobacter species have been associated with the pathogenesis of some extragastric diseases. METHODS: We retrospectively investigated the presence of DNA of Helicobacter species in samples of the cancer and the surrounding tumour-free liver tissues of patients with hepatocellular carcinoma (HCC, n=12) and cholangiocarcinoma (CC, n=13). The patients were from an area with low liver cancer incidence and with low hepatitis B and C prevalence. Patients with a benign liver disease (n=24) were included as controls. Paraffin-embedded liver samples were examined by a Helicobacter genus-specific PCR assay as well as group-specific PCR assays for Enterobacteriaceae, Bacteroides, Lactobacillus and Enterococcus. PCR products of positive samples were characterised by denaturing gradient gel electrophoresis (DGGE) and DNA sequencing. RESULTS: PCR assay detected Helicobacter DNA in seven of 12 (58%) and eight of 13 (62%) normal liver tissue specimens from HCC and CC patients, respectively. Two cancer samples from HCC patients were Helicobacter-positive but none of the CC cancers. In the control group, three of 24 (12.5%) patients with a benign liver condition were positive for Helicobacter species (p<0.01 compared to results of tumour-free liver tissue from the cancer patients). DGGE and DNA sequence analysis showed that 90% of the detected PCR products were "H. pylori-like". DNA of some other enteric bacteria was detected in the liver of one cancer patient and one control (4% of all patients). CONCLUSION: The presence of DNA of Helicobacter species in liver specimens, but not of other common gut bacteria, was associated with human hepatic carcinogenesis.
|
|
| 27. |
- Akhter, Shirin, et al.
(författare)
-
Cone-setting in spruce is regulated by conserved elements of the age-dependent flowering pathway
- 2022
-
Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 236:5, s. 1951-1963
-
Tidskriftsartikel (refereegranskat)abstract
- Reproductive phase change is well characterized in angiosperm model species, but less studied in gymnosperms. We utilize the early cone-setting acrocona mutant to study reproductive phase change in the conifer Picea abies (Norway spruce), a gymnosperm. The acrocona mutant frequently initiates cone-like structures, called transition shoots, in positions where wild-type P. abies always produces vegetative shoots. We collect acrocona and wild-type samples, and RNA-sequence their messenger RNA (mRNA) and microRNA (miRNA) fractions. We establish gene expression patterns and then use allele-specific transcript assembly to identify mutations in acrocona. We genotype a segregating population of inbred acrocona trees. A member of the SQUAMOSA BINDING PROTEIN-LIKE (SPL) gene family, PaSPL1, is active in reproductive meristems, whereas two putative negative regulators of PaSPL1, miRNA156 and the conifer specific miRNA529, are upregulated in vegetative and transition shoot meristems. We identify a mutation in a putative miRNA156/529 binding site of the acrocona PaSPL1 allele and show that the mutation renders the acrocona allele tolerant to these miRNAs. We show co-segregation between the early cone-setting phenotype and trees homozygous for the acrocona mutation. In conclusion, we demonstrate evolutionary conservation of the age-dependent flowering pathway and involvement of this pathway in regulating reproductive phase change in the conifer P. abies.
|
|
| 28. |
- Akhter, Shirin, et al.
(författare)
-
Transcriptome studies of the early cone-setting acrocona mutant provide evidence for a functional conservation of the age-dependent flowering pathway between angiosperms and gymnosperms.
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- All seed plants go through a juvenile period before they initiate seed- and pollen-bearing organs and reproduce. Reproductive phase-change is well characterized in angiosperm model species, but much less well described in gymnosperms. Here, we utilize the early cone-setting acrocona mutant to study reproductive phase change in the conifer Picea abies; a representative of the gymnosperm lineage. The acrocona mutant frequently initiates cone-like structures, called transition shoots, in positions where wild-type P. abies always produces vegetative shoots. By sequence analysis of mRNA and microRNA transcripts, we demonstrate that orthologous components of the Age-dependent flowering pathway are active at the time of cone initiation. We show that a member of the SQUAMOSA BINDING PROTEIN-LIKE (SPL) gene family, PaSPL7, is active in reproductive meristems, whereas a putative negative regulator of PaSPL7, microRNA156 is upregulated in vegetative meristem. By allele-specific assembly, we also identify a short nucleotide polymorphism (SNP) in the miRNA156 binding of PaSPL7. By genotyping a segregating population of inbred acrocona trees, we show a clear co-segregation between the early cone-setting phenotype and trees homozygous for the SNP. Hence, the data presented demonstrate evolutionary conservation of the age-dependent flowering pathway and involvement of this pathway in regulating cone-setting in the conifer P. abies.
|
|
| 29. |
- Albertsson-Wikland, Kerstin, 1947, et al.
(författare)
-
Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency
- 2008
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:11, s. 4342-4350
-
Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH).OBJECTIVE: The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls.DESIGN AND SETTING: A randomized, controlled, long-term multicenter trial was conducted in Sweden.INTERVENTION: Two doses of GH (Genotropin) were administered, 33 or 67 microg/kg.d; control subjects were untreated.SUBJECTS: A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (AllITT) population, and 108 in the per protocol (AllPP) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population.MAIN OUTCOME MEASURES: We measured FH sd score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in heightSDS.RESULTS: After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations.CONCLUSION: GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls.
|
|
| 30. |
- Aydogdu, Canan, 1978, et al.
(författare)
-
Radar Interference Mitigation for Automated Driving : Exploring Proactive Strategies
- 2020
-
Ingår i: IEEE signal processing magazine (Print). - Piscataway : Institute of Electrical and Electronics Engineers (IEEE). - 1053-5888 .- 1558-0792. ; 37:4, s. 72-84
-
Tidskriftsartikel (refereegranskat)abstract
- Autonomous driving relies on a variety of sensors, especially radars, which have unique robustness under heavy rain/fog/snow and poor light conditions. With the rapid increase of the amount of radars used on modern vehicles, where most radars operate in the same frequency band, the risk of radar interference becomes a compelling issue. This article analyzes automotive radar interference and proposes several new approaches that combine industrial and academic expertise toward the goal of achieving interference-free autonomous driving (AD). © IEEE.
|
|
| 31. |
- Aydogdu, Canan, 1978, et al.
(författare)
-
Radar Interference Mitigation through Active Coordination
- 2021
-
Ingår i: IEEE National Radar Conference - Proceedings. - : IEEE. - 1097-5659. ; 2021-May, s. 1-6
-
Konferensbidrag (refereegranskat)abstract
- Intelligent transportation is heavily reliant on radar, which have unique robustness under heavy rain/fog/snow and poor light conditions. With the rapid increase of the number of radars used on modern vehicles, most operating in the same frequency band, the risk of radar interference becomes an important issue. As in radio communication, interference can be mitigated through coordination. We present and evaluate two approaches for radar interference coordination, one for FMCW and one for OFDM, and highlight their challenges and opportunities.
|
|
| 32. |
- Bankell, Elisabeth, et al.
(författare)
-
Suppression of smooth muscle cell inflammation by myocardin-related transcription factors involves inactivation of TANK-binding kinase 1
- 2024
-
Ingår i: Scientific Reports. - 2045-2322. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Myocardin-related transcription factors (MRTFs: myocardin/MYOCD, MRTF-A/MRTFA, and MRTF-B/MRTFB) suppress production of pro-inflammatory cytokines and chemokines in human smooth muscle cells (SMCs) through sequestration of RelA in the NF-κB complex, but additional mechanisms are likely involved. The cGAS-STING pathway is activated by double-stranded DNA in the cytosolic compartment and acts through TANK-binding kinase 1 (TBK1) to spark inflammation. The present study tested if MRTFs suppress inflammation also by targeting cGAS-STING signaling. Interrogation of a transcriptomic dataset where myocardin was overexpressed using a panel of 56 cGAS-STING cytokines showed the panel to be repressed. Moreover, MYOCD, MRTFA, and SRF associated negatively with the panel in human arteries. RT-qPCR in human bronchial SMCs showed that all MRTFs reduced pro-inflammatory cytokines on the panel. MRTFs diminished phosphorylation of TBK1, while STING phosphorylation was marginally affected. The TBK1 inhibitor amlexanox, but not the STING inhibitor H-151, reduced the anti-inflammatory effect of MRTF-A. Co-immunoprecipitation and proximity ligation assays supported binding between MRTF-A and TBK1 in SMCs. MRTFs thus appear to suppress cellular inflammation in part by acting on the kinase TBK1. This may defend SMCs against pro-inflammatory insults in disease.
|
|
| 33. |
- Bankell, Elisabeth, et al.
(författare)
-
The antimicrobial peptide LL-37 triggers release of apoptosis-inducing factor and shows direct effects on mitochondria
- 2022
-
Ingår i: Biochemistry and Biophysics Reports. - : Elsevier BV. - 2405-5808. ; 29
-
Tidskriftsartikel (refereegranskat)abstract
- The human antimicrobial peptide LL-37 permeabilizes the plasma membrane of host cells, but LL-37-induced direct effects on mitochondrial membrane permeability and function has not been reported. Here, we demonstrate that LL-37 is rapidly (within 20 min) internalized by human osteoblast-like MG63 cells, and that the peptide co-localizes with MitoTracker arguing for accumulation in mitochondria. Subcellular fractionation and Western blot disclose that stimulation with LL-37 (8 μM) for 2 h triggers release of the mitochondrial protein apoptosis-inducing factor (AIF) to the cytosol, whereas LL-37 causes no release of cytochrome C oxidase subunit IV of the inner mitochondrial membrane, suggesting that LL-37 affects mitochondrial membrane permeability in a specific manner. Next, we investigated release of AIF and cytochrome C from isolated mitochondria by measuring immunoreactivity by dot blot. The media of mitochondria treated with LL-37 (8 μM) for 2 h contained 50% more AIF and three times more cytochrome C than that of control mitochondria, showing that LL-37 promotes release of both AIF and cytochrome C. Moreover, in vesicles reflecting mitochondrial membrane lipid composition, LL-37 stimulates membrane permeabilization and release of tracer molecules. We conclude that LL-37 is rapidly internalized by MG63 cells and accumulates in mitochondria, and that the peptide triggers release of pro-apoptotic AIF and directly affects mitochondrial membrane structural properties.
|
|
| 34. |
- Bengnér, Malin, et al.
(författare)
-
Independent skewing of the T cell and NK cell compartments associated with cytomegalovirus infection suggests division of labor between innate and adaptive immunity.
- 2014
-
Ingår i: Age (Omaha). - : Springer Science and Business Media LLC. - 0161-9152 .- 1574-4647. ; 36:2, s. 571-582
-
Tidskriftsartikel (refereegranskat)abstract
- Cytomegalovirus (CMV) infection induces profound changes in different subsets of the cellular immune system. We have previously identified an immune risk profile (IRP) where CMV-associated changes in the T cell compartment, defined as a CD4/CD8 ratio < 1, are associated with increased mortality in elderly people. Since natural killer (NK) cells have an important role in the defense against viral infections, we examined whether the expansion of CD8 + T cells seen in individuals with CD4/CD8 ratio < 1 is coupled to a parallel skewing of the NK cell compartment. A number of 151 subjects were examined with CMV serology and a flow cytometry panel for assessment of T cell and NK cell subsets. CMV-seropositive individuals had higher frequencies of CD57 + and NKG2C + NK cells and lower frequencies of NKG2A + NK cells, in line with a more differentiated NK cell compartment. Intriguingly, however, there was no correlation between CD4/CD8 ratio and NK cell repertoires among CMV-seropositive donors, despite the profound skewing of the T cell compartment in the group with CD4/CD8 ratio < 1. Conversely, donors with profound expansion of NK cells, defined as NKG2C + NK cells with high expression of CD57 and ILT-2, did not display more common changes in their T cell repertoire, suggesting that NK cell expansion is independent of the T cell-defined IRP. Altogether, these results indicate that the effect of CMV on CD8 T cells and NK cells is largely nonoverlapping and independent.
|
|
| 35. |
- Carvajal, Gisela, 1983, et al.
(författare)
-
Comparison of Automotive FMCW and OFDM Radar Under Interference
- 2020
-
Ingår i: IEEE National Radar Conference - Proceedings. - New York, NY : IEEE. - 1097-5659. ; 2020-September
-
Konferensbidrag (refereegranskat)abstract
- Automotive radars are subject to interference in spectrally congested environments. To mitigate this interference, various waveforms have been proposed. We compare two waveforms (FMCW and OFDM) in terms of their radar performance and robustness to interference, under similar parameter settings. Our results indicate that under proper windowing both waveforms can achieve similar performance, but OFDM is more sensitive to interference.
|
|
| 36. |
- Dahl, Sara, et al.
(författare)
-
Human host defense peptide LL-37 facilitates double-stranded RNA pro-inflammatory signaling through up-regulation of TLR3 expression in vascular smooth muscle cells
- 2020
-
Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 69:6, s. 579-588
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The importance of human host defense peptide LL-37 in vascular innate immunity is not understood. Here, we assess the impact of LL-37 on double-stranded RNA (dsRNA) signaling in human vascular smooth muscle cells.MATERIALS AND METHODS: Cellular import of LL-37 and synthetic dsRNA (poly I:C) were investigated by immunocytochemistry and fluorescence imaging. Transcript and protein expression were determined by qPCR, ELISA and Western blot. Knockdown of TLR3 was performed by siRNA.RESULTS: LL-37 was rapidly internalized, suggesting that it has intracellular actions. Co-stimulation with poly I:C and LL-37 enhanced pro-inflammatory IL-6 and MCP-1 transcripts several fold compared to treatment with poly I:C or LL-37 alone. Poly I:C increased IL-6 and MCP-1 protein production, and this effect was potentiated by LL-37. LL-37-induced stimulation of poly I:C signaling was not associated with enhanced import of poly I:C. Treatment with poly I:C and LL-37 in combination increased expression of dsRNA receptor TLR3 compared to stimulation with poly I:C or LL-37 alone. In TLR3 knockdown cells, treatment with poly I:C and LL-37 in combination had no effect on IL-6 and MCP-1 expression, showing loss of function.CONCLUSIONS: LL-37 potentiates dsRNA-induced cytokine production through up-regulation of TLR3 expression representing a novel pro-inflammatory mechanism.
|
|
| 37. |
|
|
| 38. |
- Grossi, Mario, et al.
(författare)
-
Inhibition of Polyamine Formation Antagonizes Vascular Smooth Muscle Cell Proliferation and Preserves the Contractile Phenotype.
- 2014
-
Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7843 .- 1742-7835. ; 115:5, s. 379-388
-
Tidskriftsartikel (refereegranskat)abstract
- The polyamines putrescine, spermidine and spermine play essential roles in cell proliferation and migration, two processes involved in the development of vascular disease. Thus, intervention with polyamine formation may represent a way to inhibit unwanted vascular smooth muscle cell (VSMC) proliferation. The aim of the present study was to assess the importance of polyamines for VSMC proliferation and vascular contractility. The rate-limiting step in polyamine biosynthesis is catalyzed by ornithine decarboxylase. Treatment with α-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, reduced DNA synthesis in primary rat VSMCs in a concentration-dependent manner with an IC50 value of 100 μM. Moreover, DFMO reduced VSMC migration assessed in a scratch assay. The DFMO-induced attenuation of VSMC proliferation was associated with lowered cellular amount of polyamines. The anti-proliferative effect of DFMO was specific since supplementation with polyamines reversed the effect of DFMO on proliferation and normalized cellular polyamine levels. Isometric force recordings in cultured rat tail artery rings showed that DFMO counteracts the decrease in contractility caused by culture with foetal bovine serum as growth stimulant. We conclude that inhibition of polyamine synthesis by DFMO may limit the first wave of cell proliferation and migration, which occurs in the acute phase after vascular injury. Besides its anti-proliferative effect, DFMO may prevent loss of the smooth muscle contractile phenotype in vascular injury. This article is protected by copyright. All rights reserved.
|
|
| 39. |
- Grossi, Mario, et al.
(författare)
-
Inhibition of polyamine uptake potentiates the anti-proliferative effect of polyamine synthesis inhibition and preserves the contractile phenotype of vascular smooth muscle cells.
- 2015
-
Ingår i: Journal of Cellular Physiology. - : Wiley. - 1097-4652 .- 0021-9541.
-
Tidskriftsartikel (refereegranskat)abstract
- Increased vascular smooth muscle cell (VSMC) proliferation is a factor in atherosclerosis and injury-induced arterial (re)stenosis. Inhibition of polyamine synthesis by α-difluoro-methylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, attenuates VSMC proliferation with high sensitivity and specificity. However, cells can escape polyamine synthesis blockade by importing polyamines from the environment. To address this issue, polyamine transport inhibitors (PTIs) have been developed. We investigated the effects of the novel trimer44NMe (PTI-1) alone and in combination with DFMO on VSMC polyamine uptake, proliferation and phenotype regulation. PTI-1 efficiently inhibited polyamine uptake in primary mouse aortic and human coronary VSMCs in the absence as well as in the presence of DFMO. Interestingly, culture with DFMO for 2 days substantially (>95%) reduced putrescine (Put) and spermidine (Spd) contents without any effect on proliferation. Culture with PTI-1 alone had no effect on either polyamine levels or proliferation rate, but the combination of both treatments reduced Put and Spd levels below the detection limit and inhibited proliferation. Treatment with DFMO for a longer time period (4 days) reduced Put and Spd below their detection limits and reduced proliferation, showing that only a small pool of polyamines is needed to sustain VSMC proliferation. Inhibited proliferation by polyamine depletion was associated with maintained expression of contractile smooth marker genes. In cultured intact mouse aorta, PTI-1 potentiated the DFMO-induced inhibition of cell proliferation. The combination of endogenous polyamine synthesis inhibition with uptake blockade is thus a viable approach for targeting unwanted vascular cell proliferation in vivo, including vascular restenosis. This article is protected by copyright. All rights reserved.
|
|
| 40. |
- Grossi, Mario, et al.
(författare)
-
Vascular smooth muscle cell proliferation depends on caveolin-1-regulated polyamine uptake
- 2014
-
Ingår i: Bioscience Reports. - 0144-8463. ; 34, s. 729-741
-
Tidskriftsartikel (refereegranskat)abstract
- Much evidence highlights the importance of polyamines for VSMC (vascular smooth muscle cell) proliferation and migration. Cav-1 (caveolin-1) was recently reported to regulate polyamine uptake in intestinal epithelial cells. The aim of the present study was to assess the importance of Cav-1 for VSMC polyamine uptake and its impact on cell proliferation and migration. Cav-1 KO (knockout) mouse aortic cells showed increased polyamine uptake and elevated proliferation and migration compared with WT (wild-type) cells. Both Cav-1 KO and WT cells expressed the smooth muscle differentiation markers SM22 and calponin. Cell-cycle phase distribution analysis revealed a higher proportion of Cav-1 KO than WT cells in the S phase. Cav-1 KO cells were hyper-proliferative in the presence but not in the absence of extracellular polyamines, and, moreover, supplementation with exogenous polyamines promoted proliferation in Cav-1 KO but not in WT cells. Expression of the solute carrier transporters Slc7a1 and Slc43a1 was higher in Cav-1 KO than in WT cells. ODC (ornithine decarboxylase) protein and mRNA expression as well as ODC activity were similar in Cav-1 KO and WT cells showing unaltered synthesis of polyamines in Cav-1 KO cells. Cav-1 was reduced in migrating cells in vitro and in carotid lesions in vivo. Our data show that Cav-1 negatively regulates VSMC polyamine uptake and that the proliferative advantage of Cav-1 KO cells is critically dependent on polyamine uptake. We provide proof-of-principle for targeting Cav-1-regulated polyamine uptake as a strategy to fight unwanted VSMC proliferation as observed in restenosis.
|
|
| 41. |
- Gullberg, Bo, et al.
(författare)
-
Incidence of hip fractures in Malmo, Sweden (1950-1991)
- 1993
-
Ingår i: Bone. - 1873-2763. ; 14:Suppl. 1, s. 23-29
-
Tidskriftsartikel (refereegranskat)abstract
- In a 24-year sub-sample taken from a 42-year period of study (1950-1991), hip fracture incidence was analysed from a defined catchment area within one hospital. During this time, 8,256 hip fractures occurred in a generated risk population of 1,915,571 person-years. Crude incidence increased three-fold in women and five-fold in men. In men, the age-specific increase was twice as large as the age drift. In women, the two components were of equal size. The more marked increase in men caused the female:male ratio to decrease from 4.2 in 1950 to 2.4 in 1991. In men, all age classes experienced a significant yearly increase (1.6% in the 50-59 age group, 3.9% over the age of 80). In women, only the 70-79 and 80+ age groups showed a significant increase (1.4%, 2.3%). In the age-standardised curve, a levelling off occurred during the mid-80s. In women, this was attributable to changes in climate during wintertime. In men, no significant association was found with temperature. The age-standardised curve followed an approximate linear trend with an increase of 6.4/100,000/year in women and 4.9/100,000/year in men. The cumulative rate for the age group 50-79 years doubled in men but increased only by one-third in women. The impact of increasing incidence in men compared with women is discussed using an osteoporosis model consisting of base risk, senile risk, and post-menopausal risk.
|
|
| 42. |
|
|
| 43. |
- Höjer, Mattias, 1966-, et al.
(författare)
-
Scenarios in selected tools for environmental systems analysis
- 2008
-
Ingår i: Journal of Cleaner Production. - : Elsevier BV. - 0959-6526 .- 1879-1786. ; 16:18, s. 1958-1970
-
Tidskriftsartikel (refereegranskat)abstract
- A number of different tools for analysing environmental impacts of different systems have been developed. These include procedural tools such as strategic environmental assessment (SEA) and environmental management systems (EMS) as well as analytical ones such as life cycle assessment (LCA), life cycle costing (LCC), cost-benefit analysis (CBA) and the system of economic and environmental accounts (SEEA) including input-output analysis (IOA). Descriptions or scenarios of the future are typically relevant elements in these tools, since they are often used to describe impacts in the future. For futures studies a number of different approaches and techniques have been developed. In an earlier paper we have presented a typology of different types of scenarios that respond to different types of questions. These include predictive scenarios, explorative scenarios and normative scenarios. The aim of this paper is to explore connections between selected tools for environmental systems analysis and different scenario types. Although there is a clear need for futures studies in several tools for environmental systems analysis, it is interesting to note that the literature on methodologies for and case studies of combinations of futures studies and environmental systems analysis tools is rather limited. This suggests that there is a need for further research in this area including both methodoloy and practical case studies.
|
|
| 44. |
- Karbalaei, Mardjaneh, et al.
(författare)
-
Detrusor Induction of miR-132/212 following Bladder Outlet Obstruction: Association with MeCP2 Repression and Cell Viability.
- 2015
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- The microRNAs (miRNAs) miR-132 and miR-212 have been found to regulate synaptic plasticity and cholinergic signaling and recent work has demonstrated roles outside of the CNS, including in smooth muscle. Here, we examined if miR-132 and miR-212 are induced in the urinary bladder following outlet obstruction and whether this correlates with effects on gene expression and cell growth. Three to seven-fold induction of miR-132/212 was found at 10 days of obstruction and this was selective for the detrusor layer. We cross-referenced putative binding sites in the miR-132/212 promoter with transcription factors that were predicted to be active in the obstruction model. This suggested involvement of Creb and Ahr in miR-132/212 induction. Creb phosphorylation (S-133) was not increased, but the number of Ahr positive nuclei increased. Moreover, we found that serum stimulation and protein kinase C activation induced miR-132/212 in human detrusor cells. To identify miR-132/212 targets, we correlated the mRNA levels of validated targets with the miRNA levels. Significant correlations between miR-132/212 and MeCP2, Ep300, Pnkd and Jarid1a were observed, and the protein levels of MeCP2, Pnkd and Ache were reduced after obstruction. Reduction of Ache however closely matched a 90% reduction of synapse density arguing that its repression was unrelated to miR-132/212 induction. Importantly, transfection of antimirs and mimics in cultured detrusor cells increased and decreased, respectively, the number of cells and led to changes in MeCP2 expression. In all, these findings show that obstruction of the urethra increases miR-132 and miR-212 in the detrusor and suggests that this influences gene expression and limits cell growth.
|
|
| 45. |
- Karlsson, Magnus, et al.
(författare)
-
Bone mineral density assessed by quantitative ultrasound and dual energy X-ray absorptiometry. Normative data in Malmo, Sweden
- 1998
-
Ingår i: Acta Orthopaedica Scandinavica. - : Medical Journals Sweden AB. - 0001-6470. ; 69:2, s. 189-193
-
Tidskriftsartikel (refereegranskat)abstract
- We measured bone mineral density (BMD) in 128 men and 143 women, aged 22-90, by dual energy X-ray absorptiometry (DEXA) and quantitative ultrasound (QUS). We found reduced bone mineral density in relation to age as measured both by DEXA and QUS. There was a correlation between 0.28 and 0.52 in men and between 0.53 and 0.77 in women when comparing DEXA and QUS measurements. When including only persons with low bone mass, the correlation was less.
|
|
| 46. |
- Karlsson, Magnus, et al.
(författare)
-
Changes in bone mineral, lean body mass and fat content as measured by dual energy X-ray absorptiometry: a longitudinal study
- 2000
-
Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 66:2, s. 97-99
-
Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) and soft tissue composition were measured by dual energy X-ray absorptiometry (DXA) 3-4 years apart in 273 men and women aged 23-90. We found different rates of BMD loss in different skeletal regions. There were also different rates of BMD loss in different regions within the hip. Average rates of loss for male subjects 50 years of age and above for BMD total body were 0.1%/year and for femoral neck 1.5%/year, whereas lumbar spine (L2-L4) increased by 0.4%/year. Average rates of loss for female subjects 50 years of age and above for BMD total body were 0.0%/year, femoral neck 0.9%/year, and lumbar spine (L2-L4) 0.1%/year.
|
|
| 47. |
- Karlsson, Magnus, et al.
(författare)
-
Changes of bone mineral mass and soft tissue composition after hip fracture
- 1996
-
Ingår i: Bone. - 1873-2763. ; 18:1, s. 19-22
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this prospective longitudinal study was to measure prospectively the bone mineral density (BMD) and anthropometric variables after a hip fracture. In particular, we studied changes in the BMD in both the injured and uninjured hips, and examined if the postoperative mortality rate and complications, including pseudarthrosis of the fracture and late segmental collapse of the head of the femur, could be predicted by early bone mass measurements. The bone mineral density and the body composition were measured with dual energy X-ray absorptiometry in 102 consecutive hip fracture patients, 31 men and 71 women, with a mean age of 74 and 79 years, respectively. All cases were operated on within 3 days. The measurements were undertaken within 10 days after the fracture, after 4 and after 12 months. The BMD of the hip fracture cases decreased, especially in the lower extremities where the patients lost 7%, during the first year after the fracture. The patients also lost lean body mass (5%) but gained fat (11%) during the same period. They lost significantly more bone mass in the fractured hip than in the uninjured hip (p < 0.05). No difference was found between those patients who survived and those who died within 2 years after their hip fracture in neither the initial measurement nor in the follow-up measurements. Also, we found no difference between those patients whose hip fracture healed and those who developed late segmental collapse or pseudarthrosis. In conclusion, osteoporotic hip fracture cases lose bone mass at an increased rate, especially in the fractured hip. Also, their soft tissue composition changes, gaining fat while losing muscle mass. Furthermore, it seems that early bone mineral measurements cannot predict postoperative failures or postoperative mortality.
|
|
| 48. |
- Karlsson, Magnus K., et al.
(författare)
-
Bone mineral normative data in Malmö, Sweden : Comparison with reference data and hip fracture incidence in other ethnic groups
- 1993
-
Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 0001-6470. ; 64:2, s. 168-172
-
Tidskriftsartikel (refereegranskat)abstract
- The bone mineral mass was measured in 324 residents of the city of Malmö Sweden, by dual energy roentgen absorptiometry (DEXA) using the Lunar DPX equipment - total body, hip, and lumbar vertebrae. the bone mineral content of the wrist was also measured with single photon absorptiometry (SPA) in 88 of the individuals. Weight, height, and vertebral height, as well as body fat, lean body mass, menarcheal age, menopausal age, and hand grip strength were determined. Measurements were compared with reference bone mineral content values from the United States, Japan, and France - also hip fracture incidence was compared. All bone mineral values decreased with age. A good correlation was found between the DEXA technique of total body bone mineral and the forearm SPA values. the bone mineral content was correlated with lean body mass and weight. the Malmö bone mineral content was on the same level as in the United States, but higher than in Japan and France. the comparatively high risk of fragility fractures in the Scandinavian countries compared with most other settings cannot be explained by low bone mass.
|
|
| 49. |
- Krawczyk, Katarzyna K., et al.
(författare)
-
Assessing the contribution of thrombospondin-4 induction and ATF6α activation to endoplasmic reticulum expansion and phenotypic modulation in bladder outlet obstruction
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Phenotypic modulation of smooth muscle cells is a hallmark of disease. The associated expansion of endoplasmic reticulum (ER) volume remains unexplained. Thrombospondin-4 was recently found to promote ATF6α activation leading to ER expansion. Using bladder outlet obstruction as a paradigm for phenotypic modulation, we tested if thrombospondin-4 is induced in association with ATF6α activation and ER expansion. Thrombospondin-4 was induced and ATF6α was activated after outlet obstruction in rodents. Increased abundance of spliced of Xbp1, another ER-stress sensor, and induction of Atf4 and Creb3l2 was also seen. Downstream of ATF6α, Calr, Manf, Sdf2l1 and Pdi increased as did ER size, whereas contractile markers were reduced. Overexpression of ATF6α, but not of thrombospondin-4, increased Calr, Manf, Sdf2l1 and Pdi and caused ER expansion, but the contractile markers were inert. Knockout of thrombospondin-4 neither affected bladder growth nor expression of ATF6α target genes, and repression of contractile markers was the same, even if ATF6α activation was curtailed. Increases of Xbp1s, Atf4 and Creb3l2 were similar. Our findings demonstrate reciprocal regulation of the unfolded protein response, including ATF6α activation and ER expansion, and reduced contractile differentiation in bladder outlet obstruction occurring independently of thrombospondin-4, which however is a sensitive indicator of obstruction.
|
|
| 50. |
- Kriström, Berit, et al.
(författare)
-
Normalization of puberty and adult height in girls with Turner syndrome : results of the Swedish Growth Hormone trials initiating transition into adulthood
- 2023
-
Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To study the impact of GH dose and age at GH start in girls with Turner syndrome (TS), aiming for normal height and age at pubertal onset (PO) and at adult height (AH). However, age at diagnosis will limit treatment possibilities.Methods: National multicenter investigator-initiated studies (TNR 87-052-01 and TNR 88-072) in girls with TS, age 3–16 years at GH start during year 1987–1998, with AH in 2003–2011. Of the 144 prepubertal girls with TS, 132 girls were followed to AH (intention to treat), while 43 girls reduced dose or stopped treatment prematurely, making n=89 for Per Protocol population. Age at GH start was 3–9 years (young; n=79) or 9–16 years (old; n=53). Treatment given were recombinant human (rh)GH (Genotropin® Kabi Peptide Hormones, Sweden) 33 or 67 µg/kg/day, oral ethinyl-estradiol (2/3) or transdermal 17β-estradiol (1/3), and, after age 11 years, mostly oxandrolone. Gain in heightSDS, AHSDS, and age at PO and at AH were evaluated.Results: At GH start, heightSDS was −2.8 (versus non-TS girls) for all subgroups and mean age for young was 5.7 years and that of old was 11.6 years. There was a clear dose–response in both young and old TS girls; the mean difference was (95%CI) 0.66 (−0.91 to −0.26) and 0.57 (−1.0 to −0.13), respectively. The prepubertal gainSDS (1.3–2.1) was partly lost during puberty (−0.4 to −2.1). Age/heightSDS at PO ranged from 13 years/−0.42 for GH67young to 15.2 years/−1.47 for GH33old. At AH, GH67old group became tallest (17.2 years; 159.9 cm; −1.27 SDS; total gainSDS, 1.55) compared to GH67young group being least delayed (16.1 years; 157.1 cm; −1.73 SDS; total, 1.08). The shortest was the GH33young group (17.3 years; 153.7 cm: −2.28 SDS; total gainSDS, 0.53), and the most delayed was the GH33old group, (18.5 years; 156.5 cm; −1.82 SDS; total gainSDS, 0.98).Conclusion: For both young and old TS girls, there was a GH-dose growth response, and for the young, there was less delayed age at PO and at AH. All four groups reached an AH within normal range, despite partly losing the prepubertal gain during puberty. Depending on age at diagnosis, low age at start with higher GH dose resulted in greater prepubertal height gain, permitting estrogen to start earlier at normal age and attaining normal AH at normal age, favoring physiological treatment and possibly also bone health, hearing, uterine growth and fertility, psychosocial wellbeing during adolescence, and the transition to adulthood.
|
|
