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1.
  • Ambarki, Khalid, et al. (författare)
  • Evaluation of automatic measurement of the intracranial volume based on quantitative MR imaging
  • 2012
  • Ingår i: American Journal of Neuroradiology. - 0195-6108 .- 1936-959X. ; 33:10, s. 1951-1956
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>BACKGROUND AND PURPOSE</strong>: Brain size is commonly described in relation to ICV, whereby accurate assessment of this quantity is fundamental. Recently, an optimized MR sequence (QRAPMASTER) was developed for simultaneous quantification of T1, T2, and proton density. ICV can be measured automatically within minutes from QRAPMASTER outputs and a dedicated software, SyMRI. Automatic estimations of ICV were evaluated against the manual segmentation.</p><p><strong>MATERIALS AND METHODS</strong>: In 19 healthy subjects, manual segmentation of ICV was performed by 2 neuroradiologists (Obs1, Obs2) by using QBrain software and conventional T2-weighted images. The automatic segmentation from the QRAPMASTER output was performed by using SyMRI. Manual corrections of the automatic segmentation were performed (corrected-automatic) by Obs1 and Obs2, who were blinded from each other. Finally, the repeatability of the automatic method was evaluated in 6 additional healthy subjects, each having 6 repeated QRAPMASTER scans. The time required to measure ICV was recorded.</p><p><strong>RESULTS</strong>: No significant difference was found between reference and automatic (and corrected-automatic) ICV (P &gt; .25). The mean difference between the reference and automatic measurement was -4.84 ± 19.57 mL (or 0.31 ± 1.35%). Mean differences between the reference and the corrected-automatic measurements were -0.47 ± 17.95 mL (-0.01 ± 1.24%) and -1.26 ± 17.68 mL (-0.06 ± 1.22%) for Obs1 and Obs2, respectively. The repeatability errors of the automatic and the corrected-automatic method were &lt;1%. The automatic method required 1 minute 11 seconds (SD = 12 seconds) of processing. Adding manual corrections required another 1 minute 32 seconds (SD = 38 seconds).</p><p><strong>CONCLUSIONS</strong>: Automatic and corrected-automatic quantification of ICV showed good agreement with the reference method. SyMRI software provided a fast and reproducible measure of ICV.</p>
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2.
  • Kadkhodaei, Banafsheh, et al. (författare)
  • Nurr1 Is Required for Maintenance of Maturing and Adult Midbrain Dopamine Neurons
  • 2009
  • Ingår i: Journal of Neuroscience. - Society for Neuroscience. - 1529-2401. ; 29:50, s. 15923-15932
  • Tidskriftsartikel (refereegranskat)abstract
    • Transcription factors involved in the specification and differentiation of neurons often continue to be expressed in the adult brain, but remarkably little is known about their late functions. Nurr1, one such transcription factor, is essential for early differentiation of midbrain dopamine (mDA) neurons but continues to be expressed into adulthood. In Parkinson's disease, Nurr1 expression is diminished and mutations in the Nurr1 gene have been identified in rare cases of disease; however, the significance of these observations remains unclear. Here, a mouse strain for conditional targeting of the Nurr1 gene was generated, and Nurr1 was ablated either at late stages of mDA neuron development by crossing with mice carrying Cre under control of the dopamine transporter locus or in the adult brain by transduction of adeno-associated virus Cre-encoding vectors. Nurr1 deficiency in maturing mDA neurons resulted in rapid loss of striatal DA, loss of mDA neuron markers, and neuron degeneration. In contrast, a more slowly progressing loss of striatal DA and mDA neuron markers was observed after ablation in the adult brain. As in Parkinson's disease, neurons of the substantia nigra compacta were more vulnerable than cells in the ventral tegmental area when Nurr1 was ablated at late embryogenesis. The results show that developmental pathways play key roles for the maintenance of terminally differentiated neurons and suggest that disrupted function of Nurr1 and other developmental transcription factors may contribute to neurodegenerative disease.
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3.
  • Lindqvist, Ebba K., et al. (författare)
  • Personal and family history of immune-related conditions increase the risk of plasma cell disorders: a population-based study
  • 2011
  • Ingår i: Blood. - American Society of Hematology. - 1528-0020. ; 118:24, s. 6284-6291
  • Tidskriftsartikel (refereegranskat)abstract
    • The associations between immune-related conditions and multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) have previously been investigated with inconsistent results. In a large population-based study, we identified 19 112 patients with MM, 5403 patients with MGUS, 96 617 matched control subjects, and 262 931 first-degree relatives. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for the association of MM and MGUS with immune-related conditions by use of logistic regression. A personal history of all infections combined was associated with a significantly increased risk of MM (OR = 1.2; 95% CI, 1.1-1.3), and a personal history of all conditions in the categories infections (OR = 1.6; 95% CI, 1.5-1.7), inflammatory conditions (OR = 1.4; 95% CI, 1.2-1.5), and autoimmune diseases (OR = 2.1; 95% CI, 1.9-2.4) was associated with a significantly increased risk of MGUS. Several specific immune-related conditions elevated the risk of MM and/or MGUS. A family history of autoimmune disease was associated with a significantly increased risk of MGUS (OR = 1.1; 95% CI, 1.00-1.2), but not MM. Our findings suggest that immune-related conditions and/or their treatment are of importance in the etiology of MGUS and possibly MM. The association of both personal and family history of autoimmune disease with MGUS indicates the potential for shared susceptibility for these conditions. (Blood. 2011; 118(24): 6284-6291)
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4.
  • Lindqvist, Markus, et al. (författare)
  • Abdominal aortic aneurysm and the association with serum levels of Homocysteine, vitamins B6, B12 and Folate.
  • 2012
  • Ingår i: American Journal of Cardiovascular Disease. - 2160-200X. ; 2:4, s. 318-22
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Previous investigations have shown hyperhomocysteinemi in patients with abdominal aortic aneurysm (AAA). In the present study we evaluated the circulating level of homocysteine (Hcy) in relation to renal function, vitamins B6, B12 and folate status in AAA patients with special regard to aneurysm size, and rupture. Hcy, Creatinine, B6, B12 and folate were measured in 119 patients with AAA and 36 controls without aneurysm matched by age, gender and smoking habit. As expected there was a weak correlation between Hcy and vitamins B6, B12 or folate. We found similar levels of Hcy, B6 and folic acid in patients with nonruptured AAA compared to the control group matched by age, gender and smoking habit. There was no correlation between maximum diameter of the nonruptured AAA (n=78) and Hcy, B6 or folate. However, the present study shows a significant inverse correlation between maximum diameter of the nonruptured AAA (n=78) and B12 (r = -0.304, p=0.007) with significant higher levels in small AAA compared to large AAA. In conclusion, Hcy does not seem to be a useful biomarker in AAA disease. The unexpected finding of B12 levels correlating to aneurysm diameter warrants urgent further investigation of B12 supplement to prevent progression of small AAA.</p>
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5.
  • Lindqvist, Per, et al. (författare)
  • Are suicides by jumping off bridges preventable? An analysis of 50 cases from Sweden.
  • 2004
  • Ingår i: Accident; analysis and prevention. - 0001-4575. ; 36:4, s. 691-4
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>This is a community-based sequential case series of 50 individuals who committed suicide by jumping from bridges in two regions of Sweden. Of the 50 subjects, 32 were men and 18 women, with a median age of 35 years. At least 40 had psychiatric problems. The frequency of suicide was highest during the summer months and during the weekends. A total of 27 bridges were used, with a total length of just under 9 km. Three bridges accounted for almost half of all suicides. Limiting the availability of one method of committing suicide is reported to reduce the overall suicide rate; why suicide and injury suicide preventive measures might be considered. Since this study demonstrates that few bridges attract suicide candidates, this injury mechanism needs to be acknowledged by the road system owners and included in the safety work.</p>
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6.
  • Lindqvist, Per, et al. (författare)
  • Mortality among homicide offenders : a retrospective population-based long-term follow-up.
  • 2007
  • Ingår i: Criminal behaviour and mental health. - 0957-9664. ; 17:2, s. 107-12
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background Empirical data on homicide and homicide offenders are needed in the ongoing discussion on violence and crime prevention. One issue, insufficiently investigated, is the post-trial life course of homicide offenders.Aim To examine whether the mortality rate, as well as cause and manner of death, of homicide offenders is different from the general population.Method An incidence cohort of Swedish homicide offenders from 1970 to 1980 (n = 153) was re-examined by computerized record linkage with the National Cause-of-Death Register for the period between trial and 1 October 2002, i.e. 22-32 years after the offence. Death certificates were analysed, and standard procedures for calculating Standard Mortality Rate (SMR) and survival analysis were employed.Results Half of the study subjects had died by 2002. The overall mortality rate was about three times higher than that of the general population. In particular, the risk of suicide was salient.Implications It can be argued that offenders' self-neglect and self-contempt merge with public and professional views, predisposing to an increased risk of premature death. Copyright (c) 2007 John Wiley &amp; Sons, Ltd.</p>
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8.
  • Mårtensson, Gunnar, et al. (författare)
  • The sensitivity of hyaluronan analysis of pleural fluid from patients with malignant mesothelioma and a comparison of different methods
  • 1994
  • Ingår i: Cancer. - 0008-543X .- 1097-0142. ; 73:5, s. 1406-1410
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>BACKGROUND: Hyaluronan may be used as a marker for malignant mesothelioma, thus indicating its mesodermal origin. METHODS: The sensitivity as a diagnostic test of three different methods for hyaluronan analyses of pleural fluid was examined in patients with biopsy-verified malignant pleural mesothelioma. RESULTS: A quantitative high-performance liquid-chromatography (HPLC) method was performed on fluids from 43 patients. Using a cutoff level of 100 mg/l, higher levels were noted in 30 (70%) patients, with a median value of 220 mg/l (mean, 560 mg/l; range, 20-6600 mg/l). An identical median value (220 mg/l) was obtained with a radioassay method when simultaneously performed on paired samples from 21 patients (correlation coefficient, 0.91). A qualitative precipitation test using 0.5% cetylpyridinium chloride combined with a quantitative viscosimetric method was significantly less sensitive (P &lt; 0.01). CONCLUSION: Hyaluronan analyses is beneficial in distinguishing malignant mesothelioma if methods such as the evaluated HPLC or radioassay with a sensitivity of 70% toward mesothelioma are used and other known causes of elevated content are considered.</p>
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9.
  • Sandmark, Jenny, et al. (författare)
  • Identification and analyses of inhibitors targeting apolipoprotein(a) kringle domains KIV-7, KIV-10, and KV provide insight into kringle domain function
  • 2020
  • Ingår i: The Journal of biological chemistry. - ASBMB. - 1083-351X. ; 295:15, s. 5136-5151
  • Tidskriftsartikel (refereegranskat)abstract
    • Increased plasma concentrations of lipoprotein(a) (Lp(a)) are associated with an increased risk for cardiovascular disease. Lp(a) is composed of apolipoprotein(a) (apo(a)) covalently bound to apolipoprotein B of low-density lipoprotein (LDL). Many of apo(a)'s potential pathological properties, such as inhibition of plasmin generation, have been attributed to its main structural domains, the kringles, and have been proposed to be mediated by their lysine-binding sites. However, available small-molecule inhibitors, such as lysine analogs, bind unselectively to kringle domains and are therefore unsuitable for functional characterization of specific kringle domains. Here, we discovered small molecules that specifically bind to the apo(a) kringle domains KIV-7, KIV-10, and KV. Chemical synthesis yielded compound AZ-05, which bound to KIV-10 with a Kd of 0.8 μm and exhibited more than 100-fold selectivity for KIV-10, compared with the other kringle domains tested, including plasminogen kringle 1. To better understand and further improve ligand selectivity, we determined the crystal structures of KIV-7, KIV-10, and KV in complex with small-molecule ligands at 1.6-2.1 Å resolutions. Furthermore, we used these small molecules as chemical probes to characterize the roles of the different apo(a) kringle domains in in vitro assays. These assays revealed the assembly of Lp(a) from apo(a) and LDL, as well as potential pathophysiological mechanisms of Lp(a), including (i) binding to fibrin, (ii) stimulation of smooth-muscle cell proliferation, and (iii) stimulation of LDL uptake into differentiated monocytes. Our results indicate that a small-molecule inhibitor targeting the lysine-binding site of KIV-10 can combat the pathophysiological effects of Lp(a).
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10.
  • Teigland, Robin, et al. (författare)
  • Investigating the Uppsala Biotech Cluster Baseline Results from the 2004 Uppsala Biotech Cluster Survey
  • 2004
  • Rapport (övrigt vetenskapligt)abstract
    • <p>Just 65 kilometers to the north of Stockholm, Sweden, the Uppsala region has beenincreasingly receiving worldwide recognition during the past five years as a strongand dynamic cluster in the field of biotechnology. In 2003, Vinnova and theVinnväxt Program awarded Uppsala BIO – the Life Science Initiative a package offinancial support for a period of ten years to further support the region’sdevelopment and competitiveness. Uppsala BIO contracted CIND to facilitate inthis process, and one of CIND’s first activities was to conduct the 2004 UppsalaBiotech Cluster Survey. This survey was designed to gain an understanding of thecurrent “state of affairs” in the Uppsala biotech cluster, and selected survey resultsare presented in this report.</p>
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