| 1. |
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| 2. |
- Jarbo, Caroline, et al.
(författare)
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Detailed assessment of chromosome 22 aberrations in sporadic pheochromocytoma using array-CGH.
- 2006
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 118:5, s. 1159-64
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Tidskriftsartikel (refereegranskat)abstract
- Pheochromocytoma is a predominantly sporadic neuroendocrine tumor derived from the adrenal medulla. Previous low resolution LOH and metaphase-CGH studies reported the loss of chromosomes 1p, 3q, 17p and 22q at various frequencies. However, the molecular mechanism(s) behind development of sporadic pheochromocytoma remains largely unknown. We have applied high-resolution tiling-path microarray-CGH with the primary aim to characterize copy number imbalances affecting chromosome 22 in 66 sporadic pheochromocytomas. We detected copy number alterations on 22q at a frequency of 44%. The predominant finding was monosomy 22 (30%), followed by terminal deletions in 8 samples (12%) and a single interstitial deletion. We further applied a chromosome 1 tiling-path array in 7 tumors with terminal deletions of 22q and found deletions of 1p in all cases. Our overall results suggest that at least 2 distinct regions on both 22q and 1p are important in the tumorigenesis of sporadic pheochromocytoma. A large proportion of pheochromocytomas also displayed indications of cellular heterogeneity. Our study is to our knowledge the first array-CGH study of sporadic pheochromocytoma. Future analysis of this tumor type should preferably be performed in the context of the entire human genome using genome-wide array-CGH, which is a superior methodological approach. Supplemental material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.htm
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| 3. |
- Centlow, Magnus, et al.
(författare)
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Die in-vitro Perfusion der menschlichen Plazenta mit Eryhtrozyten und Xanthine Oxidase als in vitro Simulation von Praeeklampsie.
- 2009
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Ingår i: Zeitschrift für Geburtshilfe und Neonatologie. - : Georg Thieme Verlag KG. - 0948-2393 .- 1439-1651. ; 213:3, s. 89-95
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Preeclampsia is a major obstetric problem of unknown etiology. The fact that removal of the placenta is the only cure for preeclampsia, has led to the well-established hypothesis, that the placenta is central in the etiology. Gene profiling and proteomics studies have suggested oxidative stress caused by reperfusion and free oxygen radicals as a potential pathophysiological mechanism in preeclampsia. In this study, the dual placental perfusion model was used in order to evaluate the damaging effects of oxidative stress induced by xanthine/xanthine oxides and free hemoglobin.MATERIAL AND METHODS: The dual placenta perfusion model is a well-established in vitro model for functional placental studies. Placentas were perfused with medium containing either xanthine/xanthine oxidase or erythrocytes as a source of free hemoglobin. Concentration of free hemoglobin in the medium was measured by means of ELISA. Whole genome microarray technique and bioinformatics were used to evaluate the gene expression profile in the two groups.RESULTS: Substantial levels of free adult hemoglobin were detected in the perfusions. A total of 58 genes showed altered gene expression, the most altered were hemoglobin alpha, beta and gamma, tissue factor pathway inhibitor 2 and superoxide dismutase 2. Bioinformatics revealed that biological processes related to oxidative stress, anti-apoptosis and iron ion binding were significantly altered.CONCLUSIONS: The results suggest that perfusion with xanthine/xanthine oxidase and free hemoglobin induce changes in gene expression similar to what has been described for the preeclamptic placenta.
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| 4. |
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| 5. |
- De Château, M, et al.
(författare)
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On the interaction between protein L and immunoglobulins of various mammalian species
- 1993
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 37:4, s. 399-405
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Tidskriftsartikel (refereegranskat)abstract
- Protein L, a cell wall molecule of certain strains of the anaerobic bacterial species Peptostreptococcus magnus, shows high affinity for human immunoglobulin (Ig) light chains. In the present study protein L was tested against a panel of human myeloma proteins of the IgG, IgM, IgA and IgE classes, and strong binding was seen with antibodies carrying kappa light chains. A high degree of specificity for Ig was demonstrated in binding experiments with human plasma proteins. Apart from human Ig, strong protein L-binding activity was also detected in the serum of 12 out of 23 tested additional mammalian species, including other primates and rodents. Subsequent analysis with purified Ig samples demonstrated the binding of protein L to Ig of important laboratory animal species such as the mouse, the rat and the rabbit. The affinity constants for the interactions between protein L and polyclonal IgG of these species were 2.6 x 10(9), 3.9 x 10(8) and 7.4 x 10(7), respectively. In non-human species, the binding of protein L was also found to be mediated through Ig light chains, and the results demonstrate the potential value of protein L as an immunochemical tool.
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| 6. |
- Dolberg Anderson, Ulrik, et al.
(författare)
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Review: Biochemical markers to predict preeclampsia.
- 2012
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Ingår i: Placenta. - : Elsevier BV. - 1532-3102 .- 0143-4004. ; 33, s. 42-47
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Tidskriftsartikel (refereegranskat)abstract
- Worldwide the prevalence of preeclampsia (PE) ranges from 3 to 8% of pregnancies. 8.5 million cases are reported yearly, but this is probably an underestimate due to the lack of proper diagnosis. PE is the most common cause of fetal and maternal death and yet no specific treatment is available. Reliable biochemical markers for prediction and diagnosis of PE would have a great impact on maternal health and several have been suggested. This review describes PE biochemical markers in general and first trimester PE biochemical markers specifically. The main categories described are angiogenic/anti-angiogenic factors, placental proteins, free fetal hemoglobin (HbF), kidney markers, ultrasound and maternal risk factors. The specific biochemical markers discussed are: PAPP-A, s-Flt-1/PlGF, s-Endoglin, PP13, cystatin-C, HbF, and α(1)-microglobulin (A1M). PAPP-A and HbF both show potential as predictive biochemical markers in the first trimester with 70% sensitivity at 95% specificity. However, PAPP-A is not PE-specific and needs to be combined with Doppler ultrasound to obtain the same sensitivity as HbF/A1M. Soluble Flt -1 and PlGF are promising biochemical markers that together show high sensitivity from the mid-second trimester. PlGF is somewhat useful from the end of the first trimester. Screening pregnant women with biochemical markers for PE can reduce unnecessary suffering and health care costs by early detection of mothers at increased risk for PE, thus avoiding unnecessary hospitalization of pregnant women with suspect or mild PE and enabling monitoring of the progression of the disease thereby optimizing time for delivery and hopefully reducing the number of premature births.
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| 7. |
- Falkenberg, C, et al.
(författare)
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Alpha1-microglobulin and bikunin in rats with collagen II-induced arthritis : plasma levels and liver mRNA content
- 1997
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 46:2, s. 8-122
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Tidskriftsartikel (refereegranskat)abstract
- The plasma proteins alpha1-microglobulin (alpha1-m) and bikunin are synthesized in the liver as a common precursor which is cleaved just before secretion. Half of plasma alpha1-m is covalently linked to fibronectin and alpha1-inhibitor-3, and more than 95% of bikunin is part of pre-alpha-inhibitor, inter-alpha-inhibitor and related large molecules. Both alpha1-m and bikunin have been shown to be involved in inflammation, but the regulation of their synthesis is not clear. The authors have measured the plasma and urinary concentrations of alpha1-m and bikunin as well as their hepatic mRNA levels in rats during the development of collagen-induced arthritis. Also, the plasma concentrations of acknowledged acute-phase proteins were measured. The results suggested a biphasic inflammatory reaction: an early response after 1 week, represented by an elevated fibronectin level; and a late response after 3 weeks, represented by elevated alpha1-acid glycoprotein and decreased albumin and alpha1-inhibitor-3 levels. The alpha1-m-bikunin mRNA content in liver was slightly reduced after 1 week and elevated after 3 weeks, but the total concentrations of free and bound alpha1-m and bikunin in plasma were unchanged. The free bikunin fraction as well as the fibronectin/alpha1-m complex in plasma, however, were elevated after 1 week. Urinary bikunin levels were also elevated after 1 week, whereas urinary alpha1-m levels remained unchanged. The results thus suggest that free bikunin in plasma is increased and excreted in the urine at an early stage during the development of collagen-induced arthritis. Later, when the synthesis rate of alpha1-m-bikunin is elevated, both proteins are most likely directed to other locations in the body.
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| 8. |
- Ferreira, Alexandra G, et al.
(författare)
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Reprogramming Cancer Cells to Antigen-presenting Cells
- 2023
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Ingår i: Bio-protocol. - 2331-8325. ; 13:22, s. 1-25
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Tidskriftsartikel (refereegranskat)abstract
- Cancer cells evade the immune system by downregulating antigen presentation. Although immune checkpoint inhibitors (ICI) and adoptive T-cell therapies revolutionized cancer treatment, their efficacy relies on the intrinsic immunogenicity of tumor cells and antigen presentation by dendritic cells. Here, we describe a protocol to directly reprogram murine and human cancer cells into tumor-antigen-presenting cells (tumor-APCs), using the type 1 conventional dendritic cell (cDC1) transcription factors PU.1, IRF8, and BATF3 delivered by a lentiviral vector. Tumor-APCs acquire a cDC1 cell-like phenotype, transcriptional and epigenetic programs, and function within nine days (Zimmermannova et al., 2023). Tumor-APCs express the hematopoietic marker CD45 and acquire the antigen presentation complexes MHC class I and II as well as co-stimulatory molecules required for antigen presentation to T cells, but do not express high levels of negative immune checkpoint regulators. Enriched tumor-APCs present antigens to Naïve CD8 + and CD4 + T cells, are targeted by activated cytotoxic T lymphocytes, and elicit anti-tumor responses in vivo. The tumor-APC reprogramming protocol described here provides a simple and robust method to revert tumor evasion mechanisms by increasing antigen presentation in cancer cells. This platform has the potential to prime antigen-specific T-cell expansion, which can be leveraged for developing new cancer vaccines, neoantigen discovery, and expansion of tumor-infiltrating lymphocytes. Key features • This protocol describes the generation of antigen-presenting cells from cancer cells by direct reprogramming using lineage-instructive transcription factors of conventional dendritic cells type I. • Verification of reprogramming efficiency by flow cytometry and functional assessment of tumor-APCs by antigen presentation assays.
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| 9. |
- Fransson, M. N., et al.
(författare)
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Physiologically-Based Toxicokinetic Model for Cadmium Using Markov-Chain Monte Carlo Analysis of Concentrations in Blood, Urine, and Kidney Cortex from Living Kidney Donors
- 2014
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 141:2, s. 365-376
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Tidskriftsartikel (refereegranskat)abstract
- The health effects of low-level chronic exposure to cadmium are increasingly recognized. To improve the risk assessment, it is essential to know the relation between cadmium intake, body burden, and biomarker levels of cadmium. We combined a physiologically-based toxicokinetic (PBTK) model for cadmium with a data set from healthy kidney donors to re-estimate the model parameters and to test the effects of gender and serum ferritin on systemic uptake. Cadmium levels in whole blood, blood plasma, kidney cortex, and urinary excretion from 82 men and women were used to calculate posterior distributions for model parameters using Markov-chain Monte Carlo analysis. For never-and ever-smokers combined, the daily systemic uptake was estimated at 0.0063 mu g cadmium/kg body weight in men, with 35% increased uptake in women and a daily uptake of 1.2 mu g for each pack-year per calendar year of smoking. The rate of urinary excretion from cadmium accumulated in the kidney was estimated at 0.000042 day(-1), corresponding to a half-life of 45 years in the kidneys. We have provided an improved model of cadmium kinetics. As the new parameter estimates derive from a single study with measurements in several compartments in each individual, these new estimates are likely to be more accurate than the previous ones where the data used originated from unrelated data sets. The estimated urinary excretion of cadmium accumulated in the kidneys was much lower than previous estimates, neglecting this finding may result in a marked under-prediction of the true kidney burden.
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| 10. |
- Gram, Magnus, et al.
(författare)
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Increased levels of cell-free hemoglobin, oxidation markers, and the antioxidative heme scavenger alpha(1)-microglobulin in preeclampsia.
- 2010
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Ingår i: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849. ; 48, s. 284-291
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia is a major cause of morbidity and mortality during pregnancy. To date, the pathogenesis of the disease is not fully understood. Recent studies show that preeclampsia is associated with overexpression of the hemoglobin genes alpha2 and gamma and accumulation of the protein in the vascular lumen of the placenta. Hypothesizing that cell-free hemoglobin leaks from the placenta into the maternal circulation and contributes to the endothelial damage and symptoms by inducing oxidative stress, we analyzed fetal and adult hemoglobin (HbF, HbA), haptoglobin, oxidation markers, and the heme scavenger and antioxidant alpha(1)-microglobulin in plasma, urine, and placenta in preeclamptic women (n=28) and women with normal pregnancy (n=27). The mean plasma concentrations of HbF, HbA, protein carbonyl groups, membrane peroxidation capacity, and alpha(1)-microglobulin were significantly increased in preeclamptic women. The levels of total plasma Hb correlated strongly with the systolic blood pressure. The plasma haptoglobin concentrations of women with preeclampsia were significantly depressed. Increased amounts of alpha(1)-microglobulin mRNA and protein were found in placenta from preeclamptic women, and the levels of plasma and placenta alpha(1)-microglobulin correlated with the plasma Hb concentrations. The heme-degrading form t-alpha(1)-microglobulin was significantly increased in urine in preeclampsia. These results support the idea that hemoglobin-induced oxidative stress is a pathogenic factor in preeclampsia.
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| 11. |
- Gram, Magnus, et al.
(författare)
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Up-Regulation of A1M/α(1)-Microglobulin in Skin by Heme and Reactive Oxygen Species Gives Protection from Oxidative Damage.
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- During bleeding the skin is subjected to oxidative insults from free heme and radicals, generated from extracellular hemoglobin. The lipocalin α(1)-microglobulin (A1M) was recently shown to have reductase properties, reducing heme-proteins and other substrates, and to scavenge heme and radicals. We investigated the expression and localization of A1M in skin and the possible role of A1M in the protection of skin tissue from damage induced by heme and reactive oxygen species. Skin explants, keratinocyte cultures and purified collagen I were exposed to heme, reactive oxygen species, and/or A1M and investigated by biochemical methods and electron microscopy. The results demonstrate that A1M is localized ubiquitously in the dermal and epidermal layers, and that the A1M-gene is expressed in keratinocytes and up-regulated after exposure to heme and reactive oxygen species. A1M inhibited the heme- and reactive oxygen species-induced ultrastructural damage, up-regulation of antioxidation and cell cycle regulatory genes, and protein carbonyl formation in skin and keratinocytes. Finally, A1M bound to purified collagen I (K(d) = 0.96×10(-6) M) and could inhibit and repair the destruction of collagen fibrils by heme and reactive oxygen species. The results suggest that A1M may have a physiological role in protection of skin cells and matrix against oxidative damage following bleeding.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Hellman, Per, et al.
(författare)
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Positron emission tomography with 11C-methionine in hyperparathyroidism
- 1994
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Ingår i: Surgery. - 0039-6060 .- 1532-7361. ; 116:6, s. 974-981
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Positron emission tomography (PET) has not been evaluated for preoperative localization and functional characterization of the parathyroid tissue in hyperparathyroidism. METHODS: Images of the neck and upper mediastinum of 23 patients with hyperparathyroidism were obtained by PET after intravenous administration of 400 to 800 MBq L-[methyl-11C]-methionine. The investigation was repeated in six patients after Na2-ethylenediamine tetraacetic acid infusion, whereby stable 65% to 157% rise in intact serum parathyroid hormone values was attained. RESULTS: Parathyroid surgical procedure revealed single (21 patients) or two enlarged parathyroid glands (two patients) that were characterized as chief cell adenoma (n = 13), hyperplasia (n = 10), or carcinoma (n = 2) and weighed 80 to 6000 mg. Twenty (80%) of these glands were localized by PET. The remaining examinations (20%) were false negative and mainly encompassed small parathyroids in juxtathyroid position. Among 15 patients undergoing parathyroid reoperation true-positive localizations were obtained for 87% of the glands. The images displayed lower tracer uptake in residual thyroid lobes (n = 40), esophagus, and cervical vertebrae. Na2-ethylenediamine tetraacetic acid infusion failed to enhance parathyroid uptake values. Ultrasonography, computed tomography, technetium-thallium scintigraphy, and venous sampling revealed 25% to 53% of the pathologic parathyroid tissues of the patients undergoing reoperation and was largely complementary to PET. CONCLUSIONS: The results suggest that PET may provide novel possibilities for the imaging of pathologic parathyroid glands in hyperparathyroidism.
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| 17. |
- Lindstedt, B A, et al.
(författare)
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Use of multilocus variable-number tandem repeat analysis (MLVA) in eight European countries, 2012
- 2013
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Ingår i: Eurosurveillance. - : European Centre for Disease Prevention and Control. - 1025-496X .- 1560-7917. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- Genotyping of important medical or veterinary prokaryotes has become a very important tool during the last decades. Rapid development of fragment-separation and sequencing technologies has made many new genotyping strategies possible. Among these new methods is multilocus variable-number tandem repeat analysis (MLVA). Here we present an update on the use of MLVA in eight European countries (Denmark, France, Germany, Ireland, Italy, the Netherlands, Norway and Sweden). Researchers in Europe have been active in developing and implementing a large array of different assays. MLVA has been used as a typing tool in several contexts, from aiding in resolving outbreaks of foodborne bacteria to typing organisms that may pose a bioterrorist threat, as well as in scientific studies.
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| 18. |
- Ljunghall, S., et al.
(författare)
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Disturbance of basal and stimulated serum levels of intact parathyroid hormone in primary hyperparathyroidism
- 1991
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Ingår i: Surgery. - 0039-6060 .- 1532-7361. ; 110:1, s. 47-53
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Tidskriftsartikel (refereegranskat)abstract
- In patients with primary hyperparathyroidism, measurements were made of basal and stimulated levels of intact parathyroid hormone (PTH). The basal PTH values were elevated in all but six of 89 patients and provided clear separation towards normal individuals (n = 75) and patients with hypercalcemia of other origin (n = 34). The PTH value correlated with the serum calcium concentration in hyperparathyroidism and with the weight of excised parathyroid adenomas but not with that of chief cell hyperplasias. A constant ethylenediaminetetraacetic acid infusion during 60 minutes of induced essentially linear reductions of plasma-ionized calcium concentrations, averaging 0.02 mmol/L/10 minutes, which were associated with swift, curvilinear, elevations of PTH levels that reached a plateau after 10 to 20 minutes. The increment in serum PTH level correlated with the basal PTH value both in patients with hyperparathyroidism and controls. However, in proportion to the much greater glandular mass in the patients with hyperparathyroidism, the secretion of PTH was relatively reduced. The findings support the value of the intact PTH assay in the differential diagnosis of hypercalcemia and show that PTH secretion in vivo is extremely sensitive to hypocalcemic stimulation, that the pathological parathyroid tissue in hyperparathyroidism is characterized by a reduction of hormone release per unit weight, and that the hormone secretion in hyperparathyroidism operates closer to its maximal capacity than under normal circumstances.
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| 19. |
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| 20. |
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| 21. |
- Oldenburg, Mats, et al.
(författare)
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Modelling of microstructure and material response in the press hardening process
- 2008
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Ingår i: Conference Best in Class Stamping, June 16 - 18, 2008, Olofström, Sweden. - Olofström : Industriellt utvecklingscentrum i Olofström AB. - 9789163329487 ; , s. 463-474
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Konferensbidrag (refereegranskat)abstract
- The use of ultra-high strength components in automotive structures is rapidly increasing due to strong driving forces to reduce weight in order to minimise fuel consumption. This should also be accomplished with maintained or increased passenger safety. Components manufactured with the press hardening process meet most of the requirements and the market for such products is currently growing very fast. The quenching results in a material with a very high yield and tensile strength falling into the category of martensitic ultra high strength steels. Simulation of the complete press hardening process requires coupled thermo-mechanical transient analysis with the possibility to account for mechanical end thermal contact conditions between the tool and the blank. In addition, one sided or two sided contact areas may occur. Thus, large temperature variations through the thickness of the blank may be present during the process. In an earlier work, Bergman and Oldenburg formulated a thermal shell element with quadratic temperature interpolation through the thickness of the shell while there is a linear interpolation in the plane of the element. This formulation is implemented in the LS-Dyna code and is used in coupled thermomechanical analysis of hot forming processes. The modelling of the press hardening process has been developed in several steps. The model development involves e.g. determination of the flow stress, austenite decomposition modelling, constitutive modelling, experimental studies and evaluation of simulation results. The presented model accounts for the most significant phenomena occurring in the thermo-mechanical press hardening process. The mechanical response and the micro-structure evolution as well as the final material state can be predicted with good accuracy.
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| 22. |
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| 23. |
- Åkerström, JH, et al.
(författare)
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Reply
- 2024
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Ingår i: Gastroenterology. - 1528-0012. ; 166:5, s. 945-946
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 24. |
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