1. |
- Gretarsdottir, Solveig, et al.
(author)
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Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:8, s. 71-692
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Journal article (peer-reviewed)abstract
- We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.
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2. |
- Gustafson, Jenny, et al.
(author)
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Langerin-expressing and CD83-expressing cells in oral lichen planus lesions.
- 2007
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In: Acta odontologica Scandinavica. - : Informa UK Limited. - 0001-6357 .- 1502-3850. ; 65:3, s. 156-61
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Dendritic Langerhans cells (LCs) have been attributed a role in the pathogenesis of lichen planus as autoantigen-presenting cells initiating expansion of autoreactive T cells. Langerin and CD83, which are cell molecules expressed on LCs, are associated with antigen presentation. The present study examined expression of Langerin and CD83 molecules on LCs in patients with oral lichen planus (OLP). MATERIAL AND METHODS: Biopsies were obtained from seven patients with OLP. Oral mucosa from seven healthy subjects served as controls. Monoclonal antibodies (mAbs) were used in standard immunohistochemical procedures to visualize CD1a-, Langerin-, and CD83-molecule-expressing cells. RESULTS: CD1a+ and Langerin+ cells were found in significantly higher frequencies in OLP epithelium compared with healthy oral epithelium (p<0.01 and p<0.05, respectively); however, the frequency of CD83+ cells did not differ (p>0.05). The connective tissue in OLP lesions showed significantly higher frequencies of CD1a+, Langerin+, and CD83+ cells compared with healthy connective tissue (p<0.01, p<0.01, and p<0.05). CD1a+ and Langerin+ cells in OLP and healthy epithelium had a dendritic morphology. CONCLUSIONS: The study shows increased numbers of CD1a- and Langerin-expressing LCs in OLP compared with healthy controls. In the connective tissue, CD83+ cells with dendritic morphology were localized to regions of lymphocyte clusters. The presence of CD83+ dendritic cells in areas of lymphocyte clusters in the connective tissue of OLP lesions indicates the possibility of ongoing autoantigen presentation.
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3. |
- Jäwert, Fredrik, et al.
(author)
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Loss of 5-Hydroxymethylcytosine and TET2 in Oral Squamous Cell Carcinoma.
- 2013
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In: Anticancer research. - 1791-7530 .- 0250-7005. ; 33:10, s. 4325-8
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Journal article (peer-reviewed)abstract
- Aim: Epigenetic modifications, such as DNA methylation, are considered important in the regulation of target genes in cancer development. 5-Hydroxymethylcytosine (5hmC) was recently discovered to be related to the process of malignant transformation. The influence of DNA methylation in oral squamous cell carcinomas (OSCC) is not fully-understood. Therefore, the aim of the present study was to investigate the DNA methylation pattern in OSCC compared to healthy oral epithelium.
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4. |
- Larsson, Lena, 1969, et al.
(author)
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Expression of High Mobility Group A proteins in oral leukoplakia
- 2013
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 33:10, s. 4261-4266
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Journal article (peer-reviewed)abstract
- Background: Oral leukoplakia (LPL) is considered a potentially malignant disorder in the oral cavity and the gastric tract. The high mobility group A (HMGA) proteins are important in the transformation of normal cells into cancer cells, but there is a lack of knowledge about their importance in development of oral cancer. The aim of the current project was to investigate HMGA expression in LPLs with different levels of dysplasia. Materials and Methods: Biopsies were histologically processed to visualize the expression of HMGA1 and HMGA2 using immunohistochemistry. Results: An increase of HMGA1-positive cells correlating to the degree of dysplasia was registered in the epithelium and in the connective tissue. HMGA2 expression was seen in the epithelium and in the connective tissue but with no obvious correlation to the level of dysplasia. Conclusion: This is, to our knowledge, the first study showing the expression of HMGA proteins in healthy and non-healthy oral mucosa.
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5. |
- Magnusson, Peter S., et al.
(author)
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SimICS/sun4m : A virtual workstation
- 2019
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In: USENIX 1998 Annual Technical Conference. - New Orleans, LA, USA : USENIX Association.
-
Conference paper (peer-reviewed)abstract
- System level simulators allow computer architects and system software designers to recreate an accurate and complete replica of the program behavior of a target system, regardless of the availability, existence, or instrumentation support of such a system. Applications include evaluation of architectural design alternatives as well as software engineering tasks such as traditional debugging and performance tuning. We present an implementation of a simulator acting as a virtual workstation fully compatible with the sun4m architecture from Sun Microsystems. Built using the system-level SPARC V8 simulator SimICS, SimICS/sun4m models one or more SPARC V8 processors, supports user-developed modules for data cache and instruction cache simulation and execution profiling of all code, and provides a symbolic and performance debugging environment for operating systems. SimICS/sun4m can boot unmodified operating systems, including Linux 2.0.30 and Solaris 2.6, directly from snapshots of disk partitions. To support essentially arbitrary code, we implemented binary-compatible simulators for several devices, including SCSI, console, interrupt, timers, EEPROM, and Ethernet. The Ethernet simulation hooks into the host and allows the virtual workstation to appear on the local network with full services available (NFS, NIS, rsh, etc). Ethernet and console traffic can be recorded for future playback. The performance of SimICS/sun4m is sufficient to run realistic workloads, such as the database benchmark TPC-D, scaling factor 1/100, or an interactive network application such as Mozilla. The slowdown in relation to native hardware is in the range of 25 to 75 (measured using SPECint95). We also demonstrate some applications, including modeling an 8-processor sun4m version (which does not exist), modeling future memory hierarchies, and debugging an operating system.
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6. |
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7. |
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8. |
- Sundström, Johan, Professor, 1971-, et al.
(author)
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Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
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In: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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9. |
- Öhman, Jenny, et al.
(author)
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Langerhans Cells and T Cells Sense Cell Dysplasia in Oral Leukoplakias and Oral Squamous Cell Carcinomas - Evidence for Immunosurveillance
- 2012
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In: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475. ; 76:1, s. 39-48
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Journal article (peer-reviewed)abstract
- Leukoplakias (LPLs) are lesions in the oral mucosa that may develop into oral squamous cell carcinoma (OSCC). The objective of this study was to assess presence and distribution of dendritic Langerhans cells (LCs) and T cells in patients with LPLs with or without cell dysplasia and in oral squamous cell carcinoma (OSCC). Biopsy specimens from patients with leukoplakias (LPLs) with or without dysplasia and oral squamous cell carcinoma (OSCC) were immunostained with antibodies against CD1a, Langerin, CD3, CD4, CD8 and Ki67, followed by quantitative analysis. Analyses of epithelium and connective tissue revealed a significantly higher number of CD1a + LCs in LPLs with dysplasia compared with LPLs without dysplasia. Presence of Langerin + LCs in epithelium did not differ significantly between LPLs either with or without dysplasia and OSCC. T cells were found in significantly increased numbers in LPLs with dysplasia and OSCC. The number of CD4+ cells did not differ significantly between LPLs with and without dysplasia, but a significant increase was detected when comparing LPLs with dysplasia with OSCC. CD8+ cells were significantly more abundant in OSCC and LPLs with dysplasia compared with LPLs without dysplasia. Proliferating cells (Ki67+) were significantly more abundant in OSCC compared to LPLs with dysplasia. Confocal laser scanning microscopy revealed colocalization of LCs and T cells in LPLs with dysplasia and in OSCC. LCs and T cells are more numerous in tissue compartments with dysplastic epithelial cells and dramatically increase in OSCC. This indicates an ongoing immune response against cells with dysplasia.
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10. |
- Öhman, Jenny, et al.
(author)
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Presence of CD3-Positive T-Cells in Oral Premalignant Leukoplakia Indicates Prevention of Cancer Transformation
- 2015
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In: Anticancer Research. - 0250-7005. ; 35:1, s. 311-317
-
Journal article (peer-reviewed)abstract
- Aim: Leukoplakias (LPLs) are lesions in the oral mucosa that have a potential to transform into oral squamous cell carcinoma (OSCC). As the degree of immunosurveillance may be important for this transformation to occur, the aim of this study was to determine the presence of immune cells in LPLs with dysplasia in relation to later development of OSCC. Materials and Methods: Biopsies from 16 patients with clinical diagnosis of LPL and histopathological diagnosis of hyperkeratosis with dysplasia were immunostained with antibodies to detect CD3(+) T cells, CD1a(+) LCs, Ki-67(+) and p53-expressing cells. Patients were divided into two groups: LPL with dysplasia that transformed into OSCC (LPL-dys) and that which did not (LPL-ca). Results: Quantitative analyses showed significantly lower numbers of CD3+ T-cells in LPL-ca than in LPL-dys. No significant differences were detected when comparing LPL-dys and LPL-ca regarding CD1a(+), p53(+) and Ki-67(+) cells. Conclusion: The number of CD3-expressing T-cells may be important for preventing malignant transformation of LPL.
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12. |
- Abdulla, Aree, et al.
(author)
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Platelets regulate P-selectin expression and leukocyte rolling in inflamed venules of the pancreas
- 2012
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In: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 682:1-3, s. 153-160
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Journal article (peer-reviewed)abstract
- Recent data suggest that platelets regulate inflammatory changes and tissue damage in acute pancreatitis although the role of platelets in leukocyte-endothelium interactions in the pancreatic microcirculation is not known. The aim of this study was to define the impact of platelets on leukocyte rolling and adhesion in acute pancreatitis. Acute pancreatitis was induced in C57BL/6 mice by caerulein challenge. Mice were treated with an a anti-GP1b alpha (CD42b) antibody, which depletes platelets, or a control antibody before caerulein. Leukocyte rolling and adhesion were determined by the use of intravital fluorescence microscopy 18 h after the last dose of caerulein. In separate experiments, leukocyte-endothelium interactions were determined before and after administration of an anti-P-selectin, anti-PSGL-1 and a control antibody in mice with caerulein pancreatitis. Circulating platelet-neutrophil aggregates and pancreatic P-selectin mRNA were quantified 1 and 6 h respectively after caerulein challenge. Caerulein administration increased leukocyte and platelet interactions in the pancreatic microvasculature, increased tissue damage and expression of P-selectin mRNA in the pancreas as well as platelet-neutrophil complexes in the circulation. Notably, platelet depletion markedly reduced caerulein-provoked leukocyte rolling and adhesion in postcapillary venules. Interestingly, depletion of platelets significantly decreased caerulein-induced gene expression of P-selectin in the pancreas. Moreover, immunoneutralization of P-selectin and PSGL-1 abolished leukocyte rolling in the pancreatic venules triggered by caerulein. Our novel findings demonstrate that platelets regulate leukocyte rolling in acute pancreatitis via induction of P-selectin, which was critical in supporting leukocyte rolling in inflamed venules of the pancreas. (C) 2012 Elsevier B.V. All rights reserved.
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13. |
- Abdulla, Aree, et al.
(author)
-
Role of platelets in experimental acute pancreatitis.
- 2011
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In: British Journal of Surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 98, s. 93-103
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Journal article (peer-reviewed)abstract
- BACKGROUND:: Platelets not only control thrombosis and haemostasis but may also regulate inflammatory processes. Acute pancreatitis (AP) is characterized by changes in both coagulation and proinflammatory activities. The role of platelets in AP is not yet known. METHODS:: AP was induced in C57BL/6 mice by repeated caerulein administration (50 µg/kg intraperitoneally). Mice received a platelet-depleting or control antibody before caerulein challenge. Neutrophil infiltration, myeloperoxidase (MPO) and macrophage inflammatory protein (MIP) 2 levels, acinar cell necrosis and haemorrhage in the pancreas, as well as serum amylase activity, were determined 24 h after caerulein injection. In an alternative model of pancreatitis, L-arginine (4 g/kg intraperitoneally) was given twice with an interval of 1 h and tissue samples were taken after 72 h [Correction added after online publication 29 September 2010: in the preceding sentence, 4 mg/kg was corrected to 4 g/kg]. RESULTS:: Caerulein administration increased acinar cell necrosis, neutrophil infiltration, focal haemorrhage and serum amylase levels. Platelet depletion reduced acinar cell necrosis, haemorrhage and serum amylase levels in AP. Depletion of platelets decreased caerulein-induced MPO levels and neutrophil recruitment in the pancreas. Platelet depletion abolished caerulein-induced MIP-2 generation in the pancreas and circulation. The effects of platelet depletion on necrosis, neutrophils and MPO levels were confirmed in L-arginine-induced pancreatitis. CONCLUSION:: Platelets play a crucial role in AP by regulating neutrophil infiltration, most likely mediated by MIP-2 production in the pancreas. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
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14. |
- Akdeniz, BG, et al.
(author)
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Accuracy of proximal caries depth measurements: comparison between limited cone beam computed tomography, storage phosphor and film radiography
- 2006
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In: Caries Res. ; 40:3, s. 202-207
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Journal article (peer-reviewed)abstract
- The aim of this study was to compare the accuracy of limited cone beam computed tomography (LCBCT), an image plate system and F-speed film in assessing the depth of proximal carious lesions. Radiographs of a dry mandible with sound and carious teeth were obtained with all three methods. In 41 molar and premolar proximal surfaces, 2 observers independently measured lesion depth on the images from the three modalities. The correlation of measurements was assessed with Pearson's correlation analysis. Results from imaging modalities and histological sectioning (gold standard) were compared using Bland-Altman plots. Overall comparison of the depth measurements from the imaging modalities and the gold standard was done using repeated-measures ANOVA. Pairwise comparisons of systems were done by the Bonferroni t test. The correlation between the measurements of the two observers was 0.977 for film, 0.997 for image plate system and 0.998 for LCBCT. Bland-Altman plots revealed that LCBCT agreed very closely with the gold standard while the agreement between the latter and the image plate--or film--images was moderate. The mean difference and 95% limits of agreement between LCBCT and the gold standard were smaller than those between either image plate or F-speed film and the gold standard. The LCBCT method appears as a promising tool for detection and monitoring of proximal carious lesions.
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15. |
- Arshadi, Mehrdad, et al.
(author)
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Gas chromatography-mass spectrometry determination of the pentafluorobenzoyl derivative of methylhydrazine in false morel (Gyromitra esculenta) as a monitor for the content of the toxin gyromitrin
- 2006
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In: Journal of Chromatography A. - Amsterdam : Elsevier. - 0021-9673 .- 1873-3778. ; 1125:2, s. 229-233
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Journal article (peer-reviewed)abstract
- The main toxic compound found in false morel (Gyromitra esculenta) is acetaldehyde-N-methyl-N-formylhydrazone (gyromitrin). This paper describes a method of determining the total hydrazones content based on acid hydrolysis of gyromitrin and other related hydrazones in air-dried false morel followed by derivatisation of methylhydrazine with pentafluorobenzoyl chloride. The derivative, tris-pentafluorobenzoyl methylhydrazine (tris-PFB-MH) is analyzed by gas chromatography–mass spectrometry. The overall precision of the method is better than 10% (relative standard deviation) for 0.5 ng/μl methylhydrazine in solution. The minimum detectable concentration of methylhydrazine (tris-PFB-MH) by this method is estimated to be approximately 12 pg/μl, which is equal to 0.3 μg/g dry matter (DM) of false morel.
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18. |
- Bergh, Anders, et al.
(author)
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Didecyl squarate — A practical amino-reactive cross-linking reagent for neoglycoconjugate synthesis
- 2001
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In: Glycoconjugate Journal. - 1573-4986. ; 18:8, s. 615-621
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Journal article (peer-reviewed)abstract
- The present paper describes the synthesis and use of the hydrophobic squaric decyl ester glycosides in neoglycoconjugate chemistry. The 2-aminoethyl glycosides of agr-D-mannopyranose, lactose, globotriose, globotetraose, GM3, and sialyl Lewisx, as well as the 2-(2-aminoethylthio)ethyl glycoside of agr-D-mannopyranose, beta-D-glucopyranose, and galabiose were reacted with squaric acid didecyl ester to afford the hydrophobic squaric decyl ester glycosides. These glycosides were efficient reagents for the conjugation to amino-functional microtiter plates, BSA and aminated Sepharose EAH 4B. The decyl ester moiety of the squaric decyl ester glycosides constitutes a traceless hydrophobic tag, which has the major advantage, as compared to the corresponding ethyl esters, that it enables easy purification of the glycosides with silica chromatography and that unreacted excesses glycosides from conjugation reaction mixtures can easily be recovered by means of C18 solid phase extraction.
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19. |
- Bhattacharyya, Sumita, et al.
(author)
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The p-methoxybenzyl ether as an in situ-removable carbohydrate-protecting group : A simple one-pot synthesis of the globotetraose tetrasaccharide
- 2001
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In: Journal of the Chemical Society - Perkin Transactions 1. - : Royal Society of Chemistry (RSC). - 1472-7781 .- 1364-5463. ; :8, s. 886-890
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Journal article (peer-reviewed)abstract
- A one-pot synthesis of the globotetraose tetrasaccharide is reported. The synthetic method relies on the use of a p-methoxybenzyl ether as an in situ-removable protecting group. N-Iodosuccinimide/trifluoromethanesulfonic acid-promoted glycosylation of 2-bromoethyl-2,3,6-tri-O-benzoyl-4-O-(2,3,6-tri-O-benzoyl-β-D-galactopyranosyl)-β-D-glucopyranoside 5 at −45 °C with phenyl 2,4,6-tri-O-benzyl-3-O-(4-methoxybenzyl)-1-thio-β-D-galactopyranoside 6 gives an intermediate trisaccharide from which the p-methoxybenzyl ether is removed by allowing the reaction temperature to rise to 0 °C for 40 min. Again lowering the temperature to −45 °C, followed by addition of methyl 3,4,6-tri-O-acetyl-2-trichloroethoxycarbonylamino-2-deoxy-1-thio-β-D-galactopyranoside 8, affords the globotetraose tetrasaccharide 11 in one-pot in an excellent yield of 76%.
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20. |
- Biglarnia, Ali-Reza, et al.
(author)
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Prompt reversal of a severe complement activation by eculizumab in a patient undergoing intentional ABO-incompatible pancreas and kidney transplantation
- 2011
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In: Transplant International. - : John Wiley & Sons. - 0934-0874 .- 1432-2277. ; 24:8, s. e61-e66
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Journal article (peer-reviewed)abstract
- We describe the presumably first intentional ABO-incompatible deceased-donor kidney and pancreas transplantation with a severe antibody-mediated rejection during a rebound of isoagglutinins. Rejection was successfully treated with eculizumab, which inhibits the terminal pathway of complement. Complement analysis (C3, C3d,g, and a modified assay of classical complement-related hemolytic function) documented complement activation and confirmed that eculizumab completely blocked complement function. At 6 months, the patient had normal kidney and pancreas function, and histological evaluations revealed no evidence of sustained graft damage. This successful transplantation suggests that ABO barriers can safely be overcome without extensive preconditioning, when the complement inhibitor eculizumab is included.
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21. |
- Biglarnia, Ali-Reza, et al.
(author)
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Prompt reversal of a severe complement activation by eculizumab in a patient undergoing intentional ABO-incompatible pancreas and kidney transplantation
- 2011
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In: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 24:8, s. e61-e66
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Journal article (peer-reviewed)abstract
- We describe the presumably first intentional ABO-incompatible deceased-donor kidney and pancreas transplantation with a severe antibody-mediated rejection during a rebound of isoagglutinins. Rejection was successfully treated with eculizumab, which inhibits the terminal pathway of complement. Complement analysis (C3, C3d,g, and a modified assay of classical complement-related hemolytic function) documented complement activation and confirmed that eculizumab completely blocked complement function. At 6 months, the patient had normal kidney and pancreas function, and histological evaluations revealed no evidence of sustained graft damage. This successful transplantation suggests that ABO barriers can safely be overcome without extensive preconditioning, when the complement inhibitor eculizumab is included.
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23. |
- Brown, C., et al.
(author)
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On the physics of the infant feeding bottle and middle ear sequela : Ear disease in infants can be associated with bottle feeding
- 2000
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In: International Journal of Pediatric Otorhinolaryngology. - 0165-5876 .- 1872-8464. ; 54:1, s. 13-20
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Journal article (peer-reviewed)abstract
- Background: When using conventional feeding bottles, negative pressure is generated in the oral cavity, as well as, in the bottle when fluid is removed by sucking. The negative pressure inside the bottle causes the infant to suck excessively and the intraoral negative pressure may subsequently be transmitted to the middle ear via the eustachian tube. Methods: In seven infants, simultaneous pressure recordings were performed in the feeding vessel and the middle ear using three types of feeding bottles. Results: With conventional non-ventilated and under-ventilated bottles a negative pressure formed while the infant sucked and negative intratympanic pressure was frequently generated. Conclusions: It is suggested that this sequence of events may lead to secretory otitis and it's accompanying consequences. In contrast, a fully ventilated bottle showed positive pressure throughout the feeding procedure, which is similar to normal breast-feeding, and negative pressure changes were not recorded in the middle ear.
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