| 1. |
- Barrett, Jennifer H., et al.
(författare)
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Genome-wide association study identifies three new melanoma susceptibility loci
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1108-1113
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Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 x 10(-9)), an SNP in MX2 (rs45430, P = 2.9 x 10-9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 x 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 x 10(-7) under a fixed-effects model and P = 1.2 x 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
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| 2. |
- Berens, Friedbert, et al.
(författare)
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Modulation and Coding
- 2000
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Ingår i: Third Generation Mobile Communication Systems (Ramjee Prasad, Werner Mohr and Walter Konhäuser editors), chapter 5. - 1580530826
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Calafat, J, et al.
(författare)
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The bactericidal/permeability-increasing protein (BPI) is membrane-associated in azurophil granules of human neutrophils, and relocation occurs upon cellular activation
- 2000
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - 1600-0463. ; 108:3, s. 201-208
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophilic granulocytes contain the 55 kDa bactericidal/permeability-increasing protein (BPI). BPI binds to lipopolysaccharides (LPS), and exerts bacteriostatic and bactericidal effects against a wide variety of Gram-negative bacterial species. We have investigated the subcellular location of BPI in immature and mature neutrophils using cryotechnique for immunoelectron microscopy. BPI was found to colocate with myeloperoxidase (MPO), a marker for azurophil granules, and it also showed the same pattern of distribution as CD63, a transmembrane-anchored protein. This suggests that BPI is membrane-associated in the azurophil granules in neutrophils. Its presence in azurophil granules was further confirmed by the finding of BPI in the azurophil granules of neutrophil promyelocytes of the bone marrow. Induction of selective release of azurophilic granules by the Na-ionophore monensin resulted in fusion of endosomes with azurophil granules, leading to the formation of large vacuoles containing MPO, CD63, and BPI. After phagocytosis of serum-treated zymosan (STZ), BPI was detected in phagosomes, both in association with membranes as well as in the lumen, suggesting the release of BPI into activated compartments. The results show that BPI is present in azurophil granules, is probably primarily membrane-associated, and is relocated after activation, following the same route as MPO and CD63.
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| 4. |
- Calafat, J, et al.
(författare)
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The bactericidal/permeability-increasing protein (BPI) is present in specific granules of human eosinophils
- 1998
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Ingår i: Blood. - 1528-0020. ; 91:12, s. 4770-4775
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils participate in the inflammatory response seen in allergy and parasitic infestation, but a role in host defense against bacterial infection is not settled. The bactericidal/permeability-increasing protein (BPI) has been demonstrated in neutrophils and it exerts bacteriostatic and bactericidal effects against a wide variety of Gram-negative bacterial species. Using the Western blot technique, a 55-kD band, corresponding to BPI, was detected in lysates from both neutrophils and eosinophils. The localization of BPI in immature and mature eosinophils was investigated using immunoelectron microscopy. BPI was found in immature and mature specific granules of eosinophils and was detected in phagosomes as well, indicating release of the protein from the granules into the phagosomes. Using a specific enzyme-linked immunosorbent assay, eosinophils were shown to contain 179 ng of BPI/5 x 10(6) eosinophils compared with 710 ng BPI/5 x 10(6) neutrophils. The presence of BPI in eosinophils suggests a role for these cells in host defense against Gram-negative bacterial invasion or may suggest a role for BPI against parasitic infestation.
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| 5. |
- Calafat, J, et al.
(författare)
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Ultrastructural localization of Charcot-Leyden crystal protein in human eosinophils and basophils
- 1997
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Ingår i: European Journal of Haematology. - 1600-0609. ; 58:1, s. 56-66
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Tidskriftsartikel (refereegranskat)abstract
- The Charcot-Leyden crystal (CLC) protein with lysophospholipase activity and carbohydrate-binding properties is a characteristic constituent of eosinophils and basophils. We investigated its subcellular distribution using immunoelectron microscopy. Eosinophil progenitors, mature eosinophils and basophils all contained CLC protein in their cytosol and in the euchromatin of the nucleus. A minor population of granules in eosinophils, increasing in number with maturation, and a more abundant granule-population in basophils, were found to contain CLC protein. Double-labeling experiments showed, in eosinophils, that CLC protein-containing granules contain also eosinophil peroxidase, a characteristic specific granule protein. This suggests a relationship between the CLC protein-containing organelle and the specific granule. In basophils both the CLC protein positive and the negative granules showed the same characteristic particulate-like structure of the granular matrix and both share the same membrane marker CD63. In nasal polyps, macrophages were observed phagocytosing necrotic eosinophils. In these macrophages CLC protein-containing vesicles were observed, probably representing late endosomes. The dual (cytosolic/nuclear and granular) localization of CLC protein suggests that this protein enters both a secretory and a nonsecretory pathway during its biosynthesis, indicating functional roles for this protein both within the cell and extracellularly.
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| 6. |
- Egesten, Arne, et al.
(författare)
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Eosinophil granulocyte interaction with serum-opsonized particles: binding and degranulation are enhanced by tumor necrosis factor alpha
- 1998
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 115:2, s. 121-128
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils participate in the inflammatory response seen in allergy and helminthic infestation. Their release of granule-bound cationic proteins may play a role in these diseases. Therefore, we investigated mechanisms involved in the release of eosinophil cationic protein (ECP). Serum-opsonized zymosan was phagocytosed by eosinophils, and ECP was released into the phagosomes as judged by immunoelectron microscopy. Degranulation to the external milieu was induced by serum-opsonized, non-phagocytosable Sephadex beads (SOS), and ECP release was determined by use of an enzyme-linked immunosorbent assay. CD11b, CD18, and CD32 monoclonal antibodies inhibited degranulation, demonstrating dependence on complement receptor type 3 (CR3), and the low-affinity Fc receptor for IgG. Tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-5 both rapidly enhanced the binding of eosinophils to serum-opsonized zymosan, and also the release of ECP upon interaction with SOS. The cytokine-induced increase in ECP release was inhibited by the phospholipase A2 (PLA2) inhibitor mepacrine, indicating an involvement of PLA2 in the enhanced response but not in baseline degranulation. Autocrine stimulation by the platelet-activating factor (PAF) is unlikely since the PAF receptor antagonist WEB 2086 did not inhibit the enhanced response. In conclusion, the main signals for eosinophil degranulation on serum-opsonized particles are mediated by CR3 and receptors for immunoglobulins. As for IL-5, TNF-alpha changes eosinophil phenotype from a resting to an activated state.
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| 7. |
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| 8. |
- Egesten, Arne, et al.
(författare)
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Localization of granule proteins in human eosinophil bone marrow progenitors
- 1997
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Ingår i: International Archives of Allergy and Immunology. - 1423-0097. ; 114:2, s. 8-130
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils have a characteristic content of cationic proteins, stored in core-containing specific granules and released at sites of inflammation; coreless granules (sometimes called primary) are present in eosinophil promyelocytes. In order to determine a possible relationship between the two granule subsets, immunoelectron-microscopic techniques were used to determine the presence and precise intragranular distribution of major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and arylsulfatase B of eosinophil granules, as well as the Charcot-Leyden crystal (CLC) protein, in eosinophil progenitors of the bone marrow. MBP, ECP, EPO, and arylsulfatase B were observed in both coreless and core-containing (specific) granules. The difference in the distribution of MBP, having a uniform distribution in coreless granules and a crystalloid distribution in core-containing (specific) granules, could indicate a maturational process of a common organelle. CLC protein was distributed in the cytosol, in the euchromatin of the nuclei, but was also present in a rare granular compartment of both immature and mature eosinophils. The present findings suggest that coreless granules develop into core-containing specific granules.
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| 9. |
- Egesten, Arne, et al.
(författare)
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Subcellular localization of transforming growth factor-alpha in human eosinophil granulocytes
- 1996
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Ingår i: Blood. - 1528-0020. ; 87:9, s. 8-3910
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils are involved in the inflammatory response seen in allergy and helminthic infestations. Eosinophils synthesize transforming growth factor-alpha (TGF-alpha), which may play a role in the development of the characteristic fibrosis seen in longstanding high eosinophilia. Using immunoelectron microscopic techniques, eosinophils from peripheral blood of healthy individuals and from one patient with high eosinophilia showed presence TGF-alpha in matrix of the specific crystalloid-containing granules. In cryosections, TGF-alpha was also visualized in a vesicular compartment of the cytoplasm. In double-labeling experiments, the TGF-alpha of this latter compartment did not colocalize with CD63, a marker for lysosomes, nor with albumin of secretory vesicles. In extracts from eosinophils, obtained from healthy donors, immunoreactive TGF-alpha could be detected by enzyme-linked immunosorbent assay-technique. In addition, sera from two patients with high eosinophilia showed TGF-alpha concentrations of 1.5 ng/mL and 164 pg/mL, respectively, whereas TGF-alpha could not be detected in serum from healthy controls. In conclusion, TGF-alpha is present in the specific granules, and in an additional vesicular compartment of the cytoplasm of eosinophils.
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| 10. |
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| 11. |
- Gardai, Shyra J, et al.
(författare)
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Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte
- 2005
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 123:2, s. 321-334
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Tidskriftsartikel (refereegranskat)abstract
- Apoptotic-cell removal is critical for development, tissue homeostasis, and resolution of inflammation. Although many candidate systems exist, only phosphatidylserine has been identified as a general recognition ligand on apoptotic cells. We demonstrate here that calreticulin acts as a second general recognition ligand by binding and activating LDL-receptor-related protein (LRP) on the engulfing cell. Since surface calreticulin is also found on viable cells, a mechanism preventing inadvertent uptake was sought. Disruption of interactions between CD47 (integrin-associated protein) on the target cell and SIRPalpha (SHPS-1), a heavily glycosylated transmembrane protein on the engulfing cell, permitted uptake of viable cells in a calreticulin/LRP-dependent manner. On apoptotic cells, CD47 was altered and/or lost and no longer activated SIRPalpha. These changes on the apoptotic cell create an environment where "don't eat me" signals are rendered inactive and "eat me" signals, including calreticulin and phosphatidylserine, congregate together and signal for removal.
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| 12. |
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| 13. |
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| 14. |
- Uchmanowicz, Izabella, et al.
(författare)
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Optimising implementation of European guidelines on cardiovascular disease prevention in clinical practice : what is needed?
- 2021
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Ingår i: European Journal of Preventive Cardiology. - : Oxford Academic. - 2047-4873 .- 2047-4881. ; 28:4, s. 426-431
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular disease is a model example of a preventable condition for which practice guidelines are particularly important. In 2016, the joint task force created by the European Society of Cardiology (ESC) together with 10 other societies released the new version of the European guidelines on cardiovascular disease prevention. To facilitate the implementation of the ESC guidelines, a dedicated prevention implementation committee has been established within the European Association of Preventive Cardiology. The paper will first explore potential barriers to the guidelines' implementation. It then develops a discussion that seeks to inform the future development of the committee's work, including a new definition of the guidelines' stakeholders (health policy-makers, healthcare professionals and health educators, patient organisations, entrepreneurs and the general public), future activities within four specific areas: strengthening awareness of the guidelines among stakeholders; supporting organisational changes to facilitate the guidelines' implementation; motivating stakeholders to utilise the guidelines; and present ideas on new implementation strategies. Providing multifaceted cooperation between healthcare professionals, healthcare management executives and health policy-makers, the novel approach proposed in this paper should contribute to a wider use of the 2016 ESC guidelines and produce desired effects of less cardiovascular disease morbidity and mortality. Furthermore, the solutions presented within the paper may constitute a benchmark for the implementation of practice guidelines in other medical disciplines.
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