| 1. |
- Aggarwal, M. M., et al.
(author)
-
Pion freeze-out time in Pb plus Pb collisions at 158 AGeV/c studied via pi(-)/pi(+) and K-/K+ ratios
- 2006
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 48:2, s. 343-352
-
Journal article (peer-reviewed)abstract
- The effect of the final state Coulomb interaction on particles produced in Pb + Pb collisions at 158AGeV/c has been investigated in the WA98 experiment through the study of the pi(-)/pi(+) and K-/K+ ratios measured as a function of T-m- (m)0. While the ratio for kaons shows no significant T-m dependence, the pi(-)/pi(+) ratio is enhanced at small T-m - (m)0 values with an enhancement that increases with centrality. A silicon pad detector located near the target is used to estimate the contribution of hyperon decays to the pi(-)/pi(+) ratio. The comparison of results with predictions of the RQMD model in which the Coulomb interaction has been incorporated allows to place constraints on the time of the pion freeze-out.
|
|
| 2. |
- Aggarwal, M. M., et al.
(author)
-
Suppression of high-p(T) neutral pion production in central Pb+Pb collisions at root s(NN)=17.3 GeV relative to p+C and p+Pb collisions
- 2008
-
In: Physical Review Letters. - 1079-7114. ; 100:24
-
Journal article (peer-reviewed)abstract
- Neutral pion transverse momentum spectra were measured in p+C and p+Pb collisions at root s(NN) = 17.4 GeV at midrapidity (2.3 less than or similar to eta(lab)less than or similar to 3.0) over the range 0.7 less than or similar to p(T)less than or similar to 3.5 GeV/c. The spectra are compared to pi(0) spectra measured in Pb+Pb collisions at root s(NN) = 17.3 GeV in the same experiment. For a wide range of Pb+Pb centralities (N-part less than or similar to 300), the yield of pi(0)'s with p(T)greater than or similar to 2 GeV/c is larger than or consistent with the p+C or p+Pb yields scaled with the number of nucleon-nucleon collisions (N-coll), while for central Pb+Pb collisions with N-part greater than or similar to 350, the pi(0) yield is suppressed.
|
|
| 3. |
- Godambe, S. V., et al.
(author)
-
Very high energy γ-ray and near infrared observations of 1ES2344+514 during 2004 05
- 2007
-
In: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 34, s. 1683-1695
-
Journal article (peer-reviewed)abstract
- We have observed the BL Lac object 1ES2344+514 (z = 0.044) in very high energy (VHE) gamma-ray and near-infrared wavelength bands with TACTIC and MIRO telescopes, respectively. The observations were made from 18th October to 9th December 2004 and 27th October 2005 to 1st January 2006. Detailed analysis of the TACTIC data indicates the absence of a statistically significant gamma-ray signal both in overall data and on a nightly basis from the source direction. We estimate an upper limit of I(≥1.5 TeV) ≤ 3.84 × 10−12 photons cm−2 s−1 at a 3σ confidence level on the integrated γ-ray flux. In addition, we have also compared TACTIC TeV light curves with those of the RXTE ASM (2–12 keV) for the contemporary period and find that there are no statistically significant increases in the signal strengths from the source in both these energy regions. During 2004 IR observations, 1ES2344+514 shows low level (0.06 magnitude) day-to-day variation in both, J and H bands. However, during the 2005 observation epoch, the source brightens up by about 0.41 magnitude from its October 2005 level J magnitude = 12.64 to J = 12.23 on December 6, 2005. It then fades by about 0.2 magnitude during 6 to 10 December, 2005. The variation is seen in both, J and H, bands simultaneously. The light travel time arguments suggest that the emission region size is of the order of 1017 cm.
|
|
| 4. |
- Adolph, C, et al.
(author)
-
Measurement of the eta -> 3 pi(0) Dalitz plot distribution with the WASA detector at COSY
- 2009
-
In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 677:1-2, s. 24-29
-
Journal article (peer-reviewed)abstract
- In the first production run of the WASA experiment at COSY, the eta decay into three neutral pions was measured in proton-proton interactions at a proton beam kinetic energy of 1.4 GeV. The Dalitz plot of the three pious was Studied using 1.2 x 10(5) fully reconstructed events. and the quadratic slope parameter alpha was determined to be -0.027 +/- 0.008(stat) +/- 0.005(syst). The result is consistent with previous measurements and further corroborates the importance of pion-pion final state interactions. (C) 2009 Elsevier B.V. All rights reserved.
|
|
| 5. |
- Godambe, S. V., et al.
(author)
-
Very High Energy Gamma-ray and Near Infrared observations of 1ES2344+514 with TACTIC and MIRO Telescopes
- 2005
-
In: 29th International Cosmic Ray Conference Pune (2005).
-
Conference paper (peer-reviewed)abstract
- 1ES2344+514 (z = 0.04) is one of the rst BL Lac objects to be reported as an extreme synchrotron blazar withsynchotron peak energy reaching up to 100keV and was discovered as a source of Very High Energy (VHE)gamma- rays by the Whipple group in 1995. Subsequently, it was observed by the HEGRA group in 1997/98and 2002. We have recently (Oct.- Dec. 2004) observed the 1ES2344+514 using the imaging element of theTACTIC array and have collected data for 53 hours in on/off mode. The source was also observed in nearinfrared bands J, H and K, for some nights using NICMOS-3 array mounted on 1.2m MIRO infrared telescope.Such a study is expected to provide clues to the dominance or otherwise of the Compton component. Afterdetailed analysis of the TACTIC data we have placed an upper limit of photons cmsata 3condence level on the gamma-ray ux from the source. In the near infrared band the source shows lowlevel variations without any aring activity.
|
|
| 6. |
- Aggarwal, MM, et al.
(author)
-
Centrality and transverse momentum dependence of collective flow in 158 A GeV Pb+Pb collisions measured via inclusive photons
- 2005
-
In: Nuclear Physics, Section A. - : Elsevier BV. - 0375-9474. ; 762:1-2, s. 129-146
-
Journal article (peer-reviewed)abstract
- Directed and elliptic flow of inclusive photons near mid-rapidity in 158 A GeV Pb + Pb collisions has been studied. The data have been obtained with the photon spectrometer LEDA of the WA98 experiment at the CERN SPS. The flow strength has been measured for various centralities as a function of p(T) and rapidity over 0. 18 < p(T) < 1.5 GeV/c and 2.3 < y < 2.9. The angular anisotropy has been studied relative to an event plane obtained in the target fragmentation region that shows the elliptic flow to be in-plane. The elliptic flow has also been studied using two-particle correlations and shown to give similar results. A small directed flow component is observed. Both the directed and elliptic flow strengths increase with p(T). The photon flow results are used to estimate the corresponding neutral pion flow.
|
|
| 7. |
- Aggarwal, M M, et al.
(author)
-
Azimuthal anisotropy of photon and charged particle emission in Pb-208+Pb-208 collisions at 158 center dot A GeV/c
- 2005
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 41:3, s. 287-296
-
Journal article (peer-reviewed)abstract
- The azimuthal distributions of photons and charged particles with respect to the event plane are investigated as a function of centrality in Pb-208 + Pb-208 collisions at 158 (.) A GeV/c in the WA98 experiment at the CERN SPS. The anisotropy of the azimuthal distributions is characterized using a Fourier analysis. For both the photon and charged particle distributions the first two Fourier coefficients are observed to decrease with increasing centrality. The observed anisotropies of the photon distributions compare well with the expectations from the charged particle measurements for all centralities.
|
|
| 8. |
|
|
| 9. |
- Mustjoki, S., et al.
(author)
-
Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy
- 2009
-
In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 23:8, s. 1398-1405
-
Journal article (peer-reviewed)abstract
- Dasatinib, a broad-spectrum tyrosine kinase inhibitor (TKI), predominantly targets BCR-ABL and SRC oncoproteins and also inhibits off-target kinases, which may result in unexpected drug responses. We identified 22 patients with marked lymphoproliferation in blood while on dasatinib therapy. Clonality and immunophenotype were analyzed and related clinical information was collected. An abrupt lymphocytosis (peak count range 4-20 x 10(9)/l) with large granular lymphocyte (LGL) morphology was observed after a median of 3 months from the start of therapy and it persisted throughout the therapy. Fifteen patients had a cytotoxic T-cell and seven patients had an NK-cell phenotype. All T-cell expansions were clonal. Adverse effects, such as colitis and pleuritis, were common (18 of 22 patients) and were preceded by LGL lymphocytosis. Accumulation of identical cytotoxic T cells was also detected in pleural effusion and colon biopsy samples. Responses to dasatinib were good and included complete, unexpectedly long-lasting remissions in patients with advanced leukemia. In a phase II clinical study on 46 Philadelphia chromosome-positive acute lymphoblastic leukemia, patients with lymphocytosis had superior survival compared with patients without lymphocytosis. By inhibiting immunoregulatory kinases, dasatinib may induce a reversible state of aberrant immune reactivity associated with good clinical responses and a distinct adverse effect profile. Leukemia (2009) 23, 1398-1405; doi:10.1038/leu.2009.46; published online 19 March 2009
|
|
| 10. |
- Nilsson, Jan, et al.
(author)
-
Immunomodulation of Atherosclerosis. Implications for Vaccine Development.
- 2005
-
In: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 25:1, s. 18-28
-
Research review (peer-reviewed)abstract
- A number of studies have shown activation of the immune system throughout various stages of atherosclerosis. Recent observations have suggested that activation of immune responses may promote atherosclerosis on one hand by inducing and perpetuating arterial inflammation, whereas on the other hand, selective activation of certain immune functions may inhibit atherosclerosis and arterial inflammation. These observations suggest the possibility that selective suppression of proatherogenic immune responses or selective activation of antiatherogenic immune responses may provide new approaches for atherosclerosis prevention and treatment. Several antigens activating immune responses affecting development of atherosclerosis have been identified. These immune responses may be modulated by presenting the antigens together with different types of adjuvants as well as through the route of administration. In this review, we summarize recent experimental studies using immunomodulatory approaches for treatment of atherosclerosis.
|
|
| 11. |
- Nilsson, Jan, et al.
(author)
-
Vaccines modulating lipoprotein autoimmunity as a possible future therapy for cardiovascular disease.
- 2009
-
In: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 266:3, s. 221-231
-
Journal article (peer-reviewed)abstract
- Current strategies for prevention of cardiovascular disease focus on risk factor intervention. Although these have been proven both safe and effective results from randomized clinical trials suggest that it is difficult to achieve relative risk reductions exceeding 40% with this approach. To further improve efficacy future therapies must aim at targeting the actual disease process in the arterial wall. Emerging evidence have identified an important role of the immune system in atherosclerosis and suggest that modulation of autoimmune responses against oxidized LDL and other antigens in the atherosclerotic plaque represent one possible new approach to disease prevention. Oxidized LDL is targeted by both antibody-mediated and cellular immune responses and as much as 10% of the T cells in atherosclerotic plaques are oxidized LDL-specific. Immune activation in the atherosclerotic plaque is primarily of the pro-inflammatory Th1-type and inhibition Th1 immunity reduces atherosclerosis in experimental animals. Atherosclerosis vaccines based on antigens derived from LDL have been developed to modulate these processes. Their mechanisms of action remain to be full characterized but may involve expression of protective antibodies that facilitate the removal of oxidized LDL and antigen-specific regulatory T cells that counteract Th1 autoimmunity against oxidized LDL. In this review we will discuss the possibilities and challenges encountering the translation of immune-modulatory therapy for atherosclerosis from the experimental stage into the clinic.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Chyu, Kuang-Yuh, et al.
(author)
-
Active and passive immunization for atherosclerosis
- 2007
-
In: Current Opinion in Molecular Therapeutics. - 2040-3445. ; 9:2, s. 176-182
-
Research review (peer-reviewed)abstract
- This review summarizes experimental findings that highlight the role of immune mechanisms in atherosclerosis and the potential atheroprotective effects of active or passive immunization strategies. Immunomodulation therapy appears to be feasible and effective, suggesting that a vaccine for atherosclerosis can be developed for clinical testing. Given the increasing number of patients with atherosclerotic disease on current therapy, a new therapy is needed and an immunization strategy could provide such a possibility. Several questions regarding this approach remain unanswered, however, such as choice of optimal antigens, choice of most effective adjuvants, the optimal route of administration, durability of effects and safety, but cautious optimism remains that a vaccine-based approach has the potential to become a part of the armamentarium for atherosclerotic vascular disease.
|
|
| 16. |
- Chyu, Kuang-Yuh, et al.
(author)
-
Immunization for atherosclerosis
- 2007
-
In: Current Atherosclerosis Reports. - : Springer Science and Business Media LLC. - 1523-3804 .- 1534-6242. ; 9:2, s. 104-109
-
Research review (peer-reviewed)abstract
- This review summarizes experimental findings that highlight the complex roles of the immune system in atherogenesis. Immune activation can have either proatherogenic or atheroprotective effects. Immune-modulation therapy via an active or passive immunization strategy aims to exploit the atheroprotective aspects of the immune system to modulate atherosclerosis. Several experimental studies have demonstrated that such an approach is feasible and effective, raising the tantalizing possibility that an atheroprotective vaccine can be developed for clinical testing. Several potential immunogens have been identified and tested for their atheroprotective efficacy with variable results. Although several questions such as choice of optimal antigens, choice of most effective adjuvants, the optimal route of administration, durability of effects, and safety remain to be answered, we believe that a vaccine-based approach to manage atherosclerotic cardiovascular disease is a potentially viable paradigm.
|
|
| 17. |
- Dimayuga, Paul C, et al.
(author)
-
T Cell Modulation of Intimal Thickening After Vascular Injury. The Bimodal Role of IFN-{gamma} in Immune Deficiency.
- 2005
-
In: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 25:Oct 13, s. 2528-2534
-
Journal article (peer-reviewed)abstract
- Background - Immune deficiency results in exuberant intimal thickening after arterial injury. The mechanisms involved are not well defined. We investigated the role of T cells and IFN-gamma in the response to injury in normal and immune-deficient Rag-1KO mice. Methods and Results - Carotid arterial injury was induced in wild-type (WT), Rag-1KO mice, and Rag-1KO mice reconstituted with T cell-enriched splenocytes. The exuberant intimal thickening in Rag-1KO mice compared with WT mice 21 days after injury was reduced by T cell transfer (P < 0.01). Exogenous IFN-gamma starting on the day of injury inhibited intimal thickening in Rag-1KO mice. However, antibody neutralization of endogenous IFN-gamma in Rag-1KO mice starting 7 days after injury decreased intimal thickening, indicating that late presence of IFN-gamma promoted intimal thickening in Rag-1KO mice. Results further suggest that the effect of late IFN-gamma in Rag-1KO mice is mediated in part by increased IRF-1 and iNOS expression, coupled with low SOCS1 expression. Conclusion - T cells inhibit intimal thickening in the early stages of the response to injury through basal IFN-gamma secretion. In the Rag-1KO mice, late IFN-gamma expression promotes intimal thickening. These findings add novel insight to conditions of immune deficiency that affect intimal thickening.
|
|
| 18. |
|
|
| 19. |
- Kaufman, E. D., et al.
(author)
-
Probing Protein Adsorption onto Mercaptoundecanoic Acid Stabilized Gold Nanoparticles and Surfaces by Quartz Crystal Microbalance and ζ-Potential Measurements
- 2007
-
In: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 23:11, s. 6053-6062
-
Journal article (peer-reviewed)abstract
- The adsorption characteristics of three proteins [bovine serum albumin (BSA), myoglobin (Mb), and cytochrome c (CytC)] onto self-assembled monolayers of mercaptoundecanoic acid (MUA) on both gold nanoparticles (AuNP) and gold surfaces (Au) are described. The combination of quartz crystal microbalance measurements with dissipation (QCM-D) and pH titrations of the zeta-potential provide information on layer structure, surface coverage, and potential. All three proteins formed adsorption layers consisting of an irreversibly adsorbed fraction and a reversibly adsorbed fraction. BSA showed the highest affinity for the MUA/Au, forming an irreversibly adsorbed rigid monolayer with a side-down orientation and packing close to that expected in the jamming limit. In addition, BSA showed a large change in the adsorbed mass due to reversibly bound protein. The data indicate that the irreversibly adsorbed fraction of CytC is a monolayer structure, whereas the irreversibly adsorbed Mb is present in form of a bilayer. The observation of stable BSA complexes on MUA/AuNPs at the isoelectric point by zeta-potential measurements demonstrates that BSA can sterically stabilize MUA/AuNP. On the other hand, MUA/AuNP coated with either Mb or CytC formed a reversible flocculated state at the isoelectric point. The colloidal stability differences may be correlated with weaker binding in the reversibly bound overlayer in the case of Mb and CytC as compared to BSA.
|
|
| 20. |
- Kumar, B, et al.
(author)
-
Upregulated TRPC1 Channel in Vascular Injury In Vivo and Its Role in Human Neointimal Hyperplasia.
- 2006
-
In: Circulation Research. - 0009-7330. ; 98:4, s. 557-563
-
Journal article (peer-reviewed)abstract
- Occlusive vascular disease is a widespread abnormality leading to lethal or debilitating outcomes such as myocardial infarction and stroke. It is part of atherosclerosis and is evoked by clinical procedures including angioplasty and grafting of saphenous vein in bypass surgery. A causative factor is the switch in smooth muscle cells to an invasive and proliferative mode, leading to neointimal hyperplasia. Here we reveal the importance to this process of TRPC1, a homolog of Drosophila transient receptor potential. Using 2 different in vivo models of vascular injury in rodents we show hyperplasic smooth muscle cells have upregulated TRPC1 associated with enhanced calcium entry and cell cycle activity. Neointimal smooth muscle cells after balloon angioplasty of pig coronary artery also express TRPC1. Furthermore, human vein samples obtained during coronary artery bypass graft surgery commonly exhibit an intimal structure containing smooth muscle cells that expressed more TRPC1 than the medial layer cells. Veins were organ cultured to allow growth of neointimal smooth muscle cells over a 2-week period. To explore the functional relevance of TRPC1, we used a specific E3-targeted antibody to TRPC1 and chemical blocker 2-aminoethoxydiphenyl borate. Both agents significantly reduced neointimal growth in human vein, as well as calcium entry and proliferation of smooth muscle cells in culture. The data suggest upregulated TRPC1 is a general feature of smooth muscle cells in occlusive vascular disease and that TRPC1 inhibitors have potential as protective agents against human vascular failure.
|
|
| 21. |
- Lindgren, Cecilia M, et al.
(author)
-
Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.
- 2009
-
In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:6, s. e1000508-
-
Journal article (peer-reviewed)abstract
- To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Nilsson, Jan, et al.
(author)
-
Oxidants and antioxidants
- 2006
-
In: Risk factors in coronary artery disease. - 9780824740955 - 0824740955 ; , s. 199-199
-
Book chapter (other academic/artistic)
|
|
| 26. |
- Nilsson, Jan, et al.
(author)
-
Oxidized LDL antibodies in treatment and risk assessment of atherosclerosis and associated cardiovascular disease.
- 2007
-
In: Current Pharmaceutical Design. - : Bentham Science Publishers Ltd.. - 1381-6128. ; 13:10, s. 1021-1030
-
Research review (peer-reviewed)abstract
- Immune responses against oxidized forms of LDL play a critical role in activation and regulation of the inflammatory process that characterizes all stages of atherosclerosis. In humans oxidized LDL is targeted by both IgM and IgG autoantibodies. Immunization of hypercholesterolemic animals with oxidized LDL has been shown to inhibit atherosclerosis demonstrating that at least some of these immune responses have a protective effect. The identification of the structures in oxidized LDL that are responsible for activation of immunity has made it possible to develop novel therapeutic approaches for treatment of atherosclerosis based on active (vaccines) and passive (antibodies) immunization. Studies performed in atherosclerosis-prone mice demonstrate that both peptide-based vaccines and recombinant IgG targeting epitopes in oxidized LDL significantly reduce atherosclerosis. There is also evidence antibodies against oxidized LDL could also be used for imaging atherosclerosis.
|
|
| 27. |
- Nilsson, Jan, et al.
(author)
-
Oxidized lipoprotein autoimmunity: an emerging drug target in cardiovascular disease
- 2006
-
In: Future Lipidology. - : Informa UK Limited. - 1746-0875. ; 1:3, s. 321-330
-
Research review (peer-reviewed)abstract
- Oxidative modification of low-density lipoprotein (LDL) in the arterial wall is believed to be one of the most important mechanisms involved in the development of atherosclerosis. It is well established that oxidized (Ox)-LDL uptake is responsible for the formation of macrophage foam cells, one of the most characteristic hallmarks of the atherosclerotic plaque, and that the proinflammatory and cytotoxic effects of Ox-LDL play an important role in vascular inflammation and lesion development. More recently, it has become apparent that Ox-LDL is also recognized by the immune system, thus resulting in innate and adaptive immune reactions modulating both Ox-LDL clearance and the vascular inflammatory response. The finding that some of these immune responses have a protective effect against plaque development has focused attention on the potential to develop novel therapies for the prevention and treatment of cardiovascular disease based on the selective activation of this protective immunity by vaccines, or mimicking them directly by using Ox-LDL-specific antibodies.
|
|
| 28. |
- Nilsson, Jan, et al.
(author)
-
Regulatory T cells and the control of modified lipoprotein autoimmunity-driven atherosclerosis.
- 2009
-
In: Trends in Cardiovascular Medicine. - : Elsevier BV. - 1873-2615 .- 1050-1738. ; 19:8, s. 272-276
-
Journal article (peer-reviewed)abstract
- It has long been recognized that arterial inflammation plays a key role in the development of atherosclerosis. More recent evidence has suggested that this inflammation is modulated by autoimmune responses against modified self-antigens, such as oxidized low-density lipoprotein, in the vascular wall. However, the role of the immune system in atherosclerosis appears to be more complex than in classic autoimmune diseases; and a number of protective immune responses have also been identified. One of the most important of these is carried out by the regulatory T cells. Regulatory T cells inhibit the development of autoimmunity by controlling the activity of autoreactive T cells. If the function of regulatory T cells is compromised in hypercholesterolemic mouse models of atherosclerosis, the development of disease becomes much more aggressive. In this review, we will discuss the possibility that the inflammatory activity in atherosclerotic lesions depends on the balance between plaque antigen-specific proinflammatory Th1-type T cells and anti-inflammatory regulatory T cells specific for the same antigen. We will also discuss the role of hypercholesterolemia in generation of these modified self-antigens as well as ongoing research aiming to develop novel immune-modulating therapy for prevention of cardiovascular disease by targeting these processes.
|
|
| 29. |
- Nordin Fredrikson, Gunilla, et al.
(author)
-
Association between IgM against an aldehyde-modified peptide in apo B-100 and progression of carotid disease.
- 2007
-
In: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 38, s. 1495-1500
-
Journal article (peer-reviewed)abstract
- Background and Purpose— Autoantibodies against antigens in oxidized low-density lipoprotein are common in people; experimental studies suggest that these immune responses have a functional role in the disease process. The aim of this study was to evaluate the relationship between the immune response against one defined oxidized low-density lipoprotein antigen, the aldehyde-modified peptide corresponding amino acids 3136 and 3155 (MDA-p210) in apolipoprotein (apo) B-100, and progression of carotid intima media thickness (IMT).Methods— IgM and IgG against MDA-p210 were determined by enzyme-linked immunosorbent assay at baseline and after 12 months of treatment with placebo, metoprolol, fluvastatin, or metoprolol/fluvastatin in 751 individuals participating in the BCAPS. Carotid IMT was assessed by ultrasonography at baseline and after 18 and 36 months of treatment.Results— Antibody levels did not change in response to treatment, but high baseline MDA-p210 IgM levels were associated with a more rapid progression of carotid disease both at 18 (r=0.09, P<0.05) and 36 months (r=0.12, P<0.005). At 36 months, the difference in IMT progression rate per year between those with high MDA-p210 IgM levels and those with low was 0.011 mm (95% CI=0.005 to 0.018 mm, P<0.0001). Treatment with fluvastatin markedly decreased the progression of IMT among subjects with high but not with low MDA-p210 IgM levels. There was no association between MDA-p210 IgG and carotid IMT progression.Conclusions— IgM against the aldehyde-modified peptide corresponding amino acids 3136 and 3155 in apo B-100 is common in subjects with asymptomatic carotid disease, and high levels are associated with a more rapid progression of carotid IMT. The observation that the effect of fluvastatin was restricted to subjects with high MDA-p210 IgM levels may reflect the increased rate of disease progression in this group.
|
|
| 30. |
- Nordin Fredrikson, Gunilla, et al.
(author)
-
Association between IgM against an aldehyde-modified peptide in apolipoprotein B-100 and progression of carotid disease
- 2007
-
In: Stroke: a journal of cerebral circulation. - 1524-4628. ; 38:5, s. 1495-1500
-
Journal article (peer-reviewed)abstract
- Background and Purpose - Autoantibodies against antigens in oxidized low-density lipoprotein are common in people; experimental studies suggest that these immune responses have a functional role in the disease process. The aim of this study was to evaluate the relationship between the immune response against one defined oxidized low-density lipoprotein antigen, the aldehyde-modified peptide corresponding amino acids 3136 and 3155 (MDA-p210) in apolipoprotein (apo) B-100, and progression of carotid intima media thickness (IMT). Methods - IgM and IgG against MDA-p210 were determined by enzyme-linked immunosorbent assay at baseline and after 12 months of treatment with placebo, metoprolol, fluvastatin, or metoprolol/ fluvastatin in 751 individuals participating in the BCAPS. Carotid IMT was assessed by ultrasonography at baseline and after 18 and 36 months of treatment. Results - Antibody levels did not change in response to treatment, but high baseline MDA-p210 IgM levels were associated with a more rapid progression of carotid disease both at 18 ( r = 0.09, P < 0.05) and 36 months ( r = 0.12, P < 0.005). At 36 months, the difference in IMT progression rate per year between those with high MDA-p210 IgM levels and those with low was 0.011 mm ( 95% CI = 0.005 to 0.018 mm, P < 0.0001). Treatment with fluvastatin markedly decreased the progression of IMT among subjects with high but not with low MDA-p210 IgM levels. There was no association between MDA-p210 IgG and carotid IMT progression. Conclusions - IgM against the aldehyde-modified peptide corresponding amino acids 3136 and 3155 in apo B-100 is common in subjects with asymptomatic carotid disease, and high levels are associated with a more rapid progression of carotid IMT. The observation that the effect of fluvastatin was restricted to subjects with high MDA-p210 IgM levels may reflect the increased rate of disease progression in this group.
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
- Nordin Fredrikson, Gunilla, et al.
(author)
-
Autoimmune responses against the apo B-100 LDL receptor-binding site protect against arterial accumulation of lipids in LDL receptor deficient mice.
- 2007
-
In: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 40:2, s. 122-130
-
Journal article (peer-reviewed)abstract
- Background: Oxidation of LDL is associated with generation of autoantibodies against a large number of different aldehyde-modified peptide sequences in apo B-100. Autoantibodies recognizing peptide sequences in the LDL receptor-binding region of apo B-100 could potentially affect both cholesterol metabolism and atherosclerosis. The aim of the present study was to determine physiological effects of induction of immune responses against the apo B-100 LDL receptor-binding site in mice deficient for the LDL receptor. Methods and results: Mice received three immunizations, beginning at 6 weeks of age, with aldehyde-modified or nonmodified peptides corresponding to the amino acid sequence of the LDL receptor-binding site. Analysis of antibody response by ELISA unexpectedly revealed high titers of pre-existing IgG against both native and aldehyde-modified binding site sequences in non-immunized mice. Immunization with aldehyde-modified binding site sequences resulted in an almost complete down-regulation of this autoimmune response. It was also associated with a rapid increase in lipid-rich plaques in the aorta and a substantial depletion of the lipid content of the liver, whereas plasma lipid and apo B values were similar in all groups. Conclusions: These observations demonstrate existence of an endogenous T cell-dependent autoimmune response against the LDL receptor-binding site in LDL receptor(-/-) mice and suggest that this may help to prevent accumulation of lipoprotein lipids in the artery wall, whereas immunization with the corresponding aldehyde modified sequence down-regulates this response and induces substantial atherosclerotic development.
|
|
| 34. |
|
|
| 35. |
- Nordin Fredrikson, Gunilla, et al.
(author)
-
Identification of autoantibodies in human plasma recognizing an apoB-100 LDL receptor binding site peptide
- 2006
-
In: Journal of Lipid Research. - 1539-7262 .- 0022-2275. ; 47:9, s. 2049-2054
-
Journal article (peer-reviewed)abstract
- The aim of this study was to test the hypothesis that autoantibodies recognize amino acid sequences in the LDL receptor binding region of apolipoprotein B-100 (apoB-100). Autoantibodies against an unmodified or malondialdehyde (MDA)-modified LDL receptor binding site peptide were determined by ELISA in baseline plasma samples of 78 cases with coronary events and 149 matched controls recruited from the prospective Malmo Diet Cancer Study. IgG and IgM recognizing this peptide were detected in all subjects but did not differ between cases and controls. Inverse associations were observed between IgG against the native binding site and plasma oxidized LDL (r = -0.21, P < 0.005), but there were no significant associations with total or LDL cholesterol levels. In univariate analyses, inverse associations were found between baseline carotid intima-media thickness and IgG against the MDA-modified binding site (r = -0.14, P < 0.05), but this association was lost when controlling for other major cardiovascular risk factors. Specificity studies demonstrated that the binding of autoantibodies to these sequences could be inhibited by oxidized but not by native LDL. Autoantibodies recognizing the LDL receptor binding site in apoB-100 are frequently expressed. Their association with plasma oxidized LDL suggests that they have been generated in response to breakdown products of LDL oxidation, but their influence on cholesterol metabolism and the development of atherosclerosis appears limited.
|
|
| 36. |
- Schiopu, Alexandru, et al.
(author)
-
Recombinant antibodies to an oxidized low-density lipoprotein epitope induce rapid regression of atherosclerosis in apobec-1(-/-)/low-density lipoprotein receptor(-/-) mice.
- 2007
-
In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 50:24, s. 2313-2318
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: The present study tested the hypothesis that treatment with human recombinant immunoglobulin G1 (IgG1) antibodies against a specific oxidized low-density lipoprotein (oxLDL) epitope will induce regression of existing atherosclerotic lesions in LDL receptor-deficient mice expressing apolipoprotein B-100 (apoB-100) (Apobec-1(-/-)/LDLR(-/-)). BACKGROUND: Oxidized LDL plays an essential role in the pathogenesis of atherosclerosis. We previously showed that an antibody against oxLDL reduces progression of atherosclerosis in mice. METHODS: Apobec-1(-/-)/LDLR(-/-) mice were fed a high-fat diet until they were 24 weeks and were subsequently transferred to chow. Starting at 25 weeks, mice were given 3 weekly injections of either of 2 recombinant human IgG1 antibodies (IEI-E3 or 2D03) against a malondialdehyde-modified apoB-100 peptide sequence. RESULTS: At 25 weeks, atherosclerotic lesions covered 10.3 +/- 3.7% of the descending aorta. Transfer to chow diet resulted in a modest regression of atherosclerosis over a 5-week period (8.28 +/- 4.36%; p = NS). Antibody treatment induced additional regression of atherosclerosis by 50% (2D03; p = 0.001) and 36% (IEI-E3; p = 0.004) compared with control IgG1. The 2D03 treatment also reduced plaque inflammation, enhanced plaque expression of the adenosine triphosphate-binding cassette transporter A1, and inhibited expression of monocyte chemoattractant protein-1 in cultured monocytes. CONCLUSIONS: Human IgG1 against a specific oxLDL epitope can induce rapid and substantial regression of atherosclerotic lesions, possibly by stimulating lipid efflux and inhibiting macrophage recruitment. These recombinant human antibodies could represent a novel strategy for rapid regression/stabilization of atherosclerotic lesions.
|
|
| 37. |
- Schwartz, Gregory G, et al.
(author)
-
Rationale and design of the dal-OUTCOMES trial: Efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome
- 2009
-
In: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 158:6, s. 896-U34
-
Journal article (peer-reviewed)abstract
- Background Despite contemporary therapies for acute coronary syndrome (ACS), morbidity and mortality remain high. Low levels of high-density lipoprotein (HDL) cholesterol are common among patients with ACS and may contribute to ongoing risk. Strategies that raise levels of HDL cholesterol, such as inhibition of cholesterol ester transfer protein (CETP), might reduce risk after ACS. Dal-OUTCOMES is a multicenter, randomized, double-blind, placebo-controlled trial designed to test the hypothesis that CETP inhibition with dalcetrapib reduces cardiovascular morbidity and mortality in patients with recent ACS. Design The study will randomize approximately 15,600 patients to receive daily doses of dalcetrapib 600 mg or matching placebo, beginning 4 to 12 weeks after an index ACS event. There are no prespecified boundaries for HDL cholesterol levels at entry. Other elements of care, including management of low-density lipoprotein cholesterol, are to follow best evidence-based practice. The primary efficacy measure is time to first occurrence of coronary heart disease death, nonfatal acute myocardial infarction, unstable angina requiring hospital admission, resuscitated cardiac arrest, or atherothrombotic stroke. The trial will continue until 1,600 primary end point events have occurred, all evaluable subjects have been followed for at least 2 years, and 80% of evaluable subjects have been followed for at least 2.5 years. Summary Dal-OUTCOMES will determine whether CETP inhibition with dalcetrapib, added to current evidence-based care, reduces cardiovascular morbidity and mortality after ACS.
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
- Sundén, Bengt, et al.
(author)
-
Advances in Compact Heat Exchangers
- 2007
-
Book (other academic/artistic)abstract
- State-of-the-art coverage of compact heat exchanger design and technology. This book, a special supplemental issue of the International Journal of Heat Exchangers, contains a selection of papers originally presented at the Fifth International Conference on Enhanced, Compact, and Ultra-Compact Heat Exchangers: Science, Engineering and Technology, which was held in Whistler, British Columbia, Canada in September 2005. These papers represent well the width and depth of the conference, and reflect the state-of-the-art in compact heat exchanger research, design, and technology.
|
|
| 42. |
- Sundén, Bengt, et al.
(author)
-
High temperature heat exchangers
- 2005
-
In: Enhanced, Compact and Ultra-Compact Heat Exchangers: Science, Engineering and Technology. ; , s. 226-238
-
Conference paper (peer-reviewed)
|
|
| 43. |
- Sundén, Bengt, et al.
(author)
-
High temperature heat exchangers
- 2007
-
In: Advances in Compact Heat Exchangers. - 9781930217164 ; , s. 33-33
-
Book chapter (other academic/artistic)
|
|
| 44. |
|
|
