| 1. |
- Fang, Fang, et al.
(författare)
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Loss of a child and the risk of amyotrophic lateral sclerosis
- 2008
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Ingår i: American Journal of Epidemiology. - Cary, USA : Oxford University Press. - 0002-9262 .- 1476-6256. ; 167:2, s. 203-10
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Tidskriftsartikel (refereegranskat)abstract
- Between 1987 and 2005, the authors conducted a case-control study nested within the entire Swedish population to investigate whether loss of a child due to death is associated with the risk of amyotrophic lateral sclerosis (ALS). The study comprised 2,694 incident ALS cases and five controls per case individually matched by year of birth, gender, and parity. Odds ratios and their corresponding 95% confidence intervals for ALS were estimated by using conditional logistic regression models. Compared with that for parents who never lost a child, the overall odds ratio of ALS for bereaved parents was 0.7 (95% confidence interval (CI): 0.6, 0.8) and decreased to 0.4 (95% CI: 0.2, 0.8) 11-15 years after the loss. The risk reduction was also modified by parental age at the time of loss, with the lowest odds ratio of 0.4 (95% CI: 0.2, 0.9) for parents older than age 75 years. Loss of a child due to malignancy appeared to confer a lower risk of ALS (odds ratio = 0.5, 95% CI: 0.3, 0.8) than loss due to other causes. These data indicate that the risk of developing ALS decreases following the severe stress of parental bereavement. Further studies are needed to explore potential underlying mechanisms.
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| 2. |
- Lobell, Anna, et al.
(författare)
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Suppressive DNA vaccination in myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis involves a T1-biased immune response
- 2003
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 170:4, s. 1806-1813
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Vaccination with DNA encoding a myelin basic protein peptide suppresses Lewis rat experimental autoimmune encephalomyelitis (EAE) induced with the same peptide. Additional myelin proteins, such as myelin oligodendrocyte glycoprotein (MOG), may be important in multiple sclerosis. Here we demonstrate that DNA vaccination also suppresses MOG peptide-induced EAE. MOG(91-108) is encephalitogenic in DA rats and MHC-congenic LEW.1AV1 (RT1(av1)) and LEW.1N (RT1(n)) rats. We examined the effects of DNA vaccines encoding MOG(91-108) in tandem, with or without targeting of the hybrid gene product to IgG. In all investigated rat strains DNA vaccination suppressed clinical signs of EAE. There was no requirement for targeting the gene product to IgG, but T1-promoting CpG DNA motifs in the plasmid backbone of the construct were necessary for efficient DNA vaccination, similar to the case in DNA vaccination in myelin basic protein-induced EAE. We failed to detect any effects on ex vivo MOG-peptide-induced IFN-gamma, TNF-alpha, IL-6, IL-4, IL-10, and brain-derived neurotropic factor expression in splenocytes or CNS-derived lymphocytes. In CNS-derived lymphocytes, Fas ligand expression was down-regulated in DNA-vaccinated rats compared with controls. However, MOG-specific IgG2b responses were enhanced after DNA vaccination. The enhanced IgG2b responses together with the requirement for CpG DNA motifs in the vaccine suggest a protective mechanism involving induction of a T1-biased immune response.
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| 3. |
- Lobell, Anna, et al.
(författare)
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Vaccination with DNA encoding an immunodominant myelin basic protein peptide targeted to Fc of immunoglobulin G suppresses experimental autoimmune encephalomyelitis
- 1998
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 187:9, s. 1543-1548
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Tidskriftsartikel (refereegranskat)abstract
- We explore here if vaccination with DNA encoding an autoantigenic peptide can suppress autoimmune disease. For this purpose we used experimental autoimmune encephalomyelitis (EAE), which is an autoaggressive disease in the central nervous system and an animal model for multiple sclerosis. Lewis rats were vaccinated with DNA encoding an encephalitogenic T cell epitope, guinea pig myelin basic protein peptide 68-85 (MBP68-85), before induction of EAE with MBP68-85 in complete Freund's adjuvant. Compared to vaccination with a control DNA construct, the vaccination suppressed clinical and histopathological signs of EAE, and reduced the interferon gamma production after challenge with MBP68-85. Targeting of the gene product to Fc of IgG was essential for this effect. There were no signs of a Th2 cytokine bias. Our data suggest that DNA vaccines encoding autoantigenic peptides may be useful tools in controlling autoimmune disease.
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| 4. |
- Eriksson, Emma, et al.
(författare)
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CD44-regulated intracellular proliferation of Listeria monocytogenes.
- 2003
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Ingår i: Infect Immun. - 0019-9567. ; 71:7, s. 4102-11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- CD44 has been implicated in immune and inflammatory processes. We have analyzed the role of CD44 in the outcome of Listeria monocytogenes infection in murine bone marrow-derived macrophages (BMM). Surprisingly, a dramatically decreased intracellular survival of L. monocytogenes was observed in CD44(-/-) BMM. CD44(-/-) heart or lung fibroblast cultures also showed reduced bacterial levels. Moreover, livers from CD44(-/-)-infected mice showed diminished levels of L. monocytogenes. In contrast, intracellular growth of Salmonella enterica serovar Typhimurium was the same in CD44(-/-) and control BMM. The CD44-mediated increased bacterial proliferation was not linked to altered BMM differentiation or to secretion of soluble factors. CD44 did not mediate listerial uptake, and it played no role in bacterial escape from the primary phagosome or formation of actin tails. Furthermore, CD44-enhanced listerial proliferation occurred in the absence of intracellular bacterial spreading. Interestingly, coincubation of BMM with hyaluronidase or anti-CD44 antibodies that selectively inhibit hyaluronan binding increased intracellular listerial proliferation. Treatment of cells with hyaluronan, in contrast, diminished listerial growth and induced proinflammatory transcript levels. We suggest that L. monocytogenes takes advantage of the CD44-mediated signaling to proliferate intracellularly, although binding of CD44 to certain ligands will inhibit such response.
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| 5. |
- Hagbom, Marie, et al.
(författare)
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Ionizing air affects influenza virus infectivity and prevents airborne-transmission
- 2015
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Ingår i: Scientific Reports. - : Nature Publishing Group: Open Access Journals - Option C / Nature Publishing Group. - 2045-2322. ; 5:11431
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Tidskriftsartikel (refereegranskat)abstract
- By the use of a modified ionizer device we describe effective prevention of airborne transmitted influenza A (strain Panama 99) virus infection between animals and inactivation of virus (greater than 97%). Active ionizer prevented 100% (4/4) of guinea pigs from infection. Moreover, the device effectively captured airborne transmitted calicivirus, rotavirus and influenza virus, with recovery rates up to 21% after 40 min in a 19 m(3) room. The ionizer generates negative ions, rendering airborne particles/aerosol droplets negatively charged and electrostatically attracts them to a positively charged collector plate. Trapped viruses are then identified by reverse transcription quantitative real-time PCR. The device enables unique possibilities for rapid and simple removal of virus from air and offers possibilities to simultaneously identify and prevent airborne transmission of viruses.
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| 6. |
- Hagbom, Marie, et al.
(författare)
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The Cholinergic Anti-Inflammatory Pathway Contributes to the Limited Inflammatory Response following Rotavirus Infection
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Rotavirus causes acute gastroenteritis in young children and is characterized by severe diarrhoea and vomiting. Surprisingly, although rotavirus infection results in significant intestinal pathology, the inflammatory response is limited. We tested the novel hypothesis that rotavirus infection stimulates the cholinergic anti-inflammatory pathway to suppress gut inflammation. The role of the vagus nerve and the α7 nicotinic acetylcholine receptor (α7 nAChR) in rotavirus infection were explored in α7 nAChR gene-deficient mice, vagotomized mice and wild-type mice treated with the α7 nAChR antagonist mecamylamine. TNF-α, IL-1β and IL-6 were measured in serum, spleen, duodenum, jejunum and ileum at 48 hours post infection. To determine if modulation of the inflammatory response affects virus shedding, α7 nAChRs was blocked and virus quantified in faeces. To investigate if stimulation of α7 nAChRs could attenuate rotavirus toxin NSP4-induced cytokine release, mouse peritoneal- and human blood-macrophages were treated with nicotine before NSP4 stimulation.Our results shows that stimulation of the vagus nerve and α7 nAChRs attenuated the pro- inflammatory response during rotavirus infection and blockade of the α7 nAChR reduced virus shedding from infected mice. IL-6 was increased in duodenum (p<0.05) and serum (p<0.05) of vagotomized mice and in jejunum (p<0.05) and spleen (p<0.05) of α7 nAChR gene-deficient mice. Furthermore, IL-6 mRNA (p<0.01) and TNF-α mRNA (p<0.05) were increased in duodenum of vagotomized animals. Similarly, nicotine attenuated the release of TNF-α (p<0.05) and IL-6 (p<0.05) from macrophages stimulated by NSP4 in vitro, all suggesting that the cholinergic anti- inflammatory pathway contributes to attenuate inflammation during rotavirus infection.
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| 7. |
- Lobell, Anna, et al.
(författare)
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Presence of CpG DNA and the local cytokine milieu determine the efficacy of suppressive DNA vaccination in experimental autoimmune encephalomyelitis
- 1999
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Ingår i: Journal of Immunology. - 0022-1767 .- 1550-6606. ; 163:9, s. 4754-4762
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Tidskriftsartikel (refereegranskat)abstract
- We here study the adjuvant properties of immunostimulatory DNA sequences (ISS) and coinjected cytokine-coding cDNA in suppressive vaccination with DNA encoding an autoantigenic peptide, myelin basic protein peptide 68-85, against Lewis rat experimental autoimmune encephalomyelitis (EAE). EAE is an autoaggressive, T1-mediated disease of the CNS. ISS are unmethylated CpG motifs found in bacterial DNA, which can induce production of type 1 cytokines in vertebrates through the innate immune system. Because ISS in the plasmid backbone are necessary for efficient DNA vaccination, we studied the effect of one such ISS, the 5'-AACGTT-3' motif, in our system. Treatment with a DNA vaccine encoding myelin basic protein peptide 68-85 and containing three ISS of 5'-AACGTT-3' sequence suppressed clinical signs of EAE, while a corresponding DNA vaccine without such ISS had no effect. We further observed reduced proliferative T cell responses in rats treated with the ISS-containing DNA vaccine, compared with controls. We also studied the possible impact of coinjection of plasmid DNA encoding rat cytokines IL-4, IL-10, GM-CSF, and TNF-alpha with the ISS-containing DNA vaccine. Coinjection of IL-4-, IL-10-, or TNF-alpha-coding cDNA inhibited the suppressive effect of the DNA vaccine on EAE, whereas GM-CSF-coding cDNA had no effect. Coinjection of cytokine-coding cDNA with the ISS-deficient DNA vaccine failed to alter clinical signs of EAE. We conclude that the presence of ISS and induction of a local T1 cytokine milieu is decisive for specific protective DNA vaccination in EAE.
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| 8. |
- Lobell, Anna, et al.
(författare)
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Protective DNA vaccination against organ-specific autoimmunity is highly specific and discriminates between single amino acid substitutions in the peptide autoantigen
- 2000
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 97:4, s. 1689-1694
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- DNA vaccines that encode encephalitogenic sequences in tandem can protect from subsequent experimental autoimmune encephalomyelitis induced with the corresponding peptide. The mechanism for this protection and, in particular, if it is specific for the amino acid sequence encoding the vaccine are not known. We show here that a single amino acid exchange in position 79 from serine (nonself) to threonine (self) in myelin basic protein peptide MBP68-85, which is a major encephalitogenic determinant for Lewis rats, dramatically alters the protection. Moreover, vaccines encoding the encephalitogenic sequence MBP68-85 do not protect against the second encephalitogenic sequence MBP89-101 in Lewis rats and vice versa. Thus, protective immunity conferred by DNA vaccination exquisitely discriminates between peptide target autoantigens. No bystander suppression was observed. The exact underlying mechanisms remain elusive because no simple correlation between impact on ex vivo responses and protection against disease were noted.
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| 9. |
- Svanholm, Cecilia, et al.
(författare)
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Enhancement of antibody responses by DNA immunization using expression vectors mediating efficient antigen secretion
- 1999
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Ingår i: JIM - Journal of Immunological Methods. - 0022-1759 .- 1872-7905. ; 228:1-2, s. 121-130
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Tidskriftsartikel (refereegranskat)abstract
- The immune responses elicited in mice, after intradermal (i.d.) immunization with plasmids encoding secreted or intracellular forms of HIV-1 nef, HIV-1 tat or C. pneumoniae omp2 proteins, respectively, were compared. To mediate secretion of these proteins the genes were fused to a heterologous signal sequence from murine heavy chain IgG. The nef- and omp2-specific antibody responses were dramatically increased when mice were inoculated with the plasmid encoding the secreted form of these proteins. In contrast, HIV-1 tat comprising an internal strong nuclear targeting sequence could not be induced to secretion and subsequently no enhanced antibody response was observed. Slight improvement of the HIV-1 nef antibody response was achieved after co-inoculation with a granulocyte-macrophage colony-stimulating factor (GM-CSF) expression vector. Further, nef-specific T-cell responses were induced after nef DNA injections, and were of Th1-like phenotype regardless of whether the nef protein was secreted or not. The system described in this study, using a plasmid vector with a strong heterologous signal sequence that mediate efficient antigen secretion in vivo, may have wide applicability for the induction of high antibody levels to normally non-secreted antigens.
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