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- Adam, Lucille, et al.
(författare)
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Early Resistance of Non-virulent Mycobacterial Infection in C57BL/6 Mice Is Associated With Rapid Up-Regulation of Antimicrobial Cathelicidin Camp
- 2018
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Early clearance of tuberculosis is the successful eradication of inhaled bacteria before the development of an adaptive immune response. We previously showed, by utilizing a non-virulent mycobacteria infection model, that C57BL/6 mice are more efficient than BALB/c in their control of bacterial growth in the lungs during the first weeks of the infection. Here, we assessed early (within 1-3 days) innate immune events locally in the lungs to identify factors that may contribute to the control of non-virulent mycobacterial burden. We confirmed that C57BL/6 mice are more resistant to infection compared with BALB/c after intranasal inoculation with mycobacterium. Transcriptomic analyses revealed a remarkably silent signature in C57BL/6 mice despite effective control of bacterial growth. In contrast, BALB/c mice up-regulated genes associated with neutrophil and myeloid cell chemotaxis and migration. Flow cytometry analyses corroborated the transcriptomic analyses and demonstrated influx of both neutrophil and myeloid cell populations in BALB/c mice, while these did not increase in C57BL/6 mice. We further detected increased release of TNF-alpha from BALB/c lung cells but limited release from C57BL/6-derived cells. However, C57BL/6 mice showed a marked early up-regulation of the Camp gene, encoding the cathelicidin CRAMP peptide, post-mycobacterial exposure. CRAMP (LL-37 in human) expression in the lungs was confirmed using immunofluorescence staining. Altogether, these findings show that C57BL/6 mice can clear the mycobacterial infection early and that this early control is associated with high CRAMP expression in the lungs without concomitant influx of immune cells. The role of CRAMP/LL-37 during mycobacterial infection may be relevant for novel protective strategies, and warrants further studies of human cohorts.
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| 2. |
- Albin, Maria, et al.
(författare)
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Acute myeloid leukemia and clonal chromosome aberrations in relation to past exposure to organic solvents
- 2000
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Ingår i: Scandinavian Journal of Work, Environment and Health. - 0355-3140. ; 26:6, s. 482-491
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The effects of occupational and leisure-time exposures on the risk of acute myeloid leukemia (AML) were investigated with emphasis on clonal chromosome aberrations (CCA) and morphological subtypes. METHODS: Consecutively diagnosed cases of AML (N=333) and 1 population referent per case were retrospectively included in the study. Information on worktasks, companies, and leisure-time activities was obtained with telephone interviews. Exposure probability and intensity were assessed by occupational hygienists. Associations were evaluated with logistic regression. RESULTS: Exposure to organic solvents was associated with an increased risk of AML [low exposure: OR 1.5 (95% confidence interval (95% CI) 1.0-2.3, moderate-high exposure: OR 2.3 (95% CI 1.0-5.0)]. For exposure to solvents, but not to benzene, the OR was 1.2 (95% CI 0.69-2.0) for "low" and 2.7 (95% CI 1.0-7.3) for "moderate-high" exposure. The observed effects increased with intensity and duration of exposure. The estimated effects were higher for patients >60 years of age at the time of diagnosis. The effect of exposure to organic solvents was not differential with regard to morphology [except possibly erythroleukemia: OR 4.2, 95% CI 1.0-17 or the presence of CCA in general]. No increased risk for AML with complex CCA or with total or partial losses of chromosomes 5 or 7 were observed, but a higher risk was found for AML with trisomy 8 (OR 11, 95% CI 2.7-42) as the sole aberration. CONCLUSIONS: Exposure to organic solvents was associated with an increased risk of AML. This association was not due to benzene exposure alone and may be modified by age. Furthermore, specific associations with trisomy 8, and possibly also erythroleukemia, were suggested.
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| 3. |
- Albin, Maria; Björk, Jonas; Lövkvist, Håkan,
(författare)
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Exponering för omgivningsbuller i Skåne: Omfattning och miljömedicinsk bedömning
- 2003
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- En kartläggning av exponering för omgivningsbuller i Skåne och en miljömedicinsk bedömning av dess effekter har genomförts. Som underlag har använts trafik på statliga vägar, med beräkningar baserade på GIS-metodik, samt modeller för vägbullerbelastning i tätorter av olika storlek från såväl statliga som kommunala vägar. Uppgifter om störning och hälsotillstånd har hämtats från Folkhälsoenkät Skåne 2000. Den övervägande delen av befolkningen (3 av 4) bor i områden som inte är tysta (ekvivalentnivå över 40 dB(A). Nära var femte person i Skåne beräknas vara utsatt för omgivningsbuller från vägtrafik överskridande 55 dB(A) ekvivalentnivå över dygnet. I Malmö och Burlöv beräknas minst var fjärde invånare ha sådan exponering. För tåg- och flygtrafik saknas underlag för motsvarande beräkningar. Det fanns bland personer som beräknades vara exponerade över dessa nivåer en tendens till att oftare rapportera koncentrationsstörning. För personer som i större utsträckning kan antas vistas och arbeta hemma dagtid (hemarbetande, pensionärer, studerande, arbetslösa) var ökningen statistiskt signifikant (Oddskvot=3,5, 95% konfidensintervall 1,3-8.9), medan ingen effekt sågs hos de förvärvsarbetande. Inga statistiskt säkerställda samband sågs med sömnstörning eller blodtrycksmedicinering. Trafikbuller i bostaden upplevs som ganska mycket, eller mycket störande av var femtonde person i Skåne (7%). Flertalet av dessa, motsvarande 5% i hela befolkningen, anger att det är vägtrafiken som stör dem. Motsvarande 2-3% av befolkningen anger att trafikbullret ofta ger störd vila/avkoppling, insomning, respektive väckning. Kartläggningen visar att underlaget för hälsorelaterad miljöövervakning av exponering för trafikbuller är bristfälligt i flera avseenden. Trots detta visar kartläggningen att exponeringen för trafikbuller är ett betydande problem för befolkningen i Skåne. Problemet är särskilt uttalat i vissa kommuner där riktade insatser är befogade. Det är ur miljömedicinsk synpunkt angeläget att underlaget för fortsatt miljöövervakning av exponering för trafikbuller förbättras och därefter fortsatt uppdateras, med god tillgänglighet för olika samhällsinstanser.
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| 4. |
- Albin, Maria, et al.
(författare)
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Cytogenetic and morphologic subgroups of myelodysplastic syndromes in relation to occupational and hobby exposures.
- 2003
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Ingår i: Scandinavian Journal of Work, Environment and Health. - 0355-3140. ; 29:5, s. 378-387
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study investigated the association between occupational and hobby exposure and the risk of myelodysplastic syndromes (MDS) while focusing on differential patterns of clonal chromosome aberrations and morphologic subgroups. METHODS: A case-referent study was conducted with 330 MDS patients investigated cytogenetically in 1976-1993 (cases) and matched referents. Telephone interviews with either the person or a next-of-kin were used. The participation rate of the cases and referents was 85% and 60%, respectively. Information was obtained from the next-of-kin more often for the cases (88%) than for the referents (26%). Occupational hygienists assessed the exposure using interview data on worktasks and hobbies. Associations with disease risk were evaluated for 10 exposures with a logistic regression analysis. RESULTS: The investigated exposures were generally not associated with cytogenetically abnormal MDS. Effect estimates for specific cytogenetic or morphologic subgroups were generally imprecise. Occupational exposure to extremely low-frequency magnetic fields (EMF) was associated with MDS with a normal karyotype [odds ratio (OR) 2.0, 95% confidence interval (95% CI) 1.0-4.0]. The exposure-response association was consistent for intensity but inconclusive for duration. A decreased risk was observed for MDS, irrespective of karyotypic pattern, among farmers and farmhands (OR 0.53, 95% CI 0.35-0.81). CONCLUSIONS: Cytogenetically abnormal MDS was generally not associated with occupational or hobby exposure to known or suspected genotoxic agents. However, exposure prevalences and intensities were low for several agents. An association was suggested between occupational exposure to EMF and MDS with a normal karyotype. Biases due to differential information quality and selective participation cannot be ruled out.
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| 9. |
- Axberg Pålsson, Sandra, et al.
(författare)
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Single-Stranded Oligonucleotide-Mediated Inhibition of Respiratory Syncytial Virus Infection
- 2020
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in young children. Currently, there is no RSV vaccine or universally accessible antiviral treatment available. Addressing the urgent need for new antiviral agents, we have investigated the capacity of a non-coding single-stranded oligonucleotide (ssON) to inhibit RSV infection. By utilizing a GFP-expressing RSV, we demonstrate that the ssON significantly reduced the proportion of RSV infected A549 cells (lung epithelial cells). Furthermore, we show that ssON's antiviral activity was length dependent and that both RNA and DNA of this class of oligonucleotides have antiviral activity. We reveal that ssON inhibited RSV infection by competing with the virus for binding to the cellular receptor nucleolin in vitro. Additionally, using a recombinant RSV that expresses luciferase we show that ssON effectively blocked RSV infection in mice. Treatment with ssON in vivo resulted in the upregulation of RSV-induced interferon stimulated genes (ISGs) such as Stat1, Stat2, Cxcl10, and Ccl2. This study highlights the possibility of using oligonucleotides as therapeutic agents against RSV infection. We demonstrate that the mechanism of action of ssON is the inhibition of viral entry in vitro, likely through the binding of the receptor, nucleolin and that ssON treatment against RSV infection in vivo additionally results in the upregulation of ISGs.
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