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Susceptibility of human macrophages to <em>Chlamydia pneumoniae</em> infection <em>in vitro</em>
No full textAbstractChlamydia pneumoniae is an obligate intracellular gram-negative bacterium, which causes respiratory infections in humans and may participate in the development of chronic diseases like atherosclerosis, chronic obstructive lung disease, adult-onset asthma and late-onset Alzheimer’s disease. It can infect various cell types, e.g. vascular endothelial cells, smooth muscle cells and monocyte-derived macrophages in vitro. It has been speculated that circulating macrophages disseminate the infection in the body, and that genetically susceptible individuals become chronically infected.Quantification of C. pneumoniae growth inside cultured cells is needed when studying e.g. the effect of drugs or host cell factors on infectivity and replication. Conventionally this has been done by immunofluorescence staining and microscopic counting of chlamydial inclusions. However, this method is usable only if the cell numbers do not fluctuate in cell culture vials and the inclusions are uniform. In macrophages, inclusions are often aberrant, their sizes vary and multiple inclusions are also seen. Therefore we developed a new method based on the real-time PCR quantification of chlamydial genomes adjusted to the number of human genomes and used it to quantify the exact amounts of C. pneumoniae in infected cells.The susceptibility of monocyte-macrophages from healthy individuals to C. pneumoniae infection in vitro was studied first. Intracellular growth of C. pneumoniae was used as an indicator of susceptibility to infection, and it was compared to serum levels of CRP, soluble CD14, human HSP-IgG, human HSP-IgA, C. pneumoniae IgG and IgA antibodies. The growth of C. pneumoniae in infected macrophages was highly variable, ranging from 0 to 638 chlamydial genomes per human genome. C. pneumoniae growth associated positively with serum C. pneumoniae IgA (titer ≥10) and hHSP-IgG and negatively with soluble CD14 concentration. The association between chlamydial IgA antibodies, hHSP-IgG and C. pneumoniae growth was statistically significant only among men. Age did not correlate with the growth. Therefore we hypothesize that persons whose macrophages cannot restrict the growth of C. pneumoniae are more prone to chronic infection by this agent.In the next study, we evaluated the effects of innate immunity genes CD14 -260 C>T, TLR2 Arg753Gln, TLR4 Asp299Gly, LBP Phe436Leu and IL-6 -174 G>C polymorphisms on C. pneumoniae growth in human macrophages in vitro. The growth of C. pneumoniae was highest in CD14 -260 C>T TT genotype cells and the difference to CC or CT genotype was statistically significant. The G-allele of the IL6 -174 G>C polymorphism had a positive influence on chlamydial growth; the difference was statistically significant only between CC and GC genotypes. TLR2 Arg753Gln, TLR4 Asp299Gly, LBP Phe436Leu polymorphisms showed no effect on chlamydial growth.Academic dissertation to be presented with the assent of the Faculty of Medicine of the University of Oulu for public defence in the Auditorium of Kastelli Research Centre (Aapistie 1), on 28 May 2010, at 12 noonAbstract
Chlamydia pneumoniae is an obligate intracellular gram-negative bacterium, which causes respiratory infections in humans and may participate in the development of chronic diseases like atherosclerosis, chronic obstructive lung disease, adult-onset asthma and late-onset Alzheimer’s disease. It can infect various cell types, e.g. vascular endothelial cells, smooth muscle cells and monocyte-derived macrophages in vitro. It has been speculated that circulating macrophages disseminate the infection in the body, and that genetically susceptible individuals become chronically infected.
Quantification of C. pneumoniae growth inside cultured cells is needed when studying e.g. the effect of drugs or host cell factors on infectivity and replication. Conventionally this has been done by immunofluorescence staining and microscopic counting of chlamydial inclusions. However, this method is usable only if the cell numbers do not fluctuate in cell culture vials and the inclusions are uniform. In macrophages, inclusions are often aberrant, their sizes vary and multiple inclusions are also seen. Therefore we developed a new method based on the real-time PCR quantification of chlamydial genomes adjusted to the number of human genomes and used it to quantify the exact amounts of C. pneumoniae in infected cells.
The susceptibility of monocyte-macrophages from healthy individuals to C. pneumoniae infection in vitro was studied first. Intracellular growth of C. pneumoniae was used as an indicator of susceptibility to infection, and it was compared to serum levels of CRP, soluble CD14, human HSP-IgG, human HSP-IgA, C. pneumoniae IgG and IgA antibodies. The growth of C. pneumoniae in infected macrophages was highly variable, ranging from 0 to 638 chlamydial genomes per human genome. C. pneumoniae growth associated positively with serum C. pneumoniae IgA (titer ≥10) and hHSP-IgG and negatively with soluble CD14 concentration. The association between chlamydial IgA antibodies, hHSP-IgG and C. pneumoniae growth was statistically significant only among men. Age did not correlate with the growth. Therefore we hypothesize that persons whose macrophages cannot restrict the growth of C. pneumoniae are more prone to chronic infection by this agent.
In the next study, we evaluated the effects of innate immunity genes CD14 -260 C>T, TLR2 Arg753Gln, TLR4 Asp299Gly, LBP Phe436Leu and IL-6 -174 G>C polymorphisms on C. pneumoniae growth in human macrophages in vitro. The growth of C. pneumoniae was highest in CD14 -260 C>T TT genotype cells and the difference to CC or CT genotype was statistically significant. The G-allele of the IL6 -174 G>C polymorphism had a positive influence on chlamydial growth; the difference was statistically significant only between CC and GC genotypes. TLR2 Arg753Gln, TLR4 Asp299Gly, LBP Phe436Leu polymorphisms showed no effect on chlamydial growth
Persistent <em>Chlamydia pneumoniae</em> infection, inflammation and innate immunity
No full textAbstractChlamydia pneumoniae is an obligatory intracellular pathogen that causes upper and lower respiratory tract infections. Like other Chlamydial species, also C. pneumoniae has a tendency to cause persistent infections, which have been associated with different cardiovascular, neurological, and respiratory diseases. In addition, a few studies have reported an association between C. pneumoniae seropositivity and an elevated body mass index (BMI), and it has been shown that C. pneumoniae is capable of infecting preadipocytes and adipocytes. The main aims of this study were to study if certain gene polymorphisms regulate the serum levels of innate immunity and inflammation proteins, and if the polymorphisms are associated with markers of C. pneumoniae infection; to compare different methods in detection of C pneumoniae in atherosclerotic tissue; and to study if serum levels of chlamydial LPS (cLPS) are associated with BMI. The serum levels of inflammatory and innate immunity markers, namely interleukin 6 (IL-6), C-reactive protein (CRP), LPS-binding protein (LBP), and soluble CD14, in apparently healthy individuals were found to correlate with each other and possibly be regulated by the polymorphisms of genes important in inflammation and innate immunity. Especially the serum LBP levels may be regulated by the LBP (rs2232618) and toll-like receptor 4 (rs4986790) polymorphisms. The IL-6 (rs1800795) polymorphism was found to be associated with C. pneumoniae antibody positivity. C. pneumoniae DNA and cLPS could be found from atherosclerotic tissue. A new, cLPS enzyme immunoassay method was developed in this study, and it might provide a standardized, commercial method for the detection of chlamydia in tissue samples, if the sensitivity of the method could be increased e.g. by testing multiple pieces of tissue. In situ hybridization method was found to be complicated by technical problems and the repeatability of polymerase chain reaction was poor. C. pneumoniae IgG positivity and elevated serum cLPS and CRP levels were associated with an elevated BMI. There was also a strong association between cLPS levels and inflammation as measured by CRP levels. The lack of association between serum total endotoxin activity and BMI implies that the association between infection and an elevated BMI may be specific to certain pathogens. Academic dissertation to be presented, with the assent of the Faculty of Medicine of the University of Oulu, for public defence in the Auditorium of Kastelli Research Centre (Aapistie 1), on January 9th, 2009, at 12 noonAbstract
Chlamydia pneumoniae is an obligatory intracellular pathogen that causes upper and lower respiratory tract infections. Like other Chlamydial species, also C. pneumoniae has a tendency to cause persistent infections, which have been associated with different cardiovascular, neurological, and respiratory diseases. In addition, a few studies have reported an association between C. pneumoniae seropositivity and an elevated body mass index (BMI), and it has been shown that C. pneumoniae is capable of infecting preadipocytes and adipocytes. The main aims of this study were to study if certain gene polymorphisms regulate the serum levels of innate immunity and inflammation proteins, and if the polymorphisms are associated with markers of C. pneumoniae infection; to compare different methods in detection of C pneumoniae in atherosclerotic tissue; and to study if serum levels of chlamydial LPS (cLPS) are associated with BMI.
The serum levels of inflammatory and innate immunity markers, namely interleukin 6 (IL-6), C-reactive protein (CRP), LPS-binding protein (LBP), and soluble CD14, in apparently healthy individuals were found to correlate with each other and possibly be regulated by the polymorphisms of genes important in inflammation and innate immunity. Especially the serum LBP levels may be regulated by the LBP (rs2232618) and toll-like receptor 4 (rs4986790) polymorphisms. The IL-6 (rs1800795) polymorphism was found to be associated with C. pneumoniae antibody positivity.
C. pneumoniae DNA and cLPS could be found from atherosclerotic tissue. A new, cLPS enzyme immunoassay method was developed in this study, and it might provide a standardized, commercial method for the detection of chlamydia in tissue samples, if the sensitivity of the method could be increased e.g. by testing multiple pieces of tissue. In situ hybridization method was found to be complicated by technical problems and the repeatability of polymerase chain reaction was poor.
C. pneumoniae IgG positivity and elevated serum cLPS and CRP levels were associated with an elevated BMI. There was also a strong association between cLPS levels and inflammation as measured by CRP levels. The lack of association between serum total endotoxin activity and BMI implies that the association between infection and an elevated BMI may be specific to certain pathogens
Genetic and immunological risk factors and carotid artery atherosclerosis
Get PDFAbstractAtherosclerosis is a multifactorial disease with numerous genes and environmental factors affecting its intiation and progression. During the past years many candidate genes for atherosclerosis have been suggested, and it has also become evident that the immune system plays a part in atherogenesis. Early atherosclerotic changes can be effectively detected by measuring carotid artery intima-media thickness (IMT). In the present study the associations between IMT and polymorphisms of three candidate genes for atherosclerosis were studied: endothelial nitric oxide synthase (eNOS), apolipoprotein E (apoE) and paraoxonase-1 (PON1). To assess the role of immunological factors determining carotid atherosclerosis, CRP and circulating autoantibodies to oxidised LDL were studied in relation to IMT. The study population consisted of 519 hypertensive and 526 control subjects from a middle-aged population in Oulu, Finland. The results showed that the investigated polymorphisms of eNOS and PON1 genes were not associated with IMT, suggesting that these polymorphisms are not major risk factors for atherosclerosis in the general Caucasian population. A significant interaction between the apoE polymorphism and smoking in relation to IMT was observed among men, indicating that carriers of the ε4 allele may be particularly prone to the atherogenic effects of smoking. This interaction was especially clear in hypertensive subjects. CRP was strongly associated with IMT before adjusting for confounding factors. After the adjustment, this association diasppeared. The finding suggests that instead of early atherosclerosis CRP may be related to the later phases of the disease. This may partly explain the strong correlation between CRP and future cardiovascular events. IgM type of autoantibodies binding to oxidised LDL were inversely associated with IMT, and this finding remained after adjusting for previously known risk factors for atherosclerosis, implying a possible protective role for these antibodies in atherogenesis.Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in the Auditorium 10 of Oulu University Hospital, on January 23rd, 2004, at 12 noon.Abstract
Atherosclerosis is a multifactorial disease with numerous genes and environmental factors affecting its intiation and progression. During the past years many candidate genes for atherosclerosis have been suggested, and it has also become evident that the immune system plays a part in atherogenesis. Early atherosclerotic changes can be effectively detected by measuring carotid artery intima-media thickness (IMT). In the present study the associations between IMT and polymorphisms of three candidate genes for atherosclerosis were studied: endothelial nitric oxide synthase (eNOS), apolipoprotein E (apoE) and paraoxonase-1 (PON1). To assess the role of immunological factors determining carotid atherosclerosis, CRP and circulating autoantibodies to oxidised LDL were studied in relation to IMT. The study population consisted of 519 hypertensive and 526 control subjects from a middle-aged population in Oulu, Finland. The results showed that the investigated polymorphisms of eNOS and PON1 genes were not associated with IMT, suggesting that these polymorphisms are not major risk factors for atherosclerosis in the general Caucasian population. A significant interaction between the apoE polymorphism and smoking in relation to IMT was observed among men, indicating that carriers of the ε4 allele may be particularly prone to the atherogenic effects of smoking. This interaction was especially clear in hypertensive subjects. CRP was strongly associated with IMT before adjusting for confounding factors. After the adjustment, this association diasppeared. The finding suggests that instead of early atherosclerosis CRP may be related to the later phases of the disease. This may partly explain the strong correlation between CRP and future cardiovascular events. IgM type of autoantibodies binding to oxidised LDL were inversely associated with IMT, and this finding remained after adjusting for previously known risk factors for atherosclerosis, implying a possible protective role for these antibodies in atherogenesis
Työterveyshuollon yhteistyö psykiatrin kanssa: käytäntöä ja kehittämistavoitteita 5.11.2008 Tampere
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Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
The gene variant for desmin rs1058261 may protect against combined cancer and cardiovascular death, the Tampere adult population cardiovascular risk study
No full textDesmin-containing intermediate filaments are a part of muscle cytoskeleton. We have previously reported that the wild-type cytosine/cytosine genotype of a common Desmin synonymous single nucleotide polymorphism (C > T) (rs1058261) associated with cardiovascular diseases in a cohort of subjects from the Tampere adult population cardiovascular risk study. We now examined whether rs1058261 also associates with early death by following the cohort of 801 subjects from the age of 50 up to the age of 65. Outcomes for death were collected from the National Statistics Centre. Linkage disequilibrium analysis and gene expression correlations for rs1058261 were done in silico. With follow-up, subjects with wild-type cytosine/cytosine genotype had higher incidence of cancer deaths (odds ratio [OR] 5.27, confidence interval [CI] 1.160–23.946, P = .031), combined deaths from cardiovascular diseases or cancers (OR 3.92, CI 1.453–10.596, P = .007), and “hard” acute cardiovascular disease events (early myocardial infarction and/or death) (OR 3.90, CI 1.287–11.855, P = .016) compared to subjects with the T-allele. The in silico results of linkage disequilibrium and gene expression analyses showed negative gene expression sizes associated with rs1058261, which theoretically decreases desmin expression. Our findings suggest that variation rs1058261 in Desmin may serve as a surrogate marker for other variations involved in decrease of deaths from combined cancer and cardiovascular disease
Association of the Collagen Type IV Alpha 1 Chain Gene rs3783107 GG Genotype with Hypertension, Asthma, and Eczema: The Tampere Adult Population Cardiovascular Risk Study
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