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Biomedical subjects

Pekka Saikku

Publications and source records attributed to Pekka Saikku.

At least 19 recordsLinked to original sources
PubMed2007

Risk of cervical cancer associated with Chlamydia trachomatis antibodies by histology, HPV type and HPV cofactors.

Human papillomavirus (HPV) is the central etiologic factor for cervical cancer, and prior studies suggested C. trachomatis may act as an HPV cofactor. We examined the C. trachomatis-cervical cancer association by serotype, histology, HPV type in the tumor, and other HPV cofactors. We conducted a population-based study in the Seattle-Puget Sound area of 302 women with invasive squamous cell carcinomas (SCC), 185 women with adenocarcinomas of the cervix (AC), and 318 HPV seropositive control women. The risk of SCC associated with antibodies to C. trachomatis was increased (OR 1.6, 95% CI 1.1-2.2) but not for AC (OR 1.0, 95% CI 0.6-1.5). This association was independent of HPV type in the SCC tumor tissue. There was an association between specific serotypes of C. trachomatis and SCC for 6 of the 10 serotypes: B (OR 3.6, 95% CI 1.5-8.4), D (OR 2.1, 95% CI, 1.2-3.5), E (OR 2.4, 95% CI, 1.4-3.9), G (OR 3.0, 95% CI, 1.1-7.9), I (OR 4.2, 95% CI, 1.5-11.7), and J (OR 2.3, 95% CI, 1.0-5.1), but not for the 4 types (C, F, H, and K) that were present at very low prevalence in this population. There was an increased risk of SCC, but not AC, associated with antibodies to C. trachomatis that was not serotype specific.

Adenocarcinoma↗
PubMed2006

Rapid genotyping of lipopolysaccharide-binding protein (LBP) C(1341)-->T (Leu(436)-->Phe) polymorphism by LightCycler real-time PCR.

Lipopolysaccharide (LPS) is an exdotoxin found in the outer membrane of gram-negative bacteria. In circulation, LPS is bound by LPS-binding protein (LBP), which participates in cell activation by transferring LPS to CD14 and Toll-like receptor 4. A high LPS concentration may give rise to an exaggerated immune response, which may lead to septic shock during septicemia. However, LBP also neutralizes and removes LPS by transferring it to plasma lipoproteins. Recently, the presence of an amino acid-changing polymorphism in the LBP gene was reported, which, in men, was associated with sepsis and its severity and with myocardial infarction. Here, we describe a new LightCycler real-time PCR method for genotyping this LBP C(1341)-->T (Leu(436)-->Phe) polymorphism. In our study population of 393 Finnish blood donors, the genotype frequencies were: 86% TT, 13% CT and 1% CC.

Acute-Phase Proteins↗
PubMed2006

Chlamydial lipopolysaccharide is present in serum during acute coronary syndrome and correlates with CRP levels.

Infections, Chlamydia pneumoniae as a major candidate, have been suggested to participate in inflammatory processes ultimately leading to atherosclerosis. In the present study we measured serum levels of chlamydial lipopolysaccharide (cLPS) and highly sensitive C-reactive protein (hsCRP) in the acute coronary syndrome (ACS) patients (n=145). During ACS, both cLPS and hsCRP were elevated and significant correlation (P=0.003, r=0.25) between them was observed. Both cLPS and hsCRP levels decreased after the event and correlation remained significant during the follow-up period. Our results suggest that cLPS is liberated from the damaged tissue persistently infected with C. pneumoniae during the ACS event. The significant correlation between cLPS and hsCRP levels further point to the possibility that both levels reflect the magnitude of tissue damage.

Acute Coronary Syndrome↗
PubMed2006

Chlamydia pneumoniae antibody levels before coronary events in the Helsinki Heart Study as measured by different methods.

The lack of specific tests for the diagnosis of chronic Chlamydia pneumoniae infection has led to the use of enzyme immunoassay (EIA) instead of the gold standard, that is, microimmunofluorescence (MIF), in the measurement of C. pneumoniae antibodies. We assessed the predictive values of C. pneumoniae antibody levels and seroconversions measured by MIF and EIA for coronary events in the prospective Helsinki Heart Study. Sera from 239 cases with coronary events and 239 controls were available at the baseline and data from 210 cases and 211 controls before and after the event. The agreement between MIF and EIA antibody levels was best in high antibody titers. In conditional logistic regression analysis, only high IgA MIF titers (>/=40) at the baseline predicted future coronary events, and the participants with MIF seroconversion between consecutive sera had a higher (nonsignificant) risk for coronary events than the controls. The difference in the kinetics of EIA and MIF antibodies demonstrated that MIF should remain the gold standard.

Antibodies, Bacterial↗
PubMed2006

Inhibitory effect of heparan sulfate-like glycosaminoglycans on the infectivity of Chlamydia pneumoniae in HL cells varies between strains.

Glycosaminoglycans are known to participate in the attachment of several chlamydial strains. We studied the effect of heparin, enoxaparin, low-molecular-weight heparin, chondroitin sulfate A, and heparinase I on the infectivity of Chlamydia pneumoniae strain CWL029 and two Finnish isolates, Kajaani 7 and Parola, in an HL cell line which is epithelial in origin. Two Chlamydia trachomatis strains, L2 and E, were used for comparison. The infectivity of all C. pneumoniae strains and C. trachomatis serovar E was inhibited not only by heparin derivatives but also by chondroitin sulfate A and heparinase treatment. Treatment of host cells with heparin derivatives and heparinase was also inhibitory. Different chlamydial strains and species seem, however, to vary in their ability to use heparin in their attachment to host cells.

Animals↗
PubMed2006

Increased prostanoid dependency of arterial relaxation in Chlamydia pneumoniae-infected mice.

Endothelial dysfunction plays an important role in the development of atherosclerosis. Previous studies have shown that inoculation with Chlamydia pneumoniae contributes to atherosclerotic development in rabbits and hypercholesterolaemic mice and causes endothelial dysfunction in apolipoprotein E-deficient mice. The effect of acute C. pneumoniae infection on endothelial function in normocholesterolaemic C57BL/6J mice was studied by measuring the force of contraction of the descending aorta after noradrenaline stimulation and in response to methacholine-induced relaxation. In addition, the effects of the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) and the cyclooxygenase inhibitor diclofenac on relaxation were assessed. Pre-treatment of the aortas with L-NAME decreased the relaxation response in both the infected and uninfected groups and no significant difference was detected between these groups, whereas diclofenac significantly attenuated the relaxation response only in the infected animals. In conclusion, infection shifted the balance of endothelium-derived relaxing factors from nitric oxide towards vasorelaxing prostanoids in C57BL/6J mice.

Animals↗
PubMed2005

Novel enzyme immunoassay utilizing lipopolysaccharide-binding protein as a capture molecule for the measurement of chlamydial lipopolysaccharide in serum.

Chlamydia pneumoniae causes respiratory tract infections. It has a tendency to cause persistent infections, which have been associated with several chronic diseases (e.g., atherosclerosis). At present, there is no reliable method for the diagnosis of chronic C. pneumoniae infection. We developed a novel enzyme immunoassay (EIA) for the quantification of chlamydial lipopolysaccharide (cLPS) in human serum. Serum cLPS was solubilized with detergent and then captured by LPS-binding protein (LBP). LBP-LPS complexes were bound to the solid phase with anti-cLPS monoclonal antibody, and the bound complexes were detected with anti-LBP antibodies. The new method was used to quantify serum cLPS in acute coronary syndrome (ACS) patients (n = 102) and their healthy controls. cLPS was detected in 77.5% of ACS patients and in 52% of controls (P < .001) with geometric mean concentrations of 1.87 and 0.61 microg/mL (P < .001), respectively. The novel cLPS EIA method will provide a potential diagnostic tool for C. pneumoniae infection.

Acute-Phase Proteins↗
PubMed2005

In vivo treatment of acute Chlamydia pneumoniae infection with the flavonoids quercetin and luteolin and an alkyl gallate, octyl gallate, in a mouse model.

Increasing evidence suggests that plant polyphenolic compounds may protect from cardiovascular diseases, which have been addressed to their antioxidative properties. In addition, these compounds have been shown to possess anti-inflammatory and anti-microbial potential. In the present study we tested the effects of two flavonoid compounds, quercetin and luteolin, and one alkyl gallate, octyl gallate, on the course of acute Chlamydia pneumoniae infection in vivo. C57BL/6J mice were treated with quercetin, luteolin or octyl gallate for 3 days prior to and 10 days after C. pneumoniae inoculation. Lung tissue was analysed for the presence of chlamydia by culture and quantitative PCR, and inflammatory responses were assessed. Luteolin was found histologically to suppress inflammation in lung tissue, the development of C. pneumoniae-specific antibodies and the presence of chlamydia in lung tissue. Octyl gallate had no significant effect on the course of infection, but quercetin increased both the inflammatory responses and the chlamydial load in the lungs. The infection and inflammation-enhancing effects of quercetin treatment may be attributable to the dose and the route of administration and should be reassessed in further studies with lower doses or with different metabolites of the compound. Contrariwise, the effects of luteolin treatment suggest this compound to have potential in decreasing the infection load and inflammatory reactions in vivo.

Animals↗
PubMed2005

Methodological aspects affecting the infectivity of Chlamydia pneumoniae in cell cultures in vitro.

The effect of culture medium, washing, temperature, and sonication on the infectivity of Chlamydia pneumoniae for HL cells in experiments with heparin or heparinase treatment was studied. The presence of fetal calf serum (FCS) was necessary, and simple washing of elementary bodies increased their infectivity titer. Prolonged sonication was detrimental. Detailed description of the experimental conditions is necessary in studies of chlamydial attachment and infectivity.

Bacteriological Techniques↗
PubMed2005

Serum C-reactive protein and Chlamydia trachomatis antibodies in preterm delivery.

OBJECTIVE: To assess the association between Chlamydia trachomatis antibodies, antibodies to C trachomatis heat shock proteins 60 and 10, and C-reactive protein (CRP) levels in maternal serum measured by highly sensitive CRP assay during the first trimester and spontaneous preterm delivery before 37 weeks of gestation. METHODS: This was a nested case-control study of 104 spontaneous preterm singleton deliveries (cases) and 402 term singleton deliveries, as controls, of mothers belonging to the population-based Northern Finland 1966 Birth Cohort. Data on 2,309 first deliveries were available from the Finnish Medical Birth Register. Serum C trachomatis and C pneumoniae antibodies were measured by the microimmunofluorescence test and chlamydial heat shock proteins 60 and 10 antibodies by enzyme immunoassay using recombinant proteins as antigens, and highly sensitive CRP levels were quantified with highly sensitive immunoenzymometric assay. RESULTS: Highly sensitive CRP levels were higher and C trachomatis immunoglobulin G levels (pools and individual serotypes) were more often present (thought not nominally significantly in all cases) in the women with preterm compared with term deliveries. Elevated immunoglobulin G levels of C trachomatis antibodies or elevated highly sensitive CRP levels alone, however, did not increase the estimated risk for preterm delivery, but when they were present simultaneously, the estimated risk for preterm delivery was 4-fold (odds ratio 4.3, 95% confidence interval 2.0-9.3). Among the women delivered at or before 34 weeks of gestation, the estimated risk was even more evident (odds ratio 5.6, 95% confidence interval 2.1-14.5). The preterm delivery rate was 26.5% for those with C trachomatis antibodies and 18.8% for those without C trachomatis antibodies. CONCLUSION: The results of the present study suggest that chlamydial infection in the first trimester is associated with preterm delivery. LEVEL OF EVIDENCE: II-2.

Adult↗
PubMed2005

Effect of simvastatin, an established lipid-lowering drug, on pulmonary Chlamydia pneumoniae infection in mice.

The effects of simvastatin treatment on Chlamydia pneumoniae lung infection, inflammation, and serum lipids in mouse model were studied. Simvastatin decreased viable chlamydial counts and increased inflammatory cell infiltrates in the lung tissue, suggesting that simvastatin treatment had both antichlamydial and immunomodulatory effects during an acute C. pneumoniae infection.

Animals↗
PubMed2005

Prevalence and persistence of Chlamydia pneumoniae antibodies in healthy laboratory personnel in Finland.

The rates of Chlamydia pneumoniae seroconversions suggesting acute primary infections or reinfections and the prevalences of antibodies were followed up among healthy laboratory workers. Annual serum samples were collected from 47 persons in Helsinki from 1958 to 1990 and from 40 persons in Oulu from 1994 to 1999. C. pneumoniae species-specific immunoglobulin G (IgG), IgA, and IgM antibodies were measured by microimmunofluorescence (MIF) in 407 sera from Helsinki. The 185 sera collected in Oulu were tested both by MIF and by commercial enzyme immunoassay (EIA). During the follow-up periods of 31 years in Helsinki and 6 years in Oulu, seroconversions were demonstrated by MIF in 45% and 15% of the study groups, respectively. In Helsinki 9% of the persons seroconverted twice during the follow-up period. By MIF, the total incidence rate per 100 person-years at risk was 6.9 in Helsinki and 4.9 in Oulu, and annual incidence rates varied from 0 to 15.4. By EIA, annual incidence rates in Oulu varied from 0 to 10.8. The seroconversions by MIF were usually not confirmed by EIA and vice versa. Prevalence and persistence rates, respectively, of IgA antibodies were higher in EIA (62% and 26%) than in MIF (26% and 17%), whereas the figures for IgG were quite similar. The prevalence of IgG and IgA antibodies was higher in older persons than in younger ones. The presence of antibodies did not offer protection from reinfection.

Adult↗
PubMed2005

Effects of repeated Chlamydia pneumoniae inoculations on aortic lipid accumulation and inflammatory response in C57BL/6J mice.

Chlamydia pneumoniae is a common respiratory tract pathogen, and persistent infections have been associated with atherosclerosis. We studied the effects of repeated chlamydial inoculations on the inflammatory response and on aortic lipid accumulation in C57BL/6J mice. Mice fed a diet supplemented with 0.2% cholesterol were infected three or six times with C. pneumoniae every fourth week. Sera and lungs were analyzed for inflammatory responses, lung tissues were tested for the presence of C. pneumoniae DNA and RNA, and intimal lipid accumulation in the aortic sinus was quantified. High levels of chlamydial heat shock protein 60 (Hsp60) immunoglobulin G2c subclass antibodies were detected in all of the infected mice, and a positive and statistically significant correlation was found between these antibodies and autoantibodies against mouse Hsp60. Both Hsp60 antibody levels correlated with the severity of lung tissue inflammation. The cholesterol supplement in the diet had no effect on serum cholesterol levels. Significantly larger intimal lipid lesions were seen in the mouse group infected six times (6,542 mum(2)) than in the control group (1,376 mum(2); P = 0.034). In conclusion, repeated inoculations increased aortic sinus lipid accumulation in normocholesterolemic mice. The correlation between the antibodies to mouse and chlamydial Hsp60 proteins and their association with lung inflammation further support the theory of the development of an autoimmune response against heat shock proteins after repeated chlamydial infections.

Animals↗
PubMed2005

Chlamydial antibodies and risk of prostate cancer.

OBJECTIVE: We assessed the risk of prostate cancer by exposure to Chlamydia trachomatis. METHOD: Seven hundred thirty eight cases of prostate cancer and 2,271 matched controls were identified from three serum sample banks in Finland, Norway, and Sweden by linkage to the population based cancer registries. RESULTS: A statistically significant inverse association (odds ratio, 0.69; 95% confidence interval, 0.51-0.94) was found. It was consistent by different serotypes and there was a consistent dose-response relationship. CONCLUSION: C. trachomatis infection is not likely to increase the risk of prostate cancer. Whether the inverse relationship is true or due to difficulties in measuring the true exposure in prostatic tissue by serology, confounders or other sources of error remain open.

Adult↗
PubMed2004

Telithromycin treatment of chronic Chlamydia pneumoniae infection in C57BL/6J mice.

Chronic Chlamydia pneumoniae infections have been associated with atherosclerosis, but clear knowledge about how these infections should be treated is lacking. We studied the effect of a new ketolide antibiotic, telithromycin, on chronic C. pneumoniae lung infection. Female C57BL/6J mice on a 0.2% cholesterol diet were inoculated intranasally with C. pneumoniae either two or three times every fourth week. Telithromycin was given to the mice subcutaneously at 75 mg/kg of body weight once daily for 5 or 10 days, starting at 3 days after the last inoculation. Samples were taken at 4 and 12 weeks after the last inoculation. The presence of C. pneumoniae DNA in lung tissue was demonstrated by PCR and the detection of lipid accumulation in the aortic sinus by Oil-Red-O staining. C. pneumoniae DNA positivity and inflammatory reactions in the lung tissue of the mice inoculated twice were significantly affected by treatment after both inoculations or only after the second inoculation at 12 weeks. Intimal lipid accumulation in the aortic sinus was also slightly but significantly less abundant in the mice treated after both inoculations compared to the levels in those treated only after the second inoculation for 10 days (geometric means, 823 and 4,324 microm(2), respectively; P = 0.033). No differences between the infected, untreated controls and the group inoculated three times and treated for 5 days were seen. We conclude that telithromycin is effective in preventing the development of chronic C. pneumoniae infection and intimal lipid accumulation in C56BL/6J mice when the treatment is given after each inoculation.

Animals↗