Biomedical subjects

Maija Leinonen

Publications and source records attributed to Maija Leinonen.

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

The association between C-reactive protein levels and depression: Results from the northern Finland 1966 birth cohort study.

BACKGROUND: To investigate whether depressive episodes (previous, current single, and recurrent) are associated in both genders with highly sensitive C-reactive protein (hs-CRP) levels, earlier recommended for risk assessment of cardiovascular disease. The impact of the severity of current single and recurrent depressive episodes on this putative association was also investigated. METHODS: The genetically homogeneous Northern Finland 1966 Birth Cohort was followed until age 31, when, in a cross-sectional setting (n = 5269), the highly sensitive enzyme immunoassay (hs-EIA) method was used to measure CRP concentration. Depressive episodes were defined through mailed questionnaires, including Hopkins Symptom Checklist-25 (HSCL-25) and information on self-reported, doctor-diagnosed depression. RESULTS: After adjusting for confounders, logistic regression analyses showed that in male subjects, elevated hs-CRP levels (> or =1.0 mg/L) increased the probability for severe current and recurrent depressive episodes 1.7-fold and 3.1-fold, respectively. Correspondingly, an hs-CRP level of >3.0 mg/L increased the probability for recurrent depression up to 4.1-fold. In female subjects, no statistically significant associations were found. CONCLUSIONS: Our results support the hypothesis that an activation of systemic inflammatory processes may contribute to the pathophysiology of severe depression in men. Further investigations are needed regarding the impact of our findings on diagnostic/treatment strategies concerning severe and, especially recurrent, depression in men.

Adult↗

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

Nasal middle meatal specimen bacteriology as a predictor of the course of acute respiratory infection in children.

AIMS: To test our hypothesis that children with potentially pathogenic bacteria (Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis) in the nasal middle meatus might have more prolonged symptoms of acute respiratory infection than children without such bacteria, we conducted a prospective cohort study of such children. MATERIALS AND METHODS: We recruited prospectively child volunteers between 6 and 13 years of age with acute respiratory infections present for fewer than 10 days. Nasal middle meatal bacterial culture was taken with a rigid endoscope at enrollment and again after 3 weeks and evaluated for presence or absence of 3 potential pathogens: S. pneumoniae, H. influenzae and M. catarrhalis. The subsequent persistence of acute symptoms (nasal discharge: clear/colored, nasal obstruction and cough) was determined by means of a diary. Viral etiology was studied with polymerase chain reaction methods. RESULTS: The 82 children had had symptoms for an average of 4 days (range, 1-10) at entry, and viruses were detected in 54% (39 of 72). The endoscopic procedure and bacteriologic sampling succeeded in all cases. Thirty-eight children (46%) had at least 1 of the 3 pathogens in the middle meatus specimen. The children with nasal pathogens present at entry had a significantly longer mean duration of symptoms than those with nonpathogenic bacteria (difference, 3.6 days; 95% confidence interval, 0.7-6.5; P = 0.025). The effect remained significant after adjustment for age, sex, allergic symptoms and the presence of virus (adjusted relative hazard of delayed recovery, 2.0; 95% confidence interval, 1.1-3.6). CONCLUSIONS: We found that the use of endoscopic swab culture sampling from the nasal middle meatus is well-tolerated by children older than 6 years of age and that it can be useful in selected situations to determine pathogenic bacteria in the culture of these specimens.

Acute Disease↗

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

Presence of viral and bacterial pathogens in the nasopharynx of otitis-prone children. A prospective study.

OBJECTIVE: The purpose of the present study was to examine and follow up the presence of respiratory viral and bacterial pathogens in the nasopharynx of otitis-prone children during the cold season and compare the findings with the child's respiratory symptoms. METHODS: We enrolled 121 otitis-prone children, aged 10 months to 4 years for a prospective study. The nasopharyngeal swab (NPS) were studied at the baseline and after 12 and 24 weeks for respiratory viruses and at the baseline and after 24 weeks for bacteria. Presence of picorna(rhino-entero-parecho)-, influenza-, adenoviruses and Mycoplasma pneumoniae was detected by PCR. NPS specimens were cultured for Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Clinical data (the rate of respiratory symptom days, otitis media, tympanometry findings, day-care attendance and the number of siblings) were compared with microbiological data. RESULTS: Rhinovirus was found in 30% of the samples at the baseline, in 8% and in 19% of the samples after 12 and 24 weeks, respectively. Enterovirus was detected in 19% of the samples, in 21% and in 12% of samples after 12 and 24 weeks, respectively. Picornavirus positivity correlated with the respiratory symptoms but not with the number of otitis media or with abnormal tympanometry. Two samples were adeno- and three samples influenzavirus positive. Parechovirus and M. pneumoniae were negative in all samples. Rhinovirus positivity correlated with that of M. catarrhalis and S. pneumonia but not with H. influenzae. Microbiological positivity was not significantly associated with the type of day-care. CONCLUSIONS: Picornaviruses as well as bacteria were commonly found in the nasopharynx of otitis-prone children during the cold season, even in the absence of clinical symptoms.

Bacteria↗

PubMed2005

Real-time pneumolysin polymerase chain reaction with melting curve analysis differentiates pneumococcus from other alpha-hemolytic streptococci.

The majority of pneumococcal isolates can be identified by the conventional methods based on phenotypic characteristics. Occasionally, however, the differentiation of alpha-hemolytic streptococci from pneumococci, especially those isolated from nasopharynx, is problematic due to the discrepant results obtained by the conventional identification methods. Several gene technological methods based on the amplification of genes encoding pneumococcal virulence factors, such as pneumolysin (ply) and autolysin, have been used as additional identification methods. Recent studies have shown that especially the ply gene is frequently also present in nonpneumococcal alpha-hemolytic streptococci. In this study, we compared the commonly used phenotypic identification methods with nucleic acid-based methods, commercial AccuProbetrade mark, conventional pneumolysin polymerase chain reaction (Ply-PCR), and real-time Ply-PCR in the identification of alpha-hemolytic streptococcal strains isolated from 100 consecutive nasopharyngeal specimens. We also studied if melting curve analysis and sequencing of the amplification products of a ply gene fragment could be helpful in the identification. Our results suggest that the ply gene present in alpha-hemolytic streptococci differs from that present in pneumococcus, and that melting curve analysis would prove useful in the differentiation of these bacteria.

Bacterial Proteins↗

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

Aetiology of community-acquired pneumonia: serological results of a paediatric survey.

Serological methods are routinely used in the diagnosis of viral and atypical bacterial respiratory infections. Recently, they have also been applied to typical bacteria, such as Streptococcus pneumoniae. The aim of this study was to determine the aetiology of paediatric community-acquired pneumonia (CAP) in both ambulatory and hospitalized patients, by using antibody assays. During a 15-month prospective surveillance, paired sera were studied for antibodies to 14 microbes in 101 children with symptoms of acute infection and infiltrates compatible with pneumonia on chest radiographs. A potential causative agent was detected in 66 (65%) patients. Evidence of bacterial, viral and mixed viral-bacterial infection was demonstrated in 44%, 42% and 20% of the CAP cases, respectively. The most commonly found agents included Mycoplasma pneumoniae (27%), Pneumococcus (18%) and respiratory syncytial virus (17%). Human metapneumovirus (hMPV) was detected in 5 (5%) children. Pneumococcal infections were evenly distributed among the age groups studied. Our results confirm the role of S. pneumoniae in paediatric CAP at all ages, those of M. pneumoniae at >2 y of age and emphasize the emerging role of hMPV. The high proportion of mixed viral-bacterial infections highlights the need to treat all children with CAP with antibiotics.

Child↗

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

Invasiveness of serotypes and clones of Streptococcus pneumoniae among children in Finland.

Streptococcus pneumoniae (the pneumococcus) causes diseases from otitis media to life-threatening invasive infection. The species is extremely antigenically and clonally diverse. We wished to determine odds ratios (ORs) for serotypes and clones of S. pneumoniae that cause invasive disease in Finland. A total of 224 isolates of S. pneumoniae from cases of invasive disease in children <2 years of age in Finland between 1995 and 1999 were serotyped, and sequence types (STs) were determined by multilocus sequence typing. These STs were compared with a previously published carriage data set. STs from invasive disease were significantly less diverse than those from carriage (invasive disease, 0.038 +/- 0.01; carriage, 0.019 +/- 0.005). The ORs of serotypes 14, 18C, 19A, and 6B were significantly greater than 1, indicating association with invasive disease. The ORs of 6A and 11A were significantly less than 1. The difference between 6A and 6B is significant, which suggests that relatively subtle changes in the capsule may have a dramatic effect upon disease potential. We found that ST 156, the Spain(9V)-3 clone which mainly expressed serotype 14 in Finland, is strongly associated with invasive disease (OR, 10.1; 95% confidence interval, 1.3 to 79.5). Significant associations with invasive disease were also detected for STs 482, 191, 124, and 138, and associations with carriage were detected for STs 485 and 62. These results demonstrate the invasive phenotype of the serotype 14 variant of the Spain(9V)-3 clone and differences between members of the same serogroup in invasive disease potential.

Carrier State↗