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Biomedical subjects

M Leinonen

Publications and source records attributed to M Leinonen.

At least 109 records · Page 6Linked to original sources

Influence of age, gender and smoking on Streptococcus pneumoniae, Haemophilus influenzae and Moraxella (Branhamella) catarrhalis antibody titres in an elderly population.

The purpose of this study was to investigate the association of serum antibody levels to Streptococcus pneumoniae, Haemophilus influenzae and Moraxella (Branhamella) catarrhalis with age, gender and smoking in an elderly population. The study population comprised all the inhabitants aged 65 years or over in a rural municipality in south-western Finland. Serum samples were obtained from 1,174 out of a total of 1,360 subjects. Bacterial antibodies were measured by enzyme immunoassay (EIA) using pneumolysin and whole bacterial cells of H. influenzae and M. catarrhalis (mixture of 10 different strains for both) as antigens. The main findings were as follows: (i) antibody levels generally decreased with increasing age both in men and in women; (ii) antibody titres against H. influenzae and M. catarrhalis were higher in men than in women; and (iii) antibody titres to H. influenzae and M. catarrhalis, but not to S. pneumoniae, were significantly higher in smokers than in non-smokers. These data suggest that antibody-mediated protection against respiratory pathogens may be impaired in the elderly, leading to a higher susceptibility to respiratory tract infections, that the exposure to H. influenzae and M. catarrhalis may be higher in men than in women, and that smokers have more respiratory infections or colonization due to these 2 bacteria than do non-smokers.

Age Factors↗

Pneumococcal capsular antigen detection after enrichment culture: an alternative to culture methods in epidemiologic research.

Bacterial culture of Streptococcus pneumoniae followed by serotyping is not always feasible under field conditions. Antigen detection methods could be an alternative, but they are associated with sensitivity problems. In an effort to improve their sensitivity, we introduced an enrichment phase before antigen detection and compared the results with direct bacterial culture, using nasopharyngeal swabs from 95 children with symptoms of acute respiratory infection. Antigen detection was performed by latex agglutination and counterimmunoelectrophoresis. Streptococcus pneumoniae was found in 29 (30%) of the samples by culture, and in 42 (44%) by antigen detection after enrichment, an excess of 45% over culture findings. This excess was shown to represent true positive samples since pneumococcal DNA could be detected by polymerase chain reaction in all 15 antigen-positive, culture-negative samples. Two culture-positive samples were antigen-negative; in one of these the bacteria were nonencapsulated. We conclude that for type-specific demonstration of S. pneumoniae, detection of pneumococcal antigen after an enrichment step is a sensitive method that can be applied for epidemiologic study purposes, e.g., in vaccine trials, in areas without ready access to a good microbiology laboratory.

Acute Disease↗

Animal models for Chlamydia pneumoniae infection.

There is accumulating evidence that persistent Chlamydia pneumoniae infections occur in vivo. Animal studies are necessary in order to evaluate the effects of different treatment regimens for eradication of such infections. A mouse model was found to be efficacious for the study of the effects of cortisone and antimicrobial agents on C. pneumoniae infection.

Animals↗

Chlamydia pneumoniae and Helicobacter pylori infections in Sámi and Finnish reindeer herders.

The Sámi people in northernmost Finland have lower mortality from cardiovascular diseases than the main population of Finland. Chronic infections caused by Chlamydia pneumoniae and Helicobacter pylori, both quite recently discovered gram-negative bacteria, have been associated with atherosclerosis. We studied the prevalence of these infections in Sámi and Finnish men by analysing the C. pneumoniae and H. pylori specific serum IgG and IgA antibodies using microimmune fluorescence and enzyme linked immunosorbent assay methods, respectively. The frequency of C. pneumoniae IgG antibodies and the age adjusted geometric mean titres differed significantly between these groups. The Finns were more often sero-positive than the Sámi (76% vs. 67%, respectively), the age adjusted geometric mean titre being 71.6 in the Finns and 38.3 in the Sámi; p = 0.001. No significant difference was found in the H. pylori IgG and IgA antibody prevalences, nor in the geometric mean titres between these groups. The difference in cardiovascular mortality between the Sámi and Finns may be partly explained by the lower incidence of chlamydial infections in the Sámi.

Adult↗

Growth of Chlamydia pneumoniae in cultured human peripheral blood mononuclear cells and induction of a cytokine response.

In vitro infection of freshly isolated human peripheral blood mononuclear cells (HPBMC) with Chlamydia pneumoniae was found to induce a production of tumour necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and interferon alpha (IFN-alpha). The secretion was dependent on the amount of infecting chlamydiae and most of it occurred during the first 12 to 24 h. Lipopolysaccharide (LPS) of Salmonella minnesota Rechemotype, used as a positive control for HPBMC activation, induced a release of TNF-alpha, IL-1 beta and IL-6, but not of IFN-alpha, similar to the effect of C. pneumoniae. Viable chlamydiae could not be recovered from HPBMCs infected immediately after their isolation, whereas HPBMCs which were cultured in vitro for 3 to 9 days before infection were able to maintain the growth of C. pneumoniae. Growth inside HPBMCs as well as induction of cytokine response may have a role in the pathogenesis of C. pneumoniae infection.

Chlamydia Infections↗

Expression of adhesion molecules on endothelial cells stimulated by Chlamydia pneumoniae.

Previous studies have shown that C. pneumoniae is able to infect human endothelial cells in vitro. In this report, the ability of C. pneumoniae to induce the expression of E-selectin or endothelial-leukocyte adhesion molecule 1 (ELAM-1), intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) on human umbilical vein endothelial (HUVE) cell surface was investigated. C. pneumoniae was found to cause a moderate upregulation of the adhesion molecules. Maximal expression of E-selectin was noted at 6 h post infection (p.i.) and that of ICAM-1 and VCAM-1 at 20 h p.i. The capability of C. pneumoniae to grow in endothelial cells and to stimulate the expression of adhesion molecules essential for leukocyte-endothelial cell interactions suggests a role for C. pneumoniae as a local pathogenetic factor in vascular inflammatory alterations, including atherogenesis.

Cells, Cultured↗

Immunization with a pneumococcal capsular polysaccharide vaccine during pregnancy.

The feasibility of preventing invasive pneumococcal infections during the first few months of life by immunization during pregnancy has been investigated. One hundred and fifty Gambian women were immunized with either a 23-valent pneumococcal polysaccharide vaccine or a meningococcal polysaccharide vaccine during the last trimester of pregnancy. Pregnant women showed a good antibody response to five of the six pneumococcal polysaccharides tested (types 1, 3, 5, 6, 14 and 19) but not to type 6 polysaccharide. Mean cord blood/maternal blood IgG antibody ratios varied from 24% (type 1) to 49% (type 3) and differed substantially between individual mother/infant pairs. Pneumococcal antibody levels were higher at birth in infants of women immunized with pneumococcal polysaccharide vaccine than in control infants. However, these antibodies disappeared rapidly during the first few months of life and it is uncertain how much clinical protection against pneumococcal infection maternal immunization would have provided.

Antibodies, Bacterial↗

Serological response to Chlamydia pneumoniae in patients with sarcoidosis.

The antigen-specific serological response to Chlamydia pneumoniae was studied in 24 patients with sarcoidosis and compared to that seen in acute C. pneumoniae respiratory infection. By the micro-immunofluorescence test, five sarcoidosis patients had acute antibody, 15 had chronic antibody and four had no antibody against C. pneumoniae. By enzyme immunoassay, 20 sarcoidosis patients had antibody against ReLPS but that cross-reacts with chlamydial LPS. Immunoblot analysis of sera using purified C. pneumoniae elementary bodies showed that recognition of the 40 kDa C. pneumoniae major outer membrane protein was rare (20%). Reactivities with proteins with Mw of 42 K (70%), 60 K (65%), 98 K (55%) and 52 K (50%) were often noted. To study reactivity of chlamydial HSP 60 in sarcoidosis sera, sarkosyl-soluble (contains the 60 kDa HSP) and sarkosyl-insoluble (contains the 60 kDa structural protein) fractions of C. pneumoniae elementary bodies were prepared. The 60 kDa structural protein was recognized with equal frequency by sera from patients with sarcoidosis and acute respiratory infection, while the HSP 60 was more frequently recognized by sera with acute respiratory infection than sarcoidosis. Recombinant fusion proteins expressed from pGEX-2T containing overlapping DNA fragments of the C. pneumoniae 60 kDa HSP gene were purified. Different recognition patterns were identified for sera from sarcoidosis patients and from patients with acute C. pneumoniae respiratory infection.

Adult↗

Chlamydia pneumoniae antibodies in chronic obstructive pulmonary disease.

BACKGROUND: The significance of persistent or recurrent respiratory infections in adult life for the development of chronic obstructive pulmonary disease (COPD) is still to a large extent unknown. A few clinical and experimental animal studies suggest that peripheral airways diseases may be due to the cumulative effects of recurrent respiratory infections over an extended period. METHODS: C. pneumoniae-specific IgG and IgA antibody levels were determined in two elderly groups of male patients with COPD and in control subjects without the disease. The first group (N = 36) consisted of patients who were hospitalized due to an acute exacerbation of COPD. The second group of patients (N = 54) and the controls (N = 321) were participants in a community survey on respiratory diseases in the elderly. The criteria for seropositivity were defined as an IgG titre of >=16. RESULTS: 89% of the hospitalized patients (group I) and 66% of the non-hospitalized patients (Group II) were IgA seropositive as compared to 55% of the controls. Derived from the logistic regression analysis, the odds ratio (OR) WAS 7.4 (95% CI : 2.1-25.7) between group I and the controls and 1.5 (0.7-2.9) between group II and controls. Furthermore, the difference in the age-adjusted geometric mean titres (GMT) of lgA antibodies between the group I and the controls was significant (53.0 for the patients versus 19.1 for the controls). On the contrary, no significant differences between the patients and the controls were found either in the proportion of IgG-seropositive or in the GMT of IgG antibodies. Two of the 29 patients with an exacerbation of COPD, for whom paired sera were available, showed an antibody response suggesting a current acute or reactivated chlamydial infection. CONCLUSIONS: The results showed that C. pneumoniae lgA antibodies are found more frequently and in higher concentrations in COPD patients than in disease-free controls. The finding may indicate a chronic C. pneumoniae infection in these patients. The association persisted after controlling for the potential confounding effect of smoking.

Aged↗

Subtyping of common pediatric pneumococcal serotypes from invasive disease and pharyngeal carriage in Finland.

Ninety-nine penicillin-sensitive Streptococcus pneumoniae strains of common pediatric serogroups/types (6, 7, 14, 19, and 23) cultured from the blood of children with invasive disease (n = 49) or asymptomatic oropharyngeal carriage (n = 50) were analyzed by multilocus enzyme electrophoresis and ribotyping; 53 distinctive multilocus enzyme genotypes (ETs) and 53 ribotypes were identified. Multilocus enzyme electrophoresis showed good correlation with ribotying. ETs and ribotypes among invasive and carriage isolates were similar. Within different S. pneumoniae serogroups/types, both clonal (7 and 14) and heterogenous (6, 19, and 23) ET and rRNA hybridization patterns were observed. Greatest diversity was observed among serotypes 6A, 6B, and 19F. Use of 12 additional restriction enzymes besides PvuII and BglII did not increase ribotype discrimination within serotype 7 and 14 isolates. Serotype 7 and 14 strains, which appear clonal by subtyping, are rare among carriers but common causes of invasive disease. Characteristics associated with their clonality may represent an advantage for invasiveness.

Adolescent↗

Antibody-secreting cells and their relation to humoral antibodies in serum and in nasopharyngeal aspirates in children with pneumococcal acute otitis media.

Mucosal and systemic antibody responses to pneumococcal capsular polysaccharide were studied in 17 children with culture-verified pneumococcal acute otitis media. Serotype-specific antibody-secreting cells (ASCs) in peripheral blood and antibodies in acute and convalescent sera and nasopharyngeal aspirates were measured. A polysaccharide-specific ASC response was induced in all subjects. The response was age dependent, and the dominant antibody class was IgA. Three children > 24 months old had > 100 IgA-class ASCs/10(6) cells and serum and nasopharyngeal IgA responses; 2 had only a nasopharyngeal IgA response. None of 8 children < 24 months old showed a systemic response; however, a nasopharyngeal IgA response was detected in 1. Results suggest that whole pneumococci can induce a mucosal polysaccharide-specific antibody response independent of the systemic response. Results are also in accordance with earlier studies suggesting that the mucosal immune system matures earlier in life than does the systemic immune response.

Acute Disease↗

Antibody response to pneumococcal capsular polysaccharide vaccine in the elderly.

Antibody response to 23-valent pneumococcal vaccine was assessed in 350 subjects (131 men, 219 women) aged 65-91 years. IgG antibodies to pneumococcal serotypes 4, 6B, 9V, 14, 19F, and 23F were measured by EIA after blocking of antibodies to cell wall polysaccharide. Antibody concentrations in both pre- and postvaccination sera (mean interval, 35 days) were higher in elderly men than women; in the women, the concentrations decreased significantly with increasing age, but not in the men. Antibody fold increases were good in the elderly, including those > or = 85 years old. The overall percentage of the elderly with antibody concentrations > 1 microgram/mL to the 6 antigens increased by vaccination from 61% to 87%, but in the women > or = 85 years old, only to 75%. Antibody response to 23-valent pneumococcal vaccine was satisfactory in the elderly.

Adult↗

Comparison of serum antibodies to pneumolysin with those to pneumococcal capsular polysaccharides in children with acute otitis media.

BACKGROUND: Streptococcus pneumoniae is a major bacterial pathogens in acute otitis media. Pneumolysin is a species-specific protein toxin produced intracellularly by all clinically relevant pneumococcal strains, and antibodies to pneumolysin should therefore represent pneumococcal involvement in the disease, regardless of the serotype. METHODS: Antibodies to pneumococcal pneumolysin and capsular polysaccharides were measured by enzyme immunoassay in acute and convalescent sera of 121 children with acute otitis media. A pneumococcal otitis episode was defined by a positive middle ear fluid culture and/or pneumolysin PCR. RESULTS: Median age of the 10 children who developed a seroconversion response to pneumolysin was 1 year 8 months, and of the 21 children responding to polysaccharides it was 2 years 9 months. Eight of the 10 seroconversion responses to pneumolysin were of IgA class alone, whereas 17 of the 21 polysaccharide responses were of IgG class alone or IgG together with IgM and/or IgA. Of the 41 children with a pneumococcal otitis episode, 13 (39%) showed a seroconversion response, 3 (7%) to pneumolysin and 11 (27%) to capsular polysaccharides. The children with a pneumococcal otitis episode had lower titers of acute phase IgG to the capsular polysaccharide pool of S. pneumoniae (containing types 6B, 14, 19F and 23F), as compared with the titers in children with otitis caused by other pathogens and pneumococci only in the nasopharynx or not found at all (P = 0.04). CONCLUSIONS: Serum antibodies to pneumolysin can be detected at an earlier age than those to the capsular polysaccharides. However, a seroconversion is rare and therefore of no diagnostic value. The presence of serum IgG to the pneumococcal capsular polysaccharides seems beneficial in the prevention of pneumococcal otitis.

Acute Disease↗

Reactivation of Chlamydia pneumoniae infection in mice by cortisone treatment.

Reactivation of Chlamydia pneumoniae infection was studied by inducing immunosuppression by cortisone acetate treatment given every other day for 14 days in intranasally infected NIH/s mice. The treatment started 2 or 4 weeks after primary infection, when no C. pneumoniae was detected. C. pneumoniae could be recovered from the lung cultures on days 7 and 9 in 10 and 60% of the mice, respectively, when cortisone treatment was begun 30 days after infection. These results confirm the persistent nature of C. pneumoniae infection.

Animals↗