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Biomedical subjects

M Puolakkainen

Publications and source records attributed to M Puolakkainen.

At least 19 recordsLinked to original sources
PubMed2006

Intranasal administration of chlamydial outer protein N (CopN) induces protection against pulmonary Chlamydia pneumoniae infection in a mouse model.

Chlamydia pneumoniae is an intracellular pathogen that grows inside a vacuole, referred to as an inclusion. C. pneumoniae possess a type III secretion system (TTSS), which allows them to secrete effector molecules into the inclusion membrane and to the host cell cytosol. Proteins such as chlamydial outer protein N (CopN) that associate with the inclusion membrane are potential targets for the host's MHC-dependent antigen presentation, thereby representing ideal antigen candidates for T cell-based vaccination. The results of this study showed that intranasal immunization of BALB/c mice with heat-aggregated CopN protein and an Escherichia coli heat-labile toxin (LT) induced a strong immune response, detected as antigen-specific antibody production, lymphocyte proliferation and IFN-gamma production. Furthermore, the immunization induced statistically significant protection against intranasal C. pneumoniae challenge, the level of which correlated with the magnitude of CopN-specific lymphocyte proliferation. Both heat-aggregation of the antigen and the presence of LT adjuvant were required for maximal protective effect.

Administration, Intranasal↗
PubMed2005

Clearance of Chlamydia pneumoniae infection in H-2 class I human leucocyte antigen-A2.1 monochain transgenic mice.

CD8+ T cells have been suggested to play an important role in protective immunity against pulmonary Chlamydia pneumoniae infection in mice. Moreover, several classical major histocompatibility complex class I - restricted cytotoxic CD8+ T lymphocytes (CTL) specific for C. pneumoniae- derived peptides have been identified. Here, we studied the outcome of C. pneumoniae infection in human leucocyte antigen (HLA)-A2.1 transgenic mice (HHD mice) that are only able to express a classical human class I molecule (HLA-A2.1). C. pneumoniae infection was self-restricted in HHD mice which were able to develop specific immune responses and a protective immunity against a subsequent rechallenge in a manner comparable to wildtype mice. Furthermore, accumulation of functional and C. pneumoniae-specific T cells to the site of infection was detected after challenge. Antigen processing and HLA-A2.1-dependent presentation was studied by immunizing the HHD mice with chlamydial outer protein N (CopN). Isolation of a peptide-specific CTL line from the CopN-immunized mice suggests that the HLA-A2.1 molecule can support the development of CTL response against a chlamydial protein in mice. These findings suggest that the transgenic mouse model can be used for further characterization of the HLA-A2.1-restricted CD8+ T-cell response during C. pneumoniae infection and for identification of CD8 epitopes from chlamydial antigens.

Animals↗
PubMed2002

Infectious background of patients with a history of acute anterior uveitis.

OBJECTIVE: To study the infectious background of patients with a history of acute anterior uveitis (AAU) and healthy control subjects. METHODS: Sixty four patients with previous AAU and 64 sex and age matched controls were studied. Serum antibodies to Salmonellae, Yersiniae, Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, Campylobacter jejuni, and Borrelia burgdorferi were measured using enzyme linked immunosorbent assay (ELISA), and antibodies to Chlamydia trachomatis and Chlamydia pneumoniae by microimmunofluorescence test. Peripheral blood mononuclear cells (PBMCs), separated by density gradient centrifugation, were studied for Salmonella and Yersinia antigens by means of an immunofluorescence test, and for C pneumoniae DNA with a polymerase chain reaction (PCR). RESULTS: Neither prevalence nor levels of single microbial antibodies studied differed between the patients and control subjects, or between subgroups of patients created on the basis of clinical characteristics. In logistic regression analysis, the high number of recurrences (>10) of AAU was independently related to the presence of single or multiple bacterial antibodies (p=0.04). None of the PBMC samples of the patients were positive for Yersinia or Salmonella antigens. C pneumoniae PCR was positive in a patient who was negative for C pneumoniae antibodies. CONCLUSION: Although neither the prevalence nor the levels of single microbial antibodies studied differed between the patients and the controls, current data suggest that the presence of single or multiple antibodies in patients with many recurrences of AAU compared with patients with none or few recurrences may be a sign of repeated infections, antigen persistence, or raised innate immune responsiveness.

Acute Disease↗
PubMed2001

Chlamydia trachomatis infection in mothers with preterm delivery and in their newborn infants.

We studied Chlamydia trachomatis infection in mothers with preterm delivery and intrauterine transmission of the infection to their offspring. Forty-one mothers with preterm labour and their newborn infants (n=50) were studied for the presence of C. trachomatis infection using microimmunofluorescence test for detection of serum antibodies against C trachomatis and polymerase chain reaction for detection of C. trachomatis-specific DNA in mucosal swabs. Antibodies to C trachomatis were found in serum of 12 mothers (29%). Five of fourteen mothers had C. trachomatis DNA in cervical specimens. Eighteen neonates were born to the 14 mothers with positive serology and/or C. trachomatis DNA. C. trachomatis DNA was detected in specimens from 10 of the 18 neonates (55.5%). Three of the available cord blood samples contained C trachomatis IgM antibodies. Our results strongly suggest that mothers and their preterm babies may benefit from screening for active C. trachomatis infection.

Adolescent↗
PubMed2001

Infections of the central nervous system of suspected viral origin: a collaborative study from Finland.

We studied 3231 patients with acute central nervous system (CNS) symptoms of suspected viral origin to elucidate the current etiologic spectrum. In 46% of the cases, a viral finding was observed. Varicella-zoster virus (VZV) was the main agent associated with encephalitis, as well as meningitis and myelitis. VZV comprised 29% of all confirmed or probable etiologic agents. Herpes simplex virus (HSV) and enteroviruses accounted 11% each, and influenza A virus 7%. VZV seems to have achieved a major role in viral infections of CNS. In encephalitis in our population, VZV is clearly more commonly associated with these neurological diseases than HSV. The increase in VZV findings may in part be a pseudophenomenon due to improved diagnostic methods, however, a true increase may have occurred and the pathogenetic mechanisms behind this should be elucidated.

Adenoviridae Infections↗
PubMed2001

Chlamydia pneumoniae proteins induce secretion of the 92-kDa gelatinase by human monocyte- derived macrophages.

Chlamydia pneumoniae, an intracellular Gram-negative respiratory bacterium, and macrophages are present in inflammatory tissue sites such as atherosclerotic lesions, where abnormal degradation of the extracellular matrix takes place. To evaluate the potential of C pneumoniae for participation in matrix destruction, we studied the effect of this bacterium on the production of 3 matrix-degrading metalloproteinases, 92-kDa gelatinase, interstitial collagenase-1, and stromelysin-1, and their natural inhibitor TIMP-1 (tissue inhibitor of metalloproteinases-1) by human monocyte-derived macrophages differentiated in vitro. Spontaneous production of collagenase and stromelysin by these cells was minimal and was not influenced by C pneumoniae. In contrast, the cells secreted substantial basal quantities of 92-kDa gelatinase, the secretion of which was stimulated (on average, 2.5-fold) by C pneumoniae. C pneumoniae regulated the expression of 92-kDa gelatinase by macrophages at the pretranslational level. Macrophages secreted only small quantities of TIMP-1. The chlamydial proteins Omp2, MOMP, and HSP60 were also found to participate in the induction of 92-kDa gelatinase by C pneumoniae. Denaturation of chlamydial proteins by boiling reduced 92-kDa gelatinase secretion only partially (by 35%), suggesting that the heat-stabile lipopolysaccharide molecules also stimulate secretion of the enzyme. The results show that production of 92-kDa gelatinase by human macrophages is selectively upregulated by C pneumoniae, which suggests that these bacteria, when present in a macrophage-containing inflammatory environment, actively participate in the destruction of the extracellular matrix.

Antigens, Bacterial↗
PubMed2001

Chlamydia pneumoniae does not increase atherosclerosis in the aortic root of apolipoprotein E-deficient mice.

In epidemiological studies, an association between cardiovascular disease and Chlamydia pneumoniae (C pneumoniae) infection has been observed. Although C pneumoniae has been shown to be present in atherosclerotic lesions, a causal relationship between C pneumoniae infection and atherosclerosis has not been demonstrated. To study this question, we used 2 strains of apolipoprotein (apo) E-deficient mice. Eight-week-old mice on an FVB background that were maintained on either a low- or a high-fat diet were infected 3 times at 1-week intervals with C pneumoniae, and atherosclerotic lesions were measured in the aortic root at 10 weeks after the primary infection. In each of the diet groups, no difference in the extent of atherosclerosis could be observed between the C pneumoniae-infected and control animals. In further studies, 2 strains of apoE-deficient mice (FVB or C57BL/6J background) were infected 4 times at 3- to 4-week intervals, and the extent of atherosclerosis was analyzed 18 weeks later. The mice were kept on either a low- or a high-fat diet. The high-fat diet increased atherosclerosis, and a difference in atherosclerosis susceptibility between the mouse strains was observed. However, C pneumoniae infection did not influence lesion size in either mouse strain. On the other hand, C pneumoniae could not be demonstrated by polymerase chain reaction in any of the atherosclerotic lesions of the infected animals studied. A small decrease in serum cholesterol and triglyceride levels 3 days after the primary infection occurred, but after that no differences in serum lipid levels compared with those in noninfected animals were evident. In the myocardium of C pneumoniae-infected mice, no inflammatory signs could be observed. We conclude that under the experimental conditions used, C pneumoniae infection does not accelerate atherogenic changes in the aortic root of apoE-deficient mice.

Animals↗
PubMed2001

Chlamydial antibodies in patients with previous acute anterior uveitis.

PURPOSE: To determine the prevalence of antibodies to Chlamydia pneumoniae, C. trachomatis, and C. pneumoniae heat shock protein (Cpn Hsp60) in patients with acute anterior uveitis (AAU) and in sex- and age-matched healthy control subjects. METHODS: Altogether 64 patients with previous AAU were examined at the Helsinki University Eye Hospital from September through December 1999. Serum specimens from the patients and sex- and age-matched healthy control subjects were tested for antibodies to C. pneumoniae and C. trachomatis by a specific microimmunofluorescence test and for antibodies to Cpn Hsp60 by enzyme immunoassay (EIA). RESULTS: The prevalence of antibodies to C. pneumoniae (69% vs. 72%) and C. trachomatis (11% vs. 6%) did not differ significantly between the patients and control subjects, nor did the level of IgG antibodies to Cpn Hsp60 (median EIA unit, 65 vs. 48). The levels of IgA antibodies to Cpn Hsp60 were significantly higher in the patients with AAU than in the control subjects (median EIA unit, 18 vs. 10; two-tailed Wilcoxon signed rank test, P = 0.0001). CONCLUSIONS: The high frequency of IgA antibodies to Cpn Hsp60 in patients with past AAU indicates that such patients may have persisting or recurrent infections due to C. pneumoniae. This finding suggests that C. pneumoniae may play a role in the pathogenesis of AAU.

Acute Disease↗
PubMed2001

Use of a peptide based enzyme immunoassay in diagnosis of Chlamydia trachomatis triggered reactive arthritis.

OBJECTIVE: To assess the presence of circulating IgA and IgG antibodies to Chlamydia trachomatis in sera of patients with reactive arthritis (ReA) and other arthritides. METHODS: A peptide based enzyme immunoassay (EIA) was used to study 132 patients divided into 5 groups: C. trachomatis triggered ReA, uroarthritis, enteroarthritis, oligoarthritis, and rheumatoid arthritis (RA). Followup sera were available from 19 patients. RESULTS: An increased prevalence of C. trachomatis antibodies was observed in patients with ReA triggered by C. trachomatis; 18/23 (78%) had IgA and 19/23 (83%) had IgG antibodies. In patient groups with uroarthritis (n = 12), enteroarthritis (n = 56), oligoarthritis (n = 16), and RA (n = 25), C. trachomatis IgA/IgG antibodies were detected in 58%/75%, 27%/21%, 25%/31%, and 20%/32% of patients, respectively. Both the IgA and IgG antibodies were positive in 74%, 50%, 16%, 25%, and 12% of the patients with C. trachomatis triggered ReA, uroarthritis, enteroarthritis, oligoarthritis, and RA, respectively. Based on positivity of both isotypes the sensitivity of the assay was 74% and specificity 84%. In the followup sera, an association between circulating C. trachomatis-specific antibody concentrations and clinical disease outcome of the arthritis was seen in patients with culture-positive C. trachomatis triggered ReA. CONCLUSION: C. trachomatis species-specific peptide EIA correlates well with conventional diagnosis of primary C. trachomatis infection in patients with ReA. This assay may be a valuable contribution to the diagnosis of C. trachomatis triggered ReA.

Adolescent↗
PubMed2000

Immunity to Chlamydia pneumoniae induced by vaccination with DNA vectors expressing a cytoplasmic protein (Hsp60) or outer membrane proteins (MOMP and Omp2).

Immune responses induced by intramuscular DNA immunization with Chlamydia pneumoniae genes coding for the major outer membrane protein (MOMP), cysteine-rich outer membrane protein 2 (Omp2) or the heat shock protein 60 (Hsp60) were studied. BALB/c mice were vaccinated intramuscularly three times at 3-week intervals and challenged intranasally 2 weeks after the last injection. Immunization with pmomp or phsp60 showed 1.2-1.5 log reduction in the mean lung bacterial counts after the challenge. Specific antibodies were detected only in sera of the mice immunized with pomp2 and phsp60. Although immunization with pomp2 resulted in a strong serum antibody response against Omp2 protein, it failed to protect the mice. Immunization with any of the three vaccines did not reduce the severity of histologically assessed pneumonia, but resulted in significantly higher lymphoid reaction in the lung indicating immunological memory.

Animals↗
PubMed2000

Picornavirus proteins share antigenic determinants with heat shock proteins 60/65.

Immunological cross-reactions between enteroviruses and islet cell autoantigens have been suggested to play a role in the etiopathogenesis of insulin dependent diabetes mellitus (IDDM). In the nonobese diabetic mouse, an autoimmune model of IDDM, one of the reactive beta cell autoantigens is the heat shock protein 60 (HSP60). These studies were prompted by sequence homology discovered between the immunogenic region in HSP60 and two regions in enterovirus capsid proteins, one in the VP1 protein and the other in the VP0, the precursor of VP2 and VP4 proteins. Possible immunological cross-reactions between enterovirus proteins and heat shock proteins were studied by EIA and immunoblotting by using purified virus preparations, viral expression proteins VP1 and VP0, and recombinant HSP60/65 proteins, and corresponding polyclonal antisera. The HSP60/65 family of proteins is highly conserved and there is a striking degree of homology between bacterial and human heat shock proteins. Rabbit antibodies to HSP65 of Mycobacterium bovis that reacted with human HSP60 were also found to recognise capsid protein VP1 of coxsackievirus A9, VP1, and/or VP2 of coxsackievirus B4. Both viruses were also recognised by antisera raised against HSP60 of Chlamydia pneumoniae. In addition to the capsid proteins derived from native virions, antisera to both bacterial HSP proteins recognised expression protein VP1 of coxsackievirus A9. The cross-reactivity was also demonstrated the other way around; antisera to purified virus particles reacted with the HSP 60/65 proteins to some extent. These results suggest that apart from the well-documented sequence homology between the 2C protein of coxsackieviruses and the beta-cell autoantigen glutamic acid decarboxylase, there are other motifs in picornavirus proteins homologous to islet cell autoantigens, which might induce cross-reacting immune responses during picornavirus infections.

Antibodies, Bacterial↗
PubMed2000

Chlamydia trachomatis seropositivity is associated both with stillbirth and preterm delivery.

The cause of stillbirth and preterm delivery is often unknown. We studied the prevalence of Chlamydia trachomatis antibodies in mothers with stillbirth and preterm labor. Serum specimens from 72 mothers with stillbirth after the 21st gestational week, and from 48 mothers with preterm delivery between gestational weeks 23 and 29, both from the greater Helsinki area, and cord blood from 96 consecutive liveborn deliveries at the Department of Obstetrics and Gynecology, the University of Helsinki, were studied for antibodies to C. trachomatis immunotypes CJHI, GFK and BED by microimmunofluorescence test. The prevalence of C. trachomatis antibodies was highest, 33.3%, in mothers with stillbirth, 18.8% in mothers with preterm delivery, and 10.4% in cord blood. The IgM seropositivity rate was high among mothers with preterm delivery (8.3%). We conclude that C. trachomatis IgG antibodies are frequently detected in sera from mothers with stillbirth, suggesting past infection, while mothers with preterm delivery often have serum IgM antibodies, suggesting of acute infection.

Acute Disease↗
PubMed2000

Chlamydia pneumoniae serology: interlaboratory variation in microimmunofluorescence assay results.

The lack of standardization in chlamydia serology has made interpretation of published data difficult. This study was initiated to determine the extent of interlaboratory variation of microimmunofluorescence (MIF) test results for the serodiagnosis of Chlamydia pneumoniae infections. Identical panels of 22 sera were sent to 14 laboratories in eight countries for the determination of IgG and IgM antibodies by MIF. Although there was extensive variation in the numeric titer values, the overall percentage agreement with the reference standard titers from the University of Washington was 80%. For results by serodiagnostic category, the best agreement was for four-fold rise in IgG titers, while the lowest agreement was for negative or low IgG titers. Agreement for IgM titers was 50%-95%. Four laboratories failed to discern false-positive IgM titers possibly because of the presence of rheumatoid factor. Further studies are underway to determine the source of interlaboratory variation for the MIF test.

Antibodies, Bacterial↗
PubMed1999

Lack of association between serum antibodies to Chlamydia trachomatis and a history of recurrent pregnancy loss.

OBJECTIVE: To study the relation between recurrent pregnancy loss (RPL) and infection with Chlamydia trachomatis, and to compare the prevalence of antibodies to C. trachomatis in women with primary and secondary RPL. DESIGN: Prospective comparative study. SETTING: University hospital and university student health center. PATIENT(S): Seventy patients with RPL were selected from women attending an RPL outpatient clinic; 40 normal parous women and 94 asymptomatic sexually active women served as controls. INTERVENTION(S): Blood samples were collected during the clinical examinations for RPL. MAIN OUTCOME MEASURE(S): Serum immunoglobulin (Ig) G and IgA antibodies were detected by two independent methods, a recombinant ELISA specific to the genus Chlamydia and microimmunofluorescence testing specific to the species C. trachomatis. RESULT(S): There was no statistically significant difference in the frequencies of IgG or IgA between the women with RPL and the controls. The antibody frequencies were similar in the women with primary and secondary RPL. CONCLUSION(S): The presence of serum antibodies to C. trachomatis is not associated with RPL. Women with primary and secondary RPL do not differ with respect to the prevalence of antichlamydial antibodies. Thus, women with RPL do not benefit from screening for chlamydial IgG or IgA antibodies.

Abortion, Habitual↗
PubMed1999

Vaccination against infections by Chlamydia pneumoniae.

Chlamydia pneumoniae is an intracellularly growing bacterium that causes respiratory infections and is strongly associated with atherosclerosis. Antibodies against C. pneumoniae are frequently encountered in the adult population, indicating past exposure to the micro-organism. Immunity to reinfection is, however, only partial and does not prevent development of sequelae. Infections caused by and associated with C. pneumoniae are a major cause of morbidity and mortality world wide. Development of a vaccine capable of protecting against infections due to C. pneumoniae and their sequelae would prevent up to 10% of community-acquired pneumonias in adults and add a new dimension to the prevention of atherosclerosis and coronary heart disease.

Adult↗
PubMed1999

Depletion of CD8+ cells abolishes memory in acquired immunity against Chlamydia pneumoniae in BALB/c mice.

The importance of T cells in Chlamydia pneumoniae infection in mice was assessed by comparing wild-type BALB/c mice with nude mice and mice depleted in vivo of either CD4+ or CD8+ T cells. Whereas wild-type mice cleared the primary infection in 3 weeks, nude mice were only able to restrict the infection and could not clear it during the observation period of 56 days. Nude mice exhibited a greater number of macrophages in their lungs and the pulmonary cells secreted a higher level of tumour necrosis factor-alpha (TNF-alpha) than wild-type mice. Depletion of CD4+ cells did not change the overall infection kinetics of the primary infection. However, depletion of CD8+ cells resulted in a slightly impaired clearance of the bacteria in the late stages of primary infection. To assess the role of the two T-cell subsets in the acquired immunity that develops during primary infection in wild-type BALB/c mice, in vivo depletions were performed during reinfection. Prior to reinfection, immunocompetent wild-type mice were infected and natural immunity was allowed to form. During reinfection, depletion of CD4+ cells did not have any effect on infection kinetics, whereas depletion of CD8+ cells abolished the protection, reverting the infection kinetics and bacterial load to the same levels found in wild-type mice during primary infection. These results show that T cells are necessary for clearing C. pneumoniae infection in mice. Furthermore, whereas neither of the two main T-cell subsets, separately, were essential for clearance of primary infection, the induced protective immunity was strongly CD8 dependent.

Animals↗