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Biomedical subjects

I Seppälä

Publications and source records attributed to I Seppälä.

At least 19 recordsLinked to original sources
PubMed2006

Immunoglobulins and complement factor C4 in adult rhinosinusitis.

We assessed whether complement and its factor C4 or abnormal immunoglobulin levels are associated with chronic or recurrent rhinosinusitis. We used multiple patient and control groups to obtain clinically meaningful data. Adult chronic or recurrent rhinosinusitis and acute purulent rhinosinusitis patients were compared with unselected adults and controls without previous rhinosinusitis. Associated clinical factors were reviewed. Levels of immunoglobulins, plasma C3, C4 and classical pathway haemolytic activity were analysed. C4 immunophenotyping was used to detect C4A and C4B deficiencies as null alleles. Complement was up-regulated in rhinosinusitis. C4A nulls and low IgA, IgG, IgG1, IgG2, IgG3 and IgG4 levels were all more common in chronic or recurrent rhinosinusitis patients than in unselected and healthy controls. We searched for relevant differences between the patient groups. According to stepwise logistic regression analysis, nasal polyposis [odds ratio (OR) 10.64, 95% confidence interval (CI) 2.5-45.7, P = 0.001], bronchial asthma (OR 8.87, 95% CI 2.3-34.9, P = 0.002), C4A null alleles (OR 5.84, 95% CI 1.4-24.9, P = 0.017) and low levels of IgG4 together with either IgG1 or IgG2 (OR 15.25, 95% CI 1.4-166.8, P = 0.026) were more common in chronic or recurrent rhinosinusitis than in acute rhinosinusitis patients. Isolated low IgG subclasses had limited value in patient assessment. C4A null alleles are associated with chronic or recurrent rhinosinusitis, potentially through their effect on immune defence and inflammation control. Multiple clinical and immunological parameters may need to be evaluated when searching for prognostic variables.

Adult↗
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

Recombinant flagellin A proteins from Borrelia burgdorferi sensu stricto, B. afzelii, and B. garinii in serodiagnosis of Lyme borreliosis.

Genes for flagellin A (FlaA) proteins from European borrelial strains of Borrelia burgdorferi sensu stricto, B. afzelii, and B. garinii were cloned and sequenced. An identity of 92 to 93% was observed in the flaA sequences of the different species. Polyhistidine-tagged recombinant FlaA (rFlaA) proteins were produced in Escherichia coli and used as antigens in Western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). In immunoglobulin G (IgG) WB, 71% (10 of 14) of the sera from neuroborreliosis and 86% (12 of 14) of those from Lyme arthritis patients reacted with one to three rFlaAs. In IgG ELISA, 74% (14 of 19) and 79% (15 of 19) of patients with neuroborreliosis and arthritis, respectively, were positive. The immunoreactivity in local European patient sera was stronger against rFlaA from B. garinii and B. afzelii than against rFlaA from B. burgdorferi sensu stricto. Neither IgG nor IgM ELISA was sensitive in the serodiagnosis of erythema migrans. Serum samples from patients with syphilis and systemic lupus erythematosus showed mild cross-reactivity in IgG tests. Sera from Yersinia enterocolitica or beta-hemolytic Streptococcus infections showed only occasional responses. With IgM ELISA, 58% (11 of 19) and 37% (7 of 19) of patients with neuroborreliosis and arthritis, respectively, were positive. Cross-reactive antibodies to FlaA, especially in serum samples from patients with rheumatoid factor positivity and Epstein-Barr virus infection, reduced the specificity of IgM serodiagnosis. Therefore, rFlaA seems to have a limited role for IgM serodiagnosis, yet rFlaA might be useful in the IgG serodiagnosis of disseminated Lyme borreliosis.

Amino Acid Sequence↗
PubMed1999

IgG subclass distribution of antibodies after vaccination of adults with pneumococcal conjugate vaccines.

The serum IgG subclass response of adults to Streptococcus pneumoniae (Pnc) capsular polysaccharides (PS) 6B, 14 and 23F was measured for four Pnc vaccines: the 23-valent PS vaccine or PS-protein conjugates with diphtheria toxoid (PncD), tetanus protein (PncT) or CRM197 protein (PncCRM) carriers. A standardized enzyme-linked immunosorbent assay specific for IgG subclasses was employed. This assay uses pneumococcal reference serum, lot 89-SF, to which anti-Pnc PS IgG subclass concentrations have been assigned. Both IgG1 and IgG2 responses were more frequent and higher in the conjugate groups than in the PS group. IgG subclasses in subjects vaccinated with PS displayed similar IgG2 predominant distribution previously observed in both natural and vaccine-induced antibodies. Antibodies induced by PncT, however, had a significantly altered IgG2/IgG1 ratio (P < 0.05), with a higher proportion of IgG1.

Adult↗
PubMed1999

The laboratory diagnosis of ocular Lyme borreliosis.

BACKGROUND: A study was carried out to evaluate indirect enzyme-linked immunosorbent assay (ELISA), immunoblot analysis, and polymerase chain reaction (PCR) in the diagnostic work-up of ocular Lyme borreliosis. METHODS: Twenty patients with ocular Lyme borreliosis were examined. IgG and IgM antibodies to Borrelia burgdorferi were measured by ELISA in serum, and in cerebrospinal fluid (CSF) when indicated, and immunoblot analysis of B. burgdorferi IgG antibodies in serum was performed. A nested PCR was used to detect a segment of a gene coding for B. burgdorferi endoflagellin. The samples used in PCR testing were serum and CSF and in isolated cases conjunctiva and vitreous. RESULTS: Seventeen patients had elevated Borrelia antibodies in serum or CSF by ELISA. Seven patients, including two with negative ELISA, had a positive immunoblot. Seven of the 13 patients in whom PCR was examined during clinically active disease had a positive PCR result. Immunoblot analysis gave a negative result from the sera of five PCR-positive patients. CONCLUSIONS: For efficient diagnosis of ocular Lyme borreliosis, immunoblot analysis and PCR should be used in addition to ELISA. A positive PCR seems to be associated with a negative immunoblot.

Adolescent↗
PubMed1999

Evaluation of treatment responses in late Lyme borreliosis on the basis of antibody decrease during the follow-up period.

The purpose of this study was to identify a serological marker of successful treatment as distinct from treatment failure in late Lyme borreliosis. Consecutive serum samples from 68 treated patients with late Lyme borreliosis were analyzed during a 1-2 year follow-up period after the start of treatment. End-point enzyme immunoassay titres of IgG1, IgG2, IgG3, and combined IgG1+3 subclasses against a sonicate antigen of Borrelia burgdorferi were determined and compared to the IgG antibody response against Borrelia burgdorferi flagella. Individual half-lives of the antibody levels were calculated for each patient. The half-life values were compared to the patients' clinical outcome in order to find a serological marker of remaining disease activity or relapse. The levels of combined IgG1+3 subclass antibodies against the sonicate antigen and the individual levels of IgG1, IgG2, and IgG3 antibodies did not change significantly after treatment. In contrast, antibodies to flagella decreased markedly after successful treatment, with a half-life of 112+/-92 days (arithmetic mean value +/- SD). This was significantly shorter than the half-life after unsuccessful treatment (271+/-151 days), (P<0.0001). The decrease was observed mainly in IgG1 and IgG4 responses to flagella, less so for IgG2 or IgG3. The results suggest that a rapid decrease in flagella antibodies can serve as a marker for a successful treatment of Lyme borreliosis.

Animals↗
PubMed1998

Lyme borreliosis--an unusual cause of vertigo.

A total of 2055 consecutive vertigo patients were examined in a prospective study in an area endemic for Lyme borreliosis for clinical signs of Lyme borreliosis or serum antibodies against Borrelia burgdorferi. Of these, 41 patients (2%) had positive levels of serum antibodies against B. burgdorferi. The incidence of seropositivity against B. burgdorferi among the vertigo patients did not differ from the incidence of the normal Finnish population. In addition to seropositivity the criteria used for Lyme borreliosis included previous erythema migrans, a positive polymerase chain reaction (PCR) or positive serum immunoblot. Eight patients were diagnosed as having Lyme borreliosis. This disease is a rare but possible cause of vertigo. Seropositivity alone is an insufficient finding for the diagnosis of Lyme borreliosis and should be supported by the clinical findings, the patient's history and other laboratory findings, such as immunoblotting or PCR. Although Lyme borreliosis seems to be a rare cause of vertigo, it must be kept in mind in the differential diagnosis of vertigo.

Adult↗
PubMed1998

IgG subclass-specific antibodies in Chlamydia pneumoniae infections.

IgG subclass-specific antibodies to Chlamydia pneumoniae and chlamydial lipopolysaccharide (LPS) were analysed in paired sera obtained from 15 patients with primary C. pneumoniae pneumonia and from 16 pneumonia patients with reinfection, as well as in single sera of 40 subjects with possible chronic C. pneumoniae infection and 40 healthy controls. The microimmunofluorescence (MIF) method was used to measure total IgG, IgM and IgG subclass-specific antibodies to C. pneumoniae protein antigens and enzyme immunoassay (EIA) to measure antibodies against the LPS antigen. By MIF, IgG1 antibodies to C. pneumoniae were demonstrated in all individuals of the 3 patient groups and also in all healthy controls. IgG2 subclass antibodies were not found by MIF. IgG3 antibodies were detected in 40% of patients with primary infection, in 31% of patients with reinfection, in 25% of those with chronic infection and in 8% of the controls. IgG4 antibodies were associated with acute C. pneumoniae infection and were found in 13% of primary infections and 31% of reinfections. The subclass pattern of LPS antibodies resembled that of protein antibodies measured by MIF: IgG1 was the most common subclass among the antibodies to LPS.

Acute Disease↗
PubMed1998

Paediatric facial paralysis caused by Lyme borreliosis: a prospective and retrospective analysis.

The incidence of Lyme borreliosis (LB) was studied prospectively in 49 children (< 17 years of age) with 50 episodes of acute FP. In addition, 43 children with a history of FP (average follow-up of 5.2 y) were studied retrospectively for the outcome of FP and for the symptoms and signs of late LB. In the prospective study, 17 (34%) patients with FP proved to have acute LB. They all received antibiotic treatment and their FP had a favourable outcome. In the retrospective study the patients had had FP before the diagnostic tests for LB were available. Thus, none of the 43 patients had been diagnosed to have, or treated for, LB. The outcome of their FP had generally been favourable. None of them had any signs of late LB at the follow-up visit. Our results indicate that LB is a frequent cause of acute paediatric FP in an endemic area. In addition our data suggests that FP caused by LB in children has a favourable prognosis, even when left untreated.

Acute Disease↗
PubMed1998

Inadequate dosaging in general practice of tricyclic vs. other antidepressants for depression.

Several prescription database studies suggest major differences between antidepressants in the proportion of patients in general practice treated with doses likely to elicit a true drug response. However, in these studies it has been difficult to differentiate prescriptions for depression from those for other indications, or to distinguish lower starting doses from the final treatment doses. We investigated possible differences between types of antidepressant in the proportions of patients receiving adequate treatment doses for depression from the primary health care services of Helsinki. Doctors at 22 (71%) of the 31 health centres in Helsinki were surveyed with regard to their antidepressant prescriptions over a period of 2 working weeks. There were marked differences in dosaging adequacy between the various types of antidepressant prescribed for depression at final treatment doses. Overall, 71% of the prescriptions for the tricyclic antidepressants, but only 13% of those for the other antidepressants, mainly selective serotonin reuptake inhibitors, were for low doses that are generally considered to be ineffective (P<0.001). These findings endorse the emerging perception that, in general practice, tricyclic antidepressants are usually prescribed for depression in too low doses, and that a greater reliance on other antidepressants would probably improve the effectiveness of treatment in primary health care.

Adult↗
PubMed1998

Assignment of immunoglobulin G1 and G2 concentrations to pneumococcal capsular polysaccharides 3, 6B, 14, 19F, and 23F in pneumococcal reference serum 89-SF.

We describe standardization of an enzyme-linked immunosorbent assay (ELISA) for measuring immunoglobulin G1 (IgG1) and IgG2 concentrations of antibodies to pneumococcal capsular polysaccharide (Pnc PS). The ELISA uses a human pneumococcal reference serum pool, lot 89-SF, as a reference. IgG1 and IgG2 concentrations were assigned to antibodies to Pnc PS serotypes 3, 6B, 14, 19F, and 23F in 89-SF by ELISA using affinity-purified monoisotypic IgG1 and IgG2 preparations. The sum of IgG1 and IgG2 concentrations in 89-SF agrees well with the previously assigned IgG concentrations. The IgG1 and IgG2 values in 89-SF were used to measure antibodies to Pnc PS 6B, 14, and 23F in adult pre- and postimmunization sera and the sum of IgG1 and IgG2 concentrations correlated well with the IgG values. Furthermore, the IgG2/IgG1 ratio did not affect the detection of IgG1, the isotype usually represented by a lower concentration.

Adult↗
PubMed1997

The etiology of uveitis: the role of infections with special reference to Lyme borreliosis.

PURPOSE: To assess the distribution of different uveitis entities and to evaluate their associations with infections, especially Lyme borreliosis. METHODS: During a one-year period 160 consecutive uveitis patients were evaluated in a university clinic. Selected tests were performed depending on the medical history of the patient and the clinical picture of the ocular inflammation. RESULTS: Uveitis was classified into selected entities for 74.4% of the patients. A direct infection was suggested to be linked with uveitis in 23 patients (14.4%). Lyme borreliosis, toxoplasmosis, and herpetic infections were the most frequently seen, in seven patients (4.3%) each. All patients with Lyme uveitis had manifestations of the posterior segment of the eye, such as vitritis, retinal vasculitis, neuroretinitis, chorioretinitis, or optic neuropathy. CONCLUSION: Infections are an important cause of uveitis in a university clinic. Lyme borreliosis is a newly recognised uveitis entity which should be kept in mind in the differential diagnosis of intermediate or posterior uveitis in areas endemic for Lyme borreliosis.

Adolescent↗
PubMed1996

IgG subclass response to human parvovirus B19 infection.

BACKGROUND: IgG antibodies are essential to immunity against human parvovirus B19 and can neutralize infection both in bone marrow cell cultures infected in vitro and in chronically infected immunosuppressed individuals. OBJECTIVES: To assess the levels and response kinetics of IgG subclasses towards individual structural proteins of human parvovirus B19. STUDY DESIGN: Subclasses of IgG for capsid proteins VP1 or VP2 were quantified by EIA using monoclonal antibodies in 30 acutely infected and 30 convalescent patients, as well as in 32 remotely infected and 20 non-infected controls. RESULTS: In all groups of seropositive individuals the predominant subclass for either structural protein was IgG1. Subclass IgG3 was associated with acute infection. By contrast, IgG4 appeared months after infection, and occurred specifically towards VP1. The ratio of VP1-specific subclasses IgG3 and IgG4 provided a diagnostic test for recent infection with a specificity of 98% and a sensitivity of 97%. CONCLUSIONS: Comparative measurement of VP1-specific IgG3 and IgG4 is useful in diagnosis. The IgG4 results point to long-term expression of immunologically active VP1 and to T-cell help of T(h)2 type for B-cells recognizing VP1.

Journal Article↗
PubMed1996

Long-term follow-up of chronic Lyme neuroretinitis.

PURPOSE: The authors report sequential fluorescein angiographic and color photographic findings of the fundi and response to treatment in a patient with chronic Lyme neuroretinitis. METHODS: A Lyme enzyme-linked immunosorbent assay with purified 41-kd flagellin as antigen was used to detect immunoglobulin G and immunoglobulin M antibodies to Borrelia burgdorferi in serum, cerebrospinal fluid, and vitreous. The changes were documented by fluorescein angiography and color photography tests performed during a 5 1/2 year follow-up. RESULTS: The diagnosis of Lyme neuroretinitis was based on the history of erythema migrans and positive Lyme enzyme-linked immunosorbent assay tests from cerebrospinal fluid and vitreous and by the exclusion of other infectious and systemic diseases and uveitis entities. Fluorescein angiography results disclosed bilateral chronic neuroretinal edema with areas of cystoid, patchy, and diffuse hyperfluorescence peripapillary and in the macular areas. The hyperfluorescent lesions enlarged despite a 9-month period of antibiotic therapy. CONCLUSION: Lyme borreliosis may cause neuroretinitis with unusual angiographic findings. Chronic Lyme neuroretinitis may be unresponsive to antibiotic therapy.

Adult↗
PubMed1996

Antiphospholipid antibodies in children.

Sera from children (n = 173) were tested for antiphospholipid antibodies (aPL) using an enzyme immunoassay detecting IgG anti-cardiolipin antibodies (GPL). Sera from adults (n = 100) were also tested. GPL were detected more frequently and at higher levels in children than in adults. Eighty-two per cent of the children and 27% of the adults tested positive (> or = 10 GPL Uml-1) for aPL (p < 0.001). Values of 45 GPLUml-1 or higher were detected in about 5% of the children, and 25 GPLUml-1 or higher in about 5% of the adults. Normal values should be adjusted accordingly.

Adult↗
PubMed1995

Domain-specific antibodies against the B2 chain of laminin inhibit neuronal migration in the neonatal rat cerebellum.

Although the spatial and temporal patterns of neuronal migration have been analyzed in great detail, little direct evidence is available as to what extracellular matrix molecules are involved. Because there is indirect evidence implicating the extracellular matrix protein laminin in neuronal migration, we investigated the effects of antibodies against a synthetic peptide derived from a neurite outgrowth domain of the B2 chain of laminin on neuronal migration in living cerebellar slices. We show by using infrared video microscopy that divalent Fab2 fragments of these antibodies inhibit granule neuronal movement in living slices of (P8) rat cerebellum. This inhibition of neuronal movement manifests itself by cessation of both radial and horizontal translocations of nuclei inside the granule neuronal processes. Fab2 fragments of antibodies against the intact (native) laminin molecule or Fab2 fragments from the preimmune serum do not affect nuclear translocation. Immunocytochemistry shows binding of the divalent Fab2 fragments of the B2 chain-specific antibodies to the Purkinje and Bergmann glial cell areas, and as punctate deposits in between the cells of the external granule cell layer. Native laminin antibodies bind to the basement membranes, and binding of the Fab2 fragments from the preimmune sera cannot be demonstrated. These results indicate that neuronal migration in the postnatal rat cerebellum in vivo involves nuclear translocation that can be inhibited by antibodies against a neurite outgrowth domain of the B2 chain of laminin. Thus, migration of cerebellar granule neurons may depend on the interaction between a neurite outgrowth domain of the B2 chain of laminin and neuronal cytoskeleton involved in nuclear movement.

Animals↗
PubMed1995

Diagnosis and clinical characteristics of ocular Lyme borreliosis.

PURPOSE: To establish a diagnosis, in a group of patients we studied the characteristics of ocular Lyme borreliosis. METHODS: During a two-year period, 236 patients with prolonged external ocular inflammation, uveitis, retinitis, optic neuritis, or unexplained neuro-ophthalmic symptoms were examined for Lyme borreliosis. Antibodies to Borrelia burgdorferi were measured by indirect ELISA and western blot. Cerebrospinal fluid was also analyzed by polymerase chain reaction. RESULTS: Ocular Lyme borreliosis was diagnosed in ten patients on the basis of medical history, clinical findings, and serologic test results. Results of ELISA disclosed that five patients were seropositive, two patients showed borderline reactivity, and three patients were seronegative. Four of the five patients with borderline or negative results by ELISA had a positive result by western blot analysis. In one seropositive patient, polymerase chain reaction verified a gene of B. burgdorferi endoflagellin from the vitreous and cerebrospinal fluid specimen. In five of the six patients with known onset of the Borrelia infection, the ocular disorder appeared as a late manifestation. Abnormalities of the posterior segment of the eye, such as vitreitis, retinal vasculitis, neuroretinitis, choroiditis, and optic neuropathy were seen in six patients. Bilateral paralytic mydriasis, interstitial keratitis, episcleritis, and anterior uveitis were seen in one patient each. CONCLUSIONS: Late-phase ocular Lyme borreliosis is probably underdiagnosed because of weak seropositivity or seronegativity in ELISA assays. Ocular borrelial manifestations show characteristics resembling those seen in syphilis.

Adolescent↗