Biomedical subjects
K Penttinen
Publications and source records attributed to K Penttinen.
[Are new viruses being found?].
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Rapid effect on endemic measles, mumps, and rubella of nationwide vaccination programme in Finland.
An immunisation programme to eliminate measles, mumps, and rubella from Finland within 10 years was started in November, 1982. A combined live vaccine is being given twice, at the ages of 14-18 months and 6 years, but at the beginning of the project children between these age limits are also being immunised. Because vaccinations are traditionally done by the public health nurses, special attention was paid to their motivation. 2.5 years after the launch of the project, 80.9% of the target children had been vaccinated. The incidence of measles has fallen by 93% and that of mumps by 87% compared with a normal prevaccination year (1982). A similar fall in incidence was seen for rubella, but only in the vaccinated age groups. Although elimination of measles, mumps, and rubella is not likely to be achieved with the present vaccination coverage, a drastic fall in the incidence of all three target diseases has occurred already. Every effort is being made to improve the coverage and thus to achieve the ultimate goal of the project.
Vaccination of children during treatment for leukemia.
Forty-one children receiving maintenance treatment for leukemia were vaccinated with inactivated mumps virus, meningococcal polysaccharide groups A and C and polyvalent pneumococcal polysaccharide vaccines. Antibodies against pneumococcal types 3, 18C, 19F and 23F and against meningococcal groups A and C were measured by radioimmunoassay. Mumps antibodies were determined by complement fixation, hemolysis-in-gel and enzyme-linked immunosorbent assays. The antibody responses tended to be lower than those of healthy age-matched controls. The individual responses were unpredictable; the magnitude of the response correlated neither with the age nor sex of the patient, duration of the chemotherapy nor with the prevaccination antibody concentration. Nevertheless, most patients achieved and even exceeded the geometric mean of the antibody concentrations of the healthy children, considered protective against infection.
Elevated serum immune complex levels in Pogosta disease, an acute alphavirus infection with rash and arthritis.
Circulating immune complexes (CIC) were studied in Pogosta disease, an acute alphavirus infection with fever, rash and arthritis. The disease is caused by a virus antigenically closely related to Sindbis virus. 75 serum specimens from 25 patients with serologically verified infection were obtained from 1-87 days after the onset. Six different CIC detection methods were used and CICs were observed in all patients at least with one test. Tests based on CIC binding onto human platelets followed the natural course of the disease and maximal values were observed between 10-15 days after onset. Slightly elevated levels were observed 2-3 months after onset. The mean conglutinin binding test values were slightly elevated during the whole follow-up period. The severity of arthritis did not directly correlate to CIC levels. C3c and C1q-binding test were positive only in a few cases. Latex and enzyme immunoassay tests for rheumatoid factors gave low positive values in some of the sera. Agarose gel electrophoresis of serum proteins revealed non-specific changes in alpha 1-alpha 2 interzone characteristic of an acute infectious disease. The presence of CIC in the sera of patients with Pogosta disease may indicate body's natural clearange mechanisms of viral antigens. CIC may have a pathogenic role in the prolonged arthritis, even though no direct correlation with CIC levels and severity of arthritis was observed.
[Vaccines against old and new microorganisms].
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Age-specific prevalence of complement-fixing antibodies to sixteen viral antigens: a computer analysis of 58,500 patients covering a period of eight years.
The age-specific prevalence of CF antibodies against 16 viral antigens was determined by using the computerized data registry of the routine diagnostic laboratory of the authors' department. The material consisted of data based on serum specimens from about 58,500 patients. All ages from newborn infants to 90-year-olds were represented. The sera had been collected and tested with a CF screening test over a period of 8 years (1971-1978). Several different antibody prevalence patterns were distinguished in regard to the rapidity and timing of the initial increase of the prevalence, as well as to the mode of later changes in prevalence. For most respiratory viruses a rapid increase of the prevalence was seen through the childhood continuing, for some of them, up to the 30s (influenza A and coronavirus), while rather variable patterns were found in the older age groups. Herpes simplex and cytomegaloviruses showed, interestingly, another type of pattern: a slow increase of prevalence continuing through the whole age range. The frequency of herpes simplex antibodies reached 90% by the age of 80 years. Antibody levels against any antigen in infants less than one-month-old were equal to those in 20- to 40-year-old adults, and the expected rapid decrease of antibodies took place within the first 6 months of life. Possible influences of epidemics and repeated exposures to different viruses (external boosting), and of latent or chronic infections (internal boosting), as well as of technical variations, on the observed prevalence patterns are discussed.
Antibody responses to mumps virus proteins in natural mumps infection and after vaccination with live and inactivated mumps virus vaccines.
Paired sera from 20 patients with acute mumps infection, 16 from persons vaccinated with live attenuated mumps virus vaccine, and 12 from persons vaccinated with formalin-inactivated virus vaccine were studied for mumps antibodies by single radial hemolysis (SRH), hemagglutination inhibition (HI), and by enzyme immunoassays (EIA) specific for whole virus, envelope glycoprotein, and nucleocapsid antibodies. Mumps patients had diagnostic rises in serum mumps antibodies in 90-100% of the cases depending on the method of assay. Vaccination resulted in seroconversion in 75-88% (live vaccine) and in 92% (inactivated vaccine) of the cases as detected by SRH or EIAs, whereas HI detected seroconversion only in 38% and 58% of the cases, respectively. Immunoprecipitation analyses revealed that all sera from mumps patients and nearly all postvaccination sera had antibodies against the main structural proteins of mumps virus. By immunoblotting, antibodies against denatured hemagglutinin-neuraminidase (HN) and fusion protein (F) were detected in 15-25% of mumps patients and persons vaccinated with live vaccine, whereas most postvaccination sera from those vaccinated with inactivated vaccine had HN (92%) and F (83%) protein antibodies, suggesting that antibodies against the denatured form of proteins are formed.
Immune complex assays and stored normal human sera.
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Clinical correlates of circulating immune complexes in patients with recent yersiniosis.
Circulating immune complexes (CICs) and rheumatoid factor were studied in 31 patients with serologically confirmed yersiniosis (12 in a pilot series and 19 in a prospective series). Yersiniosis is an intestinal infection complicated occasionally by extraintestinal symptoms such as aseptic arthritis. Four tests representing three main principles (affinity of human platelets and of C1q for complexed IgG and of conglutinin for C3) were used for the detection of CICs, which were found in all patients. Fifty-five of 62 specimens of serum from the prospective series of 19 patients reacted positively in at least one test. The conglutinin-binding assay and the platelet-125I-labeled staphylococcal protein A test gave positive results most frequently (74% and 84% of the time). Mean levels of CICs were significantly higher in patients with prolonged gastroenteritis than in those with histocompatibility leukocyte antigen B27-positive arthritis. During follow-up, the mean level of CICs (as measured by the platelet-protein A test) decreased significantly in patients with arthritis, while CICs and rheumatoid factor persisted in patients with prolonged gastroenteritis.
[Clinical significance of immune complex determinations].
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Questionable specificity of lipid antigen in the Mycoplasma pneumoniae complement fixation test in patients with extrapulmonary manifestations.
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Circulating immune complexes, immunoconglutinins, and rheumatoid factors in nephropathia epidemica.
Circulating immune complexes (CICs), immunoconglutinins, and antiglobulins were studied in nephropathia epidemica, an acute infectious hemorrhagic fever occurring in Finland and Scandinavia. Sixty-one serum specimens from 18 serologically confirmed patients were collected between day -5 and day 230 from the onset of fever. Five CIC tests, three immunoconglutinin tests, and various other tests were used to characterize the disease immunologically. CICs were found in all patients. The percentage detection of positive cases varied in the tests from 100% to 22%. A marked stimulation of levels of the IgM class of immunoglobulins were observed. Antiglobulin tests were positive for all of the patients. No correlation between the test results and the clinical severity of the disease could be found. Of special interest was the delay in the rise of CIC levels compared with the chromologic pattern of the clinical course. In some patients a prolonged appearance of CICs for eight months was observed.
Monensin and FCCP inhibit the intracellular transport of alphavirus membrane glycoproteins.
Temperature-sensitive mutants of semliki forest virus (SFV) and sindbis virus (SIN) were used to study the intracellular transport of virus membrane glycoproteins in infected chicken embryo fibroblasts. When antisera against purified glycoproteins and (125)I- labeled protein A from staphylococcus aureus were used only small amounts of virus glycoproteins were detected at the surface of SFV ts-1 and SIN Ts-10 infected cells incubated at the restrictive temperature (39 degrees C). When the mutant-infected cells were shifted to the permissive temperature (28 degrees C), in the presence of cycloheximide, increasing amounts of virus glycoproteins appeared at the cell surface from 20 to 80 min after the shift. Both monensin (10muM) and carbonylcyanide-p- trifluoromethoxyphenylhydrazone (FCCP; 10-20 muM) inhibited the appearance of virus membrane glycoproteins at the cell surface. Vinblastine sulfate (10 mug/ml) inhibited the transport by approximately 50 percent, whereas cytochalasin B (1 mug/ml) had only a marginal effect. Intracellular distribution of virus glycoproteins in the mutant-infected cells was visualized in double-fluorescence studies using lectins as markers for endoplasmic reticulum and Golgi apparatus. At 39 degrees C, the virus membrane glycoproteins were located at the endoplasmic reticulum, whereas after shift to 28 degrees C, a bright juxtanuclear reticular fluorescence was seen in the location of the Golgi apparatus. In the presence of monensin, the virus glycoproteins could migrate to the Golgi apparatus, although transport to the cell surface did not take place. When the shift was carried out in the presence of FCCP, negligible fluorescence was seen in the Golgi apparatus and the glycoproteins apparently remained in the rough endoplasmic reticulum. A rapid inhibition in the accumulation of virus glycoproteins at the cell surface was obtained when FCCP was added during the active transport period, whereas with monensin there was a delay of approximately 10 min. These results suggest a similar intracellular pathway in the maturation of both plasma membrane and secretory glycoproteins.
Nephropathia epidemica: detection of antigen in bank voles and serologic diagnosis of human infection.
An indirect immunofluorescence test for detection of serum antibodies specific for nephropathia epidemica (NE) has been developed with use of acetone-fixed cryostat sections of the lungs of bank voles (Clethrionomys glareolus) that had been trapped from the NE-endemic area in Finland as antigen. NE antigen was detected as distinct fluorescence in the cytoplasm of alveolar and macrophage-like cells. The 16 patients studied included typical cases from an endemic area, cases from a family outbreak, and cases in a laboratory staff which had had close contact with infected bank voles. Antibodies reacting with antigen in the lung sections developed in all of the patients but they were not found in the preimmune sera of the patients, in the sera of patients with other renal diseases, or in the sera of healthy individuals, with the exception of a member of the laboratory staff who had lived in the endemic area for 20 years. No specific IgM antibodies to NE could be detected. The rise in titer of antibodies to NE was characteristically prolonged, and elevated antibody levels persisted for many years.
Enzyme-linked immunosorbent assay for mumps and parainfluenza type 1 immunoglobulin G and immunoglobulin M antibodies.
A solid-phase enzyme-linked immunosorbent assay (ELISA) for detection of mumps and parainfluenza type 1 antibodies (immunoglobulin G [IgG] and IgM classes) is described and compared with the conventional complement fixation (CF) test. A highly positive correlation was found between mumps IgG ELISA and the mumps CF test, whereas parainfluenza type 1 IgG ELISA had only a moderate positive correlation with the respective CF test. Mumps IgM antibodies could be demonstrated in all patients with serologically verified and clinically typical (parotitis, meningitis, or orchitis) mumps virus infection, but not in patients with rises in parainfluenza CF titers. Mumps IgM was already present in the acute-phase sera if they were not taken during the first 2 days after onset of disease. Mumps IgM was also found in some paired sera that were taken too late to demonstrate any significant increase in the antibody titers by CF. Therefore, mumps IgM ELISA provides an improvement over the conventional laboratory diagnosis of mumps infection, since the measurement of specific IgM antibodies in a single serum by ELISA is diagnostic, rather than the identification of a fourfold or greater rise in CF antibody titer. An unexpected finding was that parainfluenza type 1 IgM antibodies could not be demonstrated by ELISA in paired sera with rises in parainfluenza CF titers, suggesting a different antibody response from that occurring in mumps infection.
Anti-HBe and subtypes of HBsAg among asymptomatic HBsAg carriers.
Finnish HBsAg positive blood donors were analyzed for the HBsAg subtype distribution and the presence of e antigen (HBeAg) and antibody to e (anti-HBe). 88% (159 of 180) of the donors had subtype and ad and 12% (21 of 180) had ay. HBeAg was found in 1% (2 of 180) and anti-HBe in 74% (133 of 180) of the donors. Anti-HBe was significantly (p less than 0.0001) more common among donors with subtype ad than with ay: 80 and 29% respectively. The mean age of donors with both subtype ad and anti-HBe was significantly (p less than 0.001) lower than that of the other donor categories.
Benefits and risks of killed polio vaccine. Experiences in Finland.
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