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Biomedical subjects

K Hedman

Publications and source records attributed to K Hedman.

At least 55 records · Page 3Linked to original sources

Nephropathia epidemica in Finland: a retrospective study of 126 cases.

A total of 126 (99 males, 27 females) serologically confirmed hospital-treated adult cases of nephropathia epidemica (NE) were studied. The initial diagnosis suggested by the referring physician was correct in only 28%. Some rare clinical manifestations of NE were observed; acute myopericarditis in 3 patients and encephalitis in 1. Pulmonary involvement due to vascular congestion was observed in 16% and liver involvement in 34% of the patients. Thrombocytopenia was present in 75%, leukocytosis in 50% and anemia in 50%. Erythrocyte sedimentation rate (ESR) was 2-108 (mean 38) mm/h and C-reactive protein (CRP) 0-126 (mean 52) mg/l. Proteinuria was observed in 94%, hematuria in 58% and pyuria in 28%. Electrolyte abnormalities (hyponatremia, hypokalemia, hypocalcemia, hyperphosphatemia) were all common but rarely serious. Serum lipid changes caused by the acute infection and renal failure included very low total and HDL-cholesterol as well as high triglyceride levels. Renal function was transiently impaired in 94% of the patients and 7 needed transient dialysis therapy. All recovered.

Adolescent↗

Renal biopsy findings and clinicopathologic correlations in nephropathia epidemica.

A series of 126 adult patients with a serologically confirmed diagnosis of nephropathia epidemica (NE) were studied during the acute phase of the disease. In 86 cases, renal biopsy was performed. The severity of renal failure correlated slightly with blood inflammatory parameters and the degree of hematuria but not with the amount of proteinuria. The degree of hematuria correlated inversely with the level of thrombocytopenia. The most common histopathologic lesion was acute tubulointerstitial nephritis. Interstitial edema and inflammatory cell infiltrations were most usually present, followed by tubular epithelial and luminal alterations. Slight glomerular mesangial changes were present in 25% of the biopsy specimens. Except for hemorrhage in the outer renal medulla, the histologic lesions were relatively mild and unspecific. Interstitial hemorrhage should remind a pathologist of the possibility of NE. Tubular, interstitial and glomerular histologic damage were but vascular lesions were not associated with the clinical severity of renal failure. Glomerular alterations did not relate to the amount of urine protein excretion. Correlations, however, were so weak that in clinical work renal biopsy is usually not indicated for determination of the severity of renal failure in NE. Intrinsic renal events are probably important in the development of renal failure in NE.

Acute Kidney Injury↗

Toxoplasmosis acquired during pregnancy: improved serodiagnosis based on avidity of IgG.

Serodiagnostic methods were evaluated in prenatal screening for primary Toxoplasma infections acquired during pregnancy in the Helsinki area. Altogether 44,181 sera were obtained consecutively during each trimester from 16,733 mothers. All IgG-containing samples were first examined by a sensitive mu-capture (IgM) ELISA, and positive results were reassessed by IgM immunoblotting and indirect IgM ELISA. An assay measuring the avidity of toxoplasma IgG was used for the first time under screening conditions. Patients suspected to have recent toxoplasmosis were reexamined by IgA ELISA and selectively by the differential agglutination assay (HS/AC test) and IgE ELISA; 16 women with diagnostic increases in IgG titer, 36 with IgM fulfilling strict specificity criteria, and 25 with IgG of low avidity were identified. The measurement of IgG avidity was a highly specific and sensitive method suitable for verification of acute primary Toxoplasma infections during pregnancy.

Agglutination Tests↗

Puumala virus antibody and immunoglobulin G avidity assays based on a recombinant nucleocapsid antigen.

Puumala virus is the causative agent of nephropathia epidemica (NE), a hantavirus infection which occurs widely in northern and central Europe and is generally diagnosed by the indirect immunofluorescence (IF) method. We have now expressed the Puumala virus Sotkamo strain nucleocapsid (N) protein-coding S genome segment as a beta-galactosidase fusion protein in Escherichia coli by using the pEX2 expression vector. The recombinant protein was purified by cutting the protein band from an agarose gel, melting the agarose, and removing the protein by freezing, incubation on ice, and centrifugation. The recovery was about 1 to 5 mg/200 ml of bacterial suspension, sufficient for coating 100 to 500 enzyme immunoassay microtiter plates. In a study of 312 IF-positive and 233 IF-negative serum samples from NE patients, the recombinant-N-protein enzyme immunoassay detected immunoglobulin G antibodies to Puumala virus with 97.8% sensitivity and 98.5% specificity compared with the IF test results. In addition, an immunoglobulin G avidity enzyme immunoassay was developed and used successfully to diagnose acute NE from a single serum sample. The results demonstrate that the bioengineered antigen is suitable for use in routine diagnostic assays for Puumala virus immunity and recent infection.

Adolescent↗

Distribution and lateral mobility of the urokinase-receptor complex at the cell surface.

Pro-urokinase (pro-uPA) and activated uPA are confined to focal adhesions and cell-cell contacts. We studied the distribution of the uPA receptor (uPAR) on human fibroblasts (HES) and rhabdomyosarcoma (RD) cells by immunofluorescence and immunoelectron microscopy. Two monoclonal antibodies (MAb) utilized were against uPAR: MAb R4, which reacts with occupied and unoccupied uPAR, was concentrated at focal adhesions; MAb R3 reacting with unoccupied receptor stained cell surfaces diffusely. MAb R4 stained cell-cell contacts, tips of microspikes, and co-localized with vinculin. Of the matrix and integrin components tested, alpha v beta 3 integrin was found at focal adhesions but more centrally than uPAR. Since uPAR is anchored to the plasma membrane through a GPI lipid, we studied its mobility by antibody-induced clustering. This revealed that unoccupied uPAR was relatively mobile; MAb R3 redistributed it to clusters. In contrast, uPAR R4 and uPA antibodies at the focal contact sites remained mostly within focal contacts. Addition of exogenous uPA resulted in loss of R3 staining and increase of uPA in focal adhesions. These results suggest that occupancy of the receptor with uPA is associated with localization to cell contact sites and restricted lateral mobility.

Antibodies, Monoclonal↗

Prokaryotic expression of a VP1 polypeptide antigen for diagnosis by a human parvovirus B19 antibody enzyme immunoassay.

To produce parvovirus B19 antigen for diagnostic purposes, partially overlapping segments covering the genes encoding the viral structural proteins VP1 and VP2 were cloned into expression vectors. The constructs were induced in Escherichia coli, resulting in the expression of beta-galactosidase fusion proteins. In immunoblotting experiments with sera from patients with erythema infectiosum, immunoglobulin G (IgG) and IgM antibodies bound to a single polypeptide of 235 amino acids at the N terminus of VP1. The DNA fragment encoding this polypeptide was amplified by the polymerase chain reaction and cloned into an expression vector. The viral capsid antigen expressed in E. coli was purified by preparative agarose gel electrophoresis and used in IgG and IgM solid-phase enzyme immunoassays. Comparison with reference gamma- and mu-capture radioimmunoassays using whole virus antigen showed that these antibody tests are suitable for the serodiagnosis of human infections caused by parvovirus B19.

Antibodies, Viral↗

Immunoglobulin G antibody avidity in patients with respiratory syncytial virus infection.

The titer and avidity of respiratory syncytial virus-specific antibodies were measured in 196 serum specimens from 93 children with an acute, laboratory-confirmed respiratory syncytial virus infection. An enzyme immunoassay method based on the ability of urea to dissociate the bound antibodies with low avidity from the antigen was used. Three patterns of immune responses were observed. Children less than 6 months of age usually had low titers of antibodies with high avidity in their acute-phase serum samples. These antibodies were concluded to be of maternal origin, since their reaction pattern was similar to that of healthy adults. During the next few weeks, a slight increase in titers with a concurrent decrease in antibody avidity was observed. All children 6 to 24 months of age had low-avidity antibodies in their acute-phase serum samples, which matured to high avidity during the follow-up. On the contrary, about half of the children greater than 24 months of age had high-avidity antibodies already in the acute-phase serum samples. We conclude that the former children were experiencing primary infections with respiratory syncytial virus and the latter were experiencing reinfections. All adults with remote immunity had antibodies with high avidity.

Adult↗

Incidence of primary toxoplasma infections during pregnancy in southern Finland: a prospective cohort study.

Congenital toxoplasmosis may develop after maternal primary infection during pregnancy. Since toxoplasmosis in adults is usually asymptomatic, the only way to find the pregnancies at risk of acute toxoplasmosis (i.e. seronegative mothers) is to perform serological screening of all pregnant women. We studied toxoplasma-specific antibodies in 16,733 pregnant women in the first, second, and third trimesters over an 18-month period in the Helsinki area, with a population of 820,700. The participation rate in our study was 90.2% of all pregnancies in the area. The overall prevalence of toxoplasma seropositivity was 20.3%. The incidence of primary infection was 2.4/1000 pregnancies at risk. Our data on incidence suggest an annual occurrence of 131 cases of primary toxoplasma infections during pregnancy in Finland. Primary toxoplasma infection appears to be a significant risk to the fetus even in countries where the prevalence of toxoplasma seropositivity is low. The feasibility of mass screening for toxoplasma infections during pregnancy should be considered in order to reduce the morbidity and mortality due to congenital toxoplasmosis.

Adolescent↗

The program for antenatal screening of toxoplasmosis in Finland: a prospective cohort study.

16,733 pregnant women were studied for toxoplasma specific antibodies during an 18-month period. The number of specimens was 44,181. The IgG seropositivity of mothers was 20.3%. The incidence of primary toxoplasma infections during pregnancy was 4.2 per 1000 seronegative pregnancies by using the traditional criteria, IgG seroconversion and/or a positive IgM. By using the IgG activity test as an additional criterion, the incidence was 2.4 per 1000 seronegative pregnancies. Due to transmission rate of 40%, the number of congenital toxoplasma infections in Finland is more than 50 per year. The evaluation is going on and the cost-benefit analysis will reveal the effectiveness of antenatal screening.

Antibodies, Protozoan↗

Rapid diagnosis of hantavirus disease with an IgG-avidity assay.

Nephropathia epidemica (NE), due to Puumala virus, is endemic in eastern Europe and Scandinavia. Serodiagnosis of NE relies on conventional indirect immunofluorescence to detect IgG against Puumala virus. However, in conventional serology, most patients with acute NE have raised but stable non-diagnostic antibody titres. For better serodiagnosis of NE, we have developed a test that measures the avidity (functional affinity) of IgG antibodies against Puumala virus. This new assay was highly specific and sensitive; a diagnosis of NE could be confirmed or excluded rapidly from an early single serum sample. With this test we have now verified the diagnosis of NE in more than 1300 Finnish patients during 22 months in 1989-91. Our findings point to an incidence of confirmed hantavirus disease much higher than previously shown.

Antibodies, Viral↗

Measurement of avidity of specific IgG for verification of recent primary rubella.

Sixty-four subjects' serum samples, positive or equivocal by rubella IgM assays and containing rubella IgG, were examined for the avidity of rubella IgG. Four of the sera originated from rubella reinfections; others had false-positive IgM results due to interference by parvovirus infection or by other mechanisms; and the remaining were sera from the acute phase or convalescence of primary rubella. A novel IgG avidity test, avidity-ELISA, and a semiquantitative haemolysis typing assay were used. According to the avidity-ELISA, 29 subjects had recent primary rubella (low IgG avidity), and another 29 had previous rubella immunity (high IgG avidity), whereas 6 serum samples gave borderline avidity values. Comparison of these results with pre-existing clinical records and laboratory data showed that all samples with low IgG avidity were obtained during or shortly after acute primary rubella. All sera with high IgG avidity originated from the previously immune subjects; the rubella reinfections were confined within this group. Five of the six sera with borderline avidity values were obtained within 2 months from primary rubella. In conclusion, the measurement of IgG avidity is a powerful tool for the distinction of acute or recent primary rubella from pre-existing rubella immunity, including rubella reinfections.

Adult↗

Maturation of immunoglobulin G avidity after rubella vaccination studied by an enzyme linked immunosorbent assay (avidity-ELISA) and by haemolysis typing.

Two tests were introduced recently for assessment of the avidity of rubella immunoglobulin antibodies. In the quantitative test--avidity-enzyme linked immunosorbent assay (ELISA)--IgG antibodies obtained from individuals shortly after primary infection with rubella virus are distinguished from those with past immunity by their antigen-elution characteristics. This method uses agents that disrupt hydrophobic bonds in proteins [Kamoun PP (1988): Denaturation of globular proteins by urea: Breakdown of hydrophobic bonds? Trends in Biological Sciences 13:424-425.]. In the semiquantitative, presumptive test--haemolysis typing--the low-avidity rubella-IgG antibodies are distinguished from the high-avidity antibodies by the quality of their haemolytic zones in a radial haemolysis test. In the present study, both tests were applied to sera taken before and after vaccination with two different strains (Cendehill or RA 27/3) of live attenuated rubella virus. It was found that after vaccination of previously nonimmune subjects, IgG synthesized during the first 2 months had a very low avidity; IgG avidity increased dramatically during the subsequent 4 months and less markedly between 6 and 12 months after vaccination. On the contrary, the initially high IgG avidity of previous immune vaccinees remained at an elevated level postvaccination. These results provide a basis for identification of recent primary rubella virus infections, or vaccination reactions, by the avidity of specific IgG and also for their separation from rubella reinfections.

Adult↗

Recent primary toxoplasma infection indicated by a low avidity of specific IgG.

An unusual assay was developed for the serologic diagnosis of recent primary infection by Toxoplasma gondii. This test measures the antigen-binding avidity of toxoplasma-specific IgG antibodies. Serum samples from 5 patients with recent primary toxoplasma infection were compared with those from 21 subjects with preexisting toxoplasma immunity. Patients with primary infection exhibited a low avidity of toxoplasma-specific IgG, which persisted for several months after the onset of symptoms of toxoplasmosis. In contrast, all subjects with past immunity had a high avidity of toxoplasma-IgG. This IgG avidity assay should assist in the diagnosis of acquired toxoplasmosis and may be used to identify pregnancies that are at risk for congenital toxoplasmosis.

Adult↗

Recent rubella virus infection indicated by a low avidity of specific IgG.

Rubella-specific IgG in acute-phase sera produces a characteristically altered zone termed "soft hemolysis" in the radial hemolysis test. Here, the soft hemolysis was shown to be a product of the purified IgG1 subclass isolated from acute-phase sera. In contrast, ordinary hemolysis was produced by IgG1 isolated from sera of previous rubella immunity, indicating that the subclass composition of IgG was not involved in the mechanism of soft hemolysis. A novel type of solid-phase immunoassay was developed for the avidity of virus-specific IgG. Acute-phase IgG (with soft hemolysis) was dissociated from rubella antigen in an enzyme immunoassay (EIA) test by hydrogen-bond disrupting agents under conditions where IgG of previous immunity (showing ordinary hemolysis) remained mostly bound. These data suggest that the mechanism of soft hemolysis is the avidity of rubella-specific IgG. The new quantitative avidity EIA was tested with sera taken from 169 subjects. Recent infection could be shown from sera taken weeks or months after primary rubella.

Antibodies, Viral↗