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Biomedical subjects

R Salonen

Publications and source records attributed to R Salonen.

At least 91 records · Page 5Linked to original sources
PubMed1996

Measles virus hemagglutinin mediates monocyte aggregation and increased adherence to measles-infected endothelial cells.

The effect of measles virus (MV) infection on monocyte adhesion was studied using human peripheral blood monocytes and monocytic and endothelial cell lines. The infection of monocytic U-937 cells led to the formation of large cellular aggregates. Aggregation was independent of intercellular adhesion molecule-1 (ICAM-1)/lymphocyte function-associated antigen-1 (LFA-1), but could be inhibited by monoclonal antibodies (mAb) against the MV hemagglutinin glycoprotein (MV-H). mAb against the MV receptor, CD46, also blocked aggregation. No significant changes in the cell surface expression of adhesion molecules CD11a, CD11b, CD11c, CD18, CD54, CD44, CD49d (alpha 4-integrin) and CD62L (L-selectin) were observed on MV-infected monocytes. Infection of a human endothelial cell line, EAhy 926 (HEC), with MV led to a two-fold increase in 1CAM-1 expression and a two-fold increase in monocyte adherence to the HEC (from 22 +/- 1.6% to 42 +/- 4.8%). However, ICAM-1 mAb reduced monocyte adhesion to the control and MV-infected HEC to a similar degree, whereas anti-MV-H antibodies abolished the difference between binding to infected and control HEC. We conclude that MV hemagglutinin mediated both the homo typic aggregation in infected monocyte cultures and increased monocyte adherence to the infected endothelial cells.

Antibodies↗
PubMed1996

Blood-brain barrier breakdown and increased intercellular adhesion molecule (ICAM-1/CD54) expression after Semliki Forest (A7) virus infection facilitates the development of experimental allergic encephalomyelitis.

This report describes two mechanisms by which virus infection can facilitate demyelinating autoimmune inflammation in the murine CNS. In the BALB/c mouse model of experimental allergic encephalomyelitis (EAE), peripheral infection with an avirulent strain (A7) of Semliki Forest virus (SFV) increased the morbidity to EAE by infecting endothelial cells and damaging the blood-brain barrier (BBB). An influx of hematogenous CD18+ (LFA-1+ and MAC-1+) cells into the CNS compartment was followed by a local increase in intercellular adhesion molecule 1 (ICAM-1) expression on the vascular endothelium. Although SFV A7 infection without EAE induction caused multifocal cerebral vascular endothelial cell infection and BBB damage followed by cellular infiltration and transient increase of ICAM-1, inflammation and demyelination of CNS white matter with classical clinical signs of EAE was observed only in EAE-induced BALB/c mice, whereas the control mice remained neurologically healthy. The upregulation of ICAM-1 after virus infection was detected after the CD18+ (LFA-1+ and MAC-1+) cells had infiltrated the CNS both after EAE induction and also in nonsensitized control mice. The observed increase in ICAM-1 expression was transient in nonsensitized SFV A7 infected mice just as in the cellular infiltrates in the CNS, but EAE induction resulted in prolongation in both the cellular infiltrates and upregulation of ICAM-1. Thus, SFV A7 infection causes BBB damage and prolongs increased ICAM-1 expression on brain endothelium. This results in increased and more rapid morbidity to EAE in mice which have been sensitized with neuroantigen. However, SFV A7-infected mice without neuroantigen sensitization remain neurologically healthy.

Alphavirus Infections↗
PubMed1996

Perceived health status and morbidity and mortality: evidence from the Kuopio ischaemic heart disease risk factor study.

BACKGROUND: Previous studies have reported an increased risk of death in those who report their health is poor, however, the role of underlying and subclinical disease in this association has not been carefully studied. METHODS: The associations between perceived health status and mortality from all causes and cardiovascular disease, incidence of myocardial infarction, carotid atherosclerosis, forced expiratory volume, and maximal exercise capacity were studied in the Kuopio Ischaemic Heart Disease Risk Factor Study, a population-based study of 2682 men, aged 42-60, in eastern Finland. RESULTS: There were strong, statistically significant, age-adjusted associations between level of perceived health and mortality from all causes (RH(bad versus good) = 3.67), cardiovascular causes (RH(bad versus good) = 6.64), and incidence of myocardial infarction (RH(bad versus good) = 3.87). Perceived health levels were strongly associated with risk factors and disease indicators. The associations with mortality and myocardial infarction outcomes were considerably weakened with progressive adjustment for eight risk factors and prevalent disease. Higher levels of perceived health were associated with less carotid atherosclerosis, and greater forced expiratory volume and maximal exercise capacity. Associations between level of perceived health and these indicators were considerably stronger in those with prevalent diseases than in those who were healthy. CONCLUSIONS: The overall pattern of results suggests that perceived health levels mainly reflect underlying disease burden.

Adult↗
PubMed1996

Experiences of mothers participating in maternal serum screening for Down's syndrome.

The participation rate in a maternal serum screening for trisomy 21 was 84% in the Helsinki trial. Six hundred and twenty-five mothers who had a positive result and a random sample of 245 mothers who had a negative result took part in the opinion survey. Ninety-five percent of the first and 97% of the second group considered the screening tests as very or quite useful. However, 12% of those with a positive result would decide against taking the test if they could reconsider, whereas 100% of those with a negative result would take it again. Too little information about the test, worries and stress, unnecessary in cases of false timing, difficult decision-making, and anxiety while awaiting the results of the chromosome study were the main complaints. More information at all stages, earlier testing, ultrasound timing before the serum test, and fast results were considered essential.

Adult↗
PubMed1996

T-cell subpopulations in the cerebrospinal fluid and peripheral blood of patients with multiple sclerosis: a follow-up study.

We analyzed the relative and absolute numbers of CD4+ cells positive and negative for CD45RA marker as well as the numbers of CD8+ cells positive and negative for CD11b in the cerebrospinal fluid (CSF) and peripheral blood (PB) of 17 patients with multiple sclerosis (MS) during and 60 days after an exacerbation. We also studied samples from 27 control patients, 17 of whom had a noninflammatory neurologic disease and 10 of whom had an inflammatory neurologic disease other than MS. The results confirmed the small number of CD45RA-positive (naive or suppressor inducer) CD4+ cells as well as CD11b-positive (suppressor) CD8+ cells in the CSF compared with the PB for all paired CSF-blood comparisons. The relative numbers of these cells did not significantly differ between samples taken during an exacerbation and those taken 2 months later. In PB, the percentage of CD8+ CD11b-positive lymphocytes was lower in patients with MS or in patients with an inflammatory neurologic disease than in patients with a noninflammatory neurologic disease. The results indicate that there are fewer cells responsible for suppression-related phenomena in CSF than in PB but that this phenomenon is not specific to MS.

Adult↗
PubMed1995

Increased risk of non-insulin dependent diabetes mellitus at low plasma vitamin E concentrations: a four year follow up study in men.

OBJECTIVE: To investigate whether low vitamin E status is a risk factor for incident non-insulin dependent diabetes mellitus. DESIGN: Population based follow up study with diabetes assessed at baseline and at four years. SETTING: Eastern Finland. SUBJECTS: Random sample of 944 men aged 42-60 who had no diabetes at the baseline examination. INTERVENTION: Oral glucose tolerance test at four year follow up. MAIN OUTCOME MEASURES: A man was defined diabetic if he had either (a) a fasting blood glucose concentration > or = 6.7 mmol/l, or (b) a blood glucose concentration > or = 10.0 mmol/l two hours after a glucose load, or (c) a clinical diagnosis of diabetes with either dietary, oral, or insulin treatment. RESULTS: 45 men developed diabetes during the follow up period. In a multivariate logistic regression model including the strongest predictors of diabetes, a low lipid standardised plasma vitamin E (below median) concentration was associated with a 3.9-fold (95% confidence interval 1.8-fold to 8.6-fold) risk of incident diabetes. A decrement of 1 mumol/l of uncategorised unstandardised vitamin E concentration was associated with an increment of 22% in the risk of diabetes when allowing for the strongest other risk factors as well as serum low density lipoprotein cholesterol and triglyceride concentrations. CONCLUSIONS: There was a strong independent association between low vitamin E status before follow up and an excess risk of diabetes at four years. This supports the theory that free radical stress has a role in the causation of non-insulin dependent diabetes mellitus.

Adult↗
PubMed1995

Kuopio Atherosclerosis Prevention Study (KAPS). A population-based primary preventive trial of the effect of LDL lowering on atherosclerotic progression in carotid and femoral arteries.

BACKGROUND: The atherosclerotic progression-reducing effect of LDL cholesterol (LDL-C) lowering has been established in subjects with severe atherosclerotic disease but not in persons with elevated LDL cholesterols without severe atherosclerosis. KAPS (Kuopio Atherosclerosis Prevention Study) is the first population-based trial in the primary prevention of carotid and femoral atherosclerosis. METHODS AND RESULTS: The eligibility requirements were serum LDL-C > or = 4.0 mmol/L and total cholesterol < 7.5 mmol/L. Out of a geographically defined population, 447 men aged 44 to 65 years (mean, 57) were randomized to pravastatin (40 mg/d) or placebo for 3 years. Less than 10% of the subjects had prior myocardial infarction. Thirty-nine men discontinued study medication; however, efficacy data were available for 424 men. The primary outcome was the rate of carotid atherosclerotic progression, measured as the linear slope over annual ultrasound examinations in the average of the maximum carotid intima-media thickness (IMT) of the far wall of up to four arterial segments (the right and left distal common carotid artery and the right and left carotid bulb). For the carotid arteries, at the overall mean baseline IMT of 1.66 mm, the rate of progression of carotid atherosclerosis was 45% (95% CI, 16 to 69%) less in the pravastatin (0.017 mm/y) than the placebo (0.031 mm/y) group (P = .005). In the common carotid artery there was a treatment effect of 66% (95% CI, 30 to 95%; pravastatin 0.010 mm/y; placebo 0.029 mm/y; P < .002) at the overall mean baseline IMT of 1.35 mm. A treatment effect of 30% (95% CI, -1% to 54%) was found for the carotid bulb (pravastatin, 0.028; placebo, 0.040; P = .056) at the overall mean baseline IMT of 2.0 mm. The treatment effect was larger in subjects with higher baseline IMT values, in smokers and in those with low plasma vitamin E levels. There was no significant treatment effect on atherosclerotic progression in the femoral arteries. CONCLUSIONS: These data establish the antiatherogenic effect of LDL-C lowering by pravastatin in hypercholesterolemic men in a primary prevention setting and suggest a greater effect in smokers than in nonsmokers.

Anticholesteremic Agents↗
PubMed1995

Socioeconomic status and carotid atherosclerosis.

BACKGROUND: There is a consistent body of evidence that socioeconomic status (SES) is importantly associated with cardiovascular morbidity and mortality. However, little information currently exists on the relationship between SES and early manifestations of atherosclerotic vascular disease. METHODS AND RESULTS: We investigated the association between education, income, and occupation and intima-media thickness (IMT) in a population-based sample of eastern Finnish men. Data from the Kuopio Ischemic Heart Disease Risk Factor Study were used to estimate mean IMT across levels of SES in 1140 men. The association between SES and IMT was examined in relation to atherosclerotic risk factors and was also stratified by degree of atherosclerotic progression and was also stratified by degree of atherosclerotic progression and prevalent cardiovascular disease. There were significant, inverse, graded differences between levels of SES and IMT. For education, the age-adjusted mean IMTs for those with primary schooling or less, some high school, and completed high school or more were 0.96, 0.94, and 0.82 mm, respectively. The difference in mean IMT between the most extreme categories of education corresponds to a 15.4% increase in the risk of myocardial infarction. Similar patterns were found for each measure of SES, although the differences between the highest and lowest levels of SES were attenuated by adjustment for risk factors. In men who had no carotid stenosis or nonstenotic plaque and in men who had no indication of prevalent cardiovascular disease, a graded, inverse association between SES and IMT persisted, even after risk factor adjustment. CONCLUSIONS: These findings demonstrate a strong association between SES and atherosclerosis in an unselected population. The results show that this association was mediated by known atherosclerotic risk factors, was evident in the early stages of atherosclerosis, and was apparent in a healthy subgroup. Our findings suggest that the impact of SES is evident early in the natural history of atherosclerotic vascular disease.

Adult↗
PubMed1995

The Kuopio Atherosclerosis Prevention Study (KAPS): effect of pravastatin treatment on lipids, oxidation resistance of lipoproteins, and atherosclerotic progression.

The Kuopio Atherosclerosis Prevention Study is the first population-based, double-blind trial in the primary prevention of carotid and femoral atherosclerosis. A total of 447 subjects with serum low density lipoprotein (LDL) cholesterol levels > or = 155 mg/dl (> or = 4.0 mmol/liter) and total cholesterol levels < 290 mg/dl (< 7.5 mmol/liter) were randomly assigned to receive either pravastatin 40 mg/day or placebo for 3 years. Atherosclerotic progression in 424 men was assessed with B-mode ultrasonography. Pravastatin reduced the rate of progression by 45% (95% confidence interval [CI]: 16-69%, p = 0.005) in carotid arteries and by 66% (95% CI: 30-90%, p = 0.002) in the common carotid arteries. The treatment effect in the carotid arteries was greater in subjects with thick arterial walls at baseline, in smokers, and in subjects with low plasma alpha-tocopherol. Subjects who received pravastatin had a higher antioxidative capacity of LDL, a longer oxidation lag of very low density lipoprotein (VLDL) plus LDL, and a reduced oxidation rate of VLDL plus LDL in vitro. These data establish the antiatherogenic effect of lowering LDL cholesterol levels by pravastatin therapy in hypercholesterolemic men in a primary prevention setting and suggest that part of the antiatherogenic effect of pravastatin may be due to an improvement in the resistance of atherogenic lipoproteins to oxidation.

Analysis of Variance↗
PubMed1995

Intake of mercury from fish, lipid peroxidation, and the risk of myocardial infarction and coronary, cardiovascular, and any death in eastern Finnish men.

BACKGROUND: Even though previous studies have suggested an association between high fish intake and reduced coronary heart disease (CHD) mortality, men in Eastern Finland, who have a high fish intake, have an exceptionally high CHD mortality. We hypothesized that this paradox could be in part explained by high mercury content in fish. METHODS AND RESULTS: We studied the relation of the dietary intake of fish and mercury, as well as hair content and urinary excretion of mercury, to the risk of acute myocardial infarction (AMI) and death from CHD, cardiovascular disease (CVD), and any cause in 1833 men aged 42 to 60 years who were free of clinical CHD, stroke, claudication, and cancer. Of these, 73 experienced an AMI in 2 to 7 years. Of the 78 decreased men, 18 died of CHD and 24 died of CVD. Men who had consumed local nonfatty fish species had elevated hair mercury contents. In Cox models with the major cardiovascular risk factors as covariates, dietary intakes of fish and mercury were associated with significantly increased risk of AMI and death from CHD, CVD, and any death. Men in the highest tertile (> or = 2.0 micrograms/g) of hair mercury content had a 2.0-fold (95% confidence interval, 1.2 to 3.1; P = .005) age- and CHD-adjusted risk of AMI and a 2.9-fold (95% CI, 1.2 to 6.6; P = .014) adjusted risk of cardiovascular death compared with those with a lower hair mercury content. In a nested case-control subsample, the 24-hour urinary mercury excretion had a significant (P = .042) independent association with the risk of AMI. Both the hair and urinary mercury associated significantly with titers of immune complexes containing oxidized LDL. CONCLUSIONS: These data suggest that a high intake of mercury from nonfatty freshwater fish and the consequent accumulation of mercury in the body are associated with an excess risk of AMI as well as death from CHD, CVD, and any cause in Eastern Finnish men and this increased risk may be due to the promotion of lipid peroxidation by mercury.

Adult↗
PubMed1995

Influx of nonactivated T lymphocytes into the cerebrospinal fluid during relapse of multiple sclerosis.

T lymphocytes were analyzed in the cerebrospinal fluid of 17 patients with multiple sclerosis during and 2 months after an exacerbation. The percentage of activated (HLA-DR+) T lymphocytes was decreased in the cerebrospinal fluid during the relapse but returned thereafter to the level comparable to that in patients with noninflammatory neurological diseases, whereas no fluctuation in the total number of these cells was found. This suggests an influx of nonactivated T lymphocytes into the cerebrospinal fluid at the beginning of the relapse.

Adult↗
PubMed1995

Interferon-beta downregulates expression of VLA-4 antigen and antagonizes interferon-gamma-induced expression of HLA-DQ on human peripheral blood monocytes.

We have studied the effect of recombinant human IFN-beta on the basal and IFN-gamma-induced expression of adhesion molecules and class II MHC antigens on human peripheral blood monocytes and on ICAM-1 (intercellular adhesion molecule-1) expression of a human umbilical vein endothelial cell line (EAhy 926). We show that IFN-beta downregulates both basal and IFN-gamma-induced expression of VLA-4 (very late activation antigen-4) antigen on monocytes, but has no effect on the expression of CD11a, CD11b, CD11c, L-selectin, CD18, ICAM-1, beta 1-integrin or CD44 on monocytes or ICAM-1 on EAhy 926 cells. We also show that IFN-beta antagonizes the IFN-gamma-induced expression of HLA-DQ-antigen, but not HLA-DR or HLA-DP antigens on monocyte surface. These findings may partially explain the beneficial effect of IFN-beta in multiple sclerosis, since VLA-4-antigen is critical for leukocyte recruitment into inflamed brain and downregulation of HLA-class II expression diminishes antigen presenting capacity of monocytes.

Cells, Cultured↗
PubMed1995

The locus for Meckel syndrome with multiple congenital anomalies maps to chromosome 17q21-q24.

Autosomal recessive Meckel syndrome (OMIM 249000) (MES), first described in 1822 by Johann F. Meckel, is a major monogenic malformation syndrome with a neural tube defect leading to death of the fetus in utero or shortly after birth. The hallmarks of the syndrome are occipital meningoencephalocele, very large kidneys with multicystic dysplasia, cystic and fibrotic changes of the liver and polydactyly (Fig. 1). Other typical malformations for MES are cleft lip and palate, urinary tract anomalies, ambiguous genitals in the males and club feet. Although MES has been reported worldwide, reports on the true birth prevalence of MES in different populations are scarce. In Finland MES is effectively screened and relatively frequent with a birth prevalence of 1:9,000 and a disease gene frequency of 0.01 (ref.4) which is of the same order of magnitude as that of the most common recessive diseases belonging to the 'Finnish disease heritage', that is genetic disorders enriched or only encountered in Finland. However, in MES, comparable or even higher incidences are also reported from other populations. Here, we report the assignment of the MES locus to chromosome 17q21-q24 in the 13 cM region, and exclude some of the potential candidate genes located in this critical chromosomal region.

Abnormalities, Multiple↗
PubMed1995

First-trimester diagnosis of hydrolethalus syndrome.

At 12 weeks of gestation, a combination of atypical hydrocephalus with absent mid-line structures and club foot was detected during transvaginal ultrasound examination. These findings were diagnostic of hydrolethalus syndrome and were confirmed after subsequent termination of the pregnancy. This is the first known case of first-trimester prenatal diagnosis of hydrolethalus syndrome.

Adult↗
PubMed1995

Lowering of body iron stores by blood letting and oxidation resistance of serum lipoproteins: a randomized cross-over trial in male smokers.

OBJECTIVES: The purpose of this study was to test the hypothesis that the reduction of body iron stores by venesection (blood letting) would reduce the susceptibility to oxidation of atherogenic serum lipoproteins. DESIGN: This is a randomized, controlled cross-over trial in 14 regularly smoking men with elevated serum ferritin concentration. The study design comprised two 14-week study periods, with a 14-week wash-out period in between, with either blood donations or control. SETTING: The study site was the Research Institute of Public Health, University of Kuopio. Investigators from the Division of Epidemiology, University of Minnesota, Minneapolis, participated in the planning of the study. SUBJECTS: Fourteen volunteers who were heavy smokers and had previous experience in blood letting were recruited for the study. INTERVENTIONS: During the intervention periods, the subjects donated 450 mg (500 mL) of blood three times in 14 weeks. MAIN OUTCOME MEASUREMENTS: Oxidation resistance of very low density lipoprotein (VLDL)/low density lipoprotein (LDL) was measured after inducing oxidation with haemin and H2O2. RESULTS: Serum ferritin concentration was reduced by 44% [95% confidence interval (CI) 8-82%, P = 0.021] during the venesection periods, the maximal oxidation velocity was decreased by 20% (95% CI 3-30%, P = 0.032), and the lag time to start of oxidation was lengthened (oxidation resistance increased) by 33% (95% CI 1-64%, P = 0.036). CONCLUSIONS: These observations indicate that the reduction of body iron stores by venesection can increase the oxidation resistance of serum VLDL/LDL in regularly smoking men.

Adult↗