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Biomedical subjects

R Salonen

Publications and source records attributed to R Salonen.

At least 145 records · Page 8Linked to original sources

Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO syndrome).

We describe 14 patients, from 11 families, who have a progressive encephalopathy with early onset. The clinical signs of the disease are severe hypotonia, convulsions with hypsarrhythmia, profound mental retardation, hyperreflexia, transient or persistent edema, and optic atrophy. These findings and the characteristic dysmorphic features allow recognition of these patients, although no basic metabolic defect has been found. Microcephaly and atrophy of the brain develop, especially in the cerebellar and brain stem areas. An autosomal recessive mode of inheritance is likely.

Brain↗

Treatment of acute exacerbations in early multiple sclerosis: cyclosporin A or prednisolone?

Twenty-six acute exacerbations in 26 patients with early definite multiple sclerosis (MS) were treated with oral cyclosporin-A (CyA) or oral prednisolone in a double-blind, controlled and randomized trial. The duration of the treatment was 6 weeks. All of the patients showed improvement during the treatment. There were no differences in outcome between patients on CyA (7.5 mg/kg) or prednisolone (decreasing doses from 0.8 mg/kg) during the 6 week treatment. However, the improvement of clinical signs 3 months after the treatment was slightly greater in the prednisolone group. The drugs did not have significant side-effects. There was no fluctuation in the CD4/CD8 ratio during the follow-up. The two treatment groups did not differ from each other in respect to the number of CD3 (T3), CD4 (T4), CD8 (T8), CD14 (monocytes), CD20 (B cells) or CD25 (interleukin-2 receptor positive cells). The number of active T cells with the interleukin-2 receptor was high in the beginning of the exacerbation but it decreased during the treatment. To conclude, the effects of CyA and prednisolone were comparable in the treatment of acute MS relapses.

Acute Disease↗

HDL, HDL2, and HDL3 subfractions, and the risk of acute myocardial infarction. A prospective population study in eastern Finnish men.

BACKGROUND: We investigated the association of cholesterol concentrations in serum high density lipoprotein (HDL) and its subfractions HDL2 and HDL3 with the risk of acute myocardial infarction in 1,799 randomly selected men 42, 48, 54, or 60 years old. METHODS AND RESULTS: Baseline examinations in the Kuopio Ischaemic Heart Disease Risk Factor Study were done during 1984-1987. In Cox multivariate survival models adjusted for age and examination year, serum HDL cholesterol of less than 1.09 mmol/l (42 mg/dl) was associated with a 3.3-fold risk of acute myocardial infarction (95% confidence intervals [CI], 1.7-6.4), serum HDL2, cholesterol of less than 0.65 mmol/l (25 mg/dl) was associated with a 4.0-fold risk of acute myocardial infarction (95% CI, 1.9-8.3), and serum HDL3 cholesterol of less than 0.40 mmol/l (15 mg/dl) was associated with a 2.0-fold (95% CI, 1.1-4.0) risk of acute myocardial infarction. Adjustments for obesity, ischemic heart disease, other cardiovascular disease, maximal oxygen uptake, systolic blood pressure, antihypertensive medication, serum low density lipoprotein cholesterol, and triglyceride concentrations reduced the excess risks associated with serum HDL, HDL2, and HDL3 cholesterol in the lowest quartiles by 52%, 48%, and 41%, respectively. Additional adjustments for alcohol consumption, cigarettes smoked daily, smoking years, and leisure time energy expenditure reduced these excess risks associated with low HDL, HDL2, and HDL3 cholesterol levels by another 26%, 24% and 21%, respectively. CONCLUSIONS: Our data confirm that both total HDL and HDL2 levels have inverse associations with the risk of acute myocardial infarction and may thus be protective factors in ischemic heart disease, whereas the role of HDL3 remains equivocal.

Adult↗

Carotid atherosclerosis in relation to systolic and diastolic blood pressure: Kuopio Ischaemic Heart Disease Risk Factor Study.

We investigated the association of systolic and diastolic blood pressure and hypertension with two different manifestations of carotid atherosclerosis in a random population sample of 1165 Eastern Finnish men aged 42, 48, 54 or 60 years, examined in the Kuopio Ischaemic Heart Disease Risk Factor Study. Carotid atherosclerosis was assessed with high-resolution B-mode ultrasonography. Men with a casual sitting systolic blood pressure of 175 mmHg or more had a 3.17-fold (95% confidence interval 1.79-5.61) prevalence of intima-media thickening--adjusted for age, smoking, S-LDL-cholesterol, IHD history and diabetes--compared to men with lower systolic pressures. The relative prevalence of carotid plaques in men with raised systolic pressures. The relative prevalence of carotid plaques in men with raised systolic blood pressure was 2.61 (95% confidence interval 1.44-4.72) in relation to men with no lesions. Our findings suggest that systolic but not diastolic hypertension is associated with an increased prevalence of both early and advanced atherosclerotic lesions in carotid arteries.

Adult↗

Prenatal diagnosis of the infantile type of neuronal ceroid lipofuscinosis by electron microscopic investigation of human chorionic villi.

Chorionic villus biopsy specimens were studied electron microscopically in six pregnancies at risk of the infantile type of neuronal ceroid lipofuscinosis (INCL). The biopsy was performed in all cases in the first trimester of pregnancy (8-10 gestation weeks) by the transcervical route. In one case, the biopsy was repeated at 17 weeks by the transabdominal procedure. In two pregnancies, the endothelial cells and, to a lesser extent, the mesenchymal cells of the chorionic villi contained unit membrane-bound inclusions typical of INCL. In both cases, the pregnancy was terminated and in one of them identical inclusions were found in the brains and kidneys of the fetus at 20 weeks of gestational age. The children from the remaining four pregnancies are healthy and have shown no signs of the disease.

Chorionic Villi Sampling↗

Progression of carotid atherosclerosis and its determinants: a population-based ultrasonography study.

We investigated the progression of carotid atherosclerosis in a population-based sample of 100 Eastern Finnish men aged 42, 48, 54 or 60 years. A high-resolution B-mode ultrasonographic examination was repeated after a follow-up of 24 months for each subject. The intimal-medial thickness (IMT) in the common carotid artery increased by -0.06 mm to 0.90 mm (mean 0.12 mm, SD 0.20 mm). Age (standardised partial coefficient, beta = 0.325, P = 0.0003), serum LDL cholesterol concentration (beta = 0.229, P = 0.0011), pack-years of smoking (beta = 0.274, P = 0.0023), blood leukocyte count (beta = 0.201, P = 0.0239), and platelet aggregability (beta = 0.165, P = 0.0646), measured at baseline, were the strongest predictors of atherosclerosis progression. Neither hypertension, current blood pressure level, serum HDL cholesterol nor serum HDL2 cholesterol concentration at the baseline examination had any association with the change of IMT over 2 yrs.

Adult↗

Association of serum low density lipoprotein cholesterol, smoking and hypertension with different manifestations of atherosclerosis.

We investigated the association of elevated serum low density lipoprotein (LDL) cholesterol levels, smoking and hypertension with different manifestations of carotid atherosclerosis in a population-based sample of 720 Eastern Finnish men aged 42, 48, 54 or 60 years, examined in the Kuopio Ischaemic Heart Disease Risk Factor Study. Carotid atherosclerosis was assessed with high-resolution B-mode ultrasonography. Men who had neither a history nor symptoms of cardiovascular disease with serum LDL cholesterol concentration in the highest tertile (4.17 mM or more) had 3.40-fold (95% confidence interval (CI) 1.98-5.84) age-, smoking- and hypertension-adjusted probability of intimal-medial thickening as compared to men in the lowest serum LDL cholesterol tertile. The odds ratio for carotid plaque versus intimal-medial thickening was only 1.03 (95% CI 0.47-2.28). The respective odds ratios for smoking (28 pack-years or more) were 1.62 (95% CI 0.79-3.32) and 3.02 (95% CI 1.41-6.47) and those for hypertension were 1.10 (95% CI 0.70-1.73) and 0.99 (95% CI 0.53-1.84). Our findings suggest that elevated serum LDL cholesterol concentration associates with an increased risk of common carotid arterial wall thickening, whereas smoking is associated more strongly with carotid plaques than intimal-medial thickening. Our cross-sectional data do not support association between hypertension and either manifestation of carotid atherosclerosis.

Adult↗

X linked neonatal myotubular myopathy: one recombination detected with four polymorphic DNA markers from Xq28.

A three generation family with X linked myotubular myopathy (MTM1) was studied with several polymorphic markers from the distal long arm of the X chromosome. A recombination between the disease gene and four markers (loci DXS52, DXS134, DXS15, F8C) from the Xq28 cluster was detected. A new polymorphic marker (U6.2) defining the locus DXS304 in the Xq27-28 region proximal to the Xq28 cluster did not show any recombination with MTM1. These results suggest the following order of loci in distal Xq: cen-DXS42-DXS105-(DXS304, MTM1)-(DXS52, DXS134, DXS15, F8C)-tel.

Cell Nucleus↗

Lymphocyte subsets in the cerebrospinal fluid in active multiple sclerosis.

We studied the relative number of lymphocyte subsets in the cerebrospinal fluid (CSF) of patients with active multiple sclerosis. The cells were double-labeled with monoclonal antibodies and were studied using a fluorescence-activated cell analyzer. The number of Leu2+Leu15+ cells and Leu3+Leu18+ cells was markedly reduced in the CSF but not in the peripheral blood of the patients. The number of Leu3+Leu18+ cells was reduced also in the CSF of control patients (patients with other inflammatory or infectious neurological diseases).

Flow Cytometry↗

Trisomy 12 mosaicism in amniocytes and dysmorphic child despite normal chromosomes in fetal blood sample.

Trisomy 12 mosaicism (44 per cent) was detected prenatally in cultured amniocytes. A cordocentesis was performed to confirm the result. Only normal cells were found in the fetal blood sample. The fetus was estimated to be at a low risk of having a chromosomal abnormality and the pregnancy continued. Eight days after birth, a congenital heart defect was detected in the child. Several dysmorphic features were also evident. Further karyotyping of different tissues revealed normal blood and urinary cells but trisomic cells in the placenta (100 per cent) and in skin fibroblasts (25 per cent). The child died at 5 weeks of age. In this case, the fetal blood sample failed to reveal the real chromosome constitution of the fetus.

Amniocentesis↗

Infection of human peripheral blood mononuclear cells with a temperature-sensitive mutant of measles virus.

A stable temperature-sensitive mutant of measles virus (MV ts38) was used to study the mechanism of virus-mediated immune suppression of peripheral blood mononuclear cells in vitro. Both unstimulated and phytohemagglutinin-stimulated cultures released infectious virus at 32 degrees C, whereas no virus was released at 37 degrees C, although both viral RNA and viral proteins were synthesized. However, the response of the lymphoid cells to phytohemagglutinin, concanavalin A, and herpes simplex virus antigen was decreased in the presence of MV ts38 at 37 degrees C. The viability of infected cells was not diminished, therefore excluding cell death as a reason for immunosuppression. Interleukin 2 did not play a role in the inhibitory effect of MV ts38. Antibodies to alpha interferon partially reversed the inhibitory effect of the virus infection on lymphocyte mitogenesis, thus implying that alpha interferon plays a role in the immunosuppression. Depletion experiments indicated that adherent cells play a greater role in the measles virus-induced immunosuppression than nonadherent cells. However, monocyte maturation to macrophages had no effect on the degree of immunosuppression.

Cell Differentiation↗

Risk factors for carotid atherosclerosis: the Kuopio Ischaemic Heart Disease Risk Factor Study.

We assessed the severity of carotid atherosclerosis in 412 men from eastern Finland aged 42, 48, 54 or 60 years at examination with B-mode ultrasonography in 1987 in the Kuopi ischaemic Heart Disease Risk Factor Study (KIHD). Thirty-seven per cent of participants had intimal-medial thickening, 10% had plaques and 2% had stenosis. Age (P less than 0.001), cigarette-years (P less than 0.001), serum LDL cholesterol (P = 0.005), low income (P = 0.020) and low alcohol consumption (P = 0.048) had significant partial associations with the severity of carotid atherosclerosis. A linear regression model including these variables and plasma fibrinogen (NS) and serum HDL-cholesterol (NS) accounted for 33% of the variation in atherosclerosis severity. Our data provide further evidence on the role of smoking and LDL-cholesterol in atherosclerosis.

Adult↗

Low levels of mumps virus antigen induced interferon-alpha production in insulin-dependent diabetes.

The in vitro production of interferon-alpha was studied in cultures of peripheral blood mononuclear cells from children with insulin-dependent diabetes. Significantly lower levels (p less than 0.01) of interferon (median 64 IU/ml) were found in mumps antigen stimulated cultures of IDDM patients compared to control children (median 256 IU/ml) whereas no differences between groups were found in the amount of interferon induced by Coxsackie B pool antigen or live Sendai virus.

Antigens, Viral↗

Measles virus inhibits lymphocyte proliferation in vitro by two different mechanisms.

We studied the effect of two different strains of measles virus (MV) on the lymphocyte blast transformation response. Infectious virus inhibited the proliferation response to PHA early during the culture when freshly isolated PBMC were stimulated. However, MV stimulated the proliferation of T cell lines early after infection and the inhibition was a late phenomenon associated with cell death. The early inhibition by the Edmonston strain of MV was shown to be monocyte-dependent by depletion studies with monoclonal antibodies. It could be partially explained by IFN-alpha production as the addition of anti-IFN-alpha antiserum to the cultures reversed the virus-induced inhibition and the addition of IFN reduced the response of uninfected PBMC. The late inhibition by the Edmonston strain was associated neither with monocytes nor with IFN-alpha but correlated with cell death in cultures. The inhibition by the Halle strain of MV was strong and associated with cell death already early after infection. The results demonstrate that MV inhibits lymphocyte proliferation by two different mechanisms and different virus strains vary both in the magnitude and mechanism of inhibition.

Cell Line↗

Impaired interleukin 1 and interleukin 2 production following in vitro abortive infection of murine spleen mononuclear cells by Semliki Forest virus.

The effect of Semliki Forest virus (SFV) infection of murine spleen mononuclear cells was investigated in vitro. A small percentage of spleen macrophages expressed viral antigens, but no infectious virus particles were released, indicating an abortive-type infection. Wild-type SFV infected a higher percentage of macrophages than the attenuated, demyelinating mutant A7. The proliferation of spleen mononuclear cells under Con A stimulation was inhibited by the viral infection. The supernatant (SN) harvested from infected and Con A-stimulated spleen adherent cells could not stimulate thymocytes in an interleukin 1 (IL-1) assay and indomethacin treatment of infected cultures had no effect. The stimulatory effect of SN from noninfected cultures in the IL-1 assay was reduced when SN from infected cultures was added, suggesting the presence of an IL-1 inhibitor. Interleukin 2 (IL-2) production by splenocytes also decreased after viral infection, but exogenous IL-2 restored the response to Con A stimulation of infected spleen cells. This study demonstrates that abortive SFV infection of spleen macrophages has an immunosuppressive effect which may lead to an aberrant immune regulation.

Animals↗

Relationship of serum selenium and antioxidants to plasma lipoproteins, platelet aggregability and prevalent ischaemic heart disease in Eastern Finnish men.

In a cross-sectional population study of 1132 unselected Eastern Finnish men aged 54 years, serum selenium concentration had a weak positive association with plasma HDL cholesterol (standardised partial regression coefficient, beta = 0.061, P = 0.019) and a fairly strong inverse relationship (beta = -0.223, P less than 0.001) with the extent of ADP-induced platelet aggregation. Neither plasma ascorbate concentration nor alpha-tocopherol to total cholesterol ratio had any association with plasma lipoproteins, platelet aggregability or prevalent ischaemic heart disease (IHD). When a covariance-correction was applied, men with ischaemic ECG findings at exercise had a lower mean serum selenium than others (81.5 micrograms/l vs. 85.9 micrograms/l, P less than 0.01 for difference). This difference was equally large for men with neither symptoms nor previous diagnosis of IHD.

Antioxidants↗