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I Elovaara

Publications and source records attributed to I Elovaara.

At least 19 recordsLinked to original sources
PubMed2003

Linkage disequilibrium between the MBP tetranucleotide repeat and multiple sclerosis is restricted to a geographically defined subpopulation in Finland.

We have previously found evidence for linkage as well as allelic and haplotype association between the myelin basic protein (MBP) gene and multiple sclerosis (MS). These findings have, however, not been reproduced in other populations. Here, we have analyzed association between MBP and MS in a new set of 349 Finnish triad families. Families with a parent born in the Southern Ostrobothnian region in western Finland (Bothnia families, n=98) were analyzed as a separate group since our previous studies included a high proportion of patients and families from this high-incidence region. Other families (n=251) were collected at five hospitals in southern, eastern, and northern Finland. The MBP short tandem repeat was genotyped, and haplotype patterns were verified by sequencing. In the Bothnia families, the previously detected associations with the 1.27 kb allele and haplotype 1.27-B10 were confirmed (P=0.01 and 0.02, respectively), whereas in the other families there was not even a trend toward association. These results demonstrate a geographic/genealogical restriction in the association between MS and the MBP short tandem repeat, highlight the importance of genealogical information in genetic studies of complex traits, and may provide an explanation why the association has not been found in many other populations.

Alleles↗
PubMed2002

High oxidized LDL and elevated plasma homocysteine contribute to the early reduction of myocardial flow reserve in healthy adults.

BACKGROUND: Impairment of coronary blood flow reserve has been shown to be an early manifestation of atherosclerosis and coronary artery disease (CAD). We studied more closely the contribution of various risk factors on early deterioration of coronary function. MATERIALS AND METHODS: Fifty-one young, apparently healthy adults, with normal or mildly elevated serum cholesterol levels but without other major risk factors for CAD, such as diabetes or hypertension, underwent positron emission tomography (PET) studies. Coronary flow reserve (CFR) was measured using O15-water. In addition to the classical risk factors, the role of several new risk indicators, such as low-density lipoprotein (LDL) oxidation, infection (Chlamydia pneumoniae antibodies), and inflammation parameters (adhesion molecules, ICAM, VCAM, selectin, and C-reactive protein), homocysteine and body iron stores were investigated. RESULTS: Elevated lipid and lipoprotein levels were not associated with reduced coronary reactivity. However, high autoantibody titers against oxidized LDL (oxLDL) were associated with 21% lower CFR than low oxLDL (P < 0.05). Furthermore, high homocysteine levels predicted low CFR (P < 0.05). The other measured parameters, Chlamydia pneumoniae antibody levels, C-reactive protein and adhesion molecule concentrations did not associate with myocardial blood flow. In a stepwise regression model, oxLDL (P = 0.03), homocysteine (P = 0.04) and triglycerides (P = 0.018) were significant predictors of CFR. CONCLUSIONS: The present study suggests an important role for oxidized LDL and plasma homocysteine on early impairment of coronary reactivity in young adults.

Adenosine↗
PubMed2001

Increased nitric oxide products in CSF in primary progressive MS may reflect brain atrophy.

Because nitric oxide (NO) is a putative mediator of oligodendrocyte damage in the primary progressive form of MS (PPMS), the authors analyzed the levels of NO oxidation products in CSF and plasma from 25 patients with PPMS and 15 controls. The levels of nitrite + nitrate (NOx) in CSF were fourfold higher in patients with PPMS than in controls (p < 0.001), whereas the concentrations in plasma were similar. These data suggests involvement of NO in nervous tissue damage in PPMS.

Adult↗
PubMed2001

A study of interleukin-1 cluster genes in susceptibility to and severity of multiple sclerosis.

In this explorative study, interleukin-1 (IL-1) receptor antagonist (IL-1RA; polymorphism of variable number of tandem repeats: VNTR), IL-1alpha (-889), IL-1beta (-511) and IL-1beta (+3953) polymorphisms were studied in relation to susceptibility to and severity of multiple sclerosis (MS), in 93 MS patients and 400 normal controls. No associations were found for any polymorphisms, alone or in combination. However, in our MS cohort, females were found to be IL-1RA allele 2 carriers more frequently than males (33/49 vs. 16/44, p = 0.0028). Using a cohort of 109 controls, IL-1RA allele 2 carriers were more frequently women with MS than control women (33/49 vs. 23/43, odds ratio (OR) = 2.19, 95% confidence interval (CI) 1.02-4.72, p = 0.043, P(C) = ns). The data suggest that the IL-1 cluster genes make no major contribution to MS, but the tentative association between IL-1RA allele 2 and susceptibility of MS in women warrants further studies.

Adult↗
PubMed2001

Elevated levels of soluble Fas and Fas ligand in cerebrospinal fluid of patients with AIDS dementia complex.

We measured the levels of sFas and sFasL in CSF and serum of HIV-1 infected patients and related them to AIDS dementia complex (ADC). Specimens were obtained from 51 HIV-1 infected individuals (29 with ADC) and 39 HIV negative individuals. The sFas was detectable in all sera and 98% of CSF specimens. Measurable levels of sFasL were found in 79% of the CSF and 98% of sera samples. According to the presence or absence of ADC, we observed significant differences in CSF sFas (median and IQR 116, 132 vs. 30, 23 pg/ml, P<0.001) and sFasL (median and IQR 127, 290 vs. 15, 73 pg/ml, P<0.001) levels. The sFas in serum differed significantly between HIV-1 infected subjects and non-infected controls (P<0.001), with no correlation to ADC. On the contrary, sFasL in serum differed among HIV-1 infected subjects according to clinical signs of ADC. In the cross-sectional study, the number of cells present in CSF and CD4+ T cell counts in blood did not correlate to the levels of CSF sFas and sFasL. Interestingly, the number of HIV RNA copies in CSF correlated significantly to the levels of CSF sFasL (P=0.001) but not to sFas in the same compartment. Antiretroviral therapy reduced viral load and sFas levels in CSF in the majority of patients. sFas is a useful marker for ADC diagnosis and follow-up during antiviral treatment.

AIDS Dementia Complex↗
PubMed2001

The combination of HLA-DR1 and HLA-DR53 protects against MS.

The DRB1/3/4/5 loci from 97 patients with MS and 100 normal control subjects were analyzed. DRB1*15 increased the risk of MS (OR = 4.2, p < 0.0001), whereas DR1 decreased the risk (OR = 0.30, p(c )= 0.005). In analyses of the DR1 risk in relation to DR51, DR52, and DR53 alleles, DR1 in combination with DR53 was found to have the strongest protective effect against MS in all subjects (OR = 0.05, p < 0.0001) and in DRB1*15-negative subjects (OR = 0.09, p(c )= 0.026). DR53 may be an important allele or haplotype, acting together with DR1 to protect against MS.

Adult↗
PubMed2000

Plasminogen activator inhibitor 1 gene and risk of MS in women.

In view of the potential importance of the proteolytic mechanisms in the evolution of MS lesions, the authors studied the 4G/5G promoter polymorphism of the plasminogen activator inhibitor 1 (PAI-1) gene in the susceptibility of MS. The 5G5G genotype was associated with MS in women at an odds ratio of 2.3 (95% confidence interval, 1.04 to 5.23). The genotype seems to be a low producer of PAI-1, suggesting that reduced capacity for proteinase inhibition may be involved in the etiopathogenesis of MS in women.

Adult↗
PubMed2000

Adhesion molecules in multiple sclerosis: relation to subtypes of disease and methylprednisolone therapy.

OBJECTIVES: To determine levels of adhesion molecules in blood and cerebrospinal fluid (CSF) samples from patients with different subtypes and activities of multiple sclerosis (MS) and to assess the effect of intravenous methylprednisolone sodium succinate treatment on the levels of soluble adhesion molecules. DESIGN: The expressions of very late activation antigen 4 (VLA-4), lymphocyte function associated antigen 1 (LFA-1), vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) were determined immunocytochemically, and levels of soluble VCAM-1, ICAM-1, and E-selectin, by means of enzyme immunoassay technique. The volumes of T2- and T1-weighted MS plaques and brain atrophy were determined by means of the semiautomatic magnetic resonance imaging (MRI) segmentation technique. SETTING: A university hospital in Finland. PATIENTS: One hundred subjects (71 patients with MS and 29 healthy control subjects). The subtypes of MS were relapsing-remitting (RRMS [n = 26]), secondary progressive (SPMS [n = 20]), and primary progressive (PPMS [n = 25]). RESULTS: In patients with RRMS and SPMS, the expressions of VLA-4 and LFA-1 on immune cells from blood were at least 1.5- to 3-fold higher than in controls (RRMS, P = .002 and P<.001, respectively; SPMS, P = .03 and P =.001, respectively). In RRMS, LFA-1 and ICAM-1 expression in blood was more up-regulated than in SPMS (P = .03 and P = .01, respectively). The expressions of adhesion molecules on CSF lymphocytes in RRMS and SPMS were of similar magnitude, but the proportions of CSF VLA-4- and LFA-1-expressing lymphocytes were 3- to 4-fold higher than in controls (P = .04 and P = .008, respectively). The levels of serum soluble VCAM-1 were higher in SPMS than in RRMS (P = .005) or PPMS (P = .04). Intravenous methylprednisolone treatment of patients with RRMS in exacerbation caused a significant reduction in the serum levels of soluble VCAM-1 and E-selectin (P<.001). In SPMS, the volumes of T2-weighted plaques correlated with the serum level of soluble ICAM-1 (r = 0.64; P = .03). CONCLUSIONS: Up-regulated adhesion molecules in blood and CSF indicate sustained potential for inflammation in the CNS throughout the clinical spectrum of MS. Therapies interfering with cell adhesion may be of key importance in suppressing MS.

Adult↗
PubMed1999

Volumes of brain atrophy and plaques correlated with neurological disability in secondary progressive multiple sclerosis.

The objectives of the present study was to correlate the segmented magnetic resonance imaging (MRI) volumes of intracranial cerebrospinal fluid (CSF) spaces (expressing the extent of brain atrophy) and cerebral plaques with the neurological disability in secondary progressive multiple sclerosis (MS). Earlier studies have mainly correlated MS plaques and neurological disability measured by expanded disability status scale (EDSS). The data on the association between brain atrophy and EDSS or regional functional scoring scale (RFSS) are very limited. We measured the volumes of intracranial CSF spaces in 28 patients with secondary progressive MS using MRI, and semiautomatic segmentation software. The volumes of T1-weighted hypointense and T2-weighted hyperintense MS plaques were also measured. In multiple regression analysis, increasing volumes of total (P=0.006) and relative (P=0.005) intracranial CSF spaces were significantly associated with worsening neurological disability as expressed by EDSS. No associations were found between these intracranial CSF space volumes and total RFSS scores. The mean volume of T2-weighted plaques showed a tendency to associate with total RFSS score (r=0.40, P=0.03), but no correlations were detected between T1- or T2-weighted plaque volumes and EDSS. The application of a new segmentation technique in quantifying intracranial cerebrospinal fluid spaces allowed an exact and sensitive way of assessing brain atrophy. The associations between brain atrophy and neurological disability expressed by EDSS suggests that the effect of MS therapies should be evaluated by measurement of brain atrophy.

Adult↗
PubMed1999

Computerised volumetric analysis of lesions in multiple sclerosis using new semi-automatic segmentation software.

The paper describes the application of new semi-automatic segmentation software to the task of detection of anatomical structures and lesion and their three-dimensional (3D) visualisation in 23 patients with secondary progressive multiple sclerosis (MS). The purpose is to study the correlation between magnetic resonance imaging (MRI) parameters (volumes of plaques and cerebrospinal fluid spaces) and clinical deficits (neurological deficits in the form of EDSS and RFSS scores, and neuropsychological deficits). The software operates in PC/Windows and PC/NeXTstep environments and utilises graphical user interfaces. Quantitative accuracy is measured by performing segmentation of fluid-filled syringes (relative error of 1.5%), and reproducibility is measured by intra- and inter-observer studies (3% and 7% variability, respectively). The mean volumes of MS plaques show significant correlations with the total RFSS scores (p = 0.04). Relative intracranial cerebrospinal fluid (CSF) space volumes show statistically significant correlation with EDSS scores (p = 0.01). The mean volume of MS plaques shows a significant correlation with the overall neuropsychological deficits (p = 0.03). 3D visualisation helps to understand the relationship of lesions to the surrounding brain structures. The use of semiautomatic segmentation techniques is recommended in the clinical diagnosis of MS patients.

Brain↗
PubMed1999

Upregulated expression of Fas and Fas ligand in brain through the spectrum of HIV-1 infection.

Apoptosis of neurons and glial cells has been shown to occur in the brain of patients with the acquired immune deficiency syndrome (AIDS) and was postulated as contributing to brain atrophy and white matter damage in these patients. Since apoptotic events may be induced by the Fas-Fas ligand (FasL) system, we analyzed the relevance of these molecules to cell depletion in eight brains from HIV-1-infected patients and nine HIV-1-negative controls all of whom were analyzed histopathologically. The presence of Fas and FasL in brain tissue was analyzed by PCR amplification using Fas- and FasL-specific oligonucleotide primers and immunohistochemistry. The visualization of DNA fragmentation was used to evaluate apoptosis. Fas transcripts were detected in brains from each of four AIDS patients, each of three asymptomatic HIV-1 carriers and each of two HIV-1-negative controls. In the brains from AIDS patients the level of Fas expression was higher than in asymptomatic carriers and uninfected controls. FasL transcripts were seen in three of seven HIV-1-infected brains, two AIDS cases and one asymptomatic HIV-1 carrier. The predominant Fas-expressing cells were reactive astrocytes seen in each of two AIDS patients and one pre-AIDS case, but not in HIV-1-negative controls. Occasional Fas-positive oligodendrocyte-like cells were also seen in AIDS and pre-AIDS cases. No significant expression of Fas and FasL was seen in neurons. Fas-positive reactive astrocytes were more frequent in foci of HIV-1 encephalitis (HIVE). In the same area reactive apoptotic astrocytes were seen in close vicinity to FasL-expressing CD3 T lymphocytes, suggesting that apoptosis of astrocytes is mediated by Fas-FasL. The Fas expression on glial cells in asymptomatic HIV-1 infection may indicate apoptosis already in the asymptomatic stage of HIV-1 disease. In AIDS brains expression of Fas and FasL may contribute to the loss of glial cells and indirectly to the loss of neurons.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Methylprednisolone reduces adhesion molecules in blood and cerebrospinal fluid in patients with MS.

OBJECTIVE: To analyze the expression of adhesion molecules on mononuclear cells from blood and CSF of patients with exacerbations of MS before and after megadose IV methylprednisolone (MP). BACKGROUND: Adhesion molecules regulate transmigration of lymphocytes and monocytes/macrophages to the CNS and have an important role in the pathogenesis of MS. METHODS: The expression of very late activation antigen 4 (VLA-4) and vascular cell adhesion molecule 1, lymphocyte function-associated antigen 1 (LFA-1), and intercellular adhesion molecule 1 (ICAM-1) was analyzed immunocytologically on lymphocytes and monocytes from blood and CSF of 23 patients and 11 healthy control subjects. The results were correlated with the Expanded Disability Status Scale and in half of the patients with the number of T2-weighted MS plaques and brain atrophy analyzed by MRI. RESULTS: After treatment, the mean proportions of VLA-4, LFA-1, and ICAM-1 on blood lymphocytes (p < 0.0003, p < 0.00001, p < 0.01) and monocytes (p < 0.0001, p < 0.0002, p < 0.007) of 23 patients decreased. The expression of these adhesion proteins was also diminished on CSF leukocytes. However, even after treatment, the levels of VLA-4 and LFA-1 on lymphocytes from blood of MS patients remained higher than in the control subjects. The level of VLA-4 and LFA-1 on blood lymphocytes (r=0.67, p=0.023) and VLA-4 on monocytes (r=0.61, p=0.047) correlated with the number of T2-weighted lesions. CONCLUSIONS: Megadose MP may suppress brain inflammation by reducing the expression of adhesion molecules on mononuclear cells from blood and CSF of MS patients. The inhibition of cellular trafficking in MS by MP offers an important means of altering the autoimmune response in MS.

Adult↗
PubMed1996

Subjective complaints of cognitive symptoms are related to psychometric findings of memory deficits in patients with HIV-1 infection.

Eighty-five subjects at various stages of human immunodeficiency virus (HIV-1) infection and 39 seronegative controls underwent neurological and neuropsychological evaluation to assess the relationship between cognitive test results and subjective complaints (cognitive, affective, motor, and other). The effect of psychiatric disorders on the association between cognitive performance and complaints of the patients was also examined. Patients with symptomatic infection had higher frequency of complaints than subjects at asymptomatic stage. Detailed neuropsychological examination confirmed a strong association between poor verbal memory and cognitive complaints. Poor performance on cognitive speed and flexibility was associated with motor complaints and motor abnormalities. These associations were not explained by psychiatric disorders or elevated depression questionnaire scores. Our observations indicate that, especially in symptomatic HIV-1 infection cognitive changes reported by patients often reflect "objective" cognitive decline, and may be the earliest signs of HIV-1 associated cognitive disorder. No direct relationship was observed between "subjective" complaints and neuropsychological performance of asymptomatic subjects. Understanding the significance of reported cognitive changes have important therapeutic implications.

AIDS Dementia Complex↗