No abstract

The purpose of this study was to investigate the relation between APOE genotype and Multiple Sclerosis (MS) in a genetically homogeneous population. We examined 240 patients consulting the MS-clinic during a period of 3 years (1996 - 1999). The mean age of the patients was 41.7 years (range 19 - 80 Y, SD 10.0 Y). As a measure of the progression rate (PR) the last registered Expanded Disability Status Scale (EDSS) score was divided by the time span (years) from disease onset until the latest assessment. The APOE genotype was determined from saliva and/or blood samples using PCR-techniques. The prevalence of different APOE genotypes was compared with the allele-distribution in a population of 361 persons from a Danish cross-sectional population study. The frequency of APOE-epsilon 4/epsilon 4 homozygotes was significantly higher in the MS-group as compared to controls (P<0.05, odds ratio: 2.3), whereas the frequency distribution of other genotypes did not differ significantly. The rate of progression was significantly faster in the APOE-epsilon 4/epsilon 4 homozygotes compared to other genotypes in the MS group (P<0.05). This study suggests that the APOE-epsilon 4/epsilon 4 homozygotes have an increased risk of developing MS. MS patients with the APOE-epsilon 4/epsilon 4 allele may also have an increased rate of disease progression. Multiple Sclerosis (2000) 6 226 - 230

No abstract

Beneficial effects of EPO in patients with SAH cannot be excluded or concluded on the basis of this study and larger scale trials are warranted.

No abstract

Glutamine synthetase activity was investigated in developing primary astroglial cultures established from newborn mouse cerebral hemispheres. Between the 2nd and 4th week of culture there was little change in activity under our standard culturing conditions; however, when hydrocortisone (10 microM) was added to the cultures for 48 h, the enzyme activity increased two- to fourfold, depending upon the age of the culture, with maximum response in 2-week-old cultures. The addition of dibutyryl cyclic AMP (dBcAMP) to the culture medium caused morphological differentiation of the astroglial cells but eliminated the response of the cells to hydrocortisone. Culturing in elevated serum levels, which delays morphological differentiation and inhibits astroglial cytodifferentiation after exposure to dBcAMP, shifted the time of maximal response to hydrocortisone from 2 to 3 weeks and prevented the abolishment of glutamine synthetase induction by dBcAMP. The induction of glutamine synthetase by hydrocortisone was prevented by actinomycin D (0.5 microgram/ml), indicating its dependence upon RNA and protein synthesis. The present work thus confirms reports in the literature that hydrocortisone induces glutamine synthetase in neural tissues, but differs from the findings of Moscona and co-workers in the chick retina that intact tissues are required for the induction to occur.

As the understanding of the autoimmune inflammatory response in multiple sclerosis (MS) expands, polymorphic genes involved in this process become possible candidates that may determine the severity of disease. Therefore, three candidate genes DRB1*1501, CCR5 and apolipoprotein E (APOE) were examined in a population-based patient sample (n = 70) to assess an association between disease progression measured by clinical disability and MRI parameters. The total lesion area (TLA) on T2-weighted images was measured with a semi-automated threshold technique. Patients with the CCR5delta32 allele showed a non-significant trend towards a smaller lesion burden (TLA/years duration), but were not associated to a milder EDSS/years duration. Our data support previous assumptions of a modulation of severity in MS by the CCR5delta32 genotype, which may convey less inflammation and tissue destruction. Carriers of the DRB1*1501 and APOE-epsilon4 allels did not reveal more severe disease progression, neither by the EDSS/years of duration nor by the TLA/years duration. This study was performed on a population-based sample in a genetically homogeneous Danish population but, due to the limited number of patients examined, weak associations between candidate genes and disease variables cannot be excluded.

The purpose of this study was to investigate the relation between APOE genotype and Multiple Sclerosis (MS) in a genetically homogeneous population. We examined 240 patients consulting the MS-clinic during a period of 3 years (1996 - 1999). The mean age of the patients was 41.7 years (range 19 - 80 Y, SD 10.0 Y). As a measure of the progression rate (PR) the last registered Expanded Disability Status Scale (EDSS) score was divided by the time span (years) from disease onset until the latest assessment. The APOE genotype was determined from saliva and/or blood samples using PCR-techniques. The prevalence of different APOE genotypes was compared with the allele-distribution in a population of 361 persons from a Danish cross-sectional population study. The frequency of APOE-epsilon 4/epsilon 4 homozygotes was significantly higher in the MS-group as compared to controls (P<0.05, odds ratio: 2.3), whereas the frequency distribution of other genotypes did not differ significantly. The rate of progression was significantly faster in the APOE-epsilon 4/epsilon 4 homozygotes compared to other genotypes in the MS group (P<0.05). This study suggests that the APOE-epsilon 4/epsilon 4 homozygotes have an increased risk of developing MS. MS patients with the APOE-epsilon 4/epsilon 4 allele may also have an increased rate of disease progression. Multiple Sclerosis (2000) 6 226 - 230