Interaction between ESR1 and HLA-DR2 may contribute to the development of MS in women.
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Adult↗
Biomedical subjects
M Luomala
Publications and source records attributed to M Luomala.
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↗
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↗
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↗
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↗
Intercellular adhesion molecule-1 K/E 469 polymorphism and multiple sclerosis.
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Alleles↗
Inhibition by fenamates of calcium influx and proliferation of human lymphocytes.
1. Flufenamic and tolfenamic acids have recently been shown to inhibit receptor-mediated calcium influx in human neutrophils. The present work was designed to study the effects of these two nonsteroidal anti-inflammatory drugs on human peripheral blood lymphocyte activation. 2. Peripheral blood mononuclear cells (PBMNCs; containing 90% lymphocytes) were stimulated by mitogen concanavalin A (Con A) or by a combination of an inhibitor of microsomal Ca(2+)-adenosine triphosphatase thapsigargin (TG) and phorbol myristate acetate (PMA). The effects of the two fenamates on cell proliferation were compared with respective changes in calcium metabolism. 3. Flufenamic and tolfenamic acids (10-100 microM) inhibited both Con A and TG + PMA-induced [3H]-thymidine incorporation in a dose-dependent manner. At the same concentration range, the two fenamates inhibited the increase in intracellular free calcium concentration induced by Con A or TG + PMA. This effect was due to inhibition of calcium influx whereas calcium release from intracellular stores remained unaltered. 4. The inhibition of divalent cation influx was confirmed by showing that fenamates inhibited TG + PMA-induced Mn2+ influx. 5. The inhibitory effects of fenamates on PBMNC proliferation and Ca2+ influx were qualitatively similar with those of SK&F 96365, an earlier known inhibitor of receptor-mediated calcium entry. Ketoprofen, a chemically different prostaglandin synthetase inhibitor did not show similar suppressive effects on PBMNCs. 6. The data suggest that flufenamic and tolfenamic acids suppress proliferation of human peripheral blood lymphocytes by a mechanism which involves inhibition of Ca2+ influx and is not related to inhibition of prostanoid synthesis.
Analysis of Variance↗
Improved immunogenicity of oral D x RRV reassortant rotavirus vaccine by Lactobacillus casei GG.
In a search for new strategies to improve oral vaccination, the effect of orally administered Lactobacillus casei strain GG (LGG) in conjunction with D x RRV rhesus-human reassortant live oral rotavirus vaccine was tested in 2-5-month-old infants. Infants who received LGG showed an increased response with regard to rotavirus-specific IgM secreting cells, measured using an ELISPOT technique, on day 8 after vaccination. In infants receiving LGG or placebo, respectively, a rotavirus IgM seroconversion was detected in 26/27 (96%), versus 23/27 (85%) cases (p = 0.15) and rotavirus IgA seroconversion was detected in 26/28 (93%) versus 20/27 (74%) cases (p = 0.05). These findings suggest that LGG has an immunostimulating effect on oral rotavirus vaccination. The clinical significance of LGG-enhanced immune responses to oral vaccines should be further evaluated.
Administration, Oral↗
Progression of chronic renal failure.
The different modes of progression of renal diseases were studied in 73 patients by plotting the reciprocals (1/SCr) and logarithms (logSCr) of their serum creatinine values against time. The regression was linear in the reciprocal plot for 42 patients (57.5%) and in the logarithmic plot for 12 patients (16.4%). The type of renal disease did not predict the mode of progression. The deviations from the linear regression lines were probably most often due to changes in the level of blood pressure and to intensification of treatment for hypertension. The reciprocal plot turned out to be useful for predicting the date when end-stage renal failure was reached. An accuracy of 4 months was reached in 81.5% using the reciprocal plot but only in 25.9% using the logarithmic plot.
Adult↗