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R W Haile

Publications and source records attributed to R W Haile.

82 records · Page 5Linked to original sources

Relationship between measles HI titers and an MS susceptibility gene.

Recently published studies of formal linkage analyses strongly suggest that a multiple sclerosis susceptibility (MSS) gene is linked to the HLA region of the sixth chromosome. The objective of this analysis was to investigate whether or not the gene has any demonstrable relationship to the immune status with regard to measles within members of multiple-case MS families. Family members were HLA-typed, and levels of antibodies to measles were determined using the hemagglutination inhibition assay. Since a specific, HLA-defined haplotype within each family is presumably a marker for the MSS gene, family members were characterized as either carrying [(+) controls] or not carrying [(-) controls] the MSS gene by the presence of this specific haplotype. Twenty families were entered into the analyses. Results revealed that the mean titer to measles was not different between (+) and (-) controls, and that MS cases had significantly higher titers than both control groups combined.

Age Factors↗

Similar levels of immune complexes in cases of multiple sclerosis and their unaffected relatives.

To investigate the possible effect of the hypothetical multiple sclerosis susceptibility (MSS) gene on circulating immune complexes, we employed a sensitive assay to test for the presence of immune complexes in sera of MS patients and unaffected relatives classified by the presence/absence of HLA-defined markers for the MSS gene. We found no significant differences between cases and relatives. The results suggest that elevated immune complex levels in MS patients' sera reported by others may not be unique to MS cases, but may represent instead a familial phenomenon. We also report a possible association between the A3 + B7 haplotype and increased immune complexes.

Antigen-Antibody Complex↗

Segregation and linkage analysis of 40 multiplex multiple sclerosis families.

40 multiplex multiple sclerosis (MS) families were analyzed for evidence of an MS susceptibility gene linked to the HLA region of the sixth chromosome. We assumed that population associations between specific HLA alleles and MS are due to linkage disequilibrium, so preference was given to hypotheses compatible with tight linkage, and explanations were sought for conflicting evidence. The analyses proceeded in two steps: (1) segregation analysis using the computer program POINTER, and (2) linkage analysis using LINKAS, first assuming linkage equilibrium and then allowing for linkage disequilibrium and etiological heterogeneity. The results of the segregation analyses were indeterminate. The results of the linkage analyses suggest that analyses that do not allow for disequilibrium lose substantial evidence on linkage. Of the models that were investigated under linkage disequilibrium, the best fit is with a model of complete linkage (theta= 0.0) in 75% of the pedigrees and no linkage in the remaining pedigrees. We were unable, however, to statistically reject another model involving loose linkage and no heterogeneity.

Chromosomes, Human, 6-12 and X↗

Genetic susceptibility to multiple sclerosis: a linkage analysis with age-of-onset corrections.

To test the hypothesis that a multiple sclerosis susceptibility (MSS) gene is linked to the HLA loci, formal linkage analysis was conducted on 40 multiplex families, 20 each from the Seattle and Los Angeles areas. The computer program LIPED was utilized. A dominant model of inheritance was assumed. Penetrance values of 0.05, 0.35, and 0.67 were entered into the analyses, and an age-of-onset correction was incorporated. The resulting lod scores were supportive of linkage at the lower penetrance levels. The maximum lod score, 2.411, at an estimated recombination fraction of 0.10 in both males and females, was generated at a penetrance value of 0.05. With a penetrance value of 0.67, the lod scores did not support linkage. Under an autosomal dominant model of inheritance, the results were supportive of linkage when the presumed penetrance of the MSS gene is low. The results also confirmed the importance of incorporating an age-of-onset correction into linkage analyses.

Age Factors↗

Genetic susceptibility to multiple sclerosis.

Previous studies of histocompatibility (HLA) types in multiple sclerosis (MS) families did not provide convincing proof of an HLA-linked susceptibility factor. In 12 families we studied, all MS cases in each family shared at least one chromosome. The probability of this occurring in the absence of genetic linkage is approximately 0.001. The estimated penetrance is 5 percent, implying that the genetic susceptibility factor may be a necessary but not a sufficient cause of MS. Additional studies are needed to identify other differences between affected and unaffected susceptible individuals.

Female↗

Questionnaire assessment of intake of specific carotenoids.

We determined whether estimation of intake of specific carotenoids with a standard food-frequency questionnaire (FFQ) could be improved by collection of additional data on the intake of carotenoid-rich food items. The foods included on an addendum to the standard FFQ were potentially important dietary contributors of alpha- and beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin, or lycopene. Participants (n = 215), ages 50-74 years, provided fasting blood samples and completed the FFQ and the addendum. The participants were enrolled in a prepaid health plan and had undergone screening sigmoidoscopy for detection of colorectal polyps. Addendum foods were identified that accounted for variation in blood levels of specific carotenoids, conditional on intake of foods on the standard FFQ. Estimated carotenoid intakes from the standard FFQ, and from the modified FFQ with the selected addendum foods, were examined in relation to plasma carotenoid levels. The correlation coefficient between estimated carotenoid intake and plasma levels (adjusted for age, sex, serum cholesterol, alcohol intake, smoking status, and energy intake) were essentially the same for the standard and modified FFQs. The adjusted correlations for the standard FFQ only were 0.26 for alpha-carotene, 0.22 for beta-carotene, 0.36 for beta-cryptoxanthin, 0.32 for lutein+zeaxanthin, and 0.34 for lycopene. Adding carotenoid-rich foods to the FFQ did not improve estimation of intake for the carotenoids examined in this population. We conclude that assessment of intake of specific carotenoids with the FFQs currently in use may not necessarily be improved by a modified list of carotenoid-rich foods.

Adenomatous Polyps↗

Erythrocyte folate levels, oral contraceptive use and abnormal cervical cytology.

The initial hypothesis of this study was that folate depletion is a risk factor for human papillomavirus infection and cervical epithelial cell abnormalities, including dysplasia. The prevalences of low erythrocyte folate levels (defined as < 140 ng/mL erythrocytes and determined by the growth of Lactobacillus) were measured in 250 University of California at Los Angeles students. Among oral contraceptive users, low erythrocyte folate was a risk factor for an abnormal cytologic smear in both benign atypia and squamous intraepithelial lesions. Odds ratios were statistically significant for biopsied women who did not have condyloma and for those who did not have squamous intraepithelial lesions but not for those with histologically confirmed intraepithelial lesions. Low erythrocyte folate was a risk factor for a positive Virapap result in oral contraceptive users. If the folate effects are causal, the findings suggest that erythrocyte folate levels should be higher in oral contraceptive users than in nonusers to protect against an abnormal cytologic smear.

Adult↗

Red cell and plasma folate, folate consumption, and the risk of colorectal adenomatous polyps.

Epidemiological and experimental evidence suggests that dietary folate may protect against colorectal carcinogenesis. The epidemiological relationship between a biochemical measure of folate status and colorectal neoplasia in a sizeable and generally healthy population does not yet appear to have been reported. We conducted a case-control study of the relationships among red cell folate, plasma folate, folate intake, and adenomatous polyps, intermediate markers for colorectal cancer. During 1991-1993, fasting blood samples were assayed and dietary and nondietary risk factor questionnaires were administered to men and women ages 50-75 years who had a free sigmoidoscopy at a health maintenance organization. We analyzed data from 682 subjects (332 cases and 350 controls), controlling for potential confounding by sex, age, sigmoidoscopy date, and clinic. For red cell folate levels 160 ng/ml (363 nmol/liter) or more, compared to lower levels, the odds ratio was 0.76 [95% confidence interval (CI) = 0.53-1.08]. For men, the corresponding odds ratio was 0.53 (CI = 0.32-0.87); for women, it was 1.16 (CI = 0.67-2.00). Results were essentially unchanged when adjusted for levels of blood nutrients and other potential confounding variables. Plasma folate and folate intake results were similar to red cell folate results, but the associations with polyps were weaker. Results are consistent with a protective effect of red cell folate concentration against the development of colorectal polyps, at least in men. A folate effect may depend on sex-specific interactions with other nutritional or physiological factors.

Adenomatous Polyps↗