Increase In Cumulative Incidence Research Articles

CpG oligodeoxynucleotides accelerate reovirus type 2-triggered insulitis in DBA/1 suckling mice.

We reported previously that reovirus type-2 (Reo-2) triggers T-helper (Th) 1-mediated autoimmune insulitis resulting in temporal impaired glucose tolerance (IGT) approximately 10 days post infection (d.p.i) in suckling DBA/1 mice. We hypothesized that CpG motifs in bacteria may enhance virus-induced insulitis through its content of unmethylated CpG motifs. In the infected mice, the intraperitoneal treatment of synthetic 20-base oligodeoxynucleotides with CpG motifs (CpG ODN) caused increase in cumulative incidence of insulitis with IGT, increased serum interferon (IFN)-gamma concentration, and high frequency of autoantibody against pancreatic islet cells, compared to the infected mice without CpG ODN at 17 d.p.i. Also CD4+ and CD8+ lymphocytes infiltrated in and/or around pancreatic islets in the CpG ODN-treated mice. This evidence suggests that CpG ODN may contribute to accelerate Reo-2-induced autoimmune reaction against pancreatic islet cells via additional effects of Th1 cytokines especially IFN-gamma.

Assessment of genetic risk for Alzheimer's disease among first-degree relatives.

Life table methods were used to determine the relative risk of Alzheimer's disease (AD) in relatives of index cases with AD. Risk of AD was assessed in 967 first-degree relatives of 128 probands with clinically diagnosed AD and 572 first-degree relatives of a control group consisting of 84 subjects with Parkinson's disease (PD). Using a method that weights likelihood of correct diagnosis of AD, cumulative risk among AD relatives by age 93 was 24%, whereas relatives of the PD probands had a weighted risk of 16% by age 90. Overall, the total lifetime risk of developing dementia was similar among first-degree relatives of patients with AD and those of patients with PD. The age-specific risks were much different, however; from the age of 65 years to the age of 80 years, relatives of patients with AD had a twofold to fourfold increased risk of dementia. Equal risks were found for parents and siblings and for male and female relatives after adjustment for sex-specific patterns of survivorship. Relatives of probands with early-onset (less than or equal to 67 years) and late-onset (greater than 67 years) AD had equivalent risks of developing illness. Because onset age was found to cluster in families, the apparent increase in cumulative incidence for dementia in relatives of early-onset cases was likely due to relatives of the late-onset cases dying before developing illness.(ABSTRACT TRUNCATED AT 250 WORDS)