Objective: To determine whether there is a "dose-dependent" relationship between coronary atherosclerosis and the burden of exercise. Background: Recent data have suggested there may be negative consequences related to strenuous exercise. Previous studies evaluating the presence of coronary atherosclerosis as assessed by coronary calcium scores have been confounded by the presence of other cardiovascular risk factors. We aimed to assess whether there was a relationship between the burden of coronary calcium and the amount of running in a local cohort. Patients and Methods: Eighty-five runners were screened on the basis of an exercise questionnaire that was later used to determine the experimental groups from January 2016 through October 2016. Twenty-nine individuals were excluded from the study because of the presence of preexisting cardiovascular risk factors. Runners were divided into 3 categories: Group A comprised runners who had competed in at least 10 ultramarathons and/or Ironman competitions in 10 years. Group B included runners who had participated in more than 9 marathons over 10 years. Group C comprised runners who had competed in more than 9 shorter races over 10 years. Coronary artery calcium (CAC) scores were assessed by computed tomography. Statistical analysis was performed using chi-square analyses. Logistic regression models were used to assess the relationship between runner groups and calcium score greater than 100, calcium score percentile, and calcium score greater than 0. Results: There were no differences between groups A and B for CAC scores greater than 0 or greater than 100, and a similar percentage of group A and B athletes had scores greater than the 50th percentile. Groups A and B were combined for further analysis. Among those runners participating in extreme distance running (groups A and B), 73% of runners had CAC scores greater than 0 whereas only 21% of group C runners had CAC scores greater than 0 (P¼.0002). Moreover, 70% of group A þ B athletes ranked above the 50th percentile of their age and sex as assessed by a national database (Hoff JA, Chomka EV, Krainik AJ, Daviglus M, Rich S, Kondos GT. Age and gender distributions of coronary artery calcium detected by electron beam tomography in 35,246 adults. Am J Cardiol. 2001;87(12):1335-1339), whereas only 19% of group C runners were ranked above the 50th percentile (P¼.0001). One-third of runners in group A þ B had CAC scores greater than 100 as compared with only 12% of runners in group C (P¼.05). When controlling for age, sex, and number of years running, the study group was not a significant predictor of CAC greater than 100 (P¼.12). In contrast, group A þ B was 10 times more likely than group C to have CAC scores in the 50th percentile or greater (P¼.02) and 8.8 times more likely to have a abnormal calcium score when controlling for covariates (P¼.03). Conclusion: A significantly higher rate of coronary artery calcification existed in long-term marathon, ultramarathon, and extreme runners than in submarathon runners. Maratho...

Presenilin-1 (PS-1) mutations are associated with familial Alzheimer's disease (AD). Although beta-amyloid (Abeta) plaques in brain tissue are characteristic of AD patients, space occupying "cotton-wool" plaques (CWPs) lacking dense Abeta cores have also been described in patients with mutations in exon 9 of the PS-1 gene. The composition of CWPs has not been fully described. To better elucidate the composition of these space-occupying plaques, we used immunohistochemistry with antibodies to the synaptic proteins synapsin-1 and synaptophysin, as well as antibodies to tau, Abeta(-42), Abeta(-40), ubiquitin, neurofilament, and glial fibrillary acidic protein. Confocal laser scanning microscopy (CLSM) was utilized to further characterize these plaques. CWPs showed increased synapsin-1 and synaptophysin immunoreactivity relative to the background gray matter. Synaptic protein-containing CWPs occurred in all affected MTL regions, including the granule cell layer of the dentate gyrus, where synaptic terminals are usually sparse. These data suggest that in C410Y PS-1 AD patients, CWPs may constitute a major component of synaptic terminal-specific proteins, and that the C410Y PS-1 mutation may influence either synaptic structure or synaptic protein expression.

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Mammary tumor virus (Mtv29)-encoded superantigen expressed by SJL/J mouse B cell lymphomas stimulates CD4+Vβ16+ T cells and thereby acquires T cell help necessary for lymphoma growth. Mtv29 mouse mammary tumor virus env transcriptional activator (META) env-controlled Mtv29 superantigen (vSAg29) mRNA transcripts (1.8 kb) are not expressed in normal B or other somatic cells. Real-time PCR-based assays with DNA from normal SJL liver and vSAg29− lymphoma (cNJ101), digested with methylation-sensitive enzymes, showed hypermethylation at AvaI, FspI, HpaII, ThaI, and the distal HgaI sites of the META env, but vSAg29+ lymphoma cells showed significant demethylation at AvaI, HpaII, and the distal HgaI sites. The distal HgaI site that is adjacent to an Ikaros binding site is significantly demethylated in the META env DNA from primary lymphomas. Gel shift assays showed binding of Ikaros to a sequence representing this region in the META env. SJL lymphomas expressed the Ikaros isoform Ik6 that was absent in normal B cells. vSAg29+ cells exhibited increased DNaseI accessibility to chromatin at the vSAg29 initiation site. Treatment of cNJ101 cells with a demethylating agent, 5-azacytidine, and a histone deacetylase inhibitor, trichostatin A, caused hypomethylation at AvaI, HpaII, and distal HgaI sites and led to chromatin structural change at the vSAg29 initiation site, accompanied by the expression of vSAg29 transcripts. This enabled cNJ101 cells to stimulate SJL lymphoma-responsive CD4+Vβ16+ T hybridoma cells. Thus, demethylation at the distal HgaI site of the Mtv29 META env permits vSAg29 expression, which may have an impact on the development of germinal center-derived B cell lymphomas of SJL/J mice.