Early studies indicate that rats may have a repertoire of MHC class Ib-reactive Ly49 stimulatory receptors capable of mounting memory-like NK cell alloresponses. In this article, we provide molecular and functional evidence for this assumption. Pairs of Ly49 receptors with sequence similarities in the lectin-like domains, but with opposing signaling functions, showed specificity for ligands with class Ia-like structural features encoded from the first telomeric MHC class Ib gene cluster, , which is syntenic with the cluster in mice. The activating Ly49s4 receptor and its inhibitory counterparts, Ly49i4 and Ly49i3, reacted with all allelic variants of RT1-U, whereas Ly49s5 and Ly49i5 were specific for RT1-E NK cell cytolytic responses were predictably activated and inhibited, and potent in vivo NK alloresponses were induced by repeated MHC class Ib alloimmunizations. Additional Ly49-class Ib interactions, including RT1-C with the Ly49s4/Ly49i4/Ly49i3 group of receptors, were characterized using overexpressed receptor/ligand pairs, in vitro functional assays, and limited mutational analyses. Obvious, as well as subtle, Ly49-class Ib interactions led to ligand-induced receptor calibration and NK subset expansions in vivo. Together, these studies suggest that in vivo NK alloresponses are controlled by pleomorphic Ly49-class Ib interactions, some of which may not be easily detectable in vitro.

BACKGROUND

The harmful effects of marijuana on health and in particular cardiovascular health are understudied. To develop such knowledge, an efficient method of developing an informative cohort of marijuana users and non-users is needed.

METHODS

We identified patients with a diagnosis of coronary artery disease using ICD-9 codes who were seen in the San Francisco VA in 2015. We imported these patients' medical record notes into an informatics platform that facilitated text searches. We categorized patients into those with evidence of marijuana use in the past 12 months and patients with no such evidence, using the following text strings: "marijuana", "mjx", and "cannabis". We randomly selected 51 users and 51 non-users based on this preliminary classification, and sent a recruitment letter to 97 of these patients who had contact information available. Patients were interviewed on marijuana use and domains related to cardiovascular health. Data on marijuana use collected from the medical record was compared to data collected as part of the interview.

RESULTS

The interview completion rate was 71%. Among the 35 patients identified by text strings as having used marijuana in the previous year, 15 had used marijuana in the past 30 days (positive predictive value = 42.9%). The probability of use in the past month increased from 8.8% to 42.9% in people who have these keywords in their medical record compared to those who did not have these terms in their medical record.

CONCLUSION

Methods that combine text search strategies for participant recruitment with health interviews provide an efficient approach to developing prospective cohorts that can be used to study the health effects of marijuana.