Usefulness of gene expression profiling of bronchoalveolar lavage cells in acute lung allograft rejection.

BackgroundChronic lung allograft dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Because effective therapies are lacking, early identification and mitigation of risk factors is a pragmatic approach to improve outcomes. Acute cellular rejection (ACR) is the most pervasive risk factor for CLAD, but diagnosis requires transbronchial biopsy, which carries risks. We hypothesized that gene expression in the bronchoalveolar lavage (BAL) cell pellet (CP) could replace biopsy and inform on mechanisms of CLAD.MethodsWe performed RNA sequencing on BAL CPs from 219 lung transplant recipients with A-grade ACR (n = 61), lymphocytic bronchiolitis (n = 58), infection (n = 41), or no rejection/infection (n = 59). Differential gene expression was based on absolute fold difference >2.0 and Benjamini-adjusted p-value ≤0.05. We used the Database for Annotation, Visualization and Integrated Discovery Bioinformatics Resource for pathway analyses. For classifier modeling, samples were randomly split into training (n = 154) and testing sets (n = 65). A logistic regression model using recursive feature elimination and 5-fold cross-validation was trained to optimize area under the curve (AUC).ResultsDifferential gene expression identified 72 genes. Enriched pathways included T-cell receptor signaling, natural killer cell-mediated cytotoxicity, and cytokine-cytokine receptor interaction. A 4-gene model (AUC = 0.72) and classification threshold defined in the training set exhibited fair performance in the testing set; accuracy was 76%, specificity 82%, and sensitivity 60%. In addition, classification as ACR was associated with worse CLAD-free survival (hazard ratio = 2.42; 95% confidence interval = 1.29-4.53).ConclusionsBAL CP gene expression during ACR is enriched for immune response pathways and shows promise as a diagnostic tool for ACR, especially ACR that is a precursor of CLAD

The impact of conventional and nonconventional inhalants on children and adolescents

AimInhalant abuse in the adolescent population is a growing concern for care givers, communities, physicians, and medical providers. The aim of this article is to provide a review of the literature about this new challenge. In addition, it raises awareness about recent health policy rulings.MethodsReview of the literature was done.ResultsIn this review article, the prevalence of different modes of inhalant use and abuse in children and young adults and their potential health implications will be examined: Cigarettes, ENDS (E Cigarettes), Hookah, Marijuana, and Huffing. Additionally, marketing and advertising tactics will be reviewed to understand how they target this population. A review of current health policy recommendations from the FDA, American Thoracic Society, and the American Academy of Pediatrics will also be discussed.ConclusionThe rapid rise in e‐cigarette and hookah use in school aged children should trigger a call to action in the medical and public health communities. Health policy recommendations need to be made to reduce the level of adolescent substance abuse.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142898/1/ppul23836_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142898/2/ppul23836.pd

Presence of matrix-specific antibodies in affinity-purified polyclonal antibodies

In general, antigen affinity columns made with commercially prepared activated affinity supports bind antibody specific for the coupled antigen. Nonetheless, in some cases affinity purification may yield antibodies to molecules other than the molecule of interest. In this report, we demonstrate such an occurrence: an antibody which adsorbs to an Affi-Prep 10 affinity matrix was found in the serum of sheep immunized against calmodulin. The contaminating antibody bound to cell nuclei and condensed chromosomes; the composition of the Affi-Prep 10 matrix suggests that the antibody may cross-react to the sugar-phosphate backbone of DNA. We were able to remove the contaminating antibody from the anti-calmodulin by passing the affinity-purified mixture over an antigen-free Affi-Prep 10 column.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29497/1/0000583.pd

Pediatric Transplantation in the United States, 1995–2004

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72899/1/j.1600-6143.2006.01271.x.pd

Microcomputer control of radiochemical processes

A system for control of radiochemical processes has been designed and constructed. Control passes through a single 8-bit port (6522 VIA) to up to 64 on-off sensors and 64 on-off switches. The outputs are latched; they are switched one at a time.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25522/1/0000063.pd

Sensitization in Transplantation: Assessment of Risk (STAR) 2017 Working Group Meeting Report

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144684/1/ajt14752_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144684/2/ajt14752.pd

Macrophage Activation and Differentiation Signals Regulate Schlafen-4 Gene Expression: Evidence for Schlafen-4 as a Modulator of Myelopoiesis

Background: The ten mouse and six human members of the Schlafen (Slfn) gene family all contain an AAA domain. Little is known of their function, but previous studies suggest roles in immune cell development. In this report, we assessed Slfn regulation and function in macrophages, which are key cellular regulators of innate immunity