Myeloid dendritic cells display downregulation of C-type lectin receptors and aberrant lectin uptake in systemic lupus erythematosus

Abstract Introduction There is a growing body of evidence implicating aberrant dendritic cell function as a crucial component in the immunopathogenesis of systemic lupus erythematosus. The purpose of the present study was to characterize the phagocytic capacity and expression of receptors involved in pathogen recognition and self-nonself discrimination on myeloid dendritic cells from patients with lupus. Methods Unstimulated or stimulated monocyte-derived dendritic cells were obtained from lupus patients and healthy control individuals, and expression of C-type lectin receptors (mannose receptor and dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin), complement-receptor 3 and Fcγ receptors was determined by flow cytometry. Dextran uptake by lupus and control dendritic cells was also assessed by flow cytometry. Serum IFNγ was quantified by ELISA, and uptake of microbial products was measured using fluorescently labeled zymosan. Results When compared with dendritic cells from healthy control individuals, unstimulated and stimulated lupus dendritic cells displayed significantly decreased dextran uptake and mannose receptor and dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin expression. Decreased expression of the mannose receptor was associated with high serum IFNγ levels, but not with maturation status or medications. Diminished dextran uptake and mannose receptor expression correlated with lupus disease activity. There were no differences between control and lupus dendritic cells in the expression of other pattern recognition receptors or in the capacity to uptake zymosan particles Conclusions Lupus dendritic cells have diminished endocytic capacity, which correlates with decreased mannose receptor expression. While this phenomenon appears primarily intrinsic to dendritic cells, modulation by serum factors such as IFNγ could play a role. These abnormalities may be relevant to the aberrant immune homeostasis and the increased susceptibility to infections described in lupus.http://deepblue.lib.umich.edu/bitstream/2027.42/112498/1/13075_2008_Article_2366.pd

The role of aldosterone blockade in murine lupus nephritis

Abstract Background The purpose of this study was to examine the effect of aldosterone receptor blockade on the immunopathogenesis and progression of nephritis in the (NZB × NZW) F1 murine lupus model. Methods Female NZB/W F1 mice (11 weeks old) were treated daily with 25 or 50 mg/kg oral spironolactone or vehicle. Proteinuria, renal function, and serum autoantibody levels were monitored. Renal histopathology, immune complex deposition, and immunohistochemistry were analyzed at various time points. Targeted microarray analysis was performed on renal tissue, with subsequent real-time PCR analysis of several differentially expressed genes. Results Treatment with spironolactone was well tolerated by the mice throughout the course of their disease progression, with no significant differences in azotemia or serum potassium levels between vehicle-treated and spironolactone-treated animals. By 36 weeks of age, fewer spironolactone-treated mice developed nephrotic range proteinuria as compared with the control mice (control 70.8%, 25 mg/kg spironolactone 51.3%, and 50 mg/kg spironolactone 48.6%). Compared with control mice, mice treated with 25 mg/kg spironolactone had significantly lower serum anti-single-stranded DNA levels (2,042 μg/ml versus 1,036 μg/ml; P = 0.03) and anti-double-stranded DNA levels (3,433 μg/ml versus 614 μg/ml; P = 0.05). Spironolactone-treated mice exhibited decreased histopathologic evidence of inflammation and tissue damage, as compared with control mice. Additionally, spironolactone treatment resulted in decreased expression in the kidney of several inflammatory and proapoptotic genes, including those encoding interferon-γ, B lymphocyte stimulator (BlyS), tumor necrosis factor related apoptosis inducing ligand (TRAIL), tumor necrosis factor related weak inducer of apoptosis (TWEAK), and Fas ligand. Conclusion Aldosterone receptor blockade is safe and well tolerated in progressive murine lupus nephritis, and it results in decreased levels of clinical proteinuria, lower serum levels of autoantibodies, and decreased kidney damage. It appears to modulate inflammatory changes during the progression of glomerulonephritis and may also have a previously undescribed role in attenuating apoptosishttp://deepblue.lib.umich.edu/bitstream/2027.42/112839/1/13075_2007_Article_2203.pd

Assessment of musculoskeletal examination skills of 4th year medical students using a novel OSCE

Objective: Despite the high prevalence of musculoskeletal complaints presenting to physicians in the United States, there are very few opportunities for University of Michigan clinical medical students to receive formative or summative assessment of their ability to evaluate patients with these complaints. The purpose of this study was to assess 4th year students’ ability to examine and diagnose several common musculoskeletal disorders using a novel objective structured clinical examination (OSCE). Methods: A multidisciplinary team of musculoskeletal specialists developed the content and structure of three OSCE stations focusing on examination of the shoulder, back and knee. For each station, volunteer M4 students were provided a clinical vignette with three possible diagnoses to consider, and were instructed to anticipate physical examination maneuvers or findings that would discriminate between the three diagnoses. Then they would examine a professional patient simulating findings associated with one of the diagnoses and choose their favored diagnosis. Their encounter was directly observed by a faculty member who scored their performance on selected physical examination maneuvers based on a checklist (0 = not done, 1 = partially done, 2 = fully done). Each encounter was recorded to allow for later review by another faculty. Immediate feedback was provided to students at the end of the OSCE, making this a formative as well as summative assessment experience. Faculty received verbal and written instruction on how to score students. IRB exemption was obtained for this study. Results: 44 M4 students participated in the OSCE during the spring of 2012. General performance of M4 students in examining regional musculoskeletal complaints will be reported. Performance of individuals will be correlated with: anticipation of discriminatory features prior to examining the patients; self-assessment on ability to perform the relevant exam and anticipated need to do so in their future career; previous musculoskeletal elective exposure; future career choice; and performance on the M4 Comprehensive Clinical Assessment “Back pain” and “Abdominal pain” stations. Conclusions: Initial validity evidence for a multistation musculoskeletal OSCE will be presented, as will the performance of a sampling of the 2012 graduating UM medical student class. This data will be used as part of ongoing evaluation of the longitudinal musculoskeletal curriculum at the University of Michigan medical school.http://deepblue.lib.umich.edu/bitstream/2027.42/91291/1/MedEdDay2012-poster-monradetal.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/91291/3/MEDC22poster.pd

2015 American College of Rheumatology Workforce Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144285/1/art40432_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144285/2/art40432.pd

Perceptions and emotions about learning and assessment: Why should we care?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/172060/1/medu14739.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172060/2/medu14739_am.pd