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Although the mechanisms are not understood, evidence suggests that 17beta-estradiol (E2) confers protection from cardiovascular and renal complications in many diseases. We have reported that E2 decreases angiotensin type 1 receptors (AT1Rs) in different tissues and hypothesize that E2 exerts tonic inhibition on AT1Rs, reducing effects of ANG II. This study determined the effects of E2 and dihydrotestosterone (DHT) on cortical estrogen receptors (ERs) and glomerular AT1R binding in rats. Animals underwent sham operation, ovariectomy (Ovx) or orchidectomy (Cas) and were treated (Ovx +/- E2; Cas +/- DHT) for 3 wk. Cortical ERalpha protein was 2.5 times greater, and ERbeta was 80% less in females vs. males (P < 0.01). Glomerular AT1R binding was lower in females than males [4,657 +/- 838 vs. 7,457 +/- 467 counts per minute (cpm), P < 0.01]. Ovx reduced ERalpha protein by 50%, whereas E2 increased ERalpha expression after Ovx. The decrease in cortical ERalpha in Ovx rats was associated with a significant increase in AT1R binding (6,908 +/- 609 cpm), and E2 prevented this increase. There was no change in ERalpha or AT1R binding following Cas +/- DHT (25 mg) treatment, although Cas did elevate cortical ERbeta (P < 0.01). Interestingly, the high dose DHT (200 mg) elevated ERalpha 150% above intact levels and profoundly decreased AT1R binding (1,824 +/- 705 cpm, P < 0.001 vs. intact male). This indicates that under normal conditions, glomerular AT1R binding is significantly greater in male than female animals, which may be important in development of cardiovascular and renal disease in males. Furthermore, E2 regulates ERalpha and is inversely associated with glomerular AT1R binding, supporting our hypothesis that E2 tonically suppresses AT1Rs and suggesting a potential mechanism for the protective effects of estrogen.

Apoptotic debris, autoantibody, and IgG-immune complexes (ICs) have long been implicated in the inflammation associated with systemic lupus erythematosus (SLE); however, it remains unclear whether they initiate immune-mediated events that promote disease. In this study, we show that peripheral blood mononuclear cells from SLE patients experiencing active disease, and hematopoietic cells from lupus-prone MRL/lpr and NZM2410 mice accumulate markedly elevated levels of surface-bound nuclear self-antigens. On dendritic cells (DCs) and macrophages (MFs), the self-antigens are part of IgG-ICs that promote FcγRI-mediated signal transduction. Accumulation of IgG-ICs is evident on ex vivo myeloid cells from MRL/lpr mice by 10 weeks of age, and steadily increases prior to lupus nephritis. IgG and FcγRI play a critical role in disease pathology. Passive transfer of pathogenic IgG into IgG-deficient MRL/lpr mice promotes the accumulation of IgG-ICs prior to significant B cell expansion, BAFF secretion, and lupus nephritis. In contrast, diminishing the burden IgG-ICs in MRL/lpr mice through deficiency in FcγRI markedly improves these lupus pathologies. Together, our findings reveal a previously unappreciated role for the cell surface accumulation of IgG-ICs in human and murine lupus.

Objective The type 1 and type 2 systemic lupus erythematosus (SLE) categorization system was recently proposed to validate the patients’ perspective of disease and to capture a more comprehensive spectrum of symptoms. The objective of this study was to characterize the clinical manifestations of SLE subtypes and to determine the correlation between the patient‐ and physician‐reported measures used in the model. Methods This was a cross‐sectional study of patients with SLE in a university clinic. Patients completed the Systemic Lupus Activity Questionnaire (SLAQ) and 2011 American College of Rheumatology fibromyalgia (FM) criteria. Active SLE was defined as Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ≥6, clinical SLEDAI score ≥4, or active lupus nephritis. We identified 4 groups: type 1 SLE (active SLE without FM), type 2 SLE (inactive SLE with FM), mixed SLE (active SLE with FM), and minimal SLE (inactive SLE without FM). Results In this cohort of 212 patients (92% female, mean age 45 years), 30% had type 1 SLE, 8% had type 2 SLE, 13% had mixed SLE, and 49% had minimal SLE. Regardless of SLE disease activity, patients with FM (21%), reported higher SLAQ scores, patient global assessment scores, and self‐reported lupus flare that resulted in discordance between patient‐ and physician‐reported measures. Conclusion Fatigue, widespread pain, sleep dysfunction, and mood disorders are common symptoms in SLE. Identifying these symptoms as type 2 SLE may be a method to improve patient communication and understanding. The level of type 2 SLE impacts patients’ perception of disease and self‐reported symptoms. The SLAQ may need to be reinterpreted based on the FM severity scale.

This report describes the implementation and evaluation of the Bronx-Lebanon Hospital Center Dental Faculty Development Program (DFDP) for ifteen participants: ive advanced dental education faculty members and ten residents. The 100-hour DFDP, designed in the longitudinal immersion model for faculty development, was conducted in four phases at the Bronx-Lebanon Department of Dentistry in the Bronx, New York, in 2010-11. The DFDP was implemented to help underrepresented minority (URM) dental residents and clinical faculty members develop skills necessary for academic careers and enhanced teaching effectiveness. The program's curriculum had four themes: teaching and learning, scholarship, academic leadership, and career planning. For each phase, the participants completed pre-and post-training assessments of their knowledge, attitudes, and conidence, as well as qualitative evaluation of DFDP organization, content, activities, and value. The participants' pre-instruction mean knowledge score for all phases combined was 48.3 percent, and the post-test score was 81.1 percent (p=0.01). The participants showed minimal change in their attitudes about educational issues, but they reported enhanced conidence for twenty-ive skills addressed in the DFDP. The total conidence score was 77.5 (25 skills X 3.1 group mean) on all pre-tests combined and 100.2 (25 X 4.0 group mean) on the post-tests (p=0.01). The participant ratings for overall DFDP implementation and for twentyfour topical sessions were uniformly positive. The faculty and resident participants in this year-long faculty development initiative at an advanced dental education program with a high URM representation demonstrated enhanced knowledge and conidence and provided positive program evaluations. This report also describes curricular and assessment enhancements for subsequent years of the DFDP based on the irst-year outcomes.Dr. Gates is Chairman,