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Article ; Online: Endothelial cells: potential novel regulators of renal inflammation.

Oates, Jim C / Russell, Dayvia L / Van Beusecum, Justin P

American journal of physiology. Renal physiology

2022 Volume 322, Issue 3, Page(s) F309–F321

Abstract: Substantial evidence has supported the role of endothelial cell (EC) activation and dysfunction in the development of hypertension, chronic kidney disease (CKD), and lupus nephritis (LN). In both humans and experimental models of hypertension, CKD, and ... ...

Abstract	Substantial evidence has supported the role of endothelial cell (EC) activation and dysfunction in the development of hypertension, chronic kidney disease (CKD), and lupus nephritis (LN). In both humans and experimental models of hypertension, CKD, and LN, ECs become activated and release potent mediators of inflammation including cytokines, chemokines, and reactive oxygen species that cause EC dysfunction, tissue damage, and fibrosis. Factors that activate the endothelium include inflammatory cytokines, mechanical stretch, and pathological shear stress. These signals can activate the endothelium to promote upregulation of adhesion molecules, such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, which promote leukocyte adhesion and migration to the activated endothelium. More importantly, it is now recognized that some of these signals may in turn promote endothelial antigen presentation through major histocompatibility complex II. In this review, we will consider in-depth mechanisms of endothelial activation and the novel mechanism of endothelial antigen presentation. Moreover, we will discuss these proinflammatory events in renal pathologies and consider possible new therapeutic approaches to limit the untoward effects of endothelial inflammation in hypertension, CKD, and LN.
MeSH term(s)	Cytokines/metabolism ; Endothelial Cells/metabolism ; Endothelium, Vascular/metabolism ; Female ; Humans ; Hypertension/metabolism ; Inflammation/metabolism ; Intercellular Adhesion Molecule-1/metabolism ; Lupus Nephritis/metabolism ; Male ; Renal Insufficiency, Chronic/metabolism ; Vascular Cell Adhesion Molecule-1/metabolism
Chemical Substances	Cytokines ; Vascular Cell Adhesion Molecule-1 ; Intercellular Adhesion Molecule-1 (126547-89-5)
Language	English
Publishing date	2022-02-07
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00371.2021
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Article ; Online: Endothelial dysfunction in injury and inflammation.

Oates, Jim C

The American journal of the medical sciences

2014 Volume 349, Issue 1, Page(s) 2

MeSH term(s)	C-Reactive Protein/metabolism ; Endothelial Cells/metabolism ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/physiology ; Inflammation/metabolism ; Inflammation/physiopathology ; Liver Cirrhosis/metabolism ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/metabolism ; Vascular Diseases/metabolism ; Vascular Diseases/physiopathology
Chemical Substances	Nitric Oxide (31C4KY9ESH) ; C-Reactive Protein (9007-41-4) ; Nitric Oxide Synthase Type III (EC 1.14.13.39)
Language	English
Publishing date	2014-12-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	82078-7
ISSN	1538-2990 ; 0002-9629
ISSN (online)	1538-2990
ISSN	0002-9629
DOI	10.1097/MAJ.0000000000000401
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Article ; Online: Association Between the Anti-Aging Gene Klotho and Selected Rheumatologic Autoimmune Diseases.

Russell, Dayvia L / Oates, Jim C / Markiewicz, Margaret

The American journal of the medical sciences

2020 Volume 361, Issue 2, Page(s) 169–175

Abstract: Klotho long recognized for its role in anti-aging, is potentially implicated in the pathogenesis of rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. Aging of the immune system coincides with the inability of the body to ... ...

Abstract	Klotho long recognized for its role in anti-aging, is potentially implicated in the pathogenesis of rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. Aging of the immune system coincides with the inability of the body to recognize self-antigens, which often leads to autoimmune responses. The role of Klotho in these autoimmune diseases should be of high interest; however, few articles have been published exploring the role of Klotho in the pathogenesis, organ involvement, or clinical manifestation of rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. Herein, we discuss information gathered from peer-reviewed publications to describe the emerging role of Kl in these select rheumatologic autoimmune diseases.
MeSH term(s)	Aging/genetics ; Animals ; Autoimmune Diseases/genetics ; Glucuronidase/genetics ; Humans ; Klotho Proteins ; Rheumatic Diseases/genetics ; Scleroderma, Systemic/genetics
Chemical Substances	Glucuronidase (EC 3.2.1.31) ; Klotho Proteins (EC 3.2.1.31)
Language	English
Publishing date	2020-10-25
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	82078-7
ISSN	1538-2990 ; 0002-9629
ISSN (online)	1538-2990
ISSN	0002-9629
DOI	10.1016/j.amjms.2020.10.021
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Article ; Online: The magic of the Southern Society for Clinical Investigation: can we make the vanishing physician-scientist reappear?

Oates, Jim C

The American journal of the medical sciences

2013 Volume 345, Issue 4, Page(s) 259

MeSH term(s)	Biomedical Research/trends ; Clinical Trials as Topic ; Physician's Role ; Societies, Medical
Language	English
Publishing date	2013-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	82078-7
ISSN	1538-2990 ; 0002-9629
ISSN (online)	1538-2990
ISSN	0002-9629
DOI	10.1097/MAJ.0b013e31828a21ce
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Article ; Online: DEFINING THE MEDICAL RECORD: RELATIONSHIPS OF THE LEGAL MEDICAL RECORD, THE DESIGNATED RECORD SET, AND THE ELECTRONIC HEALTH RECORD.

Floyd, Phyllis T / Oates, Jim C / Acker, Julie W / Warren, Robert W

Perspectives in health information management

2021 Volume 18, Issue 4, Page(s) 1h

Abstract: Not so long ago, defining the "medical record" was simple. It was the paper chart-volume upon volume that captured the serial, dutifully recorded events of a person's health care at a hospital or physician's office. Entries were typically handwritten, ... ...

Abstract	Not so long ago, defining the "medical record" was simple. It was the paper chart-volume upon volume that captured the serial, dutifully recorded events of a person's health care at a hospital or physician's office. Entries were typically handwritten, dated and timed, and signed in ink with title (i.e., authenticated). Errors were easily identified by an authenticated strike-through. Similarly, the paper chart was synonymous with the legal medical record (LMR). In other words, a patient's paper chart was that patient's LMR by definition, even if critical data was omitted or irrelevant data was included. Fast-forward to 2021 and the use of technology for capturing the record of a patient's care. Technology has brought new challenges as well as successes. For example, pervasive and persistent mythologies include that 1) a patient's electronic health record (EHR) is the LMR, and 2) patient-specific EHR printouts to paper or disc-or displays on monitors-are necessarily equivalents to the paper chart of the 1980s. Neither are true. We now must define at the outset what is included in the LMR/designated record set to ensure the accuracy of what is retained and released.
MeSH term(s)	Electronic Health Records ; Humans
Language	English
Publishing date	2021-10-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2422433-9
ISSN	1559-4122 ; 1559-4122
ISSN (online)	1559-4122
ISSN	1559-4122
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Article: Lupus serum induces inflammatory interaction with neutrophils in human glomerular endothelial cells.

Russell, Dayvia A / Markiewicz, Margaret / Oates, Jim C

Lupus science & medicine

2020 Volume 7, Issue 1

Abstract: Objectives: SLE is associated with endothelial cell dysfunction (ECD). Understanding how ECD leads to neutrophil infiltration into glomeruli is essential to finding therapeutic targets for SLE. The aim of this study is to determine the effect of SLE ... ...

Abstract	Objectives: SLE is associated with endothelial cell dysfunction (ECD). Understanding how ECD leads to neutrophil infiltration into glomeruli is essential to finding therapeutic targets for SLE. The aim of this study is to determine the effect of SLE serum from patients with active disease to induce neutrophil adhesion to and chemotaxis towards glomerular endothelial cells and factors induced by serum that associate with neutrophil chemotaxis. Methods: Patients with SLE had serum collected during paired longitudinal visits with lower and higher activity. 13 patients with SLE (5 SLE, 5 SLE with hypertension (HTN) and 3 SLE lupus nephritis (LN) and HTN), and 10 healthy controls (5 with and 5 without HTN) were examined. The adhesion of neutrophils to serum-treated human renal glomerular endothelial cells (HRGECs) or chemotaxis of neutrophils towards conditioned media from serum-treated HRGECs was determined, and levels of cytokines in this conditioned medium were quantified. Pathway analysis of cytokines induced by SLE and LN serum that associated with neutrophil migration was performed. Results: HRGECs treated with SLE serum induced significantly greater neutrophil chemotaxis and adhesion compared with control serum. When examining specific cohorts, SLE HTN and LN HTN promoted greater neutrophil chemotaxis than control serum, while SLE HTN and LN HTN promoted greater chemotaxis than SLE serum. Serum from active disease visits promoted neutrophil chemotaxis and adhesion over paired inactive visits. Levels of platelet-derived growth factor-BB, interleukin (IL)-15 and IL-8 secreted by SLE serum-treated HRGECs positively correlated with neutrophil chemotaxis. Pathway analysis suggested that LN serum induced pathways important in endoplasmic reticulum and oxidative stress. Conclusions: SLE serum induces expression of mediators by HRGECs that promote neutrophil chemotaxis and adhesion, which increases during disease activity, and associates with factors common to pathways of endoplasmic reticulum and oxidative stress. These findings highlight the potential importance of serum factor-induced ECD in SLE and LN.
MeSH term(s)	Adult ; Endothelial Cells ; Female ; Humans ; Kidney ; Kidney Glomerulus ; Lupus Nephritis ; Male ; Middle Aged ; Neutrophils
Language	English
Publishing date	2020-10-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2779620-6
ISSN	2053-8790
ISSN	2053-8790
DOI	10.1136/lupus-2020-000418
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Article ; Online: Polymyalgia Rheumatica or Late Onset Lupus? A Case Report.

Altier, Jake / Oates, Jim / Ward, Celine

Journal of investigative medicine high impact case reports

2022 Volume 10, Page(s) 23247096221089493

Abstract: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with a peak age of presentation between the 15 and 40 years with a wide variety of disease manifestations. Although there is no formal definition, late onset SLE is generally defined ... ...

Abstract	Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with a peak age of presentation between the 15 and 40 years with a wide variety of disease manifestations. Although there is no formal definition, late onset SLE is generally defined in the literature as onset after the age of 50. It is estimated that 2% to 20% of patients with SLE overall fall into this category. It is important for the clinician to recognize this less-common entity because arthralgia, myalgia, fatigue, and sicca symptoms in the elderly can so easily be attributed as symptoms of normal aging or other common degenerative processes rather than a systemic disease similar to SLE or Sjogren's syndrome. The following report outlines a case of late onset SLE which initially was suspected to be polymyalgia rheumatica (PMR).
MeSH term(s)	Adolescent ; Adult ; Aged ; Giant Cell Arteritis ; Humans ; Lupus Erythematosus, Systemic/complications ; Lupus Erythematosus, Systemic/diagnosis ; Polymyalgia Rheumatica/complications ; Polymyalgia Rheumatica/diagnosis ; Sjogren's Syndrome/complications ; Sjogren's Syndrome/diagnosis ; Young Adult
Language	English
Publishing date	2022-04-06
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2710326-2
ISSN	2324-7096 ; 2324-7096
ISSN (online)	2324-7096
ISSN	2324-7096
DOI	10.1177/23247096221089493
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Article ; Online: Variable selection methods for identifying predictor interactions in data with repeatedly measured binary outcomes.

Wolf, Bethany J / Jiang, Yunyun / Wilson, Sylvia H / Oates, Jim C

Journal of clinical and translational science

2020 Volume 5, Issue 1, Page(s) e59

Abstract: Introduction: Identifying predictors of patient outcomes evaluated over time may require modeling interactions among variables while addressing within-subject correlation. Generalized linear mixed models (GLMMs) and generalized estimating equations ( ... ...

Abstract	Introduction: Identifying predictors of patient outcomes evaluated over time may require modeling interactions among variables while addressing within-subject correlation. Generalized linear mixed models (GLMMs) and generalized estimating equations (GEEs) address within-subject correlation, but identifying interactions can be difficult if not hypothesized Methods: We conducted simulations comparing stepwise selection, penalized GLMM, boosted GLMM, and boosted GEE for variable selection considering main effects and two-way interactions in data with repeatedly measured binary outcomes and evaluate a two-stage approach to reduce bias and error in parameter estimates. We compared these approaches in real data applications: hypothermia during surgery and treatment response in lupus nephritis. Results: Penalized and boosted approaches recovered correct predictors and interactions more frequently than stepwise selection. Penalized GLMM recovered correct predictors more often than boosting, but included many spurious predictors. Boosted GLMM yielded parsimonious models and identified correct predictors well at large sample and effect sizes, but required excessive computation time. Boosted GEE was computationally efficient and selected relatively parsimonious models, offering a compromise between computation and parsimony. The two-stage approach reduced the bias and error in regression parameters in all approaches. Conclusion: Penalized and boosted approaches are effective for variable selection in data with clustered binary outcomes. The two-stage approach reduces bias and error and should be applied regardless of method. We provide guidance for choosing the most appropriate method in real applications.
Language	English
Publishing date	2020-11-16
Publishing country	England
Document type	Journal Article
ISSN	2059-8661
ISSN (online)	2059-8661
DOI	10.1017/cts.2020.556
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Article: Development of a lupus nephritis suboptimal response prediction tool using renal histopathological and clinical laboratory variables at the time of diagnosis.

Helget, Lindsay N / Dillon, David J / Wolf, Bethany / Parks, Laura P / Self, Sally E / Bruner, Evelyn T / Oates, Evan E / Oates, Jim C

Lupus science & medicine

2021 Volume 8, Issue 1

Abstract: Objective: Lupus nephritis (LN) is an immune complex-mediated glomerular and tubulointerstitial disease in patients with SLE. Prediction of outcomes at the onset of LN diagnosis can guide decisions regarding intensity of monitoring and therapy for ... ...

Abstract	Objective: Lupus nephritis (LN) is an immune complex-mediated glomerular and tubulointerstitial disease in patients with SLE. Prediction of outcomes at the onset of LN diagnosis can guide decisions regarding intensity of monitoring and therapy for treatment success. Currently, no machine learning model of outcomes exists. Several outcomes modelling works have used univariate or linear modelling but were limited by the disease heterogeneity. We hypothesised that a combination of renal pathology results and routine clinical laboratory data could be used to develop and to cross-validate a clinically meaningful machine learning early decision support tool that predicts LN outcomes at approximately 1 year. Methods: To address this hypothesis, patients with LN from a prospective longitudinal registry at the Medical University of South Carolina enrolled between 2003 and 2017 were identified if they had renal biopsies with International Society of Nephrology/Renal Pathology Society pathological classification. Clinical laboratory values at the time of diagnosis and outcome variables at approximately 1 year were recorded. Machine learning models were developed and cross-validated to predict suboptimal response. Results: Five machine learning models predicted suboptimal response status in 10 times cross-validation with receiver operating characteristics area under the curve values >0.78. The most predictive variables were interstitial inflammation, interstitial fibrosis, activity score and chronicity score from renal pathology and urine protein-to-creatinine ratio, white blood cell count and haemoglobin from the clinical laboratories. A web-based tool was created for clinicians to enter these baseline clinical laboratory and histopathology variables to produce a probability score of suboptimal response. Conclusion: Given the heterogeneity of disease presentation in LN, it is important that risk prediction models incorporate several data elements. This report provides for the first time a clinical proof-of-concept tool that uses the five most predictive models and simplifies understanding of them through a web-based application.
MeSH term(s)	Female ; Humans ; Kidney/physiology ; Kidney/physiopathology ; Laboratories ; Lupus Nephritis/diagnosis ; Prospective Studies ; Tool Use Behavior
Language	English
Publishing date	2021-08-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2779620-6
ISSN	2053-8790
ISSN	2053-8790
DOI	10.1136/lupus-2021-000489
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Article ; Online: Camptothecin and Topotecan, Inhibitors of Transcription Factor Fli-1 and Topoisomerase, Markedly Ameliorate Lupus Nephritis in (NZB × NZW)F1 Mice and Reduce the Production of Inflammatory Mediators in Human Renal Cells.

Wang, Xuan / Oates, Jim C / Helke, Kristi L / Gilkeson, Gary S / Zhang, Xian K

Arthritis & rheumatology (Hoboken, N.J.)

2021 Volume 73, Issue 8, Page(s) 1478–1488

Abstract: Objective: To examine the therapeutic effects of camptothecin (CPT) and topotecan (TPT), inhibitors of transcription factor Fli-1 and topoisomerase, on lupus nephritis in (NZB × NZW)F1 (NZBWF1) mice, and to examine the effects of CPT and TPT on ... ...

Abstract	Objective: To examine the therapeutic effects of camptothecin (CPT) and topotecan (TPT), inhibitors of transcription factor Fli-1 and topoisomerase, on lupus nephritis in (NZB × NZW)F1 (NZBWF1) mice, and to examine the effects of CPT and TPT on inflammatory mediators in human renal cells. Methods: Female NZBWF1 mice were treated with vehicle, cyclophosphamide (CYC), CPT (1 mg/kg or 2 mg/kg), or TPT (0.03 mg/kg, 0.1 mg/kg, or 0. 3 mg/kg) by intraperitoneal injection twice a week, beginning at the age of 25 weeks (n = 8-10 mice per group). Blood and urine were collected for monitoring autoantibodies and proteinuria. Mice were euthanized at 40 weeks, and renal pathology scores were assessed. Human renal endothelial and mesangial cells were treated with CPT or TPT, and cytokine expression was measured. Results: None of the NZBWF1 mice treated with 1 mg/kg or 2 mg/kg of CPT or 0.3 mg/kg of TPT had proteinuria >100 mg/dl at the age of 40 weeks. One of 8 mice treated with 0.1 mg/kg of TPT and 1 of 10 mice treated with CYC had proteinuria >300 mg/dl, whereas 90% of the mice treated with vehicle had proteinuria >300 mg/dl. Compared to vehicle control, mice treated with 1 mg/kg or 2 mg/kg of CPT, 0.1 mg/kg or 0.3 mg/kg of TPT, or CYC had significantly prolonged survival, attenuated renal injury, diminished splenomegaly, reduced anti-double-stranded DNA autoantibody levels, and reduced IgG and C3 deposits in the glomeruli (all P < 0.05). Human renal cells treated with CPT or TPT had reduced expression of Fli-1 and decreased monocyte chemotactic protein 1 production following stimulation with interferon-α (IFNα) or IFNγ. Conclusion: Our findings indicate that low-dose CPT and TPT could be repurposed to treat lupus nephritis.
MeSH term(s)	Animals ; Autoantibodies/blood ; Autoantibodies/urine ; Camptothecin/pharmacology ; Cytokines/blood ; Disease Models, Animal ; Female ; Humans ; Inflammation Mediators/metabolism ; Kidney/metabolism ; Kidney/pathology ; Lupus Nephritis/drug therapy ; Lupus Nephritis/genetics ; Proteinuria/blood ; Proteinuria/urine ; Proto-Oncogene Protein c-fli-1/antagonists & inhibitors ; Topoisomerase Inhibitors/pharmacology ; Topotecan/pharmacology
Chemical Substances	Autoantibodies ; Cytokines ; Inflammation Mediators ; Proto-Oncogene Protein c-fli-1 ; Topoisomerase Inhibitors ; Topotecan (7M7YKX2N15) ; Camptothecin (XT3Z54Z28A)
Language	English
Publishing date	2021-06-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2756371-6
ISSN	2326-5205 ; 2326-5191
ISSN (online)	2326-5205
ISSN	2326-5191
DOI	10.1002/art.41685
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