Browsing by Author "Tarrant, Teresa K"
Now showing 1 - 5 of 5
- Results Per Page
- Sort Options
Item Open Access A Mimic of Ankylosing Spondylitis, Ochronosis: Case Report and Review of the Literature.(Current allergy and asthma reports, 2021-03-05) Chu, Philip; Cuellar, Maria C; Bracken, Sonali J; Tarrant, Teresa KPurpose of review
Ochronosis and alkaptonuria are manifestations of the same condition-a rare autosomal recessive disorder resulting from a constitutional lack of homogentisate 1,2-dioxygenase (HGD) with the consequent accumulation of homogentisic acid (HGA). In ochronosis, HGA undergoes autoxidation as well as enzymatic oxidation to form an ochronotic pigment that accumulates in cartilage and connective tissues. In the beginning, there is homogentisic aciduria and pigmentation of cartilages and other connective tissues. In later years, generalized osteoarthritis of the spine and large joints, termed ochronotic arthropathy, develops.Recent findings
The diagnosis is confirmed by quantitative measurement of HGA in urine and mutation analysis of the HGD gene. One of the differential diagnoses for the skin findings is exogenous ochronosis, a limited hyperpigmentation of skin caused by some chemicals. As for the lumbar spine findings, there can be radiographic similarities with ankylosing spondylitis (AS) including reduced intervertebral disc spaces and loss of lumbar lordosis; however, ochronosis will spare the sacroiliac joint, and the lumbar spine will show dense, wafer-like disk calcification with a vacuum disc phenomenon and broad syndesmophytes. Here, we present a case of a patient with probable ochronosis that was treated many years as ankylosing spondylitis without response, and we provide a review of the current literature on ochronosis pathogenesis, diagnosis, and treatment.Item Open Access eConsults' Impact on Care Access and Wait Times in Rheumatology.(Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 2022-04) Malcolm, Elizabeth J; Brandon, Zachary; Wilson, Lauren E; Shoup, John Paul; King, Heather A; Lewinski, Allison; Greiner, Melissa A; Malone, Shauna; Miller, Julie; Keenan, Robert T; Tarrant, Teresa K; Phinney, Donna; Cho, Alex; Bosworth, Hayden B; Shah, KevinBackground/objective
A growing number of health systems have implemented eConsults to improve access to specialty advice, but few studies have described their use in rheumatology or impact on visit wait times. We evaluated the uptake of an eConsult program and its impact on wait times for in-person rheumatology visits.Methods
In this quality improvement project, we analyzed electronic health record data from 4 intervention clinics and 4 comparison clinics, 12 months before and after implementation of an eConsult program. We compared median wait time for rheumatology appointments using a pre-post difference-in-differences analysis and quantile regression, adjusting for patient age, race, sex, clinic pair, and primary insurance payer. We also interviewed 11 primary care providers from the intervention clinics and conducted a rheumatology provider focus group (n = 4) to elucidate experiences with the program.Results
Rheumatologists recommended management in primary care or referral to another specialty for 41% of eConsults, reducing initial demand for in-person visits. The median wait times dropped in the intervention and the comparison clinics (42 and 25 days, respectively). Intervention clinic median wait time dropped 17 days more than comparison clinics, and this was nonstatistically significant (p = 0.089). eConsults fit provider care tasks best for triage or initial workup for diagnosis, and less well when tests required interpretation, or when back and forth communication was needed to manage the patient's condition.Conclusions
Implementation of eConsults for rheumatology was associated with reduced wait times for rheumatology appointments and supported primary care providers in the triage and workup for a substantial portion of patients.Item Open Access G protein-coupled receptor kinase 3 modulates mesenchymal stem cell proliferation and differentiation through sphingosine-1-phosphate receptor regulation.(Stem cell research & therapy, 2022-01-29) Brozowski, Jaime M; Timoshchenko, Roman G; Serafin, D Stephen; Allyn, Brittney; Koontz, Jessica; Rabjohns, Emily M; Rampersad, Rishi R; Ren, Yinshi; Eudy, Amanda M; Harris, Taylor F; Abraham, David; Mattox, Daniel; Rubin, Clinton T; Hilton, Matthew J; Rubin, Janet; Allbritton, Nancy L; Billard, Matthew J; Tarrant, Teresa KBackground
The bone marrow niche supports hematopoietic cell development through intimate contact with multipotent stromal mesenchymal stem cells; however, the intracellular signaling, function, and regulation of such supportive niche cells are still being defined. Our study was designed to understand how G protein receptor kinase 3 (GRK3) affects bone marrow mesenchymal stem cell function by examining primary cells from GRK3-deficient mice, which we have previously published to have a hypercellular bone marrow and leukocytosis through negative regulation of CXCL12/CXCR4 signaling.Methods
Murine GRK3-deficient bone marrow mesenchymal stromal cells were harvested and cultured to differentiate into three lineages (adipocyte, chondrocyte, and osteoblast) to confirm multipotency and compared to wild type cells. Immunoblotting, modified-TANGO experiments, and flow cytometry were used to further examine the effects of GRK3 deficiency on bone marrow mesenchymal stromal cell receptor signaling. Microcomputed tomography was used to determine trabecular and cortical bone composition of GRK3-deficient mice and standard ELISA to quantitate CXCL12 production from cellular cultures.Results
GRK3-deficient, bone marrow-derived mesenchymal stem cells exhibit enhanced and earlier osteogenic differentiation in vitro. The addition of a sphingosine kinase inhibitor abrogated the osteogenic proliferation and differentiation, suggesting that sphingosine-1-phosphate receptor signaling was a putative G protein-coupled receptor regulated by GRK3. Immunoblotting showed prolonged ERK1/2 signaling after stimulation with sphingosine-1-phosphate in GRK3-deficient cells, and modified-TANGO assays suggested the involvement of β-arrestin-2 in sphingosine-1-phosphate receptor internalization.Conclusions
Our work suggests that GRK3 regulates sphingosine-1-phosphate receptor signaling on bone marrow mesenchymal stem cells by recruiting β-arrestin to the occupied GPCR to promote internalization, and lack of such regulation affects mesenchymal stem cell functionality.Item Open Access Mesenchymal stromal cells reprogram monocytes and macrophages with processing bodies.(Stem cells (Dayton, Ohio), 2021-01) Min, Hyunjung; Xu, Li; Parrott, Roberta; Overall, Christopher C; Lillich, Melina; Rabjohns, Emily M; Rampersad, Rishi R; Tarrant, Teresa K; Meadows, Norin; Fernandez-Castaneda, Anthony; Gaultier, Alban; Kurtzberg, Joanne; Filiano, Anthony JMesenchymal stromal cells (MSCs) are widely used in clinical trials because of their ability to modulate inflammation. The success of MSCs has been variable over 25 years, most likely due to an incomplete understanding of their mechanism. After MSCs are injected, they traffic to the lungs and other tissues where they are rapidly cleared. Despite being cleared, MSCs suppress the inflammatory response in the long term. Using human cord tissue-derived MSCs (hCT-MSCs), we demonstrated that hCT-MSCs directly interact and reprogram monocytes and macrophages. After engaging hCT-MSCs, monocytes and macrophages engulfed cytoplasmic components of live hCT-MSCs, then downregulated gene programs for antigen presentation and costimulation, and functionally suppressed the activation of helper T cells. We determined that low-density lipoprotein receptor-related proteins on monocytes and macrophages mediated the engulfment of hCT-MSCs. Since a large amount of cellular information can be packaged in cytoplasmic RNA processing bodies (p-bodies), we generated p-body deficient hCT-MSCs and confirmed that they failed to reprogram monocytes and macrophages in vitro and in vivo. hCT-MSCs suppressed an inflammatory response caused by a nasal lipopolysaccharide challenge. Although both control and p-body deficient hCT-MSCs were engulfed by infiltrating lung monocytes and macrophages, p-body deficient hCT-MSCs failed to suppress inflammation and downregulate MHC-II. Overall, we identified a novel mechanism by which hCT-MSCs indirectly suppressed a T-cell response by directly interacting and reprogramming monocytes and macrophages via p-bodies. The results of this study suggest a novel mechanism for how MSCs can reprogram the inflammatory response and have long-term effects to suppress inflammation.Item Open Access Taking phototherapeutics from concept to clinical launch.(Nature reviews. Chemistry, 2021-01) Vickerman, Brianna M; Zywot, Emilia M; Tarrant, Teresa K; Lawrence, David SMore than four decades have passed since the first example of a light-activated (caged) compound was described. In the intervening years, a large number of light-responsive derivatives have been reported, several of which have found utility under a variety of in vitro conditions using cells and tissues. Light-triggered bioactivity furnishes spatial and temporal control, and offers the possibility of precision dosing and orthogonal communication with different biomolecules. These inherent attributes of light have been advocated as advantageous for the delivery and/or activation of drugs at diseased sites for a variety of indications. However, the tissue penetrance of light is profoundly wavelength-dependent. Only recently have phototherapeutics that are photoresponsive in the optical window of tissue (600-900 nm) been described. This Review highlights these recent discoveries, along with their limitations and clinical opportunities. In addition, we describe preliminary in vivo studies of prospective phototherapeutics, with an emphasis on the path that remains to be navigated in order to translate light-activated drugs into clinically useful therapeutics. Finally, the unique attributes of phototherapeutics is highlighted by discussing several potential disease applications.