A5061912155- Lymphatic System and Diseases
- Rheumatoid Arthritis Research and Therapies
- Dermatology and Skin Diseases
- Systemic Sclerosis and Related Diseases
- Myofascial pain diagnosis and treatment
- Gout, Hyperuricemia, Uric Acid
- Autoimmune and Inflammatory Disorders Research
- Orthopedic Infections and Treatments
- IL-33, ST2, and ILC Pathways
- Systemic Lupus Erythematosus Research
- Diagnosis and Treatment of Venous Diseases
- Bone Metabolism and Diseases
- Osteoarthritis Treatment and Mechanisms
- Food Allergy and Anaphylaxis Research
- Infective Endocarditis Diagnosis and Management
- Traumatic Brain Injury and Neurovascular Disturbances
- Planarian Biology and Electrostimulation
- AI in cancer detection
- Case Reports on Hematomas
- Cerebrospinal fluid and hydrocephalus
- Bone and Joint Diseases
- Tendon Structure and Treatment
- Veterinary medicine and infectious diseases
- Urticaria and Related Conditions
- Cytokine Signaling Pathways and Interactions
University of Rochester Medical Center
2020-2024
University of Rochester
2020-2024
Indiana University School of Medicine
2024
Arthritis Northwest
2014-2022
NIHR Oxford Musculoskeletal Biomedical Research Centre
2022
Center for Translational Molecular Medicine
2018-2019
The Ohio State University
1996
Despite the initial promise of immunotherapy for CNS disease, multiple recent clinical trials have failed. This may be due in part to characteristically low penetration antibodies cerebrospinal fluid (CSF) and brain parenchyma, resulting poor target engagement. We here utilized transcranial macroscopic imaging noninvasively evaluate vivo delivery pathways CSF fluorescent tracers. Tracers proved distributed through a brain-wide network periarterial spaces, previously denoted as glymphatic...
Cranial neurosurgical procedures can cause changes in brain function. There are many potential explanations, but the effect of simply opening skull has not been addressed, except for research into syndrome trephined. The glymphatic circulation, by which CSF and interstitial fluid circulate through periarterial spaces, parenchyma, perivenous depends on arterial pulsations to provide driving force bulk flow; cranial cavity could dampen this force. authors hypothesized that a craniectomy,...
Objective To examine the efficacy and safety of pegloticase in combination with methotrexate (MTX) patients uncontrolled gout an exploratory, open-label clinical trial (ClinicalTrials.gov: NCT03635957 ) prior to a randomized, controlled trial. Methods A multicenter, study MTX co-treatment was conducted gout. Patients were administered oral (15 mg/week) folic acid (1 mg/day) 4 weeks throughout treatment. The primary outcome proportion responders, defined as serum uric (sUA) < 6 mg/dL for ≥...
Staphylococcus aureus is the predominant pathogen causing osteomyelitis. Unfortunately, no immunotherapy exists to treat these very challenging and costly infections despite decades of research, numerous vaccine failures in clinical trials. This lack success can partially be attributed an overreliance on murine models where immune correlates protection often diverge from that humans. Moreover, S. secretes immunotoxins with unique tropism human leukocytes, which compromises targeting cells...
Abstract Background Lymphatic dysfunction exists in tumor necrosis factor transgenic (TNF-Tg) mice and rheumatoid arthritis (RA) patients. While joint-draining TNF-Tg popliteal lymphatic vessels (PLVs) have deficits contractility during end-stage arthritis, the nature of muscle cells (LMCs) their TNF-altered transcriptome remain unknown. Thus, we performed single-cell RNA-sequencing (scRNAseq) on LMCs PLVs efferent to inflamed joints versus wild-type (WT) controls. Methods Single-cell...
The cellular stress response is characterized by the production of heat shock proteins (HSP) which serve important cytoprotective functions. Paradoxically, in vitro induction promotes cytopathic effect mediated infection with canine distemper virus (CDV). stress-mediated increase correlated to formation complexes between viral nucleocapsid (NC) and major inducible member ≈ 70 kDa family HSP (hsp72). objective present study was document functional significance CDV NC-HSP interaction....
Objective To assess differences between lymphatic function in the affected hands of rheumatoid arthritis ( RA ) patients with active synovitis and that healthy controls, using indocyanine green ICG dye near‐infrared NIR imaging. Methods imaging 8 13 controls was performed following web space injection 0.1 ml 100 μ M . The percentage retention spaces determined by at baseline 7 days (±1 day) after initial injections; image analysis provided contraction frequency. + vessel LV length branching...
Micro-computed tomography (μCT) is a valuable imaging modality for longitudinal quantification of bone volumes to identify disease or treatment effects broad range conditions that affect health. Complex structures, such as the hindpaw with up 31 distinct bones in mice, have considerable analytic potential, but often limited single volume metric due intensive effort manual segmentation. Herein, we introduce high-throughput, user-friendly, and semi-automated method segmentation murine μCT datasets.
Introduction Defective lymphatic drainage and translocation of B-cells in inflamed (Bin) joint-draining lymph node sinuses are pathogenic phenomena patients with severe rheumatoid arthritis (RA). However, the molecular mechanisms underlying this dysfunction remain poorly understood. Herein, we utilized multi-omic spatial single-cell transcriptomics to evaluate altered cellular composition (including endothelial cells, macrophages, B-cells, T-cells) their associated phenotypic changes...
Rheumatoid arthritis (RA) is a complex immune-mediated inflammatory disorder in which patients suffer from inflammatory-erosive arthritis. Recent advances on histopathology heterogeneity of RA synovial tissue revealed three distinct phenotypes based cellular composition (pauci-immune, diffuse and lymphoid), suggesting that etiologies warrant specific targeted therapy motivates need for cost effective phenotyping tools preclinical clinical settings. To this end, we developed an automated...
Abstract Osteomyelitis is a devastating complication of orthopaedic surgery and commonly caused by Staphylococcus aureus ( S. ) Group B Streptococcus (GBS, agalactiae ). Clinically, osteomyelitis associated with local inflammation, abscesses, aggressive osteolysis, septic implant loosening. In contrast, infections generally involve soft tissue, acute life‐threatening vascular spread. While preclinical models that recapitulate the clinical features bone infection have proven useful for...
Abstract Loss of popliteal lymphatic vessel (PLV) contractions, which is associated with damage to muscle cells (LMCs), a biomarker disease progression in mice inflammatory arthritis. Currently, the nature LMC progenitors has yet be formally described. Thus, we aimed characterize PLV-LMCs during murine development, towards rational therapies that target their proliferation, recruitment, and differentiation onto PLVs. Since LMCs have been described as hybrid phenotype striated vascular smooth...
Background: Recent studies demonstrated lymphangiogenesis and expansion of draining lymph nodes during chronic inflammatory arthritis, lymphatic dysfunction associated with collapse in rheumatoid arthritis (RA) patients TNF-transgenic (TNF-Tg) mice experiencing arthritic flare. As the intrinsic differences between vessels afferent to healthy, expanding, collapsed are unknown, we characterized ex vivo behavior popliteal (PLVs) from WT TNF-Tg mice. We also interrogated mechanisms through...
Abstract While rheumatoid arthritis patients and tumor necrosis factor transgenic (TNF-Tg) mice with inflammatory-erosive display lymphatic drainage deficits, the mechanisms responsible remain unknown. As ultrastructural studies of joint-draining popliteal vessels (PLVs) in TNF-Tg revealed evidence muscle cell (LMC) damage, we aimed to evaluate PLV-LMC coverage mice. We tested hypothesis that alpha smooth actin (αSMA) + decreases severe arthritis, is recovered by anti-TNF therapy facilitated...
Although treatment options and algorithms for rheumatoid arthritis (RA) have improved remarkably in recent decades, there continues to be no definitive cure or pharmacologic intervention with reliable long-term efficacy. For this reason, the combination of medications healthy lifestyle modifications are essential controlling joint disease, extra-articular manifestations RA, such as interstitial lung disease (ILD) other pathologies, which greatly impact morbidity mortality. Generally,...
ABSTRACT The risk of osteoporosis is increased in rheumatoid arthritis (RA). Anti-tumor necrosis factor (TNF) therapy has markedly improved the outcomes RA patients but does not improve some reports. This could be a combined result disease severity and other therapeutic agents, such as glucocorticoids that accelerate progression. We evaluated effects anti-TNF on an animal model explored possible mechanisms involved. Six-week-old TNF transgenic (TNF-Tg) mice with early stage erosive were...
Abstract Genetics (i.e., mutations) has been assumed to be the major factor in rheumatoid arthritis (RA) etiology, but accounts for a minority of variance disease risk RA. In contrast genetics, environment can have dramatic impacts on epigenetics that associate with etiology. The current study used buccal cells and purified blood monocytes from two different clinical cohorts involving Caucasian or African American female populations without arthritis. differential DNA methylation regions...
Publications suggest immunomodulation co-therapy improves responder rates in uncontrolled/refractory gout patients undergoing pegloticase treatment. The MIRROR open-label trial showed a 6-month + methotrexate rate of 79%, compared to an established 42% monotherapy rate. Longer-term efficacy/safety data are presented here.
Abstract Critical knowledge gaps of orthopedic infections pertain to bacterial colonization. The established dogma termed the Race for Surface posits that contaminating bacteria compete with host cells implant post‐op, which remains unproven without real‐time in vivo evidence. Thus, we modified murine longitudinal intravital imaging bone marrow (LIMB) system allow quantification green fluorescent protein (GFP+) and enhanced cyan (ECFP+) or red (RFP+) methicillin‐resistant Staphylococcus...
Background Development of reliable disease activity biomarkers is critical for diagnostics, prognostics, and novel drug development. Although computed tomography (CT) the gold-standard quantification bone erosions, there are no consensus approaches or rationales utilization specific outcome measures erosive arthritis in complex joints. In case preclinical models, such as sexually dimorphic tumor necrosis factor transgenic (TNF-Tg) mice, severity routinely quantified ankle through manual...