- Hepatitis C virus research
- Platelet Disorders and Treatments
- Extracellular vesicles in disease
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Cardiovascular Disease and Adiposity
- Hepatitis B Virus Studies
- Liver Disease Diagnosis and Treatment
- Renal Diseases and Glomerulopathies
- Chromosomal and Genetic Variations
- Diabetes and associated disorders
- T-cell and B-cell Immunology
- Complement system in diseases
- Cancer, Hypoxia, and Metabolism
- CRISPR and Genetic Engineering
- Hemophilia Treatment and Research
- Cytokine Signaling Pathways and Interactions
- RNA and protein synthesis mechanisms
- Nitric Oxide and Endothelin Effects
- Hormonal Regulation and Hypertension
- Dialysis and Renal Disease Management
- Renin-Angiotensin System Studies
- Advanced biosensing and bioanalysis techniques
- MicroRNA in disease regulation
- Blood donation and transfusion practices
University of Virginia
2002-2017
University of Virginia Health System
2014-2017
CK-CARE
2012-2016
Durham VA Medical Center
2013
Duke University
2013
University of Southern Denmark
2013
Salem VA Medical Center
2013
Emory University
1994-1997
Tufts University
1991-1992
Boston Medical Center
1981-1987
A platelet-agglutinating factor has been detected in the plasma of some patients during episodes thrombotic thrombocytopenic purpura (TTP).1 , 2 Agglutination induced vitro by this is inhibited normal and does not require platelet production arachidonic acid metabolite thromboxane A2, release granule contents, metabolism, or calcium magnesium ions.3 These characteristics are similar to those agglutination attachment platelets large, multimeric, von Willebrand components VIII complex...
Factor-VIII-related von Willebrand factor (vWF) multimers are synthesized by endothelial cells, and plasma vWF antigen levels elevated in some disorders associated with cell perturbation. We studied 13 patients during cisplatin-basedcombination chemotherapy for squamous carcinoma of the head neck, esophagus, or lung. Before therapy, 3 had that were ≥400% normal; further elevations occurred chemotherapy. Two these cerebrovascular accidents, third complications similar to hemolytic-uremic...
Microparticles (MPs) are submicron vesicles released from cell membranes in response to activation, injury, or apoptosis. The clinical importance of MPs has become increasingly recognized, although no standardized method exists for their measurement. Flow cytometry (FCM) is the most commonly used technique, however, because small size MPs, and limitations current FCM instrumentation, accurate identification compromised by this methodology. We decided investigate whether use combined with...
Transposition of conjugative transposons proceeds by excision and formation a covalently closed circular intermediate that includes at its joint the six flanking bases from previous host (coupling sequences). To elucidate role coupling sequences in this process to determine sequence targets used Tn916, we studied insertion into plasmid following conjugation. The results differ those previously observed when Tn916 was introduced transformation. They suggest only one specific strand transposon...
Abstract As a 51‐year‐old woman recovered from an initial acute episode of thrombotic thrombocytopenic purpura (TTP), her plasma was found to contain unusually large von Willebrand factor (vWF) multimers. Clinical, hematological, and vWF studies siblings children were normal. The forms presumably derived endothelial cells, persisted in after recovery, associated with recurrent episodes TTP during the subsequent 6 months. After last relapse they disappeared following 3 ½ weeks therapy...
Collectrin is an orphan member of the renin-angiotensin system and a homolog angiotensin-converting enzyme 2, sharing ≈50% sequence identity. Unlike collectrin lacks any catalytic domain. has been shown to function as chaperone amino acid transporters. In rodents, renal expression increased after subtotal nephrectomy during high-salt feeding, raising question whether direct role in blood pressure regulation.Using susceptible genetic background, we demonstrate that deletion results...
We purified the Xis protein of conjugative transposon Tn916 and showed by nuclease protection experiments that bound specifically to sites close each end Tn916. These specific binding are to, in same relative orientation for N-terminal domain integrase protein. results suggest is involved formation nucleoprotein structures at ends help correctly align so excision can occur.
The roles of purified Int and Xis proteins the conjugative transposon Tn916 in excision a deletion derivative closely related element Tn1545 were investigated. At low salt concentration (37.5 mM NaCl), alone was able to promote limited produce covalently closed circular form transposon, showing that can catalyze both DNA cleavage strand exchange. This reaction stimulated by Xis. higher concentrations (150 reduced barely detectable levels required for excision. salt, Xis-stimulated ∼8-fold...
Mls-1 is an endogenous superantigen that leads to in vivo deletion and vitro stimulation of T cell receptor (TCR) V beta 6-, 7-, 8.1-, 9-expressing cells. The MA/MyJ mouse deletes the identical set TCR from its mature repertoire; however, it does not contain Mtv-7, murine mammary tumor provirus (MMTV), whose sag gene encodes Mls-1. Interestingly, activity this strain segregates with a new provirus, Mtv-43, seen other inbred strains. predicted amino acid sequence Mtv-43 was compared Mtv-7....
The coupling sequences of conjugative transposons are short variable derived from the DNA flanking transposon insertion site. We show here that for Tn916 left sequence is 6 bases long. right-hand end can excise with either four or five T's, but integration occurs to restore T's at transposon's right end.
It is unknown whether all hepatitis C virus (HCV) quasispecies variants found within patient serum have equal capacity to associate with the liver after transplantation; however, in vitro models of HCV infection suggest that variations hypervariable region 1 (HVR1) second envelope protein (E2) may be important infectivity. The hypothesis current study two regions (HVR1 and HVR2) E2 are initial virus–liver interaction, and, therefore, certain will isolated from reperfusion. In 8 patients...
Abstract Cross-presentation is a modular series of intracellular events dictating the internalization and subsequent MHC class I (MHC I) display extracellular Ags. This process has been defined in dendritic cells plays fundamental role induction CD8+ T cell immunity during viral, bacterial, antitumor responses. Herein, acute viral infection murine liver with adenovirus, model for intrahepatic cross-presentation, confirms hepatocytes directly contribute to cross-presentation Ags priming pool...
The second envelope protein at hypervariable region 1 (HVR1) has been implicated in contributing to hepatitis C virus (HCV)‐host cell interactions and CD81 (a multifunctional protein) demonstrated act as a surface receptor for HCV may interact directly with HVR1. purpose of the current study was determine if certain HVR1 quasispecies variants more effectively associate infect allografts after liver transplantation than other whether expression changes transplantation. Blood allograft samples...
Abstract A 38‐year‐old male patient with a life‐long history of easy bruising and mild bleeding had prolonged activated partial thromboplastin time (APTT), prothrombin (PT), thrombin (TT). Reptilase (Bathrops atrox) clotting was normal. His undiluted diluted plasma the APTT, PT, TT normal plasma. Fibrin produced from insoluble in 5 M urea. Plasma fibrinogen level increased when measured as clottable protein by Laurell electroimmunoassay. Specific assays factors II, V, VII, X, VIII, IX, XI,...
Background: Hypertension (HTN) is a leading risk factor of cardiovascular diseases. Its pathogenesis poorly understood, but activation the renin angiotensin system thought to be key event. Vascular damage an early manifestation HTN. There are currently no available clinical biomarkers for detection vascular damage. Circulating microvesicles (MVs) have gained significant attention as potential novel injury. These vesicles less than 1 micron in size and carry markers parent cell. We...