- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Streptococcal Infections and Treatments
- Cell Adhesion Molecules Research
- S100 Proteins and Annexins
- Blood disorders and treatments
- Lipid Membrane Structure and Behavior
- Immune Response and Inflammation
- Protease and Inhibitor Mechanisms
- Central Venous Catheters and Hemodialysis
- Ear Surgery and Otitis Media
- Neonatal Respiratory Health Research
- Respiratory and Cough-Related Research
- Antibiotics Pharmacokinetics and Efficacy
- Infective Endocarditis Diagnosis and Management
- Mosquito-borne diseases and control
- Immunodeficiency and Autoimmune Disorders
- Blood Coagulation and Thrombosis Mechanisms
- interferon and immune responses
- Nosocomial Infections in ICU
- Respiratory Support and Mechanisms
- Bacterial Identification and Susceptibility Testing
- Obsessive-Compulsive Spectrum Disorders
- Pneumocystis jirovecii pneumonia detection and treatment
- Cleft Lip and Palate Research
- Knee injuries and reconstruction techniques
Center for Health and Gender Equity
2016-2023
Michigan Medicine
2023
University of Michigan–Ann Arbor
2013-2022
Michigan United
2021
University of Toledo
2016
C. S. Mott Children's Hospital
1996-2012
Office of Infectious Diseases
2001-2012
Center for Non-Communicable Diseases
2006
University of California, San Francisco
1989-1992
San Francisco General Hospital
1989-1990
The annexins are a family of structurally similar, Ca2(+)-dependent, phospholipid-binding proteins. We compared six members this (calpactin I heavy chain, lipocortins and III, endonexin II, p68 protein II) to determine their specificities, as well ability promote aggregation fusion phospholipid vesicles. Ca2+ requirement for all the proteins was lowest binding vesicles composed phosphatidic acid, followed by phosphatidylserine then phosphatidylinositol. Only p68, lipocortin III II bound...
The Food and Drug Administration licensed a live-virus varicella vaccine (Varivax; Merck & Co Inc, West Point, PA) in March 1995. Prelicensure adverse events were minimal; however, since licensure increased use, rare previously undetected risks have arisen. Presented here is the clinical course of undiagnosed, human immunodeficiency virus-infected boy who developed dissemination strain zoster after immunization. chickenpox, virus, pneumonia, encephalopathy, vaccine, events, dissemination.
Intracellular ionized calcium has been strongly implicated in mediating several responses of human neutrophils to stimulation. However, proteins that serve as effectors these have not well characterized. To identify might mediators the effects Ca2+ neutrophils, we isolated bind membrane phospholipids a Ca2(+)-dependent manner. The most abundant these, protein 33 kD, was readily purified homogeneity, and found phosphatidylserine vesicles presence 2 microM Ca2+. In addition, this promoted...
Ethanol locks have been used to treat catheter infections and decrease the rate at which they occur. Catheter-related caused by Candida spp. are especially difficult manage medically usually require removal. We report 3 consecutive patients whose were successfully treated with a combination of ethanol lock therapy systemic antifungals.
BACKGROUND: Ethanol lock therapy (ELT) has been shown to reduce the incidence of catheter-related blood stream infections (CRBSI) in intestinal failure (IF) patients. Dosing and frequency remains undefined. Scrutiny pharmaceutical facilities by Food Drug Administration led voluntary shutdown sole supplier ethanol, resulting a nationwide shortage. To conserve supply, we reduced ELT from daily regimen. We examined impact that reduction had on CRBSI pediatric IF METHODS: retrospectively...
To identify disparities in compliance of and care for patients with cleft lip and/or palate (CL/P) by determining the impact sociodemographic variables on rate missed appointments Child Protective Services (CPS) involvement.A retrospective, noninterventional quality assessment improvement study were designed.This institutional was performed at University Michigan Ann Arbor, Michigan.All born between January 1, 2011, December 31, 2014, who underwent surgical CL/P repair, excluding those fewer...
Phospholipase D (PLD) activation in stimulated neutrophils results the conversion of membrane phosphatidylcholine (PC) to phosphatidic acid (PA). This change phospholipid composition has two potentially positive effects on degranulation. It 1) replaces a nonfusogenic with fusogenic one and 2) increases potential for interactions between membranes annexins. Modeling neutrophil degranulation, we examined effect PLD (Streptomyces chromofuscus) hydrolysis aggregation fusion liposomes presence...
Abstract Leukocytes use urokinase receptors (uPAR; CD87) in adhesion, migration, and proteolysis of matrix proteins. Typically, uPAR clusters at cell-substratum interfaces, focal adhesions, the leading edges migrating cells. This study was undertaken to determine whether clustering mediates activation signaling human polymorphonuclear neutrophils. Cells were labeled with fluo-3/AM quantitate intracellular Ca2+ ([Ca2+]i) by spectrofluorometry, aggregated Ab cross-linking. Aggregating induced...
Annexins are structurally related proteins that bind phospholipids in a Ca2(+)-dependent manner and possess at least four conserved 70-amino acid repeat domains. The ability of certain annexins to promote contact between vesicle membranes vitro has prompted the suggestion these regulate membrane traffic exocytosis. We have previously found I II vesicles whereas annexin V does not. In order understand mechanism I-mediated vesicle-vesicle contact, we prepared monoclonal antibody specifically...
During inflammation neutrophils receive multiple signals that are integrated, allowing a single modified response. One mechanism for this discrimination is receptor desensitization, process whereby ligand-receptor binding disassociated from cell activation. We examined the effect of heterologous desensitization on neutrophil chemotaxis, calcium mobilization, and arachidonic acid production, using interleukin-8 (IL-8), C5a, N-formyl-methionyl-leucyl-phenylalanine (fMLP). observed reciprocal...
Abstract The membrane fusion events observed during neutrophil degranulation are important aspects of the immunoregulatory system. In an attempt to understand regulation granule-plasma fusion, we have begun characterizing human cytosol for activity, finding that 50% fusogenic activity could be attributed members annexin family proteins. major non-annexin (25% total cytosolic activity) was enriched by ion exchange chromatography after depletion annexins Ca2+-dependent phospholipid affinity...
Abstract Leukocyte urokinase plasminogen activator receptors (uPARs) cluster at adhesion interfaces and migratory fronts where they participate in adhesion, chemotaxis, proteolysis. uPAR aggregation triggers activation signaling even though this glycolipid-anchored protein must associate with membrane-spanning proteins to access the cell interior. This study demonstrates a novel partnership between L-selectin human polymorphonuclear neutrophils. Fluorescence resonance energy transfer...
Objective: To identify the impact of sociodemographic and health variables on age at which patients undergo cleft lip repair, palate primary speech evaluation. Design: A retrospective, noninterventional quality assessment, improvement study was designed. Setting: This institutional performed Michigan Medicine in Ann Arbor, MI. Patients: All born between 2011 2014 who received surgical excluded those were adopted (n = 165). Main Outcome Measure: The Results: Cleft repair significantly later...
Urokinase plasminogen activator (uPA) receptors (uPAR) can be engaged for activation signaling either by aggregation or binding exogenous uPA. These mechanisms require uPAR to associate with two distinct adhesion proteins, L-selectin and complement receptor 3 (CR3), respectively. contains a glycosylphosphatidylinositol anchor, suggesting that it is concentrated within glycosphingolipid-enriched microdomains, "lipid rafts". This study was undertaken determine the extent which uPAR-mediated...
This study used ethanol lock therapy (ELT) to treat intravenous catheter infections that had failed standard antimicrobial treatment. Of 15 patients enrolled, 13 were successfully treated with ELT. Twenty-one organisms identified: 12 bacteria, 9 fungi. Eight of the fungi eradicated, and no patient became hemodynamically unstable on
Leukocytes utilize urokinase receptors (uPAR; CD87) in adhesion, migration, and matrix proteolysis. uPAR aggregate at cell-substratum interfaces leading edges of migrating cells, so this study was undertaken to determine whether aggregation is capable initiating activation signaling. Monocyte-like U937 cells were labeled with fluo-3-acetoxymethyl ester quantitate intracellular Ca2+ concentrations ([Ca2+]i) by spectrofluorometry, aggregated mAb cross-linking. induced highly reproducible...
Abstract Neutrophilic polymorphonuclear leukocytes contain glycosphingolipid- and cholesterol-enriched lipid raft microdomains within the plasma membrane. Although there is evidence that rafts function as signaling platforms for CXCR chemokine receptors, their role in recognition systems other chemotaxins such leukotriene B4 (LTB4) fMLP unknown. To address this question, human neutrophils were extracted with 1% Brij-58 fractionated on sucrose gradients. B receptor-1 (BLT-1), primary LTB4...
Diarrheal illness, frequently associated with fecal-oral transmission, is one of the leading causes death worldwide. It commonly preventable through implementation safe water practices. This experiment concerns how to best implement practices in a quasi-permanent refugee camp setting limited ability for structural changes. Specifically, we explore health promotion activities that help identify target groups hygiene interventions can play role disease prevention. An anonymous survey was...
Abstract Neutrophil stimulation results in the activation of a variety phospholipases, including phospholipase A2 (PLA2), which releases arachidonic acid from 2 position membrane phospholipids, leaving lysophospholipid. Because is known to be potent fusogen vitro, we examined effect metabolism by PLA2 on fusion complex liposomes (liposomes prepared with phospholipid composition similar that found neutrophil plasma membrane). We observed augmented each other as well specific granules isolated...
Invasive aspergillosis seems to be on the rise, especially in immunocompromised children. Historically, only systemic amphotericin B has been effective against Aspergillus. Development of newer antifungal agents, such as voriconazole and caspofungin, improved treatment options available for aspergillosis, although no definitive management strategy established. Here we describe use topical combined with agents cutaneous a pediatric patient after bone marrow transplant.