A5022011496- Sepsis Diagnosis and Treatment
- Immune Response and Inflammation
- Inflammation biomarkers and pathways
- Intensive Care Unit Cognitive Disorders
- Immune cells in cancer
- Respiratory Support and Mechanisms
- Trauma and Emergency Care Studies
- Cardiac Arrest and Resuscitation
- Immune Cell Function and Interaction
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Diabetes and associated disorders
- Neonatal and Maternal Infections
- Orthopedic Infections and Treatments
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Complement system in diseases
- Immunotherapy and Immune Responses
- Vitamin C and Antioxidants Research
- Pancreatic and Hepatic Oncology Research
- Clostridium difficile and Clostridium perfringens research
- Diabetes Management and Research
- Pregnancy-related medical research
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Immune responses and vaccinations
- Mechanical Circulatory Support Devices
- Esophageal and GI Pathology
University of Michigan–Ann Arbor
2015-2023
Michigan Medicine
2015-2021
Advocate Illinois Masonic Medical Center
2019
Ann Arbor Center for Independent Living
2018
St. Michael's Hospital
2015
University of Toronto
2015
University of Florida
2006-2014
Florida College
2006-2014
Harborview Medical Center
2010
National Institute of General Medical Sciences
2010
Polymicrobial sepsis alters the adaptive immune response and induces T cell suppression Th2 polarization. We identify a GR-1+CD11b+ population whose numbers dramatically increase remain elevated in spleen, lymph nodes, bone marrow during polymicrobial sepsis. Phenotypically, these cells are heterogeneous, immature, predominantly myeloid progenitors that express interleukin 10 several other cytokines chemokines. Splenic GR-1+ effectively suppress antigen-specific CD8+ interferon (IFN) γ...
Sepsis, the systemic inflammatory response to microbial infection, induces changes in both innate and adaptive immunity that presumably lead increased susceptibility secondary infections, multiorgan failure, death. Using a model of murine polymicrobial sepsis whose severity approximates human sepsis, we examined outcomes defined requirements for survival after Pseudomonas aeruginosa pneumonia or disseminated Listeria monocytogenes infection. We demonstrate early neutrophil numbers function...
Microbes activate pattern recognition receptors to initiate adaptive immunity. T cells affect early innate inflammatory responses viral infection, but both activation and suppression have been demonstrated. We identify a novel role for B in the immune response during bacterial sepsis. demonstrate that Rag1−/− mice display deficient reduced survival Interestingly, cell–deficient or anti-CD20 cell–depleted mice, not α/β decreased cytokine chemokine production after Both treatment of with serum...
Neonates have a higher prevalence of bacterial sepsis and greater morbidity mortality from than other infants children. Our understanding the inflammatory immunological responses to is hampered by lack appropriate neonatal murine models. In present report, we developed cecal slurry model generalized peritonitis in mice (age range, 5-7 days) compared outcome innate adaptive cellular these animals with those young adult 7-10 weeks) induced either administration or ligation puncture. Neonatal...
To determine clinical and genomic characteristics in-hospital mortality risk associated with acute kidney injury (AKI) in the multicenter prospective cohort of patients blunt trauma.Less severe stages AKI characterized by small changes serum creatinine (sCr) are inadequately studied among trauma patients.We performed a secondary analysis "Inflammation Host Response to Injury" (Glue Grant) database include adult without history disease. was defined Risk, Injury, Failure, Loss, End-stage...
Neutrophils are essential for successful host eradication of bacterial pathogens and survival to polymicrobial sepsis. During inflammation, the bone marrow provides a large reserve neutrophils that released into peripheral circulation where they traverse sites infection. Although survival, few studies have investigated mechanisms responsible neutrophil mobilization from during Using cecal ligation puncture model sepsis, we demonstrated is not dependent on TLR4, MyD88, TRIF, IFNARα/β, or...
Abstract Regulatory T cells (Tregs), including natural CD4+CD25+ Tregs and inducible IL-10 producing regulatory type 1 (TR1) cells, maintain tolerance inhibit autoimmunity. Recently, increased percentages of have been observed in the blood septic patients, ex vivo-activated were shown to prevent polymicrobial sepsis mortality. Whether endogenous contribute outcome remains unclear. Polymicrobial sepsis, induced by cecal ligation puncture, caused an number splenic compared with sham-treated...
Type I interferon (IFN) alpha/beta is critical for host defense. During endotoxicosis or highly lethal bacterial infections where systemic inflammation predominates, mice deficient in IFN-alpha/beta receptor (IFNAR) display decreased and improved outcome. However, human sepsis mortality often occurs during a prolonged period of immunosuppression not from exaggerated inflammation. We used low lethality cecal ligation puncture (CLP) model to determine the role type IFNs defense sepsis. Despite...
Abstract Bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) can be activated by type I IFNs, TLR agonists, viruses, bacteria to increase hematopoiesis. In this study, we report that endotoxin treatment in vivo induces TLR4, MyD88, Toll/IL-1 resistance domain-containing adaptor-inducing IFN-β (TRIF)-dependent expansion of BM HSPCs. Bacterial infection Staphylococcus aureus or cecal ligation puncture also HSPC expansion, but TRIF, IFN, cytokine, PG, oxidative stress pathways are...
The role of reactive oxygen species (ROS) and their dissipation in type 1 diabetes pathogenesis have garnered considerable controversy. Our recent work has demonstrated the importance NADPH oxidase (NOX) activity for development modulating T-cell autoreactivity. We previously linked decreased monocyte ROS with resistance alloxan-resistant mouse, NOD-Ncf1(m1J) mice a genetic ablation NOX had reduced delayed compared NOD mice.To determine required cellular sources that are necessary...
The appropriate triage of acutely injured patients within a trauma system is associated with improved rates mortality and optimal resource utilization. American College Surgeons Committee on Trauma (ACS-COT) put forward six minimum criteria (ACS-6) for full team activation (TTA). We hypothesized that ACS-COT-verified center compliance these low undertriage overall mortality.Data from state-wide collaborative quality initiative was used. used data collected 2014 through 2016 at 29 ACS...
Abstract The cecum contains a high concentration of microbes, which are combination Gram‐negative and Gram‐positive flora. These bacteria range from anaerobic to facultative aerobic organisms. In the procedure described in this unit, ligation produces source ischemic tissue as well polymicrobial infection. This ischemic/necrotic microbial infection distinguishes multifactorial model number other bacterial sepsis models, including but not limited to: bacteremia secondary intravenous or...
Abstract Cancer progression is associated with inflammation, increased metabolic demand, infection, cachexia, and eventually death. Myeloid-derived suppressor cells (MDSCs) commonly expand during cancer are adaptive immune suppression inflammatory metabolite production. We propose that cancer-induced cachexia driven at least in part by the expansion of MDSCs. MDSC 4T1 mammary carcinoma-bearing hosts induction a hepatic acute-phase protein response altered host energy fat metabolism, reduced...
Impaired hemostasis frequently occurs after traumatic shock and resuscitation. The prehospital fluid administered can exacerbate subsequent bleeding coagulopathy. Hypertonic solutions are recommended as first-line treatment of shock; however, their effects on coagulation unclear. This study explores the impact resuscitation with various hypertonic early coagulopathy trauma. We conducted a prospective observational subgroup analysis large clinical trial out-of-hospital single-bolus (250 mL)...