A5042938502- Immune Response and Inflammation
- Cancer-related Molecular Pathways
- Cancer Genomics and Diagnostics
- Sepsis Diagnosis and Treatment
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Extracellular vesicles in disease
- RNA modifications and cancer
- Genetic factors in colorectal cancer
- Immune cells in cancer
- Asthma and respiratory diseases
- Cancer-related gene regulation
- Clinical Nutrition and Gastroenterology
- Heat shock proteins research
- Adrenal Hormones and Disorders
- Circular RNAs in diseases
- Digestive system and related health
- Trauma and Emergency Care Studies
- Fatty Acid Research and Health
- DNA Repair Mechanisms
- Tuberculosis Research and Epidemiology
- Autophagy in Disease and Therapy
- Circadian rhythm and melatonin
- Peptidase Inhibition and Analysis
- Neonatal and Maternal Infections
Bristol-Myers Squibb (United States)
2015-2017
Rutgers, The State University of New Jersey
2006-2013
Johnson University
2002-2010
Memorial Sloan Kettering Cancer Center
1997-2001
Human toll-like receptor 4 (hTLR4) and CD14 are known to be components of the lipopolysaccharide complex. Our study investigated association between TLR4 mutations (Asp299Gly Thr399Ile) polymorphism(s) with outcome in an intensive care unit (ICU) population at risk for sepsis. By use a polymerase chain reaction-based restriction fragment-length polymorphism analysis technique, hTLR4 gene was altered 14 (18%) 77 ICU patients (all positive systemic inflammatory response syndrome) 5 (13%) 39...
Objectives: The intravenous administration of a bolus dose endotoxin to healthy human subjects triggers acute systemic inflammatory responses that include cytokine production and dynamic changes in gene expression peripheral blood leukocytes. This study sought determine the state clock leukocytes, leukocyte subpopulations, challenged with vivo at two circadian/diurnal phases clock. Design: Clinical laboratory investigation. Setting: University-based research clinical center. Subjects: Human...
The lipopolysaccharide (LPS) receptor complex consists of two interacting receptors (CD14 and TLR4) an associated protein (MD-2). When engaged by LPS, as in gram-negative infection, this transduces a signal detected MyD88 passed onward cascade the IRAKs, TRAF6, NIK, resulting activation NF-κB. A similar cascade, mediated TLR2, occurs with ligands derived from gram-positive bacteria. In vitro studies human monocytes have shown that TLR4 mRNA is paradoxically upregulated response to...
BACKGROUND HER-2/neu and p53 are two molecular markers that have been the focus of investigation in patients with invasive breast carcinoma. However, most published data relied on immunohistochemical detection proteins as a surrogate marker underlying genetic alterations, method often gives variable results due to technical factors. In addition, there limited documenting amplification mutations various histologic subtypes ductal carcinoma situ (DCIS). The authors evaluated series...
An endotoxin challenge, sepsis, and injury/trauma, trigger significant changes in human peripheral blood leukocytes (PBL) gene expression. In this study, we have sought to test the hypothesis that Toll-like receptor 4 (TLR4) induced transcription patterns elicited humans exposed vivo would parallel expression observed trauma patients with initial non-infectious injury. addition, identify functional modules are commonly affected by these two insults of differing magnitude duration. PBL were...
Background: Tumor necrosis factor-alpha (TNF-α) is a well-documented central inflammatory mediator in sepsis. Specific polymorphisms of the TNF-α and TNF-β genes (TNF2 LTA + 250, respectively) have been suggested to correlate with higher mortality septic shock. This study sought determine whether these -β are associated an increased risk infection at-risk surgical intensive care population. Materials Methods: Forty-four consecutive patients systemic response syndrome were enrolled...
In Brief Objective: The Toll-like receptor 4 (TLR4) ligand endotoxin triggers robust systemic inflammatory responses in humans at doses equal to or greater than 1 ng/kg. this study, we tested the hypothesis that evidence of TLR4-induced would be detectable leukocytes challenged with are below threshold needed trigger a characteristic phenotype humans. Methods: Subjects were 1, 0.5, 0.1 ng/kg (n = 5 per dose). Systemic monitored for 24 hours. Blood samples, collected designated intervals,...
Heat shock proteins (HSP) are induced in various stress conditions and have many cytoprotective effects, including formation of protein complexes for antigen presentation, stabilizing intracellular proteins, facilitating folding. The HSP-70 gene exhibits polymorphisms at the HSPA1B HSPA1L loci that reportedly influence cytokine levels clinical outcomes critically ill patients. These HSP variations also been linked to TNF-β associated with poor outcomes. This study further evaluated risk...
PEGylation is a proven approach to prolonging the duration of action and enhancing biophysical solubility stability peptides. 4‐Acetylphenylalanine novel amino acid with ketone side chain that uniquely reactive in proteins. The functionality can react an aminooxy functionalized polyethyleneglycol polymer form stable oxime adduct protein. One concern using unnatural acids, such as 4‐acetylphenylalanine, possibility it being cleaved from peptide becoming incorporated into endogenous To...
Background: Lipopolysaccharide (LPS) is a potent activator of human monocytic cells. We have determined that LPS stimulation the cell line, THP-1, results in an increased apoptotic rate. hypothesized cDNA expression array analysis could be used to identify target genes involved regulation this process. Methods: THP-1 cells (1 × 106/mL) were stimulated with μg/mL) or vehicle control. Apoptosis was measured at 0, 24, 48, 72 and 96 h using propidium iodide staining flow cytometry determine...
Background: Monocytes play a critical role in the inflammatory response to sepsis. Counter-regulatory hormones modulate acute clinical phenotype of Previously, we have shown that cortisol causes faster recovery blood leukocyte apoptosis endotoxin (LPS) challenged individuals. This study examined differential gene expression monocytes, and determined if similar apoptotic activity occurred cortisol. Methods: Volunteers (n=9) were randomly assigned receive either LPS (2ng/kg i.v. bolus) or LPS+...