A5102901409- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Pain Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Immune Response and Inflammation
- Stress Responses and Cortisol
- Neuroinflammation and Neurodegeneration Mechanisms
- Tryptophan and brain disorders
- NF-κB Signaling Pathways
- Helminth infection and control
- Botulinum Toxin and Related Neurological Disorders
- Anesthesia and Sedative Agents
- Cancer, Stress, Anesthesia, and Immune Response
- Lipid Membrane Structure and Behavior
- Asthma and respiratory diseases
- Nerve injury and regeneration
- S100 Proteins and Annexins
- Cell Adhesion Molecules Research
- Immune Cell Function and Interaction
- Neonatal Respiratory Health Research
- Anesthesia and Pain Management
- Anesthesia and Neurotoxicity Research
- Parasite Biology and Host Interactions
- Ion channel regulation and function
- Glaucoma and retinal disorders
University at Buffalo, State University of New York
1998-2009
State University of New York
2003
Baylor College of Medicine
1998
Texas Children's Hospital
1998
Methodist Hospital
1998
Women & Children's Hospital of Buffalo
1998
Houston Methodist
1998
University of Michigan
1988-1990
Tumor necrosis factor-alpha (TNF) is a macrophage-derived peptide that known to be an important mediator in various physiologic and immunologic events. Although the effector function of TNF has received recent attention, there relatively little information regarding factors regulate expression. Highly Ia-positive murine peritoneal macrophages obtained via complete Freund's adjuvant elicitation were challenged with lipopolysaccharide (LPS) assessed for production regulation at cellular...
Neutrophil-induced cardiomyocyte injury requires the expression of myocyte intercellular adhesion molecule (ICAM)-1 and ICAM-1-CD11b/CD18 adhesion. We have previously demonstrated interleukin (IL)-6 activity in postischemic cardiac lymph; IL-6 is primary stimulus for ICAM- 1 induction. Furthermore, we found that induction mRNA occurred very early on reperfusion infarcted myocardium. hypothesized release a preformed upstream cytokine induced leukocytes infiltrating reperfusion.Constitutive...
Accumulating evidence supports the hypothesis that neuroendocrine hormones may participate in immunologic processes. In our study we have determined UK-14304 (UK) and norepinephrine (NE), both alpha 2-adrenergic agonists, can augment LPS-stimulated TNF from elicited macrophages (MO). The increase production was concentration dependent with an EC50 for UK NE of 8.1 +/- 2.6 0.52 0.17 nM, respectively. concentration-effect curve shifted to right by 2-antagonist yohimbine (10(-6) M), new 49.7...
Evidence for the extraneuronal accumulation of norepinephrine has been demonstrated to occur in macrophage (M phi), yet physiologic role this system remains undefined. We have assessed response murine peritoneal M phi adrenergic antagonists. also defined a phi-associated pool nonspecific agonist norepinephrine. investigated constitutive involvement alpha-adrenergic and beta-adrenergic receptors LPS-induced TNF-alpha production. CFA-elicited phis were incubated with LPS (1 microgram/ml)...
The regulation of lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF) production by prostaglandin E2 (PGE2), forskolin, and dibutyryl cyclic AMP (cAMP) was examined at the cellular molecular levels. above three agents could suppress LPS (100 ng/ml)-stimulated TNF immunologically activated murine macrophages (M phi s) in a dose-dependent manner. concomitant addition PGE2, cAMP, or forskolin to LPS-challenged M s resulted 50% inhibition 10(-7), 3 X 10(-6), 10(-5) M,...
Human tumor necrosis factor-alpha (TNF), a mononuclear phagocyte (MO)-derived peptide, is increasingly being recognized for its pleomorphic immunologic effects. A number of studies have demonstrated that LPS can induce TNF synthesis, but data examining the production and regulation in human MO populations are lacking. In this study, we present demonstrating alveolar macrophages (AMO) peripheral blood monocytes (PBM) obtained from 10 normal volunteers display significant difference both their...
Recent investigations have demonstrated interleukin-2 receptor (IL-2R) expression on both human alveolar macrophages (AMø) and blood monocytes (PBM), but the function of these receptors has not been fully elucidated. In this study, we demonstrate that AMø, as well PBM, can be induced to express biologically active TNF-α after challenge with (IL-2). Furthermore, examined at mRNA level via Northern blot in situ hybridization analysis. Normal obtained by bronchoalveolar lavage, PBM were...
Neuropathic pain is a chronic syndrome that arises from nerve injury. Current treatments only offer limited relief, clearly indicating the need for more effective therapeutic strategies. Previously, we demonstrated proinflammatory tumor necrosis factor-alpha (TNF) key mediator of neuropathic pathogenesis; TNF elevated at sites neuronal injury, in spinal cord, and supraspinally during initial development pain. The inhibition action along pathways outside higher brain centers results transient...
Summary Increasing only the expression of pleiotropic cytokine tumor necrosis factor–alpha exclusively in hippocampus naïve rats induces peripheral hypersensitivity to thermal and mechanical stimulation reminiscent chronic pain behaviors. The manifestation chronic, neuropathic includes elevated levels (TNF). Previously, we have shown that hippocampus, an area brain most notable for its role learning memory formation, plays a fundamental sensation. Using animal model pain, demonstrated...
<h3>Background and Objectives</h3> Evidence implicates the pleiotropic cytokine tumor necrosis factor alpha (TNFα) in pathogenesis of persistent pain. The present study employs a chronic constriction injury (CCI) model neuropathic pain to examine TNFα production central nervous system (CNS) periphery this model. <h3>Methods</h3> CCI-induced hyperalgesia is assessed by measuring nociceptive threshold using hot-plate test. development correlated levels assessing: bioactive homogenates sciatic...
PGE2, an immune mediator, is inhibitor of LPS-stimulated TNF production and gene transcription. In the present study we determined whether pretreatment with PGE2 could desensitize suppressive function for macrophage (MO)-derived TNF. CFA-elicited MO were incubated or medium only, washed, then challenged graded doses LPS (0.001 to 1000 ng/ml) in presence absence new PGE2. The concomitant addition shifted concentration-effect curve 16-fold right a 52% decrease maximum response, while...
There is increasing recognition of the involvement immune signaling molecule, tumor necrosis factor (TNF), in pathophysiology stroke and chronic brain dysfunction. TNF plays an important role both modulating synaptic function pathogenesis neuropathic pain. Etanercept a recombinant therapeutic that neutralizes pathologic levels TNF. Brain imaging has demonstrated intracerebral microglial activation neuroinflammation following other forms acute injury. Activated microglia release TNF, which...
The present study documents a role for brain-derived tumor necrosis factor-α (TNF) in the mechanism of action antidepressant drug desmethylimipramine (desipramine). To establish this role, field stimulation and superfusion rat hippocampal slices was employed to investigate regulation norepinephrine (NE) release by TNF. Chronic desipramine administration transforms TNF-mediated inhibition NE facilitation, dependent upon α<sub>2</sub>-adrenergic receptor activation. i.c.v. microinfusion...
The analgesic properties of α2-agonists are well known. In experimental models, tumor necrosis factor (TNF)-α regulates adrenergic responses in the brain. Constitutive TNF-α, brain regions involved pain perception, is decreased after administration clonidine. We investigated patients undergoing lower-extremity revascularization. Seven were treated with clonidine 0.2 mg per os (low), and three received 0.4 (high) before surgery. Eight placebo served as controls. Continuous spinal anesthesia...