A5017239432- Nanoplatforms for cancer theranostics
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- Optical Imaging and Spectroscopy Techniques
- Immune Cell Function and Interaction
- Medical Imaging Techniques and Applications
- Protease and Inhibitor Mechanisms
- Viral Infections and Immunology Research
- Cell Adhesion Molecules Research
- T-cell and B-cell Immunology
- Neuroinflammation and Neurodegeneration Mechanisms
- Diabetes and associated disorders
- Photodynamic Therapy Research Studies
- Asthma and respiratory diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Photoacoustic and Ultrasonic Imaging
- Hepatocellular Carcinoma Treatment and Prognosis
- Inhalation and Respiratory Drug Delivery
- Animal Virus Infections Studies
- Pancreatic function and diabetes
- Monoclonal and Polyclonal Antibodies Research
- Military History and Strategy
- Adipokines, Inflammation, and Metabolic Diseases
- Drug-Induced Hepatotoxicity and Protection
- Military and Defense Studies
PerkinElmer (United States)
2011-2023
American Military Academy
2022
United States Military Academy
1999-2022
Fox Chase Cancer Center
2017
Northwestern University
1989-2012
Boehringer Ingelheim (United States)
2002-2003
Stanford University
1998
University of Colorado Anschutz Medical Campus
1998
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
1998
Millennium Engineering and Integration (United States)
1998
Current thinking attributes the balance between T helper 1 (Th1) and Th2 cytokine response patterns in immune responses to nature of antigen, genetic composition host, cytokines involved early interaction cells antigen-presenting cells. Here we introduce glutathione, a tripeptide that regulates intracellular redox other aspects cell physiology, as key regulatory element this process. By using three different methods deplete glutathione from receptor transgenic conventional mice studying vivo...
The two principal excitatory glutamatergic inputs to striatal medium spiny neurons (MSNs) arise from in the cerebral cortex and thalamus. Although there have been many electrophysiological studies of MSN synapses, little is known about how corticostriatal thalamostriatal synapses differ. Using mouse brain slices that allowed each type synapse be selectively activated, approaches were used characterize their properties identified striatopallidal striatonigral MSNs. At a single afferent volley...
Interleukin (IL)-4, a crucial modulator of the immune system and an active antitumor agent, is also potent inhibitor angiogenesis. When incorporated at concentrations 10 ng/ml or more into pellets implanted rat cornea when delivered systemically to mouse by intraperitoneal injection, IL-4 blocked induction corneal neovascularization basic fibroblast growth factor. as well IL-13 inhibited migration cultured bovine human microvascular cells, showing unusual dose–response curves that were...
When small molecules or proteins are injected into live animals, their physical and chemical properties will significantly affect pharmacokinetics, tissue penetration, the ultimate routes of metabolism clearance. Fluorescence molecular tomography (FMT) offers ability to non-invasively image quantify temporal changes in fluorescence throughout major organ systems living a manner analogous traditional approaches with radiolabeled agents. This approach is best used biotherapeutics (therapeutic...
Carbonic anhydrase IX (CA IX) is a transmembrane protein that has been shown to be greatly upregulated under conditions of hypoxia in many tumor cell lines. Tumor associated with impaired efficacy cancer therapies making CA valuable target for preclinical and diagnostic imaging. We have developed quantitative vivo optical imaging method detection as marker based on near-infrared (NIR) fluorescent derivative the inhibitor acetazolamide (AZ). The agent (HS680) showed single digit nanomolar...
Transfer of an interleukin 2/interferon-gamma-secreting islet-specific CD4+ T-cell clone, BDC-6.9, in the immunodeficient NOD-scid mouse induces destruction pancreatic beta-cells without help from host B-cells, T-cells, or CD8+ T-cells. However, a second BDC-2.5, showing same cytokine profile and receptor Vbeta expression as BDC-6.9 was not capable inducing diabetes insulitis mice. Even though BDC-2.5 by itself readily young unmanipulated NOD mice, cotransfer CD8-enriched T-cells required to...
Theiler's murine encephalomyelitis virus (TMEV) produces a chronic, inflammatory demyelinating disease in susceptible mouse strains that is used as model for multiple sclerosis. Because susceptibility correlates temporally with the development of virus-specific delayed-type hypersensitivity (DTH) responses, we studied methods and mechanisms by which DTH could be specifically inhibited. The intravenous injection UV-inactivated TMEV coupled to syngeneic splenocytes via carbodiimide linkage...
Mice carrying bacterial artificial chromosome (BAC) transgenes have become important tools for neuroscientists, providing a powerful means of dissecting complex neural circuits in the brain. Recently, it was reported that one popular line these mice--mice possessing BAC transgene with D(2) dopamine receptor (Drd2) promoter construct coupled to an enhanced green fluorescent protein (eGFP) reporter--had abnormal striatal gene expression, physiology, and motor behavior. Unlike most work using...
Abstract Strategies to enhance autophagy flux have been suggested improve outcomes in cardiac ischemic models. We explored the role of adiponectin mediating under conditions induced by permanent coronary artery ligation. studied molecular mechanisms underlying adiponectin's cardio‐protective effects knockout (Ad‐KO) compared with wild‐type (WT) mice subjected ischemia ligation and H9c2 cardiomyocyte cell line exposed hypoxia. Systemic infusion a cathepsin‐B activatable near‐infrared probe as...
ABSTRACT. PDGF-B is of central importance in mesangioproliferative diseases. PDGF-D, a new PDGF isoform, like PDGF-B, signals through the ββ-receptor. The present study first determined that PDGF-D mitogenic for rat mesangial cells and not inhibited by antagonist. Low levels mRNA were detected normal glomeruli. After induction nephritis rats anti–Thy 1.1 mAb, glomerular protein expression increased significantly from days 4 to 9 comparison with nonnephritic rats. Peak occurred 2 d later than...
Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease is a relevant mouse model of multiple sclerosis. Demyelination linked to persistent TMEV infection the central nervous system and characterized by perivascular inflammatory mononuclear infiltrates primary demyelination. Myelin damage T cell-dependent process susceptibility correlates with temporal development chronic virus-specific delayed-type hypersensitivity (DTH) responses. Our previous results have shown that...
Abstract Theiler's murine encephalomyelitis virus (TMEV), a member of the cardiovirus subfamily Picornaviridae, is natural pathogen mice. Thirty to 60 days following intracerebral infection with TMEV, susceptible inbred mouse strains develop chronic, progressive, T cell-mediated inflammatory demyelinating disease central nervous system (CNS) characterized by spastic hind limb paralysis and lifelong persistent CNS infection. We have examined effect peripheral virus-specific tolerance on...
Efficient immunologic tolerance, defined as antlgen-speclflc unresponslveness, can be peripherally induced by the l.v. Injection of syngenelc splenocytes coupled with antigen using ethylene carbodilmlde (ECDI). We have previously reported that unresponslveness via intact, UV-lnactlvated Theiler's murine encephalomyelitis virus (TMEV-SP) resulted in 'split tolerance'. Both vtrus-speclflc delayed-type hypersensltlvlty and lgG2a levels were inhibited, whereas lgG1 increased when compared sham...
Standard measurements used to assess murine models of rheumatoid arthritis, notably paw thickness and clinical score, do not align well with certain aspects disease severity as assessed by histopathology. We tested the hypothesis that non-invasive optical tomographic imaging molecular biomarkers inflammation bone turnover would provide a superior quantitative readout discriminate between disease-modifying anti-rheumatic drug (DMARD) non-DMARD treatment.Using two protease-activated...
Animal models of pulmonary inflammation are critical for understanding the pathophysiology asthma and developing new therapies. Current conventional assessments in mouse chronic obstructive disease rely on invasive measures function terminal characterization cells infiltrating into lung. The ability to noninvasively visualize quantify underlying biological processes vivo would provide a significant advance characterizing effects therapeutics. We report utility near-infrared imaging agents,...
Visualization of macrophages in live animals has been great interest for a better understanding inflammation. We developed near infrared (NIR) probe CDnir7 that can selectively detect and visualize inflammation vivo using the IVIS spectrum, Fluorescence Molecular Tomography (FMT) Multi-Spectral Optoacoustic (MSOT).
Among the physiological effects associated with excessive alcohol consumption are alterations in immune function. Alcohol impairs T-helper 1 lymphocyte (Th1) regulated, cell-mediated responses. Antibody responses, regulated by 2 (Th2), either unimpaired or enhanced. Antigen presenting cells central to development of both Th1 and Th2 We used T-cell receptor transgenic conventionally immunized mice demonstrate that ethanol directly affects antigen that, turn, determines whether response...
An imidazo[4,5-h]isoquinolin-7,9-dione (1) was identified as an adenosine 5'-triphosphate competitive inhibitor of lck by high throughput screening. Initial structure−activity relationship studies the dichlorophenyl ring and imide NH important pharmacophores. A binding model constructed to understand how 1 binds a related kinase, hck. These results suggested that removing gem-dimethyl group flattening would enhance activity. This realized converting imidazo[4,5-h]isoquinolin-9-one (20),...
We developed a neutrophil elastase-specific near-infrared fluorescence imaging agent, which, combined with molecular tomographic imaging, allowed us to detect and quantify elastase activity in vivo , real time, noninvasively an acute model of lung injury (ALI). Significantly higher fluorescent signal was quantified mice LPS/fMLP-induced ALI as compared healthy controls, correlating increases the number bronchoalveolar lavage cells, neutrophils, activity. The agent significantly activated ex...
Among the physiological effects associated with excessive alcohol consumption are alterations in immune function. Alcohol impairs T‐helper 1 lymphocyte (Th1) regulated, cell‐mediated responses. Antibody responses, regulated by 2 (Th2), either unimpaired or enhanced. Antigen presenting cells central to development of both Th1 and Th2 We used T‐cell receptor transgenic conventionally immunized mice demonstrate that ethanol directly affects antigen that, turn, determines whether response...
To investigate diabetes resistance to T cell-mediated disease transfer, we administered islet-specific cell clones the F1 progeny of nonobese diabetic (NOD) mice that were crossed with various nondiabetes-prone inbred mouse strains. We investigated four diabetogenic CD4+ and all induced insulitis full development in (SWR x NOD)F1, (SJL (C57BL/6 NOD)F1 mice. In contrast, (BALB/c (CBA susceptible transfer by some but not others, (C57/L seemed be resistant both tested. Disease strains was age...