A5027112759- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Pharmacological Receptor Mechanisms and Effects
- Cholinesterase and Neurodegenerative Diseases
- Neuropeptides and Animal Physiology
- Amino Acid Enzymes and Metabolism
- Neurotransmitter Receptor Influence on Behavior
- Histone Deacetylase Inhibitors Research
- Ion channel regulation and function
- Nitric Oxide and Endothelin Effects
- Protein Degradation and Inhibitors
- Immune Cell Function and Interaction
- Sphingolipid Metabolism and Signaling
- Epigenetics and DNA Methylation
- Inflammatory mediators and NSAID effects
- T-cell and B-cell Immunology
- Catalytic C–H Functionalization Methods
- Pain Mechanisms and Treatments
- Phytochemical compounds biological activities
- Pharmacogenetics and Drug Metabolism
- Asthma and respiratory diseases
- Asymmetric Hydrogenation and Catalysis
- Metabolism and Genetic Disorders
- Cannabis and Cannabinoid Research
Janssen (United States)
2012-2021
Johnson & Johnson (United States)
2011-2021
Johnson & Johnson (Sweden)
2018
McGill University Health Centre
2017
Indian Institute of Chemical Technology
2015
Defence Food Research Laboratory
2014
Janssen (Belgium)
2013-2014
General Atomics (United States)
2003-2008
Merck & Co., Inc., Rahway, NJ, USA (United States)
2000-2004
Monsanto (United States)
1989-1994
The RAR-related orphan receptor gamma t (RORγt) is a nuclear required for generating IL-17-producing CD4(+) Th17 T cells, which are essential in host defense and may play key pathogenic roles autoimmune diseases. Oxysterols elicit profound effects on immune inflammatory responses as well cholesterol lipid metabolism. Here, we describe the identification of several naturally occurring oxysterols RORγt agonists. most potent selective activator 7β, 27-dihydroxycholesterol (7β, 27-OHC). We show...
Demyelination is a hallmark of several human diseases, including multiple sclerosis. To understand better the process demyelination and remyelination, we explored use an in vitro organotypic cerebellar slice culture system. Parasagittal slices postnatal Day 10 (P10) rat cerebella cultured demonstrated significant myelination after 1 week culture. Treatment cultures at 7 days (DIV) with bioactive lipid lysolecithin (lysophosphatidylcholine) for 15-17 hr produced marked demyelination. This was...
The synthesis of nitric oxide by brain slices has been demonstrated in several laboratories. In addition, vitro studies have stimulation excitatory amino acid receptor agonists. These data led to the hypothesis that this readily diffusible "intercellular messenger molecule" acts generate a cascade effect activating guanylate cyclase cell types and thereby augment levels second cyclic GMP (cGMP). Therefore, we evaluated vivo, testing actions synthase inhibitor N-mono-methyl-L-arginine (NMMA)...
Intraperitoneal administration of zymosan to mice resulted in marked biosynthesis eicosanoids and influx neutrophils with distinct time course profiles. 6-Keto-prostaglandin-F1 alpha (6-KPA) increased between 30 60 min rapidly decreased thereafter. Leukotriene (LT)C4 levels showed similar patterns, but were sustained for several hours. LTB4 a biphasic manner peak increases 2 3 hr. Repeated injections suggested that incoming generate most the LTB4. Myeloperoxidase (MPO), an enzyme marker...
Abstract: Interactions of the potent phencyclidine receptor agonist MK‐801 with dopaminergic system were examined in various brain regions rat. increased dopamine (DA) metabolism pyriform cortex, entorhinal prefrontal striatum, olfactory tubercle, amygdala, and septum without affecting DA cingulate cortex nucleus accumbens. In was more than at increasing metabolism. Local injections into ventral tegmental area amygdala/pyriform interface indicated that may act cell body as well nerve...
Abstract Lysophosphatidic acid (LPA) and sphingosine‐1‐phosphate (S1P) have been proposed to play a key role in oligodendrocyte maturation myelinogenesis. In this study, we examined lysophospholipid receptor gene expression differentiated rat cultures signaling downstream of activation by LPA S1P. Differentiated oligodendrocytes express mRNAs encoding receptors with the relative abundance lpa1 > s1p5 s1p1 = s1p2 lpa3 s1p3 . S1P transiently increased phosphorylation extracellular...
Abstract We used a simple commercial magnetic immunobead method for the preparation of acutely isolated microglial cells from postnatal days 1–3 rat brain. With exception 15 min enzyme incubation, all stages are carried out at 4 °C, minimizing opportunity changes in gene expression during isolation to be reflected accumulated mRNA. The composition was compared with that cultures prepared by conventional tissue culture methods, and purity microglia comparable between two preparations. RT‐PCR...
Direct intracerebellar injections of N-methyl-D-aspartate (NMDA) or D-serine elicited dose-dependent increases in cerebellar cyclic GMP levels, vivo the mouse. The actions were antagonized by competitive NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid and phencyclidine agonist MK-801, observations supporting at NMDA-coupled glycine receptor. In addition, a partial (D-cycloserine) an (HA-966) These data are all consistent with acting represent first demonstration...
ADVERTISEMENT RETURN TO ISSUEPREVLetterNEXT(S)-(−)-5-Ethynyl-3-(1-methyl-2-pyrroli- dinyl)pyridine Maleate (SIB-1508Y): A Novel Anti-Parkinsonian Agent with Selectivity for Neuronal Nicotinic Acetylcholine ReceptorsNicholas D. P. Cosford, Leo Bleicher, Audrey Herbaut, J. Stuart McCallum, Jean-Michel Vernier, Heather Dawson, Jeffrey Whitten, Pamala Adams, Laura Chavez-Noriega, Lucia Correa, James H. Crona, Lorrence S. Mahaffy, Frederique Menzaghi, Tadimeti Rao, Richard Reid, Aida I. Sacaan,...
Excitatory amino acids have been known to increase pituitary secretion of LH in vivo and are probably involved the neuroendocrine regulation hypothalamicpituitary- gonadal axis. We found that systemic administration excitatory acid agonist N-methyl-D-aspartate (NMDA) evokes a transient profound circulating levels ACTH as well. Treatment adult male Long-Evans rats with NMDA (30 mg/kg, sc) maximally increased plasma immunoreactive β-endorphin from 7–15 min after injection, both remained...
There are three isoforms of dimeric nitric oxide synthases (NOS) that convert arginine to citrulline and oxide. Inducible NOS is implicated in numerous inflammatory diseases and, more recently, neuropathic pain states. The majority existing inhibitors either based on the structure or substrate competitive. We describe identification from an ultra high-throughput screen a novel series quinolinone small molecule, nonarginine iNOS dimerization inhibitors. SAR studies screening hit, coupled with...
Three isoforms of nitric oxide synthase (NOS), dimeric enzymes that catalyze the formation (NO) from arginine, have been identified. Inappropriate or excessive NO produced by iNOS and/or nNOS is associated with inflammatory and neuropathic pain. Previously, we described identification a series amide-quinolinone dimerization inhibitors although potent, suffered high clearance limited exposure in vivo. By conformationally restricting amide this progenitor series, describe novel...
It has been hypothesized that HLA class II alleles associated with rheumatoid arthritis (RA) preferentially present self-antigens altered by post-translational modification, such as citrullination. To understand the role of citrullination we tested four RA-associated citrullinated epitopes and their corresponding wild-type version for binding to 28 common II. Binding patterns were variable, no consistent impact was identified. Indeed, in one case significantly increased compared WT peptide,...
Rheumatoid arthritis (RA) is an autoimmune disease that primarily affects the synovial joints and can lead to bone erosion cartilage damage. One hallmark of RA anticitrullinated protein autoantibodies (ACPA) memory citrulline-specific B-cells, which have been implicated in pathogenesis. While depletion B-cells with Rituximab improves clinical responses patients, this treatment strategy leaves patients susceptible infections. Here we use Siglec-engaging Tolerance-inducing Antigenic Liposomes...