A5028692388- IL-33, ST2, and ILC Pathways
- Eosinophilic Esophagitis
- Immune Cell Function and Interaction
- Respiratory and Cough-Related Research
- Fungal Infections and Studies
- Antifungal resistance and susceptibility
- Gastroesophageal reflux and treatments
- Asthma and respiratory diseases
- Biochemical Analysis and Sensing Techniques
- Pneumocystis jirovecii pneumonia detection and treatment
- Nail Diseases and Treatments
- Plant Pathogens and Resistance
- Zoonotic diseases and public health
- Respiratory viral infections research
- Heart Rate Variability and Autonomic Control
- Plant Pathogens and Fungal Diseases
- Dermatology and Skin Diseases
- Diphtheria, Corynebacterium, and Tetanus
- Biomedical Ethics and Regulation
- Dermatological and COVID-19 studies
- Parvovirus B19 Infection Studies
- Facial Rejuvenation and Surgery Techniques
- Myasthenia Gravis and Thymoma
- Transplantation: Methods and Outcomes
- Plant-Microbe Interactions and Immunity
Merck & Co., Inc., Rahway, NJ, USA (United States)
2020-2024
University of California, San Francisco
2011-2023
Howard Hughes Medical Institute
2003-2015
University of Malawi
2009-2012
Duke University Hospital
2003-2004
Duke Medical Center
2003-2004
National Institutes of Health
1997
National Human Genome Research Institute
1997
Eosinophils in visceral adipose tissue (VAT) have been implicated metabolic homeostasis and the maintenance of alternatively activated macrophages (AAMs). The absence eosinophils can lead to adiposity systemic insulin resistance experimental animals, but what maintains is unknown. We show that interleukin-5 (IL-5) deficiency profoundly impairs VAT eosinophil accumulation results increased when animals are placed on a high-fat diet. Innate lymphoid type 2 cells (ILC2s) resident major source...
Background. Cryptococcal meningitis (CM) is a leading cause of death in individuals infected with human immunodeficiency virus (HIV). Identifying factors associated mortality informs strategies to improve outcomes.
Background. Cryptococcal meningitis is a major cause of human immunodeficiency virus (HIV)–associated morbidity and mortality in Africa. Improved oral treatment regimens are needed because amphotericin B neither available nor feasible many centers. Fluconazole at dosage 1200 mg per day more fungicidal than 800 day, but rates remain unacceptably high. Therefore, we examined the effect adding flucytosine to fluconazole. Methods. From 13 February through 2 December 2008, HIV-seropositive,...
ABSTRACT Insertional mutagenesis was applied to Cryptococcus neoformans identify genes associated with virulence attributes. Using biolistic transformation, we generated 4,300 nourseothricin ( NAT )-resistant strains, of which 590 exhibited stable resistance. We focused on mutants defects in established factors and identified two reduced growth at 37°C, four production the antioxidant pigment melanin, an increased sensitivity nitric oxide (NO). The insertion mutant phenotypes were...
Group 2 innate lymphoid cells (ILC2s) have an important role in acute allergic lung inflammation. Given their distribution and function, ILC2s are hypothesized to coordinate epithelial responses the external environment; however, how barrier surveillance is linked ILC2 activation remains unclear. Here, we demonstrate that alveolar type II main source of interleukin (IL)-33 thymic stromal lymphopoietin (TSLP) generated response chitin or migratory helminths. IL-33 TSLP synergistically induce...
ABSTRACT Arg1 is produced by AAMs and proposed to have a regulatory role during asthma allergic inflammation. Here, we use an reporter mouse identify additional cellular sources of the enzyme in lung. We demonstrate that ILC2s express at rest infection with migratory helminth Nippostrongylus brasiliensis. In contrast AAMs, which following IL-4/IL-13-mediated STAT6 activation, constitutively STAT6-independent manner. Although deficient IL-33R subunit T1/ST2 maintain expression, IL-33 can...
Cryptococcal meningitis in Africa is associated with up to 70% mortality at 3 months and 500 000 deaths annually. We examined strategies improve on fluconazole (FLU) monotherapy: addition of flucytosine (5-FC) and/or short-course amphotericin B (AmB).
The eye, which is under constant exposure to environmental pathogens, has evolved various anatomic and immunological barriers critical the protection of tissues lacking regenerative capacity, maintenance a clear optic pathway essential vision. By bypassing ocular barriers, intravitreal (IVT) injection become mainstay for delivery drugs treat conditions that affect back eye. Both small molecules biotherapeutics have been successfully administered intravitreally, several approved treatment...
Gefapixant (MK-7264, RO4926219, AF-219) is a first-in-class P2X3 antagonists being developed to treat refractory or unexplained chronic cough. The initial single- and multiple-dose safety, tolerability, pharmacokinetics of gefapixant at doses ranging from 7.5 1800 mg were assessed in four clinical trials. Following single-dose administration 10-450 mg, the pharmacokinetic (PK) profile plasma urine demonstrated low inter-subject variability dose-proportional exposure. multiple twice daily,...
Abstract Gefapixant (MK‐7264) is a first‐in‐class, selective antagonist of the P2X3 purinergic receptor currently being investigated as therapeutic agent for treatment refractory or unexplained chronic cough. In non‐clinical studies, gefapixant was eliminated primarily by renal excretion parent drug. The objective this study to assess disposition in humans. absorption, metabolism, and profiles were assessed after oral administration single dose [ 14 C]gefapixant six healthy adult males....
Abstract Gefapixant, a P2X3‐receptor antagonist, demonstrated objective and subjective efficacy in individuals with refractory or unexplained chronic cough. We report population pharmacokinetic (PopPK) analysis that characterizes gefapixant pharmacokinetics (PKs), quantifies between‐ within‐participant variability, evaluates the impact of intrinsic extrinsic factors on exposure. The PopPK model was initially developed using PK data from six phase I studies. Stepwise covariate method utilized...
Typically, to support regulatory drug approval in Japan, an appropriate justification of the dosage regimen(s) target indication proposed Japanese patient population based on overall clinical data and evidence is required. More specifically, when using foreign and/or discussing extrapolation data/interpretation into targeted population, it important understand similarity consistency between non-Japanese populations ("ethnicity") healthy participants patients, as well patients ("disease...
Obstructive sleep apnea (OSA) is a highly prevalent disorder with serious health consequences but limited therapeutic options. For subset of those OSA, key underlying mechanism hypersensitive chemoreflex control breathing. There no approved therapy that targets this endotypic trait. Here we determine whether the P2X3 receptor antagonist gefapixant, which predicted to attenuate carotid chemoreflexes, reduces OSA severity in patients chemoreflex-dependent OSA.