A5037506822- Asthma and respiratory diseases
- Inhalation and Respiratory Drug Delivery
- Respiratory and Cough-Related Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Pharmacological Effects and Assays
- Allergic Rhinitis and Sensitization
- Reproductive Physiology in Livestock
- Neuropeptides and Animal Physiology
- Respiratory Support and Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Occupational exposure and asthma
- Venous Thromboembolism Diagnosis and Management
- Diabetes and associated disorders
- Blood Coagulation and Thrombosis Mechanisms
- Sepsis Diagnosis and Treatment
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Receptor Mechanisms and Signaling
- Genetic and phenotypic traits in livestock
- Neonatal Respiratory Health Research
- T-cell and B-cell Immunology
- Cardiovascular Effects of Exercise
- Renal function and acid-base balance
- Olfactory and Sensory Function Studies
- Contact Dermatitis and Allergies
Samford University
2024
Brigham and Women's Hospital
2016-2022
Harvard University
2017-2022
Broad Institute
2017-2020
Genesys Regional Medical Center
2018
Boston University
2013-2017
OhioHealth
2017
Doctors Hospital
2017
University of Mississippi Medical Center
2017
Jackson Memorial Hospital
2017
Ten patients with exercise-induced asthma participated in a single-blind trial comparing the protective effects of inhaled verapamil (estimated dose 3 mg) and sodium cromoglycate 12 mg). Saline was used as control. Effects were assessed from mean maximal percentage fall forced expiratory volume one second (FEV1) after running on treadmill for eight minutes. There no significant change baseline FEV1 values each agent. In exercise periods, however, fell by 45.4% (SEM 4.0) saline inhalation,...
A microglial-like cellular model can be used to identify functional consequences of genetic variants associated with neurodegenerative disease.
Twenty patients with extrinsic type bronchial asthma are shown to have a significant fall in vital capacity (V.C.) and forced expiratory volume 1 second (F.E.V.<sub>1</sub>) after an intravenous infusion of 50μg. histamine dihydrochloride. In 10 these subjects the V.C. F.E.V.<sub>1</sub> produced by is inhibited alpha-receptor blocking drugs phentolamine phenoxybenzamine injected before test. The inhalation disodium cromoglycate also inhibit histamine. It suggested that smooth muscle...
The finding by several workers that biochemical responses to catecholamines are diminished in asthmatic patients during periods of active asthma as compared normal subjects has led the recognition beta-adrenergic blockade phenomenon, a common accompaniment extrinsic bronchial asthma. Using an intact cell method measure leucocyte adenyl cyclase activity, we have been able show there is noticeably reduced responsiveness this enzyme system (which now identified with beta-receptor function)...
The effect of nifedipine was studied in fifteen patients with exercise-induced asthma. Nifedipine inhibited the fall FEV1 almost completely four patients, offered partial protection a further nine and had no remaining two patients. It is suggested that mediator release which dependent on free calcium ions may play an important role asthma antagonists inhibit post-exercise bronchoconstriction by their blocking channels mast cells.
In thirteen patients with extrinsic asthma the effects of placebo, sodium cromoglycate, ipratropium bromide, and bromide plus cromoglycate were studied in a random double-blind fashion to assess their inhibitory action exercise-induced (EIA). Exercise testing consisted steady state running on an inclined treadmill for up eight minutes. 13 baseline ratio expiratory flow at 50% vital capacity (VC) breathing helium-oxygen (V50He) V50air was over 1.20 they called responders; remaining five...
Human precision-cut lung slices (hPCLSs) provide a unique ex vivo model for translational research. However, the limited and unpredictable availability of human tissue greatly impedes their use. Here, we demonstrate that cryopreservation hPCLSs facilitates banking live routine Our results show had little effect on overall cell viability vital functions immune cells, including phagocytes T lymphocytes. In addition, airway contraction relaxation in response to specific agonists antagonists,...
Pulmonary neuroendocrine cells (PNECs) are the only innervated airway epithelial cells. To what extent neural innervation regulates PNEC secretion and function is unknown. Here, we discover that neurotrophin 4 (NT4) plays an essential role in mucus overproduction after early life allergen exposure by orchestrating of GABA. We found PNECs were cellular source GABA airways. In addition, expressed NT4 as a target-derived mechanism underlying during development. Early elevated level caused...
Summary Calcium antagonist, verapamil given by inhalation did not alter histamine bronchial hyper‐reactivity in ten patients with extrinsic asthma and similarly modify methacholine‐induced bronchoconstriction further five patients. In eight non‐asthmatic subjects reduced sensitivity increase PC 20H from 8.07(±2.33) to 12.10(±2.71, P < 0.05) but failed have an effect on methacholine controls. The failure of inhaled asthmatic the beneficial calcium antagonists exercise suggests that these...
Summary Phenylephrine, a powerful alpha receptor stimulant, has been shown to cause significant fall in the FEV 1 and SGaw six patients with extrinsic bronchial asthma after prior beta blockade propranolol. In contrast, propranolol or phenylephrine failed effect change five normal subjects. The can be completely inhibited by blocking drugs, phenoxybenzamine thymoxamine. These observations suggest that bronchomotor tone is largely controlled sympathetic activity there are receptors human...
Tregs hold great promise as a cellular therapy for multiple immunologically mediated diseases, given their ability to control immune responses. The success of such strategies depends on the expansion healthy, suppressive ex vivo and in following transfer. In clinical studies, levels transferred decline sharply blood within few days have high rate apoptosis. Here, we describe new mechanism Treg self-inflicted damage. We show that granzymes A -B (GrA GrB), which are highly upregulated human...
The effects of 2, 10, and 20 mg sodium cromoglycate delivered by aerosol were compared with those placebo in a double blind study 11 patients extrinsic exercise induced asthma. effect nebulised through Wright nebuliser (estimated dose 12 mg) was also studied. Patients exercised on treadmill for six to eight minutes at submaximal work loads five days, 30 after inhaling or cromoglycate. FEV1 recorded before treatment, exercise, up exercise. Mean baseline values did not differ significantly the...
Abstract T helper 9 (Th9) cells are effector CD4 + that characterized by the production of interleukin-9 (IL-9) and have been associated with allergic responses. Here, we found expression transcription factor forkhead box O1 (Foxo1) was induced in Th9 Foxo1 plays a crucial role differentiation cells. Pharmacological inhibition or genetic disruption caused reduction IL-9 while upregulating IL-17A IFNγ production. Furthermore, chromatin immunoprecipitation (ChIP) followed luciferase assays...
It is recognized that exercise produces abnormally large increases in pulmonary artery pressure patients with vascular disease as a consequence of variety disorders, but the relationship between and cardiopulmonary performance poorly understood. This lack understanding due (in part) to difficulty making measurements haemodynamics using conventional fluid filled catheters. article seeks improve by comparing variables measured during formal testing simultaneous micro-manometer tipped catheter....
Ten patients with exercise-induced asthma participated in a single-blind dose-response study comparing the protective effect of inhaled sodium cromoglycate increasing concentrations from 2 to 40 mg/ml. Saline was used as control. Effects were assessed mean maximal percentage fall forced expiratory volume one second (FEV1) after had run on treadmill for eight minutes. There slight bronchodilation evident increase baseline FEV1 inhalation cromoglycate, difference reaching statistical...
Endothelial thrombomodulin (TM) regulates coagulation and inflammation via several mechanisms, including production of activated protein C (APC). Recombinant APC soluble fragments TM (sTM) have been tested in settings associated with insufficiency the endogenous TM/APC pathway, such as sepsis. We previously designed a fusion [single-chain variable fragment antibody (scFv)/TM] targeted to red blood cells (RBCs) improve pharmacokinetics antithrombotic effects without increasing bleeding. Here,...
Phenotypes of lung smooth muscle cells in health and disease are poorly characterized. This is due, part, to a lack methodologies that allow for the independent direct isolation bronchial (BSMCs) vascular (VSMCs) from lung. In this paper, we describe development bi-fluorescent mouse permits purification these two cell populations by sorting. By subjecting an acute allergen based-model airway inflammation exhibits many features asthma, utilized tool characterize phenotype so-called asthmatic...
Asthma often progresses from early episodes of insults. How early-life events connect to long-term airway dysfunction remains poorly understood. We demonstrated previously that increased neurotrophin 4 (NT4) levels following allergen exposure cause persistent changes in smooth muscle (ASM) innervation and hyper-reactivity (AHR) mice. Herein, we identify pulmonary mast cells as a key source aberrant NT4 expression is selectively expressed by ASM mice, nonhuman primates, humans. show mice...