A5073050363- Asthma and respiratory diseases
- Neonatal Respiratory Health Research
- Allergic Rhinitis and Sensitization
- Air Quality and Health Impacts
- Air Quality Monitoring and Forecasting
- Respiratory viral infections research
- Alzheimer's disease research and treatments
- Neuropeptides and Animal Physiology
- Neuroinflammation and Neurodegeneration Mechanisms
- Respiratory and Cough-Related Research
- Inhalation and Respiratory Drug Delivery
- Olfactory and Sensory Function Studies
- SARS-CoV-2 and COVID-19 Research
- SARS-CoV-2 detection and testing
- Phosphodiesterase function and regulation
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Noise Effects and Management
- Indoor Air Quality and Microbial Exposure
- COVID-19 Clinical Research Studies
- Occupational and environmental lung diseases
- Infant Nutrition and Health
- Congenital Diaphragmatic Hernia Studies
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Influenza Virus Research Studies
Lovelace Respiratory Research Institute
2013-2023
Biomedical Research Institute
2020-2023
Medical College of Wisconsin
2003
University of New Mexico
2002
University of Rochester
1999
University of Virginia
1994
Transmission-blocking strategies that slow the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and protect against disease 2019 (COVID-19) are needed. We have developed an orally delivered adenovirus type 5-vectored SARS-CoV-2 vaccine candidate expresses spike protein. Here, we demonstrated hamsters vaccinated by oral or intranasal route had robust cross-reactive antibody responses. then induced a postvaccination infection inoculating with SARS-CoV-2. Orally...
Aged canines (dogs) accumulate human-type β-amyloid (Aβ) in diffuse plaques the brain with parallel declines cognitive function. We hypothesized that reducing Aβ a therapeutic treatment study of aged dogs preexisting pathology and deficits would lead to improvements. To test this hypothesis, we immunized beagles (8.4–12.4 years) fibrillar 1–42 formulated aluminum salt (Alum) for 2.4 years (25 vaccinations). Cognitive testing during time revealed no improvement measures learning, spatial...
Rationale: Ultrasound-mediated opening of the Blood-Brain Barrier(BBB) has shown exciting potential for treatment Alzheimer's disease(AD).Studies in transgenic mouse models have that this approach can reduce plaque pathology and improve spatial memory.Before clinical translation occur safety method needs to be tested a larger brain allows lower frequencies used treat tissue volumes, simulating situations.Here we investigate BBB half large aged animal model with naturally occurring amyloid...
Alveolar macrophages play a key role in the development of silicosis by releasing host mediators, such as, cytokines and chemokines, which contribute to complex network interactions that result onset lung injury, inflammation, potentially fibrosis. Using murine macrophage cell line, RAW 264.7, we exposed cells cristobalite-silica (35 micrograms/cm(2)) presence or absence antioxidants various modifiers cellular antioxidant status. Treatment with dimethyl sulfoxide, extracellular glutathione,...
Epidemiologic studies suggest that in utero exposure to tobacco smoke, primarily through maternal smoking, increases the risk for asthma children; however, mechanism of this phenomenon is not clear. Cyclic adenosine monophosphate relaxes airway smooth muscles lung and acts as an antiasthmatic. In study, we examined effects cigarette smoke Balb/c mice on responsiveness, determined by Penh measurements. Animals exposed prenatally but postnatally exhibited increased hyperresponsiveness after a...
We have shown previously that epithelial cells may contribute to the inflammatory response in lung after exposure crystalline silica through production of and specific chemokines cytokines. However, exact cellular molecular responses remain unclear. hypothesize non-oxidant-mediated silica-cell interactions lead upregulation tumor necrosis factor-α (TNF-α), whereby TNF-α-induced generation reactive oxygen species (ROS) leads activation monocyte chemotactic protein (MCP)-1 macrophage (MIP)-2...
Human milk oligosaccharides (HMO) contribute to innate immunity by enhancing growth of beneficial bacteria, epithelial cell maturation and mucosal barrier integrity. They have immunomodulatory effects can block pathogen binding host surface glycans or receptors. We investigated the 2’-fucosyllactose (2’FL), 6’-sialyllactose (6’SL), 3’-sialyllactose (3’SL) lacto-N-neoTetraose (LNnT) on human respiratory lines peripheral blood mononuclear cells (PBMCs) following viral infectionin vitro....
Epidemiologic studies suggest that children raised in homes of cigarette smokers have a higher incidence asthma than who are nonsmokers. We sought to develop an experimental model understand the mechanisms involved. Female BALB/c mice were paired with male DO11.10 ovalbumin (OVA)-T cell receptor hemizygous (+/−) such offspring either transgene positive or negative (−/−). Mice exposed air mainstream smoke (100 mg/m3 total particulate matter, 6 hours/day, 7 days/week) during pregnancy....
Respiratory syncytial virus (RSV) infects approximately 90% of young children by the age 2 yr, with peak rates occurring during 2-6 mo age. Exposure to side-stream cigarette smoke (SS) may increase incidence or manifestation an RSV infection. We hypothesized that exposure SS would alter subsequent immune response infection in neonatal mice. BALB/c mice were exposed air 1.5 mg/m3 from day (d) 1 up 35 d A subset was intranasally infected 4x10(4) PFU RSV/g body wt on 7 and rechallenged at 28...
Significance Defects in myosin function are linked to a number of widespread and debilitating diseases, including asthma, chronic obstructive pulmonary disease, hypertrophic cardiomyopathy. We report here the discovery an allosteric site that modulates motor with high specificity opens path toward new therapeutic solutions. Identification specific antimyosin drugs significantly alter motor’s is imperative first step development targeted effective treatments for such diseases. Highly against...
Aerosol delivery of chemotherapeutic nanocarriers represents a promising alternative for lung cancer therapy. This study optimized gemcitabine (Gem)-loaded gelatin (GNCs) cross-linked with genipin (Gem-GNCs) to evaluate their potential nebulized treatment.
Clara cell secretory protein (CCSP) is synthesized by nonciliated bronchiolar cells in the lung and modulates inflammation to infection. To determine role of CCSP host response allergic airway disease, CCSP-deficient [(−/−)] mice were immunized twice with ovalbumin (Ova) challenged Ova (2 or 5 mg/m 3 ) aerosol. After 2, 3, days aerosol challenge (6 h/day), reactivity was increased CCSP(−/−) compared wild-type [CCSP(+/+)] mice. Neutrophils markedly bronchoalveolar lavage fluid mice,...
Hardwood smoke (HWS) from wood burning stoves and fireplaces can be a significant contributor to the composition of ambient air pollution. We hypothesize that inhalation HWS by ovalbumin (OVA)-sensitized mice with preexisting lung inflammation leads exacerbation allergic airway responses. Two different models were employed characterize effects inhaled on inflammation. In both models, male BALB/c sensitized injection OVA alum. one model, challenged 1 day prior exposure (30, 100, 300, or 1000...
Human studies suggest either a protective role or no benefit of statins against the development Alzheimer's disease (AD). We tested hypothesis that statin-mediated cholesterol reduction in aged dogs, which have cognitive impairments and amyloid-β (Aβ) pathology, would improve cognition reduce neuropathology. In study 12 animals, we treated dogs with 80 mg/day atorvastatin for 14.5 months. did not observe improvements discrimination learning; however, there were transient reversal learning,...
Abstract Neutrophil-induced oxidative stress is a mechanism of lung injury in COVID-19, and drugs with functional thiol group (“thiol drugs”), especially cysteamine, have anti-oxidant anti-inflammatory properties that could limit this injury. Thiol may also alter the redox status cysteine-rich SARS-CoV-2 spike glycoprotein (SARS-2-S) thereby disrupt ACE2 binding. Using binding assay, reporter virus pseudotyped spikes (ancestral variants) authentic (Wuhan-1), we find multiple inhibit SARS-2-S...
Cigarette smoke (CS) exposure during gestation may increase the risk of bronchopulmonary dysplasia (BPD)-a developmental lung condition primarily seen in neonates that is characterized by hypoalveolarization, decreased angiogenesis, and diminished surfactant protein production chronic obstructive pulmonary disease.We investigated whether gestational to secondhand CS (SS) induced BPD sought ascertain role nicotinic acetylcholine receptors (nAChRs) this response.We exposed BALB/c C57BL/6 mice...
The NERC Program conducted identically designed exposure-response studies of the respiratory and cardiovascular responses rodents exposed by inhalation for up to 6 months diesel gasoline exhausts (DE, GE), wood smoke (WS) simulated downwind coal emissions (CE). Concentrations four combustion-derived mixtures ranged from near upper bound plausible common occupational environmental hotspot levels. An "exposure effect" statistic was created compare strengths relationships adjustments were made...
The redox status of the cysteine-rich SARS-CoV-2 spike glycoprotein (SARS-2-S) is important for binding SARS-2-S to angiotensin-converting enzyme 2 (ACE2), suggesting that drugs with a functional thiol group (“thiol drugs”) may cleave cystines disrupt cell entry. In addition, neutrophil-induced oxidative stress mechanism COVID-19 lung injury, and antioxidant anti-inflammatory properties drugs, especially cysteamine, limit this injury. To first explore antiviral effects in COVID-19, we used...
There is a growing concern about whether the myriad of culture conditions, cell lines, and doses nonfibrous fibrous particles used in vitro are truly representative complex environment vivo particle exposure situation. The use serum as supplement to growth medium cultured cells widely accepted practice. However, little known various proteins may interact with surfaces particles, consequently altering their toxicity, inflammatory properties, or fibrogenicity, etc. observed vivo. Using murine...
In the era of combined antiretroviral therapy (cART), lung diseases such as chronic bronchitis (CB) and obstructive pulmonary disease (COPD) are common among persons living with HIV (PLWH), particularly smokers. Although smoking is highly prevalent PLWH, may be an independent risk factor for diseases; however, role cigarette smoke (CS) their potential interaction in development PLWH has not been delineated. To investigate this interaction, cynomolgus macaques were exposed to CS and/or...
Studies of myocardial aging are complex and the mechanisms involved in deterioration ventricular performance decreased functional reserve old heart remain to be properly defined. We have studied a colony beagle dogs from 3 14 yr age kept under highly regulated environment define effects on myocardium. Ventricular, myocardial, myocyte function, together with anatomical structural properties organ cardiomyocytes, were evaluated. Ventricular hypertrophy was not observed composition myocardium...