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  1. Article ; Online: Aerosolized Particulate Matter and Blunting of Ciliary Dynamic Responses: Implications for Veterans and Active Duty Military in Southwest Asia.

    Workman, Alan D / Lee, Robert J / Cohen, Noam A

    Military medicine

    2024  

    Abstract: Introduction: Respiratory diseases such as chronic rhinosinusitis and asthma are observed at increased rates in active duty and veteran military members, and they are especially prevalent in individuals who have been deployed in Southwest Asia during ... ...

    Abstract Introduction: Respiratory diseases such as chronic rhinosinusitis and asthma are observed at increased rates in active duty and veteran military members, and they are especially prevalent in individuals who have been deployed in Southwest Asia during Operation Iraqi Freedom and Operation Enduring Freedom. Particulate matter, specifically the fine-grain desert sand found in the Middle East, may be a key source of this pathology because of deleterious effects on mucociliary clearance.
    Materials and methods: With IRB approval, human sinonasal tissue was grown at an air-liquid interface and cultures were exposed to different types and sizes of particulate matter, including sand from Afghanistan and Kuwait. Ciliary dynamic responses to mechanical stimulation and ATP application were assessed following particulate exposure.
    Results: Particle size of the commercial sand was substantially larger than that of the sand of Afghan or Kuwaiti origin. Following exposure to particulate matter, normal dynamic ciliary responses to mechanical stimulation and ATP application were significantly decreased (P < .01), with corresponding decreases in ATP-induced calcium flux (P < .05). These changes were partially reversible with apical washing after a 16-h period of exposure. After 36 h of exposure to Middle Eastern sand, ciliary responses to purinergic stimulation were completely abolished.
    Conclusions: There is a neutralization of the dynamic ciliary response following chronic particulate matter exposure, similar to ciliary pathologies observed in patients with chronic rhinosinusitis. Aerosolized particulate matter endured by military personnel in the Southwest Asia may cause dysfunctional mucociliary clearance; these data help to explain the increased prevalence of respiratory pathology in individuals who are or have been deployed in this region.
    Language English
    Publishing date 2024-01-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 391061-1
    ISSN 1930-613X ; 0026-4075
    ISSN (online) 1930-613X
    ISSN 0026-4075
    DOI 10.1093/milmed/usae007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The spectrum of chronic rhinosinusitis therapy: from irrigation to the off-target effects of biologics.

    Cohen, Noam A

    International forum of allergy & rhinology

    2019  Volume 10, Issue 1, Page(s) 5–6

    MeSH term(s) Biological Products/therapeutic use ; Chronic Disease ; Humans ; Nasal Lavage ; Nasal Mucosa/metabolism ; Nasal Mucosa/pathology ; Nasal Polyps/therapy ; Olfaction Disorders/therapy ; Prognosis ; Rhinitis/diagnosis ; Rhinitis/therapy ; Sinusitis/diagnosis ; Sinusitis/therapy
    Chemical Substances Biological Products
    Language English
    Publishing date 2019-11-05
    Publishing country United States
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 2625826-2
    ISSN 2042-6984 ; 2042-6976
    ISSN (online) 2042-6984
    ISSN 2042-6976
    DOI 10.1002/alr.22515
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The genetics of the bitter taste receptor T2R38 in upper airway innate immunity and implications for chronic rhinosinusitis.

    Cohen, Noam A

    The Laryngoscope

    2016  Volume 127, Issue 1, Page(s) 44–51

    Abstract: Objective: Chronic rhinosinusitis (CRS) refractory to therapeutic intervention may involve a particularly resistant infection known as a bacterial biofilm. Critical to biofilm formation is the microbial process of quorum sensing whereby microbes secrete ...

    Abstract Objective: Chronic rhinosinusitis (CRS) refractory to therapeutic intervention may involve a particularly resistant infection known as a bacterial biofilm. Critical to biofilm formation is the microbial process of quorum sensing whereby microbes secrete factors that regulate the expression of microbial genes involved in biofilm formation, persistence, and virulence. Here, we review recent work demonstrating that the bitter taste receptor T2R38, expressed on the apical surface of the sinonasal epithelium, serves a sentinel role in eavesdropping on microbial quorum-sensing communications and regulates localized innate biocidal defenses. Furthermore, studies investigating whether cilia are necessary for T2R38 expression and function in the upper airway are presented.
    Methods: Primary human sinonasal air-liquid interface cultures were used to elucidate cellular pathways responsive to quorum-sensing molecules, whereas clinical studies investigated the contribution of T2R38 polymorphisms to recalcitrant chronic rhinosinusitis.
    Results: T2R38 is stimulated by acyl-homoserine lactones, gram-negative quorum-sensing molecules, and subsequently activates nitric oxide-dependent innate immune responses. The formation of mature cilia is necessary for T2R38 expression and function, and polymorphisms that underlie T2R38 functionality appear to be involved in susceptibility to upper respiratory infection and recalcitrant CRS.
    Conclusion: Taste receptors are emerging as critical components of early-phase respiratory innate immunity, detecting molecules used by microbes to communicate and stimulating localized host defenses. Genetic polymorphisms are very common within the taste receptors, and recent linkage studies have demonstrated associations of taste receptor genetics with CRS. Lastly, ciliogenesis, which is often impacted in CRS, is critical for the functional expression of T2R38.
    Level of evidence: N/A. Laryngoscope, 127:44-51, 2017.
    MeSH term(s) Biofilms ; Cells, Cultured ; Chronic Disease ; Cilia/physiology ; Fluorescent Antibody Technique ; Genotype ; Humans ; Immunity, Innate ; Microscopy, Confocal ; Microscopy, Electron, Scanning ; Mucociliary Clearance ; Polymorphism, Single Nucleotide ; Receptors, G-Protein-Coupled/genetics ; Respiratory Tract Infections/genetics ; Respiratory Tract Infections/immunology ; Rhinitis/genetics ; Rhinitis/immunology ; Sinusitis/genetics ; Sinusitis/immunology
    Chemical Substances Receptors, G-Protein-Coupled ; taste receptors, type 2
    Language English
    Publishing date 2016-09-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 80180-x
    ISSN 1531-4995 ; 0023-852X
    ISSN (online) 1531-4995
    ISSN 0023-852X
    DOI 10.1002/lary.26198
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  4. Article: Temporal and structural sensitivities of major biomarkers for detecting neuropathology after traumatic brain injury in the mouse.

    Xiong, Guoxiang / Jean, Ian / Farrugia, Anthony M / Metheny, Hannah / Johnson, Brian N / Cohen, Noam A / Cohen, Akiva S

    Frontiers in neuroscience

    2024  Volume 18, Page(s) 1339262

    Abstract: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality, especially in teenagers to young adults. In recent decades, different biomarkers and/or staining protocols have been employed to evaluate the post-injury development of ... ...

    Abstract Traumatic brain injury (TBI) is a leading cause of morbidity and mortality, especially in teenagers to young adults. In recent decades, different biomarkers and/or staining protocols have been employed to evaluate the post-injury development of pathological structures, but they have produced many contradictory findings. Since correctly identifying the underlying neuroanatomical changes is critical to advancing TBI research, we compared three commonly used markers for their ability to detect TBI pathological structures: Fluoro-Jade C, the rabbit monoclonal antibody Y188 against amyloid precursor protein and the NeuroSilver kit were used to stain adjacent slices from naïve or injured mouse brains harvested at different time points from 30 min to 3 months after lateral fluid percussion injury. Although not all pathological structures were stained by all markers at all time points, we found damaged neurons and deformed dendrites in gray matter, punctate and perivascular structures in white matter, and axonal blebs and Wallerian degeneration in both gray and white matter. The present study demonstrates the temporal and structural sensitivities of the three biomarkers: each marker is highly effective for a set of pathological structures, each of which in turn emerges at a particular time point. Furthermore, the different biomarkers showed different abilities at detecting identical types of pathological structures. In contrast to previous studies that have used a single biomarker at a single time range, the present report strongly recommends that a combination of different biomarkers should be adopted and different time points need to be checked when assessing neuropathology after TBI.
    Language English
    Publishing date 2024-01-30
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2024.1339262
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  5. Article ; Online: Epithelial dysregulation in chronic rhinosinusitis with nasal polyposis (CRSwNP) and aspirin-exacerbated respiratory disease (AERD).

    Kohanski, Michael A / Cohen, Noam A / Barrett, Nora A

    The Journal of allergy and clinical immunology

    2021  Volume 148, Issue 5, Page(s) 1161–1164

    MeSH term(s) Aspirin/adverse effects ; Biomarkers ; Chronic Disease ; Disease Progression ; Disease Susceptibility ; Humans ; Nasal Polyps/pathology ; Respiratory Mucosa/metabolism ; Respiratory Mucosa/pathology ; Respiratory Tract Diseases/etiology ; Respiratory Tract Diseases/metabolism ; Respiratory Tract Diseases/pathology ; Rhinitis/etiology ; Rhinitis/metabolism ; Rhinitis/pathology ; Sinusitis/etiology ; Sinusitis/metabolism ; Sinusitis/pathology
    Chemical Substances Biomarkers ; Aspirin (R16CO5Y76E)
    Language English
    Publishing date 2021-08-06
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2021.07.034
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  6. Article ; Online: Infection of Primary Nasal Epithelial Cells Grown at an Air-Liquid Interface to Characterize Human Coronavirus-Host Interactions.

    Otter, Clayton J / Fausto, Alejandra / Tan, Li Hui / Weiss, Susan R / Cohen, Noam A

    Journal of visualized experiments : JoVE

    2023  , Issue 199

    Abstract: Three highly pathogenic human coronaviruses (HCoVs) - SARS-CoV (2002), MERS-CoV (2012), and SARS-CoV-2 (2019) - have emerged and caused significant public health crises in the past 20 years. Four additional HCoVs cause a significant portion of common ... ...

    Abstract Three highly pathogenic human coronaviruses (HCoVs) - SARS-CoV (2002), MERS-CoV (2012), and SARS-CoV-2 (2019) - have emerged and caused significant public health crises in the past 20 years. Four additional HCoVs cause a significant portion of common cold cases each year (HCoV-NL63, -229E, -OC43, and -HKU1), highlighting the importance of studying these viruses in physiologically relevant systems. HCoVs enter the respiratory tract and establish infection in the nasal epithelium, the primary site encountered by all respiratory pathogens. We use a primary nasal epithelial culture system in which patient-derived nasal samples are grown at an air-liquid interface (ALI) to study host-pathogen interactions at this important sentinel site. These cultures recapitulate many features of the in vivo airway, including the cell types present, ciliary function, and mucus production. We describe methods to characterize viral replication, host cell tropism, virus-induced cytotoxicity, and innate immune induction in nasal ALI cultures following HCoV infection, using recent work comparing lethal and seasonal HCoVs as an example
    MeSH term(s) Humans ; Middle East Respiratory Syndrome Coronavirus ; Epithelial Cells ; SARS-CoV-2 ; Virus Replication ; Nasal Mucosa
    Language English
    Publishing date 2023-09-22
    Publishing country United States
    Document type Journal Article ; Video-Audio Media ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/64868
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Aerosol or droplet: critical definitions in the COVID-19 era.

    Kohanski, Michael A / Palmer, James N / Cohen, Noam A

    International forum of allergy & rhinology

    2020  Volume 10, Issue 8, Page(s) 968–969

    MeSH term(s) Aerosols ; Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2
    Chemical Substances Aerosols
    Keywords covid19
    Language English
    Publishing date 2020-06-15
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 2625826-2
    ISSN 2042-6984 ; 2042-6976
    ISSN (online) 2042-6984
    ISSN 2042-6976
    DOI 10.1002/alr.22591
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  8. Article ; Online: Persistent Inflammation and Nitric Oxide Dysregulation Are Transcriptomic Blueprints of Subglottic Stenosis.

    Nguyen, Hoang C B / Chao, Tiffany N / Cohen, Noam A / Mirza, Natasha

    Frontiers in immunology

    2021  Volume 12, Page(s) 748533

    Abstract: Subglottic stenosis (SGS) is a recurrent, obstructive, fibroinflammatory disease of the upper airway resulting in severe dyspnea, dysphonia, as well as other potentially fatal complications. Although aberrant inflammation and wound-healing are commonly ... ...

    Abstract Subglottic stenosis (SGS) is a recurrent, obstructive, fibroinflammatory disease of the upper airway resulting in severe dyspnea, dysphonia, as well as other potentially fatal complications. Although aberrant inflammation and wound-healing are commonly associated with pathogenesis, the mechanism through which such processes occur and recur in affected patients remains poorly studied. Here we report that transcriptomic profiling of laryngotracheal regions from minimally-invasive mucosal swabs of SGS patients reveals a distinctively pro-inflammatory gene signature. Surprisingly, comparative genomics between SGS patients and mice with direct laryngotracheal injury suggest that SGS patients bear more resemblance to the acute than chronic phase of injury. Furthermore, functional and regulatory network analyses identify neutrophilic involvement through hyper-activation of NF-κB and its downstream inflammasome as a potential master regulator. Interestingly, nitric oxide synthesis was found to be downregulated in SGS patients compared to healthy controls. Thus, SGS represents a state of immunodeficiency whereby defective immune clearance triggers recurrent, long-lasting production of pro-inflammatory cytokines.
    MeSH term(s) Animals ; Female ; Humans ; Inflammation/immunology ; Laryngostenosis/genetics ; Laryngostenosis/immunology ; Mice ; Mice, Inbred C57BL ; Nitric Oxide/immunology ; Transcriptome
    Chemical Substances Nitric Oxide (31C4KY9ESH)
    Language English
    Publishing date 2021-12-20
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.748533
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  9. Article: Infection of primary nasal epithelial cells differentiates among lethal and seasonal human coronaviruses.

    Otter, Clayton J / Fausto, Alejandra / Tan, Li Hui / Cohen, Noam A / Weiss, Susan R

    bioRxiv : the preprint server for biology

    2022  

    Abstract: The nasal epithelium is the initial entry portal and primary barrier to infection by all human coronaviruses (HCoVs). We utilize primary nasal epithelial cells grown at air-liquid interface, which recapitulate the heterogeneous cellular population as ... ...

    Abstract The nasal epithelium is the initial entry portal and primary barrier to infection by all human coronaviruses (HCoVs). We utilize primary nasal epithelial cells grown at air-liquid interface, which recapitulate the heterogeneous cellular population as well as mucociliary clearance functions of the
    Language English
    Publishing date 2022-10-18
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2022.10.17.512617
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  10. Article ; Online: Nicotinic acetylcholine receptor stimulation: A new approach for stimulating tear secretion in dry eye disease.

    Pflugfelder, Stephen C / Cao, Austin / Galor, Anat / Nichols, Kelly K / Cohen, Noam A / Dalton, Michelle

    The ocular surface

    2022  Volume 25, Page(s) 58–64

    Abstract: Tear secretion is regulated by the lacrimal functional unit consisting of afferent and efferent nerve innervation. The afferent arm consists of trigeminal nociceptors on the ocular surface and nasal mucosa. When stimulated by agonists, nicotinic ... ...

    Abstract Tear secretion is regulated by the lacrimal functional unit consisting of afferent and efferent nerve innervation. The afferent arm consists of trigeminal nociceptors on the ocular surface and nasal mucosa. When stimulated by agonists, nicotinic acetylcholine receptors on nerve endings in the nose initiate a reflex arc resulting in instantaneous tear secretion. Pharmacologic nasal neural stimulation to increase endogenous tear production is a novel approach to treating dry eye disease.
    MeSH term(s) Dry Eye Syndromes ; Humans ; Lacrimal Apparatus/innervation ; Nociceptors ; Receptors, Nicotinic ; Tears
    Chemical Substances Receptors, Nicotinic
    Language English
    Publishing date 2022-05-10
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2208578-6
    ISSN 1937-5913 ; 1542-0124
    ISSN (online) 1937-5913
    ISSN 1542-0124
    DOI 10.1016/j.jtos.2022.05.001
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