2026-09-19T11:32:48Zhttps://dspace.mit.edu/server/oai/requestoai:dspace.mit.edu:1721.1/93722022-01-13T07:53:45Zcom_1721.1_7582com_1721.1_7581col_1721.1_131022
Jeffrey J. Fredberg.
Inouye, David Shoichi
Harvard University--MIT Division of Health Sciences and Technology.
Harvard University--MIT Division of Health Sciences and Technology
2005-08-22T20:40:58Z
2005-08-22T20:40:58Z
2000
http://hdl.handle.net/1721.1/9372
44804247
Thesis (Ph.D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, 2000.
"September 1999."
Includes bibliographical references (leaves 139-145).
In asthma, the key effector driving acute airway narrowing is thought to be airway smooth muscle (ASM); as the muscle surrounding the airways shortens, the airway lumen narrows. Airway hyperresponsiveness (AHR) - the excessive narrowing of the airways - is one of the cardinal features of asthma. Yet, the mechanism(s) regulating the airway lumenal radius, and perhaps the failure of these mechanisms to prevent excessive airway constriction, remains largely unexplained. This thesis shows that the regulation of ASM length corresponds to a dynamically equilibrated steady-state, not the static mechanical equilibrium that had been previously assumed. This dynamic steady state requires as an essential feature a continuous supply of external mechanical energy (derived from tidal lung inflations) that act to perturb the interactions of myosin with actin, drive the molecular state of the system far away from thermodynamic equilibrium, and bias the muscle toward lengthening. This mechanism leads naturally to the suggestion that excessive airway narrowing in asthma may be associated with the destabilization of that dynamic process and its resulting collapse back to static equilibrium. With this collapse the muscle undergoes a phase transition and virtually freezes at its static equilibrium length. This mechanism may help to elucidate several unexplained phenomena including the multi-factorial origins of AHR, how allergen sensitization leads to AHR, and the inability in asthma of deep inspiration to relax ASM.
by David Shoichi Inouye.
Ph.D.
156 p.
10262982 bytes
10262739 bytes
application/pdf
application/pdf
eng
Massachusetts Institute of Technology
M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.
http://dspace.mit.edu/handle/1721.1/7582
Harvard University--MIT Division of Health Sciences and Technology.
Perturbed equilibria of myosin binding in airway smooth muscle and its implications in airway hyperresponsiveness and asthma
Thesis
application/pdf
false
Publication
unknown
unknown
<Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="09c7393e-d8e1-4549-81cb-d95604b287f7">
<Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type>
<Language>eng</Language>
<Title>Perturbed equilibria of myosin binding in airway smooth muscle and its implications in airway hyperresponsiveness and asthma</Title>
<PublishedIn>
<Publication>
</Publication>
</PublishedIn>
<PublicationDate>2000</PublicationDate>
<Authors>
<Author>
<DisplayName>Inouye, David Shoichi</DisplayName>
<Affiliation>
<OrgUnit>
</OrgUnit>
</Affiliation>
</Author>
</Authors>
<Editors>
</Editors>
<Publishers>
<Publisher>
<DisplayName>Massachusetts Institute of Technology</DisplayName>
<OrgUnit />
</Publisher>
</Publishers>
<License>http://dspace.mit.edu/handle/1721.1/7582</License>
<Keyword>Harvard University--MIT Division of Health Sciences and Technology.</Keyword>
<Abstract>In asthma, the key effector driving acute airway narrowing is thought to be airway smooth muscle (ASM); as the muscle surrounding the airways shortens, the airway lumen narrows. Airway hyperresponsiveness (AHR) - the excessive narrowing of the airways - is one of the cardinal features of asthma. Yet, the mechanism(s) regulating the airway lumenal radius, and perhaps the failure of these mechanisms to prevent excessive airway constriction, remains largely unexplained. This thesis shows that the regulation of ASM length corresponds to a dynamically equilibrated steady-state, not the static mechanical equilibrium that had been previously assumed. This dynamic steady state requires as an essential feature a continuous supply of external mechanical energy (derived from tidal lung inflations) that act to perturb the interactions of myosin with actin, drive the molecular state of the system far away from thermodynamic equilibrium, and bias the muscle toward lengthening. This mechanism leads naturally to the suggestion that excessive airway narrowing in asthma may be associated with the destabilization of that dynamic process and its resulting collapse back to static equilibrium. With this collapse the muscle undergoes a phase transition and virtually freezes at its static equilibrium length. This mechanism may help to elucidate several unexplained phenomena including the multi-factorial origins of AHR, how allergen sensitization leads to AHR, and the inability in asthma of deep inspiration to relax ASM.</Abstract>
<Access xmlns="http://purl.org/coar/access_right"
>
</Access>
</Publication>