Laryngeal Muscle

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Christy L. Ludlow - One of the best experts on this subject based on the ideXlab platform.

  • Effects of Dopamine D1 and D2 Receptor Antagonists on Laryngeal Neurophysiology in the Rat
    Journal of Neurophysiology, 2009
    Co-Authors: Xin Feng, Victor M. Henriquez, Judith R. Walters, Christy L. Ludlow
    Abstract:

    Hypophonia is an early symptom in Parkinson's disease (PD) that involves an increase in Laryngeal Muscle activity, interfering with voice production. Our aim was to use an animal model to better un...

  • Laryngeal Muscle responses to mechanical displacement of the thyroid cartilage in humans
    Journal of Applied Physiology, 2005
    Co-Authors: Torrey M J Loucks, Christopher J Poletto, Keith G Saxon, Christy L. Ludlow
    Abstract:

    Speakers may use Laryngeal sensory feedback to adjust vocal fold tension and length before initiating voice. The mechanism for accurately initiating voice at an intended pitch is unknown, given the...

  • effects of levodopa on Laryngeal Muscle activity for voice onset and offset in parkinson disease
    Journal of Speech Language and Hearing Research, 2001
    Co-Authors: Sally Gallena, Paul J Smith, Thomas Zeffiro, Christy L. Ludlow
    Abstract:

    The Laryngeal pathophysiology underlying the speech disorder in idiopathic Parkinson disease (IPD) was addressed in this electromyographic study of Laryngeal Muscle activity. This Muscle activity was examined during voice onset and offset gestures in 6 persons in the early stages of IPD who were not receiving medication. The purpose was to determine (a) if impaired voice onset and offset control for speech and vocal fold bowing were related to abnormalities in Laryngeal Muscle activity in the nonmedicated state and (b) if these attributes change with levodopa. Blinded listeners rated the IPD participants' voice onset and offset control before and after levodopa was administered. In the nonmedi-cated state, the IPD participants' vocal fold bowing was examined on nasoendo-scopy, and Laryngeal Muscle activity levels were compared with normal research volunteers. The IPD participants were then administered a therapeutic dose of levodopa, and changes in Laryngeal Muscle activity for voice onset and offset gest...

  • adductor Muscle activity abnormalities in abductor spasmodic dysphonia
    Otolaryngology-Head and Neck Surgery, 2001
    Co-Authors: Carlos B Cyrus, Steven Bielamowicz, Frank Evans, Christy L. Ludlow
    Abstract:

    Abstract Objective: To determine Laryngeal Muscle activation abnormalities associated with speech symptoms in abductor spasmodic dysphonia (ABSD). Study Design: Bilateral Laryngeal Muscle recordings from the posterior cricoarytenoid, thyroarytenoid, and cricothyroid Muscles were conducted in 12 ABSD patients. Patients' measures were compared during speech breaks and during speech without breaks and with 10 normal controls. Results: Significant group differences were found in the thyroarytenoid Muscle; the patients had significantly greater activity on the right side both during speech breaks and nonbreaks in comparison with the controls. Cricothyroid Muscle levels were also increased on the right in the patients. Conclusion: An asymmetry in adductor Muscle tone between the 2 sides in ABSD may account for difficulties with maintaining phonation and voice onset after voiceless consonants. Significance: These abnormalities may indicate why PCA BOTOX injections have not been as effective in ABSD as thyroarytenoid injections have been in adductor spasmodic dysphonia. (Otolaryngol Head Neck Surg 2001;124:23-30)

  • effects of adductor Muscle stimulation on speech in abductor spasmodic dysphonia
    Laryngoscope, 2000
    Co-Authors: Kimberly Bidus, Giovana R Thomas, Christy L. Ludlow
    Abstract:

    Objective To determine whether adductor Laryngeal Muscle stimulation might be a beneficial treatment alternative for abductor spasmodic dysphonia (ABSD). Study Design Baseline comparisons were made on measures of voiceless consonant and syllable duration between patients with ABSD and normal control subjects, and speech and voice production with and without Muscle stimulation were compared within 10 patients with ABSD. Methods Baseline group comparisons were conducted on measures of syllable and voiceless consonant duration between the patients and the control subjects. Neuromuscular stimulation was applied to the thyroarytenoid or lateral cricoarytenoid Muscles in the patients during e-tended phonation, and measures were made of fundamental frequency and sound pressure level in the stimulated and nonstimulated conditions. Voiceless consonant duration was compared with and without adductor Laryngeal Muscle stimulation during syllable repetitions and sentences in the patients. Results Before stimulation, the patients had increased syllable durations in comparison with control subjects (P = .003). Repeated within-patient comparisons with and without stimulation demonstrated significant (P < .008) reductions in voiceless consonant durations during syllable repetition. The more severely affected patients had the greatest reductions in voiceless consonant duration during sentence production. Conclusions Adductor Muscle stimulation improved speech production in patients with ABSD, and the improvement was greatest in the most severely affected patients. Therefore adductor Muscle stimulation has potential for benefiting patients with ABSD.

Paul W. Flint - One of the best experts on this subject based on the ideXlab platform.

  • myosin heavy chain composition in normal and atrophic equine Laryngeal Muscle
    Veterinary Pathology, 2006
    Co-Authors: Christine M Adreani, Paul W. Flint, Mohamed Lehar, Louise L Southwood, Perry L Habecker, Eric J Parente
    Abstract:

    The myosin heavy chain (MHC) composition of a given Muscle determines the contractile properties and, therefore, the fiber type distribution of the Muscle. MHC isoform expression in the Laryngeal Muscle is modulated by neural input and function, and it represents the cellular level changes that occur with denervation and reinnervation of skeletal Muscle. The objective of this study was to evaluate the pattern of MHC isoform expression in Laryngeal Muscle harvested from normal cadavers and cadavers with naturally occurring left Laryngeal hemiplegia secondary to recurrent Laryngeal neuropathy. Left and right thyroarytenoideus (TA) and cricoarytenoideus dorsalis (CAD) were obtained from 7 horses affected with left-sided intrinsic Laryngeal Muscle atrophy and from 2 normal horses. Frozen sections were evaluated histologically for degree of atrophy and fiber type composition. MHC isoform expression was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of Muscle protein. Histologic atrophy was seen in all atrophic Muscles and some right-sided Muscles of 3 affected horses, as well as the left TA of 1 normal horse. Fiber type grouping or loss of type I Muscle fibers was observed in the left-sided Laryngeal Muscles in all but 1 affected horse, as well as in the right Muscles of 2 affected horses, and the left TA of 1 normal horse. SDS-PAGE showed 2 bands corresponding to the type I and type IIB myosin isoforms in the CAD and TA of the 2 normal horses. Affected horses demonstrated a trend toward increased expression of the type IIB isoform and decreased expression of the type I isoform in atrophic Muscles. This study confirmed the presence of histologic abnormalities in grossly normal equine Laryngeal Muscle, and it demonstrated an increased expression of type IIB MHC with a concurrent decreased expression of type I MHC in affected Muscles. Evaluation of Muscle fiber changes at the cellular level under denervated and reinnervated conditions may aid in assessing future strategies for reinnervation or regeneration of atrophic Laryngeal Muscle.

  • high efficiency gene delivery into Laryngeal Muscle with bidirectional electroporation
    Otolaryngology-Head and Neck Surgery, 2006
    Co-Authors: Koichiro Saito, Mohamed Lehar, Robin A Samlan, Natasha Braga, Alan D King, Paul W. Flint
    Abstract:

    OBJECTIVE: The impact of polarity change on the efficiency of in vivo electroporative (EP) gene transfection was assessed in rat Laryngeal Muscle. STUDY DESIGN AND SETTING: High (HV) and low field voltage (LV) were combined with polarity changes to determine transfection in 5 different conditions: 1) without EP (EP[-]), 2) HV+LV (HL), 3) HV+LV followed by HV+LV with no change in polarity (HLHL unidirectional), 4) HV+LV followed by HV+LV with opposite polarity (HLHL bidirectional), 5) HV+LV followed by LV with opposite polarity (HLL bidirectional). RESULTS: HLL bidirectional sequence showed the best result with less interindividual variability and extended expression period. With the exception of repeated high voltage sequences, EP parameters were not likely to induce cell injury or inflammation. CONCLUSION: HLL bidirectional electroporative gene delivery produces high transfection rates with limited tissue trauma. SIGNIFICANCE: Bidirectional EP provides a safe and highly efficient method for therapeutic gene delivery into skeletal Muscle.

  • proteomic analysis of rat Laryngeal Muscle following denervation
    Proteomics, 2005
    Co-Authors: Mohamed Lehar, Robin A Samlan, Paul W. Flint
    Abstract:

    Laryngeal Muscle atrophy induced by nerve injury is a major factor contributing to the disabling symptoms associated with Laryngeal paralysis. Alterations of global proteins in rat Laryngeal Muscle following denervation were, therefore, studied using proteomic techniques. Twenty-eight adult Sprague-Dawley rats were divided into normal control and denervated groups. The thyroarytenoid (TA) Muscle was excised 60 days after right recurrent Laryngeal nerve was resected. Protein separation and identification were preformed using 2-DE and MALDI-MS with database search. Forty-four proteins were found to have significant alteration in expression level after denervation. The majority of these proteins (57%), most of them associated with energy metabolism, cellular proliferation and differentiation, signal transduction and stress reaction, were decreased levels of expression in denervated TA Muscle. The remaining 43% of the proteins, most of them involved with protein degradation, immunoreactivity, injury repair, contraction, and microtubular formation, were found to have increased levels of expression. The protein modification sites by phosphorylation were detected in 22% of the identified proteins that presented multiple-spot patterns on 2-D gel. Significant changes in protein expression in denervated Laryngeal Muscle may provide potential therapeutic strategies for the treatment of Laryngeal paralysis.

  • Laryngeal Muscle surface receptors identified using random phage library.
    The Laryngoscope, 2005
    Co-Authors: Paul W. Flint, Mohamed Lehar, Koichiro Saito, Sara I. Pai
    Abstract:

    Objectives: The ultimate goal of this study is to improve the efficiency of gene transfer in mammalian Muscle by developing targeted adenoviral vectors. Altering the tropism of viral vectors to recognize tissue specific antigens is one method to achieve this goal. This approach requires identification of cell-surface receptors and the insertion of target peptide sequences into the adenoviral fiber protein. In this study, phage biopanning was performed on cultured rat skeletal and Laryngeal Muscle to identify cell-surface receptors. Study Design: In vitro cell culture and in vivo animal model. Methods: M-13 Phage biopanning was used for Muscle cell-surface receptor analysis on cultured rat skeletal and Laryngeal Muscle. Nonbinding and binding phage to cultured skeletal and Laryngeal Muscle were screened for Muscle specific surface peptides. In vivo studies were then performed using Muscle specific phage. Results: Skeletal Muscle specific binding by the YASTNPM phage was observed by in vivo immunostaining. Phage titering demonstrated a 109-fold increase in skeletal Muscle binding compared with nontarget tissue. A peptide sequence (NPSQVKH) specific for Laryngeal Muscle yielded a 107-fold increase in Laryngeal Muscle phage titer compared with nontarget tissue. Conclusions: These results identify Muscle cell-surface receptors that may be used as potential targets for genetic modification of adenovirus tropism. Moreover, phage specificity for skeletal and Laryngeal Muscle indicates specific Muscle groups may be targeted.

  • timing of human insulin like growth factor 1 gene transfer in reinnervating Laryngeal Muscle
    Laryngoscope, 2004
    Co-Authors: Hideki Nakagawa, Akihiro Shiotani, Michael E Coleman, Bert W Omalley, Paul W. Flint
    Abstract:

    Objectives/Hypothesis The authors have designed a rat Laryngeal paralysis model to study gene transfer strategies using a Muscle-specific expression system to enhance local delivery of human insulin-like growth factor-1 (hIGF-1). In preliminary studies, a nonviral vector containing the α-actin promoter and human hIGF-1 sequence produced both neurotrophic and myotrophic effects 1 month after single injection of plasmid formulation into paralyzed rat thyroarytenoid Muscle in vivo. Based on these findings, it is hypothesized that the effects of hIGF-1 will enhance the results of Laryngeal Muscle innervation procedures. The timing of gene delivery relative to nerve repair is likely to be important, to optimize the results. Study Design Prospective analysis. Methods The effects of nonviral gene transfer for the delivery of hIGF-1 were evaluated in rats treated immediately following recurrent Laryngeal nerve transection and repair and in rats receiving a delayed treatment schedule, 30 days after nerve transection and repair. Gene transfer efficiency was determined using polymerase chain reaction and reverse transcriptase–polymerase chain reaction techniques. Muscle fiber diameter, motor endplate length, and percentage of motor endplates with nerve contact were examined to assess hIGF-1 trophic effects. Results Compared with reinnervated untreated control samples, both early and delayed hIGF-1 transfer resulted in significant increase in Muscle fiber diameter. Motor endplate length was significantly decreased and nerve/motor endplate contact was significantly increased following delayed gene transfer, but not after early treatment. Conclusion We infer from results of the study that delayed hIGF-1 gene transfer delivered by a single intramuscular injection will enhance the process of Muscle reinnervation. The clinical relevance of these findings supports the future application of gene therapy using nonviral vectors for management of Laryngeal paralysis and other peripheral nerve injuries.

Vincent J Caiozzo - One of the best experts on this subject based on the ideXlab platform.

  • Effects of denervation on cell cycle control in Laryngeal Muscle.
    Archives of otolaryngology--head & neck surgery, 2004
    Co-Authors: Vincent J Caiozzo, Michael J. Baker, Roger L Crumley
    Abstract:

    Denervation of skeletal Muscle is thought to lead to an accelerated proliferation of myogenic stem cells known as satellite cells. The transition of these cells from a quiescent to a proliferative state is thought to require satellite cells to enter the cell cycle and replicate. Little is known about the expression of genes associated with cell cycle control, and so the objective of this study was to examine the effects of denervation and reinnervation of the posterior cricoarytenoid (PCA) Muscle on key cell cycle genes. Female Sprague-Dawley rats were assigned to control, denervated, or reinnervated groups. Animals were killed at 7, 14, and 30 days after ligation of the recurrent Laryngeal nerve. The PCA Muscle was then analyzed for changes in the messenger RNA levels of key genes associated with cell cycle control, differentiation, and proliferation. Cyclin D1 is a key gene responsible for initiating progression of the cell cycle from G1 to S phase. Interestingly, neither denervation nor reinnervation affected the expression of this gene. In contrast, we found large increases in key cell cycle inhibitors (p21 and the growth arrest and DNA destruction 45 [GADD45] gene) in both the denervated and reinnervated groups. We interpret the increases in these cell cycle inhibitors to reflect (1) an inhibition of satellite cell proliferation and/or (2) a special form of apoptosis that results in the loss of myonuclei known to occur under atrophic conditions. To our knowledge, this is the first study to examine the effects of denervation on cell cycle regulation.

  • the plasticity of denervated and reinnervated Laryngeal Muscle focus on single fiber myosin heavy chain isoform expression
    Archives of Otolaryngology-head & Neck Surgery, 2004
    Co-Authors: Michael J. Baker, Roger L Crumley, Jeanpaul Marie, Vincent J Caiozzo
    Abstract:

    No studies have examined the effects of denervation on the single-fiber distribution of myosin heavy-chain (MyHC) isoforms in Laryngeal Muscle. The fast type IIB MyHC isoform represents the largest proportion of the myosin pool in the posterior cricoarytenoid (PCA) and the thyroarytenoid (TA) Muscles. However, the fast type IIB MyHC isoform is distributed differently at the single-fiber level. Hence, we hypothesized that denervation would result in markedly different patterns of MyHC isoform expression at the single-fiber level. To test this hypothesis, we assigned animals to the following 3 groups: (1) control group; (2) denervation group; or (3) reinnervation group. Animals were killed 7, 14, 30, 90, and 180 days after denervation or reinnervation. Subsequently, the distribution of MyHC isoforms were electrophoretically determined in approximately 7200 single fibers. There were 4 key findings to emerge from this study: (1) The MyHC isoform profile of the PCA Muscle, at both the whole-Muscle and single-fiber level, is more malleable than that of the TA Muscle. (2) In the PCA and TA Muscles, denervation produced some similar changes, resulting in a large increase in the pool of fibers coexpressing fast type IIX and IIB MyHC isoforms. (3) Reinnervation of the TA Muscle produced significant alterations in the single-fiber distribution of MyHC isoforms while having little effect on the whole-Muscle MyHC isoform composition. (4) Since the transitions in MyHC isoform expression associated with denervation were limited primarily to fast type IIB to fast type IIX, we postulate that only minor reductions in Muscle function would result (as defined by maximum shortening velocity and the force-velocity relationship).

  • new perspectives about human Laryngeal Muscle single fiber analyses and interspecies comparisons
    Archives of Otolaryngology-head & Neck Surgery, 2000
    Co-Authors: Roger L Crumley, William B Armstrong, Vincent J Caiozzo
    Abstract:

    Background In companion studies on canine and rodent Laryngeal Muscle, we observed that (1) Muscle fibers in both the canine and rodent posterior cricoarytenoid (PCA) Muscles have a slower myosin heavy-chain (MyHC) isoform profile than those in the thyroarytenoid (TA) Muscle; (2) the Muscle fiber composition of PCA and TA Muscles in canines and rodents is complex given the presence of so-called hybrid fibers (fibers coexpressing various combinations of MyHC isoforms); (3) the types and proportions of hybrid fibers are both Muscle specific and, in some cases, region specific; and (4) the MyHC isoform profile of canine Laryngeal Muscle appears to be slower than that of rodent Laryngeal Muscle, suggesting the possibility that larger mammals have a slower MyHC isoform profile. Objectives Given the findings of these companion studies and the fact that very little is known about the MyHC isoform composition of Laryngeal Muscle fibers, the primary objectives of this study were to determine (1) the types of MyHC isoforms found in the human PCA and TA Muscles, (2) if there were regional differences in MyHC isoform composition, (3) if hybrid fibers commonly occur in human Laryngeal Muscle, and (4) if the MyHC isoform profile of human Laryngeal Muscle is slower than that of canine and rodent Laryngeal Muscle. Results and Conclusions The findings of this study clearly demonstrate that both the PCA and TA Muscles in humans express 3 types of MyHC isoforms (ie, slow type I, fast type IIA, and fast type IIX MyHC isoforms). At the single-fiber level, there were distinct regional differences and hybrid fibers were a common occurrence. Finally, the data demonstrate that the PCA and TA Muscles of humans have a slower MyHC profile than that found in either canine or rodent Laryngeal Muscle.

  • single fiber myosin heavy chain isoform composition of rodent Laryngeal Muscle modulation by thyroid hormone
    Archives of Otolaryngology-head & Neck Surgery, 2000
    Co-Authors: Michael J. Baker, Roger L Crumley, Vincent J Caiozzo
    Abstract:

    Background Studies have shown that canine Laryngeal Muscle contains a large number of Muscle fibers that coexpress varying combinations of myosin heavy-chain (MyHC) isoforms. Currently, it is not clear whether this phenomenon is unique to canine Laryngeal Muscle or occurs in all mammals. Objectives To examine the single-fiber MyHC isoform composition of rodent Laryngeal Muscle and to examine the plasticity of single-fiber MyHC isoform composition via manipulation of thyroid state. Results (1) Findings of single-fiber electrophoretic analyses clearly demonstrate that most fibers in both the posterior cricoarytenoid and thyroarytenoid Muscles exhibit MyHC polymorphism. However, the proportions and patterns of polymorphism appear to be Muscle specific. (2) Although the fast type IIL isoform was observed in fibers from both Muscles, it was always coexpressed in combination with other MyHC isoforms (ie, no pure type IIL fibers were found), and always represented a minor proportion of the total MyHC pool. (3) Altering the thyroid state proved a useful tool for exploring the scope of MyHC isoform expression in these Muscles. While the posterior cricoarytenoid Muscle seemed more sensitive to the thyroid state, transitions in both Muscles were primarily confined to the fast type IIX and IIB MyHC isoforms. Conclusion The findings of this study support the concept that single-fiber MyHC polymorphism occurs commonly in mammalian Laryngeal Muscle.

  • a new concept in Laryngeal Muscle multiple myosin isoform types in single Muscle fibers of the lateral cricoarytenoid
    Otolaryngology-Head and Neck Surgery, 1998
    Co-Authors: Ya Zhen Wu, Roger L Crumley, Robert H I Blanks, Michael J. Baker, Vincent J Caiozzo
    Abstract:

    Abstract This report describes the first known investigation of canine Laryngeal Muscle in which single fibers were dissected and their myosin heavy chain (MHC) isoform content was analyzed. Both SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and western blot techniques were used. The data from single fiber SDS-PAGE indicate that the lateral cricoarytenoid (LCA) is predominantly a fast Muscle composed of the following MHC isoforms: Type I, 16.3%; Type IIA, 71.3%; Type IIX, 10.4%; and Type IIB, 2.0%. The results reveal a phenomenon that, to our knowledge, has not been previously described for Laryngeal Muscle: the presence of two or more MHC isoforms in a single canine LCA Muscle fiber. A large number (41%) of Muscle fibers coexpressed two or more MHC isoforms. The three most common patterns of coexpression were Type IIA/IIX (72%), Type IIA/I (16%), and Type IIA/IIX/I (8%). Interestingly, the fast Type IIX MHC isoform was typically present with other isoforms and rarely found by itself in individual fibers. Additional experiments are underway to determine whether other Laryngeal Muscles exhibit such an unusually high ratio of MHC isoform polymorphism. (Otolaryngol Head Neck Surg 1998;118:86-94.)

Dragan Gabelica - One of the best experts on this subject based on the ideXlab platform.

  • Neurophysiologic markers of primary motor cortex for Laryngeal Muscles and premotor cortex in caudal opercular part of inferior frontal gyrus investigated in motor speech disorder: a navigated transcranial magnetic stimulation (TMS) study
    Cognitive Processing, 2016
    Co-Authors: Maja Rogić Vidaković, Ana Jerković, Tomislav Jurić, Igor Vujović, Joško Šoda, Nikola Erceg, Andreja Bubić, Marina Zmajević Schönwald, Pantelis Lioumis, Dragan Gabelica
    Abstract:

    Transcranial magnetic stimulation studies have so far reported the results of mapping the primary motor cortex (M1) for hand and tongue Muscles in stuttering disorder. This study was designed to evaluate the feasibility of repetitive navigated transcranial magnetic stimulation (rTMS) for locating the M1 for Laryngeal Muscle and premotor cortical area in the caudal opercular part of inferior frontal gyrus, corresponding to Broca’s area in stuttering subjects by applying new methodology for mapping these motor speech areas. Sixteen stuttering and eleven control subjects underwent rTMS motor speech mapping using modified patterned rTMS. The subjects performed visual object naming task during rTMS applied to the (a) left M1 for Laryngeal Muscles for recording corticobulbar motor-evoked potentials (CoMEP) from cricothyroid Muscle and (b) left premotor cortical area in the caudal opercular part of inferior frontal gyrus while recording long latency responses (LLR) from cricothyroid Muscle. The latency of CoMEP in control subjects was 11.75 ± 2.07 ms and CoMEP amplitude was 294.47 ± 208.87 µV, and in stuttering subjects CoMEP latency was 12.13 ± 0.75 ms and 504.64 ± 487.93 µV CoMEP amplitude. The latency of LLR in control subjects was 52.8 ± 8.6 ms and 54.95 ± 4.86 in stuttering subjects. No significant differences were found in CoMEP latency, CoMEP amplitude, and LLR latency between stuttering and control-fluent speakers. These results indicate there are probably no differences in stuttering compared to controls in functional anatomy of the pathway used for transmission of information from premotor cortex to the M1 cortices for Laryngeal Muscle representation and from there via corticobulbar tract to Laryngeal Muscles.

Roger L Crumley - One of the best experts on this subject based on the ideXlab platform.

  • Effects of denervation on cell cycle control in Laryngeal Muscle.
    Archives of otolaryngology--head & neck surgery, 2004
    Co-Authors: Vincent J Caiozzo, Michael J. Baker, Roger L Crumley
    Abstract:

    Denervation of skeletal Muscle is thought to lead to an accelerated proliferation of myogenic stem cells known as satellite cells. The transition of these cells from a quiescent to a proliferative state is thought to require satellite cells to enter the cell cycle and replicate. Little is known about the expression of genes associated with cell cycle control, and so the objective of this study was to examine the effects of denervation and reinnervation of the posterior cricoarytenoid (PCA) Muscle on key cell cycle genes. Female Sprague-Dawley rats were assigned to control, denervated, or reinnervated groups. Animals were killed at 7, 14, and 30 days after ligation of the recurrent Laryngeal nerve. The PCA Muscle was then analyzed for changes in the messenger RNA levels of key genes associated with cell cycle control, differentiation, and proliferation. Cyclin D1 is a key gene responsible for initiating progression of the cell cycle from G1 to S phase. Interestingly, neither denervation nor reinnervation affected the expression of this gene. In contrast, we found large increases in key cell cycle inhibitors (p21 and the growth arrest and DNA destruction 45 [GADD45] gene) in both the denervated and reinnervated groups. We interpret the increases in these cell cycle inhibitors to reflect (1) an inhibition of satellite cell proliferation and/or (2) a special form of apoptosis that results in the loss of myonuclei known to occur under atrophic conditions. To our knowledge, this is the first study to examine the effects of denervation on cell cycle regulation.

  • the plasticity of denervated and reinnervated Laryngeal Muscle focus on single fiber myosin heavy chain isoform expression
    Archives of Otolaryngology-head & Neck Surgery, 2004
    Co-Authors: Michael J. Baker, Roger L Crumley, Jeanpaul Marie, Vincent J Caiozzo
    Abstract:

    No studies have examined the effects of denervation on the single-fiber distribution of myosin heavy-chain (MyHC) isoforms in Laryngeal Muscle. The fast type IIB MyHC isoform represents the largest proportion of the myosin pool in the posterior cricoarytenoid (PCA) and the thyroarytenoid (TA) Muscles. However, the fast type IIB MyHC isoform is distributed differently at the single-fiber level. Hence, we hypothesized that denervation would result in markedly different patterns of MyHC isoform expression at the single-fiber level. To test this hypothesis, we assigned animals to the following 3 groups: (1) control group; (2) denervation group; or (3) reinnervation group. Animals were killed 7, 14, 30, 90, and 180 days after denervation or reinnervation. Subsequently, the distribution of MyHC isoforms were electrophoretically determined in approximately 7200 single fibers. There were 4 key findings to emerge from this study: (1) The MyHC isoform profile of the PCA Muscle, at both the whole-Muscle and single-fiber level, is more malleable than that of the TA Muscle. (2) In the PCA and TA Muscles, denervation produced some similar changes, resulting in a large increase in the pool of fibers coexpressing fast type IIX and IIB MyHC isoforms. (3) Reinnervation of the TA Muscle produced significant alterations in the single-fiber distribution of MyHC isoforms while having little effect on the whole-Muscle MyHC isoform composition. (4) Since the transitions in MyHC isoform expression associated with denervation were limited primarily to fast type IIB to fast type IIX, we postulate that only minor reductions in Muscle function would result (as defined by maximum shortening velocity and the force-velocity relationship).

  • new perspectives about human Laryngeal Muscle single fiber analyses and interspecies comparisons
    Archives of Otolaryngology-head & Neck Surgery, 2000
    Co-Authors: Roger L Crumley, William B Armstrong, Vincent J Caiozzo
    Abstract:

    Background In companion studies on canine and rodent Laryngeal Muscle, we observed that (1) Muscle fibers in both the canine and rodent posterior cricoarytenoid (PCA) Muscles have a slower myosin heavy-chain (MyHC) isoform profile than those in the thyroarytenoid (TA) Muscle; (2) the Muscle fiber composition of PCA and TA Muscles in canines and rodents is complex given the presence of so-called hybrid fibers (fibers coexpressing various combinations of MyHC isoforms); (3) the types and proportions of hybrid fibers are both Muscle specific and, in some cases, region specific; and (4) the MyHC isoform profile of canine Laryngeal Muscle appears to be slower than that of rodent Laryngeal Muscle, suggesting the possibility that larger mammals have a slower MyHC isoform profile. Objectives Given the findings of these companion studies and the fact that very little is known about the MyHC isoform composition of Laryngeal Muscle fibers, the primary objectives of this study were to determine (1) the types of MyHC isoforms found in the human PCA and TA Muscles, (2) if there were regional differences in MyHC isoform composition, (3) if hybrid fibers commonly occur in human Laryngeal Muscle, and (4) if the MyHC isoform profile of human Laryngeal Muscle is slower than that of canine and rodent Laryngeal Muscle. Results and Conclusions The findings of this study clearly demonstrate that both the PCA and TA Muscles in humans express 3 types of MyHC isoforms (ie, slow type I, fast type IIA, and fast type IIX MyHC isoforms). At the single-fiber level, there were distinct regional differences and hybrid fibers were a common occurrence. Finally, the data demonstrate that the PCA and TA Muscles of humans have a slower MyHC profile than that found in either canine or rodent Laryngeal Muscle.

  • single fiber myosin heavy chain isoform composition of rodent Laryngeal Muscle modulation by thyroid hormone
    Archives of Otolaryngology-head & Neck Surgery, 2000
    Co-Authors: Michael J. Baker, Roger L Crumley, Vincent J Caiozzo
    Abstract:

    Background Studies have shown that canine Laryngeal Muscle contains a large number of Muscle fibers that coexpress varying combinations of myosin heavy-chain (MyHC) isoforms. Currently, it is not clear whether this phenomenon is unique to canine Laryngeal Muscle or occurs in all mammals. Objectives To examine the single-fiber MyHC isoform composition of rodent Laryngeal Muscle and to examine the plasticity of single-fiber MyHC isoform composition via manipulation of thyroid state. Results (1) Findings of single-fiber electrophoretic analyses clearly demonstrate that most fibers in both the posterior cricoarytenoid and thyroarytenoid Muscles exhibit MyHC polymorphism. However, the proportions and patterns of polymorphism appear to be Muscle specific. (2) Although the fast type IIL isoform was observed in fibers from both Muscles, it was always coexpressed in combination with other MyHC isoforms (ie, no pure type IIL fibers were found), and always represented a minor proportion of the total MyHC pool. (3) Altering the thyroid state proved a useful tool for exploring the scope of MyHC isoform expression in these Muscles. While the posterior cricoarytenoid Muscle seemed more sensitive to the thyroid state, transitions in both Muscles were primarily confined to the fast type IIX and IIB MyHC isoforms. Conclusion The findings of this study support the concept that single-fiber MyHC polymorphism occurs commonly in mammalian Laryngeal Muscle.

  • a new concept in Laryngeal Muscle multiple myosin isoform types in single Muscle fibers of the lateral cricoarytenoid
    Otolaryngology-Head and Neck Surgery, 1998
    Co-Authors: Ya Zhen Wu, Roger L Crumley, Robert H I Blanks, Michael J. Baker, Vincent J Caiozzo
    Abstract:

    Abstract This report describes the first known investigation of canine Laryngeal Muscle in which single fibers were dissected and their myosin heavy chain (MHC) isoform content was analyzed. Both SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and western blot techniques were used. The data from single fiber SDS-PAGE indicate that the lateral cricoarytenoid (LCA) is predominantly a fast Muscle composed of the following MHC isoforms: Type I, 16.3%; Type IIA, 71.3%; Type IIX, 10.4%; and Type IIB, 2.0%. The results reveal a phenomenon that, to our knowledge, has not been previously described for Laryngeal Muscle: the presence of two or more MHC isoforms in a single canine LCA Muscle fiber. A large number (41%) of Muscle fibers coexpressed two or more MHC isoforms. The three most common patterns of coexpression were Type IIA/IIX (72%), Type IIA/I (16%), and Type IIA/IIX/I (8%). Interestingly, the fast Type IIX MHC isoform was typically present with other isoforms and rarely found by itself in individual fibers. Additional experiments are underway to determine whether other Laryngeal Muscles exhibit such an unusually high ratio of MHC isoform polymorphism. (Otolaryngol Head Neck Surg 1998;118:86-94.)