scholarly journals Evaluation of Dying Vocal Fold Epithelial Cells by Ultrastructural Features and TUNEL Method

2016 ◽  
Vol 202 (5-6) ◽  
pp. 355-368 ◽  
Author(s):  
Carolyn K. Novaleski ◽  
Masanobu Mizuta ◽  
Bernard Rousseau
Keyword(s):  
Cell Death ◽  
Vocal Fold ◽  
Apoptotic Cell ◽  
Standard Technique ◽  
Vocal Folds ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Apical Surface ◽  
Cell Nuclei ◽  
Vocal Fold Vibration ◽  
Immunohistochemical Marker

Cell death is a regulated mechanism of eliminating cells to maintain tissue homeostasis. This study described 2 methodological procedures for evaluating cell death in the epithelium of immobilized, approximated and vibrated vocal folds from 12 New Zealand white breeder rabbits. The gold standard technique of transmission electron microscopy evaluated high-quality ultrastructural criteria of cell death and a common immunohistochemical marker, the terminal deoxynucleotidyl transferase dUTP nick end labeling method, to confirm cell death signaling. Results revealed that ultrastructural characteristics of apoptotic cell death, specifically condensed chromatin and apoptotic bodies, were observed after vocal fold vibration and approximation. Although episodes of necrosis were rare, few enlarged cell nuclei were present after vibration and approximation. The vocal fold expresses an immunohistochemical marker for apoptosis along the apical surface of the epithelium. This study provides a solid foundation for future investigations regarding the role of cell death in vocal fold health and disease.

scholarly journals Apoptosis and Vocal Fold Disease: Clinically Relevant Implications of Epithelial Cell Death

2017 ◽  
Vol 60 (5) ◽  
pp. 1264-1272 ◽  
Author(s):  
Carolyn K. Novaleski ◽  
Bruce D. Carter ◽  
M. Preeti Sivasankar ◽  
Sheila H. Ridner ◽  
Mary S. Dietrich ◽  
...  
Keyword(s):  
Cell Death ◽  
Vocal Fold ◽  
Apoptotic Cell ◽  
Vocal Folds ◽  
Epithelial Tissue ◽  
Tissue Properties ◽  
Vocal Function ◽  
Detrimental Impact ◽  
Epithelial Cell Death

Purpose Vocal fold diseases affecting the epithelium have a detrimental impact on vocal function. This review article provides an overview of apoptosis, the most commonly studied type of programmed cell death. Because apoptosis can damage epithelial cells, this article examines the implications of apoptosis on diseases affecting the vocal fold cover. Method A review of the extant literature was performed. We summarized the topics of epithelial tissue properties and apoptotic cell death, described what is currently understood about apoptosis in the vocal fold, and proposed several possible explanations for how the role of abnormal apoptosis during wound healing may be involved in vocal pathology. Results and Conclusions Apoptosis plays an important role in maintaining normal epithelial tissue function. The biological mechanisms responsible for vocal fold diseases of epithelial origin are only beginning to emerge. This article discusses speculations to explain the potential role of deficient versus excessive rates of apoptosis and how disorganized apoptosis may contribute to the development of common diseases of the vocal folds.

scholarly journals Ischemic Brain Injury is Mediated by the Activation of Poly(ADP-Ribose)Polymerase

1997 ◽  
Vol 17 (11) ◽  
pp. 1143-1151 ◽  
Author(s):  
Matthias Endres ◽  
Zhao-Qi Wang ◽  
Shobu Namura ◽  
Christian Waeber ◽  
Michael A. Moskowitz
Keyword(s):  
Cell Death ◽  
Brain Injury ◽  
Tissue Injury ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Ischemic Brain Injury ◽  
Cell Nuclei ◽  
Ischemic Brain ◽  
Nad Depletion

Poly(ADP-ribose)polymerase (PARP, EC 2.4.2.30), an abundant nuclear protein activated by DNA nicks, mediates cell death in vitro by nicotinamide adenine dinucleotide (NAD) depletion after exposure to nitric oxide. The authors examined whether genetic deletion of PARP (PARP null mice) or its pharmacologic inhibition by 3-aminobenzamide (3-AB) attenuates tissue injury after transient cerebral ischemia. Twenty-two hours after reperfusion following 2 hours of filamentous middle cerebral artery occlusion, ischemic injury was decreased in PARP−/− and PARP+/− mice compared with PARP+/+ litter mates, and also was attenuated in 129/SV wild-type mice after 3-AB treatment compared with controls. Infarct sparing was accompanied by functional recovery in PARP−/− and 3-AB–treated mice. Increased poly(ADP-ribose) immunostaining observed in ischemic cell nuclei 5 minutes after reperfusion was reduced by 3-AB treatment. Levels of NAD—the substrate of PARP—were reduced 2 hours after reperfusion and were 35% of contralateral levels at 24 hours. The decreases were attenuated in PARP−/− mice and in 3-AB–treated animals. Poly(ADP-ribose)polymerase cleavage by caspase-3 (CPP-32) has been proposed as an important step in apoptotic cell death. Markers of apoptosis, such as oligonucleosomal DNA damage, total DNA fragmentation, and the density of terminal deoxynucleotidyl transferase dUTP nick-end–labelled (TUNEL +) cells, however, did not differ in ischemic brain tissue of PARP−/− mice or in 3-AB–treated animals versus controls, although there were differences in the number of TUNEL-stained cells reflecting the decrease in infarct size. Thus, ischemic brain injury activates PARP and contributes to cell death most likely by NAD depletion and energy failure, although the authors have not excluded a role for PARP in apoptotic cell death at earlier or later stages in ischemic cell death. Inhibitors of PARP activation could provide a potential therapy in acute stroke.

Reinke's Edema: Phonatory Mechanisms and Management Strategies

1997 ◽  
Vol 106 (7) ◽  
pp. 533-543 ◽  
Author(s):  
Steven M. Zeitels ◽  
Glenn W. Bunting ◽  
Robert E. Hillman ◽  
Traci Vaughn
Keyword(s):  
Lamina Propria ◽  
Fundamental Frequency ◽  
Vocal Fold ◽  
Management Strategies ◽  
Vocal Folds ◽  
Vocal Fold Vibration ◽  
Reinke’S Edema ◽  
Subglottal Pressure ◽  
Almost All ◽  
Superficial Lamina

Reinke's edema (RE) has been associated typically with smoking and sometimes with vocal abuse, but aspects of the pathophysiology of RE remain unclear. To gain new insights into phonatory mechanisms associated with RE pathophysiology, weused an integrated battery of objective vocal function tests to analyze 20 patients (19 women) who underwent phonomicrosurgical resection. Preoperative stroboscopic examinations demonstrated that the superficial lamina propria is distended primarily on the superior vocal fold surface. Acoustically, these individuals have an abnormally low average speaking fundamental frequency (123 Hz), and they generate abnormally high average subglottal pressures (9.7 cm H20). The presence of elevated aerodynamic driving pressures reflects difficulties in producing vocal fold vibration that are most likely the result of mass loading associated with RE, and possibly vocal hyperfunction. Furthermore, it is hypothesized that in the environment of chronic glottal mucositis secondary to smoking and reflux, the cephalad force on the vocal folds by the subglottal driving pressure contributes to the superior distention of the superficial lamina propria. Surgical reduction of the volume of the superficial lamina propria resulted in a significant elevation in fundamental frequency (154 Hz) and improvement in perturbation measures. In almost all instances, both the clinician and the patient perceived the voice as improved. However, these patients continued to generate elevated subglottal pressure (probably a sign of persistent hyperfunction) that was accompanied by visually observed supraglottal strain despite the normalsized vocal folds. This finding suggests that persistent hyperfunctional vocal behaviors may contribute to postsurgical RE recurrence if therapeutic strategies are not instituted to modify such behavior.

Effects of Voice Therapy as Objectively Evaluated by Digitized Laryngeal Stroboscopic Imaging

2002 ◽  
Vol 111 (10) ◽  
pp. 902-908 ◽  
Author(s):  
Renée Speyer ◽  
Pieter A. Kempen ◽  
George Wieneke ◽  
Willem Kersing ◽  
Elham Ghazi Hosseini ◽  
...  
Keyword(s):  
Vocal Fold ◽  
Vocal Folds ◽  
Lesion Size ◽  
Voice Therapy ◽  
Benign Lesions ◽  
Objective Measurements ◽  
Significant Parameter ◽  
Surface Areas ◽  
Vocal Fold Vibration ◽  
Maximal Opening

Objective measurements derived from digitized laryngeal stroboscopic images were used to demonstrate changes in vocal fold vibration and in the size of benign lesions after 3 months of voice therapy. Forty chronically dysphonic patients were studied. By means of a rigid stroboscope, pretreatment and posttreatment recordings were made of the vocal folds at rest and under stroboscopic light during phonation. From each recording, images of the positions at rest and during vibration at maximal opening and at maximal closure were digitized. The surface areas of any lesions and of the glottal gap were independently measured in the digitized images by 2 experienced laryngologists. Referential distances were determined in order to compensate for discrepancies in magnification in the various recordings. After 3 months of voice therapy, significant improvement in lesion size and degree of maximal closure during vibration could be demonstrated in about 50% of the patients. The degree of maximal opening did not prove to be a significant parameter.

Videostrobolaryngoscopy of Mucus Layer during Vocal Fold Vibration in Patients with Laryngeal Tension-Fatigue Syndrome

2002 ◽  
Vol 111 (6) ◽  
pp. 537-541 ◽  
Author(s):  
Tzu-Yu Hsiao ◽  
Chia-Ming Liu ◽  
Kai-Nan Lin
Keyword(s):  
Mechanical Properties ◽  
Vocal Fold ◽  
Rough Surfaces ◽  
Voice Disorders ◽  
Vocal Folds ◽  
Voice Disorder ◽  
Mucus Layer ◽  
Vocal Fold Vibration ◽  
Fatigue Syndrome ◽  
Functional Dysphonia

The mucus layer on the vocal folds was examined by videostrobolaryngoscopy in patients with laryngeal tension-fatigue syndrome, a chronic functional dysphonia due to vocal abuse and misuse. Besides the findings in previous reports (such as abnormal glottal closure, phase or amplitude asymmetry, and the irregular mucosal wave), the vocal folds during vibration had an uneven mucus surface. The occurrence of an uneven mucus layer on vocal folds was significantly greater in subjects with this voice disorder (83% or 250 of 301 patients in this series) than in those without voice disorders (18.5% or 5 of 27). The increase of mucus viscosity, mucus aggregation, and the formation of rough surfaces on the vocal folds alter the mechanical properties that contribute to vibration of the cover of the vocal folds, and thereby worsen the symptoms of dysphonia in patients with laryngeal tension-fatigue syndrome.

Apoptosis in polycystic kidney disease: involvement of caspases

2000 ◽  
Vol 278 (3) ◽  
pp. R763-R769 ◽  
Author(s):  
Shujath M. Ali ◽  
Victoria Y. Wong ◽  
Kristine Kikly ◽  
Todd A. Fredrickson ◽  
Paul M. Keller ◽  
...  
Keyword(s):  
Cell Death ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Apoptotic Cell ◽  
Renal Cysts ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Homozygous Mutation ◽  
Polycystic Kidney ◽  
Apoptosis Pathway ◽  
Cystic Kidneys

Polycystic kidney disease (PKD) is characterized by the development of large renal cysts and progressive loss of renal function. Although the cause of the development of renal cysts is unknown, recent evidence suggests that excessive apoptosis occurs in PKD. With the use of terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, we have confirmed the presence of apoptotic bodies in cystic kidneys of congenital polycystic kidney (cpk) disease mice carrying a homozygous mutation at 3 wk of age. Apoptosis was localized primarily to the interstitium with little evidence of cell death in cyst epithelium or noncystic tubules. In addition, we observed that the expression of various caspases, bax and bcl-2, was upregulated in cystic kidneys. With the use of various substrates in enzyme activity assays, we have demonstrated a greater than sevenfold increase in caspase 4 activity and a sixfold increase in caspase 3 activity. These data suggest that there is a caspase-dependent apoptosis pathway associated with PKD and support the hypothesis that apoptotic cell death contributes to cyst formation in PKD.

scholarly journals De novo variants in MPP5 cause global developmental delay and behavioral changes

2020 ◽  
Vol 29 (20) ◽  
pp. 3388-3401 ◽  
Author(s):  
Noelle Sterling ◽  
Anna R Duncan ◽  
Raehee Park ◽  
David A Koolen ◽  
Jiahai Shi ◽  
...  
Keyword(s):  
Cell Death ◽  
Developmental Delay ◽  
Cell Polarity ◽  
De Novo ◽  
Apoptotic Cell ◽  
Ventricular Zone ◽  
Behavioral Changes ◽  
Ependymal Cells ◽  
Global Developmental Delay ◽  
Apical Surface

Abstract Membrane Protein Palmitoylated 5 (MPP5) is a highly conserved apical complex protein essential for cell polarity, fate and survival. Defects in cell polarity are associated with neurologic disorders including autism and microcephaly. MPP5 is essential for neurogenesis in animal models, but human variants leading to neurologic impairment have not been described. We identified three patients with heterozygous MPP5 de novo variants (DNV) and global developmental delay (GDD) and compared their phenotypes and magnetic resonance imaging (MRI) to ascertain how MPP5 DNV leads to GDD. All three patients with MPP5 DNV experienced GDD with language delay/regression and behavioral changes. MRI ranged from normal to decreased gyral folding and microcephaly. The effects of MPP5 depletion on the developing brain were assessed by creating a heterozygous conditional knock out (het CKO) murine model with central nervous system (CNS)-specific Nestin-Cre drivers. In the het CKO model, Mpp5 depletion led to microcephaly, decreased cerebellar volume and cortical thickness. Het CKO mice had decreased ependymal cells and Mpp5 at the apical surface of cortical ventricular zone compared with wild type. Het CKO mice also failed to maintain progenitor pools essential for neurogenesis. The proportion of cortical cells undergoing apoptotic cell death increased, suggesting that cell death reduces progenitor population and neuron number. Het CKO mice also showed behavioral changes, similar to our patients. To our knowledge, this is the first report to show that variants in MPP5 are associated with GDD, behavioral abnormalities and language regression/delay. Murine modeling shows that neurogenesis is likely altered in these individuals, with cell death and skewed cellular composition playing significant roles.

Finite Element Modeling of Vocal Fold Vibration in Normal Phonation and Hyperfunctional Dysphonia: Implications for the Pathogenesis of Vocal Nodules

1998 ◽  
Vol 107 (7) ◽  
pp. 603-610 ◽  
Author(s):  
Jack J. Jiang ◽  
Carlos E. Diaz ◽  
David G. Hanson
Keyword(s):  
Finite Element ◽  
Finite Element Modeling ◽  
Mechanical Stress ◽  
Vocal Fold ◽  
Vocal Folds ◽  
Element Modeling ◽  
Modeling Technology ◽  
Vocal Fold Vibration ◽  
Vocal Nodules ◽  
High Mechanical Stress

A computer model of the vocal fold was developed using finite element modeling technology for studying mechanical stress distribution over vibrating vocal fold tissue. In a simulated normal phonation mode, mechanical stress was found to be lowest at the midpoint of the vocal fold and highest at tendon attachments. However, when other modes predominated, high mechanical stress could occur at the midpoint of the vocal folds. When a vocal fold mass was modeled, high shearing stress occurred at the base of the modeled vocal fold mass, suggesting that the presence of a vocal nodule or polyp is associated with high mechanical stress at the margins of the mass. This finding supports a hypothesis that mechanical intraepithelial stress plays an important role in the development of vocal nodules, polyps, and other lesions that are usually ascribed to hyperfunctional dysphonia.

Empirical Eigenfunctions and Medial Surface Dynamics of a Human Vocal Fold

2005 ◽  
Vol 44 (03) ◽  
pp. 384-391 ◽  
Author(s):  
N. Tayama ◽  
D. A. Berry ◽  
M. Döllinger
Keyword(s):  
Vocal Fold ◽  
High Speed ◽  
Computational Models ◽  
Imaging System ◽  
Vocal Folds ◽  
Sustained Oscillation ◽  
Medial Surface ◽  
Physical Mechanisms ◽  
Vocal Fold Vibration ◽  
Modes Of Vibration

Summary Objectives: The purpose of this investigation was to use an excised human larynx to substantiate physical mechanisms of sustained vocal fold oscillation over a variety of phonatory conditions. During sustained, flow-induced oscillation, dynamical data was collected from the medial surface of the vocal fold. The method of Empirical Eigenfunctions was used to analyze the data and to probe physical mechanisms of sustained oscillation. Methods: Thirty microsutures were mounted on the medial margin of a human vocal fold. Across five distinct phonatory conditions, the vocal fold was set into oscillation and imaged with a high-speed digital imaging system. The position coordinates of the sutures were extracted from the images and converted into physical coordinates. Empirical Eigenfunctions were computed from the time-varying physical coordinates, and mechanisms of sustained oscillation were explored. Results: Using the method of Empirical Eigenfunctions, physical mechanisms of sustained vocal fold oscillation were substantiated. In particular, the essential dynamics of vocal fold vibration were captured by two dominant Empirical Eigenfunctions. The largest Eigenfunction primarily captured the alternating convergent/ divergent shape of the medial surface of the vocal fold, while the second largest Eigenfunction primarily captured the lateral vibrations of the vocal fold. Conclusions: The hemi-larynx setup yielded a view of the medial surface of the vocal folds, revealing the tissue vibrations which produced sound. Through the use of Empirical Eigenfunctions, the underlying modes of vibration were computed, disclosing physical mechanisms of sustained vocal fold oscillation. The investigation substantiated previous theoretical analyses and yielded significant data to help evaluate and refine computational models of vocal fold vibration.

Nonlinear behavior of vocal fold vibration: The role of coupling between the vocal folds

1999 ◽  
Vol 13 (4) ◽  
pp. 465-476 ◽  
Author(s):  
Antoine Giovanni ◽  
Maurice Ouaknine ◽  
Bruno Guelfucci ◽  
Ping Yu ◽  
Michel Zanaret ◽  
...  
Keyword(s):  
Vocal Fold ◽  
Nonlinear Behavior ◽  
Vocal Folds ◽  
Vocal Fold Vibration
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