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PubMed2005

Long-term changes of hyoid bone and pharyngeal airway size following advancement of the mandible.

OBJECTIVE: To determine long-term changes in hyoid bone position and pharyngeal airway size after mandibular advancement, including evaluation of the relationship between length of suprahyoidal musculature and skeletal relapse. STUDY DESIGN: A cephalometric follow-up study (12 years) of 15 patients who underwent mandibular advancement surgery. RESULTS: The final position of the hyoid bone was more posterior than it had been preoperatively. Suprahyoidal musculature continuously lengthened from preoperatively to 12 years postoperatively. Total skeletal relapse at B-point and pogonion correlated significantly with postoperative stretch of suprahyoidal musculature. The upper and middle pharyngeal airways were narrower than their preoperative values. CONCLUSIONS: Mandibular changes influence hyoid bone position during the entire postoperative period, whereas stretching of suprahyoidal musculature seems to contribute to skeletal relapse. Mandibular advancement surgery alone possibly does not achieve a stable increase of pharyngeal airway size over a long-term period of 12 years.

Adolescent↗

PubMed2004

The coordinate regulation of pharyngeal development in C. elegans by lin-35/Rb, pha-1, and ubc-18.

Organ development is a complex process involving the coordination of cell proliferation, differentiation, and morphogenetic events. Using a screen to identify genes that function coordinately with lin-35/Rb during animal development, we have isolated a weak loss-of-function (LOF) mutation in pha-1. lin-35; pha-1 double mutants are defective at an early step in pharyngeal morphogenesis leading to an abnormal pharyngeal architecture. pha-1 is also synthetically lethal with other class B synthetic multivulval (SynMuv) genes including the C. elegans E2F homolog, efl-1. Reporter analyses indicate that pha-1 is broadly expressed during embryonic development and that its functions reside in the cytoplasm. We also provide genetic and phenotypic evidence to support the model that PHA-1, a novel protein, and UBC-18, a ubiquitin-conjugating enzyme that we have previously shown to function with lin-35 during pharyngeal development, act in parallel pathways to regulate the activity of a common cellular target.

Animals↗

PubMed2005

Microarray analysis detects differentially expressed genes in the pharyngeal region of mice lacking Tbx1.

22q11-deletion (DiGeorge/velocardiofacial) syndrome (22q11DS) is modeled by mutation of murine transcription factor Tbx1. As part of efforts to identify transcriptional targets of Tbx1, we analyzed the transcriptome of the pharyngeal region of Df1/+;Tbx1+/- embryos at 9.5 days of embryonic development using two independent microarray platforms. In this model, embryos are null for Tbx1, with hemizygosity of genes in cis with Tbx1 on one chromosome providing a positive control for array sensitivity. Reduced mRNA levels of genes deleted from Df1 were detected on both platforms. Expression level filtering and statistical analysis identified several genes that were consistently differentially expressed between mutant and wild type embryos. Real-time quantitative PCR and in situ hybridization validated diminished expression of Pax9 and Gcm2, genes known to be required for normal thymus and parathyroid gland morphogenesis, whereas Pax1, Hoxa3, Eya1, and Foxn1, which are similarly required, were not down-regulated. Gbx2, a gene required for normal arch artery development, was down-regulated specifically in the pharyngeal endoderm and the posterior part of pharyngeal arch 1, and is a potential point of cross talk between the Tbx1 and Fgf8 controlled pathways. These experiments highlight which genes and pathways potentially affected by lack of Tbx1, and whose role may be explored further by testing for epistasis using mouse mutants.

Animals↗

PubMed2006

ARI-1, an RBR family ubiquitin-ligase, functions with UBC-18 to regulate pharyngeal development in C. elegans.

The LIN-35 retinoblastoma protein homolog and the ubiquitin-conjugating enzyme UBC-18 function redundantly to control an early step of pharyngeal morphogenesis in C. elegans. In order to identify ubiquitin-ligases acting downstream of UBC-18, we carried out a two-hybrid screen using UBC-18 as the bait molecule. Our screen identified three putative ubiquitin-ligases, one of which, ARI-1, showed genetic interactions leading to defective pharyngeal development that were identical to that previously observed for UBC-18. ARI-1 is a member of the RBR family of ubiquitin-ligases and contains a C-terminal motif that places it within the highly conserved Ariadne subfamily of RBR ligases. Our analyses indicate that ARI-1 is the principal Ariadne family member in C. elegans that is involved in the control of pharyngeal development with UBC-18. Using GFP reporters, we find that ARI-1 is expressed dynamically in a wide range of tissues including muscles and neurons during embryonic and postembryonic development. We also provide evidence that dsRNA species containing 14 or fewer base pairs of contiguous identity with closely related mRNAs are sufficient to mediate off-target silencing in C. elegans.

Amino Acid Sequence↗

PubMed2006

Patterning of the third pharyngeal pouch into thymus/parathyroid by Six and Eya1.

Previous studies have suggested a role of the homeodomain Six family proteins in patterning the developing vertebrate head that involves appropriate segmentation of three tissue layers, the endoderm, the paraxial mesoderm and the neural crest cells; however, the developmental programs and mechanisms by which the Six genes act in the pharyngeal endoderm remain largely unknown. Here, we examined their roles in pharyngeal pouch development. Six1-/- mice lack thymus and parathyroid and analysis of Six1-/- third pouch endoderm demonstrated that the patterning of the third pouch into thymus/parathyroid primordia is initiated. However, the endodermal cells of the thymus/parathyroid rudiments fail to maintain the expression of the parathyroid-specific gene Gcm2 and the thymus-specific gene Foxn1 and subsequently undergo abnormal apoptosis, leading to a complete disappearance of organ primordia by E12.5. This thus defines the thymus/parathyroid defects present in the Six1 mutant. Analyses of the thymus/parathyroid development in Six1-/-;Six4-/- double mutant show that both Six1 and Six4 act synergistically to control morphogenetic movements of early thymus/parathyroid tissues, and the threshold of Six1/Six4 appears to be crucial for the regulation of the organ primordia-specific gene expression. Previous studies in flies and mice suggested that Eya and Six genes may function downstream of Pax genes. Our data clearly show that Eya1 and Six1 expression in the pouches does not require Pax1/Pax9 function, suggesting that they may function independently from Pax1/Pax9. In contrast, Pax1 expression in all pharyngeal pouches requires both Eya1 and Six1 function. Moreover, we show that the expression of Tbx1, Fgf8 and Wnt5b in the pouch endoderm was normal in Six1-/- embryos and slightly reduced in Six1-/-;Six4-/- double mutant, but was largely reduced in Eya1-/- embryos. These results indicate that Eya1 appears to be upstream of very early events in the initiation of thymus/parathyroid organogenesis, while Six genes appear to act in an early differentiation step during thymus/parathyroid morphogenesis. Together, these analyses establish an essential role for Eya1 and Six genes in patterning the third pouch into organ-specific primordia.

Animals↗

PubMed2005

[Cervical and para-pharyngeal bone tumors: two cases report].

OBJECTIVE: The purpose of the study was to report two cases of cervical and para-pharyngeal bone tumors. MATERIAL AND METHODS: Patients were two 29 and 67-year-old men. Presentation of the lesions included respectively a right cervical mass and a left para-pharyngeal mass. Clinical features and radiological, anatomopathological and therapeutic characteristics of the tumors were retrospectively studied. RESULTS: A cervical approach was made in both cases. Tumor biopsies revealed a vertebral aneurismal cyst and a corporeo-pedicular chordoma respectively. CONCLUSION: Vertebral bone tumors with cervical expression are very uncommon entities. Diagnosis could be systematically evoked in patients with a cervical or para-pharyngeal tumor presenting vertebral lysis.

Adult↗

PubMed2002

Altered apoptosis pattern during pharyngeal arch artery remodelling is associated with aortic arch malformations in Tgfbeta2 knock-out mice.

OBJECTIVE: The morphogenetic process underlying the remodelling of the embryonic mammalian pharyngeal arch artery system is unknown. Within this process, the right sixth, carotid ducts and the distal part of the dorsal aorta (right alpha-segment) regress. In order to unravel the underlying mechanism we studied the role of apoptosis in the normal regression of pharyngeal arch artery segments and in a mouse model that develops aortic arch malformations. METHODS: Normal remodelling was studied in wild-type Swiss (CPBS) and altered remodelling in the Tgfbeta2-/- compared to the Tgfbeta2+/+ (Swiss/Bl6) strain using immunohistochemistry and morphometric analysis. RESULTS: During normal remodelling, apoptosis occurs in the mesenchyme surrounding pharyngeal arch arteries before regression starts. With the onset of regression, apoptosis spreads from the mesenchyme to the media. Morphometric evaluation confirms the increase in apoptosis in the actin-positive media of the disappearing segments. In Tgfbeta2-/-, aberrant apoptosis was found in both fourth arch arteries, whereas the right dorsal aorta lacks apoptosis associated with normal regression. Fourth arch hypoplasia is the main arch abnormality. In the most severe case, the fourth arch is interrupted and the right dorsal aorta alpha-segment persists, giving rise to aortic arch interruption type-B and an aberrant right subclavian artery. CONCLUSIONS: We have shown for the first time that specific vascular apoptosis patterns accompany normal regression and that the incidence of apoptosis is selectively altered in the case of arch artery abnormalities in Tgfbeta2 knock-out mice.

Animals↗

PubMed2004

Trauma-induced ascending pharyngeal artery-internal jugular vein fistula: case report.

BACKGROUND: Ascending pharyngeal artery-internal jugular vein fistulas are rare. Only 2 spontaneous cases and one complicated neck surgery have been reported. We describe a trauma-induced case. CASE DESCRIPTION: A 31-year-old man presented left-sided tinnitus and a pulsating bruit for 5 months after head trauma. Cerebral angiography demonstrated a fistula between the left ascending pharyngeal artery and left internal jugular vein. Embolization of the fistula was performed using platinum fibrous microcoils. CONCLUSIONS: This case and a review of the literature illustrate the causes, manifestations, image studies, and treatment for a fistula between the ascending pharyngeal artery and internal jugular vein.

Accidents, Traffic↗

PubMed2002

Decreased serum and pharyngeal antibody levels specific to streptococcal lipoteichoic acid in children with recurrent tonsillitis.

OBJECTIVE: Streptococcus (S.) pyogenes is a common cause of primary as well as recurrent tonsillitis (RT). Lipoteichoic acid (LTA) has been proposed as a possible candidate for vaccine formulation against streptococcal infections, because LTA is a common constituent of streptococci and the antibody to LTA inhibits bacterial attachment to epithelial cells in vitro. Streptolysin-O and streptococcal whole cell body are highly immunogenic and the antibodies to these antigens are reported to be better parameters for streptococcal infections The objective of the present study is to investigate how systemic and local immune activities against S. pyogenes may be associated with RT. METHODS: Sera from 178 children with or without RT aged 1-15 years with a median age of 5 years were investigated for the levels of total immunoglobulins and antibodies specific to streptococcal antigens such as whole cell body, LTA, and streptolysin-O. Pharyngeal secretions from 67 children with or without RT aged 2-14 years with a median age of 6 years were subjects to secretory IgA (SIgA) antibody levels to streptococcal LTA. The antibodies to whole cell body and LTA were measured by enzyme-linked immunosorbent assay. Total immunoglobins and the anti-streptolysin-O antibody were assayed by nephelometry. RESULTS: An age-matched comparison revealed that either levels of serum IgG antibody or pharyngeal SIgA antibody to streptococcal LTA at 2-5 years of age were significantly lower in RT children than in non-RT children (1.39 vs. 5.14 microg/ml, P=0.001; 10.6 vs. 29.9 units/ng/ml total SIgA, P=0.015; respectively) and correlated inversely to episodes of tonsillitis (r=-0.242, P=0.024; r=-0.3, P=0.024; respectively). Either serum total immunoglobulin levels of IgG or IgA correlated positively to episodes of tonsillitis in children aged 2-5 years (r=0.293, P=0.011; r=0.361, P=0.002; respectively). No difference was found on either serum levels of IgG antibody to streptococcal whole cell body or antibody to streptolysin-O between RT and non-RT children in any age-matched comparisons. High serum antibody levels to whole cell body was associated with high antibody levels to streptococcal LTA in non-RT children (r=0.198, P<0.05), but no association was found between these antibody levels in RT children. CONCLUSIONS: Selective immunologic failure in systemic and pharyngeal antibody response to streptococcal LTA may be a potential cause of RT in young children.

Adolescent↗

PubMed1998

A method for motion compensation of a moving nematode Caenorhabditis elegans and its application to frequency analysis of pharyngeal pulsation.

A new sequential image processing method for motion compensation of a moving object with stringy shape has been developed for estimating the pharyngeal pulsation of the nematode Caenorhabditis elegans under several environmental conditions. The method is based on the pixel data transfer on a new image frame while changing the boundary shape and the position but preserving the conformation of the inner structure of an object. All digitized image frames of C. elegans were first converted to motion-compensated images to arrange the pulsation site in the same region of the every transformed frame. The pulsation site was then automatically detected by determining the pixels where the temporal brightness variation was much larger than that of the other pixels. Finally, the pulsation frequency was determined by the Fourier analysis. The validity of our method has been confirmed by analyzing various test data, and the method has been applied for detecting the pharyngeal pulsation frequencies of C. elegans on some environmental conditions, i.e. feed bacteria-free/rich, doping of nerve inactivating ethyl-alcohol and nerve stimulant neurochemical substance of serotonin. The motion compensation method automatically provided reasonable pulsation frequencies which were found to be comparable to those obtained by manual counting. Thus the method is useful for systematic investigations on the variation of pharyngeal pulsation associated with the activity change of the nervous system in environments.

Algorithms↗

PubMed1987

Streptococcus pyogenes cell wall protein responsible for binding to pharyngeal epithelial cells.

The aim of this study was to identify a streptococcal cell wall substance which is able to bind to epithelial cells. The water-soluble phase of sonicated M+ and M- strains was incubated with pharyngeal and buccal epithelial cells. Electrophoretic analysis of these materials, before and after incubation, showed disappearance of one band from the M+ samples only, after incubation with pharyngeal epithelial cells. The specific anti-M protein serum did not precipitate this protein. Incubation of tested materials with buccal epithelial cells did not change their composition. The molecular mass of this band was estimated as 35,000 Daltons by the use of SDS-PAGE and marker proteins. These results suggest that an adhesin responsible for the streptococcal group A binding to pharyngeal epithelial cells is a protein closely associated with the M antigen.

Adhesins, Bacterial↗

PubMed1999

Pharyngeal branch of the vagus nerve carries intraepithelial afferent fibers in the cat pharynx: an elucidation of the origin and central and peripheral distribution of these components.

The presence of a sensory component in the pharyngeal branch of the vagus nerve (PhB), including its peripheral distribution and central projection, was studied by denervation and tracer experiments in the cat. The distribution of nerve fibers immunoreactive to protein gene product 9.5, a sensitive neuronal marker; calcitonin gene-related peptide; and substance P in the pharyngeal epithelium was analyzed in both intact animals and animals subjected to partial denervation by means of sectioning two of the three nerve trunks, the glossopharyngeal nerve, the superior laryngeal nerve, and the PhB, while leaving one intact. The results of this study show that the glossopharyngeal nerve and superior laryngeal nerve carry nerve fibers to the pharyngeal epithelium rostral and caudal to the middle level of the epiglottis, respectively, whereas the PhB carries nerve fibers to the mesopharyngeal epithelium. Tracer experiments, by applying wheat germ agglutinin-horseradish peroxidase to the PhB, demonstrated retrogradely labeled primary sensory neurons in the jugular ganglion and transganglionic labeling of terminals in the interstitial subnucleus of the nucleus of the tractus solitarius. These results indicate that the PhB contains a sensory component that originates from the jugular ganglion, innervates the mesopharyngeal epithelium, and projects to the nucleus of the tractus solitarius.

Afferent Pathways↗

PubMed2003

Pharyngeal flap surgery: protocols, complications, and outcomes at the University of Iowa.

OBJECTIVE: We sought to assess complication rates and speech outcomes in patients undergoing pharyngeal flap surgery. Study design and setting We conducted a retrospective chart and database review at a tertiary craniofacial center. PATIENTS: Eighty-seven patients were identified as having pharyngeal flaps between January 1990 and December 2000. RESULTS: Complications were rare, with an overall rate of 3.4% for all children. Craniofacial database records were identified with a follow-up examination between 2 and 5 years. Forty-four patients were identified. Of this group, 81.8% demonstrated no evidence of hypernasality or mild hypernasality, and 84.1% demonstrated no evidence of hyponasality or only mild hyponasality. Preoperative and postoperative assessments showed a statistically significant difference in hypernasality at P < 0.001 with no significant difference in hyponasality. CONCLUSIONS: Although sphincter pharyngoplasty procedures have gained a great deal of attention in the recent otolaryngologic literature, pharyngeal-flap procedures remain a valuable tool in the hands of surgeons dealing with velopharyngeal incompetence.

Adolescent↗

PubMed2003

S-carboxymethylcysteine inhibits the attachment of Streptococcus pneumoniae to human pharyngeal epithelial cells.

Streptococcus pneumoniae causes respiratory and other invasive infections. Increased resistance of this bacterium to antibiotics necessitates new approaches to the treatment of infections. Attachment of bacteria to human pharyngeal epithelial cells is the initial step in the pathogenesis of infection and S-carboxymethylcysteine (S-CMC) can modulate the attachment of Moraxella catarrhalis and nontypable Haemophilus influenzae to epithelial cells. Unlike these two, S. pneumoniae is gram-positive and has a well-defined capsule. Here we examined the effects of S-CMC on the attachment and detachment of S. pneumoniae to human pharyngeal epithelial cells in vitro. Treatment of these cells with S-CMC significantly reduced the number of attached S. pneumoniae. S-CMC also resulted in a significant increase in the detachment of already attached S. pneumoniae to epithelial cells. In addition, treatment of S. pneumoniae with S-CMC significantly reduced their ability to attach to epithelial cells, but not the number of viable bacteria. Our study shows that S-CMC modulates the attachment of S. pneumoniae to human pharyngeal epithelial cells by acting both on cells and bacteria.

Anti-Bacterial Agents↗

PubMed2001

Gcm2 and Foxn1 mark early parathyroid- and thymus-specific domains in the developing third pharyngeal pouch.

The thymus and parathyroids originate from a common primordium that develops from the third pharyngeal pouch in mice and humans. The molecular mechanism that specifies this primordium into distinct organ domains is not known. The Gcm2 and Foxn1 transcription factors are required for development of the parathyroid and thymus respectively, and are attractive candidates for this role. However, their embryonic expression patterns during pharyngeal pouch development and early thymus and parathyroid organogenesis have not been described. Here we report that Gcm2 is expressed specifically in the developing second and third pharyngeal pouches at E9.5, and is further confined to a small domain of the third pouch endoderm by E10.5. In contrast, Foxn1 is not expressed until after the common primordium is formed, beginning at E11.25. Our results show that Gcm2 and Foxn1 expression mark two complementary domains that prefigure parathyroid and thymus regions within the common primordium before morphological distinctions are present.

Animals↗

PubMed2002

Aortic arch and pharyngeal phenotype in the absence of BMP-dependent neural crest in the mouse.

Neural crest cells are essential for proper development of a variety of tissues and structures, including peripheral and autonomic nervous systems, facial skeleton, aortic arches and pharyngeal glands like the thymus and parathyroids. Previous work has shown that bone morphogenic protein (BMP) signalling is required for the production of migratory neural crest cells that contribute to the neurogenic and skeletogenic lineages. We show here that BMP-dependent neural crest cells are also required for development of the embryonic aortic arches and pharynx-derived glands. Blocking formation or migration of this crest cell population from the caudal hindbrain resulted in strong phenotypes in the cardiac outflow tract and the thymus. Thymic aplasia or hypoplasia occurs despite uncompromised gene induction in the pharyngeal endoderm. In addition, when hypoplastic thymic tissue is found, it is ectopically located, but functional in thymopoiesis. Our data indicate that thymic phenotypes produced by neural crest deficits result from aberrant formation of pharyngeal pouches and impaired migration of thymic primordia because the mesenchymal content in the branchial arches is below a threshold level.

Animals↗

PubMed1994

Pharyngeal solid-state manometry catheter movement during swallowing in dysphagic and nondysphagic participants.

RATIONALE AND OBJECTIVES: The movements of the soft palate and the larynx are crucial in pharyngeal manometry because of the potential risk of manometry sensor dislocation. METHODS: Twenty dysphagic patients and 20 nondysphagic volunteers were examined with simultaneous videoradiography and intraluminal pharyngeal solid-state manometry. The movements of the manometric sensors were analyzed from lateral videorecording. RESULTS: Two different types of catheter movement were found. The sensor in the upper esophageal sphincter (UES) could either be lifted cranially during the closure of the soft palate (type 1) or stay unaltered in the sphincter until the beginning of the laryngeal elevation and then follow the sphincter cranially during laryngeal elevation with no previous response to soft palate closure (type 2). Type 1 movement was found in eight of 20 patients but in only one of the 20 volunteers. The resting pressure of the upper esophageal sphincter was significantly higher in type 2 (P = 0.004). Nineteen of the 20 patients with a high resting pressure of the UES (83+ mm Hg) were found to have the type 2 movement. CONCLUSION: High resting pressure in the UES permitted the sphincter to grasp the manometry catheter and caused the sensor to follow the cranial movement during laryngeal elevation. Sensor movement is important during pharyngeal manometry, and sensor dislocation out of the sphincter can be misinterpreted as sphincter relaxation. Simultaneous videoradiography provides control of sensor positioning and allows for correction.

Adult↗

PubMedDate not supplied

Laryngoscopy and pharyngeal pH are complementary in the diagnosis of gastroesophageal-laryngeal reflux.

Pharyngeal pH monitoring and laryngoscopy are routinely used to diagnose gastroesophageal-laryngeal reflux as a cause of respiratory symptoms. Although their use seems intuitive, their ultimate diagnostic value is yet to be defined. We studied 10 asymptomatic (control) subjects and 76 patients with respiratory symptoms. Both patients and control subjects were given a symptom questionnaire. Each underwent direct laryngoscopy using the reflux finding score (RFS) to grade laryngeal injury, esophageal manometry, and 24-hour esophagopharyngeal pH monitoring. The patients were then classified as RFS+, if the score was greater than 7, and pharyngeal reflux (PR)+, if they had more than one episode of PR detected during pH monitoring. The most common symptoms reported by patients were hoarseness (87%), cough (53%), and heartburn (50%). Control subjects had a significantly lower RFS (2.1 vs. 9.6, P < 0.01) and fewer episodes of PR (0.2 vs. 3.4, P < 0.01), than patients. None of the control subjects had more than one episode of PR during a 24-hour period. Fifty patients (66%) were RFS+ and 26 (34%) were RFS-. Thirty-two patients (42%) were PR+ and 44 (58%) were PR-. Fifteen patients had a normal RFS and no PR (group I = RFS-/PR-). Forty patients had discordance between the laryngoscopic findings and the pH monitoring (group II = RFS-/PR+ or RFS+/PR-). Twenty-one patients had both an abnormal RFS and PR (group III = RFS+/PR+). Patients in group III had significantly higher heartburn scores and distal esophageal acid exposure. Eighty-three percent of patients in group III but only 44% in group I improved their respiratory symptoms as a result of antireflux therapy. An abnormal PR or RFS differentiates patients with laryngeal symptoms from control subjects. Agreement between PR and RFS helps establish or refute the diagnosis of gastroesophageal reflux as a cause of laryngeal symptoms. Patients who are RFS+ and PR- may have laryngeal injury from another source, whereas patients who are RFS- and PR+ may not have acid entering the larynx, despite the presence of PR. Patients who are RFS+ and PR+ have more severe gastroesophageal reflux disease and their reflux causes laryngeal damage. Laryngoscopy and pharyngeal pH monitoring should be considered complementary studies in establishing the diagnosis of laryngeal injury induced by gastroesophageal reflux. ( J GASTROINTEST SURG 2002;6:189-194.)

Case-Control Studies↗