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[Second primary cancers occurring in patients with cancers of the mouth and meso-hypo pharynx in Japan].

We evaluated the risk of development of a second primary cancer in 669 patients diagnosed with cancers of the mouth and meso-hypo pharynx at Osaka Medical Center for Cancer and Cardiovascular Diseases. During 1978-93, 70 of the patients developed a second primary cancer, yielding on observed to expected ratio (O/E) of 2.92 [95% confidence interval (CI) = 2.27-3.69]. Significant excess risk was noted for cancers of mouth and pharynx (O/E = 12.01, 95% CI = 3.87-28.04), esophagus (O/E = 25.22, 95% CI = 14.94-39.86), colon (O/E = 3.85, 95% CI = 1.41-8.39), larynx (O/E = 9.93, 95% CI = 2.00-29.02) and lung (O/E = 2.58, 95% CI = 1.24-4.75). The risks of esophageal cancer and colon cancer were significantly elevated after five years had elapsed from the initial cancer diagnoses. The risk of cancers of the oral cavity, pharynx, larynx and esophagus in patients who had a history of current smoking without current daily drinking at the initial diagnosis was elevated past one year after the initial diagnosis (less than 20 cigarettes/ day; O/E = 12.50, 95% CI = 0.16-69.55, 20 cigarettes or more; O/E = 10.00, 95% CI = 1.12-36.10). The risk of cancers of the oral cavity, pharynx, larynx and esophagus in patients who had a history of current smoking with current daily drinking at the initial diagnosis was around two times higher than those who had a history of current smoking without current daily drinking (less than 20 cigarettes/day; O/E = 20.00, 95% CI = 2.25-72.21, 20 cigarettes or more; O/ E = 19.51, 95% CI = 8.40-38.45).

Adult↗

Goblet cells in the developing rhinopharynx and pharynx.

In 60 foetuses and prematures, ranging in age from the 10th to the 30th menstrual week, the entire mucous membrane from the rhinopharynx and pharynx was removed and stained in toto with PAS-alcian blue, PAS, and osmium whole-mount methods. The development, spread, and density of goblet cells as well as the differentiation of the epithelium were studied. Goblet-cell development started in the 12th week, 3-4 weeks later than the development of ciliated cells, below the tubal orifice. Thereupon, goblet cells gradually spread behind the tubal orifice, towards the roof and further on to the nose. Thus, by the 17th week goblet cells and ciliated cells are present throughout the rhinopharynx and in the upper half of the pharynx. In the lower half of the rhinopharynx and upper part of the pharynx as well as in the posterior wall, the density is fairly low during the first weeks, and later it becomes even lower. In these sites the epithelium differentiation into startified squamous and transitional epithelium. In the roof of the rhinopharynx and in the fossa of Rosenmüller the density increases steadily, and in these sites respiratory tract epithelium is present. Transformation of the epithelium, which originally contains ciliated cells and goblet cells, into startified squamous epithelium and transitional epithelium is instituted at an early stage of development and continues throughout, but possibly it is promoted postnatally by mechanical contact between the walls.

Cell Differentiation↗

[Congenital and benign changes with regard to the pharynx].

DEVELOPMENT: The first part of this article is supposed to present a brief overview on the development of tissues and structures related to the pharynx, as far as they provide a better understanding of the most congenital lesions in this area of the body. BENIGN LESIONS: The second part of this article focuses on benign lesions originating in the pharynx or in neighbouring structures. Functional pharynx abnormalities are beyond the scope of this paper.

Humans↗

[Inflammatory diseases of the pharynx. The imaging findings and diagnostic strategy].

PURPOSE: To demonstrate imaging findings in inflammatory diseases of the pharynx and possible complications. MATERIAL AND METHODS: Radiologic imaging of the pharynx is based on the use of conventional X-ray films, computed tomography and magnetic resonance imaging, plain and contrast enhanced. RESULTS: The advantages of cross sectional imaging techniques like CT and MRT lie in the possibility to diagnose submucosal disease and localized as well as general complications. Most frequently abscesses and phlegmonous diseases have to be diagnosed. CT proves advantageous due to its fast imaging protocol and the widely availability. MRI is superior due to its superior soft tissue contrast and the multiplanar imaging. CONCLUSION: Spiral-CT and MRI mean valuable diagnostic tools for the evaluation of inflammatory diseases of the pharynx and possible complications.

Adult↗

Cardiac arterial pole alignment is sensitive to FGF8 signaling in the pharynx.

Morphogenesis of the cardiac arterial pole is dependent on addition of myocardium and smooth muscle from the secondary heart field and septation by cardiac neural crest cells. Cardiac neural crest ablation results in persistent truncus arteriosus and failure of addition of myocardium from the secondary heart field leading to malalignment of the arterial pole with the ventricles. Previously, we have shown that elevated FGF signaling after neural crest ablation causes depressed Ca2+ transients in the primary heart tube. We hypothesized that neural crest ablation results in elevated FGF8 signaling in the caudal pharynx that disrupts secondary heart field development. In this study, we show that FGF8 signaling is elevated in the caudal pharynx after cardiac neural crest ablation. In addition, treatment of cardiac neural crest-ablated embryos with FGF8b blocking antibody or an FGF receptor blocker rescues secondary heart field myocardial development in a time- and dose-dependent manner. Interestingly, reduction of FGF8 signaling in normal embryos disrupts myocardial secondary heart field development, resulting in arterial pole malalignment. These results indicate that the secondary heart field myocardium is particularly sensitive to FGF8 signaling for normal conotruncal development, and further, that cardiac neural crest cells modulate FGF8 signaling in the caudal pharynx.

Animals↗

Interference between the PHA-4 and PEB-1 transcription factors in formation of the Caenorhabditis elegans pharynx.

PHA-4 is a forkhead/winged helix transcription factor that acts as an organ identity factor in the development of the Caenorhabditis elegans pharynx. PEB-1 is a novel DNA-binding protein also involved in pharyngeal morphogenesis. PHA-4 and PEB-1 bind at overlapping sites on the C183 sequence element that controls pharynx-specific expression of the C. elegans myo-2 gene. It has been suggested that PHA-4 and PEB-1 act cooperatively on the C183 sequence. In this study, we test this model and assess the C183-dependent transcriptional activity of PHA-4 and PEB-1, both individually and in combination. We show that PHA-4 and PEB-1 are both modest transcriptional activators in yeast but that co-expression of the two factors does not result in significantly increased expression of a C183-regulated reporter gene. Electrophoretic mobility-shift assays provide no evidence for the formation of a PHA-4/PEB-1 complex in vitro but rather show that PHA-4 and PEB-1 cannot bind C183 simultaneously. As we have reported previously, ectopic expression of PHA-4 in C. elegans causes ectopic expression of a C183-regulated reporter gene. We show that ectopic expression of PEB-1 cannot cause ectopic expression of the same reporter but rather ectopic PEB-1 inhibits reporter gene activation by PHA-4. Overall, our results do not support a model in which PHA-4 and PEB-1 synergize in vivo but rather support a model in which PEB-1 may negatively modulate PHA-4's ability to activate transcription through C183 during formation of the C. elegans pharynx.

Animals↗

Alternative-splicing of serotonin receptor isoforms in the pharynx and muscle of the parasitic nematode, Ascaris suum.

Pharyngeal pumping is essential for nematode feeding and survival and is dramatically stimulated by serotonin (5-HT). In the present study, a cDNA pool was prepared from poly A + RNA isolated from pharynxes dissected from the parasitic nematode, Ascaris suum, and was used as a template for RT-PCR with degenerate primers designed from sequences conserved in 5-HT receptors from a variety of sources. A putative 5-HT receptor cDNA (AS1) was identified which exhibited most identity to the 5-HT2 family of receptors. AS1 was 1925 nucleotides, did not appear to be trans-spliced and contained a 3' untranslated region of 127 nucleotides with a polyadenylation signal (ATTAAA) and a short poly A+ tail. The coding region predicted a protein of 532 amino acids with a molecular weight of 60 176. When AS1 was transiently expressed in COS-7 cells, isolated membranes exhibited the high affinity, saturable binding of [125I]LSD. More importantly, [125I]LSD binding was inhibited by 5-HT, but not other biogenic amines, supporting the identification of AS1 as a 5-HT receptor. Additional cDNAs identical, in part, to AS1 were also identified. AS1deltaIV lacked a predicted 42 amino acids at the carboxy terminus of the third intracellular loop, while AS2 and AS3 contained different COOH-termini, regions implicated in G-protein coupling in other heptahelical receptors. A portion of the gene (5htn) encoding AS1 also was cloned and sequenced. This genomic fragment was about 10 kb, contained the entire AS1 open reading frame and included eight exons and seven introns. From this analysis, it appears that these different AS cDNAs were generated by alternative-splicing, AS1deltaIV from the deletion of exon IV, and AS2 and AS3 from the use of alternative sites within exon VII as 5' splice acceptor sites for exon VIII. Using RT-PCR and primers specific for each of the isoforms, AS1 -3 appeared to be expressed in pharynx, while only AS1 and AS2 were present in body wall muscle. More importantly, the deletion of exon IV appeared to be associated exclusively with AS1 in pharynx and AS2 in muscle.

Alternative Splicing↗

Predicting midsagittal pharynx shape from tongue position during vowel production.

The shape of the pharynx has a large effect on the acoustics of vowels, but direct measurement of this part of the vocal tract is difficult. The present study examines the efficacy of inferring midsagittal pharynx shape from the position of the tongue, which is much more amenable to measurement. Midsagittal magnetic resonance (MR) images were obtained for multiple repetitions of 11 static English vowels spoken by two subjects (one male and one female). From these, midsagittal widths were measured at approximately 3-mm intervals along the entire vocal tract. A regression analysis was then used to assess whether the pharyngeal widths could be predicted from the locations and width measurements for four positions on the tongue, namely, those likely to be the locations of a receiver coil for an electromagnetometer system. Predictability was quite high throughout the vocal tract (multiple r> 0.9), except for the extreme ends (i.e., larynx and lips) and small decreases for the male subject in the uvula region. The residuals from this analysis showed that the accuracy of predictions was generally quite high, with 89.2% of errors being less than 2 mm. The extremes of the vocal tract, where the resolution of the MRI was poorer, accounted for much of the error. For languages like English, which do not use advanced tongue root (ATR) distinctively, the midsagittal pharynx shape of static vowels can be predicted with high accuracy.

Female↗

Do laryngeal mask airway devices attenuate liquid flow between the esophagus and pharynx? A randomized, controlled cadaver study.

UNLABELLED: In this randomized, controlled cadaver study, we tested the hypothesis that the standard laryngeal mask airway (LMA) and flexible laryngeal mask airway (FLMA) attenuate liquid flow between the esophagus and pharynx. Fifty fresh cadavers were studied in four LMA groups. Ten female cadavers had a size 4 LMA and 10 had a size 4 FLMA; 10 male cadavers had a size 5 LMA and 10 had a size 5 FLMA; 5 male and 5 female cadavers functioned as controls. The chest was opened, and the infusion set of a pressure-controlled, continuous flow pump was inserted into the esophagus and ligated into place. Esophageal pressure was increased in 2-cm H2O increments. Regurgitation pressure was the esophageal pressure at which fluid was first seen with a fiberoptic scope in the hypopharynx (control group) and above the cuff or within the bowl (LMA groups). This was performed in the LMA groups at 0-40 mL cuff volume in 10-mL increments. Mean (95% confidence interval) regurgitation pressure for the control group was 7 (6-8) cm H2O and for the LMA groups combined was 19 (17-20) cm H2O at 0 mL cuff volume, 47 (41-52) cm H2O at 10 mL, 51 (44-55) cm H2O at 20 mL, 52 (45-56) cm H2O at 30 mL, and 52 (45-55) cm H2O at 40 mL. The increase in regurgitation pressure with increasing cuff volume from 0 to 10 mL was statistically significant (P < 0.0001). Regurgitation pressure was higher for the LMA groups at all cuff volumes compared with the control group (P < 0.0001). There were no differences in regurgitation pressure among the LMA groups. We conclude that the correctly placed LMA and FLMA attenuate liquid flow between the esophagus and pharynx. IMPLICATIONS: We have shown, in cadavers, that the correctly placed standard and flexible laryngeal mask airways attenuate liquid flow between the pharynx and esophagus.

Aged↗

Lateral position decreases collapsibility of the passive pharynx in patients with obstructive sleep apnea.

BACKGROUND: Reduction of nocturnal obstructive events during lateral position in patients with obstructive sleep apnea was previously reported. However, little information is available regarding mechanisms of the improvement and the precise pharyngeal site influenced by the lateral position. The authors tested the hypothesis that structural properties of the passive pharynx change by changing the body position from supine to lateral. METHOD: Total muscle paralysis was induced with general anesthesia in eight patients with obstructive sleep apnea, eliminating neuromuscular factors contributing to pharyngeal patency. The cross-sectional area of the pharynx was measured endoscopically at different static airway pressures. Comparison of static pressure-area plot between the positions allowed assessment of the influence of the position change on the mechanical properties of the pharynx. RESULTS: The static pressure-area curves of the lateral position were above those of the supine position, with increasing maximum cross-sectional area and decreasing the closing pressure at both retropalatal and retroglossal airways. CONCLUSIONS: Lateral position structurally improves maintenance of the passive pharyngeal airway in patients with obstructive sleep apnea.

Adult↗

The UNC-73/Trio RhoGEF-2 domain is required in separate isoforms for the regulation of pharynx pumping and normal neurotransmission in C. elegans.

In both Caenorhabditis elegans and Drosophila, UNC-73/Trio functions in axon guidance by signaling through the Rac GTPase to regulate cytoskeletal rearrangements necessary for growth cone migrations. Here, we show that the complex C. elegans unc-73 gene encodes at least eight differentially expressed UNC-73 intracellular protein isoforms. Previously reported mutations affecting UNC-73 isoforms encoding the Rac-specific RhoGEF-1 domain cause uncoordinated movement, correlating with defects in axon guidance. Mutations in isoforms encoding the Rho-specific RhoGEF-2 domain, which we describe here, result in L1 stage larval lethality with no associated axon guidance defects. Isoform-specific rescue experiments reveal separate functions for the various RhoGEF-2-containing UNC-73 isoforms, which would not likely be discovered by conventional genetic screening. UNC-73 D1 and D2 appear to function redundantly in pharynx muscle to regulate the rate and strength of pharynx pumping, and in the HSN neurons and vulval muscles to control egg laying. Isoforms C1, C2, E, and F act redundantly within the nervous system to regulate the speed of locomotion. The multiple UNC-73 isoforms containing Rac- and Rho-specific RhoGEF domains therefore have distinct physiological functions. In addition to its previously identified role involving RhoGEF-1 in migrating cells and growth cones, our data indicate that UNC-73 signals through RhoGEF-2 to regulate pharynx and vulva musculature and to modulate synaptic neurotransmission.

Animals↗

Pharynx: value of oblique projections for radiographic examination.

The utility of oblique views for augmenting standard posteroanterior and lateral double-contrast radiography of the pharynx was examined. Over an 8-month period, two oblique views were added to the standard posteroanterior and lateral views of the pharynx during routine upper gastrointestinal studies in 102 patients divided into two groups. Group 1 consisted of 81 patients without suspected pharyngeal or esophageal disease who demonstrated what was considered to be normal anatomy on all radiographic views. Group 2 consisted of 21 patients who were known or suspected to have pathologic abnormality of the pharynx. The members of this latter group each demonstrated various abnormal pharyngeal anatomy on the standard views. In just over half of these cases the oblique projection contributed significant information not obtained with conventional views. Therefore, the authors conclude that oblique images are a beneficial addition to the diagnostic evaluation of patients highly suspected of having pharyngeal disease.

Barium Sulfate↗

CD44 as a receptor for colonization of the pharynx by group A Streptococcus.

The pharynx is the primary reservoir for strains of group A STREPTOCOCCUS: (GAS) associated both with pharyngitis (streptococcal sore throat) and with invasive or "flesh-eating" soft tissue infections. We now report that CD44, a hyaluronic acid-binding protein that mediates human cell-cell- and cell-extracellular matrix-binding interactions, functions as a receptor for GAS colonization of the pharynx in vivo. We found that attachment of GAS to murine epithelial keratinocytes was mediated by binding of the GAS hyaluronic acid capsular polysaccharide to CD44. In studies of transgenic mice with a selective defect in epithelial expression of CD44, GAS adherence to CD44-deficient keratinocytes in vitro was reduced compared with adherence to keratinocytes expressing normal levels of CD44. After intranasal inoculation, GAS colonized the oropharynx of wild-type mice but failed to colonize transgenic mice deficient in CD44 expression. GAS colonization of wild-type mice could be blocked by coadministration of mAb to CD44 or by pretreatment of the animals with exogenous hyaluronic acid. These results provide evidence that CD44 serves as a receptor for GAS colonization of the pharynx and support the potential efficacy of disrupting the interaction between the GAS hyaluronic acid capsule and CD44 as a novel approach to preventing pharyngeal infection.

Animals↗

pha-4 is Ce-fkh-1, a fork head/HNF-3alpha,beta,gamma homolog that functions in organogenesis of the C. elegans pharynx.

The C. elegans Ce-fkh-1 gene has been cloned on the basis of its sequence similarity to the winged-helix DNA binding domain of the Drosophila fork head and mammalian HNF-3alpha,beta,gamma genes, and mutations in the zygotically active pha-4 gene have been shown to block formation of the pharynx (and rectum) at an early stage in embryogenesis. In the present paper, we show that Ce-fkh-1 and pha-4 are the same gene. We show that PHA-4 protein is present in nuclei of essentially all pharyngeal cells, of all five cell types. PHA-4 protein first appears close to the point at which a cell lineage will produce only pharyngeal cells, independently of cell type. We show that PHA-4 binds directly to a 'pan-pharyngeal enhancer element' previously identified in the promoter of the pharyngeal myosin myo-2 gene; in transgenic embryos, ectopic PHA-4 activates ectopic myo-2 expression. We also show that ectopic PHA-4 can activate ectopic expression of the ceh-22 gene, a pharyngeal-specific NK-2-type homeodomain protein previously shown to bind a muscle-specific enhancer near the PHA-4 binding site in the myo-2 promoter. We propose that it is the combination of pha-4 and regulatory molecules such as ceh-22 that produces the specific gene expression patterns during pharynx development. Overall, pha-4 can be described as an 'organ identity factor', completely necessary for organ formation, present in all cells of the organ from the earliest stages, capable of integrating upstream developmental pathways (in this case, the two distinct pathways that produce the anterior and posterior pharynx) and participating directly in the transcriptional regulation of organ specific genes. Finally, we note that the distribution of PHA-4 protein in C. elegans embryos is remarkably similar to the distribution of the fork head protein in Drosophila embryos: high levels in the foregut/pharynx and hindgut/rectum; low levels in the gut proper. Moreover, we show that pha-4 expression in the C. elegans gut is regulated by elt-2, a C. elegans gut-specific GATA-factor and possible homolog of the Drosophila gene serpent, which influences fork head expression in the fly gut. Overall, our results provide evidence for a highly conserved pathway regulating formation of the digestive tract in all (triploblastic) metazoa.

Animals↗

Food transport in the C. elegans pharynx.

Pumping of the C. elegans pharynx transports food particles (bacteria) posteriorly. We examined muscle motions to determine how this posterior transport is effected. We find that the motions of the middle section of the pharynx, the anterior isthmus, are delayed relative to the anterior section, the corpus. Simulations in which particles are assumed to move at mean fluid velocity when not captured by the walls of the pharyngeal lumen show that delayed isthmus motions do indeed cause net particle transport; however, the amount is much less than in the real pharynx. We propose that the geometry of the pharyngeal lumen forces particles to the center, where they move faster than mean fluid velocity. When this acceleration is incorporated into the simulation, particles are transported efficiently. The transport mechanism we propose explains past observations that the timing of muscle relaxation is important for effective transport. Our model also makes a prediction, which we confirm, that smaller bacteria are better food sources for C. elegans than large ones.

Algorithms↗

Control of mouth opening and pharynx protrusion during feeding in the sea anemone Calliactis parasitica.

1. Activity in all three known conducting systems (the nerve net, SS1, and SS2) may accompany feeding in Calliactis. The most marked response is an increase in pulse frequency in the SS2 (the endodermal slow conducting system) during mouth opening and pharynx protrusion. 2. Electrical stimulation of the SS2 at a frequency of one shock every 5 s elicits mouth opening and pharynx protrusion in the absence of food. 3. A rise in SS2 pulse frequency is also evoked by food extracts, some amino acids, and in particular by the tripeptide reduced glutathione, which produces a response at a concentration of 10(-5) M. 4. Although the SS2 is an endodermal system, the receptors involved in the response to food appear to be ectodermal. 5. The epithelium that lines the pharynx conducts SS1 pulses, but there is some evidence for polarization of conduction.

Action Potentials↗

[Arterial blood supply to the laryngeal part of the pharynx].

The sources, anastomoses and variations of bloodsupply of the laryngeal part of the pharynx were studied in 100 corpses of different sex and age. It has been established that the fronto-lateral divisions of the laryngeal part of the pharynx are supplied with blood by pharyngeal branches of the superior and inferior paryngeal arteries. Ligation of the pharyngeal arteries during laryngectomy prior to their entering the larynx, i. e. before the divergence of the pharyngeal branches from them, as conventional, causes restriction of supply of these parts and can contribute to disjunction of the pharyngeal suture. The trunks of laryngeal arteries with their pharyngeal branches should be preserved, if possible. The posterior wall of the laryngeal part of the pharynx is divided into three zones depending on the main arterial sources (the ascending pharyngeal, superior and inferior thyroid arteries).

Adolescent↗

Treatment of beta-hemolytic streptococcal pharyngitis with cefaclor or penicillin. Efficacy and interaction with beta-lactamase-producing organisms in the pharynx.

The recommended treatment for group A beta-hemolytic streptococcal pharyngitis has continued to be penicillin given in parenteral or oral form. Treatment failures, as determined by the continued presence of the streptococcal organism in the pharynx, however, do occur in 6% to 25% of patients treated with penicillin. Furthermore, beta-lactamase produced by other bacteria in the pharynx could potentially inactivate the penicillin, resulting in increased treatment failures or infection relapses. A study was undertaken to compare the efficacy of cefaclor, which is relatively resistant to inactivation by beta-lactamase, with penicillin for eradicating the group A beta-hemolytic streptococcal organism from the throats of 93 patients with pharyngitis. Additionally, extensive cultures for potential beta-lactamase-producing organisms were conducted on 37 patients; 27% of these had one or more pharyngeal organisms that were producing beta-lactamase. No statistically significant difference was found between the clinical responses or the bacteriological cure rates of those treated with cefaclor and those treated with penicillin when stratified by the presence or absence of beta-lactamase-producing organisms. The prevalence of beta-lactamase-producing organisms in the pharynx, however, was increased after treatment with penicillin, whereas no change was noted following treatment with cefaclor.

Adolescent↗