Normal Tongue Research Articles

The Modified Method of Tongue Reduction in Beckwith-Wiedemann Syndrome

The indications for surgical tongue reduction for syndromic macroglossia are airway obstruction, swallowing problems with failure to thrive, dental deformities, articulation disorders, recurrent tongue bitten, oral incompetency, persistent drooling, and cosmetic concerns. However, various methods of tongue reductions have yielded mixed results. Our patient 1 year 11months old with Beckwith-Wiedemann syndrome received surgical tongue reduction at China Medical University Hospital. A modified complex mucous-muscular flap without interrupting the vascular base and preserving the tongue tip was formed. The longitudinal full thickness central wedge resection spared tongue tip apex with lateral extended resection. The transverse part anterior to the circumvallate papilla, was resected in partial thickness. Our approches provide a shortened, non-ankylosed tongue. The benefits are better cosmesis, dynamic esthetic improvement when talking and relief of drooling, and one and half year, better comprehensive articulated pronunciation and her oral competency. It is important that tongue reduction addresses the global nature of the macroglossia and preserving a tapered tongue tip with length sufficient to permit normal tongue movements. Our method may be an alternative for tongue tailoring.

Human oral cancers have altered expression of Bcl‐2 family members and increased expression of the anti‐apoptotic splice variant of Mcl‐1

Expression of Bcl-2 family proteins in tumours can modulate apoptosis, influencing tumour behaviour and treatment. To investigate their role in oral tumourigenesis, nine Bcl-2 family transcripts were examined in three oral cell lines and 25 oral tumours, using ribonuclease protection assay. Since Mcl-1 mRNA was elevated in these samples, Mcl-1 splice variants were assessed by RT-PCR and Mcl-1 protein was studied in normal, premalignant and malignant oral tissues and cell lines, by immunohistochemistry and/or immunoblotting. The cell lines exhibited significantly higher levels of 7/9 Bcl-2 family transcripts as compared to those in normal tongue, and significantly higher (p=0.030, p=0.004) anti-apoptotic versus pro-apoptotic transcripts. Elevated Mcl-1 mRNA was observed in 11/25 (44%) tumours as compared to normal tissues with a five- to ten-fold higher expression of full-length anti-apoptotic Mcl-1 transcript versus the pro-apoptotic short isoform. Strong cytoplasmic Mcl-1 immunoreactivity was detected predominantly in differentiated epithelia in 27/33 (82%) oral tumours, 18/20 (90%) leukoplakia, 25/30 (83%) submucous fibrosis and 3/3 oral cell lines, with weak staining in 8/15 (53%) normal mucosa samples. Mcl-1 positivity in malignant and premalignant tissues was comparable but significantly higher (p<0.01) than that in normal mucosa. The expression of bcl-2 family genes, including Mcl-1 in tumours, did not correlate significantly with clinicopathological parameters. This is the first report delineating the in vivo expression patterns of Mcl-1 protein and Mcl-1 transcripts in oral cancers and premalignant lesions. The observed imbalance between expression of anti-apoptotic and pro-apoptotic Bcl-2 family genes may promote survival in the oral cell lines. Since the majority of oral tumours associated with tobacco-chewing evolve from premalignant lesions, the sustained expression of full-length anti-apoptotic Mcl-1 protein in these tissues suggests an important role for Mcl-1, early in oral cancer pathogenesis in protecting cells from apoptosis via neutralization of pro-apoptotic members and could be a potential therapeutic target for oral cancers.

Decreased nerve distribution in mixed venous-lymphatic malformation

In order to investigate the nerve distribution in mixed venous-lymphatic malformations (MVLMs), 57 postoperative patients diagnosed with MVLMs of the tongue were selected. Immunohistochemistry staining for neurofilament (NF) was used to detect sensory nerve fibers. Distribution of NF in samples from MVLMs was compared with distribution of NF in normal tongue tissue, venous malformations, lymphatic malformations and venular malformations. Results showed that the number of NF-positive nerve fibers in MVLMs was comparable to that in venous malformations and lymphatic malformations. The number of nerve fibers in MVLMs was significantly lower than in normal tissues. NF distribution in MVLMs was not affected by the patient’s age or the coexistence of infection. These data suggest that the decreased distribution of sensory nerve fibers in MVLMs may be involved in the pathogenesis of MVLM of the tongue.

Study on Different Proteomics of Denuded tongue coating

Objective To investigate the microbiostatic mechanism of denuded tongue coating, Proteomic methods were used to find differential expression proteins in denuded tongue. Methods The total protein of normal or denuded tongue coating was separated by means of immobilized pH gradient-based two-dimensional gel electrophoresis (2-DE). The differential expression protein was analyzed by using ImageMaster 2D analysis software. Image analysis software was used for comparative analysis to find differential expression proteins; Mass spectrometry (mass spectrometry) was applied to get the corresponding peptide fingerprint (peptide mass finger print_ PMF). Search the database to identify differences in protein.Results Establish two-dimensional gel electrophoresis for normal and denuded tongue; Segregation analysis on four groups of proteome of tongue coating showed that gel could be detected in the protein spots at 1082=t=105 and 1143±140 respectively; Compared with normal group, there are eight points of protein expression being regulated upward and seven points down.Altogether 9 differences in protein expression were identified. Conclusion The sound resolution and repeatability Two-dimensional electrophoresis silver staining pattern were established; Some differences in protein expression related to denuded tongue were identified. Key words: Tongue coating: Proteomics: Two-dimensional gel electrophoresis: Differences in protein expression profile: Methodology

Gli3‐deficient mice exhibit cleft palate associated with abnormal tongue development

Palatogenesis depends on appropriate growth, elevation, and fusion of the palatal shelves and aberration in these processes can lead to palatal clefting. We observed a high incidence of palate clefting in mice deficient in Gli3, known for its role as a repressor in the absence of Shh signaling. In contrast with several current mouse models of cleft palate, Meckel's cartilage extension, cranial neural crest migration, palatal shelf proliferation, apoptosis, and key signaling components mediated by Shh, Bmp, Fgf, and Tgfbeta, appeared unaffected in Gli3-/- mice. Palatal clefting in Gli3-/- mice was consistently associated with tongue abnormalities such as failure to flatten and improper positioning, implicating a critical role of Gli3 and normal tongue morphogenesis for timely palatal shelf elevation and joining. Furthermore, Gli3-/- palatal shelves grown in roller cultures without tongue can fuse suggesting that the abnormal tongue is likely an impediment for palatal shelf joining in Gli3-/- mutants.

Retinoic acid down‐regulates Tbx1 expression and induces abnormal differentiation of tongue muscles in fetal mice

Excess retinoic acid (RA) during pregnancy can cause various developmental anomalies in both humans and rodents. We investigated the mechanisms underlying the aberrant differentiation of tongue muscles in fetal mice exposed to exogenous RA in utero. RA-degrading enzymes (Cyp26a1 and Cyp26b1) were expressed at early stages of normal tongue development, but exogenous RA perturbed their expression in the fetal tongue. RA is normally distributed in the developing tongue muscles but its localization was disrupted by exogenous RA. After RA treatment, myogenic determination factors were reduced and the differentiation was significantly suppressed in tongue muscles. Tbx1, a candidate gene of DiGeorge syndrome, was down-regulated in the fetal tongue in response to excess RA. Moreover, Tbx1 as well as myogenic determination factors were not observed in tongue muscle primordia of Cyp26b1-/- fetuses. Our study suggests that RA signaling may play an essential role in tongue muscle differentiation via the regulation of Tbx1.

Functional reconstruction of near total glossectomy defects using composite gastro omental-dynamic gracilis flaps

The tongue is the most commonly involved structure in cancer of the oral cavity. For locally advanced tumours, adequate resection necessitates near total or total glossectomy. Such patients pose a unique surgical challenge because of the potential for severe speech and swallowing disruption and life-threatening aspiration. These patients also undergo radiotherapy, leading to xerostomia with associated poor quality of life. Present day techniques use dynamic muscles or musculocutaneous flaps for reconstruction of such defects which, although providing adequate glossopalatal contact and tongue movements, are still far from achieving normal tongue appearance and have no intrinsic secretory capability. We have tried to circumvent this problem by using two different free flaps simultaneously, the gracilis muscle to work as functional motor unit for providing tongue movements and elevation together with free stomach, turned inside-out, as an added source of secretion for dry mouth and attached omentum for providing adequate bulk. This technique has been used in two patients over the last 18 months with satisfactory functional and aesthetic results.

Integrin expression in oral hairy leukoplakia and normal tongue epithelium.

To describe the expression of integrins in the epithelium of oral hairy leukoplakia (HL) and compare to that of normal lateral tongue epithelium. Immunohistochemistry to identify integrins (alpha 2, alpha 3, alpha 5, alpha 6, alpha v, beta 1) was performed, using a standard biotin-streptavidin-peroxidase technique on five clinically and histologically confirmed frozen biopsy specimens of HL and five normal lateral tongue control tissues. Expression of integrins alpha 2, alpha 3, alpha 6, alpha v, beta 1 was seen both in HL epithelium and in normal control tissue. alpha 5 expression was not seen in HL or in control tissue epithelium. alpha 2 and alpha 3 were expressed mainly in the basal and suprabasal layers; alpha 6 expression was most intense on the basal surface of the basal cells, alpha v was expressed in the basal and suprabasal layers with more expression seen in the higher differentiated cell layers than the other integrins. beta 1 expression was seen in the basal and suprabasal layers only. No apparent difference between HL and normal oral mucosa was noted in the staining pattern of the various integrins. Integrins alpha 2, alpha 3, alpha 6, alpha v, beta 1 are expressed in HL and the expression pattern is not different from that of normal oral mucosa. alpha 5 is not expressed in HL or in normal oral epithelium.

Neutral pH Hydrogen-Enriched Electrolyzed Water Achieves Tumor-Preferential Clonal Growth Inhibition Over Normal Cells and Tumor Invasion Inhibition Concurrently With Intracellular Oxidant Repression

The properties and effects of neutral pH hydrogen-enriched electrolyzed water (NHE water) on tumor cells were examined. NHE water diminished hydroxyl radicals as demonstrated by ESR in a cell-free system. Human tongue carcinoma cells HSC-4 were inhibited for either colony formation efficiencies or colony sizes by NHE water without significant inhibition to normal human tongue epithelial-like cells DOK. Furthermore, NHE water caused growth inhibition, cell degeneration, and inhibition of invasion through the reconstituted basement membrane to human fibrosarcoma cells HT-1080. Intracellular oxidants such as hydroperoxides and hydrogen peroxides were scavenged in HSC-4 or HT-1080 cells by NHE water. In the human oral cavity, a dissolved hydrogen concentrations (DH) of NHE water was drastically declined from 1.1 to 0.5 ppm, but settled to 0.3-0.4 ppm until 180 s, upon static holding without gargling. Thus, NHE water was shown to achieve tumor-preferential growth inhibition and tumor invasion together with scavenging of intracellular oxidants, and is expected as a preventive material against tumor progression and invasion.

High interstitial fluid pressure in rat tongue cancer is related to increased lymph vessel area, tumor size, invasiveness and decreased body weight

Interstitial fluid pressure (IFP) in most tumors is high, and this high pressure has been correlated with poor prognosis. Measurements of IFP in normal tongue and in tongue cancer are lacking. Recent research suggests the existence of a relationship between increased peritumoral lymph vessels (PTLV) and survival, and a correlation of increased lymphatic vessel density with an unfavorable prognosis has been reported. In the present study, tongue squamous cell carcinoma (SCC) was induced by adding the carcinogen 4-nitroquinoline oxide in drinking water for 19 weeks. The IFP was measured by micropuncture and immunohistochemistry was used to visualize lymph vessels. In normal tongue, IFP averaged 3.1 +/- 0.3 mmHg. The IFP, both in the tumor (29.1 +/- 2.9 mmHg) and 0.5 cm anterior to it (15.4 +/- 2.1 mmHg) was consistently increased (P < 0.005) with values ranging from 10 to 40 mmHg. The highest IFP values were measured in rats with large tumors (P < 0.05) and low body weight (P < 0.001), suggesting that IFP increases with cancer progression. Lymphatic vessel area (%), as determined with the lymphatic specific marker LYVE-1 antibody, was significantly increased in the peritumoral area when compared to intratumoral and control mucosa (P < 0.05). There was a significant positive correlation between IFP, PTLV area, tumor size and invasiveness. Our data show that IFP is increased in tongue cancer. Corresponding changes in PTLV area, invasiveness, tumor area and IFP suggest that the increased pressure is caused by defective lymph drainage and solid stress generated by tumor cells growing in a low compliant environment.

Tongue palate contact patterns of velar stops in normal adult English speakers

This paper provides a more detailed description of normal tongue palate contact patterns for the occlusion phase of velar stops than currently exists. The study used electropalatography (EPG) to record seven normally speaking adults' contact patterns of voiceless velar stops in nine VkV contexts. A variety of EPG indices measured: per cent complete closures across the palate; place of articulation; articulatory distance between /k/ and /t/; and amount of contact. Complete EPG closure occurred in the majority (81%) of tokens. Some speakers almost always had complete closures regardless of context, whereas other speakers produced them only with high front vowels. As expected, place of articulation and amount of contact were heavily influenced by vowel context. The most fronted and most contact occurred in /i/ contexts and the most retracted and least contact in /a/ contexts. There was considerable interspeaker variability on all measures, particularly in the precise location of velar placement and articulatory distance between alveolar and velar placement. The implications for diagnosing and treating abnormal velar articulations are discussed.

Lupeol Suppresses Cisplatin-Induced Nuclear Factor-κB Activation in Head and Neck Squamous Cell Carcinoma and Inhibits Local Invasion and Nodal Metastasis in an Orthotopic Nude Mouse Model

A poor prognosis in head and neck squamous cell carcinoma (HNSCC) patients is commonly associated with the presence of regional metastasis. Cisplatin-based chemotherapy concurrent with radiation therapy is commonly used in the treatment of locally advanced HNSCC. However, the result is dismal due to common acquisition of chemoresistance and radioresistance. Epidemiologic studies have shown the importance of dietary substances in the prevention of HNSCC. Here, we found that lupeol, a triterpene found in fruits and vegetables, selectively induced substantial HNSCC cell death but exhibited only a minimal effect on a normal tongue fibroblast cell line in vitro. Down-regulation of NF-kappaB was identified as the major mechanism of the anticancer properties of lupeol against HNSCC. Lupeol alone was not only found to suppress tumor growth but also to impair HNSCC cell invasion by reversal of the NF-kappaB-dependent epithelial-to-mesenchymal transition. Lupeol exerted a synergistic effect with cisplatin, resulting in chemosensitization of HNSCC cell lines with high NF-kappaB activity in vitro. In in vivo studies, using an orthotopic metastatic nude mouse model of oral tongue squamous cell carcinoma, lupeol at a dose of 2 mg/animal dramatically decreased tumor volume and suppressed local metastasis, which was more effective than cisplatin alone. Lupeol exerted a significant synergistic cytotoxic effect when combined with low-dose cisplatin without side effects. Our results suggest that lupeol may be an effective agent either alone or in combination for treatment of advanced tumors.

Poster 059: Daily Concurrent Chemoradiotherapy With Docetaxel (DOC) and Cisplatin (CDDP) Using a New Superselective Intra-Arterial Infusion (HFT method) via Superficial Temporal Artery for T3 and T4 Head and Neck Cancer

correlation between GnT-V expression and the mode of invasion; the GnT-V positive group had more cases with infiltrative pattern (22/26) than the GnT-V negative group did (5/14). Cervical lymph node metastasis was found in 17 (65.4%) of the 26 GnT-V positive cases, whereas in only 3 (21.4%) of the 14 cases that were negative for GnT-V. Furthermore, among the early clinical staging of SCC, the subsequent metastatic rate was significantly higher in GnT-V positive SCCs than in GnT-V negative ones. Almost all SCC cases showed increased GnT-V, Ets-1, and Ets-2 mRNA levels in comparison to normal tongue tissues by real-time RT-PCR. In contrast, GnT-V and Ets-2 expression was not enhanced in premalignant lesions. The levels of GnT-V mRNA were correlated with Ets-1 expression (rs 0.79; p 0.01). Conclusion: These findings suggest that GnT-V expression is regulated by Ets-1 in human tongue SCC and is closely correlated with tongue SCC progression and the malignant phenotype with increased invasive and metastatic abilities.

Congenital Glossocheilognathoschisis and Persistent Frenula Linguae in a Foal: A Case Report

This paper describes clinical findings and surgical treatment of a foal with multiple craniofacial defects (glossocheilognathoschisis; congenital midline cleft of the lower lip, mandible and tongue combined with bilateral persistent frenula linguae) admitted to the Surgery Clinics of Faculty of Veterinary Medicine, University of Kafkas, Turkey. A thorough clinical examination revealed cleft of the lower lip and mandible combined with glossoschisis (glossocheilognathoschisis) and bilateral extensive and restrictive membranous band (frenula) of tissue at the base of the tongue. Physical examination and radiography of the other organs and tissues of the foal were within normal limits. After sedation and general anesthesia, the persistent frenulas on the right and left parts of the tongue were transected, starting from normal tongue tissue, with the scissors. The tongue was completely freed after the transection of the remaining part of the frenulum, where right and left frenulas united, and the accompanying mucosal tissue on the mandibular symphysis was removed and underlying bone tissue was superficially curetted. Cerclage wire was placed under the mucosa of the mandible and was then passed among two drilled holes below the two incisors. These two pieces of wire were twisted together and anchored over the labial surface of the mandibular symphysis junction. The mandibular symphysis was then stabilized after cerclage wire tensing. A nasogastric tube was placed to permit enteral feeding. The foal was discharged 5 days after surgery. Telephone follow-up revealed that the foal had died 15 days after the surgical intervention.

Tongue Measures in Individuals With Normal and Impaired Swallowing

This investigation sought to add to the extant literature on measures of normal tongue function, to provide information on measures of tongue function in a group of individuals with oral phase dysphagia, and to provide a comparison of these 2 groups matched for age and gender. The Iowa Oral Performance Instrument was utilized to measure tongue function (strength and endurance) in a group of individuals with normal (N=200) and impaired (N=50) swallowing. The peak measure of 3 encouraged trials was recorded as participants' strength, and 50% of their peak was sustained as long as possible for endurance. Results for the control group supported previous investigations wherein greater tongue strength was found in males than in females and in the youngest versus oldest groups. The experimental group demonstrated a similar trend in strength for gender. When matched for age and gender, the experimental group demonstrated significantly lower strength. Significant differences were not revealed on measures of tongue endurance. We were able to extend the normative database on tongue function and document reduced tongue strength in a group of individuals with dysphagia. The findings provide evidence that in this group, tongue weakness coincided with signs of dysphagia, adding justification for tongue-strengthening protocols.

Long-Term Outcomes of Surgical Tongue Reduction in Beckwith???Wiedemann Syndrome

Surgical tongue reduction is often performed in Beckwith-Wiedemann syndrome when macroglossia results in abnormal tongue function or cosmesis; however, no published studies have examined the long-term outcomes of this procedure. Patients older than 18 years with Beckwith-Wiedemann syndrome who had previously undergone surgical tongue reduction at the Royal Children's Hospital in Melbourne underwent assessment of speech and tongue function, mobility, sensation, and cosmesis. These assessments were performed by questionnaire on 11 subjects and by formal medical and speech pathology review in four of these 11 subjects. Eleven patients aged 19 to 31 years completed responses by means of questionnaire. The most common self-reported abnormalities were continued disproportionate tongue bulk (91 percent), abnormal tongue appearance (82 percent), specific speech sound errors (73 percent), and a short tongue tip (55 percent). Formal assessments investigated speech, swallowing, taste, and tongue mobility in four quite different subjects. One of these four subjects had no detectable deficits in tongue function. All 11 patients were of normal intelligence and did not report significant difficulties in their day-to-day life that were attributable to their macroglossia or tongue reduction surgery. Pediatric patients with symptomatic macroglossia requiring surgical tongue reduction may not achieve complete normality in tongue function and appearance in adulthood. It is important that surgical tongue reduction addresses the global nature of the macroglossia and aims to retain a tapered tongue tip with length sufficient to permit normal tongue movements.

Laser confocal endomicroscopy as a novel technique for fluorescence diagnostic imaging of the oral cavity

Malignancies of the oral cavity are conventionally diagnosed by white light endoscopy, biopsy, and histopathology. However, it is often difficult to distinguish between benign and premalignant or early lesions. A laser confocal endomicroscope (LCE) offers noninvasive, in vivo surface and subsurface fluorescence imaging of tissue. We investigate the use of an LCE with a rigid probe for diagnostic imaging of the oral cavity. Fluorescein and 5-aminolevulinic acid (ALA) were used to carry out fluorescence imaging in vivo and on resected tissue samples of the oral cavity. In human subjects, ALA-induced protoporphyrin IX (PpIX) fluorescence images from the normal tongue were compared to images obtained from patients with squamous cell carcinoma (SCC) of the tongue. Using rat models, images from normal rat tongues were compared to those from carcinogen-induced models of SCC. Good structural images of the oral cavity were obtained using ALA and fluorescein, and morphological differences between normal and lesion tissue can be distinguished. The use of a pharmaceutical-grade solvent Pharmasolve enhanced the subsurface depth from which images can be obtained. Our initial results show that laser confocal fluorescence endomicroscopy has potential as a noninvasive optical imaging method for the diagnosis of oral cavity malignancies.

Normal adult speakers' tongue palate contact patterns for alveolar oral and nasal stops

This study compared tongue palate contact patterns for oral stops (/t/, /d/) with those for the nasal stop /n/ in order to provide normative data for diagnosing and treating individuals with speech disorders. Electropalatographic (EPG) data were recorded from 15 English speaking adults for word initial /t/, /d/ and /n/ in a high and a low vowel context. EPG frames were classified according to three criteria: (1) anterior constriction; (2) bilateral constriction; and (3) zero posterior central contact. Total amount of contact and variability were also measured. The results showed that almost all (99%) stops met Criteria 1 and 3, with fewer articulations (88% of /t/; 83% of /d/ and 55% of /n/) meeting Criterion 2. Although all stops had similar spatial patterns, /t/ and /d/ had more contact and were more likely to have bilateral constriction than /n/. There were no differences in variability between /t/, /d/ and /n/, however. The clinical implications of the results for the management of individuals with sp...

Effects of the Integrin-Linked Kinase Inhibitor QLT0267 on Squamous Cell Carcinoma of the Head and Neck

To study the expression of integrin-linked kinase (ILK) in human squamous cell carcinoma of the head and neck (SCCHN) tumor specimens and cell lines and the efficacy of the novel small molecule QLT0267. Immunohistochemical analysis of 17 SCCHN tumor tissue specimens and 3 normal tongue tissue specimens for ILK expression and in vitro analysis of the effectiveness of QLT0267 on SCCHN cells. Academic medical center. Expression levels of ILK in SCCHN tumor specimens and cell lines and the efficacy of QLT0267 in inhibiting cell growth and inducing apoptosis in SCCHN cell lines. Most SCCHN tumor specimens stained for ILK, whereas none of the 3 normal tongue tissue specimens stained for ILK. Integrin-linked kinase was expressed in all 6 SCCHN cell lines tested. In 4 pairs of normal and SCCHN tumor specimens, ILK expression and activity were higher in most tumor samples tested. A kinase assay showed that QLT0267 inhibited the ILK activity of 2 SCCHN cell lines (TU167 and MDA1986). Modified tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, DNA fragmentation ladder, and TUNEL (terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end()labeling) assays showed that QLT0267 inhibited cell growth and induced apoptosis in these 2 cell lines. A dose-dependent decrease in Akt phosphorylation was observed for these 2 cell lines on treatment with QLT0267. Integrin-linked kinase is overexpressed in SCCHN tumor specimens. Targeting ILK with the small-molecule ILK inhibitor QLT0267 inhibits cell growth and induces apoptosis in SCCHN cell lines by reducing ILK activity and Akt phosphorylation. Integrin-linked kinase may be an attractive target for molecular therapy with which to enhance treatment of SCCHN.

FREE RADIAL FOREARM FLAP AFTER PARTIAL GLOSSECTOMY FOR SQUAMOUS CELL CARCINOMA OF THE TONGUE

Squamous cell carcinoma of the tongue is a highly malignant conditionand results in high mortality and morbidity in patients despite its early detection (1). Early surgical interventions have been found to reduce mortality but in many reports, tongue reconstructions using live grafts have been found to reduce normal tongue function of speech, swallow and taste. In contrast, our report using free radial forearm flap (FRFF) to reconstruct the defect left over after a radical tongue resection in a38-year-old gentleman with oral cancer has shown promising results. This type of reconstruction has left the patient with a functional and cosmetically acceptable tongue with minimal alteration in recognizable speech.