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Analysis of cell proliferation kinetics during the secondary palate development in quail.

A study was undertaken to analyze the spatio-temporal pattern of mesenchymal cell proliferation in the developing palate of quail. Quail embryos were grown in shell-less culture. The developing palates were labelled with 3H-thymidine between culture days 2-6 (which corresponded in vivo incubation days 5-9), and processed for light microscopic autoradiography. Percent labelled mesenchymal cells were determined. The data showed that, as in mammals, a high rate of random cell proliferation in mesenchyme was a major component of early palate development in quail. As the palate morphogenesis advanced, the rate of cell proliferation declined. Segmental analysis, however, indicated that, in contrast to mammals, the mesenchymal cell proliferation rates continually changed in various regions of quail palate during morphogenesis. It was suggested that the spatio-temporal changes in the distribution of dividing cells may reflect differences in the timings of cell cycles between various segments, thus resulting in a heterogeneous population of cells in the developing palate of quail. Further, the differences in the segmental pattern of cell proliferation between birds and mammals may form the basis for differences in the morphogenesis of their palates.

Animals↗

The occurrence of hypodontia in patients with cleft lip and/or palate.

The frequency of hypodontia (but for the third molar) was studied in a series of 600 patients with cleft lip and/or palate. The series was subdivided into three groups according to the type of facial cleft. As compared to the general normal population the occurrence of hypodontia was markedly increased in patients with clefts. The highest percentage of hypodontia was recorded in patients with cleft lip and palate, the lowest frequency was present in cleft lip only. In cleft lip and in cleft lip and palate girls were affected significantly more frequently than boys. The occurrence of hypodontia in the lower and in the upper jaw differed according to the type of cleft. The upper jaw was affected more often in cleft lip and in cleft lip and palate, the mandible was involved more frequently in isolated cleft palate. The dental bud of the upper lateral incisor was affected most commonly in cleft lip and in cleft lip and palate, while the second lower premolar was most frequently absent in isolated cleft palate.

Adolescent↗

The distribution of epidermal growth factor binding sites in the developing mouse palate.

The distribution of epidermal growth factor (EGF) receptors in the developing mouse palate was mapped using 125I-EGF labeling of paired palate organ cultures. 125I-EGF binding sites were localized throughout the palate mesenchyme except in a region immediately adjacent to the midline seam. The EGF receptor was detected in all palatal epithelia at the beginning of culture, but as seam formation and subsequent degeneration took place it was down-regulated in the medial edge epithelia. Using submerged culture the mechanism of this down-regulation was investigated by treating with various growth factors such as EGF, basic fibroblast growth factor (bFGF), insulin-like growth factor-II (IGF-II) and transforming growth factors alpha and beta (TGF-alpha, TGF-beta). Conventional Trowell organ culture was not used because it was observed that the Millipore filter blocked growth factor uptake. All three TGF-beta isoforms accelerated palate fusion and TGF-beta 1 reduced 125I-EGF binding throughout the palate, suggesting a potential level of regulation during palatogenesis. Contrary to previous reports, EGF treatment in the absence of serum prevented palatal shelf fusion, and also down-regulated subsequent 125I-EGF binding.

Animals↗

Deficient and delayed primary palatal fusion and mesenchymal bridge formation in cleft lip-liable strains of mice.

During mammalian primary palate formation, the facial prominences enlarge around the nasal pit, fuse and then merge to give rise to the tissue of the upper lip and premaxillary region. The mechanisms involved in successful primary palate formation and how they are affected in the cleft lip genotype remain poorly understood. The purpose of this study was to compare morphometrically internal development and growth of the primary palate in five different strains of mice. Two of the strains, BALB/cByJ, and C57BL/6J, have normal primary palate development, and three of the strains, A/J, A/WySn, and CL/Fr, have stable frequencies of cleft lip associated with genotype. In the present study, frequencies of 4, 23, and 24%, respectively, were observed on day 13. For palatal growth analysis, embryos were collected on days 10 and 11, staged by number of tail somites (TS), and the heads were photographed and serially sectioned for measurement of primary palate components. The heights of the epithelial seam and the mesenchyme bridge between the facial prominences were measured on serial sections and areas of contact were calculated. The position or depth of the maxillary prominence was determined from the number of frontal sections from its tip to the rostral end of the nasal fin. Analysis of measurements showed that in cleft lip strains enlargement of the epithelial seam and replacement of epithelia by a mesenchymal bridge were both delayed relative to somite stages. Measurements from day 11 embryos with complete failure of contact were excluded from the growth analyses. The mesenchymal bridge formed at 12--13 TS in noncleft strains, 14 TS in the A/J strains with higher cleft lip frequency, and 15--17 TS in A/WySn and CL/Fr strains with higher cleft lip frequency. Forward growth of the maxillary prominence was highly correlated with the primary palate measurements and mesenchymal bridge formation in all strains. In both cleft and noncleft strains, the primitive choanae open at 18--20 TS and the medial nasal region narrows with advancing embryonic development. As a result, cleft lip-liable strains have a narrower window in development in which a robust mesenchymal bridge must form, thus increasing the liability to cleft lip.

Animals↗

The activation of MAP kinase during vertical palatal shelf development in hamster.

Mitogen-activated protein (MAP) kinase has been implicated in signal transduction pathways that regulate cell cycle progression during the proliferation of eukaryotic cells. Previous studies have shown that a rapid burst of cell proliferation is a major event of the development of mammalian palatal shelves in a vertical direction. The present study analyzed the involvement of MAP kinase during the vertical development of the secondary palate in hamster. Palates were dissected at various times between days 10:00 and 12:00 of gestation, homogenized, centrifuged and fractionated on a Mono Q column by fast protein liquid chromatography. The fractions were assayed for phosphotransferase activity toward myelin basic protein, and also toward a synthetic peptide APRTPGGRR (S5), which was more specifically utilized by MAP kinase. The data showed that MAP kinase activity increased during the initial phase, i.e., between days 10:00 and 11:12, and then decreased during the latter half of vertical palate development, i.e., between days 11:12, and 12:00 of gestation. Western blotting studies, using antibodies raised against the subdomain I ATP binding sequence (GEGA), subdomain III (ERK1-III), and the C-terminus (ERK1-CT) of MAP kinases, demonstrated the presence of both the 42-kDa and 44-kDa MAP kinase isoforms between days 10:12 and 12:12 of gestation. A monoclonal antibody (4G10), which detects phosphotyrosine, demonstrated phosphorylation of both the 42-kDa and 44-kDa isoforms. The amount of protein remained constant during vertical palatal shelf development indicating that the differential activity of MAP kinase was most likely due to post-translational modification (i.e., phosphorylation). There was a good correlation between the temporal expression of MAP kinase activity and the rates of cell proliferation in the developing vertical palate suggesting a possible involvement of MAP kinase in regulation of cell proliferation during secondary palate development.

Animals↗

[Rhinomanometry of nasal patency in children with complete and secondary cleft palate].

The authors evaluated the morphology of nasal cavities and nasal patency using active anterior rhinomanometry in 94 children (mean age 10.2 years). Complete bilateral primary and secondary cleft palate was confirmed in 28 children (29.8%), unilateral in 66 children (70.2%), where complete right-side primary and secondary cleft palate was observed in 19 children (28.8%) and complete left side primary and secondary cleft palate in 47 children (71.2%). Measurement methods were used according to Rhinomanometric Standardization Committee. Significant relationship between nasal patency examined using active anterior rhinomanometry and complete cleft palate was confirmed. High, symmetric resistance of nasal airflow was observed in children with complete bilateral primary and secondary cleft palate. Children with complete unilateral primary and secondary cleft palate were found to have asymmetric nasal airflow, higher on the cleft side. In this group mean nasal airflow resistance was higher on non-cleft side than in population without defects, whereas on clefted side it is approximal to population without defects. In children with complete bilateral primary and secondary cleft palate mean resistances distribution was symmetric but higher than in population without defects.

Adolescent↗

[Genetic variation of MSX1 has a sexual dimorphism in non syndromic cleft palate in the Chilean population].

BACKGROUND: Recent studies in mice have demonstrated that the Msx-1 homebox gene is implicated in cleft palate. Thus, it has been suggested that its human homologue, MSX1 (HOX-7), located in chromosome 4 could be involved in the etiology of non syndromic cleft lip palate. AIM: To study the linkage between non syndromic cleft palate and variations of MSX1 gene. PATIENTS AND METHODS: Seventy three patients with non syndromic cleft lip palate (34 simplex and 37 multiplex), 127 unaffected relatives of the cases (61 relatives of simplex cases and 66 relatives of multiplex cases) and 77 controls were studied. DNA was extracted from leukocytes and the intragenic microsatellite sequence was amplified by PCR. RESULTS: A polymorphism of four alleles was observed, 1 (175 bp), 2 (173 bp), 3 (171 bp) and 4 (169 bp). Alleles 2 and 4 showed a joint variation in males with multiplex cleft lip palate and in their respective unaffected male relatives, that was significant when compared with male controls. Instead, the joint variation of alleles 1 and 4 of unaffected female relatives had significant differences with female controls. Females with multiplex cleft lip palate differed from female controls only in allele 1. CONCLUSIONS: These results support the hypothesis of a genetic heterogeneity in the etiology of non syndromic cleft lip palate.

Alleles↗

Levator palati and palatal dimples: their anatomy, relationship and clinical significance.

To achieve the best results in cleft palate repair it is necessary to be aware of the normal anatomy. In a series of cadaver dissections, the levator palati muscle was found to occupy the intermediate 40% of the length of the soft palate. This normal distribution should be the aim at cleft palate repair. Observation of the oral surface of the palate during production of the sound "Ah" reveals palatal dimpling. This has been observed in many normal and cleft palate subjects. The dimpling has been reproduced in cadavers by levator palati traction and been found on dissection and serial histological section to correspond to the levator insertion.

Adult↗

Epignathus combined with cleft palate, lobulated tongue, and lingual hamartoma: report of a case.

A case of epignathus combined with cleft palate, lobulated tongue, and lingual hamartoma is reported. A newborn female presented with a large skin-covered mass arising from the palate, cleft palate, and lobulated tongue with a soybean-sized lingual lesion. The palatal and lingual masses were removed on the 9th day after birth. A cystic lesion was also found on the nasal septum after removal of the palatal mass; this lesion was resected at its base. Glossoplasty was performed after excision of the lingual lesion. Histologically, the palatal mass was diagnosed as epignathus. The cystic lesion was suspected to be meningothelial tissues on the basis of hematoxylin-eosin (HE) and immunohistochemical staining: Vimentin and epithelial membrane antigen were positive, and factor VIII was negative. The mass of the tongue dorsum was diagnosed as hamartoma. No recurrence of epignathus or evidence of meningocele have been observed after 5 years of follow up.

Abnormalities, Multiple↗

Visual training and correction of articulation disorders by use of dynamic palatography: serial observation in a case of cleft palate.

The dynamic palatograph is an electrical apparatus that generates a visual display of constantly changing palatolingual contact as a function of time, using an artificial palatal plate with affixed electrodes. This paper describes a technique of speech therapy incorporating dynamic palatography for a cleft palate patient. The patient, a 6-year-old Japanese girl with a repaired unilateral cleft lip and palate, had been judged to demonstrate articulation disorders involving contact of the tongue with the hard palate or alveolus following surgical improvement of velopharyngeal function. Prior to therapy the tongue tended to contact the hard palate more posteriorly than normal. After therapy with the dynamic palatograph, palatolingual contact was normal in comparison with average speakers. Our findings suggest that the facility of constant visual indication of tongue posture to the clinician and patient during corrective speech therapy using dynamic palatography may expedite results with cleft palate patients in the speech clinic when implemented in a carefully structured treatment plan.

Articulation Disorders↗

Free flap closure in complex congenital and acquired defects of the palate.

Extensive palatal defects cause substantial morbidity, including nasal regurgitation, poor oral hygiene, loose-fitting obturators, and difficulty with speech. Microvascular techniques allow the surgeon to repair these complex defects with a one-stage reconstruction, in contrast to possible multistage local or regional flap reconstruction. In this retrospective review, the authors present their 5-year experience with free flap coverage of extensive palatal defects. From 1993 to 1998, 6 patients underwent free flap coverage of large palatal defects. The etiology of the large palatal defects included trauma (N = 1), neoplasm (N = 4), and a recurrent congenital cleft palatal fistula (N = 1). Three patients underwent osteocutaneous radial forearm flaps and 1 patient underwent a fasciocutaneous radial forearm flap. The remaining 2 patients underwent rectus abdominis muscle flaps. The ipsilateral facial artery and vein were used as the recipient vessels in all patients. There were no intraoperative complications (surgical or anesthetic). Postoperatively, 2 patients had surgical evacuation of small flap hematomas. One patient underwent revision of the fasciocutaneous flap. All flaps survived. In our experience, the benefits of free flap reconstruction of complex palatal fistulas seem to outweigh the risks of the operation, with reliable long-term results.

Adolescent↗

Nerve supply to the soft palate muscles with special reference to the distribution of the lesser palatine nerve.

OBJECTIVE: Descriptions of the innervation of the soft palate muscles in previous studies have varied according to the author. In the present study, distribution of the lesser palatine nerve, through which motor fibers of the facial nerve are considered to reach soft palate muscles, and that of the pharyngeal plexus in the soft palate were investigated in order to reexamine the innervation of the soft palate muscles according to anatomical evidence. RESULTS: Observations suggested that the levator veli palatini and palatopharyngeus were doubly innervated by branches of the lesser palatine nerve and pharyngeal plexus, and that the musculus uvulae was innervated by only the lesser palatine nerve. CONCLUSION: The soft palate is considered to be located in the border region between the areas of distribution of the lesser palatine nerve and pharyngeal plexus. This may be why controversies exist in previous studies about the innervation of the soft palate muscles.

Cadaver↗

Infant orthopedics has no effect on maxillary arch dimensions in the deciduous dentition of children with complete unilateral cleft lip and palate (Dutchcleft).

OBJECTIVE: Evaluation of the effect of infant orthopedics on maxillary arch dimensions in the deciduous dentition in patients with unilateral cleft lip and palate. DESIGN: Prospective two-arm randomized controlled clinical trial with three participating cleft palate centers. SETTING: Cleft palate centers of the Radboud University Nijmegen Medical Center, Academic Center of Dentistry Amsterdam, and University Medical Center Rotterdam, the Netherlands. PATIENTS: Children with complete unilateral cleft lip and palate (n = 54) were included. INTERVENTIONS: Patients were randomly divided into two groups. Half of the patients (IO+) had a presurgical orthopedic plate until surgical closure of the soft palate at the age of 52 weeks; the other half (IO-) did not undergo presurgical orthopedics. MEAN OUTCOME MEASURES: Maxillary arch dimensions were assessed on dental casts at 4 and 6 years of age with measurements for arch width, arch depth, arch length, arch form, and the vertical position of the lesser segment. Contact and collapse were assessed also. RESULTS: There were no clinically significant differences found between IO+ and IO- for any of the variables. CONCLUSIONS: Infant orthopedics had no observable effect on the maxillary arch dimensions or on the contact and collapse scores in the deciduous dentition at the ages of 4 and 6 years. Considering the Dutchcleft results to date, there is no need to perform infant orthopedics for unilateral cleft lip and palate patients.

Alveolar Process↗

Patterns of abnormal myogenesis in human cleft palates.

To test the hypothesis that soft palate muscles are abnormal in cleft palate, we compared soft palate morphogenesis in fetuses with cleft palate (n = 4) to age-matched (n = 3) and nonmatched (n = 1) control specimens. The morphologic status of all soft palate and masticatory structures were classified into one of six stages based on the level of histogenesis. At 54 mm crown-rump length (CRL), the levator veli palatini (L), palatopharyngeus (PP), and palatoglossus (PG) in cleft subjects demonstrated mesenchymal condensation into myoblastic fields, lagging behind the control specimens (97 mm CRL), which displayed definitive fields of myoblasts and myotube formation. In the 175 mm and 225 mm cleft and the 170 mm and 192 mm control specimens, muscular morphology was similar and had reached its postnatal appearance for the tensor veli palatini (175 m only) and L, PP, PG (225 mm only). Muscle fiber directions were, however, disoriented and disorganized, especially close to the medial epithelial edge of the cleft. The levator veli palatini, could not be distinguished as a discrete muscle in the cleft specimens, and what we believed to be the PP and PG seemed "normal" at the level of light microscopy, but malpositioned in a superior direction. This preliminary study demonstrates for the first time that early myogenesis in cleft palates differs from normal.

Case-Control Studies↗

Residual clefts in the hard palate: correlation between cleft size and speech.

OBJECTIVE: This study was conducted to evaluate the relationship between size of residual clefts in the hard palate and speech. SUBJECTS: Fifteen 7-year-old children born with complete cleft lip and palate were investigated. METHODS: All of the children were treated according to a surgical regimen involving early soft palate repair and delayed hard palate closure. Measures were taken of the area, length, and maximal width of the residual cleft in the hard palate about a year before its closure and correlated with a perceptual judgment of several speech variables. RESULTS: Significant positive correlations were obtained between the size of the cleft and two variables: weak pressure consonants and hypernasality. Nasal escape was very common among the patients, and almost half the children had retracted palatal or velar articulation of dental stop consonants. Neither of these two variables correlated with the size of the residual cleft. CONCLUSION: Perceived oral pressure and, perhaps, resonance seem to be related to size of the opening of the residual cleft, whereas audible nasal escape and articulatory compensations are not, at least not the latter once established.

Articulation Disorders↗

Comparison between palatal configurations in UCLP infants with and without a Hotz plate until four years of age.

OBJECTIVE: To evaluate the efficacy of presurgical orthopedic treatment three dimensionally, we previously developed a novel measuring system and described the efficacy of the treatment until 18 months of age. The aim of this study was to compare palatal configuration in complete unilateral cleft lip and palate (UCLP) infants fitted with a Hotz plate to those without it until four years of age using the same measuring system. PATIENTS: Twenty complete UCLP infants were divided into two groups. A Hotz plate was used with 12 patients who first visited our clinic from January 1990 to March 1992 and was not used with an additional eight patients who first visited from April 1992 to July 1993. MAIN OUTCOME MEASURES: Palatal casts taken from birth until four years of age were measured three dimensionally and were compared between the two groups. RESULTS AND CONCLUSIONS: The width of the palate was larger in the group with a Hotz plate than in the group without it at four years of age. No difference was observed between the anteroposterior distance of the palate in the two groups at four years of age. Similarly, the alveolar arch form did not differ between the two groups. The degree of curvature of the palatal surface was smaller in the group with a Hotz plate than in the group without it. These data were similar to data obtained at 18 months of age.

Child, Preschool↗

Response to changes in food palatability in tufted capuchin monkeys, Cebus apella.

Palatability of plant foods may change over time in relation to the concentration of toxic secondary metabolites. We investigated the behavioural response of capuchin monkeys to this type of change and assessed the influence of social conditions. Twenty-seven tufted capuchin monkeys were presented in Social or Individual conditions with a familiar palatable food (phase 1), with the same familiar food to which pepper had been added, making it unpalatable (phase 2), and with the same familiar palatable food of phase 1 (phase 3). Five sessions were carried out in each phase. The capuchins adapted quickly to the change in food palatability by reducing (phase 2) and increasing (phase 3) the amounts of food eaten. The unpalatable food prompted an increase in olfactory exploration and in food processing. The experimental conditions (Social versus Individual) did not influence consumption, or any of the other behaviours. In addition, capuchins were more often near subjects with food in phases 2 and 3 in which palatability changed than in phase 1. These findings show that capuchins readily adjust to changes in flavour and palatability of a familiar food and that sudden unpalatability has no carry-over effects. Therefore, capuchins behave differently towards a familiar food whose palatability has changed than they do towards novel foods. Copyright 2000 The Association for the Study of Animal Behaviour.

Journal Article↗

Type of test-meal affects palatability and eating style in humans.

Effects of palatability on the meal as a whole or the microstructure of meals are often inconsistent or even divergent. Is this attributable to the nature of the test meals? In the present study, three frequently used types of meals were offered to seven normal-weight women: conventional courses, sandwiches and semi-liquid items. Each meal was composed of four items of either high or medium-low palatability. The type of meal appeared to be the major factor determining the level of palatability and of every dependent variable. Energy intake was influenced by palatability level in conventional meals only. The microstructure of meals was responsive to palatability only in sandwich and semi-liquid meals. The data suggest that palatability effects are detectable beyond a minimum threshold. In addition, characteristics of eating style appeared to be very stable within individuals across meal types and palatability conditions.

Adult↗