Palatable Form Research Articles

Interferon Regulatory Factor 6 (IRF6) Gene Variants and the Risk of Isolated Cleft Lip or Palate

Cleft lip or palate (or the two in combination) is a common birth defect that results from a mixture of genetic and environmental factors. We searched for a specific genetic factor contributing to this complex trait by examining large numbers of affected patients and families and evaluating a specific candidate gene. We identified the gene that encodes interferon regulatory factor 6 (IRF6) as a candidate gene on the basis of its involvement in an autosomal dominant form of cleft lip and palate, Van der Woude's syndrome. A single-nucleotide polymorphism in this gene results in either a valine or an isoleucine at amino acid position 274 (V274I). We carried out transmission-disequilibrium testing for V274I in 8003 individual subjects in 1968 families derived from 10 populations with ancestry in Asia, Europe, and South America, haplotype and linkage analyses, and case-control analyses, and determined the risk of cleft lip or palate that is associated with genetic variation in IRF6. Strong evidence of overtransmission of the valine (V) allele was found in the entire population data set (P<10(-9)); moreover, the results for some individual populations from South America and Asia were highly significant. Variation at IRF6 was responsible for 12 percent of the genetic contribution to cleft lip or palate and tripled the risk of recurrence in families that had already had one affected child. DNA-sequence variants associated with IRF6 are major contributors to cleft lip, with or without cleft palate. The contribution of variants in single genes to cleft lip or palate is an important consideration in genetic counseling.

Three-dimensional dental arch and palatal form changes after extraction and nonextraction treatment. Part 3. Transversal and sagittal palatal form

The purpose of this study was to investigate changes in the palatal form in patients treated with and without premolar extractions. Records collected at pretreatment, at bracket removal, at the end of retention, and 5 years out of retention were examined. Stone casts were mounted on an articulator with an anatomic face-bow and a central wax record, and measurements were made with a 3-dimensional digitizer. The hypothesis that orthodontic treatment with premolar extractions changes the palatal form was verified.

Three-dimensional dental arch and palatal form changes after extraction and nonextraction treatment. Part 2. Palatal volume and height

The purpose of this study was to investigate the changes in palatal volume and palatal height in patients treated with and without premolar extractions. Records were collected at pretreatment, at bracket removal, at the end of retention, and 5 years out of retention. Stone casts were mounted in a SAM 2 articulator with an anatomic face-bow and a central wax record, and measurements were made with a 3-dimensional digitizer. The hypothesis, that orthodontic treatment with premolar extractions changes the palatal form, was verified. Increases in palatal volume and height were demonstrated in the nonextraction group. The extraction group showed a decrease in palatal volume but could compensate for some loss by an increase in volume in the anterior segment.

Three-dimensional dental arch and palatal form changes after extraction and nonextraction treatment. Part 1. Arch length and area

The purpose of this study was to investigate changes in arch length, arch area, and irregularity index in patients treated with and without premolar extractions. Records collected at pretreatment, at bracket removal, at the end of retention, and 5 years out of retention were examined. Stone casts were mounted on an articulator with an anatomic face-bow and a central wax record, and measurements were made with a 3-dimensional digitizer. In general, the maxillary arch exhibited less relapse tendency than did the mandibular arch for both patient groups. In general, the extraction group showed the same relapse tendency as the nonextraction group.

Quantitative and qualitative phenotypes for thought disorder: Implications for linkage studies of schizophrenia

The palate is considered typical of the structures in which schizophrenia-related minor physical anomalies may occur. In this study, we aimed to compare the dimensions and form of palate in patients with schizophrenia with nonpsychiatric controls in a blinded manner. Dental stone casts of 127 patients with schizophrenia and 127 controls were prepared from impressions of the maxillary dental arch. Palate dimensions were measured on the stone casts using a digital caliper and palatometer. Palate length did not differ significantly between the groups, but there was a significant difference in palate width and depth, which were significantly higher in the schizophrenia group. As a result of using multivariate analysis for assessing independent risk factors affecting patients with schizophrenia, furrowed palate shape, palate width, and ellipsoid maxillary dental arch shape were found to be significant. This study also revealed that patients with schizophrenia demonstrate certain gender-related predilections in the differences of palate parameters compared to same-sex controls. As the palate develops in conjunction with both the face and brain, our study findings can significantly contribute to the assumption that there might be structural abnormalities of the palate that could represent specific markers of embryological dysmorphogenesis underlying schizophrenia.

"The Bitter Residue of Death": Jorge Semprun and the Aesthetics of Holocaust Memory

IN HIS FASCINATING HOLOCAUST NOVEL Le grand voyage (1963), Jorge Semprun juxtaposes the pleasure of reading the childhood memories offered in Proust's A la recherche du temps perdu with the painful and deferred memory of his arrival at the Buchenwald concentration camp. By turning to Proust's layered representations of childhood desires and fears, Semprun illustrates how both his memory of Proust's peaceful (if neurotic) novel and his postwar consciousness have been colored by his experience of the camps. Semprun's treatment of Proust -both through the voice of his narrator, Gerard, in the scene of incarceration itself, and through the literary and stylistic appropriations of Proust that pepper his text-prompts us to examine how aesthetic pleasure can offer an important survival mechanism. Indeed, by analyzing how Semprun's use of Proust helps him survive Buchenwald, the first section of this article demonstrates how aesthetic pleasure affords a mode of coping with traumatic memory. In the second section I focus on Semprun's rewriting of the past through his use of Ilse Koch, the infamous Nazi commandant suspected of perpetrating sexual crimes against the inmates of Buchenwald, and Sigrid, the young woman who acts as Koch's counterbalance in the narrative. By redrawing Koch in the much more palatable form of Sigrid, Semprun manipulates aesthetic pleasure notjust to survive but to transform a painful past into a more tolerable present. Taken together, these two sections demonstrate how Semprun seeks comfort in aesthetic pleasure in order 1) to survive the Holocaust; 2) to come to terms with his painful memories of it, and 3) to rewrite his experiences of the Holocaust as a literary reflection on the brutality of history. Semprun, a Spaniard from a Catholic family, was born in 1923 and emigrated to France in 1938 after Franco became dictator. Adopting the pseudonym Gerard Sorel, he joined the French Resistance in 1941 and in 1943 was arrested, tortured, and deported to Buchenwald. Semprun's bourgeois family, deeply rooted in Spanish politics and culture, prepared him well for the appreciation of the shimmering density of Proust's prose. His grandfather, Antonio Maura, whom Semprun describes as an authoritarian but reformist man' was the Prime Minis-

Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes.

Interferon regulatory factor 6 (IRF6) belongs to a family of nine transcription factors that share a highly conserved helix-turn-helix DNA-binding domain and a less conserved protein-binding domain. Most IRFs regulate the expression of interferon-alpha and -beta after viral infection, but the function of IRF6 is unknown. The gene encoding IRF6 is located in the critical region for the Van der Woude syndrome (VWS; OMIM 119300) locus at chromosome 1q32-q41 (refs 2,3). The disorder is an autosomal dominant form of cleft lip and palate with lip pits, and is the most common syndromic form of cleft lip or palate. Popliteal pterygium syndrome (PPS; OMIM 119500) is a disorder with a similar orofacial phenotype that also includes skin and genital anomalies. Phenotypic overlap and linkage data suggest that these two disorders are allelic. We found a nonsense mutation in IRF6 in the affected twin of a pair of monozygotic twins who were discordant for VWS. Subsequently, we identified mutations in IRF6 in 45 additional unrelated families affected with VWS and distinct mutations in 13 families affected with PPS. Expression analyses showed high levels of Irf6 mRNA along the medial edge of the fusing palate, tooth buds, hair follicles, genitalia and skin. Our observations demonstrate that haploinsufficiency of IRF6 disrupts orofacial development and are consistent with dominant-negative mutations disturbing development of the skin and genitalia.

Relationship Between Primary Palatal Form and Maxillofacial Growth in Japanese Children With Unilateral Cleft Lip and Palate: Infancy to Adolescence

Abstract Objective: The purpose of this retrospective study was to evaluate the relationship between the severity of maxillary defects and maxillofacial growth from infancy to adolescence in children with complete unilateral cleft lip and palate (UCLP). Subjects: Thirty-one Japanese children with UCLP who had received cheiloplasty, palatoplasty, and orthodontic treatments at the Kyushu University Dental Hospital were selected. Materials and Methods: A three-dimensional laser scanner was used to measure maxillary dental casts taken at cheiloplasty. Surface areas and volumes of the palatal tissue were calculated. Lateral cephalographs that were taken both at cheiloplasty and 15 years of age or over (average age 16.5 years) were traced and digitized. Angular and linear measurements were calculated from the x, y-coordinates. Using correlation analyses, defects in the palatal tissue were compared with maxillofacial morphology both at cheiloplasty and in adolescence or maxillofacial growth during that time span...

Relationship between primary palatal form and maxillofacial growth in Japanese children with unilateral cleft lip and palate: infancy to adolescence.

The purpose of this retrospective study was to evaluate the relationship between the severity of maxillary defects and maxillofacial growth from infancy to adolescence in children with complete unilateral cleft lip and palate (UCLP). Thirty-one Japanese children with UCLP who had received cheiloplasty, palatoplasty, and orthodontic treatments at the Kyushu University Dental Hospital were selected. A three-dimensional laser scanner was used to measure maxillary dental casts taken at cheiloplasty. Surface areas and volumes of the palatal tissue were calculated. Lateral cephalographs that were taken both at cheiloplasty and 15 years of age or over (average age 16.5 years) were traced and digitized. Angular and linear measurements were calculated from the x, y-coordinates. Using correlation analyses, defects in the palatal tissue were compared with maxillofacial morphology both at cheiloplasty and in adolescence or maxillofacial growth during that time span. (1) The surface areas or volumes of the palatal tissue were significantly correlated with the following maxillofacial measurements at infancy and adolescence: Or-depth; A-depth; PNS-height; ANS-height; N-Ba; S-N; S-Ba; N to P.P.; A'-Ptm'; Cd-Pog; Cd-Gn; Cd-G; and the N-S-Ba, S-N-A, and A-N-B angles. (2) They were also significantly correlated with the following maxillofacial growth measures from infancy to adolescence: A-depth, S-Ba, and the N-S-Ba and S-N-A angles. Only the N-S-Ba angle showed a negative correlation. The patient who had more palatal tissue at cheiloplasty showed better maxillofacial growth.

Development of an edible subunit vaccine in corn against enterotoxigenic strains of escherichia coli

Advances in the development of subunit vaccines and in the production of foreign proteins in plants together offer the prospect of stable and inexpensive vaccine delivery systems. Various bacterial and viral proteins stably produced in plants have been shown to elicit immune responses in feeding trials. We have extended this approach by using Zea mays as the plant production system. Corn has several advantages as a vaccine delivery vehicle, most notably established technologies to generate transgenic plants, to optimize traits through breeding and to process the seed into a palatable form. Here we report on the production in corn seed of the GM1 receptor binding (B) subunit of the heat-labile toxin (Lt) from enterotoxigenic strains of Escherichia coli. Versions of the Lt-B gene were synthesized to give optimum codon usage for corn and to target the protein to either the cell surface or the cytoplasm. These synthetic genes were fused to a strong promoter and transformed into corn. Lt-B was highly expressed in corn seed at up to 1.8% of the total soluble protein and this was further increased approximately five-fold through plant breeding. As in E. coli. Lt-B produced in corn forms a functional pentamer that can bind to the GM1 receptor. Furthermore, Lt-B pentamer stored in corn seed is much more resistant to heat than is the pure protein, allowing the transgenic corn to be readily processed into an edible form. This work demonstrates the potential of using products derived from transgenic corn seed as delivery vehicles for subunit vaccines.

Three-dimensional hard tissue palatal size and shape in human adolescents and adults.

Hard tissue palatal dimensions and shape in 29 boys and 32 girls (mean age 14 years) and 30 men and 35 women (mean age 20 years), all with a complete permanent dentition including the second molars, and free from respiratory problems, were analyzed. Palatal landmarks were digitized with a computerized 3D instrument, and their coordinates were used to derive a mathematical model of palatal form. Palatal shape (size-independent) was assessed by a four-order polynomial in the sagittal and frontal plane projections. Palatal dimensions in the frontal and sagittal planes were computed, and compared between ages and sexes by two-way factorial analyses of variance. The effect of age on palatal shape was different in the two sexes: while in females the curves in both the frontal and sagittal planes were practically superimposed, in males the youngest subjects had somewhat 'lower' curves than the oldest subjects. Sex had a significant (p<0.05) effect for all variables. Age was significant only for palatal slope in the sagittal plane (p<0.01), and for raphe inclination in the horizontal plane (p<0.05). For all variables but palatal length in the sagittal plane, a significant (p<0.01) sexxage interaction was found: while in males all linear variables were larger in adults than in adolescents, the reverse was found in females. Overall, while in adolescent females palatal form appeared to have already attained adult characteristics, in males some modifications between adolescence and young adulthood were measured. These modifications should be taken into consideration as a possible factor of relapse after orthodontic treatment.

Speech after repair of isolated cleft palate and cleft lip and palate

The speech of children with isolated cleft palate (CP) repaired by one surgeon has been compared with the speech of children with some form of unilateral cleft lip and palate (CLP) repaired by the same surgeon. All palate repairs included an intravelar veloplasty. We identified 57 children (5--12 years old) with cleft palates repaired in infancy, of which three patients with other medical problems were excluded. Of the 54 patients, 44 (81%) attended for review (27 CP, 17 CLP). Video recordings were analysed by two speech and language therapists, using the Cleft Audit Protocol for Speech. The CP patients had no evidence of permanent fistulas. Final speech outcomes were similar for CP and CLP patients. Intelligibility was normal in 10 (37%) CP and nine (53%) CLP patients. Mild consistent hypernasality was present in five (18.5%) CP and four (23.5%) CLP patients. No patients had moderate or severe hypernasality or nasal emission. Mild consistent hyponasality was present in five (18.5%) CP and five (29%) CLP patients. Moderate consistent hyponasality was present in one (4%) CP patient. Dysphonia was present in eight (30%) CP and seven (41%) CLP patients. Cleft-type characteristics were noted in 11 (41%) CP and nine (53%) CLP patients. No CLP patients but 10 (37%) CP patients had required a pharyngoplasty (P=0.004, Fisher's exact test). Possible reasons for this (age, cleft type, surgeon and surgery) are discussed.

Accommodating the Apocalypse: an examination of the relationships between the economics of salvation and the enclos architecture of the Breton enclos

The distancing from notions of the apocalypse will be examined through an investigation of the architectural ensemble of the Breton enclos, or parish close. The enclos is an arrangement of religious architecture found in towns and villages all over Brittany. It is an ensemble that developed over a period of about two hundred years, and although the formal attributes of an enclos vary, its constituent parts are constant. These parts were added gradually: what is suggested here is that each architectural addition marked a further attempt to accommodate the apocalyptic or malefic dimension of the divine, in order to allow the 'good' dimension of religion to be manipulated by society. Moving from the Middle Ages to the Renaissance, the elusion of the 'fundamental question' (Bataille) - the question of the inter-relationship between individual and world - increased: the violence of the apocalypse was tempered and re-presented in a palatable form. Effectively, this violence was denied and covered over, both individually and communally, and the consequences of this shift in relationships can be observed in the enclos (as elsewhere). The economics of this situation (the economics of salvation) will be examined, along side the role of architecture, straddling both real and symbolic expenditures, which changed to suit the demands of a changing society.

Negative dimension of schizotypy associated with early developmental instability in normal adolescents

The palate is considered typical of the structures in which schizophrenia-related minor physical anomalies may occur. In this study, we aimed to compare the dimensions and form of palate in patients with schizophrenia with nonpsychiatric controls in a blinded manner. Dental stone casts of 127 patients with schizophrenia and 127 controls were prepared from impressions of the maxillary dental arch. Palate dimensions were measured on the stone casts using a digital caliper and palatometer. Palate length did not differ significantly between the groups, but there was a significant difference in palate width and depth, which were significantly higher in the schizophrenia group. As a result of using multivariate analysis for assessing independent risk factors affecting patients with schizophrenia, furrowed palate shape, palate width, and ellipsoid maxillary dental arch shape were found to be significant. This study also revealed that patients with schizophrenia demonstrate certain gender-related predilections in the differences of palate parameters compared to same-sex controls. As the palate develops in conjunction with both the face and brain, our study findings can significantly contribute to the assumption that there might be structural abnormalities of the palate that could represent specific markers of embryological dysmorphogenesis underlying schizophrenia.

チタン製補綴装置に関する基礎研究 ＣＡＤ／ＣＡＭ法の表面粗さが適合性に及ぼす影響

Owing to its high corrosion resistance and good biocompatibility, titanium has become keenly watched as a metallic material for dental application in recent years. Because of its material property, however, titanium has not yet become sufficiently prevalent in clinical practice. In this study, therefore, a possible dental application of titanium for prostheses was investigated. Namely, maxillary major connectors of different palatal forms were prepared by a CAD/CAM (Computer Aided Design/Computer Aided Manufacturing) system, to examine the influence of the manufacturing process on adaptability and surface roughness, with the following results.As to adaptability, the CAD/CAM system produced fewer gaps in bilateral residual ridges and in the center of the palate, but it produced recognizable gaps in alveolar areas. In addition, it was revealed that good adaptability is obtained with shallower palates, and the gap in alveolar areas is increased with deeper palates. As for surface roughness, stratified and linear traces were observed during the finishing process. Further, the surface roughness varied at each determination site depending on the positional change of the end mill.

Isolated cleft palate in mice with a targeted mutation of the LIM homeobox gene lhx8.

Formation of the mammalian secondary palate is a highly regulated and complex process whose impairment often results in cleft palate, a common birth defect in both humans and animals. Loss-of-function analysis has linked a growing number of genes to this process. Here we report that Lhx8, a recently identified LIM homeobox gene, is expressed in the mesenchyme of the mouse palatal structures throughout their development. To test the function of Lhx8 in vivo, we generated a mutant mouse with a targeted deletion of the Lhx8 gene. Our analysis of the mutant animals revealed a crucial role for Lhx8 in palatogenesis. In Lhx8 homozygous mutant embryos, the bilateral primordial palatal shelves formed and elevated normally, but they often failed to make contact and to fuse properly, resulting in a cleft secondary palate. Because development of other craniofacial structures appeared normal, the impaired palatal formation in Lhx8-mutant mice was most likely caused by an intrinsic primary defect in the mesenchyme of the palatal shelves. The cleft palate phenotype observed in Lhx8-mutant mice suggests that Lhx8 is a candidate gene for the isolated nonsyndromic form of cleft palate in humans.

前方部口蓋形態が発音運動に及ぼす影響について 第２報 舌運動，下顎運動との関連

Anterior palatal form affects the speech and is one of the important factors for the fabrication of upper denture. Air pressure in the incisor region was measured to examine the influence of the anterior palatal form on speech in the previous report. In the present study, the palatogram and jaw position were measured during the utterance of Japanese/sa/, /si/, /ta/, and /ci/. Subjects used and the experimental denture were the same in the report.The results were as follows:1. Palatogram was influenced by alterations of anterior palatal form. The thicker the anterior palatal counter, the posterior construction for fricative or plosive in the palatogram positioned during the utterances of /sal, /si/ and /ci/. The influence of the anterior palatal form was not observed during the utterance of /ta/.2. The alterations of anterior palatal affected significantly the mandibular position. No general tendency was observed regardless of subjects.The tongue movements primarily compensated alterations of anterior palatal form. This experiment confirmed that adequate anterior palatal form, i.e., width and location of S-ridge and the location, is important for the /s/sound production.

Dietary omega-3 and omega-9 fatty acids uniquely enhance allograft survival in cyclosporine-treated and donor-specific transfusion-treated rats.

Both laboratory and clinical studies have shown that dietary lipids may affect immunologic responses. This study was conducted to compare different classes of long-chain unsaturated fatty acids for their effect on allograft survival in animals receiving a donor-specific transfusion and a short course of low-dose cyclosporine (CsA). Heterotopic ACI strain cardiac allografts were transplanted to Lewis strain rat recipients given diets with different lipid composition. In experiment 1, animals received CsA for 14 days and different diets were enriched with lipids with high concentrations of omega-3, omega-6, or omega-9 fatty acids. In experiment 2, animals received CsA for only 8 days and different diets were enriched with corn oil (omega-6), canola oil (omega-3 and omega-9), fish oil (omega-3) or a mixture of sunflower oil and fish oil (omega-3 and omega-9). In experiment 1, animals receiving the diet with 30% sunflower oil had the best allograft survival (200+/-42 days vs. 53+/-8 days for regular chow plus donor-specific transfusion and CsA, P<0.05). In experiment 2, diets containing canola oil (a mixture of omega-3 and omega-9 fatty acids) were associated with the best survival (P=0.0011 vs. regular chow). Dietary omega-3 and omega-9 fatty acids both enhanced cardiac allograft survival in a stringent rat strain combination. Canola oil is a convenient oil for administering both alpha-linoleic acid (omega-3) and oleic acid (omega-9) in a palatable form for human consumption. Further investigation of the potential usefulness of lipids in transplant therapy is warranted.

Mechanism of Action of Nonsteroidal Anti-inflammatory Drugs

Salicylic acid and salicylates, obtained from natural sources, have long been used as medicaments. Salicylic acid was chemically synthesized in 1860 and was used as an antiseptic, an antipyretic, and an antirheumatic. Almost 40 years later, aspirin was developed as a more palatable form of salicylate. Soon after, other drugs having similar actions to aspirin were discovered, and the group was termed the “aspirin-like drugs” (also now termed the nonsteroidal anti-inflammatory drugs [NSAIDs]). Twenty-five years ago, it was proposed that the mechanism of action of NSAIDs was through their inhibition of prostaglandin biosynthesis. Since then, there has been general acceptance of the concept that these drugs work by inhibition of the enzyme cyclo-oxygenase (COX), which we now know to have at least two distinct isoforms: the constitutive isoform, COX-1, and the inducible isoform, COX-2. COX-1 has clear physiologic functions. Its activation leads, for instance, to the production of prostacyclin, which when released by the endothelium is antithrombogenic and when released by the gastric mucosa is cytoprotective. COX-2, discovered 6 years ago, is induced by inflammatory stimuli and cytokines in migratory and other cells. It is therefore attractive to suggest that the anti-inflammatory actions of NSAIDs are due to inhibition of COX-2, whereas the unwanted side-effects, such as irritation of the stomach lining, are due to inhibition of COX-1. Drugs that have the highest COX-2 activity and a more favorable COX-2 : COX-1 activity ratio will have a potent anti-inflammatory activity with fewer side-effects than drugs with a less favorable COX-2 : COX-1 activity ratio. The identification of selective inhibitors of COX-2 will therefore lead to advances in therapy.

Physical mapping and candidate gene analysis of the Van der Woude locus on Ch1q32. † 624

Van der Woude Syndrome (VWS) is the most common form of syndromic cleft lip and palate and accounts for about 2% of all cleft lip and palate cases. Distinguishing characteristics include cleft lip with or with out cleft palate, isolated cleft palate, bilateral lip pits, hypodontia, normal intelligence, and an autosomal dominat mode of transmission with a high degree of penetrance.