Yasuro Yoshimura

Fetal Jaw Movement Affects Condylar Cartilage Development

Using a mouse exo utero system to examine the effects of fetal jaw movement on the development of condylar cartilage, we assessed the effects of restraint of the animals’ mouths from opening, by suture, at embryonic day (E)15.5. We hypothesized that pre-natal jaw movement is an important mechanical factor in endochondral bone formation of the mandibular condyle. Condylar cartilage was reduced in size, and the bone-cartilage margin was ill-defined in the sutured group at E18.5. Volume, total number of cells, and number of 5-bromo-2′-deoxyuridine-positive cells in the mesenchymal zone were lower in the sutured group than in the non-sutured group at E16.5 and E18.5. Hypertrophic chondrocytes were larger, whereas fewer apoptotic chondrocytes and osteoclasts were observed in the hypertrophic zone in the sutured group at E18.5. Analysis of our data revealed that restricted fetal TMJ movement influences the process of endochondral bone formation of condylar cartilage.

APOPTOSIS IN THE DEVELOPMENT OF THE TEMPOROMANDIBULAR JOINT

Abstract Apoptosis has been shown to be involved in remodeling of organs during development, and derangement of the apoptotic process may result in temporomandibular joint (TMJ) dysfunction or congenital malformation. To investigate the relationship between the development of the TMJ and apoptosis, rat fetuses at 17.5–20.5 days of gestation (E17.5–20.5, vaginal plug=E0) and rats at postnatal days 1, 2, 3, 5, and 10 (P1, 2, 3, 5, and 10) were examined by light (LM) and transmission electron microscopy (TEM) and electrophoretic analysis of DNA fragmentation. At E17.5 and 18.5, a few layers of slender mesenchymal cells which eventually develop into the TMJ disk were observed, although TEM or electrophoresis did not reveal apoptotic cells at these stages. At E19.5 and 20.5, all structures of the TMJ except the lower joint cavity could be distinguished, but at these stages apoptotic cells were not observed. In P1 condyles, apoptotic cells were observed by TEM both at the subsurface of the condyle and in the region at which the lateral pterygoid muscle attaches to the condyle. These apoptotic cells showed irregular chromatin condensation, convolution of the cell membrane, and fragmentation and disintegration of the cytoplasm. Electrophoretic analysis of the P1 condyle further confirmed DNA fragmentation. Apoptosis was not observed in all specimens at the P1 stage. It was confirmed in 8 out of 20 animals (10 out of 27 joints) by TEM and/or electrophoretic analysis. The shape of the upper portion of the condyle flattened progressively from E20.5 to P2. At this stage, the lower joint cavity was developing, as observed by LM. These findings suggest that the morphological changes of the mandibular condyle effected by apoptosis, together with development of the lower joint cavity, play important roles in the postnatal functional adaptation to external stimuli such as mechanical strain.

FAP-1 and NF-κB expressions in oral squamous cell carcinoma as potential markers for chemo-radio sensitivity and prognosis.

This study was designed to investigate the feasibility of using Fas-associated phosphatase-1 (FAP-1), nuclear factor kappa B (NF-κB) and p53 as markers for chemo-radio sensitivity in oral squamous cell carcinoma (OSCC). FAP-1 plays a role as an anti-apoptotic factor through Fas-dependent apoptosis after chemo-radiotherapy. NF-κB and p53 might be involved in modulation of FAP-1 expression. FAP-1, NF-κB and p53 expression were immunohistochemically examined using biopsy specimens in 50 OSCC patients treated with chemotherapy and/or radiotherapy. FAP-1 was expressed in 52%, NF-κB in 52% and p53 in 46% of patients. There was no significant difference in FAP-1, p53 or NF-κB expression according to the clinicopathological features. No correlation was found among FAP-1, p53 or NF-κB expression. FAP-1-positive cases showed a poorer survival rate than FAP-1-negative cases (P = 0.0409) and NF-κB-positive cases showed a poorer survival rate than NF-κB-negative cases (P = 0.0018). Multivariate analysis showed that FAP-1 expression, NF-κB expression, clinical stage and age were significant independent variables for survival (clinical stage: P = 0.0016; age: P = 0.0016; NF-κB: P = 0.0314; FAP-1: P = 0.0366). These results suggest that FAP-1 and NF-κB might play a role as chemo-radioresistant factor during chemo-radiotherapy, and FAP-1 and NF-κB expression in OSCC would be feasible markers for chemo-radio sensitivity and prognosis.

Fetal jaw movement affects development of articular disk in the temporomandibular joint

ABSTRACT  Previous studies suggest that jaw movement is an important factor in the development of cartilage in the temporomandibular joint during the prenatal and postnatal periods. In the present study, the effects of fetal jaw movement on the articular disk were studied in mice by restraining the opening movement of the mouth using the mouse exo utero development system. At embryonic day 18.5, the articular disk was reduced in size in the embryos whose maxilla and mandible were sutured (sutured group) and there were changes in the cellular morphology of the mesenchymal cells in the disk. The volume of the articular disk, the total number of cells and the number of 5‐bromo‐2′‐deoxyuridine‐positive cells in the articular disk were significantly lower in the sutured group than in the non‐sutured control group. Our data revealed that fetal jaw movement affects the development of the articular disk in the temporomandibular joint.

Myogenic Determination and Differentiation of the Mouse Palatal Muscle in Relation to the Developing Mandibular Nerve

The vertebrate palatal muscles are derived from the cranial paraxial mesoderm and start myogenesis by the expression of myogenic regulatory factors (MRFs). Predetermined myogenic cells migrate from the cranial paraxial mesoderm into the branchial arches, followed by myogenic differentiation. The objective of this study was to elucidate whether the determination, migration, and differentiation of myogenic cells during the myogenesis of the palatal muscles, particularly the tensor veli palatini (TVP), are related to the extending mandibular nerve in mouse embryos. By immunohistochemical staining at embryonic day (E) 9.5, MyoDl and myogenin have been expressed in the mandibular arch, into which the mandibular nerve had not yet extended. At E11.5, these myogenic cells encircled the extending mandibular nerve and were distributed from the distal and lateral to the trigeminal ganglion and into the mandibular arch to form the muscle plate, a girdle-like structure. By E12.5, these myogenic cells lost their girdle-like pattern, vacated the trunk area of the mandibular nerve, and were separated into several incompletely divided masses encircling the collateral branches of the mandibular nerve. The TVP started differentiation at E13.5 with the appearance of myofilaments and acetylcholinesterase (AchE), whereas the other palatal muscles began differentiation at E14.5. We defined the differentiation process of mouse palatal muscles into five stages based on the present findings. These results suggest that the determination and initial migration of the palatal myogenic cells into the mandibular arch occur before the mandibular nerve extends out of the trigeminal ganglion, whereas the myogenic cells migrating into the final sites of differentiation intimately relate to the extending nerve.

Reconstructing the pathway of the tensor veli palatini motor nerve during early mouse development

The motor axons innervating the tensor veli palatini (TVP) navigate a long distance from the trigeminal motor nucleus to their target. The pathway and time course of the TVP motor nerve during this navigation process remain poorly understood. The aim of this study was to elucidate the peripheral development of the TVP motor nerve, and to confirm when the morphological relationship is established between the nerve and target muscle progenitors. Using immunohistochemistry, carbocyanine fluorescent labeling, and computerized three-dimensional image-reconstruction methods, we demonstrated the development of the TVP motor nerve in mouse embryos. Further, the morphological relationship between the extending mandibular nerve and myogenic cells stained for MyoD1 was examined. The peripheral pathfinding of the TVP motor nerve was divided into three continuous stages: (1) the earliest trigeminal motor axons leave the metencephalon and enter the primordium of the trigeminal ganglion at E9.5, when MyoD1- positive cells can already be detected in the mesenchymal core of the mandibular arch; (2) converging with the sensory root, the trigeminal motor root excites the trigeminal ganglion and begins to approach the mandibular muscle precursors at E10.5; (3) collateral branching occurs at E12.5. By E13.5, a nerve branch splits from the mandibular nerve to innervate the TVP, which appears as an individual muscle mass. These results suggest that the early process of mandibular motor nerve extension is correlated with the trigeminal ganglion cells, whereas when growing out of the ganglion, the mandibular nerve has a close relationship with target myogenic cells throughout the later process of pathway finding.

Oral Squamous Cell Carcinoma in Patients with Pulmonary Metastasis but no Locoregional Recurrences

Abstract Objective : This retrospective study aimed to clarify the clinicopathologicalfeatures of patients with oral squamous cell carcinoma that revealed pulmonary metastasis alone on first recognition of relapse and who died as a result of this pulmonary metastasis. Patients and Methods : This study comprised 6 patients with pulmonary and/or distant metastasis, but with no locoregional recurrences throughout their lives. These patients were selected from a base population of 104 oral squamous cell carcinoma patients. Results : Among the oral squamous cell carcinoma patients studied, 5.8% of patients (6/104) had previously experienced both primary and neck diseases. Histopathologically, the primary lesions were all well-differentiated squamous cell carcinomas. Pulmonary metastasis was most commonly observed in tongue cancer patients (67%; 4/6). Biopsy of the pulmonary metastatic lesion in 1 patient revealed moderately differentiated squamous cell carcinoma. Radical neck dissection with preservation of the internal jugular vein was done on 4 of the 6 patients. While no patient underwent radical salvage surgeries for pulmonary metastasis, all patients underwent palliative treatments, such as chemotherapy and radiotherapy, either alone or in combination. The study findings show that complete radical neck dissection was more effective than functional neck dissection. Conclusion : Six oral squamous cell carcinoma patients with pulmonary metastasis, but no locoregional recurrences, were analysed from the clinicopathological perspective, and a possible cause for the metastasis related to neck lymphatic and blood systems was identified.

Angio-oedema Caused by Angiotensin-converting Enzyme Inhibitor Therapy

Abstract This report is of an 83-year-old woman with a history of hypertension who had recurrent swelling of the tongue, oral floor, and lower lip. Angiotensin-converting enzyme inhibitor therapy was strongly suspected to be the cause of the swelling. Discontinuation of therapy resulted in disappearance of the swelling without recurrence.