Hidetaka Miyazaki

Regulation of cellular functions by nucleoside diphosphate kinases in mammals.

The role of nucleoside diphosphate (NDP) kinases in cell growth, differentiation, and tumormetastasis in relation to signal transduction was investigated. The essential role of NDP kinasein cell growth was validated by coupling between reduced NDP kinase levels, induced byantisense oligonucleotides, and the suppression of proliferative activity of a cultured cell line.In addition, because NDP kinase levels are often enhanced with development and differentiation,as has been demonstrated in postmitotic cells and tissues, such as the heart and brain, wefurther examined this possibility using the bone tissue (osteoblasts) and a cultured cell linePC12D. The enhanced NDP kinase accumulation was demonstrated in the matured osteoblastsin vivo and in vitro by immunohistochemistry. In PC12D cells neurite outgrowth took placein NDP kinase β-transfected clones without differentiation inducers, which was accompaniedby prolongation of doubling time. Neurite outgrowth, triggered by nerve growth factor and acyclic AMP analog, was down-regulated upon forced expression of inactive mutant NDPkinase by virtue of a dominant negative effect. NDP kinase α-transfected rat mammaryadenocarcinoma cells (MTLn3) and nm23-H2-transfected human oral squamous cell carcinomacells (LMF4) manifested reduced metastatic potential and were associated with an alteredsensitivity to environmental factors, such as motility and growth factors. NDP kinase α,compared to NDP kinase β, was involved in a wide variety of the cellular phenomena examined.Taken together, NDP kinase isoforms appear to elicit both their own respective and commoneffects. They may have an ability to lead cells to both proliferative and differentiated statesby modulating responsiveness to environmental factors, but their fate seems to depend on theirsurrounding milieu.

Acetylsalicylic acid reduces ischemia-induced proliferation of dentate cells in gerbils.

Transient global ischemia causes neurogenesis in the dentate gyrus of adult rodents. Ischemic insults to rodents also induce cyclooxygenase-2 (COX-2), an isoform of cyclooxygenases (COXs) and a rate-limiting enzyme for prostanoid synthesis. In the present experiments, adult Mongolian gerbils were chronically treated with acetylsalicylic acid (ASA), a non-selective COX inhibitor, and the proliferation of cells in the dentate gyrus was examined under ischemia. It was proved that BrdU-labeled cells in the dentate gyrus were significantly reduced in number following ASA treatment after 10 min global ischemia. The result strongly suggests that COX, probably COX-2, and prostanoids play an important role in the proliferation of neural cells after ischemia in gerbils.

Anatomy of deep lateral and medial orbital walls: implications in orbital decompression surgery.

Abstract Background: Isolated deep lateral and combined medial orbital wall decompressions (balanced decompression) are well accepted for treatment of disfiguring proptosis and compressive optic neuropathy in patients with Graves’ orbitopathy. However, cerebrospinal fluid leakage and/or optic nerve injury occasionally occur during these operations. Purpose: To describe the anatomy of the deep lateral and medial orbital walls and its surgical implications in orbital decompression. Methods: We reviewed literature on the anatomy of the deep lateral and medical orbital walls. In addition, we performed cadaver dissection and computed tomographics studies to illustrate the anatomy. Results: We provided an anatomical overview and elucidated the detailed surgical anatomy of the posterior and superior borders of the deep lateral orbital wall, the posterior and accessory ethmoidal foramina, and the frontoethmoidal suture. Conclusions: The anatomy of the deep lateral and medical orbital walls presented here will warrant safe and confident performance of orbital decompression surgery.

Ultrasound-guided intralesional laser treatment of venous malformation in the oral cavity

An ultrasound-guided intralesional photocoagulation (ILP) technique using a laser is described for treatment of deep venous malformations in the oral cavity. ILP is basically a blind operation and has a risk of unintended destruction of surrounding normal tissue, therefore the authors now routinely use guidance by ultrasonography using a mini-probe to improve the safety and reliability of ILP. This approach enables safe fibre insertion, appropriate laser irradiation, and intraoperative assessment of coagulation. The use of this technique is described in 8 patients. The authors conclude that ultrasound-guided ILP with a laser is a promising technique for less-invasive treatment of a vascular malformation in the oral cavity.

Comparison of bony nasolacrimal canal narrowing with or without primary acquired nasolacrimal duct obstruction in a Japanese population.

Purpose: To compare the minimum diameter of the nasolacrimal canal and its location between patients with or without primary acquired nasolacrimal duct obstruction (NLDO) in a Japanese population. Methods: One hundred one patients with unilateral primary acquired NLDO (Group A, 101 affected sides; Group B, 101 unaffected sides) and 50 non-NLDO patients (Group C, 100 sides) were included. Anteroposterior and transverse diameters were measured at the canal entrance and the shortest point using contiguous 1-mm axial computed tomographic images. Canal shapes were classified into 2 types: the “funnel” type (a canal with both minimum diameters at the canal entrance) and the “hourglass” type (a canal with at least one minimum diameter in the canal). The distance from the entrance to the part with the shortest diameter was measured on sides with the hourglass type. Results: The funnel type was found more frequently in Groups A and B than in Group C (p < 0.050), although a difference was not found between Groups A and B (p = 0.778). The distance of the transverse diameter was significantly shorter in Groups A and B than Group C (p < 0.050), although no significant difference was found in this distance between Groups A and B (p = 1.000). There were no significant differences between the groups for each value except for the above mentioned (p > 0.050). Conclusions: Primary acquired NLDO patients exhibited the funnel type more frequently or there was a shorter distance from the entrance to the part with the shortest diameter than non-NLDO patients, which may enhance the risk of primary acquired NLDO.

Treatment strategies for large oral venous malformations using intralesional laser photocoagulation

We report two treatment strategies using intralesional laser photocoagulation (ILP) for large venous malformations (VMs) in the oral cavity. ILP is considered to be an effective technique for massive vascular lesion. The satisfactory results could have been obtained, since we started ILP for the treatment of large VMs. Recently, to improve the safety, reliability, and effectiveness of the treatment, we developed modifications of ILP that include a combination of ILP and transmucosal irradiation; and compartmentalization and serial step irradiation. In the former, ILP is performed for a deep layer lesion and transmucosal irradiation with multiple spots fashioned using a single pulse is added for the superficial layer in the same session, to increase the efficacy of regression. In the latter, the lesion is divided by virtual compartment and each area will be sequentially treated by ILP. The irradiated area and total energy in a session should be limited to avoid severe reactions and excessive thermal destruction of surrounding tissue. All treatment outcomes by each technique were satisfactory without serious complications, such as deep ulcer formation, bleeding, or severe swelling developing obstruction. Both treatment strategies improve the safety, reliability, and effectiveness of ILP and make the method less traumatic for patients.

Evaluation of bone height of the free fibula flap in mandible reconstruction.

Background:Use of a vascularized free fibula flap has become a preferred method of mandible reconstruction after oncologic surgical ablation. Despite its many advantages, the low vertical height of the graft is a potential drawback and severe long-term atrophy of fibular bones may cause stress fracture and is disadvantageous for osseointegrated dental implants and facial contours. Therefore, it is important to investigate the degree of resorption based on the fibular height and the factors related to resorption over time. The influence of aspects of the intraoperative surgical procedure, such as preservation of a nutrient artery from the peroneal artery to the fibula bone marrow and the number of segmental osteotomies, has not been examined previously. Therefore, the purpose of this study was to examine the change in fibular height and the factors influencing resorption, including those associated with the surgical procedure. Patients and Methods:A retrospective analysis was performed in 19 patients who underwent free vascularized fibular mandibular reconstruction for oncologic surgical defects without radiotherapy. Postoperative Panorex examinations were used to evaluate fibular height, and 7 factors with a potential influence on long-term fibular height were evaluated: age, gender, length of the mandible defect, number of segmental osteotomies, preservation of a direct nutrient artery from the peroneal artery to the fibula bone marrow, length of follow-up, and delayed placement of osseointegrated dental implants. Results:Fibular bone height decreased in 13 patients (68%), was unchanged in 2 (11%), and increased in 4 (21%). Segmental osteotomies and female gender were significant factors promoting fibular bone resorption (P < 0.001 and P < 0.001, respectively), and preservation of a nutrient artery to the bone marrow, male gender, and delayed placement of osseointegrated dental implants were significant factors inhibiting bone resorption (P < 0.01, P < 0.001, and P < 0.05, respectively). Age, length of follow-up period, and length of the mandibular defect showed no significant relationship with bone resorption (P = 0.77, P = 0.78, and P = 0.105, respectively). Conclusion:The results of this study showed that fibular height in mandibular reconstruction can be maintained by preservation of a direct nutrient artery to bone marrow, avoidance of osteotomies, and delayed placement of osseointegrated dental implants, all of which inhibit fibular bone resorption.

Treatment of microstomia caused by burn with a nasolabial flap--an ingenious approach for tugging and fixation of the oral commissure.

AbstractThe objectives of surgical treatment for microstomia due to cicatricial contracture after burn are to obtain sufficient oral aperture, while maintaining sphincter function of the orbicularis oris muscle, and to secure favorable function for eating and conversation in addition to good oral health.The lips of the mouth have a free border, and the oral aperture, which has been enlarged by the operation, tends to be reduced, because of the actions of the orbicularis oris muscle. When the orbicularis oris muscle is resected, putting a priority on sufficient oral aperture and prevention of redevelopment of contracture, the function of the sphincter is often damaged. With the exception of those cases with deep extensive burn that damages a wide area of orbicularis oris muscle, the muscle should be preserved as expeditiously as is practical. In such cases, however, preventive measures for the redevelopment of microstomia should be established. As a postoperative adjuvant therapy, the usefulness of splint therapy has been suggested in many reports. However, a splint should be used for a long period after the surgery, and in some cases, pain is observed with therapy. When a splint is not used for an appropriate period, microstomia may redevelop. It would be ideal to take preventive measures against the redevelopment of contracture during surgery.We provided treatment with some ingenious attempts for the nasolabial flap to a patient with microstomia caused by cicatricial contracture after burn. We obtained favorable results with no postoperative use of a splint.

Movement of Internal Canalicular Orifice in Association With Blinking: Direct Observation After Dacryocystorhinostomy

PURPOSE To examine movement of the internal canalicular orifice with blinking and lacrimal drainage under endonasal endoscopic observation after dacryocystorhinostomy. DESIGN Observational anatomic study. METHODS Twenty internal canalicular orifices (right 9, left 11) from 15 patients (age range: 44-77 years) who underwent endoscopic endonasal dacryocystorhinostomy were prospectively examined. The patients sat on a chair with the chin projected slightly upward while digital images were taken. After examining the movement of the internal canalicular orifice with blinking, the patients eye was stained with fluorescein dye, and diffusion from the orifice was examined with blinking. RESULTS The internal canalicular orifice closed during eyelid opening, although always incompletely. In eyelid closing, the orifice opened, and was pulled laterally without folds. All 20 internal canalicular orifices formed a diverticulum. Three specimens illustrated the upper and lower canalicular ends emptying into the diverticulum. The closing of these canalicular ends was always incomplete. Movement of the internal canalicular orifice was slight during normal blinking, but forced blinking resulted in more movement. Movement of the lacrimal sac wall was slight. During the first few seconds without blinking, no fluorescein dye flowed from the orifice. After several blinks, fluorescein dye flowed out slowly from the orifice, and increased in volume with more blinking. The fluorescein dye traveled inferiorly by gravity. A forced blinking was related to more dye inflow. CONCLUSIONS The internal canalicular orifice incompletely closed during eyelid opening, but this orifice largely opened during eyelid closing, with a slow gravitational inflow of lacrimal fluid.

Amelioration of improper differentiation of somatostatin-positive interneurons by triiodothyronine in a growth-retarded hypothyroid mouse strain.

Thyroid hormone (TH) plays an important role in brain development, and TH deficiency during pregnancy or early postnatal periods leads to neurological disorders such as cretinism. Hypothyroidism reduces the number of parvalbumin (PV)-positive interneurons in the neocortex and hippocampus. Here we used a mouse strain (growth-retarded; grt) that shows growth retardation and hypothyroidism to examine whether somatostatin (Sst)-positive interneurons that are generated from the same pool of neural progenitor cells as PV-positive cells are also altered by TH deficiency. The number of PV-positive interneurons was significantly decreased in the neocortex and hippocampus of grt mice as compared with normal control mice. In contrast to the decrease in the number of PV neurons, the number of Sst-positive interneurons in grt mice was increased in the stratum oriens of the hippocampus and the hilus of the dentate gyrus, although their number was unchanged in the neocortex. These changes were reversed by triiodothyronine administration from postnatal day (PD) 0 to 20. TH supplementation that was initiated after PD21 did not, however, affect the number of PV- or Sst-positive cells. These results suggest that during the first three postnatal weeks, TH may be critical for the generation of subpopulations of interneurons.