Masahito Sugimura

Enhancement of the in vivo osteogenic potential of marrow/hydroxyapatite composites by bovine bone morphogenetic protein

A composite of marrow mesenchymal stem cells and porous hydroxyapatite (HA) has in vivo osteogenic potential. To investigate factors enhancing the osteogenic potential of marrow/HA composites, we prepared a bone morphogenetic protein (BMP) fraction from the 4M guanidine extract of bovine bone by heparin-sepharose affinity chromatography. Marrow/HA composites or composites containing marrow mesenchymal stem cells, BMP, and HA (marrow/BMP/HA composites) were implanted subcutaneously in 7-week-old male Fischer rats. BMP/HA composites and HA alone were also implanted. The implants were harvested after 2, 4, or 8 weeks and were prepared for histological and biochemical studies. Histological examination showed obvious de novo bone formation together with active osteoblasts at 2 weeks, as well as more extensive bone formation at 4 and 8 weeks in many pores of the marrow/BMP/HA composites. The marrow/HA composites did not induce bone formation at 2 weeks, but there was moderate bone formation at 4 weeks. At 2 weeks, only marrow/BMP/HA composites resulted in intensive osteogenic activity, judging from alkaline phosphatase and osteocalcin expression at both the protein and gene levels. These results indicate that the combination of marrow mesenchymal stem cells, porous HA, and BMP synergistically enhances osteogenic potential, and may provide a rational basis for their clinical application, although further in vivo experiment is needed.

Effect of Food Size on the Movement of the Mandibular First Molars and Condyles during Deliberate Unilateral Mastication in Humans

To date, the effect of food size on the movement of the mandibular first molars and condyles during chewing has not been fully examined due to methodological problems. The purpose of the present study was to examine the previously unknown effect of food size on masticatory jaw movement. Using a face bow, light-emitting diodes, and optical cameras, we recorded, in 16 young adults with good occlusion, mandibular movement for the first 10 strokes during the unilateral chewing of similarly shaped hard gummy jellies weighing 5 g and 10 g, respectively. The chewing cycle time for the 10-g jelly was significantly longer than that for the 5-g jelly. The jaw-closing and -opening maximum velocities, gapes at the maximum velocities, and maximum gape were significantly faster and larger when 10-g gummy jellies were chewed, compared with results with 5-g jellies, at the mandibular first molar on the chewing side and the condyle on the non-chewing side. With the exception of the velocity, similar tendencies were observed at the molar on the non-chewing side. However, such significant differences were not detected at the condyle on the chewing side. The mandibular first molar on the chewing side was that most affected by food size, and the mean value of the maximum gape coincided approximately with the height of each jelly. These results suggest that humans chew hard coherent food such that the mandibular teeth that come into contact with the food open to a height equivalent to that of the food bolus, and that the changes in movement of the other parts of the mandible are minimized, ensuring efficient mastication.

Risk factors for the postoperative local recurrence of tongue carcinoma

Clinical and histologic studies on the risk factors for the postoperative local recurrence of tongue carcinoma were analyzed in 51 patients. Postoperative local recurrence occurred in 12 (23.5%), with almost all developing within the first 12 months after surgery. A comparison of patients with and without recurrence indicated that the risk factors for recurrence were 1) endophytic tumor growth, 2) grade 4 pattern of histologic invasion, and 3) tumor within 5 mm of the surgical margin (especially the deep margin). All T1 tumors were less than 5 mm deep, indicating that it is reasonable for partial glossectomy to be performed in patients with T1 carcinoma. However, for T2 through T4 carcinoma it seems that more extensive surgery should be performed because of the variability in depth of tumor invasion. The 5-year survival rate of the patients with recurrence was 45% and that of patients without recurrence was 73.7% (P < .01). The overall prognosis of tongue carcinoma should improve when surgeons take a more prudent attitude to the treatment of patients with these risk factors.

Preoperative concurrent chemoradiotherapy plus radical surgery for advanced squamous cell carcinoma of the oral cavity: an analysis of long-term results.

Locoregionally advanced squamous cell carcinomas of the head and neck continue to be a major clinical problem. We demonstrated in 1996 that preoperative concurrent cisplatin- or carboplatin-based chemotherapy and radiotherapy plus radical surgery in advanced oral cancer had minimal toxicity, had high clinical tumor response rates, was well tolerated and produced impressive complete response rates and a high 5-year survival rate. The purpose of the present study was the long-term follow-up of this treatment regimen for advanced oral carcinoma. Forty-eight patients with squamous cell carcinoma of the oral cavity (including soft palate) were treated preoperatively with cisplatin- or carboplatin-based chemotherapy in combination with simultaneous irradiation to a target volume of 40 Gy, and 2-6 weeks later underwent curative surgery. All patients with advanced Stage II (n=7), Stage III (n=22) and Stage IV (n=19) were treated and followed for an average of 7.2 years (range: 61-144 months). The overall actuarial survival of all patients was 81.3% at 5 years and also at 10 years. Progression-free survival at both 5 and 10 years was 84.8% for all patients, and 85.7% for Stage II, 90.0% for Stage III, and 78.9% for Stage IV patients. Progression-free survival rates according to the histopathologic regression grade of primary tumor following preoperative chemoradiotherapy at 10 years were 40. 0% for Grade IIa, 88.9% for Grade IIb, 100% for Grade III, and 87.5% for Grade IV. Patients who achieved good responses histopathologically (Grades IIb, III, IV) had superior survival rates in comparison to patients with extensive residual tumor (Grade IIa) in surgically resected specimens (p=0.0012). A better histologic regression grade was also associated with a higher survival rate even in the long-term analysis. This treatment regimen for advanced oral cancer produced high clinical and pathologic complete response and survival rates with an acceptable acute toxicity profile and lack of late therapeutic complications. The long-term follow-up showed gratifying results even for advanced oral cancers without a substantial increase in distant metastasis and second primary malignancy.

Immunohistochemical Detection of p53 Oncoprotein in Human Oral Squamous Cell Carcinomas and Leukoplakias: Comparison with Proliferating Cell Nuclear Antigen Staining and Correlation with Clinicopathological Findings

Forty oral squamous cell carcinomas and 20 leukoplakias were examined for expression of p53 oncoprotein using an immunohistochemical technique with BP53-12 monoclonal antibody. Positive staining was found in 21/40 (52%) of the carcinomas and 2/20 (10%) of the leukoplakias. Furthermore, comparison of p53 expression with binding of PC10 monoclonal antibody to proliferating cell nuclear antigen (PCNA) and degree of histological malignancy in terms of invasion and histological differentiation of carcinomas demonstrated a positive correlation in both cases.

Eruption speed and rate of angulation change of a cyst-associated mandibular second premolar after marsupialization of a dentigerous cyst

The purpose of this study was to investigate the eruption speed and rate of angulation change of a cyst-associated mandibular second premolar after marsupialization of a dentigerous cyst in preadolescents. Premolars on the cyst and noncyst sides and size of the cyst were retrospectively examined with a total of 42 pairs of normalized panoramic radiographs in 20 patients who underwent neither extraction nor orthodontic traction of the cyst-associated mandibular second premolar after marsupialization. Sixteen premolars at the intraosseous eruption stage in a total of 9 preadolescents without cysts were also examined. The eruption speed and rate of angulation change of the cyst-associated mandibular second premolar were significantly faster than those of the premolars without cysts, and significantly correlated with the diminishing rate of the cyst size, which rapidly decreased for the first 3 months after marsupialization. In addition, the eruption speed of the cyst-associated mandibular second premolar correlated with that of the premolar on the noncyst side, and the rate of angulation change inversely correlated with the level of root formation. The results suggest that a cyst-associated permanent tooth erupts more rapidly regardless of the level of root formation and size and type of the cyst, and the abnormally tilted tooth axis improves more rapidly for the first three months after marsupialization of a dentigerous cyst in preadolescents.

Epstein-Barr virus in the proliferative diseases of squamous epithelium in the oral cavity**

The presence of Epstein-Barr virus was analyzed in 79 cases of oral epithelial proliferative diseases by polymerase chain reaction, in situ hybridization for Epstein-Barr virus-deoxyribonucleic acid and Epstein-Barr virus-encoded small messenger ribonucleic acid and immunohistochemistry for Epstein-Barr virus latent membrane protein. These lesions were histologically categorized as invasive squamous cell carcinoma (n = 36), carcinoma in situ (n = 10), verrucous carcinoma (n = 4), leukoplakia (n = 19), and papilloma (n = 10). Epstein-Barr virus genomes were detected in 19 squamous cell carcinoma (52.8%), four carcinoma in situ (40%), and one leukoplakia (5.3%); none of the verrucous carcinoma or papilloma cases were positive with polymerase chain reaction. By deoxyribonucleic acid in situ hybridization, positive signals were observed in the nuclei of cancer cells in 10 cases, in infiltrating lymphocytes in three, and both in one case. In patients with carcinoma in situ, only a single case was positive. In one case of leukoplakia positive signals were found in upper and middle layer squamous cells. The results by Epstein-Barr virus-encoded small messenger ribonucleic acid in situ hybridization revealed the same distribution as that by deoxyribonucleic acid in situ hybridization. Latent membrane protein was expressed only in the epithelial cells of leukoplakia but not in cases with squamous cell carcinoma and carcinoma in situ. These findings suggest that Epstein-Barr virus infection of oral squamous epithelium may be carcinogenic; alternatively, the virus may merely exist in epithelial cells of squamous cell carcinoma, carcinoma in situ, and leukoplakia as a passenger.

The Effects of Preanesthetic Oral Clonidine on Total Requirement of Propofol for General Anesthesia

STUDY OBJECTIVE To investigate the effects of preanesthetic oral clonidine on total propofol requirement for uniform minor surgery (breast conservative surgery: breast cancer removal with axillary lymph node dissection), and to compare the action of clonidine with that of preanesthetic oral diazepam, a commonly used benzodiazepine. DESIGN Randomized double-blinded study. SETTING Operating room ASA physical status I and II room and recovery room of the cancer center. PATIENTS 80 breast cancer patients scheduled for surgery. INTERVENTIONS Patients were randomized to one of four treatment groups (placebo, clonidine 75 micrograms, or 150 micrograms of clonidine, or 10 mg of diazepam were orally administered 60 min before induction of anesthesia); n = 20 per group. After evaluating the sedation and anxiety levels of patients using a visual analog scale, anesthesia was induced with propofol (1.5 mg/kg), and maintained with oxygen (O2): nitrous oxide (N2O) (30:70) with a continuous infusion of propofol. The propofol infusion was started at 10 mg/kg/h for 10 minutes, then decreased to 8 mg/kg/h, and 6 mg/kg/h thereafter, and the rate of infusion was adjusted to obtain adequate anesthesia (maintaining hemodynamic parameters within 20% of that prior to premedication). Fentanyl 0.2 mg (each 0.1 mg was given for intubation and axillary lymph node dissection, respectively) was administered. MEASUREMENTS AND MAIN RESULTS Preanesthetic oral clonidine (150 micrograms) and diazepam (10 mg) induced anxiolysis without sedation. The total requirement (the mean infusion rates) of propofol in placebo, clonidine 75 micrograms, clonidine 150 micrograms, and 10 mg of diazepam groups were 841 +/- 70 (9.0 +/- 0.3), 720 +/- 63 (7.1 +/- 0.4), 491 +/- 39 (5.6 +/- 0.2), and 829 +/- 77 mg (7.9 +/- 0.4 mg/kg/h), respectively. The cost of propofol in these groups was

Ameloblastoma accompanied by prominent bone formation

51.0 +/- 3.8,

Motion of the Human Mandibular Condyle during Mastication

45.5 +/- 3.2,