Abstract:α-tricalcium phosphate (α-TCP) granules were mixed with calcium phosphate, mono basic (MCPM) or dibasic (DCPD) and hydrated to produce hardened materials. These materials in columnar shape (2×10 mm) were implanted on the inferior surface of rabbit mandibles for 3 and 6 months for studying bone responses to the material.
Microscopically, new bone from the underlying mandibular bone and the surrounding periosteum was formed and filled the gap between the material and bone. Contact micro radiograph (CMR), scanning electron micrograph (SEM) and analytical electron micrograph showed that the contact between bone and the material was intimate or direct. CMR revealed that a low radiolucent zone was formed in the outer part of the material that was remarkably close to new bone and suggested the change of the material in vivo.
These findings were recognized in the same way in both materials of α-TCP/MCPM and α-TCP/DCPD mixtures and in both rabbits of 3 and 6 months implantation periods. It was concluded that the hydrated and hardened α-TCP mixture with MCPM or DCPD has a good biocompatibility with bone tissue and may be a bone substitute like a hydroxyapatite.

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In spite of its important role in the detection and diagnosis of malignant lesions in various fields, cytology is not highly appreciated in oral lesions because of its relatively high false-negative rate and because of easy application of biopsy.
The authors investigated the causes of false-negative cytology in order to re-evaluate the usefulness of smear cytology in oral malignant lesions.
Subjects were false negative cases from 241 oral smear cytology of malignant tumors performed in the Department of Head and Neck of the Cancer Institute Hospital from 1985-1990.
The results were as follows:
1. False-negative cytology was found to result from technical errors (29 cases, 45.4%), natures of diseases (24 cases, 37.5%) and misdiagnosis (1 case, 1.5%). No special causes could be found in the remaining ten cases.
2. The types of technical errors were as follows: errors in scrubbing (24 cases) and drying of specimens (5 cases).
3. The clinical pictures of false-negative cases due to natures of lesions were leukoplakia type (21 cases), papillomatous type (2 cases) and granulous type (1 case).
The present results suggested it is possible to reduce the incidence of false-negative cytology by using adequate techniques, selecting subjects and improving diagnostic competence.

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We experienced 5 cases of neurogenic tumors and 1 case of granular cell tumor in the 10-ear period from 1982 to 1991. It is well known that neurofibroma and neurilemmoma are neurogenic tumors. On the other hand, granular cell tumors were first described as ‘granular cell myoblastoma ’ by Abrikossoff in 1926. Recently, ultrastructural and immunohistochemical evidences in favor of a Schwann cell origin have been published. In this study, four neurilemmomas, one neurofibroma, and one granular cell tumor were examined with antisera directed against S-100 protein, neuron-specific enolase (NSE), and vimentin.
All of these tumors stained with antisera for S-100 protein and vimentin. NSE was absent from all of the tumors except for one case of neurilemmoma and the granular cell tumor. The immunohistochemical reaction pattern was heterogeneous, as follows;
1. In the neurilemmomas, almost all tumor cells had a diffuse immunoreaction product indicating S-100 protein and vimentin in their cytoplasm and nuclei.
2. In the neurofibroma, the staining pattern of S-100 protein and vimentin was similar to that of neurilemmoma: however, there were also a large number of S-100 protein-negative, spindle-shaped cells.
3. In the granular cell tumor, cytoplasmic granules showed S-100 protein and NSE localization, and the peripheral cytoplasm showed the presence of vimentin. This staining pattern appears to be a characteristic feature of the granular cell tumor.

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Sympathetic nervous system has been generally considered to be enhanced by painful stimulations. In recent years, along with the changes of the living environment/dietary habit and the increase of the aged population, the number of diseases in the blood glucose and lipids abnormalities has shown a remarkable increase by stress and painful stimulation, that may be thought to be one of the related factors of these diseases.
This study, observed and discussed the time-dependent changes on the concentration of plasma catecholamine [epinephrine (E), norepinephrine (NE), dopamine (DA)], serum glucose (GLU) and lipids [free fatty acid (FFA), triacylglycerol (TG), total cholesterol (TC)] by the electrical stimulation to the periodontium of rabbits, was investigated to elucidate the influence on the blood glucose and lipid concentrations by painful stimulation in the oral region. The results were obtained as follows.
1. Plasma E and NE concentrations showed a rapid statistically significant increase duringstimulation, and E did the same level at rest as 30 min after stimulation, but NE did the continuous slightly higher level than that of basal level after stimulation. Plasma DA concentration showed later gradual slight increase than that of E and NE during stimulation, and maintained a moderately high level after stimulation.
2. Serum GLU concentration showed a rapid statistically significant increase during stimulation, and maintained a high level after stimulation.
3. Serum FFA concentration didn't show any changes during stimulation, but did a gradual increasing tendency from 120 min after stimulation. Serum TG concentration showed an increasing response during stimulation and the same decreasing response within 60 min after stimulation, then continued to decrease thereafter. Serum TC concentration didn't show any changes during/after stimulation.
The possibility that painful stimulation in the oral region might influence on the blood glucose and lipid concentrations could be verified from above mentioned results.

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This paper describes the effects of fibrin adhesive material (Beriplast P ^®: BP) on bone induction in bone defects formed by surgical operation. Using adult Sprague-Dawley strain rats, bone defects were formed in the cortical bones of femurs with a dental round bar 1 mm in diameter, and immediately filled with BP. Bone defects without BP served as controls.
On days 1, 4, 7, 14, 30, 60, and 120 after operation, rats were fixed by transcardiac perfusion with an aldehyde mixture, and dissected bones were examined by light, transmission, and scanning-electron microscopy.
In the control bones without BP, the defective regions werefirst filled with blood clots (day 1) and then with granulated tissues containing numerous fibroblasts and macrophages (day 4). In BP-filled defects, the presence of BP and surrounding fibrous tissues significantly inhibited the formation of blood clots and granulated tissues, so bone formation from the surrounding cortical bone margins was induced faster than in control bones. In addition, granulated tissues were rapidly replaced by normal bone marrow in the BP-filled defects. Because BP is biological adhesive, at 4 days after operation, most of the BP was already absorbed, but no dead space was left in the defected regions. At 2 weeks after operation, the defects were completely filled with newly-formed bones, in which an active bone remodelling by osteoblasts and osteoclasts occurred.
These results show that BP is an effective biological tool in filling bone defects and in inducing new bone formation.

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Warfarin which antagonizes vitamin K is clinically used as a anticoaagulant agent. However, the effect of warfarin on bone remodeling is still unclear.
The present study was to investigate the effect of warfarin on the healing process of tooth extraction wounds. Sprague-Dawley male rats were injected with warfarin according to the maintenance protocol by Price as the experimental group. Rats without the injection were used as the control group. The upper first molars of rats were extracted in both groups. These rats were killed on days 1, 2, 4, 7, and 10 and on weeks 2, 3, 4, and 6 postoperatively. Serial histological sections were stained with hematoxylin and eosin for light microscopy. And the osseous healing process was observed on day 4 and on weeks 1, 2, 3, 4, and 6 after extraction by microradiography.
The results obtained were as follows:
1. Warfarin-treated rats demonstrated that the number of mesenchymal cells and new capillaries were less than that of the control in the early stage after extraction.
2. New bone formation in the sockets of control rats initiated on day 4 after operation, however, new bone formation in experimental rats was delayed and the number of osteoblasts were less than that of the control. In both groups, the new bone occupied the middle 2/3 of the socket on week 1, lower 4/5 on day 10, and whole socket on week 2, respectively. No significant difference was found in the location of new bone between the control and experimental groups. However, the thickness and volume of new bone were statistically different between the groups.
3. The control group showed that osteoclasts appeared in the socket wall and fundus on day 1. They increased and reached a maximum number on day 2, and disappeared after day 4. In contrast, the experimental group demonstrated that osteoclasts appeared within on day 2, and reached a maximum number on day 4 and dispersed on day 10.
4. 6 weeks after extraction, there were almost no remarkable differences between the experimental group and the control group.
These results prove that warfarin delayed the healing process of soft tissue and the new bone formation in the early stage of wound healing, suggesting that warfarin affected the proliferation and the metabolism of mesenchymal cells, osteoblasts and osteoclasts.

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The bone resorption is involved in the growth of ameloblastomas, however, the mechanism of bone resorption by this tumor remains unclear whether tumor cells directly resorb bone, tumor secretion enhances the activity of osteoclasts, or tumor secretion or tumor itself stimulates peripheral blood leukocytes (PBL) to release osteolytic factors.
In this study, four ameloblastomas, which were successful in primary cultures out of the cases histologically diagnosed ameloblastoma during the period of 1990 to 1991 at Second Department of Oral and Maxillofacial Surgery, Osaka Dental University, were investigated. The mechanism of bone resorption was examined using the three in vitro assays with mice: a new born calvaria culture system, a bone marrow culture system and a peritoneal macrophage chemotaxis. The tumor homogenates, the tumor conditioned media, the monocyte conditioned media stimulated by tumor homogenates or conditioned media, and the lymphocyte conditioned media stimulated by tumor homogenates or conditioned media were obtained for samples. The results were:
1. Ameloblastoma during their growth released soluble factors which had bone resorption activity and regulated the multinucleated cell formation.
2. The tumor secretion stimulated PBL and induced the release of osteolytic factors.
3. The activity of osteolytic factors was inhibited by indomethacin. Thus, it was suspected the involvement of prostaglandins in this process.
4. Tumor itself did not affect either the bone resorption activity or PBL stimulation.
5. Tumor secretion had chemotactic activity on mouse peritoneal macrophage, however, the magnitude was low. This might induce the migration of osteoclasts.
6. There is a possibility that ameloblastomas may express the different bone resorption activity along with the histological types.

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For the purpose of clarifying the growth and infiltration into the mandibular bone by carcinoma cells, VX2 carcinoma cells were transplanted into the masseter of domestic rabbits and its mode of invasion was investigated with the light microscopy and the scanning electron microscopy (SEM) as well as the electron probe X-ray microanalyser (EPMA).
The results were as follows;
1. Light microscopic examination demonstrated that VX2 carcinoma cells formed substantial cellular foci localized to the masseter in the 1st week after transplantation, then destroyed the periosteum in the 2nd week, and infiltrated and proliferated within the mandibular bone in the 3rd and 4th weeks.
2. When the bone surface adjacent to the tumor was examined with SEM, a large number of resorption lacunae being irregular in shape were found in the VX2 carcinoma cell-infiltrating site of the mandibular bone. Small bone cavities were found at the bottom of resorption lacunae. Collagen fibers were running in various directions depending on the depth, some of them formed net-like patterns while others were fragmented.
3. X-ray microanalysis of the VX2 carcinoma cell-infiltrating site using EPMA demonstrated some decrease of Ca in the region adjacent to the tumor prior to infiltration of VX2 carcinoma cells into the mandibular bone. As the infiltration of VX2 carcinoma cells into the mandibular bone progressed, the peak level of Ca decreased significantly whereas almost no change was observed in the peak of P.
These results indicate that three dimentional examination of carcinoma-infiltrating site in the jaw bone using SEM combined with investigation of Ca distribution with EPMA might be a useful clinically and applicable tool in defining the margin of carcinoma infiltration into the jaw bone.

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The distribution of intracellular keratin and lectin binding were studied in dysplastic lesions and squamous cell carcinomas of buccal pouch and lingual mucosae of the hamster induced by the application of a 0.5% DMBA mineral oil.
Comparison was made of the electrophoretic keratin polypeptide patterns of normal buccal pouch epithelia and of squamous cell carcinomas of buccal pouch mucosa. Keratin polypeptides from normal epithelia had a molecular weight (MW) range of about 47, 000 to 76, 000. In tumor extracts, the large polypeptides (above MW 58, 000), found in the normal epithelia, were absent. The majority of small polypeptides below MW 58, 000 were expressed. Antibodies against total keratin extracts from normal buccal pouch epithelia (NAG) and squamous cell carcinomas (CAAG) were raised in rabbits, respectively NAB and CAAB. NAB staining was strong in spinous cells but negative in basal cells, whereas CAAB staining was strong in spinous cells and moderate or weak in basal cells. The dysplastic epithelial cells and squamous cell carcinoma cells except for cancer pearls showed no staining for the NAB, but exhibited weak or moderate CAAB staining.
Lectin binding in normal squamous epithelium showed regional distribution patterns of spinous and basal layer types. Dysplastic cells or carcinoma cells displayed a loss of cellular surface and intercellular staining.
The present study suggests that the difference of the staining intensities of keratins using NAB and CAAB and the lectin binding among the normal epithelium, dysplasia and squamous cell carcinoma are valuable indicators of the malignant transformation in the oral mucosa of hamsters.

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The composition and dynamic properties of the plasma membrane are believed to play a central role in the regulation of cellular proliferation and differentiation. In particular, lipid composition seems to be an important factor for the dynamic properties of the plasma membrane. Cultured keratinocytes provide a useful model system for studying epidermal differentiation, because the differentiation capacity of cells is dependent upon the external calcium concentration. Recently, we have utilized this system for the study of differentiation-linked changes in lipid metabolism.
On the other hand, it has been reported that several growth factors play important roles for proliferation and differentiation in normal and transformed cells. Thus it is surmised that lipid metabolism changes during differentiation to attain a steady state where various kinds of lipids exist in dynamic equilibrium and growth factors may modify the equilibrium. It is therefore interesting to study how the changes: s occur in the process of malignant transformation, and to clarify the possible relation between change of lipid metabolism and malignant transformation.
Since lipid synthesis is dependent upon the presence of external lipoprotein, we have studied lipid metabolism of normal epithelial cells and cancer cells in serum-free culture to evaluate an intrinsic lipid metabolism in the cell. Furthermore, we have studied effects of epidermal growth factor (EGF) and acidic fibroblast growth factor (aFGF) on the lipid metabolism of the cell in a serum-free culture.

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During the 8-year period from 1983 to March 1991, 71 cases with primary carcinoma in the oral cavity were observed and treated in the Department of Oral Surgery at Hirosaki University Hospital.
Fourty-nine patients were male and 22 were female showing a male to female ratio of 2.2: 1. The age of patients ranged from 26 to 80 years, and the mean age was 59.2.
Histologically, squamous cell carcinoma accounted for 87.3% of the all cases. Stage grouping by UICC (1987) showed that 56.3% of the cases were clinically classified into stage IV. More than 1 year was spent in 28.2% of the patients until diagnosis was accomplished after chief complaint had been appeared.
On admission, serum IAP elevated for 38.2% of the cases, and serum SCC for 16.1% of the cases with squamous cell carcinoma, respectively. All cases for which serum SCC elevated were in stage IV, and histologically high differentiated squamous cell carcinoma is rare. Serum TP was low in 40.8% of the cases, and serum Hb was low in 49.3% of the cases.
The former is remarkable for the cases of lip and tongue cancer, the latter for the cases of oral floor cancer. Serum ALP elevated for 20.6% of the cases of maxillary and mandibular cancer.
Radiologic finding showed CT is effective to diagnose maxillar cancer, but not so effective on mandibular cancer, and partially to oral floor and tongue cancers.
MRI made up for the diagnosis of mandibular cancer, but only a part of oral floor and tongue cancers were diagnosed. ⁶⁷Ga Scintigraphy is more effective for the diagnosis of oral floor squamous cell carcinoma than CT or MRI.

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Impacted supernumerary anterior teeth in the upper jaw were clinico-statistically reviewed in 139 patients at our department during the past 7 years. The following results were obtained.
1. The incidence was approximately 1.5%. Extraction was performed on 120 (86.3%) of the 139 patients.
2. By sex distribution, the patients consisted of 116 males and 23 females. The incidence of impacted supernumerary upper anterior teeth was approximately five times as great in the male patients as in the female patients.
3. The ages ranged from 4 to 57 years. Patients of 7 to 10 years accounted for 66.2%(92 cases).
4. On examining the number of impacted supernumerary teeth, one was observed in 87 cases (62.6%), one with an erupted supernumerary tooth in 29 (20.9%), and two in 23 (16.5%), respectively. None of the patients had more than three impacted supernumerary teeth.
5. The state of impaction was examined in 85 patients (106 teeth) who underwent tooth extraction.
In 57 patients with one impacted supernumerary tooth, the tooth was impacted in a normal direction of eruption in 21.1% and in inverted position in 71.9%. In 21 patients with two impacted supernumerary teeth, the direction of impaction was normal+inverted in 28.6% and inverted+inverted in 66.7%. In all seven patients with an erupted supernumerary tooth, the direction of impaction was inverted.
On examining distomesially the positions of the impacted supernumerary teeth, impaction occurred between the roots of the right and left upper central incisors in 95.3%. When examined in a vertical direction, the impacted teeth were located inferiorly to the radix of the upper central incisor or at some distance away from the root in 72.6%.
6. Cystic formation on the X-ray films were 18 cases (17.0%).
7. Incision for tooth extraction was placed from the palatal side in 95 (79.2%) of the 120 cases.
8. 10 patients (8.3%) developed postoperative complications but these were all transient and mild.
9. Roentgenological diagnosis were carried out intraorally by the bisecting angle and occlusal methods and extraorally by orthopantomography, lateral projection and tomography. In some cases in which the location of impaction was unclear, two to five kinds of imaging techniques were used in combination. At the stage of mixed dentition, tomography was found more useful than lateral projection for assessing the positional relationship of the impacted supernumerary tooth and adjacent teeth.
For the treatment of impacted supernumerary upper anterior teeth, it is our plan to first continue careful observation with extraction already in mind and then perform extraction when, taking individual differences of patients into consideration, the patients grow up mentally strong enough to withstand the stress of operation.

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Of 84 primary cases of squamous cell carcinoma in the oral and maxillofacial region examined at the Department of Oral Surgery, Dokkyo University Hospital during a period of 12 years and 10 months from January 1977 to October 1987, 54 which were examinable were classified for degree of histological malignancy according to the Anneroth classification, and the relationship of the degree of histological malignancy with the prognosis was examined. The results obtained were as follows:
1. In terms of the relationship of the degree of histological malignancy with 5 year-cumulative survival rate, low-, moderate-and high-malignancy groups showed survival rates of 81.8, 46.8 and 32.8%, respectively, with a significant decrease in the survival rate being noted (P<0.05) for higher degree of malignancy.
2. In terms of the relationship of the degree of malignancy with the control of the tumor, the low-malignancy group showed control of the tumor of 87.5% compared with 30.0 (P<0.001) and 39.(P<0.05) for the moderate-and high-malignancy groups, respectively, with a higher tendency to remote metastasis being noted for higher degree of malignancy.
3. Of various parameters, degree of nuclear polymorphism, mode and degree of invasion, and lympho-plasmocytic infiltrations showed their respective correlations with the prognosis, but the evaluation of the degree of keratinization and the number of mitoses left a question about the preciseness of judgment.

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From the histological viewpoint, antitumor activity of carboplatin (CBDCA) was compared with that of cisplatin (CDDP), which had been studied previously, in the course of preoperative treatment combined with intraarterial chemotherapy and radiotherapy for head and neck cancers.
The CBDCA group consisted of 13 previously untreated patients who received both the intraarterial chemotherapy with CBDCA (80mg/m², on day 1 and 8) and peplomycin (PEP, 5mg/body/day, from day 1 to 5 and day 8 to 12) and ⁶⁰Co-radiotherapy (2 Gy/day, total to 20 Gy) before surgery. The CDDP group consisted of 14 analogous patients who had received the same therapy except for intraarterial infusion of CDDP (20mg/m², on days 1 and 8) in spite of CBDCA. The tumors in both groups were resected 7 to 10 days after the preoperative treatments and examined histologically in several portions.
Therapeutic effects were judged according to Oboshi's histological classification in the resected materials. The effect of Grade II B or more, which meaned less than 1/4 living tumor cells, was judged as respondent, and that of Grade II A or less was as irrespondent. Nine out of 13 patients (69%) in CBDCA group and 11 out of 14 patients (79%) in CDDP group were judged as respondent. Though the difference of responsibility between the two groups was not statistically significant, it was impressed that CDDP group showed slightly greater response to the chemo-and radio-therapy.
It was suggested from the above results that the CBDCA dosage should be increased within a limited dose with no severe adverse effects appearing.

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Adverse effects of carboplatin (CBDCA) was compared with that of cisplatin (CDDP) in the course of preoperative treatment combined with aintraarterial chemotherapy and radiotherapy for head and neck cancers. The CBDCA group consisted of 12 previously untreated patients who received both intraarterial chemotherapy with CBDCA (80 mg/m², on days 1 and 8) and peplomycin (PEP: 5 mg/body/day, from day 1 to 5 and day 8 to 12) and ⁶⁰Co-radiotherapy (total to 20 Gy) before surgery. For controls, seven patients, who had also received both intraarterial chemotherapy with CDDP (20 mg/m², on days 1 and 8) and PEP (5 mg/body/day, from day 1 to 5 and day 8 to 12) and ⁶⁰Co-radiotherapy (total to 20-30 Gy) preoperatively, were examined (CDDP group).
Counts of white blood cells (WBC), red blood cells (RBC), and platlets (PLAT.) for myelosuppression, blood urea nitrogen concentration (BUN), urinary N-acetyl-β-D-glucosaminidase activity (NAG) and β₂-microglobulin concentration (BMG) for nephrotoxicity, and some clinical signs (nausea or vomiting, stomatitis, and alopecia) were evaluated. The above clinical examinations were made several times before, during, and after chemo-and radio-therapy. All the above data except for the clinical signs were within the normal range through the present therapeutic courses in the CBDCA group. On the contrary, WBC, NAG, and BMG increased significantly on the next day of drug administration in the CDDP group.
Alopecia was significantly severer in the CDDP group than in the CBDCA group. It was considered that the adverse effects of CBDCA were slighter than those of CDDP in the present dosage.

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Although brain abscess related to odontogenic origin is relatively well documented, hematogenous spread of brain abscess to oral and maxillofacial regions is rare. We have encountered a case of brain abscess which manifested symptoms in buccal mucosa and submandibular regions. A 69-year-old female was admitted with a history of buccal swelling for 2 weeks. Clinically, parotid gland tumor was most suspected.
However, the histopathological finding by biopsy material revealed phlegmonous inflammation of the oral region. On the rext day of biopsy, the patient suddenly beame drowsy, followed by deep unconsciousness. Computerized tomography demonstrated an area of low density in the right lateral lobe, which suggested brain abscess or glioma. Surgically removed brain tissue was histopathologically diagosed as a brain abscess. Shortly after the operation for brain abscess, buccal swelling gradually became small and finally disappeared. On the past history, the patient had harbored a pulmonary infection about 2 months prior to this. Since pulmonary infection is the most feasible cause of brain abscess, the origin of abscess in this case is attributed to the pulmonary infection. In addition, inflammation in buccal region can be considered to be the spread of brain abscess.

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The tumors of central nervous tissue are extremely rare in the oral cavity. Two cases of congenital tumor of heterotopic neuroglial tissue of the tongue and palate are reported, with a review of the literature and some discussion on its origin.
Case 1: There was a slightly pale, elastic soft, smooth surfaced mass on the palate.
Case 2: There was a mass on the median part of the dorsal tongue. The size of the tumor was about 25×25×10 mm.

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Cementifying fibroma is a relatively rare odontogenic tumor with a predilection for the jaw bone. We reported here 4 cases of cementifying fibroma we had recently encountered.
The tumors of all 4 cases were surgically removed. Histopathological examination revealed that the tumorous lesions consisted of various amounts of fibrous tissues with extensive proliferation of cementum-like tissues.
Therefore, the tumors were histopathologically diagnosed as cementifying fibromas. The prognosis of these cases are favorable with no sign of recurrence.

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A 24-year-old policeman was shot in the right side of the face by a machinegun. The bullets made direct crushing wounds in the hit area, resulting in a shock wave and temporary cavitation. These traumatic forces produced the fracture of the zygoma, maxilla and mandible, and the laceration of the lateral pharyngeal wall.
Emergency operation was performed for controlling the bleeding and removal of the foreign bodies, such as bullets. The osteosynthesis was performed 4 days later with miniplates and wire. After 13 months, orthognathic surgery was employed to correct the malocclusion. Niether trismus nor disfunction of the mastication were observed at least 3 years later.

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