A number of biologically active polypeptides or factors have been isolated from or claimed to be present in the submandibular gland of the mouse. Among them nerve growth factor and epidermal growth factor are extensively studied growth factors that occur in the submandibular glands. Therefore, the mouse submandibular gland is regarded to be both an endocrine organ and an exocrine organ. On the other hand, we have previously shown that mouse submandibular gland-derived epithelial cells require fibroblast growth factor-1 (FGF-1) for their growth and maintain a diploid chromosome number in serumfree culture.
In this study, we therefore investigated whether mouse submandibular glands contain FGF-1 activities and whether the levels of these activities are dependent on androgen.
We purified a 16, 000 dalton protein which stimulates growth of human umbilical cord vein-derived endothelial cells (HUVEC) from mouse submandibular glands by using heparin-Sepharose affinity and C4 reverse phase chromatography. The purified molecule was identified as FGF-1 bases on its biological activities, affinity for heparin, and N-terminal amino-acidsequence. Furthemore, the concentrations of the factor in male or testosterone treated female mouse submandibular gland were about 25 times higher than those of female or castrated male submandibular glands. In addition, northern blot analysis of mouse submandibular gland mRNA revealed that 2.3 kb and 4.1 kb FGF-1 mRNAs were expressed in the glands of male mice older than 4 weeks but not in female mice
These results suggest that FGF-1 may play important roles in growth, differentiation and development of mouse submandibular glands, . and may act as an endocrine hormone.

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The relationship between histological grade, mode of invastion, DNA ploidy, and PCNA positive rate to the recurrence of primary tumors and cervical lymph node metastases was investigated in 33 cases of tongue squamous cell carcinomas. No significant relationship was observed between the occurrence of primary recurrence and any of the four variables, although the rate of recurrence was slightly higher in case showing a PCNA positive cell rate of more than 30%. In contrast a significant relationship was noted between the incidence of cervical lymph node metastasis and the mode of invasion (p<0.01), DNA ploidy (p<0.05), and rate of PCNA postive cells (p<0.05). In addition, cervical lymph node metastases were noted in 5 of 7 cases that fulfilled at least two of following three carditions: diffuse invasion, DNA aneuploidy, and a PCNA positive cell rate of more than 30%. Secondary metastases desfite control of the primary lesion were noted in 3 of these 5 cases (60%).
These results suggest that the above three factors related to cervical lymph node metastasis can be used to analyse the relative risk of secondary metastasis in squamous cell carcinomas of the tongue.

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The purpose of this study was to evaluate the long-term effects of surgical incision and suture on the retrodiscal tissue of the temporomandibular joint. Twenty rabbits were used in this study. They were killed 1 week (5 animals), 24 weeks (5 animals), and 72 weeks (5 animals) after surgery. Five animals without surgery were used as controls. The temporomandibular joints were removed en bloc. The specimens were fixed in 10% formalin for 10 days and decalcified for 7 days in a solution consisting of sodium citrate and formic acid. They were then embedded in paraffin in the conventional manner and 6-μm sections were prepared and stained with hematoxylin and eosin. The postsurgical experimental and control animals were compared by microscopic examination. The results were as follows:
One week after surgery, distinct signs of local inflammation were not seen at the retrodiscal incision. The collagen fibers in the retrodiscal incision were randomly oriented. Degenerative changes were not observed in the temporomandibular joints. Twenty-four weeks after surgery, the incision within the retrodiscal tissue had almost completely healed and appeared to be normal. Seventy-two weeks after surgery, no discontinuity defects were found in the retrodiscal tissue, and neither degenerative nor destructive changes were observed on the disc, condyle, or eminence.

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Neck dissection in which the sternocleidomastoid muscle was excised and the internal jugular vein and accessory nerve were preserved was performed in 73 patients with squamous cell carcinomas of the oral cavity or maxillary sinus. The dissection was done prophylactically in 54 patients and therapeutically in 19 patients.
Histopathological findings of the neck lymph nodes revealed that the numbers of pN (+), false negative and false positive cases were 22 (30.1%), 12 (22.2%) and 9 (47.4%), respectively. In only one case (1.4%) both recurrence in the ipsilateral neck nodes and late metastasis of the contralateral neck nodes were observed. Only late metastasis of the contralateral neck nodes was noted in three cases. The results obtained by this type of neck dissection were superior to those previously reported for radical neck dissection (RND) suggesting that this operative technique is very useful in patients without infiltration of metastatic vein as well as in patients with no neck node involvement. The technique described was here considered to be significant in that there is no interference of blood brain flow because the internal jugular vein is preserved.

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Experimental studies were conducted in rabbits to investigate the applicability of a highpressure water stream or water jet in oral surgery.
We examined histologically the effects of a saline-substituted water jet system at pressures ranging from 17-20 kg/cm² on the submandibular gland, parotid gland, tongue, palatal mucosa, facial nerve and liver.
In the salivary glands, the interlobular space showed edematous changes resulting from invasion of water and bubbles, and the blood vessels were separated from the surrounding loose connective tissues. In the tongue, the spaces between muscle bundles were torn. In contrast, the vessels were not severely damaged and bleeding was slight. The palatal mucosa was easily ablated from the palatal bone with almost no damage in the periosteum. In the liver, the vessels and ducts were separated and minimal bleeding was detected. The healing process in the parotid gland injured by conventional instruments or the water jet was investigated. At 17 kg/cm² pressure, there was resultant damage to the parotid glands. On electrophysiological examination of the ablated facial nerve, the threshold value with the water jet, did not rise as high as that with conventional instruments.
Some problems also exist with the water jet. For example, the optimal pressure suitable for application to the different organs while causing minimal damage has not yet been determined. There is also the problem of water splashing about. We believe, however, that this instrument is very useful for the preservation of blood vessels and nerves.

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In order to study the effects of temafloxacin (TMFX), a new quinoline antimicrobial agent, in dentistry and oral and maxillofacial surgery, a jaw bone infection model was prepared in rabbits with Streptococcus millefi (S. milleri) and Bacteroides fragilis (B. fragilis) according to the Satoh-Heimdal method.
Both strains were induced to be rifampicillin resistant (RFP^r), and the infected rabbit mandible was evaluated by autobacteriography (ABG). In the ABGs, the inoculated bacteria, S. millefi RFP^r and B. fragilis RFP^r, were largely confined to the infected foci, and low concentrations were observed in the submandibular lymph nodes.
TMFX therapy was instituted in both groups at 3 and 7days after infection. In both groups abscesses were more localized and there was a greater decrease in inoculated bacteria compared with the untreated control group. Irrespective of the time of starting treatment, the duration of treatment (3days or 5days) had little effect on therapeutic efficacy evaluated by ABG. However, comparing the results by the time of initiating treatment indicated that treatment should be instituted 3 days after onset of infection when the inflammation was most advanced because an adequate therapeutic effect was obtained. Initiation of treatment at this time also proved beneficial by containing the inflammation and localizing abscesses.
The concentration of TMFX in bone tissue was about half of that in serum, and penetration to the lymph nodes and glandular tissue was particularly high.

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This experimental study was designed investigate the process of bone bridge formation after the implantation of BMP to the maxillary alveolar clefts. Crude BMP obtained from bovine bone matrix was implanted into the artificial alveolar clefts of mongrel dogs, and postoperative bone formation was examined histologically. The results were as follows:(1) Two months after implantation, new bone formation was observed and the area of implantation was filled with undifferentiated mesenchymal type cells.(2) Four months after implantation, bone bridge formation was observed and new bone formation was continued.(3) Most of the bone bridges were suggested to have been formed by intramembranous ossification.(4) The area of new bone formation was limited to areas where BMP had been implanted. These results indicate that BMP is useful for treatment of alveolar clefts.

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During the 16-year period from 1975 to 1990, 141 patients with oral squamous cell carcinomas were referred to our clinic. Seven of these patients (5%) had multiple primary oral cancer within the same tissues or organs according to the criteria of Moertel. Here we report on the four most recent of these seven patients. The four patients all had advanced stage (Stage III, IV), well-differentiated squamous cell carcinomas. Initial treatment of these four patients was chemotherapy and radiotherapy with surgery. Second primary tumors occurred in the buccal mucosa in 2 patients and in the gingiva and the tongue in the other two patients. All second primary tumors were early stage (Stage I, II), well-differentiated types. The average interval between the diagnosis of the initial primary and second primaly tumors was 5 years and 9 months. Two patients with third primary tumors had white lesions or erosion-like lesions in the oral mucosa during the observation period, or at the first examination. The average interval between the diagnosis of the second and third primary tumors was one year. The results of the present study suggest that careful surgical excision of various mucosal lesions found after the treatment of oral cancer is very important, especially because precancerous lesions of patients with oral cancer have malignant potential.

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We performed a clinicostatistical study of 95 pediatric maxillofacial fracture cases under the age of 15 years and a long-term follow-up study of 42 of these cases at The First Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Tokyo Medical and Dental University during the 16-year period between 1977 and 1992. The ratio of boys to girls was 2: 1 and the horhest incidence involved boys over 13 years of age. Falling to the ground was the most frequent cause. Fracture of the mandibula and the upper alveolar bone were common.
Conservative therapy was usually performed and was found to be successful. Intramaxillary fixation was performed in alveolar fracture cases and younger patients and intermaxillary fixation was done in mandibular fracture cases and elderly patients. The long-term follow-up study demonstrated that some patients with alveolar fractures complained of abnormal arrangement of teeth and malocclusion, suggesting the importance of long-term follow-up.

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In recent years, freeze-dried dura, porcine skin, chitin membrane, and other materials have been used as occlusive wound dressings for burns, donor sites, graft sites, and oral mucosal defects. However, these are only temporary materials that have several disadvantages in terms of biocompatibility, infection, antigenicity, and breakdown.
A new bilayer artificial mucous membrane (TERUDERMIS^®, Terumo Co.) has been developed as a permanent material that promotes the reconstruction of tissue. It consists of a bottom layer of fibrillar collagen and heat-denatured collagen with dehydrothermal cross-linking, and an upper layer of a silicone elastomer.
We used TERUDERMIS^® successfully in the treatment of 32 patients in whom problems with the oral mucosa, including the gingiva and tongue, had developed during surgery. The material was found to be easy to handle, adhere well and promote hemostasis, relive pain, have little antigenicity, limit infection, promote rapid epithelialization, and produce newly, synthesized connective tissue with the infiltration of cellular tufts of fibroblasts and capillaries, and with minimum contraction.
The results suggest that the material is safe and effective for clinical use, and merits being referred to as an “artificial mucous membrane.”

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Multiple cancer may develop independently in one organ or double cancer may develop separately in different organs. Both types of cancer are collectively referred to as multiple primary cancer. In this study, we reviewed a series of patients with multiple primary cancer treated in our department. Here, we report the results.
In the 12-year period from January 1980 to December 1991 we treated 139 patients with malignancy. Among these patients we studied 18 cases of multiple primary cancer including 4 cases of triple cancer and 2 cases of multiple cancer of the oral cavity. The patient consisted of 14 males and 4 females.
Simultaneous occurrence refers to cases in which the period from the primary to secondary cancer is less than 6 months, and heterochronous occurrence refers to cases in which this interval is 6 months or longer. Only one case occurred simultaneously, and the others occurred heterochronously. Oral cancer developed in association with cancer of other organs including the oropharynx in 3 patients, the esophagus in 3, the stomach in 3, the colon and rectum in 2, the prostate in 2, the breast in 2, and the thyroid in 1. Thus 81.3% of the cases were associated with the gastrointestinal tract (13 patients) and oral multiple cancer was observed in 2 patients. In addition, 10 patients with primary cancer and 8 patients with secondary cancer visited our department. The outcome of 18 patients showed 6 survivors (33.3%) and 12 deaths (66.7%). Out of 6 survivors, 5 patients completed treatment without tumor recurrence and one patient with triple cancer is still bearing a tumor. Out of 12 deaths, 9 died due to primary disease 9 died due to unknown causes. The 9 patients who died due to primary disease consisted of one with double cancer who died of primary cancer, 5 with double cancer who died of secondary cancer, and 3 with triple cancer who died of an uncontrollable tertiary cancer.(Although one patient with triple cancer is surviving with a tumor).
In conclusion, in the diagnosis, treatment, and follow-up of oral cancer, the occurrence of double cancers of other organs, in particular the gastrointestinal tract, should be born in mild and patients with such cancers should be observed carefully in close association with other medical departments.

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Solitary metastatic tumors are estimated to represent approximately 1% of all oral malignant tumors. The most frequent primary region is the breast and metastatic tumors from the liver are rare.
A 58-year-old man with metastatic hepatocellular carcinoma to the mandible, who initially showed lower lip hypoesthesia and mandibular swelling, is presented.

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This paper describes a rare case of malignant melanoma of the palate recurring after an 11-year interval. A 66-year-old female presented in September 1980 with a pigmented tumor on the palate. Oral examination revealed a 14 × 7 mm black nodule with an adjacent brownish-black plaque and a light brown macular lesion. There were no enlarged cervical lymph nodes. Under the clinical diagnosis of malignant melanoma (stage I), she underwent surgical excision and adjuvant immunochemotherapy with DTIC, ACNU, VCR and OK-432. Histological examination of the operation material revealed acral lentiginous melanoma (ALM) type. She was clinically free from the tumor for 11 years. In September 1991, an amelanotic small nodule was found near the operation scar. A diagnosis of malignant melanoma was obtained by excisional biopsy. She underwent radical neck dissection because of late neck metastasis in April 1992. She is now free from the tumor one year after the last operation. This case is considered to be very rare because of the long interval to recurrence and the unique findings of the recurrent tumor.

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Warthin tumor is a relatively rare tumor that occurs exclusively in the parotid gland, occasionally bilaterally.
The case presented is a 53-year-old man with the chief complaint of bilateral swelling, slowly increasing with no pain, of the parotid glands. Histopathological study of the enucleated tumors revealed papillary or tubular proliferation of columnar and cuboidal epithelium cells arranged in bilayers associated with stromal lymphoid tissue in the cystic cavity. The histopathological diagnosis was Warthin tumor. The postoperative course has shown no evidence of recurrence.
Immunohistochemically, B-cells showed a positive reaction right below the epithelium and T-cells were scattered in the stromal lymphoid tissue, with the former being predominant. Likewise, IgG, IgM, and IgA were sporadically noted in the stromal lymphoid tissue, with IgG being predominant. In addition, positive reactions for IgA and secretory component (SC) were seen in the cytoplasm of the tubular epithelium. The results suggested the presence of an SC-mediated transport mechanism.

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Three cases of tuberculosis in the oral and maxillofacial region are presented. The first and second patients (cases 1 and 2) had tuberculous cervical lymphadenitis, and the third patient (case 3) had tuberculous gingival (and maxillary sinus) lesions with active pulmonary tuberculosis. In addition, we reviewed all cases of tuberculous lymphadenitis of the oral and maxillofacial region reported in Japan over the last 20 years. As the clinical stage of tuberculous lymphadenitis advanced, its specific histopathological features tended to disappear, making diagnosis more difficult.

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A patient with a secondary (radiation induced) fibrosarcoma in the mandible is presented. A 59-year-old man visited our hospital with a complaint of swelling and pain in the left mandible. He had previously undergone radiation therapy for a tonsillar tumor 7 years ago. Under the clinical diagnosis of a malignant tumor, surgical excision was performed. Final tissue analysis of the surgical specimen revealed it be fibrosarcoma. Twenty-five months later, he died from recurrence in the temporal region and neck.
In addition, a retrospective analysis presented on 80 cases of fibrosarcoma in Japan diagnosed between 1969 and 1991.

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An extremely enlarged epulis is reported. The patient was a 37-year old female. She complained of a slowly growing painless tumor on the left side of the upper jaw. This tumor was excised under general anesthesia and measured 80×85×45mm. The histopathologic features indicated epulis fibrosa.

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We have recently encountered a supposed case of a mandibular median cyst. An outline of the case is reported here.
The patient was a 42-year-old woman, who came to our hospital with a chief complaint of redness and swelling of labial gingiva corresponding to 2-2 on July 15, 1991. Radiograpnic findings included a thumb head-sized, well-delineated, unilocular translucent region at the mandibular median area, but there were no signs of resorption of the dental root.
The resected cyst was about 16×13×10 cm and spheroidal. Pathohistological examination indicated that the cystic wall was covered with thin stratified squamous epithelium. Now, two years and four months postoperatively, the patient is doing well without any signs of recurrence.

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Benign cementoblastoma is a very rare odontogenic tumor. A case of benign cementoblas-tomawith a severe percussion pain in the right molar region of the maxilla is reported. The patient wasa 16-year old male. He underwent resection of the tumor and has an excellent prognosis.

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We report two cases of benign lymphoepithelial lesions (BLL) of the salivary gland. BLL arose in the sublingual gland in case 1 and in the palatine gland in case 2. Neither patient complainted of xerostomia or xerophthalmia, and other salivary glands were normal.
In both cases histopathologic findings of lymphocytic infiltration, ectatic ducts, myoepithelial islands and acinar atrophy were observed. Immunohistological examination revealed that the predominat population of lymphocytes around the ducts and myoepithelial islands consisted of B-cells rather than T-cells.

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A case of pemphigus vulgaris presenting initially with symptoms of an incurable ulcer of the oral cavity is reported. A 57-year-old female visited our hospital owing to pain and bleeding of her oral cavity. She had consulted several departments of dermatology and internal medicine in the previous 6 months, but symptoms did not improve. Vesicles appeared on the skin and half months after the initial symptoms of stomatitis. The diagnosis of pemphigus vulgaris was supported by biopsy and histopathologic examination, which revealed spurabasal splitting of the epithelium and progressive loss of intercellular attachments. Immunofluorescence study detected IgG along the intercellular margins. Predonisolone was administered to this patient, and the stomatitis and skin vesicles improved after treatment.

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A 14-year-old girl was referred to our department on September 20, 1985 for a gross radiolucency involving the left molar-ramus region. A biopsy specimen disclosed the lesion to be a follicular-type ameloblastoma with massive proliferation of the mesenchymal stroma.
The tumor was resected, leaving a large defect. However, the bone was expected to be regenerated due to the high osteogenetic potential of the periosteum because of her young age. Maximum preservation of the periosteum and its stabilization by packing the dead space with a porous hydroxyl-apatite ceramic block was regarded to be necessary to avoid iliac bone grafting. In live with this plan, her mandible was immediately reconstructed by interposing the material, 58×25×12 mm in size and 31 g in weight, between the symphysis and the extra-articular condylar head. After 8 years of follow-up, there have been no identifiable signs of morphological or functional disturbances.

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An amelanotic malignant melanoma successfully responded to lymphokine-activated killer (LAK) therapy is reported. A 62-year-old male was referred to our department complaining of tumor on the upper right gingiva (on October 23, 1990). Clinical examination revealed tumor formation on the upper right alveolar gum and multiple lung metastases. He was diagnosed as an amelanotic malignant melanoma histopathologically. He was treated with chemotherapy (DTIC, ACNU, and VCR) and adoptive immunotherapy with LAK cells which were generated in serum-free RD5F medium. After 2 course of chemotherapy and 5 course of LAK therapy, the size of lung metastases was reduced significantly.

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