The palatine tonsil is located in the strategic area of the oropharynx, and has a characteristic lymphoid architecture of secondary organs covered with reticular crypt epithelium. Narrow epithelial diverticula form the crypt and considerably increase the available surface area for direct antigenic stimulation. The mesh of the reticular crypt epithelial cells hold T and B cells, interdigitating dendritic cells and macrophages. It is speculated that reticulation of the crypt epithelium provides a favorable environment for intimate contact between cells of the immune system and crypt epithelial cells, which express a variety of molecules related to potential antigen-presentation, such as HLA-DR, ICAM-1 (CD54), VCAM-1, and co-stimulatory molecules, B7-1/137-2 (CD80/86). These phenotypes of the crypt epithelium resemble follicular dendritic cells which are professional antigen-presenting cells of lymphoid follicles. Our findings suggest that the crypt epithelial cells clearly function as antigen-presenting cells in the paratine tonsil.

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The presence of the stratum corneum on the human skin surface is essential for the body because of its barrier function, which prevents the loss of water from living tissue and the penetration of deleterious chemicals and pathogenic microorganisms from the environment. Moreover, the stratum corneum plays a vital role in maintaining skin surface softness and smoothness due to its water-holding capacity. However, there are skin diseases such as pustulosis palmaris et plantaris and psoriasis where the presence of the stratum corneum plays a role in the production of unique sterile subcorneal pustules. In these dermatoses, there are 2 steps regarding different inflammatory processes in lesional skin. The initial step is characterized by the infiltration of autoreactive T lymphocytes that release proinflammatory lymphokines, under the influence of which epidermal keratinocytes further produce various chemokines. The second step starts when there is extensive tissue damage that directly exposes the stratum corneum to the tissue fluids. Complement in the tissue fluids is activated on the surface of the stratum conreum via the alternative pathway to release C5a and induce neutrophil chemotaxis toward the lesional stratum corneum. Tonsillectomy is considered to be effective because it removes the chronic infectious foci, under the influence of which T lymphocytes are presumed to invade the skin.

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The pathogenesis of IgA nephropathy (IGA N) is unclear. We have previously shown the glomerular deposition of Haemophilus parainfluenzae (HP) antigens and the presence of IgA antidody against HP antigens in patients with IgA N. We examined the immune response to HP antigens in tonsillar lymphocytes from patients with IgA N.
We used tonsillar lymphocytes isolated from the palatine tonsils of 13 patients with IgA N and 16 patients with chronic tonsillitis but without renal disease as controls. We examined lymphocyte proliferation and production of IgA antibody against HP antigens by measuring thymidine uptake and IgA antibody in culture supernatants after lymphocyte incubation with HP antigens.
Patients with IgA N showed a significantly higher stimulation index to HP antigens (thymidine incorporation in tonsillar lymphocytes with HP/thymidine incorporation in unstimulated tonsillar lymphocytes) than controls (P<0.002). Lymphocytes from patients with IgA N also showed a significantly higher level of IgA antibody and IgAl antibody against HP antigens in culture supernatants than lymphocytes from controls (P=0.0002 and P=0.004; respectively).
Our results suggest that HP antigens stimulate tonsillar T-and B-lymphocytes in patients with IgA N and that an immune response to HP antigens may play a role in the pathogenesis of this disease in some cases.

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There is currently no established therapy that is entirely successful for IgA nephropathy (IgAN), and the clinical benefit of tonsillectomy in patients with IgAN remains controversial. In respect to clinical remission, several reports (mostly from Japanese groups) showed positive results. On the other hand, in respect to the progression of nephropathy, most studies showed negative results.
To obtain the clinical remission of IgAN, we have used a combination therapy consisting of steroidpulse and tonsillectomy in our institute. Two years after the initiation of therapy (one year after the discontinuation of steroids) most early-stage patients in the intensive therapy group no longer had proteinuria, although the percentage of such patients decreased as the stage progressed (index of glomerular lesion, IGL≤1.5, 80%; 1.5-2.0, 70%; 2.0-2.5, 44%;>2.5, 4%) (24 h proteinuria<1.0, 79%; 1.0-2.0, 42%;≥2.0 g, 25%). Approxirnately 80% of the patients in the intensive therapy group no longer had hematuria or only had very mild hematuria (U-RBC: 0-4/hpf), irrespective of the disease stage. These results suggest that clinical remission may be expected when IgAN patients are treated with tonsillectomy and steroid pulse in the early stages of the disease. In contrast, although the resolution of hematuria can be expected regardless of the disease stage, remission of proteinuria is highly unlikely in advanced-stage patients.

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The significance of mastication is the formation of bolus that one can swallow. The effect of mastication on digestive action depends on the kind of food. Masticatory efficiency is higher when one chews food many times, but is lower in the case of malocclusion. It is believed that masticatory rhythm is formed by the central pattern generator that is thought to be in the brainstem. The central pattern generator is thought to be a multi-neuronal circuit. The simplest model of the circuit is the reciprocal inhibition circuit of Reiss. Repetitive stimulation of the cerebral cortex induces mastication-like rhythmical jaw movements in many species. In rabbits, the masticatory area is located in the antero-lateral part of the cortex. The anterior part of the masticatory area includes the primary jaw motor area, and stimulation of this area induces simple jaw opening closing movements that are superimposed in sustained jaw opening. Electromyographic activities of the digastric muscles consist of a twitch activity that is time-locked to the stimulus pulses. Stimulation of the posterior part of the masticatory area induced mastication-like movements that include lateral movement of the jaw during closing and occlusal phases of the chewing cycle. There is no sign of time-locked component in the digastric burst activities. Similar results were obtained from experiments in rats. According to the results from the HRP experiment on rats, the anterior masticatory area projects to the medial and lateral reticular formation. The posterior masticatory area, however, projects to the lateral reticular formation exclusively. Therefore, it is thought that the difference in the projection patterns from these two cortical areas to the brainstem is responsible for the difference in movement patterns evoked from both areas.

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Silent aspiration of oroplaryngeal bacterial pathogens to the lower respiratory tract is an important risk factor for pneumonia in the elderly. Impaired swallowing and cough reflexes present the most sever general hazards for the prevention of pneumonia in the elderly. Studies of these defense mechanisms of silent aspiration led us to investigate pharmacological therapeutic methods. I describe preventive approaches for lowering the risk of pneumonia.
Imidapril and amantadine may prevent pneumonia in the elderly.

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We studied 15 cases of head and neck adenocarcinoma. Poor prognosis was observed. The fiveyear survival rate was 21.6%. The patients diagnosed as in the early stage did not show better prognosis. Five patients (33%) showed distant metastases including lung, bone, liver and brain. Eight patients received chemotherapy with CDDP, CPM, and ADR. Although we could not prove any efficacy of chemotherapy, we reported two advanced cases without recurrence for more than five years. Both patients were chemo sensitive and received combination chemotherapy including 5FU. We proved high enzymatic levels of TS and a low level of DPD in adeno-, adenoid cystic, and mucoepidermoid carcinoma. This may result in high proliferation activity and high 5FU sensitivity in these tumors. We conclude that some patients with adenocarcinoma are chemo-sensitive, and combination chemotherapy including 5FU is important for a better survival rate for advanced adenocarcinoma patients. Combined therapy with Taxons will also play a key role in the future.

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In order to clarify the immunological role of palatine tonsil in pustulosis palmaris et plantaris (PPP), keratin-specific immune responses of tonsillar lymphocytes were investigated. Mononuclear cells were isolated from peripheral blood and tonsil obtained by surgery on patients with PPP, chronic tonsillitis and tonsillar hypertrophy. Keratin-specific antibody activities were determined by ELISA and the number of keratin-specific antibody-forming cells was examined by ELISPOT assay. CD4⁺T cells and B cells were isolated from tonsillar or peripheral blood mononuclear cells by a magnetic bead separation system. The cells were cultured with keratin and the helper activity of CD4⁺T for producing keratin-specific antibodies was determined. Further, CD8⁺T cells were depleted from the tonsillar mononuclear cells and the production of keratin-specific antibodies was examined. Keratin-specific antibody activity in serum and the number of keratin-specific antibody-forming cells in the tonsil and peripheral blood were increased in patients with PPP when compared with that in patients with chronic tonsillitis or tonsillar hypertrophy. CD4⁺T cells isolated from the tonsil enhanced the production of keratin-specific antibodies from peripheral blood B cells, but not CD4⁺T cells isolated from peripheral blood. The production of keratin-specific antibodies from tonsillar mononuclear cells was increased by depleting the CD8⁺T cells. The results demonstrated that keratin-specific antibodies were produced by tonsillar lymphocytes as well as peripheral blood lymphocytes and the production of the antibodies was increased in patients with PPP. The immune responses against keratin were regulated by CD4⁺T cells and CD8⁺T cells. The findings suggest that keratin-specific immune responses in the tonsil might be associated with the pathogenesis of PPP.

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To evaluate whether genetic abnormalities can serve as a molecular biological marker for the risk assessment related to the development of multiple cancers, detection of allelic loss and immunohistochemical analyses were investigated in oral and pharyngeal cancers of patients with second cancers in other organs. Three microsatellite markers, D3S 1067, IFNA and D9S171, were used to study the loss of heterozygosity (LOH) of 3p21 and 9p21 in 20 primary cancers of oral and pharyngeal origin. There were 18 informative cases, and LOH was detected in 14 out of 18 (78%) DNA samples obtained from cancer specimens when at least one marker was used. The frequency of LOH was correlated with the clinical stages of the patients, and it was extremely high (100%) in hypopharyngeal cancers. Specimens from oral and pharyngeal cancers as well as second malignancies of the same patients were analyzed by immunohistochemistry to detect the expression of p21 (Waf-1) and Bcl-2. We observed the expression of Bcl-2 and disappearance of the expression of Waf-1 in both early and advanced carcinomas. These data indicate the possibility that the detection of 3p and/or 9p LOH in a cancer may serve as a good molecular marker for the assessment of second cancer risk in the same patient.

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The use of osseous free flaps has become the preferred method for reconstructing segmental mandibular defects. Once the decision to reconstruct a segmental defect with vascularized bone has been made, the most important reconstructive choice is the flap selection. The two most important decisions to be made are the quantity/quality of bone and the amount of skin/soft tissue that are needed. The fibula donor site is the first choice for most cases. The fibula provides up to 20 cm of uniform, bicortical bone that can be osteotomized multiple times without devascularizing individual segments. The bone is also excellent for the placement of dental implants. The fibula is not as good an option for defects with very extensive lining, skin, and soft tissue requirements. It is the ideal flap for simultaneous dissection during oncologic resections because it is located far from the head and neck. The rib, vascularized with the perforator vessels connecting the latissimus dorsi muscle and the intercostal vessels, is best reserved for cases with large soft tissue and minimal bone requirements. The combined use of a fibula and MC flap is selected for cases with large soft tissue and long bone requirements. The rib's bone quality, however, is poor. Patients with very extensive lining, skin, and soft tissue excisions can chew only with their remaining intact normal teeth. Although the rib is less durable than the fibula, it is sufficiently durable for chewing in such patients.

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A sleep test was performed on 63 patients at the Self-Defence Forces Central Hospital between September 1997 and May 1999. The apnea index of the overweight group (24≤body mass index<26.4) was significantly higher than that of the normal body weight group (20≤body mass index<24). The apnea index of the obese group (26.4≤body mass index) was significantly higher than that of the overweight group (24≤body mass index<26.4).
The postoperative results of 63 cases that underwent surgery for simple snoring and obstructive sleep apnea were analyzed by questionnaire. The improvement ratio for snoring was 93% and that for apnea during sleep was 92% after surgery. Ninety percent of the patients became more aware of their health and 84% their body weight after surgery. Patients significantly decreased their body mass index after surgery. One of the reasons for the high effectiveness of surgery might be body weight control.

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We examined Ki-67 and p53 protein expression in 12 cases of mucoepidermoid carcinoma (MEC) of the parotid gland. Histological grade, clinical stage and the immunohistochemical results of tumors were compared with the clinical outcome of the patients. The MIB-1 LI ranged from 0.3 to 31.5% (mean, 9.6%). Eight (67%) of the MECs revealed positive staining for p53. The mean MIB-1 LI was higher in the high-grade malignant group than in the low-grade malignant group, with statistical significance. A high MIB-1 LI value was significantly correlated with a shorter overall survival period of patients with MEC. This study indicates that MIB-1 LI is one of the most useful prognostic indicators for MEC of the parotid gland.

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A case of carcinoma in the pleomorphic adenoma in the right palatine tonsil of a 72-year-old male was reported. The patient visited our hospital with a complaint of abnormal feeling in the throat. A physical examination revealed that the right palatine tonsil was slightly enlarged and a necrotic lesion on the surface. A biopsy from the right tonsil was performed and the pathological diagnosis was adenocarcinoma. We further examined the digestive tract and lung but found no apparent primary lesion. A partial pharyngectomy with supraomohyoid neck resection was performed with reconstruction by the forearm. flap.The final diagnosis was carcinoma in the pleomorphic adenoma. The type of pleomorphic adenoma was cellular and the carcinoma was adenocarcinoma. The neck lymph node had no metastasis. It was considered that the tumor originated from the minor salivary glands in the pharyngeal mucosa around the tonsil and extended into the tonsil. The patient has been free of recurrence or metastasis during the 8 months since surgical resection.

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Recently, submandibular cystic diseases are easy to diagnose owing greatly to the use of radiodiagnosis. Especially, preoperative CT and MRI are very important for differentiating plunging ranula from epidermoid cyst. The charcteristic appearance of these cystic diseases were studied retrospectively. During the past 10 years, we operated on 13 patients that complained of swelling in the submandibular region in our department.
In this paper, two cases are presented. We found that the shape, feature, contents and wall of the cyst during CT and MRI are capable of being used to make the diagnosis. Plunging ranula and epidermoid cyst showed that CT was low density and MRI (T2) high intensity. Plunging ranula demonstrated that the cystic mass shows a different form (e.g., dumbbell, oval, etc.) by the position of the CT and MRI slice. Epidermoid cyst demonstrated a roundish mass having an enhanced wall.
We concluded that CT and MRI were very useful in the diagnosis of these diseases.

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IgA is the predominant immunoglobulin effector molecule of mucosal immunity functioning as the first line of specific immunologic defense against many microbial pathogens. However, IgA causes IgA nephropathy. We have hypothesized that Haemophilus parainfluenzae (HP) in the tonsil and the pharynx plays an important role in the production of IgA in patients with IgAN. In this study we investigated whether synthetic oligodeoxynucleotides augment IgA production (total and HP-specific) by tonsillar mononuclear cells. No synthetic oligodeoxynucleotides had an effect on total IgA production. Four types of synthetic oligodeoxynucleotides out of 23 enhanced HP-specific IgA production, while no oligodeoxynucleotides decreased HP-specific IgA production. This preliminary study suggested that certain DNA sequences from a bacteria have a possibility to enhance HP-specific IgA production from B cells.

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We retrospectively studied the clinico-pathological findings of 5 patients with parapharyngeal space neurinoma, whom we had treated from1984 to 1999. The tumors originated from sympathetic nerve in 2 cases and hypoglossal nerve in one case, but no origin was determined for 2 cases. The common chief complaint was neck swelling mainly in the submandibular or parotid region. Preoperative neurological symptom was observed in only one case, originating from the hypoglossal nerve. Intracapsular resection as surgical intervention was conducted for 2 cases, and ultimately no postoperative nerological defect symptoms were observed in these cases. These results led us to the conclusion that intracapsular resection of the neurinoma, instead of (end-to-end) total resection, can be of great benefit if the functional aspect of each nerve is considered important.

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A retrospective review was performed on 17 patients with submandibular gland cancer initially treated in our hospital between 1972 and 1997. The most common histological type was adenoid cystic carcinoma (41%). Sixteen cases were treated with surgery and some cases received added postoperative irradiation (4 cases) and chemotherapy (2 cases). A case with distant metastasis was treated with chemotherapy.
The five-year and ten-year cumulative survival rates calculated by the Kaplan-Meier method were 74 and 41%, respectively. The five-year survival rate according to stage was as follows: stage I (11 cases), 82%; stage II (2 cases), 100%; and stage IV (4 cases), 33%. Prognosis of the cases with .neck lymph node metastatis was remarkably poor. To improve the prognosis of submandibular gland cancer, prophylactic supraomohyoid neck dissection should be necessary for the N0 cases.

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