Hiroshi Tsubota

Prognostic Factors and Treatment Outcome in Non-Hodgkin's Lymphoma of Waldeyer's Ring

Prognostic factors and treatment outcome of 71 patients with non-Hodgkins lymphoma of Waldeyers ring were analyzed retrospectively. In univariate analyses, unfavorable prognosis was associated with primary disease in the base of the tongue, stage III-IV diseases, B-symptoms, high-grade histology, T-cell phenotype, elevated serum LDH levels, decreased peripheral blood lymphocyte counts, and negative response on delayed type hypersensitivity skin reactions. Multivariate analysis showed that stage III-IV and T-cell phenotype were significant independent risk factors for death. In stage I-II lymphomas, patients with unilateral large or bilateral cervical lymph node involvement had a poorer prognosis. In stage I-II lymphomas with intermediate or high-grade histology, patients who had received radiotherapy with MTCOP-P chemotherapy (pirarubicin, cyclophosphamide, vincristine, methotrexate with leucovorin rescue, peplomycin, and predonisolone) showed significantly better 5-year disease-free survival rate compared with patients treated with radiotherapy alone.

Expression and Function of Tight Junctions in the Crypt Epithelium of Human Palatine Tonsils

The human palatine tonsils have surface and crypt stratified epithelium and may be initiated via the epithelium to mount immune responses to various presenting antigens. Here we investigated the expression and function of tight junctions in the epithelium of human palatine tonsils from patients with tonsillar hypertrophy or recurrent tonsillitis. Occludin, ZO-1, JAM-1, and claudin-1, −3, −4, −7, −8, and −14 mRNAs were detected in tonsillar hypertrophy. Occludin and claudin-14 were expressed in the uppermost layer of the tonsil surface epithelium, whereas ZO-1, JAM-1, and claudin-1, −4, and −7 were found throughout the epithelium. In the crypt epithelium, claudin-4 was preferentially expressed in the upper layers. In freeze-fracture replicas, short fragments of continuous tight junction strands were observed but never formed networks. In the crypt epithelium of recurrent tonsillitis, the tracer was leaked from the surface regions where occludin and claudin-4 disappeared. Occludin, ZO-1, JAM-1, and claudin-1, −3, −4, and −14, but not claudin-7, mRNAs were decreased in recurrent tonsillitis compared with those of tonsillar hypertrophy. These studies suggest unique expression of tight junctions in human palatine tonsillar epithelium, and the crypt epithelium may possess an epithelial barrier different from that of the surface epithelium.

Syphilitic cervical lymphadenopathy

Syphilis is well known as a great mimic, however it is not recognized as a cause of cervical lymphadenopathy. We report a case of a 21-year-old man who presented with marked unilateral cervical lymphadenopathy. He had no evidence of oropharyngeal chancres, skin or genital lesions. Computed tomography (CT) and magnetic resonance (MR) images showed multiple cervical lymphadenopathy, and serologic tests for syphilis were positive. Syphilis should still be a factor for consideration in the differential diagnosis of cervical lymphadenopathy.

Color Doppler sonography in monitoring after free jejunum transplantation

The authors assessed the usefulness of color Doppler imaging in the monitoring of vascular circulation after free jejunum transplantation. Seven male patients were examined daily with color Doppler sonography for the first postoperative week between 1999 and 2000. All sonographic examinations were performed with an SSD5500 ultrasound scanner. Arterial and venous signals were documented reliably in all patients. The flashing red spots around the serosal wall revealed the patency of the anastomosed artery and vein. No failures of the graft occurred. The presence of the color Doppler signals was considered sufficient to define vascular patency. The real-time monographic (B-mode) examination revealed the thickness and the plicae circulares of the jejunum wall. These monographic (B-mode) images supported the viability of the transplanted jejuna. The authors found color Doppler sonography to be a reliable and effective form of monitoring after free jejunum transplantation.

Immune Response of Tonsillar B Lymphocytes

The palatine tonsil, a major lymphatic organ in Waldeyers ring, has interesting characteristics, i.e., it is the immunological organ located at the entrance to the upper respiratory tract and gastrointestinal tract, and it is also the focus of infections (habitual angina in the young and tonsilla focal infection in the middle-aged and elderly). This may indicate that tonsillar lymphocytes are continuously stimulated by numerous foreign antigens.It is generally accepted that the tonsil is a B cell dominant lymphatic organ, and therefore would be one of the best models for the research of cell kinetics and differentiation of human B lymphocytes.The purpose of this study is to demonstrate the characteristics of the immune response of tonsillar B lymphocytes.

Expression and Localization of Human Defensins in Palatine Tonsils

Defensins are small antimicrobial peptides and effector components of innate immune responses. Recent studies have shed light on their beneficial functions for the prevention of infection and potential for development of new drugs. Here, we showed the expression profiles of human defensins in palatine tonsils with 3 different diseases: tonsillar hypertrophy, recurrent tonsillitis and focal infection of the tonsil. RT-PCR analysis and immunofluorescence revealed that the expression of human α-defensin 4 and β-defensin 3 (β3) in palatine tonsils with tonsillar hypertrophy was lower than that in recurrent tonsillitis and focal infection of the tonsil, suggesting that chronic inflammation induces defensin expression. Interestingly, β2 and β3 mRNAs were specifically expressed by palatine tonsil tissues but not in human peripheral blood mononuclear cells and mucosa of the small intestine. Additionally, we observed that exposure to a Toll-like receptor 4 ligand, lipopolysaccharide, which is used as a bacterial infection model, increases the production of β2 in culture supernatants from tonsillar epithelial cells in a dose-dependent manner. Taken together, these results indicate that β2 produced by tonsillar epithelial cells plays an important role in the innate immune response for bacterial infections.

Ossifying fibroma of the mandible with primary hyperparathyroidism due to non-familial parathyroid adenoma

Ossifying fibroma is an uncommon benign osteogenic neoplasm arising from cells of the periodontal ligament, typically with a slowly progressive enlargement of the affected bone. The neoplasm sometimes presents with hyperparathyroidism, most of which cases are due to familial parathyroid tumours. We report a rare case of ossifying fibroma of the mandible which showed very rapid growth and presented with primary hyperparathyroidism due to non-familial parathyroid adenoma. Despite improvement of parathyroid dysfunction after removal of the parathyroid adenoma, the tumour continued to grow very aggressively. The case required partial mandibular resection for complete resection of the tumour, and fixation of the remaining mandible with a titanium plate.

Morphometric study of the medial aspect of the human maxillary sinus with special reference to the nasal fontanelle.

OBJECTIVE The purpose of this study was to clarify configurations of the nasal fontanelle (NF) from the morphometrical point of view, especially variations of its four margins (anterior, posterior, superior, and inferior), for clinical application. METHODS We used 136 sides of hemi-sectioned heads that were obtained from 119 donated Japanese cadavers (66 men and 53 women with an average age of 77.6+/-12.0). After mucosal examination, the specimens were boiled with a small amount of powdered soap and treated with protease. The residual mucous membrane was then gently removed. These specimens were originally made for our previous study describing variations of the uncinate process (Isobe M, Murakami G, Kataura A. Variations of the uncinate process of the lateral nasal wall with clinical implications, Clin. Anat. 1998;11:295-303). Different series of measurements were conducted based on surgical approaches and angles of observation. RESULTS The superior margin of the NF is difficult to identify because the ethmoidal infundibulum, which leads the anterior end of the margin upward, often interrupts the superior margin. Because the inferior and posterior margins are modified by thin paper-like bony structures and because the anterior margin is disturbed by variations of the lacrimal bone and/or the inferior turbinate, they are also difficult to identify. Knowing these variables, we evaluated the NF morphometrically. The NF was located 12.6+/-4.3 mm posterior to the anterior nasal spine and 6.6+/-2.2 mm anterior to the sphenopalatine foramen. The size of the NF was 17.9+/-3.2 mm (anteroposterior axis) x 11.5+/-3.0 mm (inferosuperior axis). The lowest orbital floor was located 10 mm below the superior margin of the anterior NF (-10 mm), and the distance was therefore measured as -3.7+/-2.4 mm on average. Viewed from the maxillary sinus, the location of the NF varied along the anteroposterior axis, whereas it was located consistently at the most superior portion of the medial aspect of the sinus wall. CONCLUSION During endoscopic sinus surgery for tumor resection in the maxillary sinus, a large and primary window should be prepared in the posterior NF, including partial removal of the uncinate process. Preparation of an additional window in the inferior meatus is preferable to enlargement of the primary window. Approaching the anterior NF should be avoided, if possible, due to its complicated configuration as well as its proximity to the orbital floor.

Expressions of Very Late Antigen-6 and Vitronectin Receptor, and Their Interactions to Laminin and Vitronectin during Tonsillar B-Cell Activation

This study examined the expressions of a-subunits of very late antigen-6 (VLA-6; alpha 6) and vitronectin receptor (VNR; alpha V) on tonsillar B cells and interactions between those integrins and their respective ligands, laminin (LM) and vitronectin (VN). alpha 6 and alpha V were expressed on about 30 to 40% of tonsillar B cells. When purified tonsillar B cells were separated by a discontinuous Percoll gradient, the number of alpha 6- and alpha V-positive cells decreased as the cell density went down, while the number of activated cells went up. After in vitro activation of tonsillar B cells by Staphylococcus aureus Cowan I strain (SAC), the expressions of alpha 6 and alpha V and their adhesiveness to LM or VN decreased significantly. Increased proliferation of B cells was observed when tonsillar B cells were cultured with immobilized LM or VN. The results of immunohistological staining showed VLA-6, VNR, LM and VN in the follicular area. These results suggest that the expressions of VLA-6 and VNR on tonsillar B cells may be decreased during B cell activation, and the interaction between VLA-6, VNR, and LM, VN may give a costimulatory effect on B cell activation in the follicular area of the tonsil.

Interaction and immunological effect of very late antigen-4, 5, and fibronectin in tonsillar lymphocytes and their relation to age.

We examined the expressions of alpha-subunits of very late antigen (VLA)-4 (alpha4) and VLA-5 (alpha5) on tonsillar lymphocytes and the interaction between these integrin receptors and their ligand, fibronectin (FN). Immunohistological and flow cytometric analyses showed that alpha4 and alpha5 were expressed in the lymphoid follicle and were positive on about 10% each of T cells and on 55% and 35% of B cells. When tonsillar B cells were separated by a discontinuous Percoll gradient, the number of alpha4- and 5-positive cells decreased as the cell density went down, while the number of activated cells went up. After in vitro activation of tonsillar B cells by Staphylococcus aureus Cowan I strain (SAC), the expression of alpha5 and the adhesiveness to FN decreased. The increased proliferation of B cells was observed when tonsillar B cells were cultured with immobilized FN. The expressions of alpha-subunits of VLA-4 and VLA-5 on tonsillar T and B lymphocytes increased with age. These results suggest that: i) B cell activation may cause decreased expressions of VLA-4 and -5, which gives a costimulatory effect on B cell activation itself again in cooperation with FN, ii) Increased expressions of VLA-4 and -5 on tonsillar lymphocytes with age may be related to regional immune response of the palatine tonsils.