Estrogen dediciency accelerates autoimmune exocrinopathy in murine Sjogren's syndrome through Fas-dediated apoptosis

Estrogenic action has been suggested to be responsible for the strong female preponderance of autoimmune diseases, but the role of estrogens in the female has not been well characterized. We evaluated the effects of estrogen deficiency in a murine model for autoimmune exocrinopathy of Sjögren's syndrome (SS). Severe destructive autoimmune lesions developed in the salivary and lacrimal glands in estrogen-deficient mice, and these lesions were recovered by estrogen administration. We detected an intense estrogen receptor in splenic CD8(+) T cells compared with that in CD4(+) T cells, and concanavalin-A-stimulated blastogenesis of splenic CD8(+) T cells with estrogens was much higher than that of CD4(+) T cells. We found a significant increase in serum autoantibody production against the organ-specific autoantigen alpha-fodrin. Moreover, an increased proportion of TUNEL+ apoptotic epithelial duct cells was observed in estrogen-deficient mice. It was demonstrated that Fas-mediated apoptosis in cultured salivary gland cells was clearly inhibited by estrogens in vitro. These results indicate that dysfunction of regulatory T cells by estrogen deficiency may play a crucial role on acceleration of organ-specific autoimmune lesions, and estrogenic action further influences target epithelial cells through Fas-mediated apoptosis in a murine model for SS.


Requirement for splenic CD4+ T cells in the immune privilege of the anterior chamber of the eye


Anti-α-fodrin antibodies in Sjogren's syndrome and lupus erythematosus


Fas ligand-mediated exocrinopathy resembling Sjogren's syndrome in mice transgenic for IL-10

Although IL-10 has been implicated in the pathogenesis of several autoimmune diseases, the mechanisms by which this cytokine mediates inflammatory lesions remain to be elucidated. Exocrine gland destruction is an important early step in the development of Sjögren's syndrome. To better understand the role of IL-10 in Sjögren's syndrome, we made transgenic mice in which the mouse IL-10 gene was regulated by the human salivary amylase promoter. Transgenic expression of IL-10 induced apoptosis of glandular tissue destruction and lymphocyte infiltration consisting primarily of Fas-ligand (FasL)+ CD4+ T cells, as well as in vitro up-regulation of FasL expression on T cells. These data suggest that overexpression of IL-10 in the glands and their subsequent Fas/FasL-mediated bystander tissue destruction is a causal factor in the development of this disease.


Neonatal lupus erythematosus: Maternal IgG antibodies bind to a recombinant NH2-terminal fusion protein encoded by human α-fodrin cDNA

IgG antibodies to a cleavage product of alpha-fodrin (120 kDa alpha-fodrin) have recently been identified as organ-specific autoantibodies in primary Sjögren's syndrome. In this study, we examined seroreactivity of mothers and infants with neonatal lupus erythematosus (NLE) to a recombinant NH2-terminal protein (120 kDa alpha-fodrin) of human alpha-fodrin. Serum samples were collected during the perinatal period in seven pregnancies of five mothers delivering offspring with NLE. Anti-120 kDa alpha-fodrin antibodies were identified by immunoblotting in six of seven perinatal maternal sera of offspring with NLE: one of two congenital heart block offspring and all five offspring with cutaneous NLE. These antibodies were placentally transmitted to infants. One of the five mothers had primary Sjögren's syndrome, and four were asymptomatic. One asymptomatic mother did not demonstrate anti-120 kDa alpha-fodrin activity at the time of the first delivery of a congenital heart block infant, but was found to be positive at the time of subsequent delivery of a second child with cutaneous NLE. We propose that maternal antibodies to 120 kDa alpha-fodrin may be an additional serologic marker for the risk of NLE in anti-Ro/SS-A positive women.

The Journal of Investigative Dermatology


Use of topical cyclosporin A in a primary Sjogren's syndrome mouse model

A new animal model, the NFS/sld mutant mouse, was used for primary Sjögren's syndrome to investigate the efficacy of topical and systemic cyclosporin A (CyA) in preventing inflammation of the exocrine glands. Cyclosporin A was applied topically (0.01% and 0.1%, three times a day) or administered orally (10 mg/kg and 100 mg/kg, once a day) to mice from 6 to 16 weeks of age, after which the mice were killed. Topical CyA reduced lacrimal gland and submandibular gland inflammation without causing pathologic changes in other organs. Flow cytometry showed that CD44 expression of CD4 T cells from the submandibular lymph nodes was downregulated, whereas that of Mel14+ was upregulated. Using a reverse transcription-polymerase chain reaction assay, we determined that topical CyA significantly decreased the expression of mRNA of IL-2 and T-cell receptor-constant beta-chain. Topical CyA may be clinically useful in reducing the lymphocyte infiltration of lacrimal glands associated with Sjögren's syndrome.

Investigative Ophthalmology & Visual Science


Mechanisms of transfer into SCID mice reconstituted with tissue-infiltrating cells from murine model for Sjogren's syndrome


Anti-120-kDa a-fodrin immune response withTh-1-cytokine profile in the NOD mouse model of Sjogren's syndrome


Role of cytokines in the destruction of acinar structure in Sjogren's syndrome salivary glands

Laboratory Investigation; a Journal of Technical Methods and Pathology


Identification of α-fodrin as a candidate autoantigen in primary sjögren's syndrome

シェーグレン症候群において，フォドリンが自己免疫の高原である事を発見した．共同研究者として，実験，考察を担当した．


Accelerated onset of age-related autoimmune lesions in MRL/+ mice by ovariectomy


High incidence of autoimmune dacryoadenitis in male non-obese diabetic (NOD) mice depending on sex steroid


Role of cytokines of acinar structure in Sjogren's syndrome salivary glands


Analysis of T cell receptor Vb usage in the autoimmune sialadenitis of non-obese diabetic (NOD) mice


Effector Mechanism of Experimental Autoimmune Sialadenitis in the Mouse Model for Primary Sjogren's Syndrome

We have recently established a new animal model for primary Sjögren's syndrome in NFS/sld mutant mice thymectomized 3 days after birth (3dTX) bearing an autosomal recessive gene with sublingual gland differentiation arrest. In this study, we analyze developing mechanisms of experimental autoimmune sialadenitis (EAS) in the mouse model, focusing on local expressions of cytokine and cell adhesion molecule genes by reverse transcriptase-polymeric chain reaction (RT-PCR) and immunohistochemistry, kinetic analysis of splenic lymphocytes expressing activation markers, and I-Aq class-II molecules by flow cytometry (FACS). We found up-regulation of local cytokine genes (IL-1 beta, TNF-alpha, IL-2, IFN-gamma, IL-6, IL-10, IL-12p40) and cell adhesion molecule genes (ICAM-1, LFA-1, CD44, Mel-14) in the salivary glands from mice with EAS by RT-PCR, which were supported by immunohistochemistry. FACS analysis demonstrated that a significant proportion of splenic CD4+ T cells express activation markers (CD44, LFA-1, Mel-14low, CD45RB(low)) at a high level and an increase in expression of B220+ B cells bearing I-Aq class-II molecules. These data suggest that spontaneous EAS in 3dTX NFS/sld mutant mice may be triggered by an in situ activation of autoreactive CD4+ T cells comprising unique cytokine profile (high levels of IL-2, IFN-gamma, IL-10, and IL-12p40 mRNA) in the salivary glands.


Carcinoma in Pleomorphic Adenoma of the Tongue ; Report of a case

A carcinoma in pleomorphic adenoma occurring in the tongue of a 47-year-old Japanese woman is reported. The present report is the first to describe a carcinoma in pleomorphic adenoma derived from the posterior lingual glands.


Mechanism of the development of autoimmune dacryoadenitis in the mouse model for primary Sjogren's syndrome

To elucidate the mechanism of development in autoimmune lacrimal gland disease, we analyzed different aspects of autoimmune dacryoadenitis in a newly established mouse model for primary Sjögren's syndrome, focusing on the local expressions of cytokine genes, and the repertoire of T cell receptor (TCR) V beta genes transcribed within the inflammatory infiltration in the lacrimal glands. We found that the vast majority of inflammatory infiltration into the lacrimal glands were CD4+ V beta 8+ T cells. We detected the up-regulation of local cytokine genes (IL-1 beta, TNF-alpha, IL-2, IFN-gamma, IL-10, IL-12p40) in the lacrimal glands with very early inflammatory lesions by reverse transcriptase (RT)-PCR analysis. The predominant expression of the V beta 8 gene segment was detected from a very early stage, while extensive age-related diversity of TCR V beta gene usage was observed. Single-strand conformation polymorphism (SSCP) analysis demonstrated a distinct and a common binding pattern in the PCR product of the V beta 8 gene on the infiltrating cells during the course of the disease. These data suggest that in autoimmune dacryoadenitis of the mouse model for primary Sjögren's syndrome there may be a restricted usage of TCR V beta elements on a very early stage of the autoimmune lesion to recognize unknown self-antigen, and the autoreactive CD4+ T cells constitute a unique cytokine profile in the autoimmune lacrimal gland disease.


Verruciform xanthoma occurring within oral lichen planus


In vivo role of IL-10 and IL-12 during development of Sjogren's syndrome in MRL/lpr mice

Expression of local cytokine genes including interleukin 10 (IL-10) and IL-12 was analyzed in the salivary gland tissues of MRL/lpr mice with Sjögren's syndrome. We demonstrate a significant role of IL-10 and IL-12 in vivo during development of Sjögren's syndrome in MRL/lpr mice. IL-10 mRNA expression was detected before the onset of disease and was upregulated during the course of autoimmune sialadenitis by RT-PCR. A predominant level of expression of IL-12 mRNA was also detected earlier in the proinflammatory stage of autoimmune sialadenities. Moreover, MHC class II (I-Ak) mRNA was detected before the onset of inflammatory lesions until older ages in the salivary glands of MRL/lpr mice. These results suggest that endogenous IL-10 and IL-12 may play important roles on immune-mediated destruction of the salivary glands during development of organ-specific autoimmunity in MRL/lpr mice.


Sonic hedgehog is expressed in epithelial cells during development of whiskar, hair, and tooth

ソニックヘッジホッグが歯，毛，髭の発生初期の上皮に特異的に発現していることを発見した．また，担当授業科目(発生学)を教授する上できわめて有用な知見を得た．共同研究者として，実験，考察を担当した．

Biochemical and Biophysical Research Communications


Polarizing activity, Sonic headgehog, and tooth development in embryonic and postnatal mouse

マウスの歯胚にニワトリの重複肢誘導能があり，歯の発生において，ソニックヘッジホッグが関与していることを発見した．また，担当授業科目(発生学)を教授する上できわめて有用な知見を得た．共同研究者として，実験，考察を担当した．


Cytokine gene expression and autoantibody production in Sjogren's syndrome in MRL/lpr mice

In an attempt to elucidate the mechanism of development of organ-specific autoimmune lesions resembling human Sjögren's syndrome of MRL/lpr mice, we have analyzed local cytokine gene expressions and organ-specific autoantibody production in vivo. We have demonstrated that a major proportion of T cells bearing CD4 and V(beta)8 molecules are essentially responsible for triggering the autoimmunity in the salivary glands of MRL/lpr mice. The local cytokine gene expressions including interferon(IFN)-gamma, IL-12(p40) mRNAs were observed during the course of murine Sjogren's syndrome in MRL/lpr autoimmune strain. In particular, a high level of local expressions of IL-12 mRNA was detected earlier in the proinflammatory stage of autoimmune lesions. A significant level of local expression of MHC class-II(I-Ak) mRNA was detected before the onset of inflammatory lesions in the salivary glands, and I-Ak-positive epithelial duct cells were frequently observed in the salivary glands of MRL/lpr mice. In addition, we found the salivary gland-specific autoantibody in sera from MRL/lpr mice with early phase of autoimmune lesions by immunoblot analysis. These results suggest that cytokine gene stimulation and autoantibody production are essentially involved in the development of organ-specific autoimmune lesions in Sjögren's syndrome of MRL/lpr mice.


Immunopathological analysis of mucosal melanocyte distribution in the human lower lip of the elderly


Role of the ICAM-1/LFA-1 pathway during development of autoimmune dacryoadenitis in an animal model for Sjogren's syndrome

We have analyzed the role of cell adhesion molecules during the development of autoimmune dacryodenitis in an NFS/sld mouse model for primary Sjögren's syndrome. The expression of cell adhesion molecules was assessed by RT-PCR and immunohistochemistry. We detected an up-regulation of local cell adhesion molecule genes (ICAM-1, LFA-1, CD44 and Mel-14) in the course of autoimmune lacrimal gland diseases. Immunohistochemically, ICAM-1 was localized exclusively in the endothelial cells of variously sized blood vessels before the onset of disease, and LFA-1, CD44 and Mel-14, expressing infiltrating cells, were found within these lesions. When the therapeutic effects of blocking cell adhesion molecules in vivo were examined, antibodies to ICAM-1 in combination with anti-LFA-1 prevented the development of autoimmune lacrimal gland diseases in NFS/sld mice. These data suggest that in Sjögren's syndrome-like autoimmune dacryoadenitis in NFS/sld mutant mice, the ICAM-1/LFA-1 pathway may play a crucial role in the development and subsequent progression of T-cell-mediated autoimmunity in the lacrimal glands.


Expression of HLA-DR and cytokine genes on interferon-γ-stimulated human salivary gland cell line

Stimulation of a cultured human salivary gland (HSG) cell line by interferon (IFN)-gamma leads to HLA-DR gene expression concomitant with inflammatory cytokine genes such as IL-1 beta, tumor necrosis factor (TNF)-alpha, and IL-6 in vitro. IFN-gamma-induced HLA-DR mRNA expression was clearly detected at 2 h after the stimulation, and thereafter its level of gene expression increased until day 7 on HSG cells by reverse transcriptase (RT)-PCR. Immunofluorescence analysis revealed that cytoplasmic HLA-DR immunoreactivity was detected for the first time at 2 days after the stimulation, and its immunoreactivity increased gradually until day 7, while no immunoreactivity with HLA-DP and HLA-DQ was observed at any of the days. In addition, the expression of IL-1 beta, TNF-alpha, and IL-6 on the IFN-gamma-stimulated HSG cells was detected by immunohistochemistry and RT-PCR analysis. These results indicate that human salivary gland cells can be induced to express HLA-DR mRNA by IFN-gamma concomitant with inflammatory cytokine gene expressions such as IL-1 beta, TNF-alpha, and IL-6.


: In situ hybridization study of vascular cell adhesion molecule-1 messenger RNA expression in eheumatoid synovium

Upregulation of vascular cell adhesion molecule-1 (VCAM-1) has been implicated in various pathological conditions. In this study, we used in situ hybridization to determine the cell types expressing VCAM-1 mRNA in rheumatoid synovium. Synovial tissues from seven rheumatoid arthritis (RA) and four osteoarthritis (OA) patients were examined for VCAM-1 mRNA expression. In situ hybridization as well as immunohistochemical analysis showed that VCAM-1 expression was mainly localized to the hyperplastic synovial lining cells and to a lesser extent endothelial cells and synovial fibroblasts in rheumatoid synovium. VCAM-1 expression in OA is less prominent. Hyperplastic synovial lining cells expressing VCAM-1 were mainly CD13+, CD14+, CD33+ and HLA-DR+. Together with morphological features, this suggests that they are type A macrophage-like synovial cells. Our findings indicate that overexpression of VCAM-1 may contribute to the formation of hyperplastic lining layers in the synovium seen in this disorder.


Prevention of adoptive transfer of murine Sjogren's syndrome into severe combined immunodeficient (SCID) mice by antibodies against intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1)

We have analysed the role of ICAM-1 and LFA-1 during development of autoimmune sialadenitis in MRL/lpr mice by direct analysis of RNA obtained from the salivary gland tissues, and the therapeutic effects with antibody administration on adoptive transfer system into SCID mice. The expression of cell adhesion molecules was assessed by using reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blot analysis, and immunohistochemical analysis. Up-regulated expression of ICAM-1 mRNA was observed before the onset of inflammatory lesions in the salivary glands at 1 month and 2 months old, and thereafter LFA-1 mRNA was expressed within the typical inflammatory lesions, resembling human Sjögren's syndrome in MRL/lpr mice. Immunohistochemically, ICAM-1 was localized exclusively in the endothelial cells of varying sized blood vessels before the onset of disease, and LFA-1 expressing inflammatory cells were found within these lesions. When the therapeutic effects in vivo were examined, antibodies to ICAM-1 in combination with anti-LFA-1 prevented adoptive transfer of Sjögren's syndrome in MRL/lpr mice into SCID mice, while no significant effect was found when treated with either antibody. These findings indicate that in Sjögren's syndrome-like autoimmune lesions in MRL/lpr mice the ICAM-1/LFA-1 pathway may play a crucial role in the initiation and subsequent progression of T cell-mediated autoimmunity in the salivary and lacrimal glands of MRL/lpr mice.


小児顎下腺 エコ-レベルの年齢的変化

小児顎下腺 エコ-レベルの年齢的変化


Familial hyperparathyroidism associated with jaw fibroma: case report and literature review

A 53-year-old female suffering from renal stones and hypercalcaemia was diagnosed as having primary hyperparathyroidism caused by hyperplasia of the parathyroid glands. She underwent total parathyroidectomy and implantation of parathyroid tissue. After one year, she underwent surgery for a jaw tumour. The pathological findings indicated it to be a cementifying fibroma. Jackson et al. (1990) reported the familial association of hyperparathyroidism with jaw tumours, and they suggested that this condition represents a new clinical syndrome. We believe that our case belongs to this syndrome.


Localization of transforming growth factor-β type I and type II receptors in mouse development


シェーグレン症候群疾患モデルのSCIDマウスへの移入

シェーグレン症候群疾患モデルのSCIDマウスへの移入


NFS/sldミュータントマウスにおけるシェーグレン症候群疾患モデルの確立

NFS/sldミュータントマウスにおけるシェーグレン症候群疾患モデルの確立


Desmoplastic fibroma of the mandible associated with tuberous sclerosis


Biased T cell receptor Vβ gene usage during specific stages of the development of autoimmune sialadenitis in the MRL/lpr mouse model of Sjogren's syndrome


A new animal model for primary Sjogren's syndrome in NFS/sld mutant mice


Epithelial class II MHC antigen normally expressed by submandibular glands of elderly people


Transgenic Expression of IL-10 in Pancreatic Islet A cells Accelerates Autoimmune Insulitis and Diabetes in Non-Obese Diabetic Mice.


Transfer of Sjogren's syndrome-like autpoimmune lesions into SCID mice and prevention of lesions by anti-CD4 and anti-T cell receptor antibody treatment


唾液腺多形性腺腫における各種癌遺伝子産物の発現

唾液腺多形性腺腫における各種癌遺伝子産物の発現

Journal of The Japanese Stomatological Society


Expression of cytokine genes during development of autoimmune sialadenitis in MRL/lpr mice


c-myc, ras p21 and p53 expression in pleomorphic adenoma and its malignant form of the human salivary glands


Immunopathology of phenotypic change on human parotid gland adenocarcinoma

Immunopathological analysis was made of phenotypic change in a recurrent parotid gland adenocarcinoma occurring in a patient with a long clinical course of 30 years or more. At the first and second operations, in 1959 and 1978, the resected parotid gland tumors were diagnosed histopathologically as acinic cell carcinoma. However, 11 years after the second operation, in 1989, the resected recurrent tumor showed a microscopically phenotypic change towards adenocarcinoma with typical tubular arrangement. At the last operation in 1991, histopathological examination of the tumor revealed adenocarcinoma with diffuse oncocytic change in association with cervical lymph node metastasis. These findings suggest that phenotypic change may occur in vivo among human neoplasms during a long period, which may be related to the cytodifferentiation in the salivary gland tumor.


顎下腺と肺の重複癌の1例

顎下腺と肺の重複癌の1例


セメント質形成線維腫の4例

Japanese Journal of Oral & Maxillofacial Surgery


Lung carcinoma suspected to metastarize to the submandibular region by the autopsy --- Report of a case

剖検により原発性肺癌の顎下部転移と考えられた1例 --- Report of a case


ヒト口唇粘膜メラノサイトの分布とその加齢および性別変化

ヒト口唇粘膜メラノサイトの分布とその加齢および性別変化


A Cleft Child With Lobulated Tongue and Lingual Hamartoma: Report of a Case

Journal of Oral and Maxillofacial Surgery


The behavior of human ameloblastoma tissue in collagen matrix in vitro:an immunohistochemical study


Solitary neurofibroma of the tongue: Report of a case

舌に孤立性に生じた神経線維腫の1例


Coexpression of intermediate-sized filaments in sialadenoma papilliferum and other salivary gland neoplasms


Immunopathological analysis of interstitial renal lesions in elderly people


Immunopathological study of neuropeptide expression in human salivary gland neoplasms

The immunoreactivity of anti-neuron-specific enolase (NSE) and anti-Leu-7 on formalin-fixed sections of human salivary gland neoplasms was determined by the avidin-biotin-peroxidase complex method. In addition, neuropeptides, such as vasoactive intestinal polypeptide, somatostatin, and substance P, in human salivary gland neoplasms were expressed, whereas other polypeptides, including glucagon, cholecystokinin, leu-enkephalin and calcitonin, were absent. When 182 paraffin-embedded examples of human salivary gland tumors, including 112 benign and 70 malignant neoplasms, were examined immunohistochemically, positive immunoreactivity was observed in: 51 cases with NSE (59%) and 46 cases with Leu-7 (54%) of 86 pleomorphic adenomas; 11 cases with Leu-7 (61%) of 18 Warthin's tumors; 7 cases with Leu-7 (58%) of 12 acinic cell carcinomas; 5 cases with NSE (31%) of 16 adenoid cystic carcinomas; 5 cases with NSE (42%) and 4 cases with Leu-7 (33%) of 12 adenocarcinomas; 4 cases with NSE (25%) and 6 cases with Leu-7 (38%) of 16 undifferentiated carcinomas. The other tumors, such as oxyphilic adenomas, basal cell adenomas, epidermoid carcinomas, and mucoepidermoid carcinomas, were nonreactive. Neuropeptides were observed in the neoplastic epithelial cells of certain tumors such as Warthin's tumors, acinic cell carcinomas, adenocarcinomas and undifferentiated carcinomas. These findings suggest the possibility that cells of neuroendocrine origin, present in certain neoplastic salivary gland epithelia may play a significant role in the histogenesis of human salivary gland neoplasms.


Spontaneous development of organ-specific autoimmune lesions in aged C57BL/6 mice


Focal lymphocytic infiltration in the adrenal cortex of the elderly: immunohistological analysis of infiltrating lymphocytes


Expression of neuron-specific enolase, Leu-7, and neuropeptides in human fetal salivary gland epithelium

The Journal of Histochemistry and Cytochemistry


Immunopathology of experimental autoallergic sialadenitis in C3H/He mice


A new mutation involving the sublingual gland in NFS/N mice --- Partially arrested mucous cell differentiation


Spontaneous development of autoimmune sialadenitis in aging BDF1 mice

This study reports that spontaneous autoimmune sialadenitis developed in aging female, rather than male, BDF1 mice. The lesions first appeared in 6-month-old female BDF1 mice and were aggravated with advancing age, especially in 24-month-old and 30-month-old senescent mice. In contrast, significant inflammatory changes did not develop in aging male BDF1 mice. The presence of antisalivary duct antibody was found in sera from mice with sialadenitis. The infiltrating cells in the lesions of submandibular salivary glands were mainly composed of T cells, especially Lyt 1+ and L3T4+ cells. Moreover, mild inflammatory lesions were observed in parotid, sublingual salivary glands, pancreas, or kidneys in some mice that developed spontaneously occurring sialadenitis.


Expression of vasoactive intestinal polypeptide and amylase in a human parotid gland adenocarcinoma cell line in culture

Journal of the National Cancer Institute


Small cell undifferentiated carcinoma of the minor salivary gland containing exocrine, neuroendocrine, and squamous cells


Induction of cells with acinar cell phenotype including presence of intracellular amylase --- Treatment with 12-O-tetradecanoyl-phorbol-13-acetate in a neoplastic human salivary intercalated duct cell line grown in athymic nude mice


Immunoreactive vasoactive intestinal polypeptide in acinic cell carcinoma of the parotid gland


The relation of ras oncogene product p21 expression to clinocopathological status criteria and clinical outcome in squamous cell head and neck cancer


ヒト唾液VIP様免疫活性の検出

ヒト唾液VIP様免疫活性の検出


An adenoid squamous carcinoma-forming cell line established from an oral keratinizing squamous cell carcinoma expressing carcinoembryonic antigen


耳下腺腺房細胞癌におけるVIPの発現

耳下腺腺房細胞癌におけるVIPの発現

Journal of Clinical and Experimental Medicine


Immunoreactive somatostatin in Warthin's tumor


Development of allergic sialadenitis in mice immunized with mumps virus-infected submandibular salivary gland


Monoclonal antibody analysis of peripheral blood lymphocyte subpopulations in squamous cell head and neck cancer


Emergence of differentiated subclones from a human salivary adenocarcinoma cell clone in culture after treatment with sodium butyrate


Immunohistochemical demonstration of carcinoembryonic antigen (CEA) on tissue sections from squamous cell head and neck cancer and plasma CEA levels of the patients

International Journal of Oral and Maxillofacial Surgery


Immunoglobulin A circulating immune complexes in oral squamous cell cancer


Expression of epidermal growth factor and transforming growth factor-beta in human salivary gland adenocarcinoma cell line


Intermediate-sized filaments and specific markers in a human salivary gland adenocarcinoma cell line and its nude mouse tumors


Induction of other differentiation stages in neoplastic epithelial duct and myoepithelial cells from the human salivary gland grown in athymic nude mice


Induction of experimental allergic sialadenitis in mice


臨床参考値の年齢差および性差について --- 臨床科学検査19項目における検討

臨床参考値の年齢差および性差について --- 臨床科学検査19項目における検討

The Official Journal of Japanese Society of Laboratory Medicine


Interferon Activity and Its Characterization in the Sera of Patients with Head and Neck Cancer


Peripheral Tγ lymphocyte population in head and neck cancer

Peripheral T gamma lymphocytes were measured in head and neck cancer patients and controls. The percentage was significantly higher in the 59 cancer patients than in the 46 normal controls (P less than 0.001). The 12 patients with recurrent disease had elevated percentages of T gamma lymphocytes compared with the untreated group (n = 31; P less than 0.05) and the treated, disease-free group (n = 16; P less than 0.05). Moreover, the percentage of T gamma lymphocytes was significantly higher in the 31 patients with regional lymph node metastasis than in the node-negative group (n = 28; P less than 0.05). In a total of 37 patients with squamous cell carcinoma histologically graded I, II, and III, the absolute counts and percentages of T gamma lymphocytes in the grade I group (n = 13) showed significant decreases compared with those in the grade III group (P less than 0.05; n = 6). Moreover, postoperative serial determinations of the percentage of T gamma lymphocytes in the 14 treated, disease-free patients revealed a gradual decrease of T gamma lymphocytes, whereas the five patients with recurrent disease had a tendency to increases in the percentage of T gamma lymphocytes.


唾液分泌型 IgA の酵素免疫測定法とその臨床的意義

唾液分泌型 IgA の酵素免疫測定法とその臨床的意義

記事分類: 医学--免疫学・血清学・アレルギー

記事分類: 医学--免疫学・血清学・アレルギー


Peripheral K-lymphocyte population in head and neck cancer

Peripheral K-lymphocytes in head and neck cancer were measured by assay of plaque forming-cells. In the cancer patients, the percentage (4.37 +/- 0.87%, mean +/- SD, N = 42, P less than 0.01) and absolute counts (68 +/- 28/mm3, P less than 0.01) of K-lymphocytes were significantly lower than those in normal controls (8.04 +/- 1.41%; 175 +/- 53/mm3, N = 29). The untreated group showed decreased K-lymphocyte counts (63 +/- 22/mm3, N = 13) as compared with the treated, disease-free group (83 +/- 27/mm3, N = 13, P less than 0.05). There were significant correlations between absolute counts of K-lymphocytes and T-cells or B-cells within the untreated group (r = 0.79 in T-cells, P less than 0.01; r = 0.64 in B cells, P less than 0.01). Moreover, absolute counts and percentage of K-lymphocytes in the patients having regional lymph node metastasis (58 +/- 25/mm3; 4.14 +/- 0.77%, N = 22) were significantly lower than those in the negative node group (80 +/- 26/mm3, P less than 0.01; 4.63 +/- 0.91%, P less than 0.05; N = 20). In a total of 25 patients with squamous cell carcinoma who were grouped into grade I, II, and III according to classification of the histologic differentiation of the World Health Organization, the absolute counts and percentage of K-lymphocytes in the grade I group (93 +/- 33/mm3; 5.14 +/- 1.08%, N = 7) showed significant increases in comparison to those in the grade II group (62 +/- 19/mm3, P less than 0.02; 4.06 +/- 0.62%, P less than 0.02, N = 14). Moreover, the change of the K-lymphocyte population in the treated, disease-free eight patients revealed a gradual increase of K-lymphocytes. These results led us to suggest that the measurement of peripheral K-lymphocytes is a useful method of characterizing host defense in head and neck cancer.


A family with hereditary lack of T4+ inducer/helper T cell subsets in peripheral blood lymphocytes


頭頸部癌患者末梢血リンパ球サブセットの異常 --- 単クローン抗体による解析

頭頸部癌患者末梢血リンパ球サブセットの異常 --- 単クローン抗体による解析

Journal of Clinical and Experimental Medicine


Effects of intradermal administration of streptococcal preparation OK-432 on interferon and natural killer cell activities in patients with oral cancer


頭頸部眼患者からみたTγ細胞の機能

頭頸部眼患者からみたTγ細胞の機能


単クローン抗体によるヒトリンパ球サブセットの加齢および性別変化

単クローン抗体によるヒトリンパ球サブセットの加齢および性別変化


NF-kB2によるT細胞の新たな調節機構

NF-kB2によるT細胞の新たな調節機構


Epitope mapping of anti-alpha-fodrin autoantibody in juvenile Sjögren's syndrome: difference in major epitopes between primary and secondary cases.

Juvenile Sjögren's syndrome (SS) is an early-onset type of SS. Autoantibody against the N-terminal 120 kDa form of a-fodrin is a specific and sensitive disease marker for both juvenile and adult SS. We investigated the initial and major determinants of a-fodrin in SS. Sera were obtained from patients with juvenile SS, 10 with primary SS and 10 with secondary SS. Epitope specificities of IgG antibodies were examined by dot-blot analyses using overlapping fusion proteins of the N-terminal part (561 amino acid residues) of a-fodrin as antigens. All sera from patients with primary SS reacted with amino acid residues 1 to 98 and 36 to 150, but not with 91 to 199. Epitope mapping using fusion proteins with subfragments, each consisting of about 50 amino acid residues, showed reactivity with amino acid residues 27-80 and 79-132, suggesting that at least 2 epitopes are contained in the first 150 amino acid residues. All 3 cases with neurological complications had additional epitope specificities. Sera from patients with secondary SS showed more diversified specificities and strongly reacted with amino acid residues 1-98 and 334-432, whereas the reactivities to 36-150, a major epitope in primary SS, were minimal. Major and initial B cell epitopes specifically reside in N-terminal amino acids 36-132 and could be used as a diagnostic tool for primary SS. The epitope subsequently expands to other regions of a-fodrin in association with the development of neurological complications or disease progression. Secondary SS has distinct epitope specificities.


RbAp48遺伝子導入マウスにおけるシェーグレン症候群様病態の出現

RbAp48遺伝子導入マウスにおけるシェーグレン症候群様病態の出現