Tetsuo Nagai

The clinical phenotype of pemphigus is defined by the anti-desmoglein autoantibody profile

BACKGROUND Some patients with pemphigus vulgaris (PV) have mucous membrane erosions with minimal skin involvement (mucosal dominant type), and others show extensive skin blisters and erosions in addition to mucous membrane involvement (mucocutaneous type). Patients with pemphigus foliaceus (PF) show only skin involvement. OBJECTIVE The purpose of this study is to determine whether there is a difference in autoantibody profile among mucosal dominant PV, mucocutaneous PV, and PF. METHODS Antibody titer against desmoglein 1 (Dsg 1) and desmoglein 3 (Dsg3) were measured with enzyme-linked immunosorbent assay using recombinant Dsg1 and Dsg3. Sera were obtained during clinically active disease from 24 patients with mucosal dominant PV, 20 with mucocutaneous PV, and 23 with PF. RESULTS All sera samples from patients with mucosal dominant PV sera were negative against Dsgl but positive against Dsg3. All sera samples from those with mucocutaneous PV were positive against both Dsg1 and Dsg3. All sera samples from patients with PF were positive against Dsg1, but negative against Dsg3. CONCLUSION Each subtype has its own anti-Dsg autoantibody profile, indicating that the clinical phenotype of pemphigus is defined by the autoantibody profile.

Pathogenic autoantibody production requires loss of tolerance against desmoglein 3 in both T and B cells in experimental pemphigus vulgaris

Mechanisms of tolerance break against desmoglein 3 (Dsg3) in patients with pemphigus vulgaris (PV) producing pathogenic anti‐Dsg3 IgG autoantibodies are unclear. In this study, using a novel PV mouse model involving Dsg3 knockout mice, we investigated the mechanisms leading to production of autoantibodies against Dsg3. Adoptive transfer of Dsg3–/– splenocytes immunized with recombinant mouse Dsg3 to Rag2–/– recipient mice expressing Dsg3 resulted in the stable production of anti‐Dsg3 IgG and development of PV phenotypes including oral erosions with suprabasilar acantholysis. When purified T and B cells from Dsg3–/–, Dsg3+/– or Dsg3+/+ mice were mixed with various combinations and transferred to Rag2–/– mice, pathogenic anti‐Dsg3 IgG production was observed only with a combination of Dsg3–/– T and Dsg3–/– B cells but not with the other combinations. These results suggest that loss of tolerance against Dsg3 in both B and T cells is important for the development of autoimmune state of PV.

Lingual osseous choristoma, Report of 2 cases

Abstract 2 cases of lingual osseous choristoma are reported. A brief review of the literature on this lesion is presented, and possible causes for this unusual case are discussed.

Local control of squamous cell carcinoma of the mobile tongue: an experience of different modalities

From 1966 through 1983, 163 patients with squamous cell carcinoma of the mobile tongue were treated. Fifty-two patients were staged as T1N0, 77 as T2N0, 14 as T2N+, 8 as T3N0, 7 as T3N+, and 5 as T4. The follow-ups were complete. Treatment modalities varied considerably during that period, because of increasing difficulty to use radioactive sources by regulations. All T3N+ and T4 patients died shortly after treatment. Five year absolute survivals for the T1N0, T2N0, T2N+, and T3N0 patients were 87%, 60%, 27% and 63%, respectively. Local recurrence free survivals at 5 years for the T1N0, T2N0, T2N+, and T3N0 patients were 72, 48, 58, and 88%, respectively. Local recurrence free survivals seemed to be better with Ra-226 needling +/- external irradiation (EXT) than other modalities. Because many patients with local recurrence were salvaged, ultimate local-disease-free survivals should also be considered. They were 96 and 70% at 5 years for the T1N0 patients treated with Ra-226 +/- EXT, and with surgery +/- EXT, respectively; the corresponding figures for the T2N0 patients were 83 and 64%. For these reasons, Ra-226 needling may be preferable to other modalities as initial treatment. Although cervical failures did not develop after 2 years of treatment, late local recurrences were rather common, even after 5 years. Long-term follow-up is mandatory for the management of the patients, and analyzing and comparing the results.

Reticulum-cell sarcoma of the jaws: Report of two cases and comparison of incidence in Japan and other countries

The two cases presented involved a sarcoma which may arise primarily in the gingivae and mandible. These sarcomas were treated with radiation and chemical antitumor agents. The primary lesions showed complete remission, but later there was rapid extension and metastasis to many vital organs. A review of the literature demonstrates the lesions occurrence in the head and neck region in Japan and other countries.

Experimental radiosensitizer therapy of malignant tumor transplanted to nude mice. (5). Radiosensitive effect of immidazole compounds for human maxillary carcinoma.

The purpose of our investigation is to compare the radio-enhancement of three imidazole compounds to human oral malignant tumor transplanted on nude mice.Methods and evaluation: Battelle Columbus Laboratories Protocol.Tumor: PNC-1-JCK=human maxillary poorly differentiated squamous cell carcinoma.Subjects: Male CD-1 (ICR) nu/nu, BALBc nu/nu and conventional C 57 BL/6 N (age 10 weeks, 20-25g body weight).Imidazole compounds: Misonidazole (MISO) 20mg/mouse, dinitroimidazole ethanol (DNIE) 10mg/mouse and 5-methoxy carbonyl-2-methyl sulfinyl-l-methyl imidazole (KIH-3) 40mg/mouse.Tumors were transplanted to the subcutaneous region of the right thigh of CD-1 (ICR) nu/nu.Radiation: 60Co 15 Gy local radiation.These imidazole compounds were administrated into the abdomen of the CD-1 (ICR) nu/nu prior to 30 minutes of local irradiation.NK activity was compared among CD-1 (ICR) nu/nu, BALBc nu/nu and conventionalC 57 BL/6 N.Results: Radiosensitive effect was evaluated for MISO 20mg+60Co 15 Gy group. DNIE 10mg+60Co 15 Gy and KIH-3 40mg+60Co 15 Gy groups were observed to show radioprotective effects rather than radiosensitivity.% NK activity was as follows:CD-1 (ICR) nu/nu, 4.9 in YAC-1 100:1; 7.0 in RL-male 100:1. BALBc nu/nu 24.6 in YAC-1 100:1; 15.9 in RL-male 100:1. C 57 BL/6 N 21.4 in YAC-1 100:1; 24.0 in RL-male 100:1.