Koichi Sawaki

Localization of antimicrobial peptides human β‐defensins in minor salivary glands with Sjögren’s syndrome

Sjögrens syndrome is a common systemic autoimmune disease associated with inflammatory cells that infiltrate exocrine glands. The antimicrobial peptides human beta-defensin-1, human beta-defensin-2, and human beta-defensin-3 are expressed in various human epithelial cells and in normal salivary glands. Antimicrobial peptides provide local protection against infection and participate in inflammatory responses. Because of the presence of inflammation, we hypothesized that human beta-defensin expression in minor salivary glands may be increased in subjects with Sjögrens syndrome. However, the expression of human beta-defensins 1 and 2 was decreased in salivary glands affected by Sjögrens syndrome in comparison with the human beta-defensin expression patterns in salivary glands from normal subjects. In addition, the reduction in expression of human beta-defensin-2 was greater than the reduction in expression of human beta-defensin-1. The aforementioned result suggests that the reduction in expression of human beta-defensin-2 may occur earlier than the reduction in expression of human beta-defensin-1, which may lead to a greater decrease in human beta-defensin-2 than in human beta-defensin-1 during disease progression.

Expression of Human α- and β-Defensins in Odontogenic Keratocysts and Radicular Cysts

Abstract Objective: To identify the location of human β-defensin-2 and human α-defensins in odontogenic keratocysts and radicular cysts. Patients and Methods: Immunohistochemical staining of tissue sections from enucleation specimens of 14 patients with odontogenic keratocysts and 19 patients with radicular cysts, and from normal oral mucosa from 2 healthy volunteers was done using mouse monoclonal antibodies against human cytokeratin 5/6 and rabbit polyclonal antibodies against human β-defensin-2. Results: Human β-defensin-2 immunoreactivity was evident in 10 of 14 odontogenic keratocysts (72%), and in 7 of 19 radicular cysts (37%). Signals for human β-defensin-2 were detected in the cytoplasm of keratinocytes in the parakeratinised and granular layers in both types of cysts. The localisation of human Pdefensin-2 did not differ between cysts and normal mucosa. Human α-defensin immunoreactivity was detected in both types of cysts, but not in keratinocytes. Signals for human α-defensins were detected in the cytoplasm of neutrophils in the lamina propria. Conclusion: Many cysts generate human β-defensin-2 and human α-defensins suggesting that similar defence mechanisms utilising defensins exist in both types of cysts, as well as in normal oral mucosa.

Medication‐related osteonecrosis of the jaws caused lethal sepsis in an edentulous patient with multiple systemic factors

Medication‐related osteonecrosis of the jaw (MRONJ) is developed even in the patients who are edentulous and treated with short‐term bisphosphonate therapy and oral administration. It sometimes causes lethal sepsis in patients who have multiple health problems such as diabetes, cirrhosis, steroid use for interstitial pneumonia, sepsis, and spinal disk herniation.

The potential of positron emission tomography/computerized tomography (PET/CT) scanning as a detector of high-risk patients with oral infection during preoperative staging

OBJECTIVE It is sometimes difficult to determine during the preoperative period whether patients have oral infections; these patients need treatment to prevent oral infection-related complications from arising during medical therapies, such as cancer therapy and surgery. One of the reasons for this difficulty is that basic medical tests do not identify oral infections, including periodontitis and periapical periodontitis. In this report, we investigated the potential of positron emission tomography/computerized tomography (PET/CT) as a diagnostic tool in these patients. STUDY DESIGN We evaluated eight patients during the preoperative period. All patients underwent PET/CT scanning and were identified as having the signs of oral infection, as evidenced by (18)F-fludeoxyglucose (FDG) localization in the oral regions. Periodontal examination and orthopantomogram evaluation showed severe infection or bone resorption in the oral regions. RESULTS (18)F-FDG was localized in oral lesions, such as severe periodontitis, apical periodontitis, and pericoronitis of the third molar. The densities of (18)F-FDG were proportional to the degree of inflammation. CONCLUSIONS PET/CT is a potential diagnostic tool for oral infections. It may be particularly useful in patients during preoperative staging, as they frequently undergo scanning at this time, and those identified as having oral infections at this time require treatment before cancer therapy or surgery.

Presence of Human β-Defensin-2 in Oral Lichen Planus and its Histamine Releasing Effect

Abstract Objective: To determine by immunohistochemical means the localization of human β-defensin-2, a peptide with antimicrobial activity, in oral lichen planus. The release of histamine from mast cells elicited by human β-defensin-2 was also investigated. Materials and Methods: Biopsy specimens of oral lichen planus, synthetic human β-defensin-2, human α-defensin-1, and mast cells isolated from Sprague Dawley rats were used. Tissue sections were embedded in paraffin and immunostained by the streptavidin-biotin-coupled peroxidase method. Isolated rat mast cells were injected with synthetic human β-defensin-2 and human α-defensin-1. Evans blue dye was injected into the tail vein of Sprague Dawley rats, followed by various doses of histamine, human β-defensin-2, human α- defensin-1, and saline. Results: Epithelial cells in lichen planus from the corneal layer to the spinous layer, were positively stained with anti-human β-defensin-2 antibody. Mast cells in subepithelial areas were also stained by anti-human β-defensin-2 antibody. Human β-defensin-2-induced histamine release from the isolated rat mast cells occurs in a dose-dependent manner. When human β-defensin-2 was injected into rat skin intradermally, the vascular permeability increased. These responses were completely abolished upon injection of the antihistamine drug diphenhydramine hydrochloride. Conclusion: Human β-defensin-2 and histamine may play an important role in the formation of oral lichen planus.

Histamine Release from Rat Mast Cells Induced by Human α-Defensin-1 Present in Jaw Cyst Fluid

Abstract Objective: To investigate the release of histamine from rat mast cells elicited by human α-defensin-1 contained in jaw cyst fluid. Patients and Methods: Human α-defensin-1 was purified by reversed-phase high-performance liquid chromatography from human jaw cyst fluid, and the mast cells were collected from the peritoneal cavities of rats. Results: Histamine release was induced in isolated rat mast cells by both extracted and synthetic human α-defensin-1. Changes in vascular permeability induced by human α-defensin-1 were also estimated by the passive skin test in rats. Extracted and synthetic human α-defensin-1 induced histamine release from isolated rat mast cells in a dose-dependent manner over a concentration range of 1 to 15 μg/mL; the histamine release induced by the extracted and synthetic human α-defensin-1 (15 μg/mL) was 39.4 ± 2.3 and 37.6 ± 1.8%, respectively. When human α-defensin-1 was injected into rat skin intradermally, the vascular permeability increased. This response occurred with as little as 0.1 μg of human α-defensin-1, and a strong response was observed with 0.5 and 1.0 μg. These responses were completely abolished upon injection with 1 μg of the antihistamine drug diphenhydramine hydrochloride. Conclusion: Human α-defensin-1 in human jaw cyst fluid can act as an inducer of histamine release from mast cells both in vivo and in vitro.