Induction of immune responses and prevention of alveolar bone loss by intranasal administration of mice with Porphyromonas gingivalis fimbriae and recombinant cholera toxin B subunit

INTRODUCTION: Adult periodontitis is initiated by specific periodontal pathogens represented by Porphyromonas gingivalis; however, an effective measure for preventing the disease has not yet been established. In this study, the effectiveness of a vaccine composed of fimbriae of P. gingivalis and recombinant cholera toxin B subunit (rCTB) was evaluated using BALB/c mice. METHODS: Fimbriae and rCTB were co-administered intranasally to BALB/c mice on days 0, 14, 21, and 28. On day 35, mice were sacrificed to determine immunoglobulin levels in serum, saliva, and nasal and lung extracts by enzyme-linked immunosorbent assay. The prevention effect of the vaccine on P. gingivalis-induced periodontitis in mice was evaluated by measuring alveolar bone loss. RESULTS: The rCTB significantly increased serum immunoglobulin (Ig)A levels when mice were administered with a minimal amount (0.5 microg) of the fimbrial antigen. The adjuvant effect on serum IgG production was indistinct because the minimal amount of the antigen still induced a large amount of IgG. In contrast to systemic responses, a fimbria-specific secretory IgA response was strongly induced by co-administration of rCTB and 0.5 microg fimbriae; the same amount of the antigen alone scarcely induced a response. Histopathological examination revealed IgA-positive plasma cells in the nasal mucosal tissue but no observable mast cells in the area. In addition, nasal administration of the fimbrial vaccine significantly protected the mice from P. gingivalis-mediated alveolar bone loss. CONCLUSION: Nasal vaccination with a combination of fimbriae and rCTB can be an effective means of preventing P. gingivalis-mediated periodontitis.     

CD64 Surface Expression on Neutrophils and Monocytes Is Significantly Up-Regulated after Stimulation with Granulocyte Colony-Stimulating Factor during CHOP Chemotherapy for Patients with Non-Hodgkin’s Lymphoma

The present study was performed to examine whether the expression of CD64 Fc gamma receptor type I (FcgammaRI) on both neutrophils and monocytes can be modulated by multiple daily administrations of granulocyte colony-stimulating factor (G-CSF) to patients with non-Hodgkin's lymphoma in neutropenia caused by CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. The expression of CD64 was determined by flow cytometric analysis at the following time points: before chemotherapy, at the nadir of the neutrophil count, at the fifth day after the start of G-CSF administration, and at more than 8 days after the start of G-CSF administration. CD64 expression was enhanced in patients given G-CSF during CHOP treatment, whereas CD64 expression remained unchanged in patients not given G-CSF CD64 expression levels on both neutrophils and monocytes were significantly up-regulated by the daily administration of G-CSF and reached peak levels at day 5 (P = .0007). Thereafter, expression on both cell types remained at almost the same levels as on day 5 for the rest of the treatment course, even though G-CSF therapy continued for 3 to 5 more days. Interestingly, CD64 expression on monocytes was already increased significantly (P = .0001) at the nadir of the neutrophil count relative to the baseline before chemotherapy and then was additionally up-regulated by day 5 after the start of G-CSF injections (P = .019). In antibody-dependent cellular cytotoxicity assays, we found that rituximab-mediated cell lysis was significantly enhanced at day 5 after the start of G-CSF treatment (P = .01). In conclusion, this study shows that multiple doses of G-CSF administered to lymphoma patients with neutropenia due to CHOP chemotherapy can enhance CD64 expression on both neutrophils and monocytes. Peak CD64 levels are reached at day 5 of G-CSF treatment, resulting in an activation of the rituximab-mediated antitumor ability of these effector cells. This finding may be useful in determining the optimal timing of administration for an antibody such as rituximab in a chemotherapeutic strategy designed to exert a maximal effect against tumor cells.     

Left non-recurrent inferior laryngeal nerve in a patient with right-sided aortic arch and aberrant left subclavian artery

Non-recurrent inferior laryngeal nerve (NRILN) is rare but one of the important anatomical variations in thyroid and parathyroid surgery. Almost all cases were observed on the right side with aberrant right subclavian artery and left NRILN have been reported in only five cases so far. Here, we reported a 38 year-old Japanese male with left NRILN accompanying adenomatous goiter. He was referred to our hospital for the surgical treatment of left thyroid goiter. Preoperative computed tomography revealed right-sided aortic arch and aberrant left subclavian artery with no signs of complete situs inversus viscerum, suggesting possible left NRLN. Left hemithyroidectomy was performed using nerve monitoring system. Intraoperatively, left recurrent laryngeal nerve was not identified along tracheoesophageal groove, but directly originated from vagal nerve and was running horizontally to larynx. Mobility of vocal cords were not impaired and postoperative course was uneventful. During thyroid surgery for the patients with right-sided aortic arch, meticulous care should be taken using nerve monitoring system to avoid nerve injury.     

Ketoacidosis,Hypertriglyceridemia and Acute Pancreatitis Induced by Soft Drink Polydipsia in a Patient with Occult Central Diabetes Insipidus

A 21-year-old Japanese man without known diabetes mellitus had abdominal pain. The diagnosis was ketoacidosis and hypertriglyceridemia-induced acute pancreatitis. He had polydipsia and polyuria and had habitually drunk several soft drinks every day for two years. After hospitalization, despite adequate liquid intake, dehydration remained with hypotonic polyuria. Further examinations revealed the coexistence of central diabetes insipidus (CDI), possibly caused by lymphocytic infundibulo-neurohypophysitis, based on anti-rabphilin-3A antibody positivity. Although CDI had been undiagnosed for two years, over-consumption of sugar-rich soft drinks to ease thirst caused ketoacidosis, hypertriglyceridemia, and acute pancreatitis. There are no previous reports of this three-part combination of symptoms caused by CDI.     

GPR43 Suppresses Intestinal Tumor Growth by Modification of the Mammalian Target of Rapamycin Complex 1 Activity in ApcMin/+ Mice

ObjectiveG protein-coupled receptor 43 (GPR43), a receptor for short-chain fatty acids, plays a role in suppressing tumor growth; however, the detailed underlying mechanism needs to be comprehensively elucidated. In this study, we investigated the role of GPR43 in inhibiting tumor growth using Apc^Min/+, a murine model of intestinal tumors.Materials and MethodsUsing GPR43^−/− Apc^Min/+ and GPR43^+/− Apc^Min/+ mice, the number of tumors was analyzed at the end of the experimental period. Immunohistochemistry, quantitative polymerase chain reaction, and Western blotting were performed to analyze cellular proliferation and proliferation-associated signal pathways.ResultsOur results revealed that GPR43 deficiency resulted in increased tumor numbers in Apc^Min/+ mice. Ki67 was highly expressed in GPR43^−/− mice (p > 0.05). Increased expression levels of proinflammatory cytokines, including interleukin-6 and tumor necrosis factor-α, and amino acid transporters were not observed in GPR43-deficient mice compared to GPR43-sufficient mice. Furthermore, GPR43-deficient tumor tissues showed enhanced mammalian target of rapamycin-mediated phosphorylated ribosomal protein S6 kinase beta-1 (p > 0.05) and phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 (p > 0.05), but not Akt (protein kinase B) phosphorylation (p = 0.7088).ConclusionCollectively, GPR43 affords protection against tumor growth at least partly through inhibition of the mammalian target of rapamycin complex 1 pathway.