Effectiveness of intragastric immunization with protein and oligodeoxynucleotides containing a CpG motif for inducing a gastrointestinal mucosal immune response in mice

PURPOSE: To investigate a new modality of mucosal vaccines, we evaluated the effectiveness of intragastric immunization for inducing a mucosal immune response in the gastrointestinal tract. METHODS: Mice were immunized with beta-galactosidase (beta-gal) and synthesized oligodeoxynucleotides containing a CpG motif (CpG-DNA) by intragastric injection, and the immune response was compared with those induced by 3 other immunization forms: intranasal, oral, and intradermal. RESULTS: Intragastric immunization with beta-gal and CpG-DNA induced significant anti-beta-gal fecal IgA production at 2 weeks; however, at 4 weeks the response was lacking. In contrast, intranasal immunization with beta-gal and CpG-DNA induced the highest anti-beta-gal fecal IgA production at 4 weeks. CONCLUSION: Although intragastric immunization with protein and CpG-DNA induces a mucosal immune response in the gastrointestinal tract, intranasal immunization is the most effective to induce both mucosal and systemic immune responses. This finding may increase the possibility for developing vaccines against mucosal pathogens, especially Helicobacter pylori.     

A five-year review of patients admitted with the diagnosis of bacterial endophthalmitis

We conducted a retrospective, hospital-based study of patients who were diagnosed with bacterial endophthalmitis on admission to the Department of Ophthalmology, Hiroshima University Hospital, between January 1999 and December 2003. Thirty eyes of 30 patients were identified. Of these patients, 19 eyes had postoperative endophthalmitis, 8 eyes had penetrating trauma and 3 eyes were infected from an endogenous source. All of the patients underwent immediate three-port pars plana vitrectomy. Vitreous specimens of diabetic patients demonstrated a significantly higher incidence of positive bacterial culture. Diabetic vitreous appeared to be a good medium for culture. Visual acuity of hand motion or less at the latest follow-up visit was associated with the presence of diabetes. Prompt treatment with vitrectomy and intra-vitreal antibiotics is crucial for patients with bacterial endophthalmitis, especially if they are diabetic.     

A minute nonfunctioning islet cell tumor demonstrating malignant features

We report a patient with a minute nonfunctioning islet cell tumor, 8mm in diameter, which demonstrated malignant features by histology. The patient was a 43-year-old Japanese woman, who had an elevated carbohydrate antigen (CA) 19-9 level, of 59U/ml (normal range, <37U/ml) identified on a health check to rule out malignancies. Ultrasonography and computed tomography demonstrated a well-defined pancreatic tumor, 8mm in diameter, in the body of the pancreas. Serum levels of pancreatic hormones were within normal limits, and thus a tentative diagnosis was nonfunctioning islet cell tumor. The size of the tumor remained unchanged for 1¹/₂ years, but, at this time, the serum level of CA19-9 was elevated to 253U/ml. Segmental pancreatectomy was performed because malignancy could not be ruled out. The resected specimen showed an endocrine tumor invading both the pancreatic parenchyma and the perineural spaces outside the tumor. In general, minute nonfunctioning islet cell tumors have been considered to be completely benign, but the present tumor showed clear malignant features. We might have to take surgical resection into consideration even if the size of such an endocrine tumor is minute.     

RhoGTPase activation is a key step in renal epithelial mesenchymal transdifferentiation

ESRD is characterized by an interstitial infiltrate of inflammatory cells in association with tubular atrophy, epithelial mesenchymal transdifferentiation (EMT), and interstitial fibrosis. Human proximal tubular epithelial cells (HK2 cells) undergo EMT in response to activated PBMC conditioned medium (aPBMC-CM), showing acquisition of a fibroblastoid morphology, increased fibronectin-EDA (EDA) expression, loss of junctional E-cadherin localization, and cytokeratin 19 (K19) expression. The signaling pathway(s) that regulates EMT in response to aPBMC-CM is not well understood. This study shows that aPBMC-CM induces a rapid activation of RhoA, Rac1, and Cdc42 activity in HK2 cells from 15 min to 48 h. Moreover, infection with adenovirus expressing constitutively active RhoA, Rac1, and Cdc42 significantly increased the expression of EDA and downregulated expression of E-cadherin and K19. Dominant negative RhoA expression suppressed aPBMC-CM-induced upregulation of EDA but did not restore the expression of E-cadherin and K19. Constitutively active RhoA activated the Rho kinase and its downstream effectors, whereas constitutively active Rac1 and Cdc42 activated the P21-activated protein kinase in epithelial cells. In further experiments, HK2 cells were treated with toxin B, exoenzyme C3, Y-27632, and HA1077. These strategies, inhibiting the Rho/Rho kinase pathway, as well as the Rac1/Cdc42/P21-activated protein kinase pathway, blocked transdifferentiation of HK2 cells in response to aPBMC-CM. To conclude, these results indicate that aPBMC-CM activates RhoA, Rac1, and Cdc42 and their downstream effectors, leading to HK2 cells undergoing transdifferentiation. Therefore, activation of small RhoGTPases is a key step in the mechanism of EMT and likely to be a contributor to tubulointerstitial fibrosis.     

Three cases of pulmonary hamartoma appearing after radical nephrectomy for renal cell carcinoma

We report 3 patients with pulmonary hamartoma, all of whom had undergone nephrectomy for renal cell carcinoma. A lung tumor was detected 2 to 9-months following nephrectomy. Preoperative diagnosis was pulmonary metastasis from renal cell carcinoma and pulmonary tumor resection was performed in each case. There was a 9- to 12-month interval between the detection and resection of the lung tumor. The histological diagnosis of the lung tumor in all three patient was pulmonary hamartoma. Following the resection of the lung tumor, recurrence was not noted in any of the patients.