Tsutomu Ueda

Nuclear Factor-Kappa B Activation in the Nasal Polyp Epithelium: Relationship to Local Cytokine Gene Expression†

Objectives A panel of cytokines has been found to be important for eosinophil accumulation and activation in nasal polyps. The aims of this study were to ascertain whether the activation of nuclear factor‐kappa B (NF‐κB) occurred in the polyp epithelium, and to examine the relationship between the degree of activation and local cytokine gene expression.

Leukotriene Receptor Antagonist Pranlukast Suppresses Eosinophil Infiltration and Cytokine Production in Human Nasal Mucosa of Perennial Allergic Rhinitis

The purpose of this study was to investigate the influence of pranlukast on eosinophilic inflammation and cytokine production in human nasal mucosa. Twelve patients were treated with pranlukast, and samples were obtained from the nasal mucosa of the inferior turbinate. With respect to cell infiltration, a significant decrease was observed in the percentage of inflammatory cells (secreted eosinophil cationic protein [EG2] and neutrophil elastase) after treatment. The levels of cytokines and chemical mediators (interleukin [IL]–4, IL-5, RANTES [regulated on activation, normal T cell expressed and secreted], cysteinyl leukotrienes, IL-1β, tumor necrosis factor–α, and IL-8) assessed by enzyme-linked immunosorbent assay and enzyme immunoassay were significantly decreased. These results indicate that pranlukast decreased the levels of a majority of the cytokines in nasal mucosa, leading to improvement in subjective nasal symptoms. Furthermore, these results support the hypothesis that pranlukast exerts its therapeutic action primarily by blocking the leukotriene receptors on eosinophils.

Suppression of the Th2 pathway by suplatast tosilate in patients with perennial nasal allergies.

Background Suplatast tosilate (IPD-1151T), a selective Th2 cytokine inhibitor that suppresses the production of interleukin (IL)-4 and IL-5 in vitro or in animal models has been proved clinically effective for allergic rhinitis (AR). The aim of this study was to investigate changes in the Th2 pathway in human nasal mucosa after medication with IPD-1151T. Twelve patients were treated with IPD-1151T. Methods Twelve healthy volunteers served as normal controls. The following parameters were evaluated: (i) subjective nasal clinical symptoms, (ii) percentages of inflammatory cells (EG2, CD4, and CD8) by immunocytological staining, and (iii) levels of cytokines (IL-4, IL-5, IL-13, regulated on activation, normal T-cell expressed, and secreted [RANTES], and interferon [IFN] γ) by enzyme-linked immunosorbent assay. Results Nasal symptom scores significantly decreased after treatment. With respect to cell infiltration, a significant decrease was observed in the percentage of inflammatory cells (EG2 and CD4) and CD4/CD8 ratio. The levels of cytokines (IL-4, IL-5, IL-13, and IFN-γ) and the IL-5/IFN-γ ratio were significantly decreased, and the IL-4/IFN-γ ratio became not significantly different from that in normal subjects. In contrast, RANTES did not change significantly. The percentage of reduction in IL-5 correlated with that in eosinophil infiltration, whereas that in RANTES did not. Conclusion These results suggest that IPD-1151T can reduce the Th2 pathway.

Reduced expression of p27 is correlated with progression in precancerous lesions of the larynx

OBJECTIVES Factors related to malignant transformation of laryngeal precancerous lesions remain largely unknown, so we investigated the relationship between the expression of p27 and precancerous laryngeal lesion. STUDY DESIGN In this study we investigated the expressions of p27 and p53 protein in 56 cases with laryngeal precancerous or cancer lesions (20 cases of hyperplasia, 19 of dysplasia, and 17 of squamous cell carcinoma), and went on to evaluate the relationship between immunoreactivity of each of them and the histological findings. We also evaluated the correlation between immunoreactivity and proliferative activity with the aid of Ki-67 nuclear antigen staining. METHODS A retrospective study was performed in 56 cases (20 with epithelial hyperplasia, 19 with epithelial dysplasia and 17 with laryngeal cancer). Immunohistochemistry was performed to investigate expression of p27, p53 protein and Ki-67 nuclear antigen staining, using the avidian-biotin-peroxidase complex technique. RESULTS p27 immunostaining was observed in 12 out of 20 cases of hyperplasia (60%), six out of 19 cases of dysplasia (31%), and 2/17 (12%) of carcinoma. We found significant association between p27 immunostaining and the histological findings. On the other hand, p53 immunostaining was observed in 6/20 (30%) of hyperplasia, 3/19 (16%) of dysplasia, and 7/17 (41%) of carcinoma. No significant association was found between p53 and the histological findings. CONCLUSIONS Our results revealed that immunohistochemical assessment of p27 in bioptic samples of laryngeal precancerous lesions might be useful in selective patients who should undergo a more specific follow-up evaluation.

Increased exhaled nitric oxide and its oxidation metabolism in eosinophilic chronic rhinosinusitis.

OBJECTIVE Monitoring of fractional concentrations of exhaled nitric oxide (FeNO) has become a reliable marker of inflammation in human nose and paranasal sinuses. However, it is still unknown to what extent nasal NO levels contribute to the pathology of chronic rhinosinusitis (CRS). In the present study, we aimed to examine FeNO levels and the underlying mechanism of NO production and metabolism in patients with eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS. METHODS Thirty-three untreated ECRS patients, 16 non-ECRS patients, and 38 normal subjects were enrolled in this cross-sectional study of FeNO levels. Oral and nasal FeNO levels were measured before treatment using an electrochemical NO analyzer (NObreath(®)) with a nose adaptor. The mRNA expression of three nitric oxide synthase (NOS) isoforms, interleukin-5 (IL-5), and transforming growth factor-beta (TGF-β) in the ethmoid sinus mucosa and nasal polyps were analyzed by real-time PCR. Immunohistological localization of inducible NOS (iNOS) and nitrotyrosine (NT), a marker for oxidized NO metabolites, was also examined. RESULTS ECRS patients showed significantly higher oral FeNO levels compared to non-ECRS patients and normal subjects (mean values, 47.6, 13.5, and 15.3ppb, respectively). Nasal FeNO levels of the non-ECRS patients (30.5ppb) were significantly lower than those of the ECRS patients (53.9ppb) and normal subjects (45.5ppb). Positive correlations existed between the blood eosinophil percentage and FeNO levels in ECRS patients. Histologically, ECRS patients showed higher eosinophil accumulation in the ethmoid mucosa than non-ECRS patients (103.1 vs. 16.3cells/HPF). Real-time PCR analysis showed significant upregulation of iNOS and IL-5 mRNA expression in the ethmoid mucosa of the ECRS patients compared to those of non-ECRS patients. Positive iNOS immunoreactivity was observed in ciliated epithelial cells, submucosal glands and associated inflammatory cells in both groups. NT immunoreactivity was detected in the epithelium and around inflammatory cells. Intense NT staining was co-localized with eosinophil accumulation and ECRS patients showed significantly higher rates of NT-positive cells than non-ECRS patients. CONCLUSION A combination of oral and nasal FeNO measurement is a valid marker for the classification and definition of different CRS subtypes in Japan. Higher levels of oral and nasal FeNO in ECRS patients may reflect the persistence of eosinophilic inflammation in sinus mucosa with concomitant iNOS upregulation and accompanying deposition of oxidized NO metabolites.

Low-dose dexamethasone with fosaprepitant and palonosetron to prevent cisplatin-induced nausea and vomiting in head and neck cancer patients

Abstract Objective: To determine if a lower dose of dexamethasone can be used in combination with fosaprepitant and palonosetron for cisplatin-induced nausea and vomiting in head and neck cancer patients, we conducted a single-center, two-arm, cross-over comparison study. Methods: Patients were randomly assigned to either standard dose dexamethasone group: intravenous 9.9 mg on day 1 and 6.6 mg on days 2–4 or low-dose dexamethasone group: intravenous 3.3 mg on days 1–4 for the first course and crossed over to the other treatment for the second course. The primary endpoint was complete response (CR) in the overall period. Results: Twenty-five patients were screened for the study and 22 were evaluable. Eleven patients were randomly assigned to the standard dose dexamethasone group and 12 patients to the low-dose dexamethasone group. The CR rate in the overall period was 86% in the standard dose group and 73% in the low-dose group, showing no significant difference (p = .61). Conclusion: The efficacy of low-dose dexamethasone with fosaprepitant and palonosetron was not inferior to that of the standard dose dexamethasone in the highly emetogenic cisplatin-based treatment for head and neck cancer patients.

Extraskeletal osteosarcoma in the parotid gland: A case report

Extraskeletal osteosarcoma is a very rare tumor and accounts for 4-5% of all osteosarcomas. We describe a 47-year-old Japanese man who presented with a right parotid tumor. The patient underwent total resection with postoperative radiotherapy; however, the tumor recurred in the lung, whereupon he underwent chemotherapy and partial lung resection. After surgery, a hemorrhagic brain metastasis appeared; this tumor was extirpated to prevent bleeding into the brain, after which additional chemotherapy was administered. Nevertheless, the patient developed additional metastases and died 17 months after the total parotidectomy. This tumor was unique in that it arose in the parotid gland; this case provides an instructional example of an extremely rare manifestation of this type of tumor.

Clinical Efficacy of 200 mg Twice Daily Administration of Levofloxacin in the Treatment of Sinusitis

Fluoroquinolones, such as levofloxacin (LVFX), exert antibacterial effects in a dose-dependent manner and show a postantibiotic effect (PAE) that inhibits the growth of microorganisms after brief contact with the agent. In the present study, we prospectively evaluated whether the mode of administration influences the clinical efficacy of oral LVFX for infectious sinusitis. One hundred seven sinusitis patients were randomly divided into two groups (Group A (n=50): 200mg twice a day, Group B (n=57); 100mg three times a day). Both groups were treated with oral LVFX for 5-10 days then the clinical effectiveness and radiological improvement were evaluated. After treatment, 46.7% of patients in Group A and 65.1% of patients in Group B showed a clinical response, with the complete resolution rate being more pronounced in the latter group. Radiological improvement was observed in 42.0% of patients in Group A and 46.2% of patients in Group B. However, the difference was not significant. Treatment with oral LVFX proved efficacious for bacterial sinusitis, either acute or acute exacerbation. Our results also indicated that administering 200mg twice a day is an effective and applicable alternative to obtain better clinical and bacteriological efficacy based on the theoretical pharmacodynamics.

A Case of Cutaneous Leiomyosarcoma of the Cheek

Leiomyosarcoma is a malignant neoplasm of smooth muscle origin that rarely occurs in external soft tissues of the head and neck region. We report a 61-year-old male with cutaneous leiomyosarcoma of the right cheek. The tumor, which had a rough surface, was 45×35mm in size, roundish in shape and well movable from the underlying tissues but not from the skin. The consistency was hard and elastic without tenderness. The tumor was completely excised with a margin of 25mm proximally. The defect of overlaying skin was reconstructed using a D-P flap. The tumor was composed of long spindle-shaped cells with blunting nuclei. Multinucleated giant cells and mitotic cells were also found. Immunohistochemical examinations showed that these cells were positive for anti α-smooth muscle actin antibody, but negative for S-100 protein, CD34, CD68 (Kp-1) and p53. A boxed-in appearance was observed by silver staining. This tumor was diagnosed as leiomyosarcoma by these findings. No local recurrence or distant metastasis were noted one year after the excision.