PURPOSE: The pathogenesis of nasal polyposis (NP) is unclear. Eosinophils and mast cells are considered to play important roles in this process. In addition, the levels of Th2-type cells are increased, irrespective of the atopic status of the patient with NP. In this context, we and others have shown high levels of thymus and activation-related chemokine/CCL17, macrophage-derived chemokine, eotaxin, and RANTES in patients with NP. Forkhead box P3 (FOXP3) plays a key role in CD4+CD25+ regulatory T-cell function and represents a specific marker for regulatory T cells (Tregs). Decreased expression of FOXP3 has been reported in allergic diseases. The present study was designed to evaluate the presence and potential roles of Tregs, defined by the expression of FOXP3 protein, in NP. METHODS: Using immunohistochemistry, we estimated the numbers of FOXP3+ cells in the epithelium and lamina propria of the NPs of 17 patients with chronic rhinosinusitis with NP and the nasal mucosa of 15 patients with allergic rhinitis (AR). The number of FOXP3+ cells in NPs was compared with that in the nasal mucosa of patients with AR, and the numbers of FOXP3+ cells in atopic and non-atopic NP were also compared. RESULTS: The number of FOXP3+ cells in the lamina propria of patients with NP was significantly lower than that in the nasal mucosa of the AR patients (2.79 vs. 5.99, P=0.008). There was no statistically significant difference noted for the numbers of FOXP3+ cells between the epithelium of the NP and the nasal mucosa (3.60 vs. 2.39, P=0.180). Furthermore, the numbers of CD4+FOXP3+ cells were lower in NPs than in the allergic nasal mucosa. There was no difference in the number of FOXP3+ cells between the atopic and non-atopic NP patients. CONCLUSIONS: Fewer Tregs (i.e., decreased FOXP3 expression) are found in NPs than in the nasal mucosa of AR patients. As the severity of eosinophilic, Th2-type inflammation and the levels of inflammatory mediators are much higher in NPs than in the nasal mucosa of AR patients, an inverse co-relationship may exist between these parameters and the number of Tregs. The deficiency of Tregs in NP may account for the more pronounced Th2-type inflammation seen in these patients.
Chemokine CCL22 ; Chemokine CCL5 ; Eosinophils ; Epithelium ; Humans ; Immunoglobulin E ; Immunohistochemistry ; Inflammation ; Mast Cells ; Mucous Membrane ; Nasal Mucosa ; Rhinitis ; Rhinitis, Allergic, Perennial ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; Thymus Gland

PURPOSE: Nasal polyposis is a chronic inflammatory disease of the upper airways often associated with asthma and characterized by markedly increased numbers of eosinophils, Th2 type lymphocytes, fibroblasts, goblet cells and mast cells. Previous studies have shown elevated levels of thymic stromal lymphopoietin (TSLP) in atopic diseases like asthma, atopic dermatitis and mainly in animal models of allergic rhinitis (AR). Here, we investigated the expression of TSLP in nasal polyps from atopics and non-atopics in comparison with the nasal mucosa and its potential role in nasal polyposis. METHODS: Messenger RNA expression for TSLP, thymus and activation-regulated chemokine (TARC) and macrophage derived chemokine (MDC) in nasal polyps and nasal mucosa of atopics and non-atopics was analyzed by real time PCR. Immunoreactivity for TSLP in nasal polyps and in the nasal mucosa of patients with AR and non-allergic rhinitis (NAR) was analyzed by immunohistochemistry. Eosinophil counts was analyzed by Wright-Giemsa staining and nasal polyp tissue IgE, by ELISA. RESULTS: Messenger RNA expression for TSLP,TARC and MDC was markedly higher in nasal polyps as compared to the allergic nasal mucosa. Immunoreactivity for TSLP was detected in epithelial cells, endothelial cells, fibroblasts and inflammatory cells of the nasal mucosa and nasal polyps. The number of TSLP+ cells was significantly greater in the nasal mucosa of AR than NAR patients. The number of TSLP+ cells in nasal polyps from atopics was significantly greater than that of non-atopics and that in the allergic nasal mucosa. The number of TSLP+ cells correlated well with the number of eosinophils and the levels of IgE in nasal polyps. CONCLUSIONS: The high expression of TSLP in nasal polyps and its strong correlation to eosinophils and IgE suggest a potential role for TSLP in the pathogenesis of nasal polyps by regulating the Th2 type and eosinophilic inflammation.
Asthma ; Chemokine CCL17 ; Chemokine CCL22 ; Cytokines ; Dermatitis, Atopic ; Endothelial Cells ; Eosinophils ; Epithelial Cells ; Fibroblasts ; Goblet Cells ; Humans ; Immunoglobulin E ; Immunohistochemistry ; Inflammation ; Lymphocytes ; Mast Cells ; Models, Animal ; Nasal Mucosa ; Nasal Polyps ; Real-Time Polymerase Chain Reaction ; Rhinitis ; Rhinitis, Allergic, Perennial ; RNA, Messenger

Although numerous studies have shown that each neuropsychological test is effective for diagnosing mild cognitive impairment (MCI) or Alzheimer’s disease (AD), studies comparing diagnostic accuracies of various neuropsychological tests are relatively rare and practical cutoff values are not available. The present study aimed to investigate the validity of neuropsychological tests and develop cutoff values for each in differentiating healthy control (HC), MCI and AD groups. A total of 84 HC, 187 with MCI and 195 with AD were evaluated by the selected seven neuropsychological tests using receiver operating characteristic (ROC) curve analysis. Logical Memory (LM) delayed recall (cutoff, 7) and Rey Auditory Verbal Learning Test (RAVLT) delayed recall (cutoff, 6) were effective for differentiating HC from MCI. To distinguish MCI and AD, Rey Osterrieth Complex Figure Test (ROCFT) 3 mindelayed recall (cutoff, 6) and LM immediate recall (cutoff, 4) were excellent. Delayed recall of verbal materials, as indexed by LM and RAVLT was sensitive for discriminating MCI from HC. Handling visual memory traces, as indexed by ROCFT and immediate verbal information by LM were sensitive for differentiating MCI and AD.
Alzheimer Disease ; Dementia ; Neuropsychological Tests

Hepatolithiasis is the presence of calculi within the intrahepatic bile duct and has various causes, including liver operations. In the presented case, intrahepatic stones were detected in the patient 30 years ago. Three years ago, before visiting our hospital, at the age of 68, a choledojejunal anastomotic operation was performed for the distention of the common bile duct. Intrahepatic calculi also occurred postoperatively. Percutaneous transhepatic biliary drainage and lithotripsy were conducted, but the intrahepatic stones reoccurred. This treatment was performed three times in total, last year. In the patient, hepatobiliary enzymes were elevated over the past year. To prevent hepatolithiasis recurrence, the patient visited the Kampo medicine outpatient department for inchingoreisan and shigyakusan treatment. Prior to treatment, the patient experienced abdominal discomfort in the hypochondrium. Upon treatment, a transient hepatic enzyme elevation occurred, which was assumed to be a paradoxical healing response, and drug administration was suspended. The prescription was resumed after 3 months, upon stabilization of elevated liver enzyme levels. Ten years after treatment, the patient’s condition was stable, without intrahepatic stone recurrence and apparent elevation of hepatobiliary enzymes. Inchingoreisan is reported to suppress calculi. Shigyakusan, free of the occasionally liver-damaging Scutellariae Radix, was also reported to be effective for hypochondrium discomfort. In conclusion, the combination of these treatments is suggested as a useful therapy in this case of hepatolithiasis.