Correlation of Local FOXP3-Expressing T Cells and Th1-Th2 Balance in Perennial Allergic Nasal Mucosa

Regulatory T cells (Treg) play some important roles in allergic rhinitis. The most specific marker for Treg is FOXP3, a recently identified transcription factor that is essential for Treg development. In order to clarify the levels of Treg in allergic nasal mucosa, we studied the relationship between FOXP3-expressing cells and Th1-Th2 balance in nasal mucosa by means of immunohistochemistry. Human turbinates were obtained after turbinectomy from 26 patients (14 patients with perennial allergic rhinitis and 12 patients with nonallergic rhinitis). To identify the cells expressing the FOXP3 protein, double immunostaining was performed by using anti-FOXP3 antibody and anti-CD3 antibody. There was no significant difference in the percentage of FOXP3+CD3+ cells among CD3+ cells in the nasal mucosa of two groups. The proportion of FOXP3+CD3+ cells tend to be correlated positively with GATA3+CD3+ cells/T-bet+CD3+ cells ratio (R = 0.56, P = 0.04). A positive correlation with GATA3+CD3+/T-bet+CD3+ ratio and FOXP3+CD3+/CD3+ ratio suggests the role of local regulatory T cells as a minimal control of the chronic allergen exposure in nasal mucosa

Thiazolidinediones and Edema: Recent Advances in the Pathogenesis of Thiazolidinediones-Induced Renal Sodium Retention

Thiazolidinediones (TZDs) are one of the major classes of antidiabetic drugs that are used widely. TZDs improve insulin resistance by activating peroxisome proliferator-activated receptor gamma (PPARγ) and ameliorate diabetic and other nephropathies, at least, in experimental animals. However, TZDs have side effects, such as edema, congestive heart failure, and bone fracture, and may increase bladder cancer risk. Edema and heart failure, which both probably originate from renal sodium retention, are of great importance because these side effects make it difficult to continue the use of TZDs. However, the pathogenesis of edema remains a matter of controversy. Initially, upregulation of the epithelial sodium channel (ENaC) in the collecting ducts by TZDs was thought to be the primary cause of edema. However, the results of other studies do not support this view. Recent data suggest the involvement of transporters in the proximal tubule, such as sodium-bicarbonate cotransporter and sodium-proton exchanger. Other studies have suggested that sodium-potassium-chloride cotransporter 2 in the thick ascending limb of Henle and aquaporins are also possible targets for TZDs. This paper will discuss the recent advances in the pathogenesis of TZD-induced sodium reabsorption in the renal tubules and edema

Tegafur-Uracil Plus Gemcitabine Combination Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer Previously Treated with Platinum

BackgroundAn open-label, single-arm prospective study was conducted to evaluate the efficacy and toxicity of the combination of gemcitabine and tegafur-uracil (UFT) in patients with advanced nonsmall-cell lung cancer (NSCLC) after the failure of previous platinum-containing regimens.Patients and MethodsPatients with advanced NSCLC received 200 mg/m2 of UFT twice daily from day 1 through 14 plus 900 mg/m2 of gemcitabine per day via intravenous injection on days 8 and 15. This regimen was repeated every 3 or 4 weeks.ResultsA total of 40 patients were enrolled. Eleven patients (28%; 95% confidence interval [CI], 15–44%) achieved a partial response. The median progression-free survival, median overall survival, and 1-year survival rate were 4.0 months (95% CI, 3.3–6.7 months), 12.6 months (95% CI, 7.0–22.3 months), and 51% (95% CI, 33–66%), respectively. The most common grade 3 or 4 toxicity was neutropenia (38%; 95% CI, 23–54%) and the rate of grade 3 or 4 nonhematologic toxicity remained at less than 5%. A multivariate Cox model showed that adenocarcinoma, nonsmoking history, and good performance status predicted better survival.ConclusionsCombination chemotherapy with UFT and gemcitabine showed a promising effectiveness and acceptable toxicity for patients with platinum-resistant NSCLC

Need for Flexible Adjustment of the Treatment Schedule for Aprepitant Administration against Erlotinib-Induced Refractory Pruritus and Skin Rush

Common dermatological side-effects associated with erlotinib, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), include pruritus and skin rash, which are mediated by substance P, leading to the occasional discontinuation of cancer treatment. Aprepitant is an antagonist of neurokinin-1 receptor, through which substance P activates the pruritogens. Thus, aprepitant is expected to offer a promising option for the treatment of erlotinib-induced pruritus. However, the appropriate treatment schedule for aprepitant administration is under consideration. Here, we discuss the need for flexible adjustment of the treatment schedule for aprepitant administration against erlotinib-induced refractory pruritus and skin rush. A 71-year-old female smoker presented with stage IV EGFR-mutated lung adenocarcinoma. She was started on erlotinib at 150 mg/day. However, by 28 days, severe pruritus and acneiform skin rush resistant to standard therapies occurred, resulting in the interruption of erlotinib therapy. After recovery, she was restarted on erlotinib at 100 mg/day. However, severe pruritus and skin rush developed again within 2 weeks. Then, we started the first 3-day dose of aprepitant (125 mg on day 1, 80 mg on day 3, and 80 mg on day 5) based on the results of the previous prospective study, which showed the success rate of 100% with at least the second dose of aprepitant. However, the pruritus and skin rush exacerbated again within 4 weeks. Therefore, we started the second 3-day dose of aprepitant, but in vain. At this point, as the patient-centered medicine, bi-weekly schedule of the 3-day dose of aprepitant was considered and, then, adopted. As the results, the pruritus and skin rush remained well-controlled throughout the subsequent treatment with erlotinib

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C