Human bronchial intraepithelial T cells produce interferon‐γ and stimulate epithelial cells

Intraepithelial lymphocytes (IELs) can be identified among epithelial cells in systemic mucosal tissues. Although intestinal IELs play a crucial role in mucosal immunity, their bronchial counterparts have not been well studied. The purpose of this study was to determine the immunological functions of human bronchial IELs, which interact directly with epithelial cells, unlike lamina propria lymphocytes (LPLs). We isolated successfully bronchial IELs and LPLs using a magnetic cell separation system from the T cell suspensions extracted from bronchial specimens far from the tumours of resected lungs. Human bronchial IELs showed an apparent type 1 cytokine profile and proliferated more actively in response to CD2 signalling than did bronchial LPLs. CD8⁺ IELs were identified as the most significant sources of interferon (IFN)‐γ. Human bronchial epithelial cells constitutively produced the T cell growth factors interleukin (IL)‐7 and IL‐15, and levels of those factors increased when cells were stimulated by IFN‐γ. Bronchial epithelial cells expressed cell surface proteins CD58 and E‐cadherin, possibly enabling adhesion to IELs. In summary, human bronchial IELs have immunological functions distinct from bronchial LPLs and may interact with epithelial cells to maintain mucosal homeostasis.     

The impact of systematic lymphadenectomy for early-stage ovarian carcinomas

Among the 161 cases of pT1 ovarian cancer treated at our hospital during the last 25 years, the impact of systematic lymphadenectomy was evaluated in 93 cases of the pT1N0M0 group(N0 group), 59 cases of the pT1NxM0(Nx group), and 9 cases of the pT1N1M0(N1 group). Significantly greater relapse-free survival(RFS)and overall survival(OS)were observed in 108 cases of the N0+N1 group compared to the Nx group(p=0. 006, p=0. 02). Multivariate analysis showed that systematic lymphadenectomy was a significant prognostic factor(hazard ratio 0. 473(95%CI, 0. 235-0. 951; p=0. 036). The present study suggested the systematic lymphadenectomy had a significant therapeutic effect on pT1 stage ovarian cancers.     

Evaluation of limited sampling designs to estimate maximal concentration and area under the curve of mizoribine in pediatric patients with renal disease

The aim of this study was to evaluate limited sampling designs to estimate the maximal concentration (C(max)) and area under the curve (AUC) of mizoribine in pediatric patients with renal disease. We utilized 48 serum mizoribine concentration profiles obtained from the full (6-point) sampling pharmacokinetic test, and estimated 48 individual C(max) and AUC values accurately with Bayesian analysis using the full sampling data. We then developed limited sampling models (LSM) for C(max) and AUC using 1-4 serum mizoribine concentration data points. The C(max) and AUC estimation performance of the Bayesian and LSM analysis was fairly good in the 3-point (2, 3, and 6 hr after the dose) sampling design. In addition, the C(max) estimation performance of the Bayesian and LSM analysis deteriorated only marginally even in the 1-point (3 hr) sampling design. On the other hand, the AUC estimation performance seemed to be inadequate in the 1-point (3 hr) sampling design; however, it improved markedly in the 2-point (3 and 6 hr) sampling design. These findings suggested that the 1-point (3 hr) sampling design is promising for approximate C(max) estimation, but that the 2-point (3 and 6 hr) sampling design is preferable to estimate the AUC of mizoribine.     

Complete dependence on CD4+ cells in late asthmatic response, but limited contribution of the cells to airway remodeling in sensitized mice

It is known that the late asthmatic response (LAR), a characteristic feature of asthma, is closely associated with CD4+ Th2 cell-mediated allergic inflammation. Airway remodeling is also a pathogenesis of asthma, but literature reporting roles of CD4+ cells in the remodeling is controversial. There has been no study that simultaneously assessed the roles of CD4+ cells in both LAR and airway remodeling. Sensitized mice were intratracheally challenged with ovalbumin 4 times. Treatment with an anti-CD4 monoclonal antibody (mAb) before the 1st challenge almost completely abolished increase in CD4+ cells in the tissues after the 4th challenge. The late phase increase in airway resistance after the 4th challenge was also completely inhibited by anti-CD4 mAb. Parameters of airway remodeling, subepithelial fibrosis and epithelial thickening were attenuated by treatment, whereas the inhibition was only 30% - 40%. Bronchial smooth muscle thickening was not affected. Because interleukin (IL)-5 production as well as eosinophilia was effectively suppressed by anti-CD4 mAb, the effect of anti-IL-5 mAb was also examined, resulting in no inhibition of airway remodeling. Collectively, although the LAR was completely dependent on CD4+ cell activation, airway remodeling was only partially dependent on the cell.     

Esophageal fibrovascular polyp removed by cervical esophagotomy

We report a case of esophageal fibrovascular polyp (FVP) removed by cervical esophagotomy. The patient was a 74-year-old man in whom an intraesophageal mass was detected by a chest CT examination during a complete medical check-up. An upper gastrointestinal series showed a large, pedunculated, cervical esophageal mass for which our preoperative diagnosis was a FVP. We studied its features, as well as removal procedures in 45 patients in the literature. Most patients had marked symptoms, but ours had no complaints, and so this case may be a rare one. Various removal procedures were reported, but thoracotomy and esophagectomy are considered to be the inappropriate procedures since FVP is a benign disorder.     

Ethnic differences in the relationships of anthropometric measures to metabolic risk factors in Asian patients at risk of atherothrombosis : Results from the REduction of Atherothrombosis for Continued Health (REACH) Registry

The aim of the study is to examine the relationships between 4 anthropometric indices and metabolic risk factors (hypertension, atherogenic dyslipidemia, and glucose intolerance) in different Asian ethnic groups of patients at risk of atherothrombosis. We analyzed the baseline data of 11 017 Asian patients with established atherothrombotic cardiovascular diseases or at least 3 atherothrombotic risk factors. In East and South Asians, the graded relationships of body mass index (BMI) with the presence of at least 2 metabolic risk factors remained significant after adjustment for waist circumference (top vs bottom quartile—East Asians: odds ratio, 2.02; 95% confidence interval, 1.67-2.45; South Asians: 3.24, 1.18-8.95), whereas the graded relationships of waist circumference decreased or became nonsignificant after adjustment for BMI (East Asians: 1.64, 1.35-1.99; South Asians: 0.68, 0.20-2.30). In Southeast Asian men, the graded relationship of waist circumference with metabolic risk factors (2.27, 1.42-3.63) was stronger than that of BMI (1.34, 0.84-2.12), whereas in Southeast Asian women, there was a trend toward a stronger association between BMI and metabolic risk factors. In East Asians and in Southeast Asian women, the waist-to-BMI ratio decreased with the number of metabolic risk factors. The optimal cutoff points for BMI and waist circumference with regard to the presence of at least 2 metabolic risk factors were lowest in East Asians (men: 24 kg/m² and 86 cm; women: 24 kg/m² and 82 cm). Our findings suggest that both BMI and waist circumference, rather than waist circumference alone, should be included in metabolic risk assessment in this high-risk multiethnic Asian population. Uniform anthropometric cutoff values for all Asian ethnic groups are not appropriate to assess obesity-related metabolic complications, even in patients with established atherothrombotic disease.