Th2 polarization enhanced by oral administration of higher doses of antigen

Although oral administration of a soluble proteinantigen can induce various immune responses, theeffect of the dosage of oral antigen on thepredominance of Th2-type cytokine and antibodyresponses has not been well clarified yet. In thepresent study, we fed T cell receptor (TCR) transgenic(tg) mice various amounts of chicken ovalbumin (0.1,5, and 250 mg) and examined the resulting immuneresponses to this antigen. In these TCR tg mice, theresponses of antigen-specific T cells were greatlyamplified concomitantly with significantantigen-specific cytokine secretion. We found that ahigh dose (250 mg) of antigen significantlyupregulated the serum antigen-specific IgG1 and IgAantibody responses in mice later intraperitoneallyinjected with antigen plus adjuvant. The miceadministered the same oral dose but not immunizedshowed upregulation of Th2-type IL-4 and IL-5secretion and downregulation of Th1-type IL-2 andIFN-. This enhancement of Th2-type cytokineand antibody responses was more marked when largerdoses of antigen orally administered. These resultsdemonstrated that antigen feeding induces thedevelopment of T cells secreting Th2-type cytokines ina dose-dependent manner and that these T cells have ahelper function for the production of antibodies ofthe Th2-type isotypes. This experimental system shouldbe useful to screen foods and other substances thatcan modulate Th2-type responses relating to allergy.     

Serum Wisteria Floribunda Agglutinin-Positive Mac-2 Binding Protein Values Predict the Development of Hepatocellular Carcinoma among Patients with Chronic Hepatitis C after Sustained Virological Response

Measurement of Wisteria floribunda agglutinin-positive human Mac-2 binding protein (WFA⁺-M2BP) in serum was recently shown to be a noninvasive method to assess liver fibrosis. The aim of this study was to evaluate the utility of serum WFA⁺-M2BP values to predict the development of hepatocellular carcinoma (HCC) in patients who achieved a sustained virological response (SVR) by interferon treatment. For this purpose, we retrospectively analyzed 238 patients with SVR who were treated with interferon in our department. Serum WFA⁺-M2BP values were measured at pre-treatment (pre-Tx), post-treatment (24 weeks after completion of interferon; post-Tx), the time of HCC diagnosis, and the last clinical visit. Of 238 patients with SVR, HCC developed in 16 (6.8%) patients. The average follow-up period was 9.1 years. The cumulative incidence of HCC was 3.4% at 5 years and 7.5% at 10 years. The median pre-Tx and post-Tx WFA⁺-M2BP values were 1.69 (range: 0.28 to 12.04 cutoff index (COI)) and 0.80 (range: 0.17 to 5.29 COI), respectively. The WFA⁺-M2BP values decreased significantly after SVR (P < 0.001). The median post-Tx WFA⁺-M2BP value in patients who developed HCC was significantly higher than that in patients who did not (P < 0.01). Multivariate analysis disclosed that age (> 60 years), sex (male), pre-Tx platelet count (< 15.0×10³/μL), and post-Tx WFA⁺-M2BP (> 2.0 COI) were associated with the development of HCC after SVR.

Conclusion

Post-Tx WFA⁺-M2BP (> 2.0 COI) is associated with the risk for development of HCC among patients with SVR. The WFA⁺-M2BP values could be a new predictor for HCC after SVR.     

Effect of Nasal Obstruction on Continuous Positive Airway Pressure Treatment: Computational Fluid Dynamics Analyses

Objective

Nasal obstruction is a common problem in continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea and limits treatment compliance. The purpose of this study is to model the effects of nasal obstruction on airflow parameters under CPAP using computational fluid dynamics (CFD), and to clarify quantitatively the relation between airflow velocity and pressure loss coefficient in subjects with and without nasal obstruction.

Methods

We conducted an observational cross-sectional study of 16 Japanese adult subjects, of whom 9 had nasal obstruction and 7 did not (control group). Three-dimensional reconstructed models of the nasal cavity and nasopharynx with a CPAP mask fitted to the nostrils were created from each subject’s CT scans. The digital models were meshed with tetrahedral cells and stereolithography formats were created. CPAP airflow simulations were conducted using CFD software. Airflow streamlines and velocity contours in the nasal cavities and nasopharynx were compared between groups. Simulation models were confirmed to agree with actual measurements of nasal flow rate and with pressure and flow rate in the CPAP machine.

Results

Under 10 cmH₂O CPAP, average maximum airflow velocity during inspiration was 17.6 ± 5.6 m/s in the nasal obstruction group but only 11.8 ± 1.4 m/s in the control group. The average pressure drop in the nasopharynx relative to inlet static pressure was 2.44 ± 1.41 cmH₂O in the nasal obstruction group but only 1.17 ± 0.29 cmH₂O in the control group. The nasal obstruction and control groups were clearly separated by a velocity threshold of 13.5 m/s, and pressure loss coefficient threshold of approximately 10.0. In contrast, there was no significant difference in expiratory pressure in the nasopharynx between the groups.

Conclusion

This is the first CFD analysis of the effect of nasal obstruction on CPAP treatment. A strong correlation between the inspiratory pressure loss coefficient and maximum airflow velocity was found.     

Gap formation and regeneration of tropical mangrove forests in Ranong,Thailand

Tropical mangrove forests are characterized by clear zonation along a tidal gradient, and it has been supposed that the zonation is primarily controlled by soil factors. However, effects of disturbance on mangrove forests are still not well understood and may play an important role on the vegetation patterns and forest dynamics in some forest formations. In this study, the pattern of disturbance regime and its effects on regeneration of tropical mangrove forests along a tidal gradient were investigated in Ranong, Thailand. We established one or two 0.5 ha plots in four vegetation zones, i.e. Sonneratia alba–Avicennia alba zone, Rhizophora apiculata zone, Ra – Bruguiera gymnorrhiza zone, Ceriops tagal–Xylocarpus spp. zone. Gap size (percentage gap area to total study area and individual gap size) was the largest in Sa–Aa zone which is located on the most seaward fringe, and it declined from seaward to inland. Canopy trees of S. alba and A. alba had stunted trunks and showed low tree density. On the contrary, canopy dominants in the other three inland zones, e.g. R. apiculata, B. gymnorrhiza, and Xylocarpus spp., had slender trunks and showed high tree density. Accordingly, differences in disturbance regime among the four zones were resulted from the forest structural features of each zone. Disturbance regime matched with regeneration strategies of canopy dominants. Seedlings and saplings of S. alba and A. alba, which need sunny condition for their growth, were abundant in gaps than in understorey. By contrast, R. apiculata, B. gymnorrhiza, and Xylocarpus spp., which can tolerate less light than S. alba and A. alba, had greater seedling and sapling density under closed canopy than gaps. Many large gaps may enhance the abundance of S. alba and A. alba in Sa–Aa zone, and a few small gaps may prevent the light demanding species to establish and grow in the other inland zones. Correspondence of disturbance regime and regeneration strategies (e.g. light requirement) of canopy dominants may contribute to the maintenance of the present species composition in each of the vegetation zones.     

Modeling late entry bias in survival analysis

In a failure time analysis, we sometimes observe additional study subjects who enter during the study period. These late entries are treated as left-truncated data in the statistical literature. However, with real data, there is a substantial possibility that the delayed entries may have extremely different hazards compared to the other standard subjects. We focus on a situation in which such entry bias might arise in the analysis of survival data. The purpose of the present article is to develop an appropriate methodology for making inference about data including late entries. We construct a model that includes parameters for the effect of delayed entry bias having no specification for the distribution of entry time. We also discuss likelihood inference based on this model and derive the asymptotic behavior of estimates. A simulation study is conducted for a finite sample size in order to compare the analysis results using our method with those using the standard method, where independence between entry time and failure time is assumed. We apply this method to mortality analysis among atomic bomb survivors defined in a geographical study region.     

Different Impacts of Neck Circumference and Visceral Obesity on the Severity of Obstructive Sleep Apnea Syndrome

Our aim was to investigate the significance of neck circumference (NC) on the presence and severity of obstructive sleep apnea (OSA) syndrome independent of visceral fat (VF) obesity. A total of 219 subjects with suspected OSA underwent a complete polysomnography (PSG) study, along with the measurement of NC, and total body fat (TF) and VF levels (VFLs) measured by bioelectrical impedance analysis. We proposed NC divided by height (NC/H) as the simple index for height‐corrected NC in Japanese subjects. NC/H exhibited a significantly stronger correlation than NC per se with BMI (r = 0.781 vs. 0.675, P = 0.0178), TF (r = 0.531 vs. 0.156, P < 0.0001), and VF (r = 0.819 vs. 0.731, P = 0.0203), indicating that NC/H is a better indicator of visceral obesity than NC per se. Interestingly, despite the strong correlation between NC/H and VFL, VFL was significantly associated with the apnea‐hypopnea index (AHI) ≥5, ≥15, and ≥30, but not with ≥40 or ≥50, whereas NC/H was significantly associated with higher AHI values, i.e., AHI ≥50 but not with lower AHI value. Furthermore, multiple regression analyses revealed that VFL and NC/H were independently associated with the square root of AHI (AHI^0.5) levels in obese and nonobese patients, respectively. In conclusion, NC is associated with the severity of OSA independently of visceral obesity, especially in nonobese patients.     

Autophagy and neurodegeneration

The proteasome and lysosome are sophisticated apparatuses capable of shredding unnecessary proteins in eukaryotic cells. The proteasome and its partner ubiquitin (which functions as a destination signal for proteolysis) play crucial roles in selective breakdown of not only short-lived regulatory proteins but also abnormal proteins that need to be rapidly eliminated from the cells. It is generally accepted that deficits of the proteasome-ubiquitin system are associated with various neurodegenerative diseases, since ubiquitin-positive inclusions frequently appear in neurons of patients and mice models of neurodegenerative diseases. However, investigators working in the field of neuronal diseases have focused their attention in recent years on autophagy (Greek for "the eating of oneself") following the recent discovery that ablation of autophagy leads to accumulation of ubiquitin-positive inclusions, which are the pathological hallmark of neurodegenerative diseases. Here we discuss the consequences of autophagy deficiency in neurons.