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T lymphocytes (T cells) play an important role in orchestrating an adaptive immune response in complex organisms. Recent experiments have shown that when T cells recognize antigen presenting cells, a complex and large-scale reorganization of intercellular membrane proteins and cell shape occurs. The resulting motif is implicated in information transfer between T cells and antigen presenting cells, and has been labeled the immunological synapse. Numerical solutions of a mathematical model that incorporates binding kinetics, protein mobility, and down regulation, and membrane mechanics has proven successful in describing some of these observations. In this paper, we analyze the equations that describe this model, and this sheds light on the origins of pattern formation in the immunological synapse. In particular, the thermodynamic considerations and dynamic instabilities that lead to pattern formation in and out of equilibrium are elucidated. [ABSTRACT FROM AUTHOR]

Mature T cell activation and selection of immature T cells (thymocytes) are both initiated by binding of T cell receptor (TCR) molecules on the surface of T cells to MHC peptide (MHCp) molecules on the surface of antigen-presenting cells. Recent experiments have shown that the spatial pattern of receptors and ligands in the intercellular junction (synapse) is different during thymocyte selection compared with mature T cell activation. Using a statistical mechanical model, we show that lower TCR expression in thymocytes contributes to effecting these differences. An analogy with the phase behavior of simple fluids helps clarify how, for low TCR expression, thermal fluctuations lead to the dynamic synapse patterns observed for thymocytes. We suggest that a different synapse pattern resulting from lower TCR expression, which could mediate differential signaling, may be the reason why TCR expression level is low in thymocytes. [ABSTRACT FROM AUTHOR]

During antigen recognition by T cells different receptors and ligands form a pattern in the intercellular junction called the immunological synapse, which might be involved in T-cell activation. Recently, a synapse assembly model has been proposed, which enables the calculation of the propensity for synapse assembly driven by membrane-constrained protein binding interactions. We bring together model predictions of mature synapse assembly with data on the dependence of T-cell responses on T-cell receptor (TCR)–MHC–peptide (pMHC) binding kinetics. Predictions of mature synapse assembly, based on TCR–pMHC binding kinetics, correlate well with observed cytokine responses by T cells bearing the relevant TCR but not with cytotoxic T lymphocyte-mediated killing. We discuss the suggested different role for the synapse in pre- and post-nuclear activation events in T cells. The view of immunological synapse assembly given here emphasizes the importance of both the on and off rates for the TCR–pMHC interaction and in this context recent data on a positive role for analogs of self-peptides in synapse assembly is considered. [ABSTRACT FROM AUTHOR]

A framework for quantitative analysis of the mechanisms underlying immunological synapse assembly has been recently developed. This model uses partial differential equations to describe the binding interactions of receptors and ligands, with the constraint that they are embedded in apposed deformable membranes linked to a cytoskeletal complex. [ABSTRACT FROM AUTHOR]

Shigellosis cases have decreased gradually in Japan in recent years, but indigenous shigellosis outbreaks sometimes occur in childcare facilities. From national surveillance data, we identified a shigellosis outbreak involving a kindergarten. After detecting Shigella sonnei in Kitakyushu City, we conducted active case finding and epidemiological investigation in Kindergarten Z, including stool specimen collection and interviews. The stool specimens were cultured, and isolated strains were subjected to pulsed-field gel electrophoresis (PFGE) and multiple-locus variable-number tandem-repeat analysis (MLVA). Between September 1 and December 31, 2014, we identified 19 cases: 14 confirmed, 2 suspected, and 3 asymptomatic. Of the 19 cases, 16 were epidemiologically associated with Kindergarten Z (10 pupils, 5 family members, and 1 teacher). On October 19, a pupil with gastrointestinal illness participated in the kindergarten's sports festival, in which the pupils were split into "red" and "white" teams; the pupil in question belonged to the red team. Attack rates of the red and white teams were 8% (7/82) and 0% (0/108), respectively (relative risk, 10.5; 95% confidence interval, 1.3–82.1). PFGE patterns were identical or similar for the isolates in all 17 cases; 7 isolates were identical, and the others had one locus difference on MLVA. We concluded that contact during the sports festival could have been responsible for spread of the shigellosis outbreak at the kindergarten, although the infection source was not determined. It is vital to inform guardians immediately after detection of shigellosis cases that symptomatic pupils should not participate in activities such as sports festivals. [ABSTRACT FROM AUTHOR]

Anorexia is a serious problem in patients with gastric cancer who have undergone gastrectomy. Ghrelin, an orexigenic hormone primarily secreted from the stomach, has been proposed to prevent anorexia. Significant reduction in plasma ghrelin levels after gastrectomy may contribute to lack of appetite and weight loss. In this study, we investigated the effects of Z-505, a ghrelin receptor agonist, on anorexia after total gastrectomy (TG) in a rat model. Male Sprague–Dawley rats were used to establish a TG model, and then sham-operated (control) and TG rats were randomly assigned to four subgroups receiving administration of Z-505 (100 mg/kg, p.o., once daily) or vehicle for 14 d from day 14 to day 27 after TG. The food intake, body weight, and fat weight were evaluated during the test period. Moreover, the neuronal activity in the hypothalamus was evaluated on day 21 to investigate the mechanism of action of Z-505. In TG rats, Z-505 significantly improved the decrease in cumulative food intake induced by the surgery over 14 d (TG + vehicle; 213.8 ± 15.3 g, n = 12 versus TG + Z-505; 258.2 ± 13.1 g, n = 14, P < 0.05). Z-505 also significantly increased fat weight and had a milder effect on body weight over 14 d. In addition, Z-505 significantly increased the number of c-Fos-positive cells in the hypothalamic arcuate nucleus (TG + vehicle; 17.8 ± 2.0, n = 12 versus TG + Z-505; 72.2 ± 11.8, n = 12, P < 0.001). Z-505 may be a useful therapeutic treatment for anorexia after TG. [ABSTRACT FROM AUTHOR]

The optical rotation and fluorescence anisotropy for gellan aqueous systems were measured at pH 4, 7, and 10 to elucidate the effect of pH on the conformation of gellan chains. The optical rotation study suggests that pH affects the conformation of helical gellan chains and their aggregation behavior but the coil–helix transition temperature. By comparing the chain mobility estimated from the fluorescence anisotropy between different pH conditions, it has been revealed that the degree of expansion of random-coiled gellan chains varies with pH. These results indicate that the effect of pH is explained by the change in the anionic nature of gellan chains rather than in the shielding effect of hydrogen ions surrounding gellan chains as a cation species. [Copyright &y& Elsevier]

Most parotid tumors grow slowly, whether benign or malignant; thus, it is difficult to predict the malignant or benign nature of a tumor clinically. Magnetic resonance imaging may have a place in the diagnostic work-up of parotid tumors. The purpose of this article is to illustrate the MR imaging findings of parotid tumors and to correlate them to pathologic findings. The MR imaging may be helpful in differentiation of benign and malignant tumors of the parotid gland, and can provide important clues in the diagnosis of their histologies. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to investigate the formation characteristics of oil-in-water (O/W) emulsion droplets in the presence of electrolyte by microchannel (MC) emulsification using differently charged surfactants. Droplet formation was conducted by pressurizing a dispersed phase (refined soybean oil) via 23,348 asymmetric through-holes micro fabricated on a 24mm×24-mm silicon chip into a continuous phase in the presence of a surfactant (1.0wt%) and an electrolyte (NaCl) (0–1.0mol/L). Monodisperse O/W emulsions with an average droplet diameter (d av,drop) of 26μm and a coefficient of variation (CV) below 5% were produced from the asymmetric through-holes when the NaCl concentration was lower than a threshold level that is 0.3mol/L for sodium dodecyl sulfate (SDS) and 0.5mol/L for polyoxyethylene (20) sorbitan monolaurate (Tween 20). Further increase in the NaCl concentration resulted in increase of the d av,drop and CV of the resultant O/W emulsions, which is due to unstable and unsmooth motion of the oil–water interface during droplet formation. In the presence of SDS, it was found that interfacial tension must be higher than a threshold level (c.a. 0.9mN/m) in order to achieve stable droplet formation by MC emulsification. The ζ-potential on the droplet and chip surfaces was negative, and their absolute value decreased with increasing the NaCl concentration. The ζ-potential results also indicated that repulsive electrostatic interaction between the droplet and chip surfaces in the presence of NaCl is high for SDS and negligible for Tween 20. The difference in their electrostatic interaction is assumed to affect the smoothness of droplet formation and the behavior of the droplets formed. [Copyright &y& Elsevier]

Abstract: In clinical trials, acotiamide hydrochloride (acotiamide: Z-338) has been reported to be useful in the treatment of functional dyspepsia. Here, we investigated the effects of acotiamide on gastric contraction and emptying activities in rats in comparison with itopride hydrochloride (itopride) and mosapride citrate (mosapride). We also examined in vitro the compound''s inhibitory effect on acetylcholinesterase (AChE) activity derived from rat stomach. In in vivo studies, acotiamide (30 and 100mg/kg s.c.) and itopride (100mg/kg s.c.) markedly enhanced normal gastric antral motility in rats. In gastric motility dysfunction models, acotiamide (100mg/kg s.c.) and itopride (100mg/kg s.c.) improved both gastric antral hypomotility and the delayed gastric emptying induced by clonidine, an α2-adrenoceptor agonist. In contrast, mosapride (10mg/kg s.c.) had no effect on these models. Like the AChE inhibitors itopride (30mg/kg s.c.) and neostigmine (10μg/kg s.c.), acotiamide (10mg/kg s.c.) also clearly enhanced gastric body contractions induced by electrical stimulation of the vagus, which were abolished by atropine and hexamethonium, whereas mosapride (3 and 10mg/kg s.c.) did not. In in vitro studies, acotiamide concentration-dependently inhibited rat stomach-derived AChE activity (IC50 =2.3μmol/l). In addition, stomach tissue concentrations of acotiamide after administration at 10mg/kg s.c. were sufficient to produce inhibition of AChE activity in rat stomach. These results suggest that acotiamide stimulates gastric motility and improves gastric motility dysfunction in rats by inhibiting AChE activity, and may suggest a role for acotiamide in improving gastric motility dysfunction in patients with functional dyspepsia. [Copyright &y& Elsevier]

Background: Chronic pancreatitis and pancreatic adenocarcinoma often show similar clinical and imaging appearances. This study aims to differentiate chronic pancreatitis from pancreatic adenocarcinoma by defining enhancement patterns in both pathologic conditions during triple-phase helical CT. Methods: The study included 42 patients with chronic pancreatitis and 85 patients with pancreatic adenocarcinoma. CT images obtained according to protocol A (scan delays, 30, 60, and 150 s; 300 mg I/mL contrast material) or protocol B (scan delays, 40, 70, and 150 s; 370 mg I/mL contrast material) were retrospectively evaluated. Results: Mean contrast enhancement value of normal pancreas peaked in the first phase (early-washout pattern) while that of chronic pancreatitis peaked in the second phase (delayed-washout pattern), and that of pancreatic adenocarcinoma gradually rose (increasing pattern) in both protocols. Diagnostic indices for pancreatic adenocarcinoma were 82.4% and 94.1% for sensitivity, 83% and 83% for specificity, 82.7% and 90.4% for accuracy in protocols A and B, respectively, when differentiation between chronic pancreatitis and pancreatic adenocarcinoma was performed based on time-attenuation curve patterns. Conclusion: Our results indicate that time attenuation curves obtained from triple-phase helical CT in protocol B provide useful information in differentiating chronic pancreatitis from pancreatic adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Z-360 is an orally active cholecystokinin-2 (CCK2)/gastrin receptor antagonist currently under development as a therapeutic drug for pancreatic cancer. It was previously reported that Z-360 treatment in combination with gemcitabine prolonged the survival period in a lethal pancreatic cancer xenograft model in mice. In a phase Ib/IIa clinical study, Z-360 treatment displayed a trend of reduced pain in patients with advanced pancreatic cancer in combination with gemcitabine including analgesics such as opioids. Here, we investigated the mechanism of analgesic action of Z-360 in a severe cancer-induced pain model in mice, which is considered to be opioid-resistant, by examining ephrin B1 gene expression, N-methyl-D-aspartate receptor NR2B subunit phosphorylation, and interleukin-1β (IL-1β) production. Results: In a mouse model of cancer-induced pain, ephrin B1 gene expression in dorsal root ganglia (DRGs) and the phosphorylation of NR2B in the spinal cord were induced. Z-360 treatment inhibited both ephrin B1 gene expression and the phosphorylation of NR2B. In addition, IL-1β production increased in the cancer-inoculated hind paw of mice, but could be suppressed by treatment with Z-360. Moreover, we observed that the CCK1 receptor antagonist devazepide similarly suppressed up-regulation of ephrin B1 gene expression and IL-1β production, and that the intraperitoneal injection of sulfated CCK-8 induced the production of IL-1β in the cancer-inoculated region. Conclusions: We have identified a novel pain cascade, in which IL-1β production in cancer-inoculated regions induces ephrin B1 gene expression in DRGs and then ephrin B1 enhances the tyrosine phosphorylation of NR2B via Eph B receptor in the spinal cord. Notably, Z-360 relieves cancer-induced pain by preventing this pain cascade through the suppression of IL-1β production, likely via the blockade of CCK1 receptor. The pre-clinical results presented here support the analgesic action of Z-360 in pancreatic cancer patients with severe, opioid-resistant pain. Pre-clinical and clinical results have demonstrated that Z-360 combined with gemcitabine represents a promising pancreatic cancer therapy approach with characteristic analgesic effects in addition to the prolongation of survival. [ABSTRACT FROM AUTHOR]