Possible Implication of Fc γ

Leukocytes can “gnaw away” the plasma membrane of other cells. This phenomenon, called trogocytosis, occurs subsequent to cell-to-cell adhesion. Currently, two mechanisms of trogocytosis, adhesion molecule-mediated trogocytosis and Fcγ receptor-(FcγR-) mediated trogocytosis, have been identified. In our earlier study, we established an in vitro model of FcγR-mediated trogocytosis, namely, CD8 translocation model from T cells to neutrophils. By using this model, we demonstrated that the molecules transferred to neutrophils via FcγR-mediated trogocytosis were taken into the cytoplasm immediately. This result suggests that the chance of molecules transferred via FcγR-mediated trogocytosis to play a role on the cell surface could be time-limited. Thus, we consider the physiological role of FcγR-mediated trogocytosis as a means to remove antibodies (Abs) that bind with self-molecules rather than to extract molecules from other cells. This concept means that FcγR-mediated trogocytosis can be a defense mechanism to Ab-mediated autoimmune response. Moreover, the activity of FcγR-mediated trogocytosis was revealed to be parallel to the endocytotic activity of neutrophils, which was critically related to the susceptibility to systemic autoimmune diseases. The collective findings suggest that FcγR-mediated trogocytosis could physiologically play a role in removal of Abs bound to self-antigens and prevent autoimmune diseases

Observation of moisture tendencies related to shallow convection

Tropospheric moisture is a key factor controlling the global climate and its variability. For instance, moistening of the lower troposphere is necessary to trigger the convective phase of a Madden-Julian oscillation (MJO). However, the relative importance of the processes controlling this moistening has yet to be quantified. Among these processes, the importance of the moistening by shallow convection is still debated. The authors use high-frequency observations of humidity and convection from the Research Vessel (R/V) Mirai that was located in the Indian Ocean ITCZ during the Cooperative Indian Ocean Experiment on Intraseasonal Variability/Dynamics of the MJO (CINDY/DYNAMO) campaign. This study is an initial attempt to directly link shallow convection to moisture variations within the lowest 4 km of the atmosphere from the convective scale to the mesoscale. Within a few tens of minutes and near shallow convection occurrences, moisture anomalies of 0.25-0.5 g kg-1 that correspond to tendencies on the order of 10-20 g kg-1 day-1 between 1 and 4 km are observed and are attributed to shallow convective clouds. On the scale of a few hours, shallow convection is associated with anomalies of 0.5-1 g kg-1 that correspond to tendencies on the order of 1-4 g kg-1 day-1 according to two independent datasets: lidar and soundings. This can be interpreted as the resultant mesoscale effect of the population of shallow convective clouds. Large-scale advective tendencies can be stronger than the moistening by shallow convection; however, the latter is a steady moisture supply whose importance can increase with the time scale. This evaluation of the moistening tendency related to shallow convection is ultimately important to develop and constrain numerical models

Safety analysis of two different regimens of uracil–tegafur plus leucovorin as adjuvant chemotherapy for high-risk stage II and III colon cancer in a phase III trial comparing 6 with 18 months of treatment: JFMC33-0502 trial

PURPOSE: The JFMC33-0502 trial is a phase III clinical study designed to determine the most appropriate duration of postoperative adjuvant chemotherapy with uracil–tegafur (UFT) plus leucovorin in patients with stage IIB or III colon cancer. We report the interim results of preplanned safety analyses. METHODS: Patients with stage IIB or III colon cancer who had undergone curative resection were randomly assigned to receive UFT (300 mg/m(2)) plus leucovorin (75 mg/day) for 6 months (control group, 4 weeks of treatment followed by a 1-week rest, five courses) or for 18 months (study group, 5 days of treatment followed by a 2-day rest, 15 courses). Treatment status and safety were evaluated. RESULTS: A total of 1,071 patients were enrolled, and 1,063 were included in safety analyses. Treatment completion rate at 6 months was 74.0 % in the control group and 76.7 % in the study group. Treatment completion rate in the study group at 18 months was 56.0 %. The overall incidence of adverse events (AEs) was 75.3 % in the control group and 77.6 % in the study group. The incidences of grade 3 or higher AEs were low in both groups. During the first 6 months, the incidences of the subjective AEs were significantly lower in the study group. CONCLUSIONS: Oral UFT plus leucovorin given by either dosage schedule is a very safe regimen for adjuvant chemotherapy. In particular, 5 days of treatment followed by a 2-day rest was a useful treatment option from the viewpoint of toxicity even when given for longer than 6 months. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00280-014-2461-5) contains supplementary material, which is available to authorized users