Lymphocyte Responses to Chymotrypsin- or Trypsin V-Digested β-Lactoglobulin in Patients with Cow's Milk Allergy

<p/> <p>Chymotrypsin- or trypsin V- (a mixture of trypsin and chymotrypsin) digested β-lactoglobulin (BLG) peptides were prepared and were confirmed to have much less immunoglobulin (lg)G and lgE reactivity compared with intact BLG by IgG inhibition enzymelinked immunosorbent assay and IgE dot blotting. The lymphocyte responses to intact BLG and these peptides were examined using peripheral blood mononuclear cells (PBMCs) from 10 patients with cow's milk allergy. The PBMCs from most patients had lower lymphocyte responses to chymotrypsin- and trypsin V-digested BLG peptides than those to intact BLG. However, PBMCs from one and two patients retained significant proliferative responses to both peptides and to only the former peptide, respectively. Interferon-c production stimulated by chymotrypsin-digested peptides was still detectable in all five patients tested. Chymotrypsindigested BLG reduced lgE reactivity but still induced some lymphocyte responses.</p

Prognostic value of an increased in flourine-18 deoxyglucose uptake in patients with myocardial infarction: Comparision with stress thallium imaging

AbstractObjectives. This study was undertaken to evaluate the prognostic value of an increase in fluorine (F)-18 deoxyglucose uptake compared wilh clinical, angiographic and stress thallium findings in patients with myocardial infarction.Background. Positron emission tomography (PET) imaging using F-18 deoxyglucose has been applied to assess tissue viability in patients with coronary artery disease. We hypothesized that patients with a myocardial segment with augmented F-18 deoxyglucose uptake are at high risk for a future cardiac event.Methods. One hundred fifty-eight consecutive patients with myocardial infarction referred for F-18 deoxyglucose PET and stress thallium scans were studied. Follow-up was obtained in 84 patients at a mean interval of 23 months to investigate prognostic implications of radionuclide studies.Results. Seventeen patients had a cardiac event during the follow-up interval. Univariate analysis showed that an increase in F-18 deosyglucose uptake was the best predictor of a future cardiac event (p = 0.0006), followed by the number of stenosed vessels (p = 0.008). In the multivariate analysis, when an increase in F-18 deoxyglucose uptake was entered into the model, only angiographic variables had an independent value, whereas no other radionuclide variables showed value. Among patients who did not show redistribution, a future cardiac event was observed more often in patients with than in those without an increase in F-18 deoxyglucose uptake (p < 0.05).Conclusions. Thus, an increase in F-18 deoxyglucose uptake seemed to be the best predictor of a future cardiac event among all clinical, angiographic and redionuclide variables in this study of stable patients with myocardial infarction. Even when a stress thallium-201 scan does not show redistribution, those patients who have an increase in F-18 deoxyglucose uptake in a PET study may be at risk for a future cardiac event, and these patients may need aggressive treatment to prevent a future cardiac event

Reconciling biodiversity conservation and flood risk reduction : The new strategy for freshwater protected areas

Aim: Natural disaster risk reduction (DRR) is becoming a more important function of protected area (PAs) for current and future global warming. However, biodiversity conservation and DRR have been handled separately and their interrelationship has not been explicitly addressed. This is mainly because, due of prevailing strategies and criteria for PA placement, a large proportion of PAs are currently located far from human-occupied areas, and habitats in human-occupied areas have been largely ignored as potential sites for conservation despite their high biodiversity. If intensely developed lowland areas with high flooding risk overlap with important sites for biodiversity conservation, it would be reasonable to try to harmonize biodiversity conservation and human development in human-inhabited lowland areas. Here, we examined whether extant PAs can conserve macroinvertebrate and freshwater fish biodiversity and whether human-inhabited lowland flood risk management sites might be suitable to designate as freshwater protected areas (FPAs). Location: Across Japan. Methods: We examined whether extant PAs can conserve macroinvertebrate and freshwater fish biodiversity and analysed the relationship between candidate sites for new FPAs and flood disaster risk and land use intensity at a national scale across Japan based on distribution data for 131 freshwater fish species and 1395 macroinvertebrate species. Results: We found that extant PAs overlapped with approximately 30% of conservation-priority grid cells (1 km2) for both taxa. Particularly for red-listed species, only one species of freshwater fish and three species of macroinvertebrate achieved the representation target within extant PAs. Moreover, more than 40% of candidate conservation-priority grid cells were located in flood risk and human-occupied areas for both taxa. Main conclusions: Floodplain conservation provides suitable habitat for many freshwater organisms and helps control floodwaters, so establishing new FPAs in areas with high flood risk could be a win-win strategy for conserving freshwater biodiversity and enhancing ecosystem-based DRR (eco-DRR)

Metallic Pattern Fabrication in Organic Mott Insulating Crystal by Local X-Ray Irradiation

We have fabricated a metallic structure in an organic Mott insulator $\kappa$-(BEDT-TTF)$_2$Cu[N(CN)$_2$]Cl. The periodic metallic domains of approximately 90$\times$90 $\mu$m$^2$ obtained by X-ray irradiation through a molybdenum mesh mask are visualized by scanning microregion infrared reflectance spectroscopy technique. No deterioration by irradiation is found in a range of nanometer to micrometer scales. We demonstrate that the present processing method is applicable for the fabrication of molecular electronic devices.Comment: 3 pages, submitted to APE

Evaluation of oral immunotherapy efficacy and safety by maintenance dose dependency: A multicenter randomized study

Background Generally, oral immunotherapy (OIT) aims for daily administration. Recently, the efficacy of treatment with OIT at a low dose has been reported. However, the optimal dose and the evaluation of dose-dependent OIT outcome have not been described. Methods A multicenter, parallel, open-labeled, prospective, non-placebo controlled, randomized study enrolled 101 Japanese patients for treatment with OIT. We hypothesized that target dose OIT would induce short-term unresponsiveness (StU) earlier than reduced dose OIT. StU was defined as no response to 6200 mg whole egg, 3400 mg milk, and 2600 mg wheat protein, as evaluated by oral food challenge after 2-week ingestion cessation. To compare the two doses of OIT efficacy, the maximum ingestion doses during the maintenance phase of OIT were divided into 100%-dose or 25%-dose groups against their target StU dose, respectively. A total of 51 patients were assigned to the 100%-dose group [hen's egg (HE) = 26, cow's milk (CM) = 13, wheat = 12] and 50 to the 25%-dose group (HE = 25, CM = 13, wheat = 12). Primary outcome was established by comparing StU at 1 year. Secondary outcome was StU at 2 years and established by comparing allergic symptoms and immunological changes. Results The year 1 StU rates (%) for the 100%- and 25%-dose groups were 26.9 vs. 20.0 (HE), 7.7 vs. 15.4 (CM), and 50.0 vs. 16.7 (wheat), respectively. The year 2 StU rates were 30.8 vs. 36.0 (HE), 7.7 vs. 23.1 (CM), and 58.3 vs. 58.3 (wheat), respectively. There were no statistically significant differences in StU between years 1 and 2. The total allergic symptom rate in the 25%-dose group was lower than that in the 100%-dose group for egg, milk, and wheat. Antigen-specific IgE levels for egg-white, milk, and wheat decreased at 12 months. Conclusions Reduced maintenance dose of egg OIT showed similar therapeutic efficacy to the target dose. However, we were not able to clearly demonstrate the efficacy, particularly for milk and wheat. Reducing the maintenance dose for eggs, milk, and wheat may effectively lower the symptoms associated with their consumption compared to the target OIT dose. Furthermore, aggressive reduction of the maintenance dose might be important for milk and wheat, compared to the 25%-dose OIT

The surveillance of colistin resistance and mobilized colistin resistance genes in multidrug-resistant Enterobacteriaceae isolated in Japan

Background: The plasmid-mediated bacterial colistin-resistant gene, mcr, is of global concern in clini-cal healthcare. However, there are few reports of surveillance for mcr in Japan. The aim of this study was to assess the prevalence of colistin resistance by identifying nine mcr genes in extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and carbapenem-resistant Enterobacteriaceae (CRE) isolates in Japan.Methods: A total of 273 ESBL and CRE clinical isolates were collected from patients in five tertiary hospi-tals from August 2016 to March 2017. Minimum inhibitory concentration (MIC) of colistin was measured using the microdilution method. Polymerase chain reaction (PCR) was performed to detect mcr-1 to mcr-9 genes in all strains. Whole-genome sequencing (WGS) analysis was conducted for any mcr-genes identi-fied that had not been previously reported in patients from Japan.Results: The rate of colistin resistance was 7.7% in all strains, with a higher rate in the CRE strains than in the ESBL-producing strains (20.4% versus 1.1%). The mcr-5 and mcr-9 gene were detected in one ESBL-producing Escherichia coli strain (1/273, 0.37%) and three CRE strains (3/273, 1.1%), respectively. As theESBL-producing E. coli strain was the first clinical strain with mcr-5 in Japan, WGS analysis was performed for the strain. The sequence type of the mcr-5-positive strain was ST1642 and it carried two distinct plasmids, ESBL gene-carrying pN-ES-6-1, and mcr-5.1-carrying pN-ES-6-2.Conclusions: The results of this study showed that the frequency of colistin resistance and mcr-positive strains is not high in Japan. As the MIC for colistin was low in the mcr-5.1 and mcr-9 gene-positive strain, continuous monitoring of mcr genes is necessary

Macrophage-Specific Chemokines Induced via Innate Immunity by Amino Acid Copolymers and Their Role in EAE

The random amino acid copolymer poly(Y,E,A,K)n (Copaxone®) is widely used in multiple sclerosis treatment and a second generation copolymer poly(Y,F,A,K)n with enhanced efficacy in experimental autoimmune encephalomyelitis in mice has been described. A major mechanism through which copolymers function to ameliorate disease is the generation of immunosuppressive IL-10-secreting regulatory T cells entering the CNS. In addition, the antigen presenting cell to which these copolymers bind through MHC Class II proteins may have an important role. Here, both CCL22 (a Th2 cell chemoattractant) in large amounts and CXCL13 in much smaller amounts are shown to be secreted after administration of YFAK to mice and to a smaller extent by YEAK parallel to their serum concentrations. Moreover, bone marrow-derived macrophages secrete CCL22 in vitro in response to YFAK and to higher concentrations of YEAK. Strikingly, these chemokines are also secreted into serum of MHC Class II −/− mice, indicating that an innate immune receptor on these cells also has an important role. Thus, both the innate and the adaptive immune systems are involved in the mechanism of EAE amelioration by YFAK. The enhanced ability of YFAK to stimulate the innate immune system may account for its enhanced efficacy in EAE treatment