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This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (No. 16K08371)., Supplementary data related to this article can be found at https://doi.org/10.1016/j.alit.2018.04.012.

Background: Aspirin enhances food allergy symptoms by increasing absorption of ingested allergens. The objective of this study is to elucidate the role of aspirin in facilitating intestinal absorption of the wheat allergen, gliadin, in rats. Methods: Plasma concentrations of gliadin were determined after oral administration by gavage or administration into a closed intestinal loop in rats. We used an in situ intestinal re-circulating perfusion experiment to examine the effect of pepsin on aspirin-facilitated gliadin absorption. Fluorescein isothiocyanate (FITC)-labeled dextran-40 (FD-40) was used as a marker of non-specific absorption. The molecular size of gliadin and its allergenicity in plasma were examined using immunoblot analysis and intradermal reaction tests with Evans blue dye (EBD) extravasation, respectively. Results: Aspirin increased plasma concentrations of gliadin after oral administration but had no effect in the closed intestinal loop study. An in situ intestinal re-circulating perfusion study showed that FITC-labeled gliadin was absorbed similarly to FD-40. Aspirin increased absorption of both intact and pepsin-digested gliadin, with a more significant effect on absorption of pepsin-treated gliadin. Immunoblotting showed that most gliadin was absorbed in intact form. When the gliadin fraction was extracted from rat plasma after gavage and injected intradermally into gliadin-sensitized rats, EBD extravasation was observed at injection sites in a gliadin dose-dependent manner. Conclusions: Aspirin increased the absorption of intact and pepsin-digested gliadin via the paracellular pathway, maintaining their allergenicity. Moreover, the effect of aspirin on gliadin absorption was enhanced by modification and digestion of gliadin in the stomach., This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (No. 16K08371).

type:text, Background: Aspirin enhances food allergy symptoms by increasing absorption of ingested allergens. The objective of this study is to elucidate the role of aspirin in facilitating intestinal absorption of the wheat allergen, gliadin, in rats. Methods: Plasma concentrations of gliadin were determined after oral administration by gavage or administration into a closed intestinal loop in rats. We used an in situ intestinal re-circulating perfusion experiment to examine the effect of pepsin on aspirin-facilitated gliadin absorption. Fluorescein isothiocyanate (FITC)-labeled dextran-40 (FD-40) was used as a marker of non-specific absorption. The molecular size of gliadin and its allergenicity in plasma were examined using immunoblot analysis and intradermal reaction tests with Evans blue dye (EBD) extravasation, respectively. Results: Aspirin increased plasma concentrations of gliadin after oral administration but had no effect in the closed intestinal loop study. An in situ intestinal re-circulating perfusion study showed that FITC-labeled gliadin was absorbed similarly to FD-40. Aspirin increased absorption of both intact and pepsin-digested gliadin, with a more significant effect on absorption of pepsin-treated gliadin. Immunoblotting showed that most gliadin was absorbed in intact form. When the gliadin fraction was extracted from rat plasma after gavage and injected intradermally into gliadin-sensitized rats, EBD extravasation was observed at injection sites in a gliadin dose-dependent manner. Conclusions: Aspirin increased the absorption of intact and pepsin-digested gliadin via the paracellular pathway, maintaining their allergenicity. Moreover, the effect of aspirin on gliadin absorption was enhanced by modification and digestion of gliadin in the stomach., This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (No. 16K08371).

Background: Aspirin enhances food allergy symptoms by increasing absorption of ingested allergens. The objective of this study is to elucidate the role of aspirin in facilitating intestinal absorption of the wheat allergen, gliadin, in rats. Methods: Plasma concentrations of gliadin were determined after oral administration by gavage or administration into a closed intestinal loop in rats. We used an in situ intestinal re-circulating perfusion experiment to examine the effect of pepsin on aspirin-facilitated gliadin absorption. Fluorescein isothiocyanate (FITC)-labeled dextran-40 (FD-40) was used as a marker of non-specific absorption. The molecular size of gliadin and its allergenicity in plasma were examined using immunoblot analysis and intradermal reaction tests with Evans blue dye (EBD) extravasation, respectively. Results: Aspirin increased plasma concentrations of gliadin after oral administration but had no effect in the closed intestinal loop study. An in situ intestinal re-circulating perfusion study showed that FITC-labeled gliadin was absorbed similarly to FD-40. Aspirin increased absorption of both intact and pepsin-digested gliadin, with a more significant effect on absorption of pepsin-treated gliadin. Immunoblotting showed that most gliadin was absorbed in intact form. When the gliadin fraction was extracted from rat plasma after gavage and injected intradermally into gliadin-sensitized rats, EBD extravasation was observed at injection sites in a gliadin dose-dependent manner. Conclusions: Aspirin increased the absorption of intact and pepsin-digested gliadin via the paracellular pathway, maintaining their allergenicity. Moreover, the effect of aspirin on gliadin absorption was enhanced by modification and digestion of gliadin in the stomach., This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (No. 16K08371).

ニボルマブに関連した間質性肺疾患（以下，ILD）の発現については，死亡例が報告され注意喚起がなされている。ILD 等の異常が認められた場合には，ニボルマブを中止し副腎皮質ステロイド剤の投与等の処置を行うこととされているが，十分なデータが得られているとは言えない。平成28年１～12月の間に非小細胞肺癌に対してニボルマブ投与を開始した患者の中でGrade 2及びGrade 3のILD各１名を経験し，メチルプレドニゾロンコハク酸エステルナトリウム１ g/day ×３日間投与後，経口プレドニゾロン投与し漸減することで軽快した。ILD の発現時期については，ニボルマブ２～ 12回目の投与時（中央値８回目）に発現しており定まっていなかった。今回経験したGrade ２以上の症例においては，副腎皮質ステロイドに対する反応性を認めた。, The attention is given to Nivolumab induced interstitial lung disease （refered to as ILD）. In some cases, even deaths have been reported. The standard protocol is that once a sign of ILD is seen, stop Nivolumab and switch to corticosteriod, but there is no enough data to back up this protocol. Among the non-small cell lung cancer patients who were given Nivolumab between January 2016 and December 2016, there was one patient who experienced grade 2 ILD and another patient with grade 3 ILD. Both of these patients’ symptoms of ILD were mostly contained after given 1g/day of Methyprednisolone Soduim Succinate for 3 days, then oral prednisolones with gradually decreasing the dosage of it. Regarding the manifestation of ILD, it varied and it was somewhere bewteen second to 12th doses of Nivolumab with the median of 8th doses. This study was able to confirm the effective response to corticosteriod for grade 2 or higher cases of ILD.

type:text, Inadvertent leakage of noncytotoxic agents causes severe tissue injury. In this study, we macroscopically and histopathologically evaluated the extent of skin injury caused by extravasation of hyperosmolar or vasopressor agents in rats. Rats were intradermally administered saline (100 µL), the hyperosmolar agents mannitol (5–20 mg/100 µL) and glucose (5–50 mg/100 µL), or the vasopressors dopamine (2 mg/100 µL), adrenaline (0.1 mg/100 µL), and noradrenaline (0.1 mg/100 µL). Lesion size (erythema, induration, ulceration, and necrosis) was monitored after agent injection. Skin tissue biopsies were evaluated at 24 h after agent injection. Mannitol and glucose induced severe lesions in a concentration (and osmolarity)-dependent manner. Mannitol and glucose at 10–20% (w/v) induced inflammation, and lesions healed within 3–6 d. In contrast, ≥25% (w/v) glucose elicited severe skin lesions with ulceration and necrosis within 24 h, which healed gradually 16–22 d after injection. The severity of extravasation injury caused by vasopressors varied. Adrenaline and noradrenaline induced severe injury with ulceration and necrosis, which healed over 23.3 and 18.3 d, respectively. In contrast, dopamine induced erythema and induration, and damage duration was only 5.7 d. In conclusion, mannitol and glucose at osmolarities of 549–1098 and 833–1110 mOsm/L, respectively, can be classified as “irritants,” while ≥1388 mOsm/L glucose can be classified as a “vesicant.” As for vasopressors, adrenaline and noradrenaline can be classified as “vesicants” whereas dopamine can be classified as an “irritant.”

Inadvertent leakage of noncytotoxic agents causes severe tissue injury. In this study, we macroscopically and histopathologically evaluated the extent of skin injury caused by extravasation of hyperosmolar or vasopressor agents in rats. Rats were intradermally administered saline (100 µL), the hyperosmolar agents mannitol (5–20 mg/100 µL) and glucose (5–50 mg/100 µL), or the vasopressors dopamine (2 mg/100 µL), adrenaline (0.1 mg/100 µL), and noradrenaline (0.1 mg/100 µL). Lesion size (erythema, induration, ulceration, and necrosis) was monitored after agent injection. Skin tissue biopsies were evaluated at 24 h after agent injection. Mannitol and glucose induced severe lesions in a concentration (and osmolarity)-dependent manner. Mannitol and glucose at 10–20% (w/v) induced inflammation, and lesions healed within 3–6 d. In contrast, ≥25% (w/v) glucose elicited severe skin lesions with ulceration and necrosis within 24 h, which healed gradually 16–22 d after injection. The severity of extravasation injury caused by vasopressors varied. Adrenaline and noradrenaline induced severe injury with ulceration and necrosis, which healed over 23.3 and 18.3 d, respectively. In contrast, dopamine induced erythema and induration, and damage duration was only 5.7 d. In conclusion, mannitol and glucose at osmolarities of 549–1098 and 833–1110 mOsm/L, respectively, can be classified as “irritants,” while ≥1388 mOsm/L glucose can be classified as a “vesicant.” As for vasopressors, adrenaline and noradrenaline can be classified as “vesicants” whereas dopamine can be classified as an “irritant.”

type:text

type:text, Food allergy is an adverse immune response to certain kinds of food. Although any food can cause allergic reactions, chicken egg, cow's milk, wheat, shellfish, fruit, and buckwheat account for 75% of food allergies in Japan. Allergen-specific immunoglobulin E (IgE) antibodies play a pivotal role in the development of food allergy. Recent advances in molecular biological techniques have enabled the efficient analysis of food allergens. As a result, many food allergens have been identified, and their molecular structure and IgE- binding epitopes have also been identified. Studies of allergens have demonstrated that IgE antibodies specific to allergen components and/or the peptide epitopes are good indicators for the identification of patients with food allergy, prediction of clinical severity and development of tolerance. In this review, we summarize our current knowledge regarding the allergens and IgE epitopes in the well-researched allergies to chicken egg, cow's milk, wheat, shrimp, and peanut.

Food allergy is an adverse immune response to certain kinds of food. Although any food can cause allergic reactions, chicken egg, cow's milk, wheat, shellfish, fruit, and buckwheat account for 75% of food allergies in Japan. Allergen-specific immunoglobulin E (IgE) antibodies play a pivotal role in the development of food allergy. Recent advances in molecular biological techniques have enabled the efficient analysis of food allergens. As a result, many food allergens have been identified, and their molecular structure and IgE- binding epitopes have also been identified. Studies of allergens have demonstrated that IgE antibodies specific to allergen components and/or the peptide epitopes are good indicators for the identification of patients with food allergy, prediction of clinical severity and development of tolerance. In this review, we summarize our current knowledge regarding the allergens and IgE epitopes in the well-researched allergies to chicken egg, cow's milk, wheat, shrimp, and peanut.

Theaimof this study was to characterize the individualswith sacroiliac joint bridging (SIB) by analyzing the degenerative changes in theirwhole vertebral column and comparing themwith the controls.Atotal of 291modern Japanesemale skeletons,with an average age at death of 60.8 years, were examined macroscopically. They were divided into two groups: individuals with SIB and those without bridging (Non-SIB).The degenerative changes in their whole vertebral column were evaluated, and marginal osteophyte scores (MOS) of the vertebral bodies and degenerative joint scores in zygapophyseal jointswere calculated. SIBwas recognized in 30 individuals froma total of 291 males (10.3%).The average of age at death in SIB group was significantly higher than that in Non-SIB group. The values ofMOS in the thoracic spines, particularly in the anterior part of the vertebral bodies, were consecutively higher in SIB group than in Non-SIB group. Incidence of fused vertebral bodies intervertebral levels was obviously higher in SIB group than in Non-SIB group. SIB and marginal osteophyte formation in vertebral bodies could coexist in a skeletal population of men. Some systemic factors might act on these degenerative changes simultaneously both in sacroiliac joint and in vertebral column., BioMed Research International, 2014, 879645; 2014

type:text, We previously reported that fucoidan, a dietary fiber purified from seaweed, inhibited IgE production by B cells in vitro. In this study, we examined the effect of fucoidan on IgE production in vivo. The OVA-induced increase of plasma IgE was significantly suppressed when fucoidan was intraperitoneally, but not orally, administered prior to the first immunization with OVA. The production of IL-4 and IFN-gamma in response to OVA in spleen cells isolated from OVA-sensitized mice treated with fucoidan in vivo was lower than that from mice treated without fucoidan. Moreover, the flow cytometric analysis and ELISpot assay revealed that the administration of fucoidan Suppressed a number of IgE-expressing and IgE-secreting B cells, respectively. These results indicate that fucoidan inhibits the increase of plasma IgE through the suppression of IgE-producing B cell population, and the effect of fucoidan in VIVO is Crucially dependent on the route and timing of its administration.

We previously reported that fucoidan, a dietary fiber purified from seaweed, inhibited IgE production by B cells in vitro. In this study, we examined the effect of fucoidan on IgE production in vivo. The OVA-induced increase of plasma IgE was significantly suppressed when fucoidan was intraperitoneally, but not orally, administered prior to the first immunization with OVA. The production of IL-4 and IFN-gamma in response to OVA in spleen cells isolated from OVA-sensitized mice treated with fucoidan in vivo was lower than that from mice treated without fucoidan. Moreover, the flow cytometric analysis and ELISpot assay revealed that the administration of fucoidan Suppressed a number of IgE-expressing and IgE-secreting B cells, respectively. These results indicate that fucoidan inhibits the increase of plasma IgE through the suppression of IgE-producing B cell population, and the effect of fucoidan in VIVO is Crucially dependent on the route and timing of its administration.

A conceptual design work and a basic experimental study of a new beam profile monitor have been performed. The monitor will be used to measure emittance of an electron beam in the ATF damping ring at KEK, in which the transverse beam size of about 10 micron is expected. It utilizes a CW laser and an optical cavity, instead of a material wire, to minimize interference with an electron beam. A laser beam with a very thin waist is realized by employing the cavity of nearly concentric mirror configuration while the intensity is amplified by adjusting the cavity length to a Fabry-Perot resonance condition. We built a test cavity to establish a method to measure important parameters such as a laser beam waist and a power enhancement factor. Three independent methods were examined for the measurement of the beam waist. It was found that the cavity realized the beam waist of 20 micron with the power enhancement factor of 50., Comment: 19 pages, 10 figures, submitted to Nucl. Instr. and Meth. A

A conceptual design work and a basic experimental study of a new beam profile monitor have been performed. The monitor will be used to measure emittance of an electron beam in the ATF damping ring at KEK, in which the transverse beam size of about 10 micron is expected. It utilizes a CW laser and an optical cavity, instead of a material wire, to minimize interference with an electron beam. A laser beam with a very thin waist is realized by employing the cavity of nearly concentric mirror configuration while the intensity is amplified by adjusting the cavity length to a Fabry-Perot resonance condition. We built a test cavity to establish a method to measure important parameters such as a laser beam waist and a power enhancement factor. Three independent methods were examined for the measurement of the beam waist. It was found that the cavity realized the beam waist of 20 micron with the power enhancement factor of 50., Comment: 19 pages, 10 figures, submitted to Nucl. Instr. and Meth. A

広島大学(Hiroshima University), 博士(薬学), Pharmacology, doctoral

Food allergy is an adverse immune response to certain kinds of food. Although any food can cause allergic reactions, chicken egg, cow's milk, wheat, shellfish, fruit, and buckwheat account for 75% of food allergies in Japan. Allergen-specific immunoglobulin E (IgE) antibodies play a pivotal role in the development of food allergy. Recent advances in molecular biological techniques have enabled the efficient analysis of food allergens. As a result, many food allergens have been identified, and their molecular structure and IgE- binding epitopes have also been identified. Studies of allergens have demonstrated that IgE antibodies specific to allergen components and/or the peptide epitopes are good indicators for the identification of patients with food allergy, prediction of clinical severity and development of tolerance. In this review, we summarize our current knowledge regarding the allergens and IgE epitopes in the well-researched allergies to chicken egg, cow's milk, wheat, shrimp, and peanut.

Inadvertent leakage of noncytotoxic agents causes severe tissue injury. In this study, we macroscopically and histopathologically evaluated the extent of skin injury caused by extravasation of hyperosmolar or vasopressor agents in rats. Rats were intradermally administered saline (100 µL), the hyperosmolar agents mannitol (5–20 mg/100 µL) and glucose (5–50 mg/100 µL), or the vasopressors dopamine (2 mg/100 µL), adrenaline (0.1 mg/100 µL), and noradrenaline (0.1 mg/100 µL). Lesion size (erythema, induration, ulceration, and necrosis) was monitored after agent injection. Skin tissue biopsies were evaluated at 24 h after agent injection. Mannitol and glucose induced severe lesions in a concentration (and osmolarity)-dependent manner. Mannitol and glucose at 10–20% (w/v) induced inflammation, and lesions healed within 3–6 d. In contrast, ≥25% (w/v) glucose elicited severe skin lesions with ulceration and necrosis within 24 h, which healed gradually 16–22 d after injection. The severity of extravasation injury caused by vasopressors varied. Adrenaline and noradrenaline induced severe injury with ulceration and necrosis, which healed over 23.3 and 18.3 d, respectively. In contrast, dopamine induced erythema and induration, and damage duration was only 5.7 d. In conclusion, mannitol and glucose at osmolarities of 549–1098 and 833–1110 mOsm/L, respectively, can be classified as “irritants,” while ≥1388 mOsm/L glucose can be classified as a “vesicant.” As for vasopressors, adrenaline and noradrenaline can be classified as “vesicants” whereas dopamine can be classified as an “irritant.”

We previously reported that fucoidan, a dietary fiber purified from seaweed, inhibited IgE production by B cells in vitro. In this study, we examined the effect of fucoidan on IgE production in vivo. The OVA-induced increase of plasma IgE was significantly suppressed when fucoidan was intraperitoneally, but not orally, administered prior to the first immunization with OVA. The production of IL-4 and IFN-gamma in response to OVA in spleen cells isolated from OVA-sensitized mice treated with fucoidan in vivo was lower than that from mice treated without fucoidan. Moreover, the flow cytometric analysis and ELISpot assay revealed that the administration of fucoidan Suppressed a number of IgE-expressing and IgE-secreting B cells, respectively. These results indicate that fucoidan inhibits the increase of plasma IgE through the suppression of IgE-producing B cell population, and the effect of fucoidan in VIVO is Crucially dependent on the route and timing of its administration.