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Keywords: exercise; gliadin; non-steroidal anti-inflammatory drugs; prostaglandin; wheat-dependent exercise-induced anaphylaxis EN exercise gliadin non-steroidal anti-inflammatory drugs prostaglandin wheat-dependent exercise-induced anaphylaxis 359 361 3 03/15/23 20230301 NES 230301 Key messages Bread ingestion combined with exercise or aspirin increased the serum level of wheat gliadins. We measured the blood gliadin levels in patients with WDEIA during a challenge test, using a highly sensitive enzyme-linked immunosorbent assay (ELISA) that can specifically detect wheat gliadin.[[2]] As a result, the blood gliadin level increased preceding the allergic symptoms when induced by the combination of wheat ingestion and exercise, while serum gliadin was not detected or remained at a very low level in the case of the wheat ingestion alone. Blood gliadin levels were elevated for 15-120 min after gluten ingestion; however, no enhancing effects were found for aspirin, alcohol, or exercise on blood gliadin levels. [Extracted from the article]

Background: The effect of oral immunotherapy (OIT) on wheat allergy is promising in terms of the potential to obtain desensitization; however, the frequency of exercise‐induced allergic reactions on desensitization (EIARDs) and the associated risk factors remain to be determined. Methods: Twenty‐five patients underwent rush OIT for wheat allergy, and 21 achieved the full‐dose intake of wheat products (5 g of wheat protein). Exercise‐provocation tests were repeatedly performed after the ingestion of a full‐dose wheat product. The time‐course of the levels of the specific IgEs (sIgE) to wheat extract, total gliadin, deamidated gliadin, recombinant gliadin components (α/β–, γ– and ω–5–), and glutenin (high and low molecular weight) components was analyzed using ImmunoCAP®, ELISA, or IgE immunoblotting. Results: Fourteen patients (66.7%) were diagnosed as EIARD+, which remained 5 years after rush OIT in 11 patients (52.4%). There were no differences in the clinical backgrounds of the EIARD+ and EIARD− patients. However, EIARD+ patients showed significantly higher sIgE levels to all gliadin and glutenin components than EIARD‐ patients before OIT. The sIgE levels to each component decreased equally after 1 and 2 years of OIT. On IgE immunoblotting, sera from all patients reacted to the multiple gluten bands, and some reacted to the water‐soluble bands. The intensity of all IgE‐reactive bands also became equally lighter after OIT. Conclusions: EIARDs were frequently observed and remained for a long period after successful OIT for wheat allergy. None of the specific wheat components were found to contribute to EIARDs. [ABSTRACT FROM AUTHOR]

Background: Pancreaticobiliary maljunction and intrahepatic gallstones are at a high risk for biliary malignancy. Lysophosphatidylcholine (LPC) is increased in the bile of these patients, and we have previously reported that LPC‐induced cytotoxicity causes senescence‐associated secretory phenotype (SASP) in cholangiocytes. We aimed to determine the protective effect of phosphatidylcholine (PC) on LPC‐induced cholangiocyte cytotoxicity. Methods: MMNK‐1, a human immortalized cholangiocyte cell line was treated with LPC with or without PC. To assess the biological effects of SASP components on cholangiocarcinoma, HuH28 and HuCCT1 (human cholangiocarcinoma cell lines) were cultured in the conditioned media where MMNK‐1 cells treated with LPC. Results: The presence of PC reduced reactive oxygen species generation and oxidative DNA damage in MMNK‐1 treated with LPC. Moreover, SA‐β‐gal activity was markedly downregulated by PC. The secretion of SASP components, including interleukin (IL)‐8, IL‐6, and C‐C motif chemokine ligand 2 was also substantially reduced in the presence of PC. Cellular proliferation and migration were enhanced in HuCCT1 and HuH28 cells when cultured in the conditioned media, and these observations were suppressed by simultaneous addition of PC. Conclusion: PC protects cholangiocytes against LPC‐induced cytotoxicity and cellular senescence, suggesting its potential as a target for inhibiting LPC‐related carcinogenesis and its promotion. [ABSTRACT FROM AUTHOR]

Aim: Rho‐kinase (ROCK) inhibitor could ameliorate liver fibrosis by suppressing hepatic stellate cell (HSC) activation. However, because systemic administration of ROCK inhibitor causes serious adverse effects, we developed a drug delivery system selectively delivering ROCK inhibitor to HSCs. Here, we examined whether our developed vitamin A (VA)‐coupled liposomal ROCK inhibitor reduced liver fibrosis in rats without causing systemic adverse effects. Methods: LX‐2 HSCs were analyzed for morphological changes and the expression of profibrotic proteins. The inhibitory effects of VA‐coupled liposomal ROCK inhibitor on liver fibrosis were confirmed in a rat model of liver fibrosis induced by i.p. injection of carbon tetrachloride. The degree of liver fibrosis, biochemical changes, and survival rates were also investigated. Results: Vitamin A‐coupled liposomal ROCK inhibitor had an effect at approximately 1/100 the amount of the free ROCK inhibitor for inhibiting the activation of LX‐2 cells and caused significant decreases in the expression levels of α‐smooth muscle actin (SMA) and transforming growth factor (TGF)‐β1. The degree of liver fibrosis was suppressed by treatment with VA‐coupled liposomal ROCK inhibitor, and the expression of α‐SMA and TGF‐β1 in liver tissues was also significantly suppressed. In addition, serum levels of alanine aminotransferase and hyaluronic acid were significantly reduced, and there was no decline in kidney function, which has been noted as a systemic adverse effect of ROCK inhibitor. Furthermore, VA‐coupled liposomal ROCK inhibitor improved survival rates in rats with liver fibrosis. Conclusion: Vitamin A‐coupled liposomal ROCK inhibitor efficiently suppressed liver fibrosis without causing systemic adverse effects. [ABSTRACT FROM AUTHOR]

Background: Wheat protein and its derivatives can cause protein contact dermatitis (PCD), which mainly occurs in bakers. Few studies have attempted to identify the allergens responsible for wheat PCD. Objectives: The aim of this study was to identify allergenic wheat proteins in patients with wheat PCD. Methods: Water-soluble and water-insoluble wheat flour proteins were separated by 1- or 2-dimensional gel electrophoresis. IgE-binding proteins were detected by immunoblotting with sera from 3 wheat PCD patients and identified by N-terminal amino acid sequence analysis. The IgE-binding proteins were recombinantly expressed in Escherichia coli and tested against patients' sera. Results: IgE antibodies from the patients' sera reacted with water-soluble proteins rather than water-insoluble proteins, and the 2-dimensional electrophoresis and immunoblotting produced individual IgE-binding patterns. Analysis of the N-terminal amino acid sequence of the IgE-binding proteins from the 2-dimensional gel led to the identification of three glycoproteins, wheat 27-kDa allergen, peroxidase, and purple acid phosphatase. No specific IgE antibodies to their non-glycosylated recombinant proteins were observed. Conclusions: We identified wheat 27-kDa allergen, peroxidase and purple acid phosphatase as candidate allergens for wheat PCD. Our results suggest that glycan moieties in these proteins are involved in IgE binding. [ABSTRACT FROM AUTHOR]

Shrimp is known to be the most common causative agent in seafood allergy. Patients with shrimp allergy often exhibit allergic symptoms to a variety of seafoods such as crabs and clams. We experienced a 14-year-old girl with shrimp allergy who developed oral swelling and pain accompanied with an uncomfortable feeling after ingestion of scallops followed by intensive exercise. Laboratory investigation showed that she had serum immunoglobulin (Ig)E molecules reacting with several kinds of crustaceans and mollusks, including shrimp, crab and scallops. Immunoblotting revealed that her serum IgE reacted with the 38 kDa bands for shrimp, crab and scallops, suggesting that tropomyosin was the major allergen. Dot-blot inhibition analysis showed a cross-reactivity among shrimp, crab and scallops. We conclude that the cross-reactivity of IgE in this patient resulted from the high homology of tropomyosins. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF) is a powerful agent that causes hyperpermeability of blood vessels as well as endothelial cell proliferation. Recent investigations have revealed that production of VEGF increases in epidermis of psoriatic lesions, and the overproduced VEGF plays an important role in the pathogenesis of psoriasis. In this study, we used immunohistochemical staining as well as extraction of stratum corneum with physiological saline to further analyse VEGF produced in psoriatic lesions. Biological activity of VEGF in the psoriatic scales was assayed by cultured human umbilical vein endothelial cells in vitro. The immunohistochemical examination confirmed an increased production of VEGF in the keratinocytes of psoriatic lesions. In addition, we found that the content of VEGF contained in the psoriatic scales was approximately 50 times greater than that in normal stratum corneum. We also found that VEGF 121 isoform, which has an exclusive ability to cause hyperpermeability of blood vessels, was predominantly detected in psoriatic scales, suggesting a major role of VEGF 121 isoform on the altered structure of microvessels in psoriatic lesions. [ABSTRACT FROM AUTHOR]

Wheat ω-5 gliadin has been identified as a major allergen in wheat-dependent exercise-induced anaphylaxis. We have detected seven IgE-binding epitopes in primary sequence of the protein. We newly identified four additional IgE-binding epitope sequences, QQFHQQQ, QSPEQQQ, YQQYPQQ and QQPPQQ, in three patients with wheat-dependent exercise-induced anaphylaxis in this study. Diagnosis and therapy of food allergy would benefit from the availability of defined recombinant allergens. However, because ω-5 gliadin gene has not been cloned, recombinant protein is currently unavailable. We sought to clone the ω-5 gliadin gene and produce the homogeneous recombinant protein for use in an in vitro diagnostic tool. Using a PCR-based strategy we isolated two full-length ω-5 gliadin genes, designated ω-5 and ω-5b, from wheat genomic DNA and determined the nucleotide sequences. The protein encoded by ω-5a was predicted to be 439 amino acids long with a calculated mass of 53 kDa; the ω-5b gene would encode a 393 amino acid, but it contains two stop codons indicating that ω-5b is pseudogene. The C-terminal half (178 amino acids) of the ω-5a gliadin protein, including all 11 IgE-binding epitope sequences, was expressed in Escherichia coli by means of the pET system and purified using RP-HPLC. Western blot analysis and dot blot inhibition assay of recombinant and native ω-5 gliadin purified from wheat flour demonstrated that recombinant protein had IgE-binding ability. Our results suggest that the recombinant protein can be a useful tool for identifying patients with wheat-dependent exercise-induced anaphylaxis in vitro. [ABSTRACT FROM AUTHOR]

We have clinically isolated a methicillin-resistant Staphylococcus aureus (MRSA) K-1 which exhibits enhanced arbekacin (Abk) resistance. In this study, we investigated a molecular mechanism for the overproduction of a bifunctional enzyme catalyzing both 2″-O-phosphorylation and 6′-N-acetylation of aminoglycoside antibiotics that is encoded by aacA-aphD and designated [AAC(6′)/APH(2″)] and is expressed in MRSA K-1. The sequence analysis of the 5′-adjacent region of the aacA-aphD structural gene in MRSA K-1 showed that 12 bp are deleted from the aacA-aphD promoter region when compared with that in MRSA B-26, which exhibits lower resistance to Abk than K-1. By artificially deleting the 12 bp from the corresponding region in MRSA B-26, we confirmed that the strain increases Abk resistance to the same level as seen in MRSA K-1, which suggests that the 12 bp deletion from the 5′-adjacent region of the aacA-aphD structural gene created a strong promoter to overexpress the bifunctional enzyme. [Copyright &y& Elsevier]

Shrimp is known to be the most common causative agent in seafood allergy. Patients with shrimp allergy often exhibit allergic symptoms to a variety of seafoods such as crabs and clams. We experienced a 14-year-old girl with shrimp allergy who developed oral swelling and pain accompanied with an uncomfortable feeling after ingestion of scallops followed by intensive exercise. Laboratory investigation showed that she had serum immunoglobulin (Ig)E molecules reacting with several kinds of crustaceans and mollusks, including shrimp, crab and scallops. Immunoblotting revealed that her serum IgE reacted with the 38 kDa bands for shrimp, crab and scallops, suggesting that tropomyosin was the major allergen. Dot-blot inhibition analysis showed a cross-reactivity among shrimp, crab and scallops. We conclude that the cross-reactivity of IgE in this patient resulted from the high homology of tropomyosins.

Olopathadine, a newly developed histamine H1-receptor antagonist, was compared with cetirizine in its suppressive effects on histamine-induced wheal and flare reaction using an iontophoresis technique in a double-blind, crossover, placebo-controlled fashion. As a result, olopathadine was found to have effects comparable to cetirizine. This finding may predict the efficacy of this new H1-antagonist in treating pruritic skin diseases.

We report a case of atypical urticaria associated with IgA multiple myeloma. A 79-year-old man presented with a two-month history of wheal-like erythema, which lasted approximately one week without any response to anti-histamines. Histological examination of a lesion revealed leukocytoclasia as well as perivascular leukocytic infiltration, being consistent with urticarial erythema. Laboratory investigation showed markedly elevated serum IgA concentration and M-protein in serum protein electrophoresis. A bone marrow examination led to a diagnosis of myeloma. An immunofluorescence study failed to detect any IgA deposit in the lesion. However, the wheal-like eruptions disappeared when the IgA myeloma was treated and reappeared when it relapsed. We conclude that this long lasting urticaria was the cutaneous manifestation of IgA myeloma.