Alpha/Beta Gliadin MM1 Is a Novel Antigen for Wheat-Dependent Exercise-Induced Anaphylaxis.

INTRODUCTION: Screening for ω-5 gliadin specific IgE antibody (sIgE) has high diagnostic utility in cases of suspected wheat-dependent exercise-induced anaphylaxis (WDEIA); however, negative cases may require confirmatory tests, such as the oral challenge test. Thus, newly identified allergens that can be used for the serological diagnosis of WDEIA are needed. This study aimed to identify additional sIgE biomarkers of WDEIA. METHODS: Forty-two patients with WDEIA (5 negative/37 positive for ω-5 gliadin sIgE) were enrolled. For comparison, 8 patients with immediate-type wheat allergy without WDEIA and 20 healthy controls without wheat allergy were also enrolled. Extracted wheat proteins were separated by 2D-PAGE. Proteins that reacted with serum IgE antibody in 2D Western blotting (2D-WB) were identified using mass spectrometry. Recombinant proteins were synthesized in Escherichia coli, and the antigenicity was tested using ELISA and the basophil activation test. RESULTS: In 2D-WB, nine proteins reacted with the serum IgE antibody from at least 60% of patients with WDEIA (n ≥ 25/42). ELISA revealed that alpha/beta gliadin MM1 exhibited the highest positive immunoreactivity in 23 of 26 patients who were positive for ω-5 gliadin sIgE (88%) and in 5 of 5 patients who were negative for ω-5 gliadin sIgE (100%). Alpha/beta gliadin MM1 exhibited significantly higher basophil activation in 14 patients with WDEIA when compared to 5 individuals without a wheat allergy. CONCLUSIONS: Alpha/beta gliadin MM1 sIgE exhibited the highest seropositivity, even among patients who were negative for ω-5 gliadin sIgE. The inclusion of alpha/beta gliadin MM1 in allergen-sIgE tests may improve the sensitivity for diagnosing WDEIA.

The clinical cross-reactivity and immunological cross-antigenicity of wheat and barley.

BACKGROUND: Some patients with wheat allergy have been reported to show clinical cross-reactivity to barley. However, it is not clear whether the development of barley allergy in patients with wheat allergy is due to cross-antigenicity between wheat and barley. This study aimed to determine the clinical cross-reactivity and immunological cross-antigenicity of wheat and barley. METHODS: The results of barley oral food challenges (OFCs) were compared before and after oral immunotherapy (OIT) for wheat in nine patients with wheat allergy to estimate the clinical cross-reactivity of wheat and barley. Moreover, we performed enzyme-linked immunosorbent assay (ELISA) inhibition and immunoblotting inhibition using serum from seven patients allergic to wheat and barley. RESULTS: Nine patients who had positive barley-OFC results performed before OIT for wheat were all negative on barley-OFC performed after OIT. In ELISA inhibition, preincubation of serum from patients allergic to wheat and barley with a high barley extract concentration inhibited binding of IgE to wheat extract by less than 10%. On the other hand, wheat and barley extracts equally inhibited binding to barley sIgE at high concentrations. In the immunoblotting inhibition test, the spots of wheat were inhibited but weakly by barley extracts, and most of the spots of barley were inhibited even by low concentrations of the wheat and barley extract. CONCLUSIONS: We showed that barley allergy associated with wheat allergy is caused by cross-reactivity from wheat. The OIT for wheat is one of the promising options for barley allergy.

[ANAPHYLACTIC REACTION TO LYSOZYME CHLORIDE-INCLUDING DEODORANT SPRAY IN A CHILD WITH EGG ALLERGY].

BACKGROUND: Lysozyme chloride is a bactericidal substance that is included as an active ingredient in many medicines and quasi-drugs. We experienced a case of anaphylactic reaction caused by deodorant spray-containing lysozyme chloride. CASE: The patient was a 10-year-old girl who had an egg allergy. She visited an emergency department because of urticaria, wheezing, dyspnea, and pallor after she used deodorant spray that contained lysozyme chloride derived from hen's egg white. Results for deodorant spray and lysozyme chloride were positive in both skin prick tests and basophil activation tests. According to the medical history and the results, her condition was diagnosed as an anaphylactic reaction to lysozyme chloride in the deodorant spray. DISCUSSION: Although ingredient labelling is obligatory for lysozyme chloride in quasi-drugs, lysozyme chloride is not often described to be derived from egg white. It is important to alert patients with egg allergy to avoid lysozyme chloride-containing products.

Detection of Hole Pockets in the Candidate Type-II Weyl Semimetal MoTe_{2} from Shubnikov-de Haas Quantum Oscillations.

The bulk electronic structure of T_{d}-MoTe_{2} features large hole Fermi pockets at the Brillouin zone center (Γ) and two electron Fermi surfaces along the Γ-X direction. However, the large hole pockets, whose existence has important implications for the Weyl physics of T_{d}-MoTe_{2}, has never been conclusively detected in quantum oscillations. This raises doubt about the realizability of Majorana states in T_{d}-MoTe_{2}, because these exotic states rely on the existence of Weyl points, which originated from the same band structure predicted by density functional theory (DFT). Here, we report an unambiguous detection of these elusive hole pockets via Shubnikov-de Haas (SdH) quantum oscillations. At ambient pressure, the quantum oscillation frequencies for these pockets are 988 and 1513 T, when the magnetic field is applied along the c axis. The quasiparticle effective masses m^{*} associated with these frequencies are 1.50 and 2.77 m_{e}, respectively, indicating the importance of Coulomb interactions in this system. We further measure the SdH oscillations under pressure. At 13 kbar, we detected a peak at 1798 T with m^{*}=2.86m_{e}. Relative to the oscillation data at a lower pressure, the amplitude of this peak experienced an enhancement, which can be attributed to the reduced curvature of the hole pockets under pressure. Combining our experimental data with DFT+U calculations, where U is the Hubbard parameter, our results shed light on why these important hole pockets have not been detected until now.

Crystal Structure and Superconductivity of Tetragonal and Monoclinic Ce1- xPr xOBiS2.

Ce1- xPr xOBiS2 powders and Ce0.5Pr0.5OBiS2 single crystals were synthesized and their structure and superconductive properties were examined by X-ray diffraction, X-ray absorption, electronic resistivity, and magnetization. While PrOBiS2 was found to be in a monoclinic phase with one-dimensional Bi-S zigzag chains showing no superconductive transition above 0.1 K, CeOBiS2 was in a tetragonal phase with two-dimensional Bi-S planes showing zero resistivity below 1.3 K. In the range x = 0.3-0.9 in Ce1- xPr xOBiS2, both monoclinic and tetragonal phases were formed together with zero resistivity up to a maximum temperature of 2.2 K. A Ce0.5Pr0.5OBiS2 single crystal, which showed both zero resistivity and a decrease in magnetization at ∼2.4 K, presented a tetragonal structure. Short Bi-S bonding in flat two-dimensional Bi-S planes and mixed Ce3+/Ce4+ were characteristic features of the Ce0.5Pr0.5OBiS2 single crystal, which presumably triggered its superconductivity.

BMP type I receptor inhibition attenuates endothelial dysfunction in mice with chronic kidney disease.

The molecular mechanisms of endothelial dysfunction and vascular calcification have been considered independently and potential links are currently unknown in chronic kidney disease (CKD). Bone morphogenetic protein (BMP) receptor signaling mediates calcification of atherosclerotic plaques. Here we tested whether BMP receptor signaling contributes to endothelial dysfunction, as well as to osteogenic differentiation of vascular smooth muscle cells (VSMCs), in a model of short-term CKD. In C57BL/6 mice, subtotal nephrectomy activated BMP receptor and increased phosphatase-and-tensin homolog (PTEN) protein in the endothelial cells and medial VSMCs without vascular remodeling in the aorta. In the endothelial cells, PTEN induction led to inhibition of the Akt-endothelial nitric oxide synthase (eNOS) pathway and endothelial dysfunction. In VSMCs, the PTEN increase induced early osteogenic differentiation. CKD-induced inhibition of eNOS phosphorylation and the resultant endothelial dysfunction were inhibited in mice with endothelial cell-specific PTEN ablation. Knockout of the BMP type I receptor abolished endothelial dysfunction, the inhibition of eNOS phosphorylation, and VSMC osteogenic differentiation in mice with CKD. A small molecule inhibitor of BMP type I receptor, LDN-193189, prevented endothelial dysfunction and osteogenic differentiation in CKD mice. Thus, BMP receptor activation is a mechanism for endothelial dysfunction in addition to vascular osteogenic differentiation in a short-term CKD model. PTEN may be key in linking BMP receptor activation and endothelial dysfunction in CKD.

Benefit of losartan/hydrochlorothiazide-fixed dose combination treatment for isolated morning hypertension: The MAPPY study.

Morning hypertension is an established risk factor for cardiovascular events. In the Morning Hypertension and Angiotensin Receptor Blocker/Hydrochlorothiazide Combination Therapy (MAPPY) study, a 50-mg losartan/12.5-mg hydrochlorothiazide combination (Los/HCTZ) lowered morning blood pressure (BP) more effectively than 100-mg losartan (High-Los) in treated hypertensive patients with morning hypertension. The aim of this MAPPY study sub-analysis was to determine whether Los/HCTZ was effective for controlling isolated morning hypertension (morning BP ≥ 135/85 mmHg and evening BP < 135/85 mmHg), sustained hypertension (morning and evening BP ≥ 135/85 mmHg), or both. Of the 110 patients studied, 25 (22.7%) had isolated morning hypertension, and 85 (77.3%) had sustained hypertension at baseline. After 3-month treatment, isolated morning hypertension developed into controlled hypertension (morning and evening BP < 135/85 mmHg) in 9 of 11 Los/HCTZ patients (81.8%) and 3 of 14 High-Los patients (21.4%) (p = 0.003, chi-square test). Sustained hypertension developed into controlled hypertension in 21 of 44 Los/HCTZ patients (47.7%) and 13 of 41 High-Los patients (31.7%)(NS). The rates of achievement of SBP < 135 mmHg both in the morning and evening were: 81.8% and 21.4% in Los/HCTZ- and High-Los-treated isolated morning hypertension (p = 0.003), respectively; and 61.4% and 36.6% in Los/HCTX- and High-Los-treated sustained hypertension (p = 0.022), respectively. In conclusion, Los/HCTZ was effective for controlling both types of morning hypertension, especially isolated morning hypertension. Los/HCTZ was superior to High-Los in treating both types of morning hypertension.

Large blood pressure variability aggravates arteriolosclerosis and cortical sclerotic changes in the kidney in hypertensive rats.

BACKGROUND: It has been shown that increased short-term blood pressure (BP) variability (BPV) aggravates hypertensive cardiac remodeling in spontaneously hypertensive rats (SHRs) through a cardiac angiotensin II (angII) system. However, little was known about the renal damage induced by large BPV. Thus, histological changes in the kidney were investigated and candesartan, an angII type 1 receptor blocker (ARB), was also examined to see whether it would prevent renal damage in SHRs with large BPV. METHODS AND RESULTS: Bilateral sinoaortic denervation (SAD) was performed in SHRs to create a model of a combination of hypertension and large BPV. SAD increased BPV without changing mean BP. Seven weeks later, SAD induced patchy, wedge-shaped, focal sclerotic lesions accompanied by interstitial fibrosis and ischemic changes of glomeruli and tubules in the cortex. The pre-glomerular arterioles adjacent to the sclerotic lesions showed arteriolosclerotic changes associated with vascular smooth muscle cell proliferation and extracellular matrix deposition, leading to the luminal narrowing and occlusion. Chronic treatment with a subdepressor dose of candesartan prevented not only arteriolosclerotic changes but also cortical sclerotic lesions in SHRs with SAD without changing BPV. CONCLUSIONS: Large BPV aggravates pre-glomerular arteriolosclerosis, which results in the cortical sclerotic changes in SHRs through a local angII-mediated mechanism. This study raised the possibility that ARB is useful for renal protection in patients who have a combination of hypertension and increased BPV.

Inhibition of eNOS phosphorylation mediates endothelial dysfunction in renal failure: new effect of asymmetric dimethylarginine.

Patients with chronic kidney disease have elevated circulating asymmetric dimethylarginine (ADMA). Recent studies have suggested that ADMA impairs endothelial nitric oxide synthase (eNOS) by effects other than competition with the substrate L-arginine. Here, we sought to identify the molecular mechanism by which increased ADMA causes endothelial dysfunction in a chronic kidney disease model. In wild-type mice with remnant kidney disease, blood urea nitrogen, serum creatinine, and ADMA were increased by 2.5-, 2-, and 1.2-fold, respectively, without any change in blood pressure. Nephrectomy reduced endothelium-dependent relaxation and eNOS phosphorylation at Ser1177 in isolated aortic rings. In transgenic mice overexpressing dimethylarginine dimethylaminohydrolase-1, the enzyme that metabolizes ADMA, circulating ADMA was not increased by nephrectomy and was decreased to half that of wild-type mice. These mice did not exhibit the nephrectomy-induced inhibition of both endothelium-dependent relaxation and eNOS phosphorylation. In cultured human endothelial cells, agonist-induced eNOS phosphorylation and nitric oxide production were decreased by ADMA at concentrations less than that of L-arginine in the media. Thus, elevated circulating ADMA may be a cause, not an epiphenomenon, of endothelial dysfunction in chronic kidney disease. This effect may be attributable to inhibition of eNOS phosphorylation.

Successful pregnancy with stage IB2 uterine cervical cancer: A case report.

BACKGROUND: Although cervical cancer is one of the most common malignancies in pregnancy, its management mainly follows the guidelines for nonpregnant disease state. Within the limited time, patients, and healthcare workers must make difficult decisions to either delay treatment until documented fetal maturity or start immediate treatment based on the disease stage. CASE: The patient was a 37-year-old woman: gravida 1, para 0. Her cervical cytology revealed a high-grade squamous intraepithelial lesion at 8 weeks' gestation. Moreover, invasive squamous cell carcinoma was suspected based on the findings of uterine cervix biopsy. Cervical conization was performed at 11 weeks' gestation, confirming a histopathological diagnosis of squamous cell carcinoma, pT1b2. Cervical cytology findings continued to be negative for intraepithelial lesion or malignancy from 2 weeks after conization until 2 weeks before a cesarean section. In addition, we performed abdominal pelvic lymphadenectomy at 16 weeks' gestation to determine whether the patient could continue her pregnancy. No lymph node metastasis or local recurrence was observed. Finally, a cesarean section and modified radical hysterectomy were performed at 35 weeks' gestation. There was no carcinoma invasion or metastasis. A baby girl weighing 2056 g was delivered with 1- and 5-min Apgar scores of 8 and 9, respectively. Five years postoperatively, there was no evidence of cancer recurrence. CONCLUSION: Management of cervical cancer during pregnancy by using a combination strategy of deep conization and pelvic lymphadenectomy could be an effective strategy for carefully and safely assessing risks of recurrence and metastasis.

Food-Dependent Exercise-Induced Anaphylaxis Caused by Carrots: A Case Report.

Background: Most cases of food-dependent exercise-induced anaphylaxis (FDEIA) are caused by eating wheat or crustaceans. However, fruits or vegetables may rarely act as allergens for FDEIA. We report a rare case of FDEIA caused by eating carrots. Case Presentation: An 8-year-old boy developed an anaphylactic reaction while playing, after eating lunch that included cooked carrots. Serum carrot-specific immunoglobulin E level was 0.19 UA/mL. The prick-by-prick test for raw carrots was positive (wheal diameter: 4 mm). The patient developed urticaria after exercise provocation tests following ingestion of raw carrots. Carrot proteins were analyzed by 2-dimensional Western blotting to identify the causative allergens. Nine proteins were identified as candidate antigens at 21-66 kDa. Conclusions: Our patient presented with FDEIA symptoms after ingesting both raw and cooked carrots. Both raw and cooked carrots contain 9 proteins that may induce FDEIA.

Superconductivity in In-doped AgSnBiTe3 with possible band inversion.

We investigated the chemical pressure effects on structural and electronic properties of SnTe-based material using partial substitution of Sn by Ag0.5Bi0.5, which results in lattice shrinkage. For Sn1-2x(AgBi)xTe, single-phase polycrystalline samples were obtained with a wide range of x. On the basis of band calculations, we confirmed that the Sn1-2x(AgBi)xTe system is basically possessing band inversion and topologically preserved electronic states. To explore new superconducting phases related to the topological electronic states, we investigated the In-doping effects on structural and superconducting properties for x = 0.33 (AgSnBiTe3). For (AgSnBi)(1-y)/3InyTe, single-phase polycrystalline samples were obtained for y = 0-0.5 by high-pressure synthesis. Superconductivity was observed for y = 0.2-0.5. For y = 0.4, the transition temperature estimated from zero-resistivity state was 2.4 K, and the specific heat investigation confirmed the emergence of bulk superconductivity. Because the presence of band inversion was theoretically predicted, and the parameters obtained from specific heat analyses were comparable to In-doped SnTe, we expect that the (AgSnBi)(1-y)/3InyTe and other (Ag, In, Sn, Bi)Te phases are candidate systems for studying topological superconductivity.

IgG4-related tumour-forming mastitis with histological appearances of granulomatous lobular mastitis: comparison with other types of tumour-forming mastitis.

AIMS: Sometimes, mastitis needs to be differentiated from carcinoma because of its association with induration and with ultrasound findings (such as low-echo lesions) that resemble those in carcinoma. The aim was to define this type of mastitis and to examine 18 cases to clarify its clinicopathological features. METHODS AND RESULTS: All cases were categorized into three types: non-specific mastitis with neutrophilic infiltration (n = 7); non-specific mastitis with lymphoplasmacytic infiltration (n = 9); and granulomatous lobular mastitis (n = 2). The three types of mastitis presented similar ultrasound findings and shared certain histological features including fibrosis and diffuse or lobulocentric inflammation. Granulomatous lobular mastitis showed specific clinicopathological features including lobulocentric inflammation with giant cells, diffuse IgG4+ plasma cells, and also a high level of serum IgG4. CONCLUSIONS: Granulomatous lobular mastitis could be categorized into IgG4-related and non-IgG4-related granulomatous lobular mastitis. IgG4 immunohistochemistry serum IgG4 might be useful for diagnosis of IgG4-related granulomatous lobular mastitis and could help to avoid overtreatment such as wide excision.

Current density distribution by ring and diagonally arranged half-ring electrodes in bipolar and overlapping biphasic impulse stimulation.

BACKGROUND: We have studied the acute and long-term efficacy of overlapping biphasic impulse (OLBI) stimulation for atrial pacing with VDD pacemakers and demonstrated the feasibility of DDD pacing in OLBI with diagonally arranged half-ring (Half-Ring) electrodes. We made two three-dimensional computational analysis models to verify our clinical studies. METHODS AND RESULTS: Model I was composed of a heart, a pacemaker, and a human body. Model II was a cube with dimensions of 20 by 20 by 20 mm quarried from Model I for the detailed study of current density distributions. Laplace's equation was solved using the finite element method and the current density J was calculated. For Model I, the distal and proximal voltages were -10 V, 0 V in bipolar and -5 V, +5 V in OLBI, using Ring electrodes. In Model II, the actual measurements of electrode impedances obtained from the clinical study (1,180 Ω for Ring and 630 Ω for Half-Ring) were added to the analysis conditions. Model I showed that OLBI produced more concentrated current density distributions than those by bipolar. According to Model II, at the atrial myocardium position current density produced by Half-Ring was larger than that by Ring electrodes, 70 µA/mm(2) versus 30 µA/mm(2) in OLBI configuration. It also indicated that even if electrode impedances were equal between Half-Ring and Ring electrodes, the maximum current density produced by Half-Ring would be greater than that by Ring electrodes. CONCLUSIONS: It was considered that OLBI configuration with Half-Ring electrodes provides more effective current density distributions.

An efficient way of increasing the total entropy of mixing in high-entropy-alloy compounds: a case of NaCl-type (Ag,In,Pb,Bi)Te1-xSex (x = 0.0, 0.25, 0.5) superconductors.

We propose an efficient way of increasing the entropy of mixing in high-entropy-alloy-type compounds, which can be achieved by multi-site alloying. As an example of this concept, we report the synthesis and observation of polycrystalline samples of new high-entropy-alloy-type metal chalcogenides (Ag,In,Pb,Bi)Te1-xSex (x = 0.0, 0.25, and 0.5) with a NaCl-type structure. The samples were synthesized using high pressure synthesis. Superconductivity with transition temperatures of 2.7, 2.5, and 2.0 K was observed with x = 0.0, 0.25, and 0.5, respectively. To investigate the multi-site alloying effect on the entropy of mixing (ΔSmix) for the examined samples, we calculated the total ΔSmix for two crystallographic sites. For the samples with x = 0.25 and 0.5, ΔSmix reaches 1.89R and 2.00R, respectively, which exceed the ΔSmix of 1.79R for a simple (single-site) high-entropy alloy containing six different elements.

Bulk superconductivity in a four-layer-type Bi-based compound La2O2Bi3Ag0.6Sn0.4S5.7Se0.3.

Recently, we reported the observation of superconductivity at ~0.5 K in a La2O2M4S6-type (M: metal) layered compound La2O2Bi3AgS6, which is a layered system related to the BiS2-based superconductor system but possesses a thicker Bi3AgS6-type conducting layer. In this study, we have developed the La2O2Bi3AgS6-type materials by element substitutions to increase the transition temperature (Tc) and to induce bulk nature of superconductivity. A resistivity anomaly observed at 180 K in La2O2Bi3AgS6 was systematically suppressed by Sn substitution for the Ag site. By the Sn substitution, Tc increased, and the shielding volume fraction estimated from magnetization measurements also increased. The highest Tc (=2.3 K) and the highest shielding volume fraction (~20%) was observed for La2O2Bi3Ag0.6Sn0.4S6. The superconducting properties were further improved by Se substitutions for the S site. By the combinational substitutions of Sn and Se, bulk-superconducting phase of La2O2Bi3Ag0.6Sn0.4S5.7Se0.3 with a Tc of 3.0 K (Tconset = 3.6 K) was obtained.