A dominant population of optically invisible massive galaxies in the early Universe.

Our current knowledge of cosmic star-formation history during the first two billion years (corresponding to redshift z > 3) is mainly based on galaxies identified in rest-frame ultraviolet light1. However, this population of galaxies is known to under-represent the most massive galaxies, which have rich dust content and/or old stellar populations. This raises the questions of the true abundance of massive galaxies and the star-formation-rate density in the early Universe. Although several massive galaxies that are invisible in the ultraviolet have recently been confirmed at early epochs2-4, most of them are extreme starburst galaxies with star-formation rates exceeding 1,000 solar masses per year, suggesting that they are unlikely to represent the bulk population of massive galaxies. Here we report submillimetre (wavelength 870 micrometres) detections of 39 massive star-forming galaxies at z > 3, which are unseen in the spectral region from the deepest ultraviolet to the near-infrared. With a space density of about 2 × 10-5 per cubic megaparsec (two orders of magnitude higher than extreme starbursts5) and star-formation rates of 200 solar masses per year, these galaxies represent the bulk population of massive galaxies that has been missed from previous surveys. They contribute a total star-formation-rate density ten times larger than that of equivalently massive ultraviolet-bright galaxies at z > 3. Residing in the most massive dark matter haloes at their redshifts, they are probably the progenitors of the largest present-day galaxies in massive groups and clusters. Such a high abundance of massive and dusty galaxies in the early Universe challenges our understanding of massive-galaxy formation.

The gravitationally unstable gas disk of a starburst galaxy 12 billion years ago.

Galaxies in the early Universe that are bright at submillimetre wavelengths (submillimetre-bright galaxies) are forming stars at a rate roughly 1,000 times higher than the Milky Way. A large fraction of the new stars form in the central kiloparsec of the galaxy1-3, a region that is comparable in size to the massive, quiescent galaxies found at the peak of cosmic star-formation history4 and the cores of present-day giant elliptical galaxies. The physical and kinematic properties inside these compact starburst cores are poorly understood because probing them at relevant spatial scales requires extremely high angular resolution. Here we report observations with a linear resolution of 550 parsecs of gas and dust in an unlensed, submillimetre-bright galaxy at a redshift of z = 4.3, when the Universe was less than two billion years old. We resolve the spatial and kinematic structure of the molecular gas inside the heavily dust-obscured core and show that the underlying gas disk is clumpy and rotationally supported (that is, its rotation velocity is larger than the velocity dispersion). Our analysis of the molecular gas mass per unit area suggests that the starburst disk is gravitationally unstable, which implies that the self-gravity of the gas is stronger than the differential rotation of the disk and the internal pressure due to stellar-radiation feedback. As a result of the gravitational instability in the disk, the molecular gas would be consumed by star formation on a timescale of 100 million years, which is comparable to gas depletion times in merging starburst galaxies5.

Two γ-ray bursts from dusty regions with little molecular gas.

Long-duration γ-ray bursts are associated with the explosions of massive stars and are accordingly expected to reside in star-forming regions with molecular gas (the fuel for star formation). Previous searches for carbon monoxide (CO), a tracer of molecular gas, in burst host galaxies did not detect any emission. Molecules have been detected as absorption in the spectra of γ-ray burst afterglows, and the molecular gas is similar to the translucent or diffuse molecular clouds of the Milky Way. Absorption lines probe the interstellar medium only along the line of sight, so it is not clear whether the molecular gas represents the general properties of the regions where the bursts occur. Here we report spatially resolved observations of CO line emission and millimetre-wavelength continuum emission in two galaxies hosting γ-ray bursts. The bursts happened in regions rich in dust, but not particularly rich in molecular gas. The ratio of molecular gas to dust (<9-14) is significantly lower than in star-forming regions of the Milky Way and nearby star-forming galaxies, suggesting that much of the dense gas where stars form has been dissipated by other massive stars.

Postcomparison of [(18) F]-fluorodeoxyglucose uptake in the brain after short-term bright light exposure and no intervention.

OBJECTIVE: Bright light therapy is widely used as the treatment of choice for seasonal affective disorder. Nonetheless, our understanding of the mechanisms of bright light is limited and it is important to investigate the mechanisms. The purpose of this study is to examine the hypothesis that bright light exposure may increase [(18) F]-fluorodeoxyglucose (FDG) uptake in olfactory bulb and/or hippocampus which may be associated neurogenesis in the human brain. METHOD: A randomized controlled trial comparing 5-day bright light exposure + environmental light (bright light exposure group) with environmental light alone (no intervention group) was performed for 55 participants in a university hospital. The uptake of [(18) F]FDG in olfactory bulb and hippocampus using FDG positron emission tomography was compared between two groups. RESULTS: There was a significant increase of uptake in both right and left olfactory bulb for bright light exposure group vs. no intervention group. After adjustment of log-transformed illuminance, there remained a significant increase of uptake in the right olfactory bulb. CONCLUSION: The present findings suggest a possibility that 5-day bright light exposure may increase [(18) F]FDG in the right olfactory bulb of the human brain, suggesting a possibility of neurogenesis. Further studies are warranted to directly confirm this possibility.

The combination of strong expression of ZNF143 and high MIB-1 labelling index independently predicts shorter disease-specific survival in lung adenocarcinoma.

BACKGROUND: The transcription factor, zinc finger protein 143 (ZNF143), positively regulates many cell-cycle-related genes. The ZNF143 would show high expression of multiple solid tumours related closely to cancer cell growth, similar to the widely accepted Ki67 (MIB-1) protein, but the underlying mechanisms for ZNF143 remain unclear. We investigated the association of ZNF143 expression with clinicopathological features and prognoses of patients with lung adenocarcinoma. METHODS: Expressions of ZNF143 and MIB-1 were immunohistochemically analysed in 183 paraffin-embedded tumour samples of patients with lung adenocarcinoma. The ZNF143 expression was considered to be strong when >30% of the cancer cells demonstrated positive staining. RESULTS: Strong ZNF143+ expression showed a significantly close relationship to pathologically moderate to poor differentiation and highly invasive characteristics. The ZNF143 positivity potentially induced cell growth of lung adenocarcinoma, correlated significantly with high MIB-1 labelling index (⩾10%). Univariate and multivariate analyses demonstrated that both strong ZNF143+ and the high MIB-1 index group have only and significantly worse survival rates. CONCLUSIONS: The combination of strong ZNF143 expression and high MIB-1 index potentially predicts high proliferating activity and poor prognosis in patients with lung adenocarcinoma, and may offer a therapeutic target against ZNF143.

Therapeutic window of lamotrigine for mood disorders: a naturalistic retrospective study.

INTRODUCTION: Lamotrigine is widely used for mood disorders including bipolar disorder and major depression, but its therapeutic levels have yet to be determined. This study was conducted to investigate the hypothesis that lamotrigine may have a therapeutic window for mood disorders. METHODS: 25 patients with mood disorders received lamotrigine for more than one year during which time plasma lamotrigine levels were measured at least once. Their mental state was retrospectively and regularly but blindly assessed using the Clinical Global Impression-Severity (CGI-S) scale. In order to investigate our hypothesis, we depicted the relationship between the last lamotrigine levels and the last CGI scores in 25 patients. If any, the potential therapeutic window was further investigated. RESULTS: The relationship between the last lamotrigine levels and the last CGI scores in the 25 patients indicated the presence of a therapeutic window of lamotrigine from 5 to 11 µg/mL. The repeated measures of ANOVA reached a significant tendency of the effects of lamotrigine levels within 5-11 µg/mL on better CGI-S scores, and the CGI-S scores at the last observation of the 15 patients whose lamotrigine levels were within 5-11 µg/mL were significantly better than those of 10 patients whose lamotrigine levels were not within 5-11 µg/mL. CONCLUSION: These findings suggest that lamotrigine may have a therapeutic window for patients with mood disorder from 5 to 11 µg/mL.

Polypeptide N-acetylgalactosaminyl transferase 3 independently predicts high-grade tumours and poor prognosis in patients with renal cell carcinomas.

BACKGROUND: The polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) family of enzymes regulates the initial steps of mucin-type O-glycosylation. N-acetylgalactosaminyltransferases might show novel patterns of GalNAc-T glycosylation on tumour-derived proteins, which could influence cancer biology, but its mechanisms are unclear. We investigated the association of GalNAc-T3 and -T6 expressions with clinicopathological features and prognoses of patients with renal cell carcinomas (RCCs). METHODS: Expressions of GalNAc-T3/6 and cell-adhesion molecules were analysed immunohistochemically in 254 paraffin-embedded tumour samples of patients with RCC. RESULTS: Of 138 GalNAc-T3+ cases, 46 revealed significant co-expression with GalNAc-T6. N-acetylgalactosaminyltransferases-3+ expression showed a close relationship to poor clinical performance and large tumour size, or pathologically high Fuhrman's grading, and presence of vascular invasion and necrosis. The GalNAc-T3-positivity potentially suppressed adhesive effects with a significantly low ß-catenin expression. Univariate and multivariate analyses showed the GalNAc-T3+ group, but not the GalNAc-T6+ group, to have significantly worse survival rates. CONCLUSION: N-acetylgalactosaminyltransferases-3 expression independently predicts high-grade tumour and poor prognosis in patients with RCC, and may offer a therapeutic target against RCC.

Recombinant high molecular weight-glutenin subunit-specific IgE detection is useful in identifying wheat-dependent exercise-induced anaphylaxis complementary to recombinant omega-5 gliadin-specific IgE test.

BACKGROUND: Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a special form of food allergy typically induced by exercise after ingestion of wheat products. We identified wheat omega-5 gliadin and high molecular weight-glutenin subunit (HMW-glutenin) as major allergens for WDEIA and clarified that simultaneous detection of serum IgE binding to synthetic epitope peptides of these allergens identifies more than 90% of WDEIA patients. However, the short synthetic peptides are not suitable for CAP-fluorescent enzyme-immunoassay (CAP-FEIA), which is widely utilized for detecting allergen-specific IgE. OBJECTIVE: In this study, we constructed a CAP-FEIA with recombinant HMW-glutenin, and evaluated its usefulness in identifying the patients with WDEIA. METHODS: Recombinant HMW-glutenin was expressed as histidine-tag protein in E. coli and purified by histidine-tag affinity column. Wheat, gluten, recombinant omega-5 gliadin, epitope peptide of HMW-glutenin, native and recombinant HMW-glutenin specific IgE in the sera from 48 patients with WDEIA, 16 patients with atopic dermatitis (AD) who had no immediate allergic reaction after wheat ingestion and 12 healthy controls were determined by using CAP-FEIA method. RESULTS: In 16 AD patients without wheat allergy 12 of them (75%) had positive results for native HMW-glutenin test in contrast to epitope peptide of HMW-glutenin (12.5%) and recombinant HMW-glutenin test (12.5%). These results indicate the native HMW-glutenin test has low specificity. Sensitivity and specificity of the IgE test with recombinant HMW-glutenin were 16.7% and 92.9%. These are well compatible with results obtained by using epitope peptide of HMW-glutenin. However, sensitivity and specificity reached to 93.8% and 92.9%, when the test was combined to the test with recombinant omega-5 gliadin. CONCLUSIONS AND CLINICAL RELEVANCE: We demonstrated that recombinant HMW-glutenin is best for CAP-FEIA system in point of stability and specificity and confirmed that detection of specific IgE against recombinant HMW-glutenin is useful for diagnosis of WDEIA when combined with the CAP-FEIA (recombinant omega-5 gliadin) test.

CHEMORESISTANCE RELATED TO HYPOXIA ADAPTATION IN MESOTHELIOMA CELLS FROM TUMOR SPHEROIDS.

BACKGROUND: Hypoxia has been noted as a key factor for induction and maintenance of cancer stemness thereby leading to therapy resistance. Three-dimensional (3D) spheroid models demonstrate a heterogeneity of hypoxic regions replicating the in vivo situation within tumors. Utilizing an established 3D spheroid model, we investigated whether extrinsic hypoxia reinforced chemoresistance in malignant pleural mesothelioma (MPM) spheroids. MATERIALS AND METHODS: Tumor spheres were generated from Meso-1 (a typical human MPM cell line) cells having high spheroid-forming ability. To induce hypoxia condition, we utilized a hypoxia chamber with regulation of O2 and CO2 levels. Cell viability was estimated by a WST-8 assay. Real-time polymerase chain reaction and Western blot were performed to evaluate the expression at mRNA and protein levels. RESULTS: Compared with cells cultured in the two-dimensional monolayer model, tumor sphere cells showed elevated mRNA levels of cancer stemness markers (CD26, CD44 and ABCG2) and protein levels of the stemness and hypoxia adaptation markers (ABCG2, ALDH1A1 and HIFs). Correlating with this, 3D spheroid cells were more resistant to permetrexed and topotecan than the two-dimensional cells, indicative of their potential for hypoxic adaptation. Furthermore, significantly stronger resistance to both chemotherapeutic agents was observed in spheroid cells upon hypoxic challenge compared to spheroid cells under normoxia. CONCLUSION: From the present data, it is concluded that hypoxia adaptation of MPM cells from tumor spheres could enhance their chemoresistance.

Deshima 2.0: Rapid Redshift Surveys and Multi-line Spectroscopy of Dusty Galaxies.

We present a feasibility study for the high-redshift galaxy part of the Science Verification Campaign with the 220-440 GHz deshima 2.0 integrated superconducting spectrometer on the ASTE telescope. The first version of the deshima 2.0 chip has been recently manufactured and tested in the lab. Based on these realistic performance measurements, we evaluate potential target samples and prospects for detecting the [CII] and CO emission lines. The planned observations comprise two distinct, but complementary objectives: (1) acquiring spectroscopic redshifts for dusty galaxies selected in far-infrared/mm-wave surveys; (2) multi-line observations to infer physical conditions in dusty galaxies.

Polypeptide N-acetylgalactosaminyltransferase 6 expression in pancreatic cancer is an independent prognostic factor indicating better overall survival.

BACKGROUND: The family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) is responsible for the altered glycosylation in cancer. The purpose of our study was to investigate the clinical significance of two isoforms, GalNAc-T6 and -T3, and their correlation with the prognosis of pancreatic cancer. METHODS: Immunohistochemistry was used to analyse GalNAc-T6 and -T3 expressions in 70 clinicopathologically characterised pancreatic cancer cases. RESULTS: Positive expressions of GalNAc-T6 and -T3 were immunohistochemically identified in 51% (36 of 70) and in 77% (54 of 70) of patients, respectively. A close relationship was noted between GalNAc-T6 positive expression and pathological well/moderate differentiated type (P=0.001), small tumour size (P=0.044), absence of vascular invasion (P=0.009), and low stage of the American Joint Committee on Cancer systems (P=0.043). The expression of GalNAc-T3 significantly correlated with good differentiation (P=0.001), but not with other clinicopathologic features. Furthermore, univariate and multivariate analyses revealed that GalNAc-T6 expression was an independent prognosis indicator for the disease, whereas GalNAc-T3 expression had no impact on clinical outcome, even though 33 of 36 GalNAc-T6-positive cases also had a positive expression of GalNAc-T3 (P=0.001, r=0.356). CONCLUSION: Both GalNAc-T6 and -T3 expressions correlated significantly with tumour differentiation, whereas only GalNAc-T6 expression predicted prognosis in pancreatic cancer.

Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress.

Under conditions of endoplasmic reticulum (ER) stress, mammalian cells induce both translational repression and the unfolded protein response that transcriptionally activates genes encoding ER-resident molecular chaperones. To date, the only known pathway for translational repression in response to ER stress has been the phosphorylation of eIF-2alpha by the double-stranded RNA-activated protein kinase (PKR) or the transmembrane PKR-like ER kinase (PERK). Here we report another pathway in which the ER transmembrane kinase/ribonuclease IRE1beta induces translational repression through 28S ribosomal RNA cleavage in response to ER stress. The evidence suggests that both pathways are important for efficient translational repression during the ER stress response.

Antibodies against 70-kD heat shock cognate protein inhibit mediated nuclear import of karyophilic proteins.

Previously, we found that anti-DDDED antibodies strongly inhibited in vivo nuclear transport of nuclear proteins and that these antibodies recognized a protein of 69 kD (p69) from rat liver nuclear envelopes that showed specific binding activities to the nuclear location sequences (NLSs) of nucleoplasmin and SV-40 large T-antigen. Here we identified this protein as the 70-kD heat shock cognate protein (hsc70) based on its mass, isoelectric point, cellular localization, and partial amino acid sequences. Competition studies indicated that the recombinant hsc70 expressed in Escherichia coli binds to transport competent SV-40 T-antigen NLS more strongly than to the point mutated transport incompetent mutant NLS. To investigate the possible involvement of hsc70 in nuclear transport, we examined the effect of anti-hsc70 rabbit antibodies on the nuclear accumulation of karyophilic proteins. When injected into the cytoplasm of tissue culture cells, anti-hsc70 strongly inhibited the nuclear import of nucleoplasmin, SV-40 T-antigen NLS bearing BSA and histone H1. In contrast, anti-hsc70 IgG did not prevent the diffusion of lysozyme or 17.4-kD FITC-dextran into the nuclei. After injection of these antibodies, cells continued RNA synthesis and were viable. These results indicate that hsc70 interacts with NLS-containing proteins in the cytoplasm before their nuclear import.

Infectious complications in patients receiving autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases.

Long-term analysis of infectious complication after high-dose immunosuppressive therapy with CD34-selected autologous hematopoietic stem cell transplantation for patients with severe autoimmune diseases (AD) was performed. Theoretically, CD34 selection can reduce the risk of reinfusion of autoreactive lymphocytes. However, it is also associated with a significant reduction in T cells, natural killer cells, and monocytes, which in turn may compromise immune reconstitution, thereby increasing the risk of infection. Moreover, AD compromises host immunity and causes organ damage resulting in dysfunction of the cutaneous or mucosal barrier. In this study, the incidence rate of infections is reported in 14 patients who underwent high-dose (200 mg/kg) cyclophosphamide therapy followed by reinfusion of CD34-selected autologous peripheral blood stem cells. Bacterial complication occurred in 3 of 14 (21%) patients. Cytomegalovirus reactivation and adenovirus hemorrhagic cystitis were observed in 9 (64%) and 2 (14%) patients, respectively. As for late infectious complications, 7 patients (50%) developed dermatomal varicella zoster virus infection. No infection-related mortality was seen in this case series. Because the risk for infections approaches that seen in allogeneic transplant recipients, infection surveillance, diagnostic workup, and prophylactic strategies similar to those applicable to allogeneic recipients are warranted.

Gas filaments of the cosmic web located around active galaxies in a protocluster.

Cosmological simulations predict that the Universe contains a network of intergalactic gas filaments, within which galaxies form and evolve. However, the faintness of any emission from these filaments has limited tests of this prediction. We report the detection of rest-frame ultraviolet Lyman-α radiation from multiple filaments extending more than one megaparsec between galaxies within the SSA22 protocluster at a redshift of 3.1. Intense star formation and supermassive black-hole activity is occurring within the galaxies embedded in these structures, which are the likely sources of the elevated ionizing radiation powering the observed Lyman-α emission. Our observations map the gas in filamentary structures of the type thought to fuel the growth of galaxies and black holes in massive protoclusters.

Relationship Between Stress Coping Mechanisms and Depression in Kidney Transplant Recipients.

BACKGROUND: It has been reported that transplant recipients are exposed to physical and psychosocial stresses even after transplant surgery and exhibit psychological disorders such as depression. PURPOSE: In this study, we extracted trends concerning how recipients of kidney transplants cope with stress, and we also examined how they cope with depression and its countermeasures. METHOD: We administered questionnaire surveys to 109 kidney transplant recipients. These included items on personal attributes, medical information, depression, and stress-coping type scales. Statistical analysis was performed using factor analysis and multiple regression analysis. RESULTS: Fifteen out of 109 (13.8%) were found to be high-risk patients for depression based on responses to the questionnaire using the depression scale. We extracted 2 factors of stress-coping type, namely Factor 1, "Directly coping with the problem," of patients who try to directly resolve the problem in a positive manner and Factor 2, "Stress-release while avoiding the problem," for those who relieve their feelings in response to the stress without resolving the problem itself. When multiple regression analysis was conducted with the depression scale as the dependent variable and the stress-coping factor as the independent variable, Factor 1 tended to be associated with reduced depression and Factor 2 with increased depression. CONCLUSIONS: Results showed that to improve the mental health of those who receive kidney transplants, it is necessary to examine the depression and stress-coping types of such patients at an early stage and carry out education on stress-coping, focusing on resolving the actual problem.

ZNF143 interacts with p73 and is involved in cisplatin resistance through the transcriptional regulation of DNA repair genes.

Zinc-finger protein 143 (ZNF143) is a human homolog of Xenopus transcriptional activator staf that is involved in selenocystyl tRNA transcription. We previously showed that ZNF143 expression is induced by treatment with DNA-damaging agents and that it preferentially binds to cisplatin-modified DNA. In this study, the potential function of ZNF143 was investigated. ZNF143 was overexpressed in cisplatin-resistant cells. ZNF143 knockdown in prostate cancer caused increased sensitivity for cisplatin, but not for oxaliplatin, etoposide and vincristine. We also showed that ZNF143 is associated with tumor suppressor gene product p73 but not with p53. p73 could stimulate the binding of ZNF143 to both ZNF143 binding site and cisplatin-modified DNA, and modulate the function of ZNF143. We provide a direct evidence that both Rad51 and flap endonuclease-1 are target genes of ZNF143 and overexpressed in cisplatin-resistant cells. Taken together, these experiments demonstrate that an interplay of ZNF143, p73 and ZNF143 target genes is involved in DNA repair gene expression and cisplatin resistance.

Clock and ATF4 transcription system regulates drug resistance in human cancer cell lines.

The mechanisms underlying cellular drug resistance have been extensively studied, but little is known about its regulation. We have previously reported that activating transcription factor 4 (ATF4) is upregulated in cisplatin-resistant cells and plays a role in cisplatin resistance. Here, we find out a novel relationship between the circadian transcription factor Clock and drug resistance. Clock drives the periodical expression of many genes that regulate hormone release, cell division, sleep-awake cycle and tumor growth. We demonstrate that ATF4 is a direct target of Clock, and that Clock is overexpressed in cisplatin-resistant cells. Furthermore, Clock expression significantly correlates with cisplatin sensitivity, and that the downregulation of either Clock or ATF4 confers sensitivity of A549 cells to cisplatin and etoposide. Notably, ATF4-overexpressing cells show multidrug resistance and marked elevation of intracellular glutathione. The microarray study reveals that genes for glutathione metabolism are generally downregulated by the knockdown of ATF4 expression. These results suggest that the Clock and ATF4 transcription system might play an important role in multidrug resistance through glutathione-dependent redox system, and also indicate that physiological potentials of Clock-controlled redox system might be important to better understand the oxidative stress-associated disorders including cancer and systemic chronotherapy.

Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells.

Y-box-binding protein 1 (YB-1), which is a member of the DNA-binding protein family containing a cold-shock domain, has pleiotropic functions in response to various environmental stimuli. As we previously showed that YB-1 is a global marker of multidrug resistance in ovarian cancer and other tumor types. To identify YB-1-regulated genes in ovarian cancers, we investigated the expression profile of YB-1 small-interfering RNA (siRNA)-transfected ovarian cancer cells using a high-density oligonucleotide array. YB-1 knockdown by siRNA upregulated 344 genes, including MDR1, thymidylate synthetase, S100 calcium binding protein and cyclin B, and downregulated 534 genes, including CXCR4, N-myc downstream regulated gene 1, E-cadherin and phospholipase C. Exogenous serum addition stimulated YB-1 translocation from the cytoplasm to the nucleus, and treatment with Akt inhibitors as well as Akt siRNA and integrin-linked kinase (ILK) siRNA specifically blocked YB-1 nuclear localization. Inhibition of Akt activation downregulated CXCR4 and upregulated MDR1 (ABCB1) gene expression. Administration of Akt inhibitor resulted in decrease in nuclear YB-1-positive cancer cells in a xenograft animal model. Akt activation thus regulates the nuclear translocation of YB-1, affecting the expression of drug-resistance genes and other genes associated with the malignant characteristics in ovarian cancer cells. Therefore, the Akt pathway could be a novel target of disrupting the nuclear translocation of YB-1 that has important implications for further development of therapeutic strategy against ovarian cancers.

Sensitivity and specificity of recombinant omega-5 gliadin-specific IgE measurement for the diagnosis of wheat-dependent exercise-induced anaphylaxis.

BACKGROUND: A recent study has shown that the measurement of specific IgE antibodies to B-cell epitope peptides of wheat omega-5 gliadin (Pep A) and high molecular weight glutenin subunit (Pep B) are useful to diagnose wheat-dependent exercise-induced anaphylaxis (WDEIA). AIMS OF THE STUDY: We sought to compare the sensitivity and specificity of the in vitro tests for measuring the specific IgE antibodies to recombinant omega-5 gliadin (romega-5 gliadin) with those for wheat, gluten, Pep A, and Pep B in identification of patients with WDEIA. METHODS: Fifty patients with WDEIA, 25 healthy subjects and 25 patients with atopic dermatitis with specific IgE antibodies to wheat but without experience of allergic reactions after ingestion of wheat products were enrolled in this study. The concentrations of specific IgE antibodies were measured using ImmunoCAP. The empirical receiver operating characteristics curves (ROC) for each test were prepared and the areas under the ROC curve (AUC) were compared. RESULTS: In patients with WDEIA, the sensitivities of the allergen-specific IgE tests for wheat, gluten, Pep A, Pep B and romega-5 gliadin were 48%, 56%, 76%, 22%, and 80%, respectively. The seven of 10 WDEIA patients with no specific IgE antibodies to romega-5 gliadin had specific IgE antibodies to Pep B. The highest AUC (0.850) was observed in the test for romega-5 gliadin. CONCLUSIONS: Measuring the concentration of specific IgE antibodies to romega-5 gliadin is more useful than to wheat, gluten, or Pep A in the identification of patients with WDEIA.