Allergic Potency of Japanese Cedar Pollen Cry j 1 Is Reduced by a Low Concentration of Hypochlorous Acid Generated by Electolysis

ABSTRACTBackgroundAlthough Japanese cedar (Cryptomeria japonica) pollinosis has developed into a health problem, few methods eradicate indoor allergens completely. In a recent study, however, the effectiveness of inactivation with sodium hypochlorite (NaOCl) treatment was revealed. Therefore, the present study aimed to elucidate the ability of chlorine bleach (NaOCl) to reduce the immunogenicity of the major allergenic protein of Japanese cedar (Cry j 1).MethodsSodium dodecyl sulfate polyacrylamide gel electrophoresis, Western blotting, enzyme-linked immunosorbant assay, and skin testing were carried out in 7 individuals.ResultsThe allergenic protein was undetectable using sodium dodecyl sulfate polyacrylamide gel electrophoresis and silver staining at a sodium hypochlorite/allergenic protein molar ratio of 457. Western blotting with human sera showed the same dose-dependent efficacy. The immunogenicity of the purified protein and cedar pollen was also demonstrated on enzyme-linked immunosorbant assay to be reduced by sodium hypochlorite treatment in a dose- and time-dependent manner. Moreover, sodium hypochlorite-treatment inhibited the skin test response to the protein in all 7 individuals.ConclusionsHypochlorous acid generated by electrolysis is an effective method for significantly reducing the immunogenicity of Cry j 1

Clinical Relevance of Parafoveal Intercapillary Spaces and Foveal Avascular Zone in Diabetic Retinopathy Without Macular Edema

Purpose: To investigate the clinical significance of intercapillary spaces on swept source optical coherence tomography angiography images in diabetic retinopathy. Methods: We retrospectively reviewed 110 eyes of 110 patients suffering from diabetic retinopathy without macular edema for whom 3 × 3 mm swept source optical coherence tomography angiography images centered on the fovea were obtained. Automatic image processing of the superficial slab images allowed us to define the areas encircled by retinal vessels as intercapillary spaces within the central 2-mm circle. We evaluated how the quantitative parameters of intercapillary spaces are associated with logMAR and feasible to diagnose diabetic macular ischemia. Results: Total counts (ρ = −0.419; P < 0.001) rather than morphologic parameters of the intercapillary spaces showed a significant correlation with logMAR. There were individual levels of correlations between logMAR and counts of intercapillary spaces in individual sectors. In particular, the summed numbers of the spaces in three highly significant sectors were more significantly associated with logMAR (ρ = −0.515; P < 0.001). Multivariate analyses confirmed that the number of the intercapillary spaces (β = −0.266; P = 0.016) and foveal avascular zone area (β = 0.227; P = 0.042) were related to logMAR. The clustering using the foveal avascular zone area and the number of intercapillary spaces revealed two major clusters; one had fewer intercapillary spaces (P < 0.001) and poorer logMAR (P < 0.001) than the other, with a wide range of the foveal avascular zone area. Conclusions: Decreased intercapillary spaces contribute to visual impairment in diabetic retinopathy and suggest one possible criterion of objective diagnosis of diabetic macular ischemia

The intercapillary space spectrum as a marker of diabetic retinopathy severity on optical coherence tomography angiography

Microcirculatory disturbance plays a pivotal role in the pathogenesis in diabetic retinopathy (DR). We retrospectively quantified the total counts and morphological features of intercapillary spaces, i.e., intercapillary areas and nonperfusion areas (NPAs), on swept-source optical coherence tomography angiography (SS-OCTA) images and to evaluate their associations with DR severity grades. We acquired 3 × 3 mm OCTA images in 75 eyes of 62 diabetic patients and 22 eyes of 22 nondiabetic subjects. In the en-face superficial images within the central 2 mm, the areas enclosed by retinal vessels were automatically detected. Their total numbers decreased in some eyes with no apparent retinopathy and most eyes with DR, which allowed us to discriminate diabetic subjects from nondiabetic subjects [area under the receiver operating characteristic curve (AUC) = 0.907]. The areas and area/perimeter ratios continuously increased in DR, indicating a continuum between healthy intercapillary areas and NPAs. The number of intercapillary spaces with a high area/perimeter ratio increased according to DR severity, which showed modest performance in discriminating moderate NPDR or higher grades (AUC = 0.868). These quantified parameters of intercapillary spaces can feasibly be used for the early detection of microcirculatory impairment and the diagnosis of referable DR

Clinically Significant Nonperfusion Areas on Widefield OCT Angiography in Diabetic Retinopathy

[Purpose] To investigate the distribution of clinically significant nonperfusion areas (NPAs) on widefield OCT angiography (OCTA) images in patients with diabetes. [Design] Prospective, cross-sectional, observational study. [Participants] One hundred and forty-four eyes of 114 patients with diabetes. [Methods] Nominal 20 × 23 mm OCTA images were obtained using a swept-source OCTA device (Xephilio OCT-S1), followed by the creation of en face images 20-mm (1614 pixels) in diameter centering on the fovea. The nonperfusion squares (NPSs) were defined as the 10 × 10 pixel squares without retinal vessels, and the ratio of eyes with the NPSs to all eyes in each square was referred to as the NPS ratio. The areas with probabilistic differences (APD) for proliferative diabetic retinopathy (PDR) and nonproliferative diabetic retinopathy (NPDR) (APD[PDR] and APD[NPDR]) were defined as sets of squares with higher NPS ratios in eyes with PDR and NPDR, respectively. The P ratio (NPSs within APD[PDR] but not APD[NPDR]/all NPSs) was also calculated. [Main Outcome Measures] The probabilistic distribution of the NPSs and the association with diabetic retinopathy (DR) severity. [Results] The NPSs developed randomly in eyes with mild and moderate NPDR and were more prevalent in the extramacular areas and the temporal quadrant in eyes with severe NPDR and PDR. The APD(PDR) was distributed mainly in the extramacular areas, sparing the areas around the vascular arcades and radially peripapillary capillaries. The APD(PDR) contained retinal neovascularization more frequently than the non-APD(PDR) (P = 0.023). The P ratio was higher in eyes with PDR than in those with NPDR (P < 0.001). The multivariate analysis designated the P ratio (odds ratio, 8.293 × 107; 95% confidence interval, 6.529 × 102–1.053 × 1013; P = 0.002) and the total NPSs (odds ratio, 1.002; 95% confidence interval, 1.001–1.003; P < 0.001) as independent risk factors of PDR. Most eyes with NPDR and 4-2-1 rule findings of DR severity had higher P ratios but not necessarily greater NPS numbers. [Conclusions] The APD(PDR) is uniquely distributed on widefield OCTA images, and the NPA location patterns are associated with DR severity, independent of the entire area of NPAs. [Financial Disclosure(s)] Proprietary or commercial disclosure may be found after the references

A Phthalimide Derivative That Inhibits Centrosomal Clustering Is Effective on Multiple Myeloma

Despite the introduction of newly developed drugs such as lenalidomide and bortezomib, patients with multiple myeloma are still difficult to treat and have a poor prognosis. In order to find novel drugs that are effective for multiple myeloma, we tested the antitumor activity of 29 phthalimide derivatives against several multiple myeloma cell lines. Among these derivatives, 2-(2,6-diisopropylphenyl)-5-amino-1H-isoindole-1,3- dione (TC11) was found to be a potent inhibitor of tumor cell proliferation and an inducer of apoptosis via activation of caspase-3, 8 and 9. This compound also showed in vivo activity against multiple myeloma cell line KMS34 tumor xenografts in ICR/SCID mice. By means of mRNA display selection on a microfluidic chip, the target protein of TC11 was identified as nucleophosmin 1 (NPM). Binding of TC11 and NPM monomer was confirmed by surface plasmon resonance. Immunofluorescence and NPM knockdown studies in HeLa cells suggested that TC11 inhibits centrosomal clustering by inhibiting the centrosomal-regulatory function of NPM, thereby inducing multipolar mitotic cells, which undergo apoptosis. NPM may become a novel target for development of antitumor drugs active against multiple myeloma

Associations of pulmonary and extrapulmonary computed tomographic manifestations with impaired physical activity in symptomatic patients with chronic obstructive pulmonary disease

In patients with chronic obstructive pulmonary disease (COPD), emphysema, airway disease, and extrapulmonary comorbidities may cause various symptoms and impair physical activity. To investigate the relative associations of pulmonary and extrapulmonary manifestations with physical activity in symptomatic patients, this study enrolled 193 patients with COPD who underwent chest inspiratory/expiratory CT and completed COPD assessment test (CAT) and the Life-Space Assessment (LSA) questionnaires to evaluate symptom and physical activity. In symptomatic patients (CAT ≥ 10, n = 100), emphysema on inspiratory CT and air-trapping on expiratory CT were more severe and height-adjusted cross-sectional areas of pectoralis muscles (PM index) and adjacent subcutaneous adipose tissue (SAT index) on inspiratory CT were smaller in those with impaired physical activity (LSA < 60) than those without. In contrast, these findings were not observed in less symptomatic patients (CAT < 10). In multivariable analyses of the symptomatic patients, severe air-trapping and lower PM index and SAT index, but not CT-measured thoracic vertebrae bone density and coronary artery calcification, were associated with impaired physical activity. These suggest that increased air-trapping and decreased skeletal muscle and subcutaneous adipose tissue quantity are independently associated with impaired physical activity in symptomatic patients with COPD

A Spectral Study of the Black Hole Candidate XTE J1752-223 in the High/Soft State with MAXI, Suzaku and Swift

We report on the X-ray spectral analysis of the black hole candidate XTE\ J1752--223 in the 2009--2010 outburst, utilizing data obtained with the MAXI/Gas Slit Camera (GSC), the Swift/XRT, and Suzaku, which work complementarily. As already reported by Nakahira et al. (2010) MAXI monitored the source continuously throughout the entire outburst for about eight months. All the MAXI/GSC energy spectra in the high/soft state lasting for 2 months are well represented by a multi-color disk plus power-law model. The innermost disk temperature changed from $\sim$0.7 keV to $\sim$0.4 keV and the disk flux decreased by an order of magnitude. Nevertheless, the innermost radius is constant at $\sim$41 $D_{3.5}(\cos{\it i})^{-1/2}$ km, where $D_{3.5}$ is the source distance in units of 3.5 kpc and $i$ the inclination. The multi-color disk parameters obtained with the MAXI/GSC are consistent with those with the Swift/XRT and Suzaku. The Suzaku data also suggests a possibility that the disk emission is slightly Comptonized, which could account for broad iron-K features reported previously. Assuming that the obtained innermost radius represents the innermost stable circular orbit for a non-rotating black hole, we estimate the mass of the black hole to be 5.51$\pm$0.28 $M_{\odot}$ $D_{3.5}(\cos{\it i})^{-1/2}$, where the correction for the stress-free inner boundary condition and color hardening factor of 1.7 are taken into account. If the inclination is less than 49$^{\circ}$ as suggested from the radio monitoring of transient jets and the soft-to-hard transition in 2010 April occurred at 1--4% of Eddignton luminosity, the fitting of the Suzaku spectra with a relativistic accretion-disk model derives constraints on the mass and the distance to be 3.1--55 $M_{\odot}$ and 2.3--22 {\rm kpc}, respectively. This confirms that the compact object in XTE J1752--223 is a black hole.Comment: 12 pages including 7 figures and 4 tables, accepted for publication in PAS