Anticardiolipin Antibodies Recognize β(2)-Glycoprotein I Structure Altered by Interacting with an Oxygen Modified Solid Phase Surface

Anticardiolipin antibodies (aCL) derived from the sera of individuals exhibiting the antiphospholipid syndrome (APS) directly bind to beta(2)-glycoprotein I (beta(2)-GPI), which is adsorbed to an oxidized polystyrene surface. Oxygen atoms were introduced on a polystyrene surface by irradiation with electron or gamma-ray radiation. X-ray photoelectron spectroscopy revealed the irradiated surfaces were oxidized to generate C-O and C=O moieties. aCL derived from either APS patients or (NZW x BXSB)F-1 mice bound to beta(2)-GPI coated on the irradiated plates, depending on the radiation dose. Antibody binding to beta(2)-GPI on the irradiated plates was competitively inhibited by simultaneous addition of cardiolipin (CL)-coated latex beads mixed together with beta(2)-GPI but were unaffected by addition of excess beta(2)-GPI, CL micelles, or CL-coated latex beads alone. There was a high correlation between binding values of aCL in sera from 40 APS patients obtained by the anti-beta(2)-GPI enzyme-linked immunosorbent assay (ELISA) using the irradiated plates and those by the beta(2)-GPI-dependent aCL ELISA. Therefore, aCL have specificity for an epitope on beta(2)-GPI. This epitope is expressed by a conformational change occurring when beta(2)-GPI interacts with an oxygen-substituted solid phase surface

Quenching-Chemiluminescence Determination of Trace Amounts of l-Tyrosine Contained in Dietary Supplement by Chemiluminescence Reaction of an Iron-Phthalocyanine Complex

The chemiluminescence (CL) signal immediately appeared when a hydrogen peroxide solution was injected into an iron-phthalocyanine tetrasulfonic acid (Fe-PTS) aqueous solution. Moreover, the CL intensity of Fe-PTS decreased by adding l-tyrosine. Based on these results, the determination of trace amounts of l-tyrosine was developed using the quenching-chemiluminescence. The calibration curve of l-tyrosine was obtained in the concentration range of 2.0 × 10−7 M to 2.0 × 10−5 M. Moreover, the relative standard deviation (RSD) was 1.63 % (n = 5) for 2.0 × 10−6 M l-tyrosine, and its detection limits (3σ) were 1.81 × 10−7 M. The spike and recovery experiments for l-tyrosine were performed using a soft drink. Furthermore, the determination of l-tyrosine was applied to supplements containing various kinds of amino acids. Each satisfactory relative recovery was obtained at 98 to 102%

ISOLATION AND CHARACTERIZATION OF A NOVEL HYALURONIDASE INHIBITOR FROM A MARINE ACTINOMYCETES STRAIN

A novel hyaluronidase inhibitor (HI) was isolated from the culture extract of a marine- derived actinomycete strain. This strain MB-PO13 was isolated from ascidian (Molgula manhattensis) in Tokyo Bay. Out of about 1,000 isolates from various marine organisms, strain MB-PO13 had the strongest inhibitory activity and was selected for further study. The strain showed abundant-to-moderate growth on most media, forming a grayish mycelium. On the basis of the taxonomical characteristics, the strain was classified as belonging to the genus of Streptomyces and was named as Streptomyces sp. strain MB-PO13. The structure of HI was elucidated by interpretation of NMR data. HI displayed about 25-fold potent hyaluronidase inhibitory activity against hyaluronidase than glycyrrhizin. Keywords: marine actinomycetes; Streptomyces; hyaluronidase inhibitor

Differentiation between non-hypervascular pancreatic neuroendocrine tumour and pancreatic ductal adenocarcinoma on dynamic computed tomography and non-enhanced magnetic resonance imaging

Purpose: To determine the differentiating features between non-hypervascular pancreatic neuroendocrine tumour (PNET) and pancreatic ductal adenocarcinoma (PDAC) on dynamic computed tomography (CT) and non-enhanced magnetic resonance imaging (MRI). Material and methods: We enrolled 102 patients with non-hypervascular PNET (n = 15) or PDAC (n = 87), who had undergone dynamic CT and non-enhanced MRI. One radiologist evaluated all images, and the results were subjected to univariate and multivariate analyses. To investigate reproducibility, a second radiologist re-evaluated features that were significantly different between PNET and PDAC on multivariate analysis. Results: Tumour margin (well-defined or ill-defined) and enhancement ratio of tumour (ERT) showed significant differences in univariate and multivariate analyses. Multivariate analysis revealed a predominance of well-defined tumour margins in non-hypervascular PNET, with an odds ratio of 168.86 (95% confidence interval [CI]: 10.62-2685.29; p < 0.001). Furthermore, ERT was significantly lower in non-hypervascular PNET than in PDAC, with an odds ratio of 85.80 (95% CI: 2.57-2860.95; p = 0.01). Sensitivity, specificity, and accuracy were 86.7%, 96.6%, and 95.1%, respectively, when the tumour margin was used as the criteria. The values for ERT were 66.7%, 98.9%, and 94.1%, respectively. In reproducibility tests, both tumour margin and ERT showed substantial agreement (margin of tumour, κ = 0.6356; ERT, intraclass correlation coefficients (ICC) = 0.6155). Conclusions: Non-hypervascular PNET showed well-defined margins and lower ERT compared to PDAC, with significant differences. Our results showed that non-hypervascular PNET can be differentiated from PDAC via dynamic CT and non-enhanced MRI

Evaluating the malignant potential of intraductal papillary mucinous neoplasms of the pancreas : added value of non-enhanced endoscopic ultrasound to supplement non-enhanced magnetic resonance imaging

Purpose: To evaluate the diagnostic performance of combining non-enhanced magnetic resonance imaging (MRI) and non-enhanced endoscopic ultrasonography (EUS) for assessing the malignant potential of lesions in patients with intraductal papillary mucinous neoplasms of the pancreas (IPMNs). Material and methods: Data from 38 patients histopathologically diagnosed with IPMN adenomas or IPMN adenocarcinomas were retrospectively analysed. Preliminary univariate and multivariate analyses were conducted to identify statistically significant associations. Three blinded radiologists evaluated the image sets to assess the diagnostic performance of combined use of non-enhanced MRI and EUS as opposed to non-enhanced MRI alone in distinguishing malignant from benign lesions. Observer performance and interobserver variability were determined using receiver-operating-characteristic curve analysis and weighted κ statistics. Results: Multivariate analyses identified a significant difference between the abrupt change in the main pancreatic duct (MPD) calibre with distal pancreatic atrophy and the signal intensity of lesion-to-spinal cord ratio on MRI; a significant difference was observed in MPD size on EUS. Diagnostic performance assessments of the image sets did not differ significantly between the blinded radiologists. Conclusions: The clinical utility of non-enhanced EUS may be attributive in evaluating IPMN that has already been evaluated by non-enhanced MRI

3D quantitative analysis of diffusion-weighted imaging for predicting the malignant potential of intraductal papillary mucinous neoplasms of the pancreas

Purpose: To investigate the predictors of intraductal papillary mucinous neoplasms of the pancreas (IPMNs) with high-grade dysplasia, using 2-dimensional (2D) analysis and 3-dimensional (3D) volume-of-interest-based apparent diffusion coefficient (ADC) histogram analysis. Material and methods: The data of 45 patients with histopathologically confirmed IPMNs with high-grade or lowgrade dysplasia were retrospectively assessed. The 2D analysis included lesion-to-spinal cord signal intensity ratio (LSR), minimum ADC value ($ADC_{min}$), and mean ADC value ($ADC_{mean}$). The 3D analysis included the overall mean ($ADC_{overall mean}$), mean of the bottom 10th percentile ($ADC_{mean0-10}$), mean of the bottom 10-25th percentile ($ADC_{mean10-25}$), mean of the bottom 25-50th percentile ($ADC_{mean25-50}$), skewness ($ADC_{skewness}$), kurtosis ($ADC_{kurtosis}$), and entropy ($ADC_{entropy}$). Diagnostic performance was compared by analysing the area under the receiver operating characteristic curve (AUC). Inter-rater reliability was assessed by blinded evaluation using the intraclass correlation coefficient. Results: There were 16 and 29 IPMNs with high- and low-grade dysplasia, respectively. The LSR, $ADC_{overall mean}$, $ADC_{mean0-10}$, $ADC_{mean10-25}$, $ADC_{mean25-50}$, and $ADC_{entropy}$ showed significant between-group differences (AUC = 72-93%; p < 0.05). Inter-rater reliability assessment showed almost perfect agreement for LSR and substantial agreement for $ADC_{overall mean}$ and $ADC_{entropy}$. Multivariate logistic regression showed that $ADC_{overall mean}$ and $ADC_{entropy}$ were significant independent predictors of malignancy (p < 0.05), with diagnostic accuracies of 80% and 73%, respectively. Conclusion: $ADC_{overall mean}$ and $ADC_{entropy}$ from 3D analysis may assist in predicting IPMNs with high-grade dysplasia

Potent and broad anticancer activities of leaf extracts from Melia azedarach L. of the subtropical Okinawa islands

Plant extracts have been traditionally used for various therapeutic applications. By conducting an initial screening of several subtropical plants, in this study, we evaluated the anticancer activities of Melia azedarach L. The extract from Melia azedarach L. leaves (MLE) show high cytotoxic effects on cancer cells and in vivo mouse and dog tumor models. During the initial screening, MLE showed strong antiproliferative activity against HT-29 colon, A549 lung, and MKN1 gastric cancer cells. In subsequent tests, using 39 human tumor cell lines, we confirmed the potent anticancer activities of MLE. The anticancer activity of MLE was also confirmed in vivo. MLE markedly inhibited the growth of transplanted gastric MKN1 cancer xenografts in mice. To elucidate the mechanism underlying the anticancer effects of MLE, MLE-treated MKN1 cells were observed using an electron microscope; MLE treatment induced autophagy. Furthermore, western blot analysis of proteins in lysates of MLE-treated cells revealed induction of light chain 3 (LC3)-II autophagosomal proteins. Thus, MLE appeared to suppress MKN1 cell proliferation by inducing autophagy. In addition, in the mouse macrophage cell line J774A.1, MLE treatment induced TNF-alpha production, which might play a role in tumor growth suppression in vivo. We also performed a preclinical evaluation of MLE treatment on dogs with various cancers in veterinary hospitals. Dogs with various types of cancers showed a mean recovery of 76% when treated with MLE. Finally, we tried to identify the active substances present in MLE. All the active fractions obtained by reverse-phase chromatography contained azedarachin B-related moieties, such as 3-deacetyl-12-hydroxy-amoorastatin, 12-hydroxy-amoorastatin, and 12-hydroxyamoorastaton. In conclusion, MLE contains substances with promising anticancer effects, suggesting their future use as safe and effective anticancer agents

Genes adopt non-optimal codon usage to generate cell cycle-dependent oscillations in protein levels

Most cell cycle-regulated genes adopt non-optimal codon usage, namely, their translation involves wobbly matching codons. Here, the authors show that tRNA expression is cyclic and that codon usage, therefore, can give rise to cell-cycle regulation of proteins