Correction to: Epicardial fat volume measured on nongated chest CT is a predictor of coronary artery disease.

The original version of this article, published on 11 March 2019, unfortunately contained a mistake. The following correction has therefore been made in the original: the presentation of Fig. 5 was incorrect. The corrected figure is given below.

Epicardial fat volume measured on nongated chest CT is a predictor of coronary artery disease.

OBJECTIVE: To investigate whether epicardial fat volume (EFV) quantified on ECG-nongated noncontrast CT (nongated-NCCT) could be used as a reliable and reproducible predictor for coronary artery disease (CAD). METHODS: One hundred seventeen subjects (65 men, mean age 66.6 ± 11.9 years) underwent coronary CT angiography (CCTA) and nongated-NCCT during a single session because of symptoms suggestive of CAD. Two observers independently quantified EFV on both images. Correlation between CCTA-EFV and nongated-NCCT-EFV was assessed using Pearson's correlation coefficient and Bland-Altman plots. Inter-observer agreement was analyzed using concordance correlation coefficients (CCC). Coronary risk factors including EFV were compared between CAD-positive (> 50% stenosis) and CAD-negative groups. The association between EFV and CAD was analyzed using multivariate logistic regression. ROC analysis was performed, and AUC was compared with DeLong's method. RESULTS: Seventy-four subjects were diagnosed with CAD. An excellent correlation was noted between CCTA-EFV and nongated-NCCT-EFV (r = 0.948, p < 0.001), despite the systematic difference between both measurements (mean bias, 1.26). Inter-observer agreement was nearly perfect (CCC, 0.988 and 0.985 for CCTA and nongated-NCCT, respectively, p < 0.001). Significant differences were noted between subjects with versus without CAD in age, hypertension, and EFV on both types of images (p ≤ 0.026). Multivariate analysis revealed that increased EFV on CCTA (odds ratio 1.185, p = 0.003) and nongated-NCCT (odds ratio 1.20, p = 0.015) was independently associated with CAD. There was no significant difference between CCTA-EFV and nongated-NCCT-EFV in AUC for the prediction of CAD (0.659 vs 0.665, p = 0.706). CONCLUSIONS: Despite the absence of ECG gating, EFV measured on NCCT may serve as a reproducible predictor for CAD with accuracy equivalent to EFV measured on CCTA. KEY POINTS: • Despite the absence of ECG gating, the EFV on NCCT provides nearly perfect inter-observer reproducibility and shows excellent correlation with measurements on gated CCTA. • EFV on nongated-NCCT may serve as an independent biomarker for predicting coronary artery disease with accuracy equivalent to that of EFV on gated CCTA.

Usefulness of the Short-Echo Time Cube Sequence at 3-T Magnetic Resonance Cholangiopancreatography: Prospective Comparison With the Conventional 3-Dimensional Fast Spin-Echo Sequence.

OBJECTIVES: We evaluated prospectively the clinical use of the short-echo time (TE) Cube sequence for magnetic resonance cholangiopancreatography (MRCP) at 3 T. METHODS: Using a 3-T unit, we subjected 41 consecutive patients to short-TE Cube MRCP and conventional 3-dimensional fast spin-echo (3D-FSE) MRCP. Two radiologists independently rated the image quality and the visibility of the right and left hepatic, cystic, common bile, and main pancreatic ducts and the gallbladder on a 4-point scale. The averaged visual scores by 2 readers for the image quality were calculated, and the artifacts were evaluated in cases with relatively lower (<3) score. The signal-to-noise ratio, contrast-to-noise ratio, and acquisition time were evaluated by quantitative analysis. RESULTS: The visual scores of the common bile duct (P < 0.05), cystic duct (P < 0.01), and gallbladder (P < 0.01) were significantly higher for Cube than 3D-FSE MRCP. Signal-to-noise ratio was also significantly higher for Cube than 3D-FSE MRCP (P < 0.01). There was no significant difference in the image acquisition time (352.1 ± 93.0 vs 314.1 ± 126.2 seconds, P = 0.059). Four cases on 3D-FSE MRCP and 2 cases on Cube MRCP have relatively lower image quality; however, the difference was not significant (P = 0.18). CONCLUSIONS: The visibility of biliary structures is significantly better on short-TE Cube MRCP than conventional 3D-FSE MRCP images at a clinically acceptable acquisition time.

Ca²âº influx-linked protein kinase C activity regulates the ß-catenin localization, micromere induction signalling and the oral-aboral axis formation in early sea urchin embryos.

Sea urchin embryos initiate cell specifications at the 16-cell stage by forming the mesomeres, macromeres and micromeres according to the relative position of the cells in the animal-vegetal axis. The most vegetal cells, micromeres, autonomously differentiate into skeletons and induce the neighbouring macromere cells to become mesoendoderm in the ß-catenin-dependent Wnt8 signalling pathway. Although the underlying molecular mechanism for this progression is largely unknown, we have previously reported that the initial events might be triggered by the Ca2+ influxes through the egg-originated L-type Ca2+ channels distributed asymmetrically along the animal-vegetal axis and through the stretch-dependent Ca2+channels expressed specifically in the micromere at the 4th cleavage. In this communication, we have examined whether one of the earliest Ca2+ targets, protein kinase C (PKC), plays a role in cell specification upstream of ß-catenin. To this end, we surveyed the expression pattern of ß-catenin in early embryos in the presence or absence of the specific peptide inhibitor of Hemicentrotus pulcherrimus PKC (HpPKC-I). Unlike previous knowledge, we have found that the initial nuclear entrance of ß-catenin does not take place in the micromeres, but in the macromeres at the 16-cell stage. Using the HpPKC-I, we have demonstrated further that PKC not only determines cell-specific nucleation of ß-catenin, but also regulates a variety of cell specification events in the early sea urchin embryos by modulating the cell adhesion structures, actin dynamics, intracellular Ca2+ signalling, and the expression of key transcription factors.

Novel structure of hepatic extracellular matrices containing arylsulfatase A.

Arylsulfatase A (ArsA) has been regarded as a lysosomal enzyme involved in the degradation of sulfolipids. We previously reported the colocalization of non-enzymatic ArsA with heparan sulfate proteoglycan on cell surfaces in the mouse liver using tissues processed with phosphate-buffered saline containing Ca2+ and Mg2+. In vitro analysis also revealed the tight binding of ArsA to heparin. These results suggest that ArsA functions as a component of the extracellular matrix (ECM). To characterize ArsA as a component of ECMs, we extended our comparison to the distribution patterns of ArsA and the major hepatic ECM components (types I, III, IV and V collagen, fibronectin, and laminin) in the mouse liver at the ultrastructural level under the same conditions that allow the detection of ArsA. Here, we show that ArsA is distributed not only on the cell surfaces of endothelial cells and hepatocytes, but also on the collagen fibrils in the space of Disse. ArsA is additionally colocalized with these major hepatic ECM components on both the luminal and abluminal sides of sinusoidal endothelial cells as well as in the space of Disse. These findings reveal a novel structure of hepatic ECMs containing ArsA.

Cell-surface arylsulfatase A and B on sinusoidal endothelial cells, hepatocytes, and Kupffer cells in mammalian livers.

Arylsulfatase A (ARSA) and B (ARSB) have been regarded as lysosomal enzymes because of their hydrolytic activity on synthetic aromatic substrates and the lysosomal localization of their enzymatic activity. Using sea urchin embryos, we previously demonstrated that the bulk of ARS is located on the cell surface of the epithelium, colocalizing with sulfated polysaccharides, and that it does not exhibit enzymatic activity. To examine whether ARSA and ARSB exist on the cell surface in mammalian tissues, we raised antibodies against ARSA and ARSB and examined immunohistochemically their localization in the liver using light and electron microscopy. Here we show that mammalian ARSA and ARSB exist on the cell surface of sinusoidal endothelial cells, hepatocytes, and sinusoidal macrophages (Kupffer cells), as well as in the lysosome. They are also colocalized with heparan sulfate proteoglycan. These results suggest that ARSA and ARSB also may function in the cell surface of mammals. This is the first report to show cell-surface localization of ARS in mammalian somatic cells. The extracellular localization of ARS will provide new insight for human ARS deficiency disorders, such as metachromatic leukodystrophy and mucopolysaccharidosis VI.

Synthesis and intracellular transportation of type I procollagen during functional differentiation of odontoblasts.

The expression of type I collagen, the most component of dentin extracellular matrix proteins (ECMs) in odontoblast is correlated with the activity of dentin formation. Since odontoblast possesses a distinct cellular process for protein transport into the dentinal tubule, it is important to examine the intracellular protein localization. However, a study focusing on odontoblast processes has not been performed. Type I collagen is synthesized as procollagen, which is immediately converted to collagen upon secretion. After characterization of antiserum to rat type I procollagen, we investigated the intracellular localization of type I procollagen in odontoblasts during and after dentinogenesis, using immunohistochemistry and in situ hybridization. The level of mRNA expression decreased during dentinogenesis, whereas the intracellular localization of type I procollagen in odontoblast processes become more distinct. The percentage of dentinal tubules with type I procollagen increased significantly with aging. Odontoblasts in pulp horn, in particular, showed moderate expression of type I procollagen after dentinogenesis. Since loss of occlusion also caused a significant decrease in type I procollagen, we concluded that occlusal stimulation activated type I procollagen synthesis in odontoblasts. We also suggest that analysis of intracellular transport of type I procollagen via odontoblast processes may be a new approach to evaluation of odontoblast function.

Automated hepatic volumetry for living related liver transplantation at multisection CT.

PURPOSE: To prospectively compare in vivo hepatic automated volumetry with manual volumetry and measured liver volume. MATERIALS AND METHODS: The study was conducted in accordance with the guidelines of the Institutional Review Board of Kumamoto University (Japan). Patient informed consent was obtained. Preoperative multisection computed tomography (CT) was performed in 35 consecutive patients (21 men, 14 women; mean age, 42.8 years; range, 28-72 years) with hepatic disease awaiting living related liver transplantation. The CT scans covered the entire liver at a section thickness of 2.5 mm. Liver volume was estimated by using both the automated and the manual methods. Actual liver weight was obtained for all patients and was converted to hepatic volume on the basis of a predetermined relationship between actual liver weight and volume. Processing time required for both methods was also recorded. Two-tailed paired t test, correlation coefficient, and Bland-Altman tests were used for statistical analyses. RESULTS: Mean liver weight was 881.7 g +/- 249.8 (standard deviation), and mean measured liver volume was 956.00 cm(3) +/- 280.10. Volumetry performed with the automated and manual methods provided liver volumes of 982.99 cm(3) +/- 301.98 and 937.10 cm(3) +/- 301.31, respectively. There was good correlation between measured and estimated volumes obtained with the automated method (r = 0.792, P < .01). The manual and automated methods required 32.8 minutes +/- 6.9 and 4.4 minutes +/- 1.9, respectively. CONCLUSION: The automated method reduced the time required for volumetry of the liver and provided acceptable measurements.

Unichrom, a novel nuclear matrix protein, binds to the Ars insulator and canonical MARs.

Eukaryotic genomic DNA is organized into loop structures by attachments to the nuclear matrix. These attachments to the nuclear matrix have been supposed to form the boundaries of chromosomal DNA. Insulators or boundary elements are defined by two characteristics: they interrupt promoter-enhancer communications when inserted between them, and they suppress the silencing of transgenes stably integrated into inactive chromosomal domains. We recently identified an insulator element in the upstream region of the sea urchin arylsulfatase (HpArs) gene that shows both enhancer blocking and suppression of position effects. Here, we report that Unichrom, originally identified by its G-stretch DNA binding capability, is a nuclear matrix protein that binds to the Ars insulator and canonical nuclear matrix attachment regions (MARs). We also show that Unichrom recognizes the minor groove of the AT-rich region within the Ars insulator, which may have a base-unpairing property, as well as the G-stretch DNA. Furthermore, Unichrom selectively interacts with poly(dG).poly(dC), poly(dA).poly(dT) and poly(dAT).poly(dAT), but not with poly(dGC).poly(dGC). Unichrom also shows high affinity for single-stranded G- and C-stretches. We discuss the DNA binding motif of Unichrom and the function of Unichrom in the nuclear matrix.

Simulation of aortic peak enhancement on MDCT using a contrast material flow phantom: feasibility study.

OBJECTIVE: The objective of our study was to develop a flow phantom simulating aortic peak enhancement after the injection of contrast material on CT and to investigate the validity of the flow phantom by comparing the time-enhancement curves obtained for the flow phantom and humans. MATERIALS AND METHODS: We developed a flow phantom simulating the enhancement pattern of the aorta after the injection of contrast material. In protocols 1, 2, and 3 of the phantom study, 90, 102, and 150 mL of iohexol, respectively, was administered over 35 sec. In protocol 4, 102 mL of iohexol was administered over 25 sec. In phantom protocols 1', 2', and 3', the dose and contrast injection duration were the same as in protocols 1, 2, and 3; however, saline (10 mL) was injected during the 20 sec after contrast delivery. In the human study, 20 patients were randomized into four groups: Groups A, B, and C received 1.5, 1.7, and 2.5 mL of iohexol per kilogram of body weight, respectively, over 35 sec; and group D received 1.7 mL/kg over 25 sec. In patient groups A, B, C, and D, phantom protocols 1, 2, 3, and 4 were used, respectively. Single-level serial CT scans were obtained using a 16-MDCT scanner on the simulated and real aortas after the injection of contrast material. Time-enhancement curves of simulated and real aortas were generated, and aortic peak times and aortic peak enhancement values were calculated. RESULTS: Aortic peak enhancement and aortic peak times in protocols 1-4 and 1'-3' of the phantom study were 2-8% larger and 6-18% longer, respectively, than in the corresponding patient study. The shape of the time-enhancement curves before aortic peak time in protocols 1-3 and 1'-3' of the phantom study closely resembled that of the corresponding patient study. After the aortic peak time, the shape of time-enhancement curves in protocols 1, 2, and 3 of the phantom study was different from the corresponding patient study; however, it was similar in phantom protocols 1'-3' and the corresponding patient study. In all four phantom protocols, the difference between maximal and minimal aortic peak enhancement was less than the SD of the corresponding patient study. CONCLUSION: The level of peak aortic enhancement and the time to peak aortic enhancement were similar in the phantom and human studies when we used our different contrast injection protocols for MDCT.

T-brain homologue (HpTb) is involved in the archenteron induction signals of micromere descendant cells in the sea urchin embryo.

Signals from micromere descendants play a crucial role in sea urchin development. In this study, we demonstrate that these micromere descendants express HpTb, a T-brain homolog of Hemicentrotus pulcherrimus. HpTb is expressed transiently from the hatched blastula stage through the mesenchyme blastula stage to the gastrula stage. By a combination of embryo microsurgery and antisense morpholino experiments, we show that HpTb is involved in the production of archenteron induction signals. However, HpTb is not involved in the production of signals responsible for the specification of secondary mesenchyme cells, the initial specification of primary mesenchyme cells, or the specification of endoderm. HpTb expression is controlled by nuclear localization of beta-catenin, suggesting that HpTb is in a downstream component of the Wnt signaling cascade. We also propose the possibility that HpTb is involved in the cascade responsible for the production of signals required for the spicule formation as well as signals from the vegetal hemisphere required for the differentiation of aboral ectoderm.

Stimulation of Unfertilized Eggs of the Echiuroid, Urechis unicinctus by Polyamines: (echiuroid eggs/parthenogenesis/polyamines/spermine/spermidine).

Unfertilized eggs of the echiuroid, Urechis unicinctus, were activated by polyamines, such as putrescine, spermidine and spermine at concentrations above 10 µM. Fertilization membrane elevated and germinal vesicle disappeared in unfertilized eggs kept for several min in sea water containing these polyamines. Following the addition of these polyamines, a decrease of pH value in the egg suspension, occurred in a similar manner as observed following fertilization. Several sec after the addition of polyamines to the egg suspension, the respiratoy rate increased very slightly and the sensitivity of the respiration to 2, 4-dinitrophenol, which was lower in unfertilized eggs than in fertilized eggs, became as high as in fertilized ones. Irregular cleavage occurred in the eggs stimulated by polyamines. The incorporation of [3 H]-deoxyadenosine into DNA was initiated by adding polyamines in the unfertilized eggs preloaded with the isotope. The rate of [3 H]-leucine incorporation into protein in the preloaded unfertilized eggs was also enhanced by polyamines, in almost the same manner as observed following fertilization.

INHIBITION OF DIHYDROFOLATE REDUCTASE BY PALMITOYL-CoA AND THE REVERSAL OF THE INHIBITION BY SPERMINE AND SPERMIDINE IN THE EGGS OF THE SEA URCHIN, HEMICENTROTUS PULCHERRIMUS.

Dihydrofolate reductase activity in fertilized eggs of the sea urchin, Hemicentrotus pulcherrimus, was almost the same as in unfertilized eggs. Aminopterin inhibited the enzyme competitively with dihydrofolate (FH2 ). The apparent Km value for FH2 in the dihydrofolate reductase reaction was about 0.1 µM in the crude homogenate of both unfertilized and fertilized eggs. Dihydrofolate reductase in the eggs was also inhibited by palmitoyl-CoA. The inhibition was canceled by polyamines, especially by spermine, but putrescine failed to prevent the enzyme from the inhibition. The change in long-chain acyl-CoA and polyamine concentrations during fertilization are discussed as possible regulatory factors of the enzyme.