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1.
Mol Plant Microbe Interact ; 37(5): 467-476, 2024 May.
Article in English | MEDLINE | ID: mdl-38805410

ABSTRACT

The soil-borne phytopathogenic gram-negative bacterium Ralstonia solanacearum species complex (RSSC) produces staphyloferrin B and micacocidin as siderophores that scavenge for trivalent iron (Fe3+) in the environment, depending on the intracellular divalent iron (Fe2+) concentration. The staphyloferrin B-deficient mutant reportedly retains its virulence, but the relationship between micacocidin and virulence remains unconfirmed. To elucidate the effect of micacocidin on RSSC virulence, we generated the micacocidin productivity-deficient mutant (ΔRSc1806) that lacks RSc1806, which encodes a putative polyketide synthase/non-ribosomal peptide synthetase, using the RSSC phylotype I Ralstonia pseudosolanacearum strain OE1-1. When incubated in the condition without Fe2+, ΔRSc1806 showed significantly lower Fe3+-scavenging activity, compared with OE1-1. Until 8 days after inoculation on tomato plants, ΔRSc1806 was not virulent, similar to the mutant (ΔphcA) missing phcA, which encodes the LysR-type transcriptional regulator PhcA that regulates the expression of the genes responsible for quorum sensing (QS)-dependent phenotypes including virulence. The transcriptome analysis revealed that RSc1806 deletion significantly altered the expression of more than 80% of the PhcA-regulated genes in the mutant grown in medium with or without Fe2+. Among the PhcA-regulated genes, the transcript levels of the genes whose expression was affected by the deletion of RSc1806 were strongly and positively correlated between the ΔRSc1806 and the phcA-deletion mutant. Furthermore, the deletion of RSc1806 significantly modified QS-dependent phenotypes, similar to the effects of the deletion of phcA. Collectively, our findings suggest that the deletion of micacocidin production-related RSc1806 alters the regulation of PhcA-regulated genes responsible for QS-dependent phenotypes including virulence as well as Fe3+-scavenging activity. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Subject(s)
Bacterial Proteins , Gene Expression Regulation, Bacterial , Plant Diseases , Quorum Sensing , Solanum lycopersicum , Quorum Sensing/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Virulence , Solanum lycopersicum/microbiology , Plant Diseases/microbiology , Iron/metabolism , Ralstonia/genetics , Ralstonia/pathogenicity , Siderophores/metabolism , Gene Deletion , Peptide Synthases/genetics , Peptide Synthases/metabolism
2.
Sci Rep ; 11(1): 11995, 2021 06 07.
Article in English | MEDLINE | ID: mdl-34099847

ABSTRACT

Light-Oxygen-Voltage (LOV) domains are responsible for detecting blue light (BL) and regulating the activities of effector domains in various organisms. Photozipper (PZ), an N-terminally truncated aureochrome-1 protein, contains a LOV domain and a basic leucin zipper (bZIP) domain and plays a role as a light-activatable transcription factor. PZ is monomeric in the dark state and undergoes non-covalent dimerization upon illumination with BL, subsequently increasing its affinity for the target DNA. To clarify the molecular mechanism of aureochromes, we prepared site-directed mutants of PZ and performed quantitative analyses in the dark and light states. Although the amino acid substitutions in the hinge region between the LOV core and A'α helix had minor effects on the dimerization and DNA-binding properties of PZ, the substitutions in the ß-sheet region of the LOV core and in the A'α helix significantly affected these properties. We found that light signals are transmitted from the LOV core to the effector bZIP domain via the hydrophobic residues on the ß-sheet. The light-induced conformational change possibly deforms the hydrophobic regions of the LOV core and induces the detachment of the A'α helix to expose the dimerization surface, likely activating the bZIP domain in a light-dependent manner.

3.
Sci Rep ; 11(1): 10757, 2021 05 24.
Article in English | MEDLINE | ID: mdl-34031429

ABSTRACT

In this study, we investigated a new application of bubble-eye goldfish (commercially available strain with large bubble-shaped eye sacs) for immunological studies in fishes utilizing the technical advantage of examining immune cells in the eye sac fluid ex vivo without sacrificing animals. As known in many aquatic species, the common goldfish strain showed an increased infection sensitivity at elevated temperature, which we demonstrate may be due to an immune impairment using the bubble-eye goldfish model. Injection of heat-killed bacterial cells into the eye sac resulted in an inflammatory symptom (surface reddening) and increased gene expression of pro-inflammatory cytokines observed in vivo, and elevated rearing temperature suppressed the induction of pro-inflammatory gene expressions. We further conducted ex vivo experiments using the immune cells harvested from the eye sac and found that the induced expression of pro-inflammatory cytokines was suppressed when we increased the temperature of ex vivo culture, suggesting that the temperature response of the eye-sac immune cells is a cell autonomous function. These results indicate that the bubble-eye goldfish is a suitable model for ex vivo investigation of fish immune cells and that the temperature-induced infection susceptibility in the goldfish may be due to functional impairments of immune cells.


Subject(s)
Cytokines/genetics , Fish Diseases/microbiology , Goldfish/immunology , Pseudomonas Infections/genetics , Animals , Eye/immunology , Eye/microbiology , Fish Diseases/genetics , Fish Proteins/genetics , Gene Expression Regulation , Goldfish/microbiology , Hot Temperature , Pseudomonas Infections/immunology , Pseudomonas Infections/veterinary , Pseudomonas aeruginosa/immunology
4.
Drug Discov Ther ; 15(1): 9-13, 2021 Mar 10.
Article in English | MEDLINE | ID: mdl-33642540

ABSTRACT

In this study, we designed a method for conducting a human study by the following process. (1) The host computer stores the subject information. (2) The sample preparer prepares a food sample. (3) The subject (healthy human volunteer) sends the information of an intake of the food sample to the host computer, which creates an event entry for the event. (4) The medical professional (typically a physician) collects and stores the subject's blood sample in a container with the subject's identification (e.g., ID number). (5) The sample analyst analyzes the blood biochemical profiles. (6)The host computer stores the blood biochemical data, and by matching the blood biochemical data with the subject IDs, a final analysis report will automatically be created. In this study, we also run a test case, based on this design, where we obtained a blood biochemical dataset from healthy volunteers. This scheme can reduce the cost of human trials for functional foods and will help acquiring the scientific basis of functional foods.


Subject(s)
Clinical Trials as Topic , Functional Food , Research Design , Humans
5.
Biochemistry ; 59(28): 2592-2601, 2020 07 21.
Article in English | MEDLINE | ID: mdl-32567839

ABSTRACT

Light oxygen voltage-sensing (LOV) domains are widely found in photoreceptor proteins of plants, algae, fungi, and bacteria. Structural studies of LOV domains suggest that Phe and Gln residues located in the proximity of the chromophore undergo conformational changes upon illumination; however, the molecular mechanism associated with activation of the effector domain remains to be elucidated. Photozipper (PZ) protein is an N-terminally truncated aureochrome-1 comprising a LOV domain and a basic leucine zipper domain. Blue light (BL) induces PZ dimerization and subsequently increases its affinity for target DNA. In this study, we prepared PZ mutants with substitutions of F298 and Q317 and performed quantitative analyses in dark and light states. Substitutions of Q317 significantly reduced the light-induced changes in PZ affinity for the target DNA, especially in the case of the high affinities observed in the dark state. Upon illumination, all PZ mutants showed increased affinity for the target sequence, which demonstrated a clear correlation with the dimer fraction of each PZ mutant. These results suggest the existence of a conformational equilibrium and that its shift by a synergistic interaction between the chromophore and protein moiety probably enables BL-regulated switching of aureochrome-1.


Subject(s)
DNA-Binding Proteins/chemistry , Stramenopiles/chemistry , DNA/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Light , Models, Molecular , Point Mutation , Protein Conformation/radiation effects , Protein Domains/radiation effects , Protein Multimerization/radiation effects , Stramenopiles/genetics , Stramenopiles/metabolism
6.
Drug Discov Ther ; 12(5): 291-294, 2018.
Article in English | MEDLINE | ID: mdl-30464160

ABSTRACT

Gnotobiotic animals are useful for investigation of the effects of specific lactic acid bacteria on individual animals. Here we report that lactic acid bacteria colonize and proliferate in the intestinal tract of germ-free silkworms. When silkworms hatching from formalin-treated eggs were reared to fifth-instar larvae with an artificial diet containing antibiotics, bacteria and fungi were not observed in their intestines. An antibiotic-free diet supplemented with viable lactic acid bacteria, such as Enterococcus faecalis 0831-07, Lactococcus lactis 11/19-B1, or Leuconostoc carnosum #7-2, was fed to the germ-free silkworms for 1 day. After feeding the larvae on a diet without lactic acid bacteria for 5 days, each type of lactic acid bacterium was found in the intestine. Moreover, an increase in the number of Enterococcus faecalis 0831-07 was observed in the intestine 2-5 days after ingestion. These findings suggest that we successfully established a method to construct a gnotobiotic silkworm model.


Subject(s)
Bombyx/microbiology , Lactobacillales/growth & development , Animals , Bombyx/growth & development , Diet , Gastrointestinal Tract/microbiology , Germ-Free Life , Models, Animal
7.
EMBO Rep ; 13(5): 455-61, 2012 May 01.
Article in English | MEDLINE | ID: mdl-22441692

ABSTRACT

The posttranslational regulation of mammalian clock proteins has been assigned a time-keeping function, but seems to have more essential roles. Here we show that c-Jun N-terminal kinase (JNK), identified by inhibitor screening of BMAL1 phosphorylation at Ser 520/Thr 527/Ser 592, confers dynamic regulation on the clock. Knockdown of JNK1 and JNK2 abrogates BMAL1 phosphorylation and lengthens circadian period in fibroblasts. Mice deficient for neuron-specific isoform JNK3 have altered behavioural rhythms, with longer free-running period and compromised phase shifts to light. The locomotor rhythms are insensitive to intensity variance of constant light, deviating from Aschoff's rule. Thus, JNK regulates a core characteristic of the circadian clock by controlling the oscillation speed and the phase in response to light.


Subject(s)
JNK Mitogen-Activated Protein Kinases/metabolism , ARNTL Transcription Factors/metabolism , Animals , Cell Line , Circadian Clocks/physiology , Humans , Immunoblotting , Immunoprecipitation , JNK Mitogen-Activated Protein Kinases/genetics , Mammals/metabolism , Mammals/physiology , Mice , Mitogen-Activated Protein Kinase 10/genetics , Mitogen-Activated Protein Kinase 10/metabolism , Mitogen-Activated Protein Kinase 8/genetics , Mitogen-Activated Protein Kinase 8/metabolism , Mitogen-Activated Protein Kinase 9/genetics , Mitogen-Activated Protein Kinase 9/metabolism , Motor Activity/physiology , NIH 3T3 Cells , Phosphorylation/genetics , Phosphorylation/physiology , Suprachiasmatic Nucleus/metabolism
8.
J Magn Reson Imaging ; 34(2): 326-35, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21780227

ABSTRACT

PURPOSE: To compare the diagnostic accuracy of contrast-enhanced computed tomography (CE-CT), contrast-enhanced ultrasonography (CE-US), superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI), and gadoxetic acid-enhanced MRI (Gd-EOB-MRI) in the evaluation of colorectal hepatic metastases. MATERIALS AND METHODS: In all, 111 patients with colorectal cancers were enrolled in this study. Of the 112 metastases identified in 46 patients, 31 in 18 patients were confirmed histologically and the remaining 81 in 28 patients were confirmed by follow-up imaging. CE-CT, CE-US, SPIO-MRI, and Gd-EOB-MRI were evaluated. Mean (of three readers, except for CE-US) area under the receiver operating characteristic curve (A(z) ), sensitivities, and positive predictive values (PPV) were calculated. Each value was compared to the others by variance z-test or chi-square test with Bonferroni correction. RESULTS: For all lesions, mean A(z) and sensitivity of Gd-EOB-MRI (0.992, 95% [56/59]) were significantly greater than those of CE-CT (0.847, 63% [71/112]) and CE-US (0.844, 73% [77/106]). For lesions ≤1 cm, mean A(z) and sensitivity of Gd-EOB-MRI (0.999, 92% [22/24]) were significantly greater than those of CE-CT (0.685, 26% [13/50]) and CE-US (0.7, 41% [18/44]). Mean A(z) (95% CI) of SPIO-MRI for all lesions (0.966 [0.929-0.987]) and lesions ≤ 1 cm (0.961 [0.911-0.988]) were significantly greater than those of CE-CT and CE-US. Mean sensitivity of SPIO-MRI for lesions ≤1 cm (63%, 26/41) was significantly greater than that of CE-CT. CONCLUSION: Gd-EOB-MRI and SPIO-MRI were more accurate than CE-CT and CE-US for evaluation of liver metastasis in patients with colorectal carcinoma.


Subject(s)
Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/pathology , Contrast Media/pharmacology , Ferric Compounds/pharmacology , Gadolinium DTPA/pharmacology , Liver Neoplasms/diagnosis , Liver Neoplasms/secondary , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Ultrasonography/methods , Adult , Aged , Female , Humans , Image Processing, Computer-Assisted/methods , Male , Middle Aged , Predictive Value of Tests , ROC Curve
9.
Biochem Biophys Res Commun ; 405(2): 216-21, 2011 Feb 11.
Article in English | MEDLINE | ID: mdl-21219870

ABSTRACT

We found a novel protein-protein interaction between ubiquitin-specific protease 15 (USP15) and skeletal muscle LIM protein 1 (SLIM1): USP15 and SLIM1 directly bound under cell-free conditions and co-immunoprecipitated from the lysates of the cells, where they were co-expressed; and USP15 deubiquitinated SLIM1, resulting in the increase of protein levels of SLIM1. Because SLIM1 is strongly implicated in the pathogenesis of myopathies and cardiomyopathies, we generated transgenic (TG) mice with cardiac-specific overexpression of human USP15. Heart weight to body weight ratios and mRNA levels of fetal gene markers in the heart were significantly higher in USP15-TG mice than in wild-type (WT) mice. Also, protein levels of endogenous murine SLIM1 in the heart were significantly higher in USP15-TG mice than in WT mice. Furthermore, the protein of alternatively spliced isoform of SLIM1 was only detected in the heart of USP15-TG mice, and mRNA levels of this isoform were higher as compared to WT mice. These results indicate that USP15 is involved in the regulation of hypertrophic responses in cardiac muscle through transcriptional and post-translational modulation of SLIM1.


Subject(s)
Cardiomegaly/metabolism , Endopeptidases/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Muscle Proteins/metabolism , Myocardium/enzymology , Animals , Cardiomegaly/genetics , Cardiomegaly/pathology , Humans , Intracellular Signaling Peptides and Proteins/genetics , LIM Domain Proteins , Mice , Mice, Transgenic , Muscle Proteins/genetics , Myocardium/pathology , Protein Processing, Post-Translational , Ubiquitin-Specific Proteases
10.
J Magn Reson Imaging ; 32(5): 1132-40, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21031519

ABSTRACT

PURPOSE: To compare the diagnostic accuracy of contrast-enhanced ultrasonography (CE-US), contrast-enhanced CT (CE-CT), and superparamagnetic iron oxide-enhanced MRI (SPIO-MRI) with diffusion-weighted imaging (DWI) in the evaluation of colorectal hepatic metastases. MATERIALS AND METHODS: Thirty-six patients with colorectal cancers were prospectively enrolled and retrospectively evaluated. Of the 86 metastases identified, 16 were confirmed histologically and the remaining 70 were confirmed by follow-up imaging. CE-CT and SPIO-MRI + DWI were independently evaluated by two readers, whereas CE-US was evaluated by consensus reading of two different readers. Area under receiver operating characteristic curve (A(z)), sensitivities, and positive predictive values (PPVs) were calculated and compared. RESULTS: For both readers, SPIO-MRI+DWI had significantly greater A(z) (0.879 and 0.904) and sensitivity (78% and 87%) for all lesions compared with CE-CT (0.779 and 0.793; 59% and 59%) and CE-US (0.811; 69%), and significantly greater A(z) (0.783 and 0.837) and sensitivity (56% and 73%) for lesions ≤1 cm compared with CE-CT (0.562 and 0.601; 20% and 22%) and CE-US (0.66; 37%). For lesions >1 cm, there was no significant difference in A(z), sensitivity and PPV between all the image sets. CONCLUSION: SPIO-MRI with DWI was the most reliable modality for evaluation of liver metastases particularly for lesions ≤1 cm.


Subject(s)
Colorectal Neoplasms/pathology , Contrast Media , Dextrans , Diffusion Magnetic Resonance Imaging , Ferric Compounds , Iron , Liver Neoplasms/diagnosis , Liver Neoplasms/secondary , Magnetite Nanoparticles , Oxides , Tomography, X-Ray Computed , Ultrasonography , Humans , Liver Neoplasms/diagnostic imaging , Predictive Value of Tests , ROC Curve , Sensitivity and Specificity
11.
J Vasc Interv Radiol ; 21(5): 663-70, 2010 May.
Article in English | MEDLINE | ID: mdl-20430296

ABSTRACT

PURPOSE: To evaluate the feasibility for balloon-occluded retrograde transvenous obliteration (BRTO) for gastric varices without gastrorenal shunts. MATERIALS AND METHODS: Of 76 patients with gastric varices who were referred for treatment by BRTO, 11 did not have gastrorenal shunts. Contrast medium-enhanced computed tomography (CT) was performed in all patients; seven patients also underwent CT during splenic arteriography. BRTO was performed to insert a balloon catheter into the main draining vein and inject 5% ethanolamine oleate into gastric varices under the temporary balloon occlusion. RESULTS: The main draining veins were the subphrenic transverse part of the inferior phrenic vein to the inferior vena cava in five patients, the pericardial vein to the left brachiocephalic vein in two, and the paraesophageal vein to the azygos vein in two. In two patients, the main draining vein was unknown. The overall success rate of BRTO in the nine cases with main draining veins was 67%; BRTO was successful in four of the patients in whom the inferior phrenic vein was the main draining vein, one of the patients in whom the pericardial vein was the main draining vein, and one of the patients in whom the paraesophageal vein was the main draining vein. In the other cases in which the inferior phrenic vein or pericardial vein was the main draining vein, BRTO could not be performed because of extravasation. In another patient in whom the paraesophageal vein was the main draining vein, the main draining pathway could not be identified at angiography because of a complicated azygos venous network. CONCLUSIONS: It is feasible to use BRTO to treat cases of gastric varices in which the inferior phrenic vein is the main draining vein. Cases in which the main draining pathway is the pericardial vein are less feasibile for BRTO. The use of BRTO in cases in which the paraesophageal vein is the main draining vein is possible but may be difficult because of a complicated venous network.


Subject(s)
Balloon Occlusion/methods , Esophageal and Gastric Varices/surgery , Aged , Female , Humans , Male , Middle Aged , Treatment Outcome
12.
J Comput Assist Tomogr ; 33(5): 682-8, 2009.
Article in English | MEDLINE | ID: mdl-19820492

ABSTRACT

OBJECTIVE: Cholangiolocellular carcinoma (CLC) is a rare subtype of intrahepatic cholangiocarcinoma as categorized according to the World Health Organization criteria. Recent study also revealed that CLC would originate from hepatic progenitor cells, which are liver-specific stem cells. We reviewed the imaging findings of CLCs, including those of intrahepatic metastases. METHODS: Eight patients who underwent partial hepatectomy were included in this study. Images, including dynamic computed tomographic and magnetic resonance images, were reviewed. RESULTS: On arterial phase images, the lesions appeared as masses exhibiting early and complete enhancement or predominantly peripheral enhancement. Retention of the contrast media in the lesions was observed in half of the lesions. The metastatic nodules had indistinct borders and showed early enhancement along with delayed central enhancement. CONCLUSIONS: Although CLC with dense central fibrosis exhibits imaging features similar to those exhibited by intrahepatic cholangiocarcinoma, early enhancement in most lesions with persistent delayed enhancement is one of the characteristic imaging findings of this rare tumor.


Subject(s)
Cholangiocarcinoma/diagnosis , Liver Neoplasms/diagnosis , Aged , Cholangiocarcinoma/pathology , Cholangiocarcinoma/secondary , Cholangiocarcinoma/surgery , Female , Humans , Image Enhancement , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Magnetic Resonance Imaging , Male , Middle Aged , Portography , Tomography, X-Ray Computed
13.
AJR Am J Roentgenol ; 193(2): 438-44, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19620441

ABSTRACT

OBJECTIVE: The objective of our study was to determine the relationship between the signal intensity of hepatocellular carcinoma (HCC) assessed with diffusion-weighted imaging (DWI) and T2-weighted imaging and the apparent diffusion coefficient (ADC) with the histopathologic grade of each nodule. MATERIALS AND METHODS: MR examinations including DWI and T2-weighted imaging of 125 surgically resected hypervascular HCCs in 99 patients were retrospectively reviewed. Pathologic examinations revealed 25 well-, 61 moderately, and 39 poorly differentiated HCCs. Two radiologists reviewed the images and classified the signal intensity of each tumor on DWI and T2-weighted imaging by mutual agreement. The incidence of each signal intensity and the relationship between signal intensity and histopathologic grade were assessed for each sequence. The relationship between the ADC and histopathologic grade was also evaluated. RESULTS: On DWI, 11 of 125 HCCs appeared hypo- to isointense, 27 tumors appeared slightly hyperintense, and the remaining 87 tumors appeared obviously hyperintense to the surrounding liver. Overall, 91.2% (114/125) of HCCs showed hyperintensity to the surrounding hepatic parenchyma. Statistical analysis showed that this rate on DWI was significantly higher than that on T2 turbo spin-echo (TSE) imaging (p < 0.001). On DWI, the tumors tended to show a brighter signal with rising histopathologic grade (p = 0.031), but this trend was not observed on T2-weighted imaging. ADC measurements revealed that the mean ADCs of well-, moderately, and poorly differentiated HCCs were approximately 1.45, 1.46, and 1.36 x 10(-3) mm(2)/s, respectively. There was no significant correlation between ADC and histopathologic grade. CONCLUSION: The histopathologic grade of HCC had no correlation with the ADC, but HCC tumors tended to show a higher signal on DWI as the histopathologic grade rose. However, predicting the correct histopathologic grade of each HCC before surgery on the basis of DWI findings was difficult because of the large overlap among histopathologic grades.


Subject(s)
Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Aged , Carcinoma, Hepatocellular/diagnosis , Cell Differentiation , Diffusion Magnetic Resonance Imaging/methods , Female , Humans , Liver Neoplasms/diagnosis , Male , Middle Aged , Retrospective Studies
14.
J Comput Assist Tomogr ; 33(2): 266-72, 2009.
Article in English | MEDLINE | ID: mdl-19346857

ABSTRACT

PURPOSE: To compare the accuracy of dynamic contrast-enhanced multidetector-row computed tomography (CT) and superparamagnetic iron oxide-enhanced magnetic resonance imaging (MRI) in the evaluation of small hepatic metastases of colorectal carcinoma. MATERIALS AND METHODS: Of 94 patients with colorectal carcinoma analyzed, 76 hepatic metastases (<2 cm) were diagnosed in 17 patients. Superparamagnetic iron oxide (SPIO)-magnetic resonance (precontrast and postcontrast MRI) and dynamic contrast-enhanced multidetector-row CT (dynamic CT [precontrast, arterial, portal-venous, and delayed phase]) were evaluated. The alternative free-response receiver operating characteristic analysis was performed, and the sensitivities and positive predictive values were analyzed. RESULTS: The Az values and sensitivities of portal-venous phase CT, dynamic CT, and SPIO-MRI (0.62/59%, 0.69/61%, and 0.67/61%) were identical. The mean positive predictive value of dynamic CT (82%) was inferior to that of SPIO-MRI (91%). CONCLUSIONS: The diagnostic ability of dynamic CT is identical to that of SPIO-MRI in Az value and sensitivity. Superparamagnetic iron oxide-MRI should be recommended only if an equivocal lesion is detected by dynamic CT.


Subject(s)
Liver Neoplasms/diagnosis , Liver Neoplasms/secondary , Magnetic Resonance Imaging/methods , Aged , Colorectal Neoplasms/pathology , Contrast Media , Dextrans , False Negative Reactions , Female , Ferrosoferric Oxide , Humans , Image Enhancement/methods , Iohexol , Iron , Magnetite Nanoparticles , Middle Aged , Oxides , Predictive Value of Tests , Sensitivity and Specificity , Tomography, X-Ray Computed
15.
J Comput Assist Tomogr ; 32(5): 724-9, 2008.
Article in English | MEDLINE | ID: mdl-18830101

ABSTRACT

PURPOSE: To compare single arterial-phase (SAP) computed tomography (CT) imaging with bolus tracking (BT) with double arterial-phase (DAP) CT imaging for detecting hypervascular hepatocellular carcinoma. MATERIALS AND METHODS: The DAP images were obtained at 25 (DAP-early) and 40 seconds (DAP-late) after the start of contrast material injection. All patients underwent SAP-BT imaging where images were obtained 10 seconds after the CT attenuation value of the aorta reached the threshold value of 120 Hounsfield unit (HU) in 29 (group 120-HU), 160 HU in 30 (group 160-HU), and 200 HU in 32 patients (group 200-HU). Attenuation conspicuity with SAP-BT technique was compared with that with DAP technique using repeated-measures analysis of variance. Attenuation conspicuity and mean scan delays with SAP-BT images obtained with different threshold values were compared using analysis of variance. The sensitivities were compared using McNemar and Fisher exact tests. RESULTS: Within all groups, mean attenuation conspicuity with SAP-BT and DAP-late was significantly higher than that with DAP-early. Regarding SAP-BT, mean attenuation conspicuity in group 200-HU (42 +/- 18 HU) was significantly higher than those in groups 120-HU (23 +/- 11 HU) and 160-HU (25 +/- 11 HU). Mean scan delays for SAP-BT were 24.2 seconds in group-120 HU, 26.8 seconds in group-160 HU, and 31.1 seconds in group-200 HU (P < 0.001). The mean sensitivity with SAP-BT technique in group 200-HU (92.7%) was significantly higher than those in groups 120-HU (72.4%) and 160-HU (71.1%). CONCLUSIONS: Single arterial-phase CT scanning with bolus tracking can be effectively used to detect hepatocellular carcinoma when a threshold value of 200 HU is used.


Subject(s)
Carcinoma, Hepatocellular/blood supply , Liver Neoplasms/blood supply , Liver Neoplasms/diagnostic imaging , Tomography, X-Ray Computed/methods , Humans , Sensitivity and Specificity
16.
Biochem Biophys Res Commun ; 368(4): 1007-13, 2008 Apr 18.
Article in English | MEDLINE | ID: mdl-18275844

ABSTRACT

The inducible transcription factor NF-kappaB regulates divergent signaling pathways including inflammatory response and cancer development. Selective inhibitors for NF-kappaB signaling are potentially useful for treatment of inflammation and cancer. NF-kappaB is canonically activated by preferential disposal of its inhibitory protein; IkappaB, which suppresses the nuclear translocation of NF-kappaB. IkappaBalpha (a major member of IkappaB family proteins) is phosphorylated with an IkappaB kinase (IKK) and subsequently polyubiquitylated by SCF(betaTrCP1) ubiquitin-ligase in the presence of E1 and E2 prior to proteasomal degradation. Here, we describe a novel inhibitor termed GS143, which suppressed IkappaBalpha ubiquitylation, but not IkappaBalpha phosphorylation, MDM2-directed p53 ubiquitylation, and proteasome activity in vitro. GS143 markedly suppressed the destruction of IkappaBalpha stimulated by TNFalpha and a set of downstream responses coupled to NF-kappaB signaling but not those of p53 and beta-catenin in vivo. Our results indicate that GS143 serves as an effective inhibitor of multiple pathways served by NF-kappaB signaling.


Subject(s)
Benzoates/pharmacology , NF-kappa B/antagonists & inhibitors , Pyrazoles/pharmacology , Signal Transduction/drug effects , Fluorescence Resonance Energy Transfer , I-kappa B Proteins/antagonists & inhibitors , NF-KappaB Inhibitor alpha , Reproducibility of Results , Ubiquitin-Protein Ligases/metabolism
17.
AJR Am J Roentgenol ; 188(1): 147-53, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17179357

ABSTRACT

OBJECTIVE: The purpose of this retrospective study was to determine the usefulness of delayed phase imaging for detecting small (< or = 2 cm) hepatocellular carcinomas (HCCs) in patients with liver cirrhosis. MATERIALS AND METHODS: Triphasic (arterial, portal venous, and delayed phases) dynamic CT was performed in 33 patients with 48 HCCs proven histopathologically and in 65 control subjects. Arterial, portal venous, and delayed phase images were obtained 30 seconds, 68-70 seconds, and 5 minutes after the start of contrast material injection, respectively. Three blinded observers reviewed the images independently and evaluated tumor attenuation. Diagnostic performance for the combination of phases was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: On arterial phase images, 28 of the 48 HCCs were hyperattenuating, nine were isoattenuating, and 11 were hypoattenuating. On portal venous phase images, three tumors were hyperattenuating, 17 were isoattenuating, and 28 were hypoattenuating. On delayed phase images, five tumors were isoattenuating, and 43 were hypoattenuating. The mean sensitivity for the combination of arterial and portal venous phase imaging was 86.8%, that for the combination of arterial and delayed phase imaging was 90.3%, and that for the combination of all three phase imaging was 93.8%. The area underneath composite ROC curve (A(Z)) for the combination of all three phase imaging (A(Z) = 0.940) was significantly higher than that for the combination of arterial and portal venous phase imaging (A(Z) = 0.917) and for the combination of arterial and delayed phase imaging (A(Z) = 0.922). CONCLUSION: Delayed phase imaging is useful for detecting small HCCs and should be included in dynamic CT examinations of patients with liver cirrhosis.


Subject(s)
Algorithms , Carcinoma, Hepatocellular/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Radiographic Image Enhancement/methods , Radiographic Image Interpretation, Computer-Assisted/methods , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Time Factors
18.
AJR Am J Roentgenol ; 187(6): 1513-20, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17114545

ABSTRACT

OBJECTIVE: The objective of our study was to evaluate the individual contributions of arterial, pancreatic parenchymal, and portal venous phase (PVP) images and the utility of coronal and sagittal multiplanar reformatted (MPR) images in the assessment of pancreatic adenocarcinoma using triple-phase MDCT. MATERIALS AND METHODS: Thirty-one patients with and 35 patients without pancreatic adenocarcinoma underwent triple-phase MDCT. Three radiologists independently attempted to detect pancreatic adenocarcinoma and assess local extension using the MDCT images in five sessions. The first three sessions involved sets of images obtained in arterial phase, pancreatic parenchymal phase, and PVP separately and respectively. In the fourth session, a combination of axial images from all phases was evaluated. During the fifth session, radiologists had access to coronal and sagittal MPR images together with the axial images obtained in all phases. Results were compared with surgical findings using receiver operating characteristic (ROC) analysis and kappa statistics. RESULTS: Regarding tumor detection, the image set composed of coronal and sagittal MPR images and of axial images obtained in all phases had a significantly higher value for the area under the ROC curve (A(Z), 0.98 +/- 0.01) than the other image sets and yielded the highest sensitivity (93.5%). The sensitivity of the arterial phase image set (80.6%) was significantly lower than that of all other image sets. Whereas the image set composed of coronal and sagittal MPR images and axial images obtained in all phases yielded the highest kappa values for all local extension factors evaluated, the image set composed of only arterial phase images yielded the lowest kappa values for almost all of the factors. CONCLUSION: A combination of pancreatic parenchymal phase and PVP imaging is necessary and efficient for the assessment of pancreatic adenocarcinoma. The addition of coronal and sagittal MPR images increased the performance of MDCT, especially in the evaluation of local extension.


Subject(s)
Adenocarcinoma/diagnostic imaging , Pancreatic Neoplasms/diagnostic imaging , Tomography, X-Ray Computed/methods , Aged , Female , Humans , Male , Middle Aged , Observer Variation , Retrospective Studies , Sensitivity and Specificity
19.
Radiat Med ; 24(6): 438-44, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16958425

ABSTRACT

PURPOSE: The aim of this study was to determine the validity of the hepatic apparent diffusion coefficient (ADC) measurement. The influence of differences in measured location and administration of Buscopan (hyoscine butylbromide) for ADC were assessed. MATERIALS AND METHODS: SENSE-DWI (b = 0, 500) was obtained before and after Buscopan administration to 30 patients suspected of having a liver tumor. In this sequence, respiration gating was employed, but cardiac triggering was not. ADC measurement was performed in the hepatic parenchyma of both right and left lobes in selected slices. A statistical analysis was performed to estimate the correlation among ADC, measured location, Buscopan, and pulse rate. The images were visually evaluated to categorize the subcardiac signal loss in the left lobe. RESULTS: The ADC showed higher values in the left lobe than in the right lobe in both pre- and postloaded studies (P < 0.001). In a comparison between ADCs in the pre- and postloaded studies, the differences were not significant in the left lobe (P = 0.93) or the right lobe (P = 0.41). No correlation was noted between ADCs and the pulse rate. Visual evaluation revealed that the subcardiac signal loss was more prominent in the postloaded study. CONCLUSION: ADC measurement of the left hepatic lobe was far more incorrect than that of the right lobe if cardiac gating was not employed. The administration of Buscopan worsened the image quality of the left lobe and made visual evaluation difficult.


Subject(s)
Diffusion Magnetic Resonance Imaging , Hemangioma/pathology , Liver Neoplasms/pathology , Adult , Aged , Butylscopolammonium Bromide , Colorectal Neoplasms/pathology , Female , Heart Rate/drug effects , Hemangioma/diagnosis , Humans , Image Processing, Computer-Assisted , Japan , Liver Neoplasms/diagnosis , Liver Neoplasms/secondary , Male , Middle Aged , Muscarinic Antagonists , Neoplasm Staging , Reproducibility of Results , Sensitivity and Specificity
20.
AJR Am J Roentgenol ; 186(5): 1413-8, 2006 May.
Article in English | MEDLINE | ID: mdl-16632738

ABSTRACT

OBJECTIVE: The purpose of this study was to assess the effect of two injection rates of contrast material (3 mL/sec and 5 mL/sec) in hepatic arterial dominant phase MDCT for the detection of small (< 2 cm) hepatocellular carcinomas. MATERIALS AND METHODS: The injection rates 3 mL/sec and 5 mL/sec were used prospectively in imaging examinations of patients with the suspected diagnosis of hepatocellular carcinoma. Each group consisted of 30 patients by chance. The group that received injections at 3 mL/sec had 35 hepatocellular carcinoma lesions, and the 5 mL/sec group had 41 lesions. In all patients the dose and concentration of contrast material were 100 mL and 350 mg/mL iodine (total dose of iodine, 35 g). In each patient a mini-test-bolus technique was used with an additional 15 mL of contrast material to determine optimal scan delay after administration of contrast material. Receiver operating characteristic analysis was used to assess diagnostic performance with the two injection rates of contrast material. RESULTS: There were no statistically significant differences between the two groups in regard to area under the curve and sensitivity. These values for the 3 mL/sec group were 0.97 and 28/35 (80%) and for the 5 mL/sec group were 0.96 and 36/41 (88%). However, the specificity and positive predictive values at 3 mL/sec (236/250 [95%] and 28/42 [67%]) were significantly higher than those at 5 mL/sec (227/265 [86%] and 36/73 [49%]) (p < 0.05). These results suggest there were more false-positive findings of contrast-enhanced lesions in cirrhotic livers on hepatic arterial dominant phase images obtained after injection of contrast material at 5 mL/sec than on images obtained after injection at 3 mL/sec. CONCLUSION: In the detection of small hypervascular hepatocellular carcinoma in cirrhotic liver, the risk of false-positive findings of lesions on hepatic arterial dominant phase images is significantly greater with the higher injection rate (5 mL/sec) than with the medium rate (3 mL/sec).


Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Contrast Media/administration & dosage , Liver Neoplasms/diagnostic imaging , Tomography, X-Ray Computed , Adult , Aged , Contrast Media/pharmacology , Female , Humans , Injections , Male , Middle Aged , Prospective Studies , ROC Curve , Time Factors
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