Crohn disease: magnetic resonance enterocolonography features of endoscopic ulcer stages reclassified with the healing process and the relationships to prognoses.

PURPOSE: This study aimed to compare magnetic resonance enterocolonography (MREC) features among the endoscopic ulcer stages reclassified to include healing ulcers and to assess the prognoses in Crohn disease (CD). METHODS: Altogether, 89 consecutive patients with CD who had undergone MREC and ileocolonoscopy or balloon-assisted enteroscopy were retrospectively studied. Patients were reclassified into 38 patients with no deep ulcer, seven with healing deep ulcer, and 44 with active deep ulcer stage. MREC score derived from a 5-point MR classification and MR index of activity (MaRIA) were evaluated, and patients were followed-up. The primary endpoint was hospitalization. RESULTS: Healing deep ulcers had higher values in MREC score and MaRIA than no deep ulcers (p < 0.001), and lower values than active deep ulcers (p < 0.001). The 5-year cumulative rates of hospitalization for no deep ulcer, healing deep ulcer, and active deep ulcers were 24.9, 0, and 52.4% (p < 0.05), respectively. MREC score or MaRIA-positive patients had a higher 5-year cumulative rate of hospitalization than the negative patients (p < 0.01 and p < 0.05, respectively). CONCLUSION: MREC could reflect the healing stages, and the identification was revealed to be important because of the good prognosis. MREC might be useful to predict prognosis of CD.

Prediction of histological grade of hepatocellular carcinoma using quantitative diffusion-weighted MRI: a retrospective multivendor study.

OBJECTIVE: To evaluate the usefulness of quantitative diffusion-weighted (DW) imaging acquired by multivendor magnetic resonance units for predicting grade of hepatocellular carcinoma (HCC). METHODS: 83 patients with 100 histologically diagnosed HCCs who underwent pre-operative liver DW imaging with b = 0 and1000 s mm-2 or b = 0 and800 s mm-2 at any of six institutions were included. Two radiologists independently measured the apparent diffusion coefficient (ADC) of the lesion as well as non-ADC parameters, such as the relative contrast ratio and the contrast-to-noise ratio (CNR) between the lesion and the liver parenchyma on high b-value DW images. The diagnostic performance of the DW parameters in discriminating poorly-differentiated HCCs was compared using receiver operating characteristic (ROC) analysis. RESULTS: The areas under the receiver operating characteristic curves for the CNR (86.4% [95% confidence interval (CI) (77.2-95.6] and 83.9% [95% CI 71.2-96.6] for b = 1000 and 800 s mm-2, respectively] and the relative contrast ratio (85.3% [95% CI 75.5-94.8] and 83.5% [95% CI 70.5-96.4]) tended to be superior to the ADC [71.1% [95% CI (56.9-85.2)] and 75.7% [95% CI (55.1-96.2)]; p < 0.05 for CNR vs ADC for b = 1000 s mm-2, but not significant for other parameters) for discrimination of poorly-differentiated HCCs. CONCLUSION: All DW parameters could discriminate HCC grade. Non-ADC parameters might be more useful than the ADC for predicting poorly-differentiated HCCs. Advances in knowledge: The utility of quantitative DW parameters for predicting HCC grade was demonstrated by using multivendor MR units.

Immunomodulatory Effects of Adipose Tissue-Derived Stem Cells on Concanavalin A-Induced Acute Liver Injury in Mice.

Cell therapy with adipose tissue-derived stem cells (ASCs) is expected to be a candidate for the treatment of fulminant hepatic failure (FHF), which is caused by excessive immune responses. In order to evaluate the therapeutic effects of ASCs on FHF, the in vitro and in vivo immunomodulatory effects of ASCs were examined in detail in the mouse model. The in vitro effects of ASCs were examined by assessing their influence on the proliferation of lymphomononuclear cells (LMCs) stimulated with three kinds of mitogens: phorbol 12-myristate 13-acetate (PMA) plus ionomycin, concanavalin A (ConA), and lipopolysaccharide (LPS). The proliferation of LMCs was efficiently suppressed in a dose-dependent manner by ASCs in the cases of PMA plus ionomycin stimulation and ConA stimulation, but not in the case of LPS stimulation. The in vivo effects of transplanted ASCs were examined in the murine FHF model induced by ConA administration. The ALT levels and histological inflammatory changes in the ConA-administered mice were apparently relieved by the transplantation of ASCs. The analysis of mRNA expression patterns in the livers indicated that the expressions of the cytokines such as Il-6, Il-10, Ifn-γ, and Tnf-α, and the cell surface markers such as Cd3γ, Cd4, Cd8α, Cd11b, and Cd11c were downregulated in the ASC-transplanted mice. The immunomodulatory and therapeutic effects of ASCs were confirmed in the mouse model both in vitro and in vivo. These suggest that the cell therapy with ASCs is beneficial for the treatment of FHF.

Transduction Function of a Magnetic Nanoparticle TMADM for Stem-Cell Imaging with Quantum Dots.

We investigated the transduction function of a cationic dextran hydroxypropyltrimethyl ammonium chloride-coated magnetic iron oxide nanoparticle (TMADM-03) for transducing quantum dots (QDs) into adipose tissue-derived stem cells (ASCs). As a result, the fluorescence intensity of ASCs labeled with QDs using TMADM-03 was much higher than that of QDs only labeling. These data suggest that TMADM-03 can be useful as a transduction agent for QDs in stem-cell imaging.

Labeling and in vivo visualization of transplanted adipose tissue-derived stem cells with safe cadmium-free aqueous ZnS coating of ZnS-AgInS2 nanoparticles.

The facile synthesis of ZnS-AgInS2 (ZAIS) as cadmium-free QDs and their application, mainly in solar cells, has been reported by our groups. In the present study, we investigated the safety and the usefulness for labeling and in vivo imaging of a newly synthesized aqueous ZnS-coated ZAIS (ZnS-ZAIS) carboxylated nanoparticles (ZZC) to stem cells. ZZC shows the strong fluorescence in aqueous solutions such as PBS and cell culture medium, and a complex of ZZC and octa-arginine (R8) peptides (R8-ZZC) can achieve the highly efficient labeling of adipose tissue-derived stem cells (ASCs). The cytotoxicity of R8-ZZC to ASCs was found to be extremely low in comparison to that of CdSe-based QDs, and R8-ZZC was confirmed to have no influence on the proliferation rate or the differentiation ability of ASCs. Moreover, R8-ZZC was not found to induce the production of major inflammatory cytokines (TNF-α, IFN-γ, IL-12p70, IL-6 and MCP-1) in ASCs. Transplanted R8-ZZC-labeled ASCs could be quantitatively detected in the lungs and liver mainly using an in vivo imaging system. In addition, high-speed multiphoton confocal laser microscopy revealed the presence of aggregates of transplanted ASCs at many sites in the lungs, whereas individual ASCs were found to have accumulated in the liver.

Ab Initio Trajectory Study on Triplet Ketene Photodissociation via Statistical Sampling of the Crossing Seam.

Triplet ketene exhibits a steplike structure in the experimentally observed dissociation rate, but its mechanism is still unclear despite many theoretical efforts. A previous surface-hopping simulation at the CASSCF level suggests that nonadiabatic transition from the S0 to T1 states creates the T1 species in a highly nonstatistical manner, which raises the question of whether the use of statistical rate theory is valid in itself for the T1 state. Here, we study this problem by performing ab initio trajectory simulation at the multireference second-order Möller-Plesset perturbation (MRMP) level of theory. Since the MRMP theory is too expensive for such a trajectory calculation, we first construct dual-level potential energy surfaces (PESs) for the S0 and T1 states by calibrating the PESs at the B3LYP level with a limited set of MRMP energies. We then introduce the assumption of vibrational equilibrium on the S0 surface and characterize the S0 → T1 crossing points using the conditional microcanonical distribution on the S0/T1 seam surface. The latter distribution is obtained by running a constrained trajectory on the seam surface by use of an efficient SHAKE-like method. Subsequently, we propagate a number of T1 trajectories from the seam surface to obtain the dissociation rate. The result shows that (i) the S0 → T1 crossing points are localized mainly in the T1 reactant region; (ii) the lifetime on the T1 surface is about 30 ps at the MRMP level, which is 2 orders of magnitude greater than the previous estimate obtained from the surface-hopping simulation at the CASSCF level (∼100 fs); and (iii) the calculated T1 dissociation rate agrees reasonably well with classical transition state theory. These results suggest that the T1 dissociation is rather statistical, given that the T1 trajectories are initiated from the conditional microcanonical distribution on the seam surface.

Quantum mechanical reaction probability of triplet ketene at the multireference second-order perturbation level of theory.

Triplet ketene exhibits a steplike structure in the experimentally observed dissociation rates, but its mechanism is still unknown despite many theoretical efforts in the past decades. In this paper we revisit this problem by quantum mechanically calculating the reaction probability with multireference-based electronic structure theory. Specifically, we first construct an analytical potential energy surface of triplet state by fitting it to about 6000 ab initio energies computed at the multireference second-order Mller-Plesset perturbation (MRMP2) level. We then evaluate the cumulative reaction probability by using the transition state wave packet method together with an adiabatically constrained Hamiltonian. The result shows that the imaginary barrier frequency on the triplet surface is 328i cm-1, which is close to the CCSD(T) result (321i cm-1) but is likely too large for reproducing the experimentally observed steps. Indeed, our calculated reaction probability exhibits no signature of steps, reflecting too strong tunneling effect along the reaction coordinate. Nevertheless, it is emphasized that the flatness of the potential profile in the transition-state region (which governs the degree of tunneling) depends strongly on the level of electronic structure calculation, thus leaving some possibility that the use of more accurate theories might lead to the observed steps. We also demonstrate that the triplet potential surface differs significantly between the CASSCF and MRMP2 results, particularly in the transition-state region. This fact seems to require more attention when studying the "nonadiabatic" scenario for the steps, in which the crossing seam between S0 and T1 surfaces is assumed to play a central role.

Visualization of radiation-induced cell cycle-associated events in tumor cells expressing the fusion protein of Azami Green and the destruction box of human Geminin.

Ionizing radiation (IR) influences cell cycle-associated events in tumor cells. We expressed the fusion protein of Azami Green (AG) and the destruction box plus nuclear localization signal of human Geminin, an inhibitor of DNA replication licensing factor, in oral tumor cells. This approach allowed us to visualize G2 arrest in living cells following irradiation. The combination of time-lapse imaging analysis allowed us to observe the nuclear envelope break down (NEBD) at early M phase, and disappearance of fluorescence (DF) at the end of M phase. The duration from NEBD to DF was not much affected in irradiated cells; however, most of daughter cells harbored double-strand breaks. Complete DF was also observed in cells exhibiting abnormal mitosis or cytokinesis. We conclude that the fluorescent Geminin probe could function as a stable cell cycle indicator irrespective of genome integrity.