Abstract
Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative pluripotent stem cells present in the bone marrow, peripheral blood, and organ connective tissues. We ...assessed the homing and therapeutic effects of systemically administered nafimestrocel, a clinical-grade human Muse cell-based product, without immunosuppressants in a neonatal hypoxic–ischemic (HI) rat model. HI injury was induced on postnatal day 7 (P7) and was confirmed by T2-weighted magnetic resonance imaging on P10. HI rats received a single dose nafimestrocel (1 × 10
6
cells/body) or Hank’s balanced salt solution (vehicle group) intravenously at either three days (on P10; M3 group) or seven days (on P14; M7 group) after HI insult. Radioisotope experiment demonstrated the homing of chromium-51-labeled nafimestrocel to the both cerebral hemispheres. The cylinder test (M3 and M7 groups) and open-field test (M7 group) showed significant amelioration of paralysis and hyperactivity at five weeks of age compared with those in the vehicle group. Nafimestrocel did not cause adverse events such as death or pathological changes in the lung at ten weeks in the both groups. Nafimestrocel attenuated the production of tumor necrosis factor-α and inducible nitric oxide synthase from activated cultured microglia in vitro. These results demonstrate the potential therapeutic benefits and safety of nafimestrocel.
Blood flow in the hepatic veins and superior vena cava (SVC) reflects right heart filling; however, their Doppler profiles are often not identical, and no studies have compared their diagnostic ...efficacies. We aimed to determine which venous Doppler profile is reliable for detecting elevated right atrial pressure (RAP).
In 193 patients with cardiovascular diseases who underwent cardiac catheterization within 2 d of echocardiography, the hepatic vein systolic filling fraction (HV-SFF) and the ratio of the peak systolic to diastolic forward velocities of the SVC (SVC-S/D) were measured. HV-SFF < 55% and SVC-S/D < 1.9 were regarded as elevated RAP. We also calculated the fibrosis 4 index (FIB-4) as a serum liver fibrosis marker.
HV-SFF and SVC-S/D were feasible in 177 (92%) and 173 (90%) patients, respectively. In the 161 patients in whom both venous Doppler waveforms could be measured, HV-SFF and SVC-S/D were inversely correlated with RAP (r = −0.350, p < 0.001; r = −0.430, p < 0.001, respectively). SVC-S/D > 1.9 showed a significantly higher diagnostic accuracy of RAP elevation compared with HV-SFF < 55% (area under the curve, 0.842 vs. 0.614, p < 0.001). Multivariate analyses showed that both FIB-4 (β = −0.211, p = 0.013) and mean RAP (β = −0.319, p < 0.001) were independent determinants of HV-SFF. In contrast, not FIB-4 but mean RAP (β = −0.471, p < 0.001) was an independent determinant of SVC-S/D. The diagnostic accuracy remained unchanged when HV-SFF < 55% was considered in conjunction with the estimated RAP based on the inferior vena cava morphology. Conversely, SVC-S/D showed an incremental diagnostic value over the estimated RAP.
SVC-S/D enabled a more accurate diagnosis of RAP elevation than HV-SFF.
Reorientational relaxation times and densities of binary mixtures of 4-cyano-4′-pentylbiphenyl (5CB)–triphenylphosphite (TPP) were measured as functions of composition and temperature. The ...reorientational relaxation time was determined from the polarized light scattering spectra by the optical heterodyne technique. The effect of the addition of TPP molecule was discussed in terms of the effective volume of molecular reorientation, which was estimated from the extended Debye–Einstein equation. The excess volumes and partial molar volumes were calculated from the density of the mixtures. The relationship between the reorientational correlation and the partial volume was discussed from the point of view of the local structure of 5CB molecules in the mixtures.
At least four genes involved in DNA mismatch repair (MMR), hMSH2, hMLH1, hPMS1 and hPMS2, have been cloned and characterized. These genes have been demonstrated to be altered in the germline of ...patients with hereditary non-polyposis colorectal cancer (HNPCC). HNPCC is an autosomal dominant disease characterized by a preponderance of proximal colon, young age of onset, increased multiplicity, and improved stage-specific survival. In this study, we examined the expression of hMSH2 protein in sporadic colorectal cancer (CRC). As a result, the frequency of right-sided CRC and multiple CRCs were significantly higher in the patients with hMSH2-negative CRC than in those with hMSH2-positive CRC. The rate of p53 positivity was significantly lower in the hMSH2-negative tumours than that in the hMSH2-positive tumours. The disease-free survival rate tended to be higher in the patients with hMSH2-negative CRC than in the patients with hMSH2-positive CRC. Our findings suggest that both the clinicopathological and biological features of hMSH2-negative sporadic CRC seemed to be similar to those of HNPCC. To clarify the mechanism of carcinogenesis in HNPCC and sporadic CRC, further investigations of genetic alterations caused by MMR genes will be needed.
One monoclonal antibody 115A10 (MAb 5A10) specifically stained a subpopulation of retinal bipolar cells in various vertebrates. In the bullfrog retina, MAb 5A10 stained the large bipolar cells, but ...not the small bipolar cells. Labeling of the living bipolar cells was observed in isolated cell preparation of the frog retina. MAb 5A10 can serve as a cell-specific marker of the bipolar cells.
