Hepatocyte growth factor prevents lupus nephritis in a murine lupus model of chronic graft-versus-host disease

Chronic graft-versus-host disease (GVHD) induced in (C57BL/6 × DBA/2) F1 (BDF1) mice by the injection of DBA/2 mouse spleen cells represents histopathological changes associated with systemic lupus erythematosus (SLE), primary biliary cirrhosis (PBC) and Sjogren's syndrome (SS), as indicated by glomerulonephritis, lymphocyte infiltration into the periportal area of the liver and salivary glands. We determined the therapeutic effect of hepatocyte growth factor (HGF) gene transfection on lupus using this chronic GVHD model. Chronic GVHD mice were injected in the gluteal muscle with either HVJ liposomes containing 8 μg of the human HGF expression vector (HGF-HVJ liposomes) or mock vector (untreated control). Gene transfer was repeated at 2-week intervals during 12 weeks. HGF gene transfection effectively prevented the proteinuria and histopathological changes associated with glomerulonephritis. While liver and salivary gland sections from untreated GVHD mice showed prominent PBC- and SS-like changes, HGF gene transfection reduced these histopathological changes. HGF gene transfection greatly reduced the number of splenic B cells, host B cell major histocompatibility complex class II expression, and serum levels of IgG and anti-DNA antibodies. IL-4 mRNA expression in the spleen, liver, and kidneys was significantly decreased by HGF gene transfection. CD28 expression on DBA/2 CD4+ T cells was decreased by the addition of recombinant HGF in vitro. Furthermore, IL-4 production by DBA/2 CD4+ T cells stimulated by irradiated BDF1 dendritic cells was significantly inhibited by the addition of recombinant HGF in vitro. These results suggest that HGF gene transfection inhibited T helper 2 immune responses and reduced lupus nephritis, autoimmune sialoadenitis, and cholangitis in chronic GVHD mice. HGF may represent a novel strategy for the treatment of SLE, SS and PBC

Scintigraphic studies on the etiology of Ampulla Cardiomyopathy

SummaryBackgroundAlthough there are many reports on Ampulla Cardiomyopathy, its etiologic mechanisms are not well known.AimEtiology of Ampulla Cardiomyopathy was investigated by myocardial scintigraphy with various nuclear tracers.Subjects and methodsIn nine patients with Ampulla Cardiomyopathy, myocardial scintigraphy was performed at acute, subacute and chronic phases. Total defect score (TDS) of tallium-201 (Tl) or technetrium-99m sestamibi (MIBI) myocardial perfusion and iodine-123-beta-methyl-p-iodophenyl penta-decanoic acid (BMIPP) scintigraphies was calculated. Cardio-mediastinal ratio (H/M) and washout rate (WR) of early and delayed images of iodine-123-meta-iodobenzylguanidine (MIBG) scintigraphy were also calculated. The patients in whom TDS of myocardial perfusion scintigraphy at acute phase was 0, were classified into group N (n=5) and those with TDS≥1 into group D (n=4).ResultsTDS of BMIPP at acute, subacute and chronic phases was higher in D than in N; 28.8±10.3 vs. 7.2±4.7 (p=0.0039), 15.5±2.1 vs. 1.0±0.8 (p<0.0001) and 2.7±1.2 vs. 0 (p=0.05), respectively. WR of MIBG at acute phase was also higher in D (50.3±5.7% vs. 36.6±10.5%, p=0.05). H/M (dH/M) on the delayed images and WR at chronic phase were not different between the two groups. H/M (eH/M) on the early images was lower in D. Blood noradrenaline (ng/ml) at acute phase was higher in D than in N (1.21±0.55 vs. 0.45±0.33, p<0.05). Left ventricular ejection fraction (LVEF) was decreased in both at acute phase but it was lower in D than in N (48.1±3.7% vs. 69.9±9.7%, p<0.05) at subacute phase.ConclusionThese findings suggest that the etiology of Ampulla Cardiomyopathy is neurologically stunned myocardium induced by coronary microcirculatory disorder.Due to the significant amount of time that was necessary for normalization of wall motion in the D group, myocardial scintigraphy is believed to be also useful in assessment of severity

CpG oligodeoxynucleotides induce strong up-regulation of interleukin 33 via Toll-like receptor 9

We previously reported the strong immunostimulatory effects of a CpG oligodeoxynucleotide (ODN), designated MsST, from the lacZ gene of Streptococcus (S.) thermophilus ATCC19258. Here we show that 24 h of stimulation with MsST in mouse splenocytes and peritoneal macrophages strongly induces expression of interleukin (IL)-33, a cytokine in the IL-1 superfamily. Other IL-1 superfamily members, including IL-1 alpha, IL-1 beta and IL-18, are down-regulated after 24 h of stimulation of MsST. We also found that MsST-induced IL-33 mRNA expression is inhibited by the suppressive ODN A151, which can inhibit Toll-like receptor 9 (TLR9)-mediated responses. This is the first report to show that IL-33 can be induced by CpG ODNs. The strong induction of IL-33 by MsST suggests that it may be a potential therapeutic ODN for the treatment of inflammatory disease. The presence of a strong CpG ODN in S. thermophilus also suggests that the bacterium may be a good candidate as a starter culture for the development of new physiologically functional foods.ArticleBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 394(1):81-86 (2010)journal articl

Ionization States and Plasma Structures of Mixed-morphology SNRs Observed with ASCA

We present the results of a systematic study using ASCA of the ionization state for six ``mixed-morphology'' supernova emnants (MMSNRs): IC 443, W49B, W28, W44, 3C391, and Kes 27. MMSNRs show centrally filled thermal X-ray emission, which contrasts to shell-like radio morphology, a set of haracteristics at odds with the standard model of SNR evolution (e.g., the Sedov model). We have therefore studied the evolution of the MMSNRs from the ionization conditions inferred from the X-ray spectra, independent of X-ray morphology. We find highly ionized plasmas approaching ionization equilibrium in all the mmsnrs. The degree of ionization is systematically higher than the plasma usually seen in shell-like SNRs. Radial temperature gradients are also observed in five remnants, with cooler plasma toward the limb. In IC 443 and W49B, we find a plasma structure consistent with shell-like SNRs, suggesting that at least some MMSNRs have experienced similar evolution to shell-like SNRs. In addition to the results above, we have discovered an ``overionized'' ionization state in W49B, in addition to that previously found in IC 443. Thermal conduction can cause the hot interior plasma to become overionized by reducing the temperature and density gradients, leading to an interior density increase and temperature decrease. Therefore, we suggest that the ``center-filled'' X-ray morphology develops as the result of thermal conduction, and should arise in all SNRs. This is consistent with the results that MMSNRs are near collisional ionization equilibrium since the conduction timescale is roughly similar to the ionization timescale. Hence, we conclude that MMSNRs are those that have evolved over$\sim10^4$ yr. We call this phase as the ``conduction phase.''Comment: 34 pages, 20 figures, 9 tables, accepted for publication in The Astrophysical Journa

再灌流後急性心筋梗塞患者におけるリバースリモデリングと非造影T1低信号梗塞コア

Background: Non-contrast T1 hypointense infarct cores (ICs) within infarcted myocardium detected using cardiac magnetic resonance imaging (CMR) T1 mapping may help assess the severity of left ventricular (LV) injury. However, because the relationship of ICs with chronic LV reverse remodeling (LVRR) is unknown, this study aimed to clarify it. Methods and Results: We enrolled patients with reperfused AMI who underwent baseline CMR on day-7 post-primary percutaneous coronary intervention (n=109) and 12-month follow-up CMR (n=94). Correlations between ICs and chronic LVRR (end-systolic volume decrease ≥15% at 12-month follow-up from baseline CMR) were investigated. We detected 52 (47.7%) ICs on baseline CMR by non-contrast-T1 mapping. LVRR was found in 52.1% of patients with reperfused AMI at 12-month follow-up. Patients with ICs demonstrated higher peak creatine kinase levels, higher B-type natriuretic peptide levels at discharge, lower LV ejection fraction at discharge, and lower incidence of LVRR than those without ICs (26.5% vs. 73.3%, P<0.001) at follow-up. Multivariate logistic regression analysis showed that the presence of ICs was an independent and the strongest negative predictor for LVRR at 12-month followup (hazard ratio: 0.087, 95% confidence interval: 0.017–0.459, P=0.004). Peak creatine kinase levels, native T1 values at myocardial edema, and myocardial salvaged indices also correlated with ICs. Conclusions: ICs detected by non-contrast-T1 mapping with 3.0-T CMR were an independent negative predictor of LVRR in patients with reperfused AMI.博士（医学）・乙第1529号・令和5年3月15

Five-minute resolved spatial distribution of radiocesium in sea sediment derived from the Fukushima Dai-ichi Nuclear Power Plant

AbstractThe spatial distributions of radiocesium concentration in sea sediment to a core depth of 14 cm were investigated in the offshore region from the Fukushima Prefecture to the northern part of the Ibaraki Prefecture in February and July 2012, at a spatial resolution of 5 min of latitude and longitude. The concentrations in the area south of the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) were generally higher than those in the area north of it. In the southern area, a band of especially high concentration with a width about 20 km was present in the region shallower than 100 m, and a narrow minimal concentration band was found along the 200-m isobaths. In more than half of all cases, the vertical core profiles of radiocesium concentration generally showed an exponential decreasing trend with depth. However, in the area north of the FDNPP, where the radiocesium concentrations tended to be very low, radiocesium concentrations that had similar or larger magnitude compared with those of the most-surface layer were often found in deeper layers. Relatively good correlations were found between radiocesium concentrations and grain sizes of the most-surface sediment. The vertical profile of radiocesium concentration also had a relationship with grain size. In other case, the radiocesium concentration in the sediment seems to have had a dependence on the radiocesium concentration in bottom seawater, suggesting that the quantity of radiocesium supplied and the grain size were major factors determining the spatial distribution pattern of the radiocesium concentration after the FDNPP accident