OCT で検出された冠動脈のlipid-richプラークに対する至適薬物療法施行後の臨床経過

Background: The aim of this study was to evaluate optical coherence tomography (OCT)-detected lipid-rich coronary plaques (LRCPs) with coronary computed tomography angiography (CCTA) 10 months after optimal medical therapy (OMT). Methods and Results: Baseline OCT detected 28 LRCPs in non-culprit lesions. High-risk plaque features (HRPFs), such as positive remodeling, very low attenuation plaques, napkin-ring sign, and spotty calcification, were observed in 67.9%, 67.9%, 21.4%, and 64.3% of LRCPs, respectively, at the 10-month follow-up CCTA. Lesions with ≥3 HRPFs were defined as high-risk LRCPs (n=12); the remaining were defined as low-risk LRCPs (n=16). The maximum lipid arc on baseline OCT was larger in high- than low-risk LRCPs (221±62° vs. 179±44°, respectively; P=0.04). Receiver operating characteristic curve analysis indicated that a maximum lipid arc >154° on baseline OCT was the optimal cut-off value to predict high-risk LRCPs 10 months after OMT. Patients with high-risk LRCPs had worse clinical outcomes, defined as a composite of cardiac death, target lesion-related myocardial infarction, and target lesion-related revascularization, during follow-up than those with low-risk LRCPs (33.3% vs. 0%; P=0.01). Conclusions: A high-risk LRCP at follow-up CCTA was correlated with a larger maximum lipid arc on baseline OCT. Further aggressive treatment for patients with large LRCPs may reduce vulnerable plaque features and prevent future cardiac events.博士（医学）・甲第869号・令和5年3月15

Comprehensive genomic characterization of five canine lymphoid tumor cell lines

Abstract Background Leukemia/lymphoma cell lines have been critical in the investigation of the pathogenesis and therapy of hematological malignancies. While human LL cell lines have generally been found to recapitulate the primary tumors from which they were derived, appropriate characterization including cytogenetic and transcriptional assessment is crucial for assessing their clinical predictive value. Results In the following study, five canine LL cell lines, CLBL-1, Ema, TL-1 (Nody-1), UL-1, and 3132, were characterized using extensive immunophenotyping, karyotypic analysis, oligonucleotide array comparative genomic hybridization (oaCGH), and gene expression profiling. Genome-wide DNA copy number data from the cell lines were also directly compared with 299 primary canine round cell tumors to determine whether the cell lines represent primary tumors, and, if so, what subtype each most closely resembled. Conclusions Based on integrated analyses, CLBL-1 was classified as B-cell lymphoma, Ema and TL-1 as T-cell lymphoma, and UL-1 as T-cell acute lymphoblastic leukemia. 3132, originally classified as a B-cell lymphoma, was reclassified as a histiocytic sarcoma based on characteristic cytogenomic properties. In combination, these data begin to elucidate the clinical predictive value of these cell lines which will enhance the appropriate selection of in vitro models for future studies of canine hematological malignancies

A Novel Extraction Method of Fetal Electrocardiogram From the Composite Abdominal Signal

科研費報告書収録論文(課題番号:18390306/研究代表者:木村芳孝/多電極母体腹壁誘導胎児心電図による全週数型胎児心筋虚血モニタリングの基礎研究

An investigation of the differential therapeutic effects of romosozumab on postmenopausal osteoporosis patients with or without rheumatoid arthritis complications: a case–control study

The version of record of this article, first published in Osteoporosis International, is available online at Publisher’s website: https://doi.org/10.1007/s00198-024-07019-2Summary: The impact of ROMO on the width of anabolic windows and the increase in BMD was reduced in the RA group compared to the non-RA group, and this reduction was associated with correlations to RA-related factors. Purpose: To investigate the effects of romosozumab (ROMO) in postmenopausal osteoporosis, with and without comorbid rheumatoid arthritis (RA). Methods: In this retrospective, case-controlled, multicenter study, 171 postmenopausal patients who did not receive oral glucocorticoid, comprising 59 in the RA group and 121 in the non-RA group, received uninterrupted ROMO treatment for 12 months. Propensity score matching was employed to ensure comparability in clinical backgrounds, resulting in 41 patients in each group. Baseline characteristics were as follows: overall (mean age, 76.3 years; T-score of lumbar spine (LS), − 3.0; 45.1% were treatment-naive for osteoporosis); RA group (anti-cyclic citrullinated peptide antibody (ACPA) positivity, 80.5%; titer, 206.2 U/ml; clinical disease activity index (CDAI), 13.6; health assessment questionnaire disability index (HAQ-DI), 0.9). Bone mineral density (BMD) and serum bone turnover markers were monitored over a 12-month period. Results: The rate of increase in the bone formation marker, PINP, and the rates of decrease in the bone resorption marker, TRACP-5b, exhibited a trend toward smaller changes in the RA group compared to the non-RA group, implying a smaller anabolic window. After 12 months, the RA group displayed lower BMD increases in the LS (9.1% vs. 12.6%; P = 0.013) and total hip (2.4% vs. 4.8%; P = 0.025) compared to the non-RA group. Multiple regression analysis in the all RA group (n = 59) for the association between RA-specific factors and 12-month BMD changes revealed negative correlations between ACPA titer and LS BMD and between HAQ-DI and femoral neck BMD. Conclusions: The efficacy of ROMO may be attenuated by RA-related factors

Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomyinduced osteoporosis in mice

NF-κB is a transcription factor that is activated with aging. It plays a key role in the development of osteoporosis by promoting osteoclast differentiation and inhibiting osteoblast differentiation. In this study, we developed a small anti-NF-κB peptide called 6A-8R from a nuclear acidic protein (also known as macromolecular translocation inhibitor II, Zn2+-binding protein, or parathymosin) that inhibits transcriptional activity of NF-κB without altering its nuclear translocation and binding to DNA. Intraperitoneal injection of 6A-8R attenuated ovariectomy-induced osteoporosis in mice by inhibiting osteoclast differentiation, promoting osteoblast differentiation, and inhibiting sclerostin production by osteocytes in vivo with no apparent side effects. Conversely, in vitro, 6A-8R inhibited osteoclast differentiation by inhibiting NF-κB transcriptional activity, promoted osteoblast differentiation by promoting Smad1 phosphorylation, and inhibited sclerostin expression in osteocytes by inhibiting myocyte enhancer factors 2C and 2D. These findings suggest that 6A-8R has the potential to be an antiosteoporotic therapeutic agent with uncoupling properties.Takami K., Okamoto K., Etani Y., et al. Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomyinduced osteoporosis in mice. JCI Insight 8, e171962 (2023); https://doi.org/10.1172/jci.insight.171962

Gas Motion Study of Lya Emitters at z~2 Using UV and Optical Spectral Lines

We present the results of Magellan/MMIRS and Keck/NIRSPEC spectroscopy for five Lya emitters (LAEs) at z=2.2 for which high-resolution FUV spectra from Magellan/MagE are available. We detect nebular emission lines including Ha on the individual basis and low-ionization interstellar (LIS) absorption lines in a stacked FUV spectrum, and measure average offset velocities of the Lya line, Delta_v_Lya, and LIS absorption lines, Delta_v_abs, with respect to the systemic velocity defined by the nebular lines. For a sample of eight z~2-3 LAEs without AGN from our study and the literature, we obtain Delta_v_Lya = 175+/-35 km s^{-1}, which is significantly smaller than that of Lyman-break Galaxies (LBGs), Delta_v_Lya=400 km s^{-1}. The stacked FUV spectrum gives Delta_v_abs = -179 +/- 73 km s^{-1}, comparable to that of LBGs. These positive Delta_v_Lya and negative Delta_v_abs suggest that LAEs also have outflows. In contrast to LBGs, however, the LAEs' Delta_v_Lya is as small as |Delta_v_abs|, suggesting low neutral hydrogen column densities. Such a low column density with a small number of resonant scattering may cause the observed strong Lya emission of LAEs. We find an anti-correlation between Lya equivalent width (EW) and Delta_v_Lya in a compilation of LAE and LBG samples. Although its physical origin is not clear, this anti-correlation result appears to challenge the hypothesis that a strong outflow, by means of a reduced number of resonant scattering, produces a large EW. If LAEs at z>6 have similarly small Delta_v_Lya values, constraints on the reionization history derived from the Lya transmissivity may need to be revised.Comment: 15 pages, 13 figures, 7 tables. Accepted for publication in Ap

Effects of mosapride on motility of the small intestine and caecum in normal horses after jejunocaecostomy

The purpose of the present study was to evaluate the prokinetic effects of mosapride with non-invasive assessment of myoelectrical activity in the small intestine and caecum of healthy horses after jejunocaecostomy. Six horses underwent celiotomy and jejunocaecostomy, and were treated with mosapride (treated group) at 1.5 mg/kg per osos once daily for 5 days after surgery. The other six horses did not receive treatment and were used as controls (non-treated group). The electrointestinography (EIG) maximum amplitude was used to measure intestinal motility. Motility significantly decreased following surgery. In the treated group, the EIG maximum amplitude of the small intestine was significantly higher than in the controls from day 6~31 after treatment. These findings clearly indicate that mosapride could overcome the decline of intestinal motility after jejunocaecostomy in normal horses

Promoting effect of basic fibroblast growth factor in synovial mesenchymal stem cell-based cartilage regeneration

Synovial mesenchymal stem cell (SMSC) is the promising cell source of cartilage regeneration but has several issues to overcome such as limited cell proliferation and heterogeneity of cartilage regeneration ability. Previous reports demonstrated that basic fibroblast growth factor (bFGF) can promote proliferation and cartilage differentiation potential of MSCs in vitro, although no reports show its beneficial effect in vivo. The purpose of this study is to investigate the promoting effect of bFGF on cartilage regeneration using human SMSC in vivo. SMSCs were cultured with or without bFGF in a growth medium, and 2 × 105 cells were aggregated to form a synovial pellet. Synovial pellets were implanted into osteochondral defects induced in the femoral trochlea of severe combined immunodeficient mice, and histological evaluation was performed after eight weeks. The presence of implanted SMSCs was confirmed by the observation of human vimentin immunostaining-positive cells. Interestingly, broad lacunae structures and cartilage substrate stained by Safranin-O were observed only in the bFGF (+) group. The bFGF (+) group had significantly higher O’Driscoll scores in the cartilage repair than the bFGF (−) group. The addition of bFGF to SMSC growth culture may be a useful treatment option to promote cartilage regeneration in vivo.Okamura G., Ebina K., Hirao M., et al. Promoting effect of basic fibroblast growth factor in synovial mesenchymal stem cell-based cartilage regeneration. International Journal of Molecular Sciences, 22, 1, 1. https://doi.org/10.3390/ijms22010300