Chapter I. Prognostic impacts of nutritional status on long-term outcome in patients with acute myocardial infarction / Chapter II. The clinical value of the PRECISE-DAPT score in predicting long-term prognosis in patients with acute myocardial infarction

博士（医学）福島県立医科大

オーキシン機能発現制御剤の化学生物学的応用に関する研究

学位の種別:課程博士University of Tokyo(東京大学

Soluble CD26 is inversely Associated with Disease Severity in Patients with Chronic Eosinophilic Pneumonia

Backgrounds: CD26, a multifunctional T cell surface glycoprotein, is a type II transmembrane protein containing only six amino acid residues in its cytoplasmic region. In addition to its membrane form, CD26 exists in plasma in a soluble form (sCD26), which is thought to be the extracellular domain of the molecule cleaved from the cell surface. Recent studies indicated CD26 have an important role in the pathogenesis of asthma, known as Th2 like disease. The function of CD26 in the esosinophlic lung disease is not well understood.Methods: Serum sCD26 was determined by enzyme-linked Immunosorbent assay in patients with acute eosinophilic pneumonia, chronic eosinophilic pneumonia (CEP), and sarcoidosis, and in healthy volunteers, to establish its value for discriminating between disease entities and as marker of disease activity.Results: Soluble CD26 was signifi cantly reduced in CEP and was related to disease severity. In particular, sCD26 was inversely correlated with arterial oxygen tension in CEP.Conclusion: Serum levels of sCD26 might appear to be useful as a new marker of CEP disease activity

Concanavalin A-mediated T cell proliferation is regulated by herpes virus entry mediator costimulatory molecule

T cell activation is regulated by two distinct signals, signals one and two. Concanavalin A (ConA) is an antigen-independent mitogen and functions as signal one inducer, leading T cells to polyclonal proliferation. CD28 is known to be one of major costimulatory receptors and to provide signal two in the ConA-induced T cell proliferation. Here, we have studied the implication of other costimulatory pathways in the ConA-mediated T cell proliferation by using soluble recombinant proteins consisting of an extracellular domain of costimulatory receptors and Fc portion of human IgG. We found that T cell proliferation induced by ConA, but not PMA plus ionomycin or anti-CD3 mAb, is significantly inhibited by herpes virus entry mediator (HVEM)-Ig, even in the presence of CD28 signaling. Moreover, the high concentration of HVEM-Ig molecules almost completely suppressed ConA-mediated T cell proliferation. These results suggest that HVEM might play more important roles than CD28 in ConA-mediated T cell proliferation. © 2013 The Society for In Vitro Biology

Metataxonomic Analysis of the Uterine Microbiota Associated with Low Fertility in Dairy Cows Using Endometrial Tissues Prior to First Artificial Insemination

The deterioration in reproductive performance in association with low fertility leads to significant economic losses on dairy farms. The uterine microbiota has begun to attract attention as a possible cause of unexplained low fertility. We analyzed the uterine microbiota associated with fertility by 16S rRNA gene amplicon sequencing in dairy cows. First, the alpha (Chao1 and Shannon) and beta (unweighted and weighted UniFrac) diversities of 69 cows at four dairy farms that had passed the voluntary waiting period before the first artificial insemination (AI) were analyzed with respect to factors including farm, housing style, feeding management, parity, and AI frequency to conception. Significant differences were observed in the farm, housing style, and feeding management, except parity and AI frequency to conception. The other diversity metrics did not show significant differences in the tested factors. Similar results were obtained for the predicted functional profile. Next, the microbial diversity analysis of 31 cows at a single farm using weighted UniFrac distance matrices revealed a correlation with AI frequency to conception but not with parity. In correlation with AI frequency to conception, the predicted function profile appeared to be slightly modified and a single bacterial taxon, Arcobacter, was detected. The bacterial associations related to fertility were estimated. Considering these, the uterine microbiota in dairy cows can be varied depending on the farm management practices and may become one of the measures for low fertility

Faraday Rotation Measure due to the Intergalactic Magnetic Field II: the Cosmological Contribution

We investigate the Faraday rotation measure (RM) due to the intergalactic magnetic field (IGMF) through the cosmic web up to cosmological distances, using a model IGMF based on turbulence dynamo in the large-scale structure of the universe. By stacking the IGMF and gas density data up to redshift $z=5$ and taking account of the redshift distribution of polarized background radio sources against which the RM is measured, we simulate the sky map of the RM. The contribution from galaxy clusters is subtracted from the map, based on several different criteria of X-ray brightness and temperature. Our findings are as follows. The distribution of RM for radio sources of different redshifts shows that the root-mean-square (rms) value increases with redshift and saturates for z \ga 1. The saturated value is RM$_{\rm rms} \approx$ several ${\rm rad m^{-2}}$. The probability distribution function of $|{\rm RM}|$ follows the lognormal distribution. The power spectrum has a broad plateau over the angular scale of $\sim 1 - 0.1^\circ$ with a peak around $\sim 0.15^\circ$. The second-order structure function has a flat profile in the angular separation of \ga 0.2^\circ. Our results could provide useful insights for surveys to explore the IGMF with the Square Kilometer Array (SKA) and upcoming SKA pathfinders.Comment: To appear in ApJ. Pdf with full resolution figures can be downloaded from http://canopus.cnu.ac.kr/ryu/ar2.pd

Rapid proliferation of activated lymph node CD4+ T cells is achieved by greatly curtailing the duration of gap phases in cell cycle progression

Peripheral T cells are in G0 phase and do not proliferate. When they encounter an antigen, they enter the cell cycle and proliferate in order to initiate an active immune response. Here, we have determined the first two cell cycle times of a leading population of CD4+ T cells stimulated by PMA plus ionomycin in vitro. The first cell cycle began around 10 h after stimulation and took approximately 16 h. Surprisingly, the second cell cycle was extremely rapid and required only 6 h. T cells might have a unique regulatory mechanism to compensate for the shortage of the gap phases in cell cycle progression. This unique feature might be a basis for a quick immune response against pathogens, as it maximizes the rate of proliferation.In Pres

The Rax homeoprotein in Müller glial cells is required for homeostasis maintenance of the postnatal mouse retina

Müller glial cells, which are the most predominant glial subtype in the retina, play multiple important roles, including the maintenance of structural integrity, homeostasis, and physiological functions of the retina. We have previously found that the Rax homeoprotein is expressed in postnatal and mature Müller glial cells in the mouse retina. However, the function of Rax in postnatal and mature Müller glial cells remains to be elucidated. In the current study, we first investigated Rax function in retinal development using retroviral lineage analysis and found that Rax controls the specification of late-born retinal cell types, including Müller glial cells in the postnatal retina. We next generated Rax tamoxifen–induced conditional KO (Rax iCKO) mice, where Rax can be depleted in mTFP-labeled Müller glial cells upon tamoxifen treatment, by crossing Raxflox/flox mice with Rlbp1-CreERT2 mice, which we have produced. Immunohistochemical analysis showed a characteristic of reactive gliosis and enhanced gliosis of Müller glial cells in Rax iCKO retinas under normal and stress conditions, respectively. We performed RNA-seq analysis on mTFP-positive cells purified from the Rax iCKO retina and found significantly reduced expression of suppressor of cytokine signaling-3 (Socs3). Reporter gene assays showed that Rax directly transactivates the Socs3 promoter. We observed decreased expression of Socs3 in Müller glial cells of Rax iCKO retinas by immunostaining. Taken together, the present results suggest that Rax suppresses inflammation in Müller glial cells by transactivating Socs3. This study sheds light on the transcriptional regulatory mechanisms underlying retinal Müller glial cell homeostasis.Yoshimoto T., Chaya T., Varner L.R., et al. The Rax homeoprotein in Müller glial cells is required for homeostasis maintenance of the postnatal mouse retina. Journal of Biological Chemistry 299, 105461 (2023); https://doi.org/10.1016/j.jbc.2023.105461