Increased Expression of Proliferating Cell Nuclear Antigen in Rejecting Rat Lung Allografts

The aim of this study was to investigate the expression of proliferating cell nuclear antigen (PCNA) as an index of cell proliferation in the Brown Norway (BN) to Lewis (LEW) rat lung allograft model.Following transplantation of BN left lungs into LEW recipients, counts of PCNA-positive cells in the perivascular cellular infiltrate and bronchus-associated lymphoid tissue (BALT) were compared with the histological grade of rejection. Lungs were excised on postoperative days 3 and 5. LEW-to-LEW donor-recipient transplantation was performed as a control. Routinely processed, paraffinembedded sections were selected and stained with PCNA. The PCNA index (% of nuclei positive for PCNA) in the BALT was significantly higher in allograft (19.1%, p < 0.05) compared with isograft (4.2%) at 3 days following transplantation. Similarly, the PCNA index was also greater in the perivascular cellular infiltrates of rejecting lungs (23.9% at 3 days, 31.6% at 5 days). These findings indicate that the cells stimulated by the rejection reaction could be increase the expression of PCNA, and the increasing severity of rejection was paralleled by an increase in the number of PCNA-positive cells. In conclusion, PCNA may be a useful marker of acute cellular rejection in lung allografts

Oxidative Neurodegeneration Is Prevented by UCP0045037, an Allosteric Modulator for the Reduced Form of DJ-1, a Wild-Type of Familial Parkinson’s Disease-Linked PARK7

Although a loss-of-function mutation has been identified in familial Parkinson’s disease PARK7, the wild-type of DJ-1 is known to act as an oxidative stress sensor in neuronal cells. Recently, we identified UCP0045037 as a compound that bound to the reduced form of DJ-1 by in silico virtual screening. In this study, we determined the neuroprotective effects of UCP0045037 against focal cerebral ischemia-induced neurodegeneration in rats. Hydrogen peroxide-induced cell death was significantly inhibited by UCP0045037 in both rat mesencephalic dopaminergic neurons and human normal SH-SY5Y cells. In contrast, DJ-1-knockdown SH-SY5Y cells lost the protective activity of UCP0045037. These results suggest that UCP0045037 interacts with endogenous DJ-1 and produces a neuroprotective response

ヒトハッケツビョウサイボウノRNAタイシャニカンスルケンキュウ

京都大学0048新制・課程博士医学博士甲第1371号医博第443号新制||医||180(附属図書館)3642UT51-48-J9京都大学大学院医学研究科内科系専攻(主査)教授 沼 正作, 教授 早石 修, 教授 脇坂 行一学位規則第5条第1項該当Kyoto UniversityDA