We tested the hypothesis that oxytocin-induced labor augmented IL-1β-induced/-stimulated lung fluid absorption in preterm guinea pig fetuses. IL-1β was administered subcutaneously daily to timed-pregnant guinea pigs for 3 days with and without simultaneous cortisol synthesis inhibition by metyrapone. At day 3, oxytocin was administered, and fetuses were delivered by abdominal hysterotomy at 61 and by oxytocin-induced birth at 68 days gestation. Delivered fetuses were instilled with isosmolar 5% albumin into the lungs, and lung fluid movement was measured over 1 h by mass balance. Lung fluid absorption was induced in 61-day and stimulated in 68-day gestation lungs by IL-1β. Labor induction by oxytocin augmented IL-1β-induced/- stimulated lung fluid absorption. Metyrapone pretreatment did not affect oxytocin-induced/-stimulated lung fluid absorption, while completely blocking IL-1β-induced/-stimulated fluid absorption. Fetal lung fluid absorption, when present, was always propranolol and amiloride sensitive, suggesting that β-adrenoceptor stimulation and amiloride-sensitive sodium channels were critical for fluid absorption. Epithelial sodium channel and Na-K-ATPase subunit expressions were both increased by IL-1β, but not further by oxytocin. Our results indicate that IL-1β release into the maternal blood circulation positively affects lung maturation due to the IL-1β-induced release of cortisol and thus prepares the lungs for the epinephrine surge associated with labor.

The prevalence of cardiovascular disease in the United States dramatically increases with age. A hallmark feature of the aged myocardium is increased fibrosis resulting in diastolic dysfunction. Moreover, the survival of patients subsequent to a myocardial infarction is inversely related to age because of a certain extent to maladaptive remodeling mediated by cardiac fibroblasts. Our hypothesis is that cardiac fibroblast (CF) dysfunction results in overexpressed TGF-β1 leading to increased cardiac collagen content in the aged population. TGF-β1 stimulates the synthesis of the extracellular matrix proteins, including collagen in the cardiac tissues. The RT-PCR analysis of mRNA expression of TGF-β1 of the CF was increased by 43% in the aged mice as compared to the younger. The stiffness of the left ventricle is expressed with the slope of the end-diastolic pressure-volume relationship parameter, β (mmHg/μL). In a mouse model, we demonstrated that β was 0.30 ± 0.05 in the young as compared to 0.52 ± 0.10 in the aged (p < .05). The ventricular stiffness was associated with the myocardial collagen content; namely, young versus the aged was 9.5 ± 4.0 as compared to 16.4 ± 2.3% of total protein, respectively (p < .05). In conclusion, the gene structure-function relationships support our hypothesis that cardiac fibroblast disregulation contributes to diastolic filling dysfunction in elderly persons. These data provide a potential contributory mechanism for diastolic dysfunction that may be vital in caring for the aged open-heart surgical patient.

Indiana University-Purdue University Indianapolis (IUPUI) / Intervertebral discs (IVD) degenerate earlier than many other musculoskeletal tissues and will continue to degenerate with aging. IVD degeneration affects up to 80 percent of the adult population and is a major contributing factor to low back pain. Anti-sclerostin antibody is an FDA-approved treatment for osteoporosis in postmenopausal women at high-risk for fracture and, as a systemic stimulant of the Wnt/LRP5/β-Catenin signaling pathway, may impact the IVD. Stabilization of β-Catenin in the IVD increases Wnt signaling and is anabolic to the extracellular matrix (ECM), while deletion of β-catenin or LRP5 decreases Wnt signaling and is catabolic to the ECM. Here, we hypothesized that a reduction of Sost would stimulate ECM anabolism. Lumbar and caudal (tail) IVD and vertebrae of Sost KO and WT (wildtype) mice (n=8 each) were harvested at 16 weeks of age and tested by MRI, histology, immunohistochemistry, Western Blot, qPCR, and microCT. Compared to WT, Sost KO reduced sclerostin protein and Sost gene expression. Next, Sost KO increased the hydration of the IVD and the proteoglycan stain in the nucleus pulposus and decreased the expression of genes associated with IVD degeneration, e.g., heat shock proteins. However, deletion of Sost was compensated by less unphosphorylated (active) β-Catenin protein in the cell nucleus, upregulation of Wnt signaling inhibitors Dkk1 and sFRP4, and catabolic ECM gene expression. Consequently, notochordal and early chondrocyte-like cells (CLCs) were replaced by mature CLCs. Overall, Sost deletion increased hydration and proteoglycan protein content, but activated a compensatory suppression of Wnt signaling that may trigger chondrogenesis and may potentially be iatrogenic to the IVD in the long-term.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12816号 / 論医博第2078号 / 新制||医||1004(附属図書館) / 31303 / 京都大学大学院医学研究科医学専攻 / (主査)教授 岩井 一宏, 教授 長田 重一, 教授 川口 義弥 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18162号 / 医博第3882号 / 新制||医||1003(附属図書館) / 31020 / 京都大学大学院医学研究科医学専攻 / (主査)教授 福原 俊一, 教授 佐藤 俊哉, 教授 坂田 隆造 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(人間健康科学) / 甲第18194号 / 人健博第11号 / 新制||人健||1(附属図書館) / 31052 / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 細田 公則, 教授 高桑 徹也, 教授 任 和子 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第18318号 / 農博第2043号 / 新制||農||1021(附属図書館) / 学位論文||H26||N4825(農学部図書室) / 31176 / 京都大学大学院農学研究科地域環境科学専攻 / (主査)教授 本田 与一, 教授 星野 敏, 教授 縄田 栄治 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第19021号 / 農博第2099号 / 新制||農||1030(附属図書館) / 学位論文||H27||N4903(農学部図書室) / 31972 / 京都大学大学院農学研究科応用生物科学専攻 / (主査)教授 久米 新一, 教授 祝前 博明, 教授 廣岡 博之 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19580号 / 医博第4087号 / 新制||医||1013(附属図書館) / 32616 / 京都大学大学院医学研究科医学専攻 / (主査)教授 妹尾 浩, 教授 木村 剛, 教授 柳田 素子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Previously developed Zn decay schemes were limited by a number of factors including low production rates and detector efficiencies making it impossible to place weak transitions. Furthermore, most of the published results are from initial exploratory measurements while subsequent studies in this region either ignored the data obtained from the Zn decays or was not analyzed due to the focus on more exotic nuclei. In the current experiments, a nearly pure beam of the Cu isotope was provided by the Holifield Radioactive Ion Beam Facility (HRIBF) for the study of the Cu -> Zn -> Ga -> Ge β-decay chain using the Low-energy Radioactive Ion Beam Spectroscopy Station (LeRIBSS) setup. The high efficiency of the detector system along with the nearly pure primary beam allowed a detailed study of the γ-ray emission from the decay chain without any member of the decay chain being dominant. The γγ and βγ gamma coincidence data obtained from the experiment was used to develop revised decay schemes in which statistical significance for each observed coincidence peak was determined quantitatively. Presented in this work are updated and expanded decay schemes with new energy levels along with new βeeding intensities and logft values for the Zn -> Ga decays. In each of the Zn decays, a number of new energy levels and transitions have been proposed to the structure of respective Ga isotopes in addition to correcting discrepancies from previous works. The 74Zn β decay now has 29 new γ rays assigned to 74Ga in addition to previous 35 transitions (Winger et al., 1989} depopulating 19 energy states, including 7 new ones. The maximum level energy is increased from previous 1086- to 1555-keV. Similarly, the updated 75Zn decay scheme has its level energy increased from previous (Ekstrom et al., 1986) 3209- to 3924-keV, with addition of 37 new energy levels and 53 new γ rays. New decay scheme for 76Zn is established up to 2603 keV, similar to previous literature (Ekstrom et al.) with addition of 4 new energy levels and total of 5 new γ-ray transitions. In case of 77Zn decay, we proposed the decay scheme up to 3948 keV with addition of 8 new energy levels and 10 new γ-ray transitions.