Epigenetic memory in induced pluripotent stem cells.

Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment.

Establishment of a normal hematopoietic and leukemia stem cell hierarchy.

Many types of adult tissues, especially for high turnover tissues such as the blood and intestinal system, stand on a hierarchical tissue-specific stem cell system. Tissue-specific stem cells concurrently have self-renewal capacity and potential to give rise to all types of mature cells in their tissue. The differentiation process of the tissue-specific stem cell is successive restriction of these capacities. The first progeny of tissue-specific stem cells are multipotent progenitors (MPPs) that lose long-term self-renewal capacity yet have full lineage potential. MPPs in turn give rise to oligopotent progenitors, which then commit into lineage-restricted progenitors. This hierarchical system enables a lifelong supply of matured functional cells that generally have a short life span and a relatively high turnover rate. In this chapter, we review our findings and other key experiments that have led to the establishment of the current cellular stem and progenitor hierarchy in the blood-forming systems of mice and humans for both normal and leukemic hematopoiesis. We also review select signaling pathways intrinsic to normal hematopoietic and leukemic stem cell populations as well our recent findings elucidating the possible origin of the leukemia stem cell.

[Management of mediastinitis after pediatric cardiac surgery with continuous closed irrigation method].

Two cases are presented as a successful management for mediastinitis with the continuous closed irrigation method after pediatric cardiac surgery. The continuous closed irrigation method has significant advantages over conventional open irrigation method or muscle flap in pediatric cases, because the system is simple to handle and easy to wash out any infectious tissue debris without additional invasive intervention. However, adequate duration of the irrigation and subsequent antibiotic regimen is still unclear. We conclude that the continuous closed irrigation method is an effective management which is applicable to most of mediastinitis cases after pediatric cardiac surgery.

Simultaneous surgery for ischemic heart disease, type A aortic dissection and abdominal aneurysm.

The patient was a 72-year-old male with three-vessel coronary artery disease, chronic dissecting aneurysm of the ascending aorta with moderate aortic regurgitation, and abdominal aortic aneurysm 7 cm in diameter. Because staged procedure seemed to exacerbate the risk due to the remaining lesion, simultaneous procedures (double coronary artery bypass, aortic root remodeling, tube replacement of the ascending aorta and Y-graft replacement of the abdominal aneurysm) were performed. The patient recovered completely without any serious complication.

Surgical management of a penetrated greenfield inferior vena cava filter.

This is a case report of an IVC filter penetration identified during lymph-node dissection for endometrial carcinoma. Although the spread strut put the adjacent abdominal aorta in danger of penetration, surgical removal of the filter could not be performed because there was still an increased risk of pulmonary embolism. Instead of IVC interruption, we used a wrapping technique as a prophylaxis against major bleeding complication due to IVC filter dislocation and recurrent pulmonary embolism.

Bilateral radial arterial T graft and the left thoracotomy approach for second redo coronary artery bypass grafting.

We herein report a case of third coronary artery bypass grafting (CABG) using a bilateral radial artery T graft. There were patent grafts on the anterior aspect of the heart other than the occluded left internal thoracic artery to the left anterior descending (LAD) artery. A T shaped bilateral radial artery conduit was anastomosed from the left subclavian artery to the LAD and first diagonal branch through a left thoracotomy approach. Postoperative angiography demonstrated excellent flow of radial artery conduits. Left thoracotomy with the use of a bilateral radial artery T graft is a useful substitute for anterior re-sternotomy entry in redo CABG.

In our best interest: three necessary shifts for child welfare workers and children.

In contrast to medicine, technology, and other fields, where great advances have been made in the past century, child welfare has yet to reach its full potential. The author, a former youth in care, proposes three practical shifts in child welfare policy and practice, changes that would cost little but would do much to build a better future for children and families: (1) renaming and reclaiming our children; (2) emphasizing communities, not agencies; and (3) valuing principles more than programs. Suggestions for implementing these shifts are highlighted.

Carotid and aortic screening for coronary artery bypass grafting.

BACKGROUND: To identify risk factors for preexisting carotid and aortic disease in coronary artery bypass grafting (CABG), preoperative parameters were analyzed. METHODS: Three-hundred eight consecutive patients undergoing elective isolated CABG were investigated through preoperative duplex scanning of the carotid artery, computed tomography of the chest, and intraoperative ultrasonography of the ascending aorta. RESULTS: Prevalence of carotid stenosis and ascending aortic atherosclerosis was 14.3% (44 of 308) and 30.2% (93 of 308), respectively. Multivariate analysis indicated that significant independent risk factors for carotid stenosis were atherosclerosis of the ascending aorta (p = 0.028, odds ratio [OR] = 2.16), peripheral vascular disease (p = 0.008, OR = 4.08), and history of stroke (p = 0.0004, OR = 3.73). Significant independent risk factors for ascending aortic atherosclerosis were peripheral vascular disease (p = 0.029, OR = 3.05), age older than 60 years (p = 0.009, OR = 2.94), and carotid stenosis (p = 0.018, OR = 2.27). Modifications on the operative procedure for aortic atherosclerosis were carried out in 49 patients. Overall hospital mortality and morbidity for stroke were 0.97% and 0.65%, respectively. CONCLUSIONS: Prevalence of carotid and aortic disease was not low among candidates for CABG. Carotid and aortic screening may help to modify the operative strategy to reduce morbidity of stroke.

Murine peritoneal macrophages induce a novel 60-kDa protein with structural similarity to a tyrosine kinase p56lck-associated protein in response to oxidative stress.

Using differential screening we have cloned a cDNA encoding a novel oxidative stress protein designated A170 from murine peritoneal macrophages. It has a Zn-finger domain, a PEST domain and several potential phosphorylation sites for kinases. Treatments with oxidative stress agents such as diethyl maleate and paraquat increased a 2.0-kilobase A170 mRNA about twofold in the macrophages after 12 hours in culture. However, H2O2 or glucose/glucose oxidase did not increase the level of the A170 mRNA. Using an A170-specific antibody we have detected in the macrophages a 60-kDa protein that was induced 5 to 10 hours after the addition of the oxidative stress agents. A search of sequence databases revealed that the A170 protein is roughly 90% identical to a human protein that binds to the Src homology 2 domain of the T-cell-specific tyrosine kinase p56lck. These features suggest that the A170 protein plays a significant role in oxidative stress-responsive signal transduction in macrophages.

A New Oleanic Acid Derivative from Securinega tinctoria.

The triterpenoid constituents of the chloroform extract of previously defatted material of the stems of SECURINEGA TINCTORIA were examined and, besides beta-sitosterol beta- D-glucopyranoside, a new oleanolic acid derivative was isolated and identified as 3beta( P-hydroxy- TRANS-cinnamoyloxy)olean-12-en-28-oicacid.