Growth of donor-derived dendritic cells from the bone marrow of murine liver auograft recipients in response to granulocyte/macrophage colony-stimulating factor

Allografts of the liver, which has a comparatively heavy leukocyte content compared with other vascularized organs, are accepted permanently across major histocompatibility complex barriers in many murine strain combinations without immunosuppressive therapy. It has been postulated that this inherent tolerogenicity of the liver may be a consequence of the migration and perpetuation within host lymphoid tissues of potentially tolerogenic donor-derived ("chimeric") leukocytes, in particular, the precursors of chimeric dendritic cells (DC). In this study, we have used granulocyte/macrophage colony-stimulating factor to induce the propagation of progenitors that give rise to DC (CD45+, CDllc+, 33D1+, nonlymphoid dendritic cell 145 +, major histocompatibility complex class II+, B7-1+) in li-tuid cultures of murine bone marrow cells. Using this technique, together with immunocytochemical and molecular methods, we show that, in addition to cells expressing female host (C3H) phenotype (H-2Kk+; I-E+; Y chromosome-), a minor population of male donor (B10)-derived cells (H-2Kb+; I-A+; Y chromosome+) can also be grown in 10-d DC cultures from the bone marrow of liver allograft recipients 14 d after transplant. Highly purified nonlymphoid dendritic cell 145+ DC sorted from these bone marrow-derived cell cultures were shown to comprise ~1-10% cells of donor origin (Y chromosome +) by polymerase chain reaction analysis. In addition, sorted DC stimulated naive, recipient strain T lymphocytes in primary mixed leukocyte cultures. Evidence was also obtained for the growth of donor-derived cells from the spleen but not the thymus. In contrast, donor ceils could not be propagated from the bone marrow or other lymphoid tissues of nonimmunosuppressed C3H mice rejecting cardiac allografrs from the same donor strain (B10). These findings provide a basis for the establishment and perpetuation of cell chimerism after organ transplantation. © 1995, Rockefeller University Press., All rights reserved

On A Simple Method For Analyzing Multivariate Survival Data Using Sample Survey Methods

A simple technique is illustrated for analyzing multivariate survival data. The data situation arises when an individual records multiple survival events, or when individuals recording single survival events are grouped into clusters. Past work has focused on developing new methods to handle such data. Here, we use a connection between Poisson regression and survival modeling and a cluster sampling approach to adjust the variance estimates. The approach requires parametric assumption for the marginal hazard function, but avoids specification of a joint multivariate survival distribution. A simulation study demonstrates the proposed approach is a competing method of recent developed marginal approaches in the literature

Robust Estimation Of Multivariate Failure Data With Time-Modulated Frailty

A time-modulated frailty model is proposed for analyzing multivariate failure data. The effect of frailties, which may not be constant over time, is discussed. We assume a parametric model for the baseline hazard, but avoid the parametric assumption for the frailty distribution. The well-known connection between survival times and Poisson regression model is used. The parameters of interest are estimated by generalized estimating equations (GEE) or by penalized GEE. Simulation studies show that the procedure is successful to detect the effect of time-modulated frailty. The method is also applied to a placebo controlled randomized clinical trial of gamma interferon, a study of chronic granulomatous disease (CGD)

Estradiol regulates miR-135b and mismatch repair gene expressions via estrogen receptor-β in colorectal cells.

Estrogen has anti-colorectal cancer effects which are thought to be mediated by mismatch repair gene (MMR) activity. Estrogen receptor (ER) expression is associated with microRNA (miRNA) expression in ER-positive tumors. However, studies of direct link between estrogen (especially estradiol E2), miRNA expression, and MMR in colorectal cancer (CRC) have not been done. In this study, we first evaluated the effects of estradiol (E2) and its antagonist ICI182,780 on the expression of miRNAs (miR-31, miR-155 and miR-135b) using COLO205, SW480 and MCF-7 cell lines, followed by examining the association of tissue miRNA expression and serum E2 levels using samples collected from 18 colorectal cancer patients. E2 inhibited the expressions of miRNAs in COLO205 cells, which could be reversed by E2 antagonist ICI 182.780. The expression of miR-135b was inversely correlated with serum E2 level and ER-β mRNA expression in CRC patients' cancer tissues. There were significant correlations between serum E2 level and expression of ER-β, miR-135b, and MMR in colon cancer tissue. This study suggests that the effects of estrogen on MMR function may be related to regulating miRNA expression via ER-β, which may be the basis for the anti-cancer effect in colorectal cells