Misao Satomi

Breast milk macrophages spontaneously produce granulocyte–macrophage colony‐stimulating factor and differentiate into dendritic cells in the presence of exogenous interleukin‐4 alone

Peripheral blood monocytes extravasate and differentiate into tissue macrophages to mediate effective local defence, but how tissue‐specific stimuli and environments may influence their functions remains unknown. Here, we found that peripheral blood monocytes gained the ability to produce granulocyte–macrophage colony‐stimulating factor (GM‐CSF) upon exposure to breast milk and differentiated into CD1+ dendritic cells (DCs) in the presence of exogenous interleukin‐4 (IL‐4) alone. This in vitro observation appeared physiologically relevant since macrophages that were freshly isolated from breast milk were also found to produce GM‐CSF spontaneously. Furthermore, in contrast to peripheral blood monocytes that differentiated into DCs only in the presence of both exogenous GM‐CSF and IL‐4, differentiation of breast milk macrophages into DCs was induced by incubation with exogenous IL‐4 alone. These IL‐4‐stimulated breast milk macrophages were efficient in stimulating T cells, suggesting their potential role in mediating T‐cell‐dependent immune responses in situ. On the other hand, unexpected expression of DC‐SIGN, a DC‐specific receptor for human immunodeficiency virus (HIV), even in unstimulated breast milk macrophages, may favour HIV infection, resulting in an increased risk of mother‐to‐infant vertical transmission of the virus via breast milk. Thus, tissue‐specific development of macrophages is often linked to effective local immunity, but may potentially provide an opportunity for a pathogen to spread and transmit.

Transmission of Macrophage-Tropic HIV-1 by Breast-Milk Macrophages via DC-SIGN

Recent findings suggest that macrophage-tropic human immunodeficiency virus type 1 (HIV-1) produced in colostrum/early breast milk may hold a clue to determine the mechanisms of transmission of HIV-1 via breast-feeding. Here, we show that the majority of CD4(+) cells in the colostrum are CD14(+) macrophages expressing both chemokine receptors and DC-SIGN, a dendritic cell-specific receptor for HIV-1. The R5-type macrophage-tropic HIV-1 isolate NL(AD8) infected such breast-milk macrophages and caused them to secrete virus particles efficiently; however, the secreted virions showed only a weak transmissibility to their susceptible target, MAGIC-5 cells. When stimulated with interleukin-4, the breast-milk macrophages demonstrated a striking enhancement of expression of DC-SIGN and showed a strong capacity to transmit NL(AD8) virions to MAGIC-5 cells, which was specifically blocked by anti-DC-SIGN-specific antibody. These results suggest that HIV-1 virions captured by DC-SIGN, but not secreted cell-free virions, may be more efficiently transmitted to other compartments, such as the gastrointestinal tract, through acidic gastric juice.

Inhibition of DC-SIGN-mediated transmission of human immunodeficiency virus type 1 by Toll-like receptor 3 signalling in breast milk macrophages

The majority of cells in early/colostrum milk are breast milk macrophages (BrMMø) expressing dendritic cell (DC)‐specific intercellular adhesion molecule 3 (ICAM3) grabbing nonintegrin (DC‐SIGN), and the expression level of DC‐SIGN on BrMMø will determine cell‐to‐cell human immunodeficiency virus type 1 (HIV‐1) transmissibility. Thus, one of the strategies to prevent vertical transmission of HIV‐1 through breast‐feeding is to find a way to suppress DC‐SIGN expression on BrMMø. As for the expression of Toll‐like receptors (TLRs) in BrMMø, TLR3 was always seen in BrMMø but not in peripheral blood monocytes (PBMo). Also, the expression of TLR3 was slightly enhanced in BrMMø when the cells were treated with interleukin (IL)‐4. Moreover, when TLR3 was stimulated with its specific ligand, the double‐stranded RNA (dsRNA) poly(I:C), DC‐SIGN expression on BrMMø was reduced even in the IL‐4‐mediated enhanced state. Some reduction may be caused by type I interferons (IFNs), such as IFN‐α/β, secreted from BrMMø. Indeed, both IFNs, particularly IFN‐β, showed a strong capacity to suppress the enhancement of DC‐SIGN expression on IL‐4‐treated BrMMø and such TLR3‐mediated DC‐SIGN suppression was partially abrogated by the addition of anti‐IFN‐α/β‐receptor‐specific antibodies. As expected, DC‐SIGN‐mediated HIV‐1 transmission to CD4‐positive cells by BrMMø was inhibited by either poly(I:C) stimulation or by treatment with type I IFNs. These findings suggest a possible strategy for preventing mother‐to‐child transmission (MTCT) of HIV‐1 via breast‐feeding through TLR3 signalling.

Midwife-led care unit for 'low risk' pregnant women in a Japanese hospital

Objectives. To examine the obstetric outcomes of our ‘low risk’ pregnant women under the midwife-led delivery care compared with those under the obstetric shared care. Methods. A retrospective cohort study compared outcomes of labor under midwife ‘primary’ care with those under obstetric shared care. The factors examined were: maternal age, parity, gestational age at delivery, length of labor, augmentation of labor pains, delivery mode, episiotomy, perineal laceration, postpartum hemorrhage, neonatal birth weight, Apgar score, and umbilical artery pH. In this study, pregnant women were initially considered ‘low risk’ at admission when they had no history of medical, gynecological, or obstetric problems and no complications during the present pregnancy. Results. There were 1031 pregnant women initially considered ‘low risk’ at admission. At admission, 878 of them (85%) requested to give birth under midwife care; however 364 of these women (42%) were transferred to obstetric shared care during labor. The average length of labor under the midwife ‘primary’ care was significantly longer than that under the obstetric shared care. However, there were no significant differences in the rate of prolonged labor (≥24 h). There were no significant differences in other obstetric or neonatal outcomes between the two groups. Conclusions. There was no evidence indicating that midwife ‘primary’ care is unsafe for ‘low risk’ pregnant women. Therefore, midwifery care is recommended for ‘low risk’ pregnant women.

Placental Villotrophoblastic Pulmonary Emboli After Elective Abortion: Immunohistochemical Diagnosis and Comparison with Ten Control Cases

Although pulmonary trophoblastic embolism is now considered a physiologic phenomenon of normal pregnancy, this phenomenon has not been demonstrated in a living asymptomatic patient. Recently we encountered a 26-year-old woman suspected of pulmonary embolism of villotrophoblastic tissues after therapeutic abortion. Although her serum beta-hCG was low, a computed tomography scan showed multiple nodules in both lungs. Histological examination of a nodule in a lung-biopsy specimen showed granulation tissue surrounding a hemorrhagic mass within which were structures resembling degenerating chorionic villi. Immunohistochemical study on the patients lung nodule, and a second endometrial-curettage specimen, six control endometrial and tubal specimens containing degenerating chorionic villi, and four endometrial specimens containing viable chorionic villi were performed. The patterns of immunostaining for cytokeratin, human chorionic gonadotropin, human placental lactogen, placental alkaline phosphatase, and inhibin-alpha of the chorionic villus-like structures in the lung nodule were almost identical to those in the degenerating chorionic villi, but different from those of viable villi. This is a unique case of embolism of chorionic villi and trophoblast to the lung in a living patient after therapeutic abortion.

Optimal Interval for Ultrasound Surveillance in Monochorionic Twin Gestations

In Reply: We appreciate the interest of Drs. Koskas and Rouzier in our work. The goal of our analysis was to compare the survival of women with endometrial cancer staged with both the 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) staging systems for uterine corpus cancer. A priori, we set out to provide easily interpretable survival estimates for clinicians. The concordance index (or cindex) is a statistical tool to predict ordered survival. In essence, the concordance index determines the probability of concordance between predicted and observed survival. Although the concordance index provides important data, we believe that reporting 5-year survival estimates, survival by the Kaplan Meier method, and multivariable estimates of survival using Cox proportional hazards models is more informative for clinicians. The approach we used is similar to that of a number of investigators who recently have compared revised staging schemata for a number of different primary tumor types.1–3 In our analysis, we presented Kaplan Meier curves for overall survival. As pointed out, many women with endometrial cancer die from causes unrelated to their cancer. We chose to present overall survival curves for simplicity. In our analysis, we also examined cancer-specific survival, and the P values for women with early-stage (I-II) and advanced-stage tumors (III-IV) (both based on 1988 and 2009 staging criteria) were similar to those of overall survival ( .001). Dr. Koskas and Rouzier also raise the question of survival for women with stage IIIB neoplasms. In the Kaplan Meier plots, survival for stage IIIB tumors is worse than that for stage IIIC malignancies. The 5-year survival for women with stage IIIB tumors was 36.2% (95% confidence interval 30–42%), inferior to that of stage IIIC patients in the FIGO 1988 system and inferior to both stage IIIC1 and IIIC2 patients in the FIGO 2009 system. The poor outcome of women with stage IIIB tumors clearly warrants further study. Because the 2009 staging system is likely not the last revision of the corpus staging system, reclassification of patients with IIIB neoplasms certainly deserves consideration in future versions of the staging system.

Maternal risk factors for small-for-gestational age newborns in Japanese dichorionic twins.

Aim:  To investigate the maternal risk factors for small‐for‐gestational age (SGA) newborns in Japanese dichorionic (DC) twins.

Preventive effect of monoclonal antibodies to intercellular adhesion molecule-1 and leukocyte function-associate antigen-1 on murine spontaneous fetal resorption

PROBLEM: Are cell adhesion molecules involved in the murine model of immunologically‐mediated spontaneous abortion?
 METHOD OF STUDY: Pregnant CBA/J female mice mated with DBA/2 male mice were injected with monoclonal antibodies (MAbs) to intercellular adhesion molecule‐1 (ICAM‐1) and leukocyte function‐associate antigen‐1 (LFA‐1). On day 13 of gestation, viable and resorbed embryos were counted. Natural killer (NK) cell activity in the spleen, mixed lymphocyte reactions (MLR), mixed lymphocyte‐placenta reactions (MLPR), and levels of interferon (IFN)‐Γ were assayed.
 RESULTS: Significant suppression of fetal resorption was observed by the injection of MAb to ICAM‐1 and LFA‐1. NK cell activity and the MLR anti‐(CBA/J×DBA/2)F1 were reduced in the antibody‐treated CBA/J spleen. Moreover, the level of IFN‐Γ was significantly lower in the MLPR supernatants from the antibody‐treated group than those of the control group.
 CONCLUSIONS: One mechanism in the murine model of spontaneous abortion may be through the interaction of cell adhesion molecules, which may modulate NK cell activities and cytokine production.

Effect of sera on the adhesion of natural killer cells to the endothelium in severe pre‐eclampsia

Objective:  To investigate the effect of serum on the interaction between natural killer (NK) cells and endothelial cells in pre‐eclampsia.

Unexpected intrauterine fetal death in monochorionic-diamniotic twins near term.

No abstract available