The balance between cytotoxic NK cells and regulatory NK cells in human pregnancy.

NK cells kill tumor cells and virus-infected cells as well as secrete a variety of cytokines. These effector functions are regulated by the balance between activating receptor signals and inhibitory receptor signals which are triggered by specific major histocompatibility complex (MHC) or non-MHC ligands. It is thought currently that the balance between immunostimulation and immunoregulation in T cell immunity is achieved by a Th1/Th2/Th3/Tr1 and CD4(+)CD25(+) regulatory T (Treg) cell paradigm. Here, we discuss the cytokine paradigm of NK cells in human pregnancy. During normal, intact pregnancy, peripheral blood NKr1 cells and decidual NK3 cells increase, while these NK cell populations decrease significantly in miscarriage cases, suggesting that an imbalance in NK1/NK2/NK3/NKr1 is correlated with miscarriage. Recent investigations have shown that not only Treg cells, but also regulatory NK (NK reg) cells, play very important roles in the maintenance of pregnancy. We summarize the progress in studying NK reg cells and focus on how NK reg cells and cytotoxic NK cells affect the reproductive immune response.

Fermented foods and preterm birth risk from a prospective large cohort study: the Japan Environment and Children's study

BACKGROUND@#The dietary pattern of pregnant women is known to be associated with preterm birth (PTB). We investigated whether PTB was associated with intake of fermented food by using data from the Japan Environment and Children's Study.@*METHODS@#From a data set of 103,099 pregnancies, 77,667 cases at low risk for PTB were analyzed. The primary outcome measurements were based on PTB. Fermented food (miso soup, yogurt, cheese, and fermented soybeans) consumption was assessed by using a semi-quantitative food frequency questionnaire.@*RESULTS@#Intake of miso soup, yogurt, and fermented soybeans before pregnancy significantly reduced the risk of early PTB (< 34 weeks). The adjusted odds ratio (OR) for early PTB in women who had miso soup 1-2 days/week, 3-4 days/week, or ≥ 5 days/week were 0.58, 0.69, and 0.62, respectively, compared with those who had miso soup < 1 day/week (95% confidence interval (CI) 0.40-0.85, 0.49-0.98, and 0.44-0.87). The adjusted OR for early PTB in women who ate yogurt ≥ 3 times/week was 0.62 (95% CI, 0.44-0.87) compared to those who ate yogurt < 1 time/week. The adjusted OR for early PTB in women who ate fermented soybeans ≥ 3 times/week was 0.60 (95% CI, 0.43-0.84) compared to those who ate < 1 time/week. However, the incidence of overall PTB and late PTB (34-36 weeks) was not associated with fermented food intake.@*CONCLUSION@#PTB low-risk women with a high consumption of miso soup, yogurt, and fermented soybeans before pregnancy have a reduced risk of early PTB.

OP0011. Impaired autophagy in extravillous trophoblast may induce poor placentation in preeclampsia.

Shallow invasion of extravillous trophoblast (EVT) and inadequate vascular remodeling by EVT are the major cause of poor placentation in preeclampsia. In early pregnancy period, trophoblast experience hypoxic and low-nutrient condition. Autophagy is a cellular bulk degradation system to maintain cellular homeostasis under stress. We examined whether autophagy sustained the EVT functions under the harsh condition. An enhancement of autophagy was observed in primary cultured EVT and EVT cell line under 2% oxygen condition or cobalt treatment which induce HIF1α. The invasion and vascular remodeling under hypoxic condition were significantly reduced in autophagy-deficient EVT cells compared with wild-type EVT cells. Treatment of ATP partially rescued the poor invation under hypoxic condition suggesting that getting energy using autophagy play important role for cell invasion under hypoxia. Soluble endoglin (sENG), that is increased in sera in preeclamptic cases, suppressed EVT invasion and vascular remodeling by EVT by inhibiting autophagy. Next we have examined the impaired autophagy by immunohistochemical staining for p62. p62 is selectively degradated in autophagosome, so if impaired autophagy is present, p62 is accumulated in the cytoplasma. Enhanced imunostainings for p62 in interstitial EVT and endovascular EVT in preeclamptic cases were observed showing impaired autophagy in EVT of preeclamptic cases. sENG is known to inhibit TGFß that is a essential factor for differentiation of regulatory T cells. Impaired autophagy and decreased regulatory T cells by increased sENG may play important roles in pathophysiology of preeclampsia.

Comparison of Drug-Eluting Stents in Acute Myocardial Infarction Patients with Chronic Kidney Disease

BACKGROUND/AIMS: To determine which drug-eluting stents are more effective in acute myocardial infarction (MI) patients with chronic kidney disease (CKD). METHODS: This study included a total of 3,566 acute MI survivors with CKD from the Korea Acute Myocardial Infarction Registry who were treated with stenting and followed up for 12 months: 1,845 patients who received sirolimus-eluting stents (SES), 1,356 who received paclitaxel-eluting stents (PES), and 365 who received zotarolimus-eluting stents (ZES). CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 calculated by the modification of diet in renal disease method. RESULTS: At the 12-month follow-up, patients receiving ZES demonstrated a higher incidence (14.8%) of major adverse cardiac events (MACEs) compared to those receiving SES (10.1%) and PES (12%, p = 0.019). The ZES patients also had a higher incidence (3.9%) of target lesion revascularization (TLR) compared to those receiving SES (1.5%) and PES (2.4%, p = 0.011). After adjusting for confounding factors, ZES was associated with a higher incidence of MACE and TLR than SES (adjusted hazard ratio [HR], 0.623; 95% confidence interval [CI], 0.442 to 0.879; p = 0.007; adjusted HR, 0.350; 95% CI, 0.165 to 0.743; p = 0.006, respectively), and with a higher rate of TLR than PES (adjusted HR, 0.471; 95% CI, 0.223 to 0.997; p = 0.049). CONCLUSIONS: Our findings suggest that ZES is less effective than SES and PES in terms of 12-month TLR, and has a higher incidence of MACE due to a higher TLR rate compared with SES, in acute MI patients with CKD.

Effects of maternal dioxin exposure on newborn size at birth among Japanese mother-infant pairs

<p><b>OBJECTIVE</b>Maternal exposure to dioxins [polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (DFs)] during pregnancy is known to affect infant growth and neurodevelopment in humans and animals. The aim of this study was to investigate the relationship between newborn size and the concentration of dioxin isomers in breast milk and to subsequently evaluate the potential toxicity of each dioxin isomer among mothers living in sea coast areas who are at a high risk of contamination due to a high consumption of fish.</p><p><b>METHODS</b>A total of 75 milk samples were obtained within 1 month of delivery from Japanese mothers living in the coastal areas of the Japan Sea. The relationships between the levels of seven dioxins and ten furan isomers in maternal breast milk, measured by high-resolution-gas chromatography/mass spectrometry, and the birth size of newborns, which is related to fetal growth, were investigated after adjustment for confounding factors.</p><p><b>RESULTS</b>The concentrations of 1,2,3,6,7,8-HxCDD (hexachlorodibenzo-p-dioxin), 2,3,4,7,8-PeCDF (pentachlorodibenzofuran), 2,3,4,6,7,8-HxCDF, and three dioxin toxic equivalent (TEQ) levels (PCDDs-TEQ, PCDFs-TEQ, and total-TEQ) in maternal breast milk were inversely correlated to newborn length even after adjustment for gestational weeks, infant sex, and maternal age and height. These isomers were abundant among the 17 isomers tested and reflected the TEQ levels. Only 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), the most toxic isomer, was negatively correlated with newborn head circumference, even after adjustment for gestational weeks, infant birth weight, and other confounding factors.</p><p><b>CONCLUSIONS</b>Based on our results, fetal growth may be influenced by maternal total exposure to dioxins, but only exposure to 2,3,7,8-TCDD would appear to possibly affect fetal head size during pregnancy.</p>

Qualitative and quantitative evaluation of coronary plaques with 64-slice computed tomography in comparison with intravascular ultrasound / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the diagnostic feasibility of noninvasive assessment of coronary atherosclerotic plaques with MSCT in comparison with IVUS.</p><p><b>METHODS</b>Contrast-enhanced MSCT angiography (Sensation 64, Siemens Medical Solutions) was performed before percutaneous coronary intervention (PCI), and three-vessel IVUS (Boston Scientific, Natick, MA) was performed during procedure in 12 patients with stable angina pectoris. Complete investigation was digitally stored, and assessed offline with EchoPlaque (Indec Systems, Mountain View, CA). The comparison of MSCT with IVUS was performed based on segment at plaque site (American Heart Association 15-segment model).</p><p><b>RESULTS</b>A total of 88 segments in 31 vessels (left anterior descending: 12, left circumflex: 10, and right coronary artery: 9) were investigated by both IVUS and MSCT. Among 68 assessable segments (54 proximal-middle segments and 14 distal segments) by MSCT (20 segments were excluded for poor image quality: 16 for severe calcification, 2 for motion artifact, 2 for poor opacification), MSCT correctly detected 47 of the 51 segments with plaques (sensitivity: 92%), and correctly evaluated 16 of 17 segments without plaques (specificity: 94%). Concerning plaque quantification, MSCT correlated well with IVUS in grading whether the vessel obstruction was less or more than 50% (simple kappa: 0.63, 95% CI: from 0.47 to 0.78). Plaque area by MSCT also correlated with that by IVUS (r = 0.53, P < 0.01), but overestimated plaque area [(9.09 +/- 3.89) mm(2) vs. (6.80 +/- 2.81) mm(2), P < 0.01]. In addition, 30 of 43 hypoechoic compositions were detected as low-density compositions by MSCT with average CT number as 67.39 HU.</p><p><b>CONCLUSIONS</b>In segments without severe calcification, contrast-enhanced 64-slice CT angiography could detect plaques in coronary artery with high accuracy. Plaque area quantification by MSCT correlated with that of IVUS though with limited accuracy.</p>