Elevated Expression of T-Cell Immunoglobulin and Mucin Domain 3 on T Cells from Peripheral Blood in Patients with Cervical Carcinoma.

OBJECTIVE: To investigate the expression of T-cell immunoglobulin and mucin domain 3 (TIM-3) on peripheral T cells of cervical carcinoma patients. METHODS: Peripheral blood samples from 15 high-grade cervical squamous intraepithelial lesion (HSIL) patients, 24 cervical carcinoma patients, and 21 healthy controls were collected. TIM-3 expressions on the surface of peripheral CD4+ T cells and CD8+ T cells were analyzed with flow cytometry. RESULTS: There was significantly lower expression of CD4+ T cells and CD8+ T cells in HSIL patients and cervical carcinoma patients compared with healthy controls. We also found that TIM-3 expression on peripheral CD4+ T and CD8+ T cells of both HSIL patients and cervical carcinoma patients was significantly increased compared to the control group. Further analyses revealed that the expression of TIM-3 on peripheral CD4+ T and CD8+ T cells significantly increased in stage III-IV cervical carcinoma patients compared to stages I-II. CONCLUSION: The increased expression of TIM-3 on CD4+ T cells and CD8+ T cells of patients with cervical carcinoma and HSIL suggests the potential role of TIM-3 in the development and progression of cervical carcinoma, which may be a novel therapy target for cervical carcinoma.

The Significance of Galectin-1 and Galectin-9 Expression in Endometrial Carcinoma.

OBJECTIVES: To explore the expression of Galectin-1 and -9 and clinicopathological features in endometrial carcinoma (EC). METHODS: Normal endometrium (NE), atypical endometrial hyperplasia (AH), and endometrial cancer were collected, and immunohistochemistry was used to detect the expression of Galectin-1 and -9 in all specimens in the same condition. RESULTS: The positive rate of Galectin-1 expression in NE, AH, and endometrial cancer was 30, 70, and 90.2%. The positive rate of Galectin-9 expression in them was 20, 75, and 78.4%, respectively. The expression of Galectin-1 and -9 in the EC and AH was significantly higher than that in the NE (p< 0.05). However, there was no significant difference between the EC and the AH (p > 0.05). The expression of Galectin-1 in endometrial adenocarcinoma was significantly different among tissues of different histological grades, pathological stages, degrees of myometrial infiltration, or lymph node metastasis (p > 0.05). The expression of Galectin-9 in endometrial adenocarcinoma was significantly different among different historical grades, pathological stages, degrees of myometrial infiltration, and lymph node metastasis (p < 0.05). The expression of Galectin-9 in tissues at an early stage, with the degree of myometrial infiltration <1/2, and without lymph node metastasis, was significantly stronger than in those in the late stage, with a degree of myometrial infiltration ≥1/2 and lymph node metastasis. CONCLUSION: Both Galectin-1 and -9 were associated with the occurrence of EC and its pathological behavior. High expression of Galectin-1 suggests a poor prognosis, whereas high expression of Galectin-9 was associated with early pathological changes. Galectin-1 and -9 can provide references for early screening and indicate the prognosis of endometrial lesions, which are of great significance for patients' quality of life.

Central Infusion of Angiotensin II Type 2 Receptor Agonist Compound 21 Attenuates DOCA/NaCl-Induced Hypertension in Female Rats.

The present study investigated whether central activation of angiotensin II type 2 receptor (AT2-R) attenuates deoxycorticosterone acetate (DOCA)/NaCl-induced hypertension in intact and ovariectomized (OVX) female rats and whether female sex hormone status has influence on the effects of AT2-R activation. DOCA/NaCl elicited a greater increase in blood pressure in OVX females than that in intact females. Central infusion of compound 21, a specific AT2-R agonist, abolished DOCA/NaCl pressor effect in intact females, whereas same treatment in OVX females produced an inhibitory effect. Real-time RT-PCR analysis revealed that DOCA/NaCl enhanced the mRNA expression of hypertensive components including AT1-R, ACE-1, and TNF-α in the paraventricular nucleus of hypothalamus in both intact and OVX females. However, the mRNA expressions of antihypertensive components such as AT2-R, ACE-2, and IL-10 were increased only in intact females. Central AT2-R agonist reversed the changes in the hypertensive components in all females, while this agonist further upregulated the expression of ACE2 and IL-10 in intact females, but only IL-10 in OVX females. These results indicate that brain AT2-R activation plays an inhibitory role in the development of DOCA/NaCl-induced hypertension in females. This beneficial effect of AT2-R activation involves regulation of renin-angiotensin system and proinflammatory cytokines.

Brain endogenous angiotensin II receptor type 2 (AT2-R) protects against DOCA/salt-induced hypertension in female rats.

BACKGROUND: Recent studies demonstrate that there are sex differences in the expression of angiotensin receptor type 2 (AT2-R) in the kidney and that AT2-R plays an enhanced role in regulating blood pressure (BP) in females. Also, brain AT2-R activation has been reported to negatively modulate BP and sympathetic outflow. The present study investigated whether the central blockade of endogenous AT2-R augments deoxycorticosterone acetate (DOCA)/salt-induced hypertension in both male and female rats. METHODS: All rats were subcutaneously infused with DOCA combined with 1% NaCl solution as the sole drinking fluid. BP and heart rate (HR) were recorded by telemetric transmitters. To determine the effect of central AT2-R on DOCA/salt-induced hypertension, male and female rats were intracerebroventricularly (icv) infused with AT2-R antagonist, PD123,319, during DOCA/salt treatment. Subsequently, the paraventricular nucleus (PVN) of the hypothalamus, a key cardiovascular regulatory region of the brain, was analyzed by quantitative real-time PCR and Western blot. RESULTS: DOCA/salt treatment elicited a greater increase in BP in male rats than that in females. Icv infusions of the AT2-R antagonist significantly augmented DOCA/salt pressor effects in females. However, this same treatment had no enhanced effect on DOCA/salt-induced increase in the BP in males. Real-time PCR and Western blot analysis of the female brain revealed that DOCA/salt treatment enhanced the mRNA and protein expression for both antihypertensive components including AT2-R, angiotensin-converting enzyme (ACE)-2, and interleukin (IL)-10 and hypertensive components including angiotensin receptor type 1 (AT1-R), ACE-1, tumor necrosis factor (TNF)-α, and IL-1ß, but decreased mRNA expression of renin in the PVN. The central blockade of AT2-R reversed the changes in mRNA and protein expressions of ACE-2, IL-10, and renin, further increased the expressions of TNF-α and IL-1ß, and kept higher the expressions of AT1-R, ACE-1, and AT2-R. CONCLUSIONS: These results indicate that endogenous AT2-R activation in the brain plays an important protective role in the development of DOCA/salt-induced hypertension in females, but not in males. The protective effect of AT2-R in females involves regulating the expression of brain renin-angiotensin system components and proinflammatory cytokines.

Four-dimensional volume-rendered imaging of the fetal ventricular outflow tracts and great arteries using inversion mode for detection of congenital heart disease.

AIM: Using four-dimensional (4D) sonography with an inversion mode, we evaluated fetal ventricular outflow tracts and great vessels for the detection of congenital heart disease. METHODS: Volume datasets of the fetal heart were acquired with spatiotemporal image correlation (STIC), which uses automated transverse and longitudinal sweeps of the anterior chest wall. A total of 12 normal fetuses and seven fetuses with congenital heart disease (one case of double-outlet right ventricle, one case of tetralogy of Fallot, one case of transposition of the great arteries, one case of hypoplastic pulmonary artery with a large ventricular septal defect, and three cases of hypoplastic left heart syndrome) at 16-37 weeks of gestation were studied using transabdominal 4D sonography with an inversion mode. 4D inversion mode images of great arteries were evaluated. RESULTS: 4D ultrasound with an inversion mode demonstrated real-time 3D angiographic features of fetal cardiac outflow tracts in both normal and abnormal fetal hearts. This modality facilitated visualization of the relationships, size, and course of the outflow tracts, thus helping the examiner to more effectively understand the spatial relationships between the vessels. In normal fetal hearts, it was clearly shown that the pulmonary artery crosses in front of the aorta. In the three cases of hypoplastic left heart syndrome, an extremely small ascending aorta was evident. In the one case of tetralogy of Fallot, a relatively small pulmonary artery was noted. In the one case of hypoplastic pulmonary artery with a large ventricular septal defect, a markedly small main pulmonary artery was depicted. In the case of transposition of the great arteries, the vessels left the ventricles parallel to each other. In the case of double-outlet right ventricle, great arteries leaving the right ventricle in parallel were shown. CONCLUSION: 4D ultrasound in the inversion mode provides a means of evaluating fetal cardiac outflow tracts in 3D in real time. This technique may assist in the evaluation of spatial relationships between the great vessels and both ventricles, and the difference in the size of great vessels. Moreover, the inversion mode images should be more readily discernible than those obtained by conventional ultrasonography. 4D ultrasound in the inversion mode may be an important modality in future fetal cardiac research and in the evaluation of fetal congenital heart disease.

Three-dimensional volume-rendered imaging of embryonic brain vesicles using inversion mode.

AIM: The purpose of this study was to present our first experience of normal embryonic brain vesicle shapes in the early first trimester of pregnancy, reconstructed by three-dimensional (3D) volume-rendered imaging using the inversion mode. METHODS: Twenty-three women who were between 7.4 and 9.7 weeks of gestation were studied using 3D ultrasound with a mechanical 3.7-9.3 or 4.5-11.9 MHz 3D transvaginal probe. In order to clarify the anatomical correlation of the embryonic and fetal brain vesicles, the inversion mode was used. RESULTS: One patient who was at 7.4 weeks of gestation was excluded from the study because of the relative shallow scanning range of the 3D transvaginal transducer and very small embryonic brain structures. When viewed by means of transvaginal 3D volume-rendered imaging using the inversion mode, the brain vesicles were the most prominent structures at each week, and were clearly seen as multilobular consecutive structures. All embryos studied had five secondary brain vesicles. Moreover, the dramatic change of embryonic brain vesicle shapes with advancing gestation was noted during this period. CONCLUSION: Our results suggest that transvaginal 3D volume-rendered imaging using the inversion mode provides accurate visualization of embryonic brain vesicle structures in utero.

Immunological effect of subunit influenza vaccine entrapped by liposomes.

OBJECTIVE: To elevate the immunological effect of subunit influenza vaccine in infants and aged people (over 60) using liposomal adjuvant in the context of its relatively low immunity and to investigate the relation between vaccine antigens and liposomal characteristics. METHODS: Several formulations of liposomal subunit influenza vaccine were prepared. Their relevant characteristics were investigated to optimize the preparation method. Antisera obtained from immunizinged mice were used to evaluate the antibody titers of various samples by HI and ELISA. RESULTS: Liposomal trivalent influenza vaccine prepared by film evaporation in combinedation with freeze-drying significantly increased its immunological effect in SPF Balb/c mice. Liposomal vaccine stimulated the antibody titer of H3N2, H1N1, and B much stronger than conventional influenza vaccine. As a result, liposomal vaccine (mean size: 4.5-5.5 microm, entrapment efficiency: 30%-40%) significantly increased the immunological effect of subunit influenza vaccine. CONCLUSION: The immune effect of liposomal vaccine depends on different antigens, and enhanced immunity is not positively correlated with the mean size of liposome or its entrapped efficiency.

Real-time three-dimensional color Doppler fetal echocardiographic features of congenital heart disease.

The purpose of this report is to describe the real-time three-dimensional (3D) color Doppler fetal echocardiographic findings of congenital heart diseases. Two cases of fetal congenital heart disease were diagnosed antenatally by conventional two-dimensional fetal echocardiography and real-time 3D color Doppler fetal echocardiography. Conventional two-dimensional (2D) fetal echocardiography showed a hypoplastic left heart in one case, and a double-outlet right ventricle in the second case. Real-time 3D fetal echocardiography with instantaneous volume-rendered displays showed surgeon's eye views of intracardiac abnormal cardiac structures of the beating heart in both cases. Real-time 3D color Doppler fetal echocardiography depicted a subtle tricuspid regurgitant jet in hypoplastic left heart syndrome, and great arteries, left from the right ventricle, in parallel in a double-outlet right ventricle. Real-time 3D color Doppler fetal echocardiography may assist in the evaluation of fetal cardiac anatomy and hemodynamics, and offer the potential advantages relative to conventional 2D fetal echocardiography and Doppler flow mapping.

Does three-dimensional power Doppler ultrasound improve the diagnostic accuracy for the prediction of adnexal malignancy?

OBJECTIVE: The aim of the present study was to investigate the diagnostic accuracy of three-dimensional power Doppler ultrasound (3DPD) in the differentiation between benign and malignant adnexal masses and evaluate 3DPD for assessing malignancy in comparison with two-dimensional transvaginal gray-scale sonography (2DTVS), magnetic resonance imaging (MRI) and positron emission tomography (PET). SUBJECTS AND METHODS: Thirty-six patients with suspicious adnexal masses were included in this study. 2DTVS and 3DPD were performed preoperatively. MRI and PET examinations were also carried on within two weeks of initial sonography. All the results of diagnostic imaging techniques were evaluated separately. Final diagnosis was confirmed by the postoperative histopathology. The mature cystic teratomas and endometriomas with typical gray-scale sonographic appearance were excluded from the study. RESULTS: Of the 36 patients, 25 had a malignancy, 5 had a borderline tumor, and 6 had a benign mass. Sensitivity of 2DTVS, 3DPD, MRI and PET were 96.7%, 76.7%, 96.7% and 83.3%, respectively. The sensitivity of 2DTVS was as high as that of MRI, and both of them were significantly higher than those of 3DPD and PET, respectively. There were no significant differences both in specificity and accuracy among these 4 techniques. CONCLUSION: 3DPD did not improve the diagnostic accuracy for the prediction of malignancy in adnexal masses. 2DTVS may still remain an important modality for the prediction of adnexal malignancy.

Four-dimensional sonography with B-flow imaging and spatiotemporal image correlation for visualization of the fetal heart.

PURPOSE: To use B-flow imaging with 4-dimensional (4D) sonography and spatiotemporal image correlation (STIC) in the evaluation of normal fetal heart and congenital heart disease during pregnancy. METHOD: Volume data sets of the fetal heart were acquired with automated transverse and longitudinal sweeps of the anterior chest wall. We studied 13 normal fetuses and 2 fetuses with congenital heart disease (1 double-outlet right ventricle and 1 hypoplastic left heart syndrome) at gestation ages ranging from 13 to 39 weeks using transabdominal 4D B-flow sonography with STIC (4D BF-STIC). RESULTS: 4D BF-STIC demonstrated dynamic angiographic features in both normal and abnormal fetal hearts. 4D BF-STIC images could not be obtained in 2 normal fetuses at 18.1 and 33.1 weeks because of the high fetal heart rate and inappropriate fetal position. In normal fetal heart, characteristic hemodynamic changes in both atria and ventricles were clearly demonstrated in systole and diastole. 4D BF-STIC also allowed visualization of the relationship, size, and course of the outflow tracts, thus helping the examiner to better understand the relationships between the vessels. In a case of hypoplastic left heart syndrome, dramatic hemodynamic changes including the right atrium, right ventricle, and pulmonary artery were evident. In a case of double-outlet right ventricle with ventricular septal defect, left-to-right shunt flow through a ventricular septal defect was clearly shown, as were great arteries originating in parallel from the right ventricle. CONCLUSION: 4D BF-STIC provides a means of real-time 3-dimensional evaluation of fetal intracardiac and extracardiac hemodynamics in the second and third trimesters. This novel technique assists in the evaluation of fetal cardiac hemodynamics and may play an important role in future fetal cardiac research and in the evaluation of congenital heart disease in the fetus.

Beneficial effect of galectin 9 on rheumatoid arthritis by induction of apoptosis of synovial fibroblasts.

OBJECTIVE: To compare the expression of galectin 9 (Gal-9) in synovial tissue (ST) from rheumatoid arthritis (RA) patients and osteoarthritis (OA) patients and to evaluate the effects of Gal-9 on fibroblast-like synoviocytes (FLS) in these patients. METHODS: The expression of Gal-9 in ST and FLS was compared using immunohistochemical techniques. Apoptotic cells in RA and OA ST samples were detected by TUNEL assay. Apoptosis of FLS was analyzed by the sub-G(1) method in vitro. The in vivo suppressive effects of Gal-9 on collagen-induced arthritis (CIA) in a mouse model were also elucidated. RESULTS: The percentage of Gal-9-positive cells in ST samples and the amount of Gal-9 in synovial fluid samples were significantly higher in patients with RA than in patients with OA, suggesting the involvement of Gal-9 in the development of RA. Compared with the 2 wild-type Gal-9 forms, stable Gal-9, a mutant protein resistant to proteolysis, significantly induced apoptosis of FLS from RA patients. In contrast, other galectins, such as Gal-1, Gal-3, and Gal-8, did not induce apoptosis or suppress the proliferation of human RA FLS. Stable Gal-9 preferentially induced apoptosis and suppressed the proliferation of RA FLS in vitro. It also induced apoptosis of cells in RA ST implanted into SCID mice in vivo. In a mouse model of CIA, apoptotic cells were detected in the joints of stable Gal-9-treated mice, but not phosphate buffered saline-treated mice, and suppressed CIA characterized by pannus formation with inflammatory cell infiltration and bone/cartilage destruction. CONCLUSION: Gal-9-induced apoptosis of hyperproliferative RA FLS may play a critical role in the suppression of RA.

Three-dimensional sonographic volume measurement of the fetal lung.

AIM: The objective of this longitudinal study was to evaluate the growth of the fetal lung in normal pregnancies, using 3-D ultrasound. METHODS: 3-D sonographic examinations were performed on 14 appropriate-for-gestational-age fetuses. Fetal lung volumes (left, right, and total lung volumes) were measured every 2-3 weeks from 20 weeks of gestational age until delivery. The common multiplanar technique was used to calculate fetal lung volume. RESULTS: Curvilinear relationships were found between the gestational age and left (R2 = 86.9%, P < 0.0001), right (R2 = 83.9%, P < 0.0001) and total (R2 = 83.8%, P < 0.0001) lung volumes. The data described in this study were fairly comparable with previous data from autopsy series. However, there were big differences for predicted values of the fetal total lung volumes using 3-D ultrasound among the present study and previous investigations. CONCLUSION: Our findings suggest that the standard curve for fetal lung volume using 3-D ultrasound provides a role for evaluating the normal lung growth in the fetus. However, we do cast doubt on the reliability and reproducibility of fetal lung volume measurements using 3-D ultrasound. Moreover, the data and its interpretation in our study should be taken with some degree of caution because of the small number of subjects studied. Further studies involving a larger sample size would be needed to confirm these findings.

Three-dimensional sonographic volume measurement of the fetal spleen.

AIM: The objective of this longitudinal study was to evaluate the growth of the fetal spleen in normal pregnancies, using three-dimensional ultrasound. METHODS: Three-dimensional sonographic examinations were performed on 14 appropriate-for-gestational-age fetuses. Fetal splenic volume was measured every 2-3 weeks after 20 weeks of gestational age until delivery. RESULTS: Curvilinear relationships were found between the gestational age and splenic volume (R(2) = 80.2%, P < 0.0001), and normal ranges of splenic volume measurements for estimating the growth of the fetal spleen during normal pregnancy were generated. We found that the splenic volume calculation based on the equation for the volume of the ellipsoid by conventional two-dimensional ultrasound in previous investigations is about twice as large as that using three-dimensional ultrasound in our study, whereas the present data described in this study is quite comparable with previous data from an autopsy series. CONCLUSION: Our findings suggest that the standard curve for the fetal splenic volume using three-dimensional ultrasound provides a superior means for evaluating the normal splenic growth in the fetus and for identifying splenic abnormalities in utero. However, the data and its interpretation in our study should be taken with some degree of caution because of the small number of subjects studied. Further studies involving a larger sample size would be needed to confirm these findings.

Galectin-9 inhibits CD44-hyaluronan interaction and suppresses a murine model of allergic asthma.

RATIONALE: Galectin-9 (Gal-9) belongs to the galectin family, which exhibits affinity for beta-galactosides. Gal-9 has a variety of biological activities; however, its role in allergic inflammation is unknown. OBJECTIVES: We evaluated the effect of a stable form of the human protein on allergic airway inflammation in a mite allergen-induced asthma model. METHODS: Human stable Gal-9 was given by intravenous injection to mice during antigen challenge. The effect of Gal-9 on airway inflammation and airway hyperresponsiveness (AHR) was then evaluated. MEASUREMENTS AND MAIN RESULTS: Gal-9 reduced AHR as well as Th2-associated airway inflammation. Furthermore, administration of Gal-9 as well as anti-CD44 monoclonal antibody inhibited the infiltration of peripheral blood Th2 cells into the airway. Interestingly, Gal-9 directly bound the CD44 adhesion molecule and inhibited interactions with hyaluronan (HA). Consistent with the concept that CD44-HA interactions mediate the migration of T cells into the lung, Gal-9 blocked CD44-dependent adhesion of BW5147 mouse T cells to HA. CONCLUSIONS: We conclude that Gal-9 inhibits allergic inflammation of the airway and AHR by modulating CD44-dependent leukocyte recognition of the extracellular matrix.

Real-time 3-dimensional echocardiographic features of fetal cardiac tumor.

We present a case of fetal cardiac tumors diagnosed using conventional 2-dimensional (2D) fetal echocardiography and real-time 3-dimensional (3D) echocardiography. Conventional 2D echocardiography revealed multiple cardiac tumors involving the right atrium, interventricular septum, and right and left ventricles. Real-time 3D echocardiography with instantaneous volume rendering showed the cardiac tumors in motion. The advantages and disadvantages of real-time 3D fetal echocardiography are discussed.

Three-dimensional sonographic volume measurement of the fetal cerebellum.

PURPOSE: The objective of this longitudinal study was to evaluate the growth of the fetal cerebellum in normal pregnancy by using three-dimensional ultrasound. METHODS: Three-dimensional sonographic examinations were performed for 13 appropriate-for-gestational-age fetuses. Fetal cerebellar volume was measured every 2 to 3 weeks after 20 weeks of gestational age until delivery. The common multiplanar technique was used to calculate the fetal cerebellar volume. RESULTS: A curvilinear relationship was found between gestational age and cerebellar volume (R(2) = 78.6%, P < 0.0001), and normal ranges of cerebellar volume measurements for estimating the growth of the fetal cerebellum during normal pregnancy were generated. The data gathered in this study were fairly comparable with previous data obtained using three-dimensional ultrasound. However, the normal ranges of cerebellar volume that we determined were relatively wide throughout pregnancy. CONCLUSIONS: Our findings suggest that a standard curve for fetal cerebellar volume using three-dimensional ultrasound can play a role in the evaluation of normal cerebellar growth in the fetus. However, we do cast doubt on the reliability and reproducibility of cerebellar volume measurement using three-dimensional ultrasound. Further studies involving a larger sample size and another technique (the rotational method with VOCAL) would be needed to confirm these findings.

Four-dimensional sonographic assessment of fetal facial expression early in the third trimester.

OBJECTIVE: To evaluate the characteristic patterns of facial expression in fetuses aged from 28 to 34 weeks using 4-dimensional (4-D) ultrasonography. METHODS: The faces of 10 healthy fetuses aged from 28 to 34 weeks were recorded continuously for 15 min with a 4-D ultrasonographic machine performing up to 25 frames per second. The occurrence rates of blinking, mouthing, yawning, tongue expulsion, smiling, scowling, and sucking were evaluated. RESULTS: Mouthing was the most frequent facial expression (median, 6.5; range, 2-19) whereas the least frequent were scowling (median, 1; range, 0-9) and sucking (median, 1; range, 0-2). Mouthing was evident in all fetuses and significantly more frequent than any other movement (P<.05). Yawning (median, 3; range, 0-6), smiling (median, 2; range, 0-9), and blinking (median, 1.5; range, 0-6) were observed in most cases. Tongue expulsion (median, 1.5; range, 0-5), scowling, and sucking were each observed in 6 cases. CONCLUSION: 4-D sonography provides a means of evaluating fetal facial expression early in the third trimester. It may be a key to predicting fetal brain function and well-being and an important modality in future fetal neurophysiologic research.

Galectin-9 induces maturation of human monocyte-derived dendritic cells.

Maturation of dendritic cells (DCs) is critical for initiation of immune responses and is regulated by various stimulatory signals. We assessed the role of galectin (Gal)-9 in DC maturation. Culture of immature DCs with exogenous Gal-9 markedly increased the surface expression of CD40, CD54, CD80, CD83, CD86, and HLA-DR in a dose-dependent manner, although Gal-9 had no or little effect on differentiation of human monocytes into immature DCs. Gal-9-treated DCs secreted IL-12 but not IL-10, and they elicited the production of Th1 cytokines (IFN-gamma and IL-2) but not that of the Th2 cytokines (IL-4 and IL-5) by allogeneic CD4+ T cells. These effects of Gal-9 on immature DCs were not essentially dependent on its lectin properties, given that they were inhibited only slightly by lactose. We further found that a Gal-9 mutant that lacks beta-galactoside binding activity reproduced the above activities and that an anti-Gal-9 mAb suppressed them. Gal-9 induced phosphorylation of the MAPK p38 and ERK1/2 in DCs, and an inhibitor of p38 signaling, but not inhibitors of signaling by either ERK1/2 or PI3K, blocked Gal-9-induced up-regulation of costimulatory molecule expression and IL-12 production. These findings suggest that Gal-9 plays a role not only in innate immunity but also in acquired immunity by inducing DC maturation and promoting Th1 immune responses.

[Galectin-9 induces maturation of human monocyte-derived dendritic cells].

We investigated the role of galectin-9 (Gal-9) in maturation of dendritic cells (DC). Culture of immature DCs with exogenous Gal-9 markedly increased the surface expression of CD40, CD54, CD80, CD83, CD86, and HLA-DR in a concentration-dependent manner, although Gal-9 had no effect on differentiation of human monocytes into immature DCs. Gal-9-treated DCs secreted IL-12 but not IL-10, and they elicited the production of Th1 cytokines (IFN-gamma and IL-2), but not that of the Th2 cytokines (IL-4 and IL-5) by allogeneic CD4(+) T cells. These effects of Gal-9 on immature DCs were not essentially dependent on its lectin properties, given that they were only slightly inhibited by lactose. We further found that a Gal-9 mutant that lacks beta-galactoside binding activity reproduced the above activities, and that an anti-Gal-9 mAb suppressed them. Gal-9 induced phosphorylation of the p38 MAPK and ERK1/2 in DCs, and an inhibitor of p38 signaling, but not inhibitors of signaling by either ERK1/2 or phosphatidylinositol 3-kinase, blocked Gal-9-induced up-regulation of costimulatory molecule expression and IL-12 production. These findings suggest that Gal-9 plays a role not only in innate immunity but also in acquired immunity by inducing DC maturation and promoting Th1 immune responses.

Hypoxia-inducible factor-2alpha is involved in enhanced apoptosis in the placenta from pregnancies with fetal growth restriction.

The aim of the present study is to investigate whether hypoxia-inducible factors (HIF-1alpha, HIF-2alpha, HIF-1beta) are involved in enhanced apoptosis in the human placenta from pregnancies with fetal growth restriction (FGR). Placental samples were obtained from women with normal term pregnancy (n = 18) or from pregnancy with FGR (n = 12). Placenta apoptosis was assessed by the terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling (TUNEL) staining. The expressions of HIF-1alpha, HIF-2alpha, and HIF-1beta were examined by immunohistochemical analysis. Enhanced apoptosis was observed in the placenta from pregnancies with FGR compared with normal term placenta. The apoptosis index in FGR group (1.45 +/- 1.26%) was significantly higher than that in the normal control group (0.18 +/- 0.16%; P < 0.01). There were no significant differences in the intensity of the staining for HIF-1alpha and HIF-1beta expressions between two groups, while HIF-2alpha was overexpressed in the placenta from pregnancies with FGR group (P < 0.05). The upregulation of HIF-2alpha protein expression in the placenta from pregnancies with FGR may, at least in part, be involved in the increased placental apoptosis.