Evaluation of a high-speed but low-throughput RT-qPCR system for detection of SARS-CoV-2.

With the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), a high-speed and convenient detection technology should be at the forefront of medical care worldwide. This study evaluated the usefulness of GeneSoC, a compact, high-speed reciprocal flow quantitative reverse transcription polymerase chain reaction system, for the detection of SARS-CoV-2. The results support the use of this system for the rapid identification of SARS-CoV-2. This approach can contribute to the strategic selection of initial management strategies for patients with COVID-19.

Preferential expression of the vasoactive intestinal peptide (VIP) receptor VPAC1 in human cord blood-derived CD34+CD38- cells: possible role of VIP as a growth-promoting factor for hematopoietic stem/progenitor cells.

Primitive hematopoietic progenitor cells such as severe combined immunodeficiency- repopulating cells and long-term culture-initiating cells are enriched in CD34+CD38- cells derived from various stem cell sources. In this study, to elucidate the features of such primitive cells at the molecular level, we tried to isolate genes that were preferentially expressed in umbilical cord blood (CB)-derived CD34+CD38- cells by subtractive hybridization. The gene for VPAC1 receptor, a receptor for the neuropeptide vasoactive intestinal peptide (VIP), was thereby isolated and it was shown that this gene was expressed in both CD34+CD38- and CD34+CD38+ CB cells and that the expression levels were higher in CD34+CD38- CB cells. Next, we assessed the effects of VIP on the proliferation of CD34+ CB cells using in vitro culture systems. In serum-free single-cell suspension culture, VIP enhanced clonal growth of CD34+ CB cells in synergy with FLT3 ligand (FL), stem cell factor (SCF), and thrombopoietin (TPO). In serum-free clonogenic assays, VIP promoted myeloid (colony-forming unit-granulocyte/macrophage (CFU-GM)) and mixed (CFU-Mix) colony formations. Furthermore, in Dexter-type long-term cultures, VIP increased colony-forming cells at week 5 of culture. These results suggest that VIP functions as a growth-promoting factor of CB-derived hematopoetic progenitor cells.

Chorioamnionitis decreased incidence of respiratory distress syndrome by elevating fetal interleukin-6 serum concentration.

Respiratory distress syndrome (RDS) of newborns is one of the most important factors determining neonatal morbidity and mortality. The interleukin-6 (IL-6) titre in cord sera of RDS-free neonates born to mothers with histological chorioamnionitis was significantly higher than that in RDS-complicated neonates without chorioamnionitis. Maternal administration of glucocorticoid suppressed the IL-6 concentrations in the cord sera of fetuses with chorioamnionitis. The fetuses without chorioamnionitis who suffered from RDS even after maternal glucocorticoid administration showed a similar IL-6 titre to that of RDS-affected neonates without chorioamnionitis. Examination of the mechanism by which IL-6 decreased the incidence of fetal RDS revealed that H441-4, a human pulmonary adenocarcinoma cell line, stimulated with recombinant (r)-IL-6 started the synthesis of mRNA and protein of pulmonary surfactant protein (SP)-A. The present study shows that IL-6 elevation in fetuses with chorioamnionitis promotes fetal lung maturation by inducing SP-A synthesis, thereby decreasing the incidence of RDS in the preterm neonates.

Triple marker screening for trisomy 21, trisomy 18 and open neural tube defects in singleton pregnancies of native Japanese pregnant women.

OBJECTIVE: To report the results of prenatal triple marker screening on a population of Japanese pregnant women. METHODS: From April 1994 through March 1999, a total of 32,925 native Japanese women with singleton pregnancies requested a triple marker-screening test. Multiples of the median values for 3 markers and individual risks for each patient were calculated following adjustment for the Japanese weight correction factor. The risk cut-off values used for Down syndrome (T21), open spina bifida (OSB) and trisomy 18 (T18) were 1: 295, 1: 290, and 1: 100, respectively. Follow-up information was collected postpartum and statistically analyzed. RESULTS: Detection rates (DR) of T21 for women less than 35 years, over 35 years and overall were 58, 94, and 83%, respectively. DR of T18 for women less than 35 years, over 35 years and overall were 75, 79, and 79%, respectively. DR of open neural tube defects (ONTD) was 100%. CONCLUSIONS: The first cumulative data of an intervention program and prospective follow-up studies in Japan have proven to be similar to other published reports. Individual risk values were calculated for each pregnancy for T21, T18 and ONTD. This screening program is more effective than age-dependent screening for detecting T21, T18 and ONTD pregnancies.

Human placental cells show enhanced production of interleukin (IL)-8 in response to lipopolysaccharide (LPS), IL-1 and tumour necrosis factor (TNF)-alpha, but not to IL-6.

Interleukin-8 (IL-8) is a chemotactic and activating factor for neutrophils which play important roles in host defence mechanisms. The human placenta constitutively produces IL-8 during pregnancy and enhances its production in chorioamnionitis. The present study was designed to investigate in vitro the regulatory mechanism for IL-8 production in the placentas in normal and inflammatory states. Placental cells produced IL-8 in a dose-dependent fashion when stimulated with lipopolysaccharide (LPS). The purified trophoblasts showed significantly higher IL-8 production than untreated placental cells. The expression of IL-8 gene in the trophoblasts in the third trimester was observed by reverse transcription-polymerase chain reaction (RT-PCR). The placental cells also release IL-8 in a dose-dependent manner, in response to r-(recombinant) IL-1alpha and tumour necrosis factor (TNF)-alpha, but not rIL-6. Moreover, LPS-activated placental cells spontaneously produced a much larger amount of IL-8 and showed increased responses to rIL-1alpha and TNF-alpha. It may, therefore, be proposed that placental cells with multiple endocrine functions exert immunological functions by constitutive production of IL-1 and TNF-alpha, which stimulate placental IL-8 release. This cytokine cascade in the placenta may be augmented by LPS in chorioamnionitis, thereby potentiating the feto-maternal defence mechanisms against infection.

Regulation of placental monocyte chemotactic and activating factor during pregnancy and chorioamnionitis.

A number of placental cytokines participate in the feto-maternal defence mechanism. Monocyte chemotactic and activating factor (MCAF) is one of these chemokines. We investigated the pattern of placental MCAF production, the localization of MCAF-producing cells in the placenta, and alterations in its expression in chorioamnionitis. The amounts of MCAF protein produced by the placenta increased during pregnancy irrespective of the presence of uterine contraction. MCAF mRNA was expressed at equivalent levels in the first and second trimester placenta, but at higher levels in the third trimester placenta. Chorioamnionitis in the third trimester placenta induced a 10-fold increase in MCAF protein production and a 3-fold increase in MCAF mRNA level. Immunohistochemical analysis of the placenta revealed the MCAF-producing cells to be trophoblasts. Stimulation of placental cells with lipopolysaccharide augmented MCAF production. These results indicate unique transcriptional and developmental regulation of MCAF mRNA and protein production during pregnancy and chorioamnionitis. Placental MCAF may be involved in the feto-maternal defence mechanism by activating feto-placental and maternal monocytes in chorioamnionitis.

Interleukin-8 level in maternal serum as a marker for screening of histological chorioamnionitis at term.

OBJECTIVE: To establish a clinical method for immediate diagnosis of histological chorioamnionitis, by maternal blood sampling at term. METHOD: The sera of 22 mothers with chorioamnionitis and 81 mothers without chorioamnionitis at term delivery were collected. The serum levels of cytokines including interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8) were titered and other conventional markers such as white blood cell and CRP were measured simultaneously. Chorioamnionitis was histopathologically confirmed after delivery. RESULT: The sera of mothers with histological chorioamnionitis showed a significant increase in IL-8 titer, but not in those of other cytokines or conventional markers, compared with those without chorioamnionitis. A positive correlation was observed between maternal and cord serum IL-8 levels. Maternal IL-8 showed the highest predictive value for diagnosis of histological chorioamnionitis. CONCLUSION: Measurement of maternal IL-8 is useful for rapid prenatal screening of histological chorioamnionitis at term.

Human decidual cell biosynthesis of leukemia inhibitory factor: regulation by decidual cytokines and steroid hormones.

The production of leukemia inhibitory factor (LIF) is suggested to be critical for the successful implantation of blastocysts into decidua, because LIF expression is essential for the implantation of mouse blastocytes. We investigated the regulation of LIF production by decidual cytokines and steroid hormones. Stimulation of decidual cells by interleukin-1, tumor necrosis factor alpha, or transforming growth factor beta augmented LIF production in a dose-dependent manner. Moreover, estradiol, a steroid hormone that increases during ovulation and early pregnancy, also enhanced LIF production in a dose-dependent manner. These responses were blocked by protein kinase C (PKC) inhibitor but not by other kinase inhibitors, suggesting an important role of PKC in decidual LIF production mediated by cytokines and estradiol. We also showed that stimulating decidual cells with LIF failed to stimulate DNA synthesis and prolactin production in these cells. In summary, LIF was mainly localized in the decidual glands and stroma, and its production was increased by cytokines and estradiol in a dose-dependent fashion; but stimulation of decidual cells by LIF did not influence their proliferation or their prolactin production.

Alteration of p16 and p15 genes in common epithelial ovarian tumors.

We have examined the roles of 2 putative tumor-suppressor genes, the p16 and p15 inhibitor-of-cyclin-dependent-kinase genes, in the most commonly occurring epithelial tumors of the human ovary. Expression of p16 mRNA, examined by RT-PCR, was significantly reduced in 15 of the 48 tumors. Aberrant expression of p16 protein, detected by immunohistochemistry, occurred in 22 of 60 tumors, more frequently in low-grade tumors, and had significant correlation with low p16 mRNA expression. Hypermethylation of a site within the 5'-CpG island of the p16 gene was significantly associated with loss of p16 mRNA and protein expression. Homozygous gene deletion, evaluated by differential PCR analysis, was found in 2 tumors for the p16 gene and in 1 tumor for the p15 gene among 70 ovarian tumors examined. PCR-SSCP analysis detected point mutations in p16 in 4 tumors and in p15 in 1 tumor. One was a 38-bp deletion, from codons 48 to 60, in a mucinous tumor of low malignant potential; another was a non-sense mutation in codon 60 in a mucinous adenocarcinoma. The remaining 2 mutations were mis-sense mutations, one in codon 58 and the other in codon 60, in 2 endometrioid adenocarcinomas. We conclude that inactivation of p16, by loss of p16 mRNA and protein expression as a consequence of hypermethylation of the 5'-CpG island, rather than by gene deletion or point mutation, may play an important role in the genesis of human ovarian epithelial tumors.

Value of the maternal interleukin 6 level for determination of histologic chorioamnionitis in preterm delivery.

The present study examined whether maternal serum cytokine levels are useful for the diagnosis of histologic chorioamnionitis. The blood samples of 29 women who delivered preterm between 22 and 34 weeks of gestation were collected at delivery, and placentas were histopathologically examined for chorioamnionitis. The interleukin (IL) 6 titer was higher in 18 mothers with histologic chorioamnionitis (median 12.0 pg/ml, range 4.9-63.5 pg/ml) than that in 11 mothers without histologic chorioamnionitis (median 3.5 pg/ml, range 1.7-14.9 pg/ml; p < 0.0001). The C-reactive protein (CRP) titer also differed significantly between these two groups (chorioamnionitis group: median 5.2 mg/dl, range 0.1-12.3 mg/dl; no chorioamnionitis group: median 0.2 mg/dl, range 0.1-0.5 mg/dl; p = 0.0001). The IL-6 titer showed better clinical diagnostic indices and a higher odds ratio (9.78, 95% confidence interval 1.50-63.82) than did CRP (3.26, 95% confidence interval 1.22-8.67). The levels of IL-8, monocyte chemotactic and activating factor, and soluble IL-6 receptor did not differ between the two groups. These data suggest that the level of maternal serum IL-6 is more useful than other markers, including CRP, for the identification of women at risk of impending preterm labor with histologic chorioamnionitis.

Chorioamnionitis reduces placental endocrine functions: the role of bacterial lipopolysaccharide and superoxide anion.

Chorioamnionitis has been shown to be one of the most important factors in inducing preterm delivery. The present study was undertaken to examine the effects of chorioamnionitis on placental endocrine functions. Preterm placentas with histologic chorioamnionitis produced smaller amounts of human chorionic gonadotropin (hCG) and human placental lactogen (hPL) than those without chorioamnionitis (P < 0.001). To examine the mechanism involved in the suppression of placental endocrine functions induced by chorioamnionitis, we initially confirmed the expression of lipopolysaccharide (LPS) receptor, i.e. the CD14 molecule, on trophoblasts by Northern blot analysis and immunohistochemistry. We then stimulated purified trophoblasts with LPS, which is the major agent which induces inflammatory responses in the host via the LPS receptor. The trophoblasts stimulated with LPS produced reduced amounts of hCG, hPL, and progesterone in a time- and dose-dependent fashion in spite of the induced manganese-superoxide dismutase (SOD) synthesis. Stimulation of trophoblasts with hypoxanthine and xanthine oxidase resulted in suppressed hCG production, while the simultaneous addition of SOD into the culture medium reversed the suppression of hCG production. LPS in the placenta with chorioamnionitis might directly stimulate trophoblasts through the LPS receptor (CD14), thus reducing placental endocrine functions. Superoxide anions which exogenously act on trophoblasts might be generated by simultaneous stimulation of neutrophils and monocytes at the feto-maternal interface by LPS, and additively reduce placental endocrine functions.

Elevated nitric oxide concentration in the seminal plasma of infertile males: nitric oxide inhibits sperm motility.

PROBLEM: To evaluate the effect of nitric oxide in the seminal plasma on sperm motility. METHOD: Seminal plasma concentrations of NO2-, a stable end product of nitric oxide, of 108 males of infertile couples and 15 proven fertile donors were measured and compared with spermatogram parameters. Motile sperm was incubated with a nitric oxide-generating drug, sodium nitroprusside, for 6 hr in the absence or presence of oxyhemoglobin, an inhibitor of nitric oxide. RESULTS: The NO2- concentration in the seminal plasma was 6.58 +/- 0.5.6 microM in 26 infertile males with leukocytospermia, 5.51 +/- 0.25 microM in 82 infertile males without leukocytospermia, and 3.91 +/- 0.16 microM in 15 controls. There was a significant correlation between the NO2- concentration and sperm motility. Sodium nitroprusside reduced the sperm motility in a dose- and time-dependent manner and its reduction was completely inhibited by the addition of oxyhemoglobin. CONCLUSION: These findings indicate that nitric oxide concentration in the seminal plasma of infertile males is elevated and that nitric oxide is an inhibitor of sperm motion.

Plasma nitric oxide levels in pregnant patients with preeclampsia and essential hypertension.

Nitric oxide (NO) production may be an important causal factor in hypertensive disorders during pregnancy. The plasma concentrations of NO2-(+) NO3-, stable metabolites of NO, were measured in 70 nonpregnant women, 323 normotensive pregnant women, 23 pregnant patients with preeclampsia, and 7 pregnant patients with essential hypertension. The normotensive women had higher plasma concentrations (30.0 +/- 0.6 mumol/l) than nonpregnant women (18.3 +/- 1.0 mumol/l; p < 0.0001). The plasma concentrations in the patients with preeclampsia (45.6 +/- 2.3 mumol/l) were higher than in the normotensive women (30.3 +/- 1.0 mumol/l; p < 0.0001) and were correlated with the systolic blood pressure (r = 0.442; p < 0.05). However, pregnant patients with underlying essential hypertension had significantly lower plasma concentrations (19.1 +/- 3.0 mumol/l; p < 0.005). These findings suggest that NO contributes to maternal vasodilation, the maintenance of uterine quiescence, and the pathogenesis and clinical features of hypertensive disorders during pregnancy.

Detection of monocyte chemotactic and activating factor (MCAF) and interleukin (IL)-6 in human seminal plasma and effect of leukospermia on these cytokine levels.

PROBLEM: To demonstrate whether monocyte chemotactic and activating factor (MCAF) and interleukin-6 (IL-6) are present in the seminal plasma, and whether these presence is modulated by leukospermia. METHODS: Semen samples from 53 men were obtained by masturbation and examined for the presence of MCAF and IL-6 by enzyme immunoassay (EIA). Semen samples were obtained from 28 infertile men without leukospermia, 16 infertile men with leukospermia, and nine proven-fertile men. The correlation between the amount of MCAF in the seminal plasma with some spermiogram parameters and other cytokines such as IL-6 and IL-8 was statistically evaluated. RESULTS: Immunoreactive MCAF was detected in the seminal plasmas of all 53 subjects. The MCAF titer in the seminal plasma of patients with leukospermia (11.19 +/- 2.75 micrograms/l) was significantly higher than that in the seminal plasma of the patients without leukospermia (3.24 +/- 0.53 micrograms/l) and the fertile men (2.78 +/- 0.35 micrograms/l) (P < 0.001). The IL-6 titer in the seminal plasma of the patients with leukospermia (21.05 +/- 4.49 ng/l) was also significantly higher than that in the seminal plasma of the patients without leukospermia (8.77 +/- 1.92 ng/l) and the fertile men (6.94 +/- 1.27 ng/l) (P < 0.01). There was a high degree of correlation among the levels of MCAF, IL-6 and IL-8 in the seminal plasma. CONCLUSIONS: These findings demonstrated the presence of MCAF and IL-6 in the seminal plasma, and that the levels of these cytokines were elevated in the seminal plasma of the infertile patients with leukospermia.

Soluble interleukin-6 (IL-6) receptor in the sera of pregnant women forms a complex with IL-6 and augments human chorionic gonadotropin production by normal human trophoblasts through binding to the IL-6 signal transducer.

To study the role of soluble interleukin-6 receptor (sIL-6R) during pregnancy, sIL-6R levels in the sera of pregnant women in the first, second, and third trimesters were determined and found to remain unchanged during pregnancy, but were significantly higher than those in nonpregnant women in the follicular, ovulatory, and luteal phases of the menstrual cycle (P < 0.001). IL-6 levels, however, in the sera of pregnant women at all trimesters showed no difference from those in nonpregnant women at any stage of the menstrual cycle. Recombinant sIL-6R (rsIL-6R) augmented hCG production by rIL-6-stimulated trophoblasts dose dependently, but failed to enhance hCG production by unstimulated trophoblasts. rIL-6- and rsIL-6R-induced hCG production was significantly blocked by anti-IL-6R antibody, PM1; antisignal transducing glycoprotein 130 (gp130) antibody, GPX7; or a tyrosine kinase inhibitor, genistein. Thus, sIL-6R in serum from pregnant women forms a complex with placental and decidual IL-6 in a manner similar to trophoblast membrane-bound IL-6R. These two discrete types of IL-6R and IL-6 complex might act cooperatively by binding to gp130 and subsequently evoking tyrosine kinase activity in the trophoblasts to produce hCG in vivo.

Leukemia inhibitory factor produced at the fetomaternal interface stimulates chorionic gonadotropin production: its possible implication during pregnancy, including implantation period.

We investigated the role of leukemia inhibitory factor (LIF) at the implantation site of human embryos. The first trimester decidual tissue produced higher levels of LIF than chorionic tissue, but the decidua produced much smaller amounts of interleukin-6 (IL-6) than the chorion in vitro, as determined by enzyme-linked immunosorbent assay. The reverse transcription-polymerase chain reaction and immunohistochemical analysis revealed the expression and localization, on the trophoblasts, of glycoprotein 130 (gp130), an IL-6 signal transducer receptor component shared by the cytokines such as LIF and IL-6. Trophoblasts stimulated by recombinant LIF (rLIF) produced CG titer at the amount similar to that induced by rIL-6. Recombinant LIF-induced CG production was significantly blocked by anti-gp130 antibody but not by anti-IL-6 receptor antibody, whereas rIL-6-induced CG was completely blocked by both antibodies. Recombinant LIF- and rIL-6-induced CG productions were both significantly blocked by genistein, a tyrosine kinase inhibitor, suggesting an involvement of tyrosine kinase in gp130-mediated CG production. Since CG is capable of stimulating trophoblast growth and differentiation as well as placental metabolism, LIF produced at the fetomaternal interface are considered to stimulate the trophoblasts to produce CG, which may contribute to the maintenance of the placental functions and embryonal growth.

Analysis of carbohydrate-intolerant profiles of mothers with normal glucose tolerance tests and their large for gestational age neonates.

OBJECTIVE: To examine endocrine states of mothers with normal 75-g oral glucose tolerance tests (GTTs) who gave birth to large for gestational age (LGA) neonates (group I) and to examine those neonates. METHODS: We examined plasma glucose levels and serum immunoreactive insulin responses after the 75-g oral GTT was given to group I mothers (N = 34), mothers with an abnormal oral GTT who gave birth to LGA neonates (group II, N = 21), and those with normal oral GTTs having appropriate for gestational age neonates (group III, N = 173). We also examined the infants, checking neonatal birth weight, levels of immunoreactive insulin and C-peptide immunoreactivity in cord sera at birth and the lowest blood sugar level after birth to see if a correlation existed between them. RESULTS: Group I and II mothers showed higher titers in plasma glucose levels and remarkably enhanced ratios of 60- to 30-minute immunoreactive insulin values (immunoreactive insulin up-ratio) after load compared with those of group III mothers. Cord serum immunoreactive insulin and C-peptide immunoreactivity were significantly higher and the lowest blood sugar level was significantly reduced in group I and II neonates compared with those in group III. We observed a positive correlation between cord serum immunoreactive insulin, C-peptide immunoreactivity, and birth weight, but a negative correlation between cord serum immunoreactive insulin, birth weight, and the lowest blood sugar level in group I and II neonates (strongest tendency in group II), but not in group III neonates. CONCLUSION: All of the abnormal carbohydrate metabolic responses in group I mothers and neonates may result in the promotion of growth in LGA fetuses similar to group II, but to a lesser extent. Identification of group I mothers by the immunoreactive insulin up-ratio after oral GTT will help predict the occurrence of LGA neonates and their possible hypoglycemia.

[Immunological analysis of the mechanism of maternal tolerance of a fetus and the cytokine-mediated regulation of feto-placental functions].

Recent analysis of a various kinds of cytokines revealed that the cytokines are actively involved in a number of important biological functions including immunological and endocrine functions. The present study investigated the unique cytokine-mediated immunological and endocrinological functions in the intra-uterine space during pregnancy. A human placenta which expresses paternal and maternal antigens was revealed to escape from maternal immune systems by releasing immunosuppressive cytokines derived from the placenta. Placental cytokines such as interleukin-6 (IL-6) activated IL-6-receptor-mediated signal transduction pathways to produce human chorionic gonadotropin (hCG). IL-1 and tumor necrosis factor-alpha (TNF-alpha) synergistically augmented IL-6 production to stimulate hCG production. However, transforming growth factor-beta (TGF-beta) suppressed these cytokine-mediated hCG production as well as IL-6 production. Thus, these placental cytokines, mainly derived from trophoblasts, cooperatively contributed to hCG production. IL-8 and monocyte chemotactic and activating factor (MCAF) activate host defense mechanism by activating neutrophils and monocytes as well as macrophages, respectively. IL-6 also activates immune responses and promote synthesis of acute-phase reactant proteins, contributing to augmentation of host defense mechanism in a different way from IL-8 and MCAF. Human placenta in the 3rd trimester actively produced these cytokines for potentiation of placental defense mechanism during pregnancy and in chorioamnionitis. A fetus in chorioamnionitis also produced these cytokines in utero for potentiation of fetal defense mechanism. Among these cytokines, IL-8 in a cord serum was a very sensitive and useful marker for clinical diagnosis of chorioamnionitis. Cord serum IL-6, in contrast, stimulated the synthesis of surfactant protein-A (SP-A) to promote fetal lung maturation and reduce the incidence of RDS. Collectively, the present study revealed the cytokine network in the placenta regulating maternal immune responses, placental endocrine functions, feto-maternal defense mechanism and fetal respiratory maturation.

Current topic: human placental Fc receptors.

Human immunoglobulin G (IgG) Fc receptors are important in the materno-fetal relationship. Three classes of IgG Fc receptors are recognized which generate multiple isoforms, most of which are expressed in different cellular components of human placenta at different times during pregnancy. Although the distinct biological functions of Fc gamma R phenotypes expressed in human placenta are still unknown, recent data provide evidence for an important association between the Fc gamma R phenotype and transcytosis of IgG in the placenta. Selective transfer of maternal IgG across the placenta provides passive immunity to the fetus during the period when its own immune system is gaining protective potential. Furthermore, placenta-specific macrophages may contribute through Fc gamma R-mediated phagocytosis to the protection of the fetus from either infection or maternal immune attack against paternally inherited fetal antigens. Ontogeny and expression of various isoforms of Fc gamma R subtypes may be the key to the elucidation of the transport mechanism of maternal IgG to the fetus, in addition to the determination of the mechanisms of placental protection of the fetus against the maternal immune system.

Prenatal detection of ischemic changes in the placenta of the growth-retarded fetus by Doppler flow velocimetry of the maternal uterine artery.

OBJECTIVE: To determine the relationships among the pregnancy outcomes of growth-retarded fetuses, Doppler flow velocimetry of the fetomaternal circulation, and pathologic changes in the placenta. METHODS: Forty-seven fetuses confirmed to be growth-retarded by ultrasonographic biometry were monitored during pregnancy in terms of the resistance indexes of the maternal uterine, fetal umbilical, and fetal middle cerebral arteries. After delivery, the placentas were examined for pathologic changes such as infarction and villous ischemia. RESULTS: Compared with 23 fetuses with nonischemic placentas, 24 growth-retarded fetuses whose placentas showed ischemic lesions were more frequently delivered preterm (P < .001) and by cesarean for fetal distress (P < .01), and they also had lower mean pH, higher carbon dioxide pressure, and lower oxygen pressure values (P < .05). Compared with the fetal umbilical and middle cerebral artery resistance indexes, the uterine artery resistance index showed the highest sensitivity (91.7%), specificity (78.3%), and positive predictive value (81.5%) for detecting placental ischemic changes. Linear discriminative analysis also showed that the uterine artery resistance index had the strongest correlation (P < .00001) with the placental ischemic changes. CONCLUSION: Ischemia of the placenta is associated with an adverse pregnancy outcome in growth-retarded fetuses. The placental ischemic changes can be detected using Doppler flow velocimetry. Measurement of the uterine artery resistance index might be useful for determining the clinical management of growth-retarded fetuses.