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This study was performed to evaluate the application of fetal middle cerebral artery peak systolic velocity (MCA-PSV) for prediction of newborn anemia with umbilical cord blood hemoglobin concentration at birth (UCB-Hb) < 10.0 g/dL among infants born at gestational week (GW) ≥ 36 to unselected women.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/S0002-9378(97)80045-2 Byline: Hisanori Minakami, Shigeki Matsubara, Ikuo Sato Author Affiliation: Department of Obstetrics and Gynecology, Jichi Medical School, Minamikawachi-machi Tochigi, 329-04 Japan

BackgroundGenetic variants responsible for childhood interstitial lung disease (chILD) have not been studied extensively in Japanese patients.MethodsThe study population consisted of 62 Japanese chILD patients. Twenty-one and four patients had pulmonary hypertension resistant to treatment (PH) and hypothyroidism, respectively. Analyses of genetic variants were performed in all 62 patients for SFTPC and ABCA3, in all 21 PH patients for FOXF1, and in a limited number of patients for NKX2.1.ResultsCausative genetic variants for chILD were identified in 11 (18%) patients: SFTPC variants in six, NKX2.1 variants in three, and FOXF1 variants in two patients. No patients had ABCA3 variants. All three and two patients with NKX2.1 variants had hypothyroidism and developmental delay, respectively. We found six novel variants in this study.ConclusionMutations in SFTPC, NKX2.1, and FOXF1 were identified among Japanese infants and children with chILD, whereas ABCA3 mutations were rare.

Changes in hemodynamics and blood pressure occur shortly before and after childbirth regardless of the mode of delivery. This study aimed to test the hypothesis that parturition induces a temporal increase in podocyturia monitored by podocyte-specific protein podocin mRNA expression levels (Pod-mRNA). A total of 105 urine specimens, consisting of 43 and 62 from 18 and 20 otherwise healthy women with vaginal delivery (VD) and elective cesarean delivery (ECS), respectively, were studied. Determination of urine protein and creatinine (Cr) concentrations and quantitative analyses of Pod-mRNA, nephrin mRNA (Nep-mRNA), synaptopodin mRNA (Syn-mRNA), and aquaporin 2 mRNA expression were performed using RT-PCR in pelleted urine samples. Levels of mRNA expression were corrected by urine Cr concentration. Podocyturia increased significantly, concomitant with a significantly decreased Nep:Pod-mRNA ratio (NPR) in the urine, collected immediately before or after childbirth regardless of the delivery mode compared with urine collected before commencement of labor or on postpartum day 3or later. Podocyturia was significantly negatively correlated with NPR [correlation coefficient (r) = −0.614/−0.750 for VD/ECS women, respectively], as well as the Syn:Pod-mRNA ratio. Systolic blood pressure exceeded 140 mmHg during labor in 50% of VD women, and mean arterial pressure was significantly positively correlated with podocyturia during labor in VD women (r= 0.733). Thus parturition induces a transient increase in urine podocytes with reduced Nep- and Syn-mRNA expressions. Glomerular podocytes with reduced Nep- and Syn-mRNA levels were suggested to be likely to detach from the glomerular basement membrane around childbirth.

Byline: Hisanori Minakami, Tomoyuki Kuwata, Ikuo Sato Author Affiliation: Department of Obstetrics and Gynecology, Jichi Medical School, Minamikawachi-machi, Tochigi, 329-04 Japan

This study was performed to determine how often Japanese women diagnosed as normoglycemic on first-trimester 75-g glucose tolerance test (75gGTT) later develop gestational diabetes mellitus (GDM).

Autophagy is activated by environment unfavorable for survival and requires Atg9a protein. Mice heterozygous for p57Kip2, devoid of the imprinted paternal allele (p57Kip2+/−), are known to develop hypertension during pregnancy. To determine whether fetal Atg9ais involved in the intrauterine survival and growth of fetal mice, this study was performed on Atg9aheterozygous (Atg9a+/−) pregnant mice with and without p57Kip2+/−. The pregnant mice heterozygous for both knockout alleles of Atg9aand p57Kip2(Atg9a+/−/p57Kip2+/−), but not those heterozygous for Atg9aalone, developed hypertension during pregnancy. Placental expression of Atg9amRNA was significantly decreased in the Atg9a−/−mice compared to Atg9a+/−or Atg9a+/+mice. The Atg9a−/−fetal mice exhibited significantly retarded growth and were more likely to die in uterocompared to Atg9a+/+and Atg9a+/−fetal mice. Growth retardation was observed in the presence of maternal hypertension in Atg9a−/−fetal mice. These results suggest that Atg9a−/−fetal mice from pregnant dams heterozygous for both knockout alleles of Atg9aand p57Kip2are more susceptible to hypertensive stress than fetuses with intact autophagic machinery.

Background:Genetic variations associated with interstitial lung diseases (ILD) have not been extensively studied in Japanese infants.Methods:Forty-three infants with unexplained lung dysfunction were studied. All 43, 22, and 17 infants underwent analyses of surfactant protein (SP)-C gene (SFTPC) and ATP-binding cassette A3 gene (ABCA3), SP-B gene (SFTPB), and SP-B western blotting, respectively. Two and four underwent assessment of granulocyte macrophage colony-stimulating factor–stimulating phosphorylation of signal transducer and activator of transcription-5 (pSTAT-5) and analyses of FOXF1 gene (FOXF1), respectively.Results:ILD were diagnosed clinically in nine infants: four, three, and two had interstitial pneumonitis, hereditary pulmonary alveolar proteinosis (hPAP), and alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), respectively. Genetic variations considered responsible were detected in six (67%) of the nine infants with ILD: three with hPAP (SFTPC p.Leu45Arg and p.Gln145fs, and ABCA3 p.Arg1583Trp/p.Val1495CysfsX21), two with interstitial pneumonitis (SFTPC p.Lys63Glu and p.Ser72Asn/p.Gly100Ala), and one with ACD/MPV (FOXF1 p.Leu300ArgfsX79). None showed SFTPB mutations or defects in pSTAT-5. The 17 bronchoalveolar lavage or tracheal aspirates contained enough SP-B protein.Conclusion:The SP-C abnormality was most prevalent, and SP-B deficiency was rare in Japanese infants with hereditary ILD.

Mucosal-associated invariant T (MAIT) cells play an important physiological role in host pathogen defense and may also be involved in inflammatory disorders and multiple sclerosis. The rarity and inefficient expansion of these cells have hampered detailed analysis and application. Here, we report an induced pluripotent stem cell (iPSC)-based reprogramming approach for the expansion of functional MAIT cells. We found that human MAIT cells can be reprogrammed into iPSCs using a Sendai virus harboring standard reprogramming factors. Under T cell-permissive conditions, these iPSCs efficiently redifferentiate into MAIT-like lymphocytes expressing the T cell receptor Vα7.2, CD161, and interleukin-18 receptor chain α. Upon incubation with bacteria-fed monocytes, the derived MAIT cells show enhanced production of a broad range of cytokines. Following adoptive transfer into immunocompromised mice, these cells migrate to the bone marrow, liver, spleen, and intestine and protect against Mycobacterium abscessus. Our findings pave the way for further functional analysis of MAIT cells and determination of their therapeutic potential.

The outcome of pregnancy in patients with isolated proteinuria is believed to be favorable. However, whether women with isolated proteinuria are at risk for progressing to preeclampsia has not been extensively studied.

Perterm labour continues to complicate a substantial number of pregnancies, and preterm delivery accounts for most early neonatal deaths not due to congenital abnormalities.[1] Ritodrine hydrochloide, a β sympathomimetic agent [...]

The pathophysiologic processes that occur at the cellular and molecular levels in intrauterine fetal growth restriction are largely unknown. Catechol-O-methyltransferase (COMT) is a phase II enzyme that inactivates catechol estrogens by transfer of a methyl group. A functional Val158Met polymorphism in the COMTgene has been known as a susceptible marker for breast cancer. The aim of this study was to examine the association between this polymorphism and fetal growth.

Steroidogenic acute regulatory (StAR) protein plays a critical role in steroid hormone synthesis. Tropic hormones induce human StARgene expression by a cAMP-dependent pathway. Steroidogenic factor-1/adrenal-4-binding protein (SF-1/Ad4BP) plays an important role in the expression of human StARgene. We investigated the mechanism of cAMP responsiveness in human StARgene expression in NCI-H295R cells. The StAR promoter activity and protein levels in cells subjected to various treatments were examined. Anti-SF-1/Ad4BP IgG transfection treatment resulted in decreases in the basal StAR promoter activity and StAR protein levels, but did not affect cAMP-stimulated promoter activity and protein levels. The basal and cAMP-stimulated StAR promoter activity levels were reduced in SF-1/Ad4BP mutant (G35E)-transfected cells, but the cAMP induction of StAR promoter activity in response to 1 mM 8-Br-cAMP was not inhibited when G35E SF-1/Ad4BP mutant expression vectors were co-transfected with cAMP-response element-binding (CREB) expression vectors. Although the basal StAR mRNA expression and protein levels were decreased by SF-1/Ad4BP-siRNA treatment, the cAMP-stimulated StAR mRNA expression and protein levels did not change. The basal StAR promoter activity level was not decreased by cAMP-response element modulator (CREM)-siRNA treatment, but the cAMP-stimulated StAR promoter activity level, the magnitude of cAMP induction of StAR promoter, and the cAMP-stimulated StAR protein level were decreased. The cAMP induction of StAR promoter activity in cells was inhibited when S117ACREM mutant expressionvectors were transfected. We conclude that inhibition of the function of SF-1/Ad4BP does not reduce the cAMP induction of StAR promoter activity and protein level. CREM is needed to confer cAMP responsiveness in human StAR protein expression.

A possible association between intrauterine inflammation and impairments of lung development has been suggested. The purpose of this study is to determine the influence of a potent proinflammatory agent, intra-amniotic lipopolysaccharide (LPS), on lung development. At 21 d gestation, an intra-amniotic injection of 1 g LPS was administered to two subgroups of WKAH rats. One subgroup received only LPS and the other received LPS plus a fetal intraperitoneal dose of 0.25 g granulocyte-colony stimulating factor (hrG-CSF) to produce peripheral blood neutrophilia. A third subgroup received hrG-CSF only, and a control group received maternal intraamniotic and fetal intraperitoneal normal saline. All pups were delivered by cesarean section at 22 d (term, 22.5 d) and maintained under identical conditions. Left upper lungs were obtained for morphometric analysis at 1, 3, 7, 14, 21, 45, and 60 d of age. Morphometric analysis indicated that changes in alveolar surface density (Sv), average alveolar radius (r), and numerical density of alveoli (nv) all showed that there were fewer and larger alveoli in rat lungs that had been exposed to LPS, but not to hrG-CSF alone or saline. LPS-exposed alveoli showed fewer secondary septa, suggesting an arrest of alveolarization. No destructive changes were observed in any alveoli. We concluded that these changes could be caused purely by intra-amniotic LPS. These abnormalities closely mimic those of new bronchopulmonary dysplasia. The LPS damage model may be applicable to further studies of the pathophysiology of new BPD.

ABSTRACTTo examine the association between colonization by two newly classified species of genital ureaplasmas (Ureaplasma parvumand U. urealyticum) in early pregnancy and subsequent late abortion or preterm birth at <34 weeks of gestation, four species of genital mycoplasmas—Mycoplasma genitalium, M. hominis, U. parvum, and U. urealyticum—as well as Chlamydia trachomatisand Neisseria gonorrhoeaewere examined by PCR-based methods in a prospective cohort study of 877 women with singleton pregnancies at <11 weeks of gestation. Antibiotics were used only in cases in which C. trachomatisand/or N. gonorrhoeaewas detected. Multivariate logistic-regression analysis was used to assess independent risk factors after taking maternal low body weight and past history of preterm birth into account. M. genitalium, M. hominis, U. parvum, U. urealyticum, C. trachomatis, and N. gonorrhoeaewere detected in 0.8%, 11.2%, 52.0%, 8.7%, 3.2%, and 0.1% of these 877 women, respectively. Twenty-one (2.4%) women experienced late abortion or preterm birth at <34 weeks of gestation. Three factors—detection of U. parvumin the vagina (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.1 to 8.5); use of antibiotics, such as penicillin and cefatrizine, for incidental inflammatory complications before 22 weeks of gestation (OR, 4.2; 95% CI, 1.6 to 10.0); and past history of preterm birth (OR, 10.4; 95% CI, 2.7 to 40.5)—were independently associated with late abortion and preterm birth. In conclusion, vaginal colonization with U. parvum, but not U. urealyticum, is associated with late abortion or early preterm birth.

Mn‐ and Cu‐Zn superoxide dismutase (SOD) activities and generation of superoxide radicals (O2−) were assessed in leukemic cells from 10 patients with acute myeloid or monocytic leukemia (AML) and 10 patients with acute lymphoblastic leukemia (ALL), using a sensitive, specific chemiluminescence method. Leukemic cells were classified according to the French–American–British classification. M4 AML cells from two patients produced some O2−upon stimulation with opsonized zymosan (OZ), phorbol myristate acetate (PMA) or N‐formyl‐methionyl‐leucyl‐phenylalanine (FMLP), but less than normal granulocytes or monocytes. M5b AML cells from one patient produced as much O2−in response to these stimulants as normal monocytes. No O2−generation was induced in other types of leukemic cells. Total SOD activity in AML cells was significantly greater in normal granulocytes, but was only half of the activity in ALL cells. Mn‐SOD in AML cells was very low or undetectable. These results suggest that except in M5b cells, decreased O2−production may contribute to susceptibility to infections in AML patients. Decreased Mn‐SOD activity in AML cells may predispose them to oxidative stress. Copyright © 2002 John Wiley & Sons, Ltd.

ABSTRACT We experienced five pregnancy cases with type I congenital cystic adenomatoid malformation (CCAM) of fetuses and summarized here their clinical characteristics, pregnancy outcomes, and fetal therapies. Four of five cases were prenatally diagnosed using magnetic resonance imaging (MRI) as having lung abnormality, and the remaining case was prenatally diagnosed as having congenital diaphragmatic herniation (CDH). One fetus underwent the puncture of cysts in the lung, and two fetuses received in utero thoracoshunts between cysts and the amniotic fluid cavity (thoracoamniotic shunt). One pregnancy ended in artificial termination at 17 gestational weeks, and 4 pregnancies succeeded in live births. All these 4 infants underwent surgical operations for CCAM, and 1 infant underwent an additional operation for CDH. The MRI examinations were useful to prenatally identify CCAM, and the in utero thoracoamniotic shunt appears to be beneficial in preventing lung hypoplasia in the affected fetuses.

The aim of this study was to determine serum concentrations of macrophage migration inhibition factor (MIF) during normal pregnancies, and to assess whether serum MIF concentrations early in pregnancies predict the subsequent outcome in women with recurrent miscarriage (RM).

PROBLEM: It is unknown whether the number of vaginal polymorphonuclear leukocytes (vPMNs) of healthy pregnant women changes during pregnancy.

The syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome) and of acute fatty liver of pregnancy (AFLP) do not have an abrupt onset. Thrombocytopenia or reduced antithrombin activity, or both, seen at presentation do not result from these complications. There are a small number of pregnant women who exhibit a gradual antenatal decline in platelet counts or antithrombin activity, or both, irrespective of the presence or absence of preeclampsia. Those who develop a profound decrease in either platelet counts or antithrombin activity are at an increased risk for developing perinatal aspartate aminotransferase (AST) elevation. Thrombocytopenia or reduced antithrombin activity, or both, precede the onset of these diseases. Therefore, monitoring of platelet counts and antithrombin activity during pregnancy is clinically useful for identifying women at an increased risk of the HELLP syndrome and AFLP. Because women with twin pregnancies are likely to exhibit a decrease in platelet counts or antithrombin activity, or both, compared with women with singleton pregnancies, HELLP syndrome and AFLP are more likely to occur in women with twin pregnancies.

There may be an increased risk of preterm birth due to preeclampsia among women whose previous pregnancies ended in preterm birth due to preeclampsia. We studied 1,130 women who delivered 2 successive singleton infants in our hospital, excluding women who delivered an abnormally formed infant during the study period. We reviewed the gestational week at delivery in these 2,260 pregnancies and found a total of 182 preterm deliveries (8.1%) by 156 women. The causes of preterm birth were reviewed. Failed tocolysis, including premature rupture of membranes and clinical chorioamnionitis, and preeclampsia accounted for 135 (74.2%) and 30 (16.5%) of the 182 preterm deliveries, respectively. Women whose 1st delivery was preterm had a 3.26 times (95% CI 2.21–4.79) higher risk of a subsequent preterm delivery than women whose 1st delivery was term (26/96 vs. 60/1,034). The risk of preeclampsia-related preterm delivery was 54.4 times (17.2 to 172.5) higher in women with a previous preeclampsia-related preterm delivery than in women with a previous term delivery (5/19 vs. 5/1034). Women who had a history of preeclampsia-related preterm birth had a greater risk of preeclampsia-related preterm birth in a subsequent pregnancy as compared with women with a previous term birth.

Ultraviolet B (UVB) irradiation causes cell death by apoptosis in murine fibroblast cells. Tumor necrosis factor-α (TNF-α) is also a well known inducer of apoptosis, although the physiological significance of this activity is poorly understood. We investigated the effects of pretreatment with UVB (312nm) on TNF-α-induced apoptosis in murine fibroblast cells. UVB enhanced susceptibility to cell death by TNF-α in a dose-dependent manner. UVB but not TNF-α induced the expression of TNF receptor type-1 (TNFR-1) and type-2 (TNFR-2) in a dose-dependent manner. Expression of Fas (CD95) and Fas-ligand (Fas-L), and significant DNA fragmentation were observed in the cells that died. These results suggest that UVB irradiation modulates susceptibility to TNF-α-induced apoptosis through the induction of TNFRs, Fas, and Fas-L in murine fibroblasts.

PROBLEM: The fractions of Th1 cells and Tc1 cells may be increased in preeclamptic women compared with healthy pregnant women.
 METHOD OF STUDY: Eleven healthy non‐pregnant women, nine healthy pregnant women (34.1±3.1 weeks of gestation), and 10 women with preeclampsia (32.0±5.4 weeks) were studied. The fractions of Th1 cells, Th2 cells, Tc1 cells, and Tc2 cells in the peripheral blood mononuclear cells were determined using a three‐color flow cytometric technique. The concentrations of plasma plasminogen activator inhibitor‐2 (PAI‐2) were simultaneously determined.
 RESULTS: The fraction of Th1 cells was significantly larger in women with preeclampsia (18.7±5.2%) than in normal pregnant women (11.0±5.7%), and it increased with a decrease in the PAI‐2 level (r=−0.706, P=0.002), which was significantly lower in preeclamptic women (83.4±46.8 ng/mL) than in normal pregnant women (225.3±82.0 ng/mL). The fraction of Tc1 cells increased with increases in the fraction of Th1 cells (r=0.657, P<0.001) and the ratio of Th1‐to‐Th2 cells (r=0.535, P=0.002). The ratio of Tc1‐to‐Tc2 cells also increased with an increase in the ratio of Th1‐to‐Th2 cells (r=0.394, P=0.031).
 CONCLUSIONS: The fraction of Th1 cells appears to be expanded in women with preeclampsia compared with healthy pregnant women.

The Japanese cedar pollen (JCP) is a major allergen with respect to pollinosis in Japan. It is believed that interleukin-4 (IL-4) and interleukin-5 (IL-5) derived from lymphocytes and other cells play a pivotal role in allergic reactions. We investigated whether the JCP antigen stimulates the release of these cytokines by peripheral blood mononuclear cells (PBMCs). PBMCs from eight adults (five adults with JCP pollinosis and three adults without JCP pollinosis) were co-incubated with purified JCP antigens. IL-4 was released in response to JCP antigens in six of the eight subjects at 24h and in three subjects at 48h. IL-4 release at 24h occurred in all five subjects with JCP pollinosis but in only one of the three subjects without pollinosis. IL-5 was released in response to the JCP antigen in five of the eight subjects at 24h and 48h, including four of the five subjects with JCP pollinosis and one of the three subjects without pollinosis. These results suggest that PBMCs were more likely to release IL-4 and IL-5 in the presence of JCP pollinosis.

We investigated the effects of TNF receptor 1 (TNFR1) and 2 (TNFR2) modulation on the death of human aortic endothelial cells (HAECs) resistant to TNF-α-induced cell death. Alteration of the transcription of anti-apoptotic proteins, including inhibitor of apoptosis protein 1, 2 (cIAP1, 2), TNF receptor-associated factor 1 (TRAF1), nuclear factor kappa B1 protein (NFκB1), and FLICE-inhibitory protein (FLIP) was assessed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). TNF-α (200ng/ml) or actinomycin D (ActD) (5ng/ml) did not kill cells, while 5ng/ml of TNF-α and 5ng/ml of ActD increased expression of Fas (CD95) and FasL (CD95L), and 45% of cells died. TNFR2 blockade suppressed NFκB1 and FLIP expression and increased cell death. TNFR1 blockade enhanced FLIP expression and decreased cell death. Cells insensitive to TNF-α may respond to TNF-α through TNFR that induces transcription of NFκB1 and FLIP. Down-regulation of these proteins may facilitate death of cells insensitive to TNF-α-induced cell death.

AbstractWe counted nucleated red blood cells (NRBC) per 100 white blood cells (WBC) in the umbilical cord blood from 98 twins born to 49 women with uncomplicated twin pregnancies at ≥ 34 weeks of gestation to better characterize NRBC in twins. Twelve women with monochorionic (MC) placentas and 37 with dichorionic (DC) placentas gave birth at 36.7 ± .9 and 36.5 ± 2 weeks of gestation, respectively. All twins were born with an Apgar score of ≥ 7 at 1 min. Log10(NRBC/100 BC) in 98 twins exhibited a nearly normal distribution, and was significantly associated with gestational age for both MC (r=−0.457, p = 0.025) and DC twins (r =−0.275, p = 0.018), and with birth weight for both MC (r=−0.682, p < 0.001) and DC twins (r=−0.336, p = 0.003). Log10(NRBC/100 WBC) tended to be larger in smaller twins than in larger twins in the MC group, and significantly larger in smaller twins than in larger twins in the DC group (p < 0.05). Intertwin difference in Log10(NRBC/100 WBC) was defined as the value of Log10(NRBC/100 WBC) of the smaller twin minus Log10(NRBC/100 WBC) of the larger twin, and became greater with increasing intertwin difference in birth weight (r = 0.411, p = 0.003). These findings suggest that neonatal NRBC reflected gestational age and birth weight in twins. This preliminary observation using a small number of twins suggests that the smaller twin may have experienced a relative lack of oxygen compared with the larger twin in utero.

The exaggerated prolongation of the activated partial thromboplastin time (APTT) by heparin prophylaxis for postoperative thromboembolism may cause bleeding complications. We examined the effects of various doses of unfractionated heparin on the APTT in patients who underwent a gynecologic or obstetric operation. A total of 68 patients who underwent a gynecologic operation (n = 47) or a cesarean section (n = 21) with risk factors for thromboembolism received a continuous intravenous infusion of unfractionated heparin (110–285 IU/kg/day) after surgery until the patient was mobilized the next day. A group of 61 postoperative patients who did not receive heparin served as controls. The APTT was measured in these 129 patients preoperatively and on postoperative day 1. A clinical deep vein thrombosis occurred in only 1 patient, who was in the control group. No bleeding complications occurred in any patient. The percent change in the APTT was significantly correlated with the dose of heparin administered (p < 0.001). Compared with the control group, the mean APTT was not prolonged in the patients who received heparin at 110–149 IU/kg/day. It was prolonged significantly in the patients who received heparin at greater than 150 IU/kg/day. An exaggerated prolongation of the APTT, defined as an APTT greater than 150% of the preoperative value, was found in 0 of 32 patients in the 110–149 IU/kg/day group, 1 of 28 patients (3.6%) in the 150–199 IU/kg/day group and 2 of 8 patients (25%) in the 200–285 IU/kg/day group. The continuous postoperative administration of intravenous heparin at less than 200 IU/kg/day does not result in an exaggerated prolongation of the APTT.

AbstractOptions for the treatment of thoracoabdominally conjoined twins are dependent on the anatomy of the cardiovascular system. It is important to increase the accuracy of diagnosis of conjoined twins with a fused heart. Color Doppler imaging performed in a 23-year-old nulliparous Japanese woman at 12 weeks of gestation revealed synchronized blood flow in 2 aortic arches arising from a single heart. The patient underwent a therapeutic abortion, and the diagnosis of conjoined twins with a fused heart was confirmed. Thus, color Doppler imaging is useful for investigating the cardiovascular anatomy in conjoined twins suspected of having a fused heart, even in an early gestational age.

PROBLEM: Our previous study indicated that meconium‐stained amniotic fluid (turbid AF) possessed a potent chemotactic activity for leukocytes, which may be dependent on interleukin‐8. It is not known, however, whether meconium itself possesses this chemotactic activity.
 METHOD OF STUDY: Meconium samples were collected from mature neonates with and without turbid AF. A 5% meconium suspension in phosphate buffered saline was prepared and measured for its chemotactic activity for leukocytes using the blind well chamber technique. Concentrations of IL‐8, TNFα and IL‐1β were also measured with ELISA.
 RESULTS: The number of leukocytes that migrated to the meconium suspension (35±27) was comparable with that of the clear AF (31±37), but was significantly lower than that of the turbid AF (184±62, P<0.0001). The meconium suspension contained much lower levels of IL‐8, TNFα and IL‐1β than the turbid AF.
 CONCLUSIONS: Meconium itself exhibits a lower chemotactic activity for polymorphonuclear leukocytes than turbid AF in vitro. The leukocyte chemotactic activity of turbid AF does not originate from meconium itself.

AbstractInterferon-α (IFα) is used for the treatment of myeloproliferative diseases and chronic viral illnesses. Because the agent has antiproliferative activity, its effects on a fetus are a concern. We encountered a 40-year-old Japanese woman who inadvertently received IFα during pregnancy for the treatment of HCV hepatitis. The patient received 5 million units of IFα 2 to 4 times per week (total dose of 315 million units) between 13 and 33 weeks gestation. The patient delivered a normally formed healthy male infant, weighing 2,252 g at 37 weeks of gestation. The infant at 20-month-old exhibited normal growth and neurological development when last examined. Literatures were reviewed to determine the effects of IFα on the fetus. There have been 27 infants born to 26 mothers, including the present case, who were exposed to IFα in utero. Six women (23%) were administered IFα inadvertently during pregnancy. Four women (15%) gave birth prematurely. Although 6 infants (22%) were affected by intrauterine growth retardation (IUGR), there were no IFα-related malformed infants. These results suggested that an inadvertent administration of IFα during pregnancy may occur, but in that case IFα may not induce congenital malformations. These findings may encourage such women to continue pregnancy.

The effects of adding Cu–Zn superoxide dismutase (Cu–Zn SOD) to culture medium of the murine fibroblast cell line, L-929, pretreated with UV-B (312nm, 480mJ/cm2) have been investigated. Cell injury was monitored by the release of lactate dehydrogenase (LDH) into the medium, and cell death by the trypan blue exclusion test. UV-B radiation induced cell death by apoptosis, as demonstrated by DNA fragmentation. Over the range 0.1–0.3μmCu–Zn SOD, a significant dose-dependent protection against cell death was obtained of the UV-B exposed cells. Cell death correlated with the amount of LDH released into the medium, and Cu–Zn SOD treatment inhibited this. Heat-denatured Cu–Zn SOD did not affect either cell viability or the release of LDH from the cells. Endogenous Cu–Zn SOD activity, monitored by chemiluminescence, decreased by 20% in UV-B-irradiated cells; the addition of 0.3μmexogenous Cu–Zn SOD to the medium did not affect intracellular Cu–Zn SOD activity. These results establish that Cu–Zn SOD added to extracellular medium can protect cells against injury caused by UV-B exposure.

Objectives: To determine the incidences of complications and uterine malignancies among women undergoing hysterectomies for presumed benign leiomyomas. Methods: We retrospectively reviewed the medical records of 923 women who underwent total hysterectomies between January 1983 and December 1997 at our hospital due to presumed benign leiomyomas. Results:The mean age (SD) of the patients was 44.5 ± 5.2 years, 105 ± 35 minutes was required for the procedure, and 405 ± 312 ml of blood was lost during the procedure. Forty-one (4.4%) women demonstrated complications of intraoperative hemorrhages and required transfused blood. Urinary tract and bowel injuries occurred in 10 (1.1%) and 2 (0.2%) women, respectively. One woman (0.1%) died from pulmonary embolism that occurred on postoperative day 1. One woman (0.1%) required relaparotomy to control intraabdominal hemorrhage. Uterine malignancies were discovered postoperatively in 4 (0.4%) women, including 2 endometrial carcinoma, 1 leiomyosarcoma, and 1 endometrial stromal sarcoma. Conclusions: The incidences of complications and unrecognized uterine malignancies were similar to the results of previous studies. Of patients undergoing hysterectomy for presumed benign leiomyomas, the risk of major complications was 6.0% (55/923) and the risk of preoperatively undiagnosed uterine malignancies was 0.4%.

Objective:To assess the relation between the preoperative serum level of C-reactive protein (CRP) and the WBC count and the efficacy of emergency cervical cerclage. Study Design:We retrospectively reviewed the medical records of 17 women (16 singleton pregnancies and 1 twin pregnancy) who underwent emergency cervical cerclage (McDonald technique) between 21 and 26 weeks of gestation. The uterine cervix was dilated ≥3.0 cm and the intact (not ruptured) fetal membranes were visible or protruded into the vagina in all patients. The serum level of CRP and the WBC count were determined preoperatively and postoperatively. Emergency cervical cerclage was considered successful if delivery occurred ≥14 days after the procedure. Results:Emergency cervical cerclage was successful in 12 women, including the woman with a twin pregnancy, but failed in 5 women. The preoperative serum level of CRP and the WBC count were significantly lower and dilatation of the cervix was significantly less in the success group than in the failure group. Cerclage was successful in all eight patients with cervical dilatation ≤4.0 cm, but in only 4 of 9 patients with cervical dilatation >4.0 cm (p < 0.05). Cerclage was successful in all 11 women with a preoperative serum level of CRP ≤4.0 mg/dl and a WBC count ≤14,000/µl compared with 1 of 6 women with either a CRP level >4.0 mg/dl or a WBC count >14,000/µl (p < 0.01). Conclusion:A preoperative CRP value ≤4.0 mg/dl, a WBC count ≤14,000/µl, and cervical dilatation ≤4.0 cm were significantly associated with prolongation of pregnancy after emergency cervical cerclage.

Paraquat, which mediates increased O2−production within Escherichia coli, inhibits growth without causing cell death in a minimal medium, whereas it allows growth while decreasing viability in a rich medium. Agents or conditions that inhibit growth in the paraquat‐containing rich medium prevent this loss of viability. Antibiotics, chelating agents, nutritional paucity, and excess paraquat all acted this way. NaCl added to 0.2 M to the plates used for enumeration after paraquat exposure did not significantly decrease viable cell counts, although it did so after exposure to a cationic detergent. DNA, rather than cell membranes, thus seems to be a more likely target for the oxygen‐derived free radicals engendered by the cycles of enzymatic reduction and autoxidation of paraquat. Inhibition of growth decreases the likelihood that DNA replication will precede DNA repair. Investigators seeking to evaluate the bactericidal actions of paraquat under a variety of conditions will need to be cognizant of this need for growth.— Minakami, H.; Fridovich, I. Relationship between growth of Escherichia coliand susceptibility to the lethal effect of paraquat. FASEB J.4: 3239‐3244; 1990.

Alcohols protect Escherichia coliagainst cold shock, and the concentration of alcohol which provided optimal protection declined with increasing hydrophobicity of the alcohol. The rate of loss of viability after the chilling transition was decreased by n-octanol, even when it was added after that chilling transition. Cold-shocked cells exhibited a sensitivity toward dioxygen, seen as greater enumeration on anaerobic, rather than on aerobic, trypticase-yeast extract agar plates, and addition of catalase or antioxidants, such as α-tocopherol or probucol, to the agar plates did not lessen this dioxygen sensitivity. Respiratory capacity was diminished by cold shock, and cyanide-sensitive respiration was more affected than was cyanide-resistant respiration. Discharging the proton gradient, with the uncoupler carbonyl cyanide trifluoromethoxyphenylhydrazone, did not change sensitivity to cold shock. There was no evidence for minimal medium recovery after cold shock. The data presented, as well as that already in the literature, are explained on the basis of membrane damage caused by patches of ordering transitions in one membrane leaflet, unmatched by comparable transitions in the mating leaflet.

Objective. To evaluate the accuracy of a new pulse oximeter inestimating the oxyhemoglobin (O2Hb) concentration in fetalarterial blood (SaO2) with either a high concentration ofhemoglobin F (HbF) or a low concentration of O2Hb duringlabor. Patients and Methods. Fetal forehead arterial oxygenation wasdetermined in 44 fetuses by reflectance pulse oximeter (SpO2)during labor and was compared with SaO2determined immediatelyafter birth. Because HbF has little or no known effect on pulse oximetry, butdoes affect the laboratory multiwavelength “CO-oximeter” typereading, the SaO2was corrected by HbF concentration.SpO2and SaO2were simultaneously measured infive hypoxic adult volunteers achieved by inhaling 11% oxygen. Results.A gradual decline in HbF concentration was seen during weeks 37 to 40 ofgestation. HbF concentration varied near term, ranging between 53 and 88% ofthe fetal hemoglobin concentration (mean ± SD = 74.6 ± 6.3%).This alteration produced a lower %O2Hb percentby 4% at the most. The corrected SaO2in cord blood correlatedwith fetal SpO2(y = 0.974, x −7.279, r = 0.90). In five adults, SpO2reflected wellSaO2with a mean ± SD of bias of −1.1 ± 2.9%. Conclusions.SpO2determined by a new reflectance pulse oximeter at theend of labor correlated with an immediate post-natal cord arterial bloodsample before the first breath, with a mean and SD of bias of 8.5 ±6.2%. Reflectance pulse oximetry is a useful tool for continuousnoninvasive monitoring of the fetal oxygen status during labor.

Objective:To investigate the relation between birth weight and perinatal mortality in multifetal pregnancies, which is more than 5 times higher than for singleton infants. Methods:We assessed the incidence of perinatal deaths based on birth weight in 89,566 infants of multifetal pregnancies and 6,025,199 infants of singleton pregnancies in Japan. Perinatal death was defined as stillbirth and early neonatal death (death <1 week of age). Results:The incidence of perinatal death was consistently lower for infants of multifetal pregnancies than for infants of singleton pregnancies at birth weights of 500–2,499 g. However, the incidence of infants of multifetal pregnancies with birth weights ≥2,500 g consistently exceeded that in singleton infants weighing ≥2,500 g. The relative risk (95% CI) of perinatal death among infants of multifetal pregnancies compared with singleton infants in the same category of birth weight was 0.88 (0.84–0.93) at 500 g. The relative risk decreased to 0.31 (0.25–0.39) at 1,900 g, increased to >1.0 at 2,500 g, to 3.7 (2.2–6.1) at 3,000 g, and to 14.9 (7.8–28.4) at ≥3,500 g. Conclusions:Japanese infants of multifetal pregnancies reaching ≥2,500 g in body weight have a significantly higher risk of perinatal death than singleton infants in the same category of body weight. Increased monitoring of fetuses of multifetal pregnancies who weigh ≥2,500 g may be helpful in reducing the incidence of perinatal mortality.