Malignant transformation of nontrophoblastic cells is associated with the expression of chorionic gonadotropin beta genes normally transcribed in trophoblastic cells.

The beta subunit of human chorionic gonadotropin (hCGbeta) is encoded by four nonallelic CGbeta genes. An assay was developed for distinguishing type I CGbeta allelic genes beta7 and beta6, which possess a GCC codon corresponding to an alanine at position 117 of hCGbeta, from type II CGbeta genes beta8, beta5, and beta3 and its allele beta9, which possess a GAC codon corresponding to an aspartic acid at the same position. In normal trophoblast, hCGbeta is encoded by type II CGbeta genes, whereas normal nontrophoblastic tissues of differing histological origin (breast, prostate, skeletal muscle, bladder, adrenal glands, thyroid, colon, and uterus) express only type I CGbeta genes. We studied the expression of CGbeta genes in 86 tumor specimens collected from patients with breast, bladder, prostate, and thyroid cancer and found that up to 61% of these nontrophoblastic tumors expressed type II CGbeta genes. Experiments performed on tumor tissues and their normal counterparts confirmed that the malignant transformation of nontrophoblastic cells is associated with the expression of type II CGbeta genes. These findings provide the basis for a simple test (the CG117 assay) that may be useful for the diagnosis of the most frequent malignancies.

Expression of human chorionic gonadotropin beta subunit genes in superficial and invasive bladder carcinomas.

Increased serum levels of human chorionic gonadotropin beta subunit (hCG beta) were described previously in patients with bladder cancer. To obtain insight into such production of hCG beta, the expression of hCG beta 7, 8, 5, and 3 genes in bladder carcinomas and normal urothelia was investigated by reverse transcription PCR. Surprisingly, hCG beta mRNAs were detected in both normal urothelial and carcinomatous cells. However, tumor progression was characterized by different patterns of transcription of the hCG beta genes; the beta 7 gene was the only gene transcribed in normal urothelia and Ta tumors included in this study, whereas in addition to beta 7, genes beta 5, 8, and 3 were transcribed in T1 to T4 tumors. Moreover, transcription levels of the latter three genes increased with the stage of the disease. These observations showed that dramatic modifications in the expression of hCG beta genes accompany progression of bladder carcinomas.

Nosocomial outbreak of staphylococcal scalded skin syndrome in neonates: epidemiological investigation and control.

Over a three-month period, 13 neonates developed staphylococcal scalded skin syndrome (SSSS) in a maternity unit, between four and 18 days after their birth. An epidemiological and descriptive study followed by a case-control study was performed. A case was defined as a neonate with blistering or peeling skin, and exfoliative toxin A Staphylococcus aureus positive cultures. Controls were selected at random from the asymptomatic, non-colonized neonates born on the same day as the cases. All staff members and all neonates born during the outbreak period were screened for carriage by nasal swabs and umbilical swabs, respectively. S. aureus isolates were polymerase chain reaction (PCR) screened for etA gene and genotyped by pulsed-field gel electrophoresis (PFGE). Two clusters of eight and five cases were identified. Receiving more than one early umbilical care procedure by the same ancillary nurse was the only risk factor identified in the case-control study (odds ratio=15, 95% confidence intervals 2-328). The ancillary nurse suffered from chronic dermatitis on her hands that favoured S. aureus carriage. Exfoliative-toxin-A-producing strains, as evidenced by PCR and indistinguishable by PFGE, were isolated from all but one of the SSSS cases, from four asymptomatic neonates, from two staff members and from the ancillary nurse's hands. Removal of the ancillary nurse from duty, infection control measures (isolation precautions, chlorhexidine handwashing and barrier protections), and treatment of the carriers (nasal mupirocin and chlorhexidine showers) led to control of the epidemic. In conclusion, this study emphasizes the need for tight surveillance of chronic dermatitis in healthcare workers.

Prognostic value of chorionic gonadotropin beta gene transcripts in human breast carcinoma.

The beta subunit of human chorionic gonadotropin is potentially encoded by six genes, which can be categorized into two types based on a sequence change at codon 117: GCC for the type I and GAC for the type II genes. We previously showed that, whereas type I genes were exclusively expressed in normal breast tissues, expression of type II genes was associated with malignant transformation (Bellet, D., et al. Cancer Res., 57: 516-523, 1997). We designed a simple and robust test (the CG117 assay) that measures the percentage of type II over both types of chorionic gonadotropin beta mRNAs. Normal breast tissues consistently had a negative CG117 index, whereas cancer breast tissues showed indexes ranging from 0 to 100%. The prognostic significance of the CG117 index was investigated in a series of 99 unilateral invasive primary breast cancer patients with known long-term outcome (median follow-up, 9 years). The CG117 index was positive in 48 (48.5%) of the 99 tumor mRNA samples. The index was not significantly associated with standard prognostic parameters, including clinical and macroscopic tumor size, histopathological grade, and lymph node status or steroid receptor status. Patients with a positive CG117 index in primary tumor mRNA had significantly shorter metastasis-free survival (P = 0.014) and overall survival (P = 0.038) after surgery, compared to patients with a negative index. The prognostic significance of the CG117 index persisted in Cox multivariate regression analysis, both for metastasis-free survival (P = 0.008) and overall survival (P = 0.016), together with lymph node status (P = 0.027 and P = 0.009, respectively). These findings indicate that the CG117 index may contribute to the identification of high-risk breast cancer patients.

Trophoblast production of a weakly bioactive human chorionic gonadotropin in trisomy 21-affected pregnancy.

Total human chorionic gonadotropin (hCG) is high in maternal serum at 14-18 wk of trisomy 21 (T21)-affected pregnancy, despite low placental hCG synthesis. We sought an explanation for this paradox. We first observed that, in T21-affected pregnancies, maternal serum hCG levels peaked at around 10 wk and then followed the same pattern throughout pregnancy as in controls, albeit at a higher (2.2-fold) level. After delivery, hCG clearance was not significantly different from that in controls. We isolated cytotrophoblasts from 29 T21-affected placentas (12-25 wk) and 13 gestational age-matched control placentas and cultured them for 3 d. In this large series, we confirmed that, in the culture medium of trophoblasts isolated from T21 placentas, hCG secretion was significantly lower (P < 0.003) than in controls, in contrast to the high hCG in maternal serum of the same patients. In T21 cultured trophoblasts, transcripts of sialyltransferase-1 and fucosyltransferase-1 were abnormally high. In corresponding culture medium, hCG was abnormally glycosylated; highly acidic [isoelectric points (pHi) = 4.5] as shown by isoelectric focusing, immunoblotting, and lectin binding; and weakly bioactive (46% of control) as determined using the Leydig cell model. In conclusion, T21 trophoblast cells produced hCG that was weakly bioactive and abnormally glycosylated but whose maternal clearance was unaltered.

Analysis of the human CGB/LHB gene cluster in breast tumors by real-time quantitative RT-PCR assays.

The six genes of the human chorionic gonadotropin beta subunit (CGB) and the gene of the luteinizing hormone beta subunit (LHB) are located in a cluster that spans 50 kb on chromosome 19q13.3. Only genes CGB7, B8, B5 and B3 can generate the human chorionic gonadotropin (hCG) beta molecule. The other two genes, CGB1 and B2, encode unidentified proteins. We have previously shown that malignant breast transformation is associated with the emergence of the 'trophoblastic' CGB genes (B8, B5 and B3), in addition to the CGB7 gene, which is the only CGB gene expressed in normal breast tissue. To better understand the dysregulation of the CGB/LHB gene cluster in breast cancer, we have developed real-time quantitative RT-PCR assays to analyze each subgroup of genes (the overall CGB genes, CGB1 and B2 together, and LHB alone) in 17 unilateral invasive primary breast tumor RNAs. We also analyzed the chorionic gonadotropin alpha (CGA) gene coding for the human CGA subunit. We found that the emergence of the 'trophoblastic' CGB genes in breast tumors is (i) accompanied by an increase in the total CGB mRNA steady-state level, (ii) mainly due to overexpression of genes CGB8, B5 and B3 (expression of other genes in the CGB/LHB gene cluster (CGB7, B2, B1 and LHB) changes little if at all), and (iii) not accompanied by overexpression of the CGA gene which is necessary to produce ectopic hCG heterodimeric hormone in breast tumor cells, these latter which yet expressed the LH/CG receptor. These observations suggest that it is mainly the CGB8, B5 and B3 genes which are upregulated in the 19q13.3 CGB gene cluster in breast tumors. They also point to a role (like growth factor) of the CGbeta subunit in breast tumorigenesis, via a novel pathway independent of the LH/CG receptor.

Defect of syncytiotrophoblast formation and human chorionic gonadotropin expression in Down's syndrome.

The syncytiotrophoblast (ST) is a major component of the human placenta as it is involved in feto-maternal exchanges and the secretion of pregnancy-specific hormones. We have studied the formation and function of the ST in normal and trisomy 21 (T21)-affected placenta using the in vitro model of cytotrophoblast differentiation into ST. Cytotrophoblast cells were isolated from first trimester, second trimester and term placentae. In vitro cytotrophoblast cells isolated from normal placenta fused to form the ST. This was associated with an increase in the transcript levels and the secretion of human chorionic gonadotropin (hCG). However, the secretion of hCG decreased through pregnancy. In T21-affected placentae, we observed a defect (or a delay) in ST formation and a dramatic decrease in the synthesis and secretion of this hormone compared with cultured cells isolated from control age-matched placentae. These results were confirmed by a significant (P < 0.05) decrease in transcript levels of alpha and beta subunits of hCG in total homogenates of T21-affected placentae compared with controls. These results suggest a decrease in functional mass of ST in T21 placenta, and therefore a decrease in production of placental pregnancy-specific polypeptide hormones.

The relationship of anti-endothelial cell antibodies to anti-phospholipid antibodies in patients with giant cell arteritis and/or polymyalgia rheumatica.

Sera from patients with giant cell arteritis and/or polymyalgia rheumatica were tested for the presence of IgG, IgM and IgA antibody to endothelial cells (AEC), cardiolipin (ACL) and phosphatidylethanolamine (APE) using enzyme-linked immunosorbent assays. There were strong correlations between ACL and APE, but also between AEC and ACL IgM (p < 0.02) and between AEC and APE IgA (p < 0.003). Inhibition of AEC binding was achieved by absorption onto EC, but ACL and APE binding was also significantly reduced. In contrast, the binding of AEC antibody could not be inhibited by incubation with CL. Our data suggest that AEC constitute a heterogeneous population of autoantibodies.

Acute fetal distress after fetal blood sampling (case report).

The authors report a case of acute fetal distress after fetal blood sampling, performed for fetal karyotype because of a precocious and symmetrical fetal growth retardation without maternal hypertension or ultrasonographic evidence of fetal malformation. A cesarean section performed because of acute fetal distress showed the newborn to be hypotrophic, with a major acidosis and a refractory hypoxemia. The new born died despite intensive care. Acute fetal anemia was assumed to be the cause of acute fetal distress. The authors emphasize the use of FHR in fetal survey after fetal blood sampling.

[Importance and significance of the determination of pH in the diagnosis of fetal distress during labor and delivery]. / Intérêt et signification de la mesure du pH dans le diagnostic de la souffrance foetale au cours du travail et à la naissance.

The authors have used a microprocessor which is calibrated by a cartridge to be used once only for measuring the pH; as they systematically monitor the fetal acid base balance by measuring the pH and blood gases at birth, as well as in labour, when there is evidence of fetal heart rhythm abnormalities. They have been able to compare the results that they obtained using a classical membrane apparatus as against that using a microprocessor. The two types of apparatus give identical results. The costs of using the two apparatuses, including maintenance and cleaning, are comparable. The significance of evaluating the degree of fetal distress from isolated pH measurements is discussed in connection with measuring the level of lactic acid in the plasma and blood gases coupled with the measure of excess base.

[Ovarian seminoma and pregnancy. Apropos of a new case]. / Séminome ovarien et grossesse. A propos d'un nouveau cas.

The case of a 35-year-old primigravida with a 21-week intrauterine gestation and concurrent dysgerminoma of the ovary (stage Ic) is presented. A total hysterectomy with bilateral salpingo-oophorectomy was performed, followed by postoperative chemotherapy using cisplatin, bleomycin and vinblastine. The patient has done well since treatment, and is without evidence of recurrent disease 19 months later. Both radiation and chemotherapy are highly effective treatment modalities for dysgerminoma. For those patients with disease presenting in stages Ib, Ic, II and III who wish to maintain fertility, unilateral oophorectomy followed by combination chemotherapy may be curative and spare ovarian function.

[Hepatic subcapsular hematoma: a case report and management update]. / Hématome sous-capsulaire du foie : cas clinique et mise au point actualisée sur la prise en charge.

Hepatic subcapsular hematoma (HSH) is a rare complication of pregnancy that keeps a materno-fetal high mortality rate. Given this severity, HSH management requires a prompt diagnosis and an appropriate care. Before focusing on the current management strategy of HSH, we illustrate this article with a clinical case presenting an original method of abdominal exploration, which has not been described to our knowledge. Thus, taking into account the presence of a moderate hemoperitoneum during a caesarean section procedure for HSH, introduction of laparoscopy through the same incision allowed a satisfactory evaluation of the abdominal cavity and hepatic area without performing an invasive midline laparotomy.

[Cerebral Doppler technic during labor using signal monitoring at the level of the fetal scalp]. / Döppler cérébral au cours du travail par prélèvement du signal au niveau du scalp foetal.

The purpose of modern obstetrics is to obtain tracers of the fetal cerebral risk during labor, enabling to deliver the child before cerebral ischemia occurs. Recording of the fetal heart and measurement of acid-base balance are remarkable tracers; however, a much better precision is desired to avoid unnecessary or too late caesarean sections. Blood velocity measurement by Döppler at the level of the vessels at the base of the fetal skull is technically possible during labor; this has been demonstrated in 8 fetuses. The major cerebral index D/S during labor is 0.40 +/- 0.04, i.e. slightly lower than the mean index measured at the cord (0.50 +/- 0.07). In case of decelerations, it decreases to a mean value of 0.22 +/- 0.02. These preliminary results permit to hope that long-term measurements with continuous Döppler, of the arterial fetal cerebral flow, provide a direct and accurate tracer of the risk of cerebral ischemia during labor.

[Improvement in the prenatal etiologic diagnosis of severe 2d trimester oligo-amnios by intra-amniotic injection of physiologic solution]. / Amélioration du diagnostic étiologique anténatal des oligo-amnios sévères du second trimestre par injection intra-amniotique de sérum physiologique.

In reference to 4 severe cases of oligo-amnios of the second trimester of pregnancy, the authors advocate a method in order to improve the pre-natal diagnosis by intra-amniotic injection of a normal saline solution. This method facilitates the morphological exploration of the fetus by sonogram and enables to obtain a fetal karyotype by umbilical or amniotic tap. The potential risk of this technique are described.

Prenatal diagnosis of fetal cytomegalovirus infection.

Twelve fetuses were evaluated with a combination of ultrasonography, amniocentesis, and blood sampling for possible cytomegalovirus infection. In seven the mother had a documented primary cytomegalovirus infection. All seven women had normal ultrasonographic findings and one fetus was found to be infected. In the other five cases fetal cytomegalovirus infection was diagnosed in association with abnormal ultrasonographic findings. There was no history of maternal infection in the latter group. All positive and negative diagnoses were confirmed and none of the six infected fetuses survived. In this series, the most reliable parameters of infection were the isolation of the virus from amniotic fluid and elevations of total immunoglobulin M and gamma-glutamyl transpeptidase in fetal blood. In the majority of infected fetuses cytomegalovirus-specific immunoglobulin M was not detected in blood. Prenatal diagnosis of fetal cytomegalovirus infection is possible with a combination of amniocentesis and fetal blood sampling.

Fetal toxoplasmosis: ultrasonographic signs.

Eighty-nine cases of proven Toxoplasma gondii fetal infection were studied in order to describe the morphological lesions which could be demonstrated on ultrasound examination; these were present in 32 of the infected cases. Cerebral ventricular dilatation was the most common sign and was generally bilateral and symmetrical. Its evolution was always very rapid over a period of a few days. Other signs observed included intracranial and intrahepatic densities, increased thickness and hyperdensity of the placenta, ascites and rarely pericardial and pleural effusions. Thirteen fetuses demonstrated two or more ultrasound features. Intrauterine growth retardation and microcephaly were not observed. Ultrasonographic assessment of the fetus injected with Toxoplasma gondii is important. It improves the reliability of prenatal diagnosis and is of important prognostic value in cases with severe brain lesions, but is of little value in detecting brain necrosis without ventricular dilatation.

Insulin-like 4 (INSL4) gene expression in human embryonic and trophoblastic tissues.

Polypeptide growth factors play an important role in the regulation of human embryonic development. Insulin-like 4 gene (INSL4) is a member of the insulin family, which includes insulin, IGF-I, IGF-II, relaxin, and INSL3. Using RT-PCR, we previously found abundant INSL4 mRNA in the human placenta. In this study, we examined the chronology and spatial expression of this gene in sections of human placenta and conceptus by means of in situ hybridization. Expression of the IGF-II gene was studied as a positive control. INSL4 distribution was tissue- and cell-specific. Indeed, INSL4 mRNA was most abundant in syncytiotrophoblast cells. In fetal tissues, INSL4 mRNA was identified in the perichondrium of all four limbs, vertebrae, and ribs. Moreover, INSL4 mRNA was abundant in interbone ligaments. These findings indicate that the INSL4 gene may play an important role in trophoblast development and regulation of bone formation. IGF-II mRNA, in agreement with the literature, are mainly located in the mesodermal core in the villous trophoblast and in most embryonic tissues.