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Previous reports have demonstrated the presence of DNA of the human helper virus-dependent adeno-associated parvovirus (AAV) in uterine tissue and curettage material from early miscarriage. To examine infection of embryonic tissue during pregnancy, amnion fluids were analysed for the presence of AAV. Using polymerase chain reaction, AAV DNA was detected in 64 out of 238 DNA samples extracted from amnion cells. DNA of helper viruses were found in 12% (papillomavirus) and 18% (cytomegalovirus) of the samples (double infections with AAV in eight and nine cases, respectively). Furthermore, infectious AAV virions were found in 13 out of 43 AAV DNA-containing samples. In mothers with AAV DNA-positive amnion fluids, premature amniorrhexis and premature labour occurred significantly more frequently (P < 0.001). Using an immunofluorescence assay, 24% of newborn sera (unrelated to the amnion fluid samples) were found to contain IgM antibodies to AAV, in most cases paralleled by IgM antibodies in the mother's sera. The data demonstrate that AAV infection can occur in utero at early and at late stages of pregnancy. The observed complications at delivery should encourage studies to clarify possible pathological consequences of AAV infection in pregnancy and a possible latent infection of the fetus. [ABSTRACT FROM AUTHOR]

Objectives: Viruses and tumour cells may regulate the expression of HLA molecules on the cell surface to escape immune system surveillance. Absence of classical HLA class I molecules may impair the action of specific cytotoxic cells, whereas non-classical HLA class I molecules may regulate innate and adaptive immune cells. We assess here the possible associations between classical/non-classical class I HLA and p16(INK4a) molecule expression in cervical biopsies of women infected with HPV, stratified according to grade of the lesion and HPV type., Study Design: Cervical biopsies (N=74) presenting cervical intraepithelial neoplasia grade 1 (CIN1) (n=31), CIN2-3 (n=19), and invasive cancer (n=14) were evaluated alongside 10 normal cervical specimens., Results: HLA-A/B/C/G staining was observed in the early stages of HPV infection. A significant association was detected between HLA-A/B/C staining and HPV16/18 infection (OR=0.12, 95%CI: 0.0163-0.7899; p=0.04). HLA-E expression increased with the progression of the lesion (chi(2)-test for trend=4.01; p=0.05), and a significant association was found between HLA-E staining and HPV16/18 infection (OR=11.25, 95%CI: 2.324-54.465; p=0.003). Irrespective of the grade of the lesion, HLA-A/B/C staining and p16(INK4a) presented a good concordance (Kappa: 0.67)., Conclusions: HLA-E overexpression seemed to be associated with invasive cancer and HPV16/18 infection.

Definite causes for several pathologies of pregnancy remain unknown. In light of several recent studies, however, diminished or aberrant HLA-G expression may be associated with certain complication of pregnancy and be linked to HLA-G polymorphism. We analyzed DNA from 60 normal placentas (controls), 140 placentas from miscarriage, 36 placentas from preeclampsia, 76 placentas from fetal hypotrophy, and 34 placentas with hypoxia for variations in coding regions (allelic groups G*0101 to G*0107) and the 14-bp deletion/insertion into the 3'-untranslated region. No statistically significant differences were observed in the distribution of allelic group between pathological placentas and controls with the exception of G*0106 allele frequency in preeclamptic compared with control placentas (21.2% and 6.6%, respectively). A greater frequency of this allele also was observed in the two subgroups of miscarriage and hypoxia compared with that in controls. In addition, presence of the 14-bp sequence was prominent in preeclampsia compared with controls (60.8% vs. 35%, respectively), and homozygotes with deletion were not detected in the pathology. The results suggest that the G*0106 allele, which is coupled with the presence of the 14-bp sequence, contributes and/or is a relevant marker in some specific complications of pregnancy, especially preeclampsia.

The initial steps of primitive hematopoiesis and endothelial vascular formation in the human embryo remain to be defined. Here, we report the identification of a novel marker, namely the nonclassical HLA-G class I molecule, which targets both primitive erythroid cells of the yolk sac and endothelial cells from developing vessels. Moreover, HLA-G was present in its soluble form in the erythropoietic lineage in all organs sustaining primitive to definitive erythropoiesis (ie, aorta-gonad-mesonephros, liver, spleen, and bone marrow). The alternatively spliced transcript coding the soluble HLA-G5 molecule was detected in erythroid cells. The corresponding intron 4-retaining 37-kDa HLA-G5 isoform was secreted from the erythroid progenitor stage to the reticulocyte but was lost in mature erythrocytes and in endothelial cells from differentiated vessels. This study constitutes the first description of an HLA class I antigen expression on the primitive erythroid lineage and provides a way of seeking both primitive and definitive erythropoiesis using HLA-G5. This new marker, previously known by its immunotolerogeneic properties, may be involved in erythroid differentiation, angiogenesis, or both.

The phenomenon of implantation anchors the embryo into the uterine wall and produces a hemochorial placenta that maintains the pregnancy and fetal growth. Implantation and placentation are intimately linked and cannot be dissociated either in time or in space. Preeclampsia is characterized by hypertension and proteinuria. It is secondary to an anomaly of the invasion of the uterine spiral arteries by extra-villous cytotrophoblast cells, associated with local disruptions of vascular tone, of immunological balance and inflammatory status, and sometimes with genetic predispositions. Preeclampsia is a disease of early pregnancy, a form of incomplete spontaneous abortion, but is expressed late in pregnancy. Aspirin may play a favorable role in implantation which is related to the genesis of preeclampsia and some cases of intra-uterine growth restriction. The most important points in obtaining a preventive effect from low-dose aspirin during the pregnancy are early treatment (before 13 weeks of gestation) and the prescription of a sufficient dose (more than 100 mg per day).

The trophoblast and vascular cell lineages have been studied by immunohistochemistry at 6 and 12-14 weeks of pregnancy. Perivillous and extravillous cytotrophoblasts were specifically stained by anti-cytokeratin 7 whereas endothelial cells were labelled by anti-CD34 at these two stages of pregnancy. Perivillous and extravillous cytotrophoblasts together with erythroblasts showed mitotic figures and anti-Ki67 positive nuclei at the 6th week. In the perivillous cytotrophoblast, the number of Ki67 positive nuclei decreased by 12-14 weeks and the staining was limited to the proximal extravillous trophoblast of cell islands. Some endothelial and perivascular cells were labelled with anti-Ki67 at 12-14 weeks. Erythroblasts did not stain at all at this stage. Endothelial cells bound lectin UEA1 and vessels exhibited a fluorescent signal after anti-myosin staining at 12-14 weeks. These data showed that the cytotrophoblast and endothelial cell lineages are not related from 6 to 12-14 weeks of pregnancy. Because mitotic figures or anti-Ki67 staining were not observed in endothelium or perivascular cells at the 6th week, it seems likely that the endothelial cells committed to vasculogenesis derived from stromal cells. By 12-14 weeks, endothelial cells had nearly achieved their maturation by acquiring 1-fucosyl-binding sites revealed by UEA1-lectin binding and insuring their own renewal by mitosis. The maturation of perivascular cells at 12-14 weeks was shown by the anti-sm-myosin staining. We conclude that placental vasculogenesis involves mesenchymal cells rather than trophoblast. The differenciation of vessels organizing from random plexi to a vascular arborescence may involve paracrine regulatory loops with the trophoblast.

We recently demonstrated that the product of the HERV-W env gene, a retroviral envelope protein also dubbed syncytin, is a highly fusogenic membrane glycoprotein inducing the formation of syncytia on interaction with the type D mammalian retrovirus receptor. In addition, the detection of HERV-W Env protein (Env-W) expression in placental tissue sections led us to propose a role for this fusogenic glycoprotein in placenta formation. To evaluate this hypothesis, we analyzed the involvement of Env-W in the differentiation of primary cultures of human villous cytotrophoblasts that spontaneously differentiate by cell fusion into syncytiotrophoblasts in vitro. First, we observed that HERV-W env mRNA and glycoprotein expression are colinear with primary cytotrophoblast differentiation and with expression of human chorionic gonadotropin (hCG), a marker of syncytiotrophoblast formation. Second, we observed that in vitro stimulation of trophoblast cell fusion and differentiation by cyclic AMP is also associated with a concomitant increase in HERV-W env and hCG mRNA and protein expression. Finally, by using specific antisense oligonucleotides, we demonstrated that inhibition of Env-W protein expression leads to a decrease of trophoblast fusion and differentiation, with the secretion of hCG in culture medium of antisense oligonucleotide-treated cells being decreased by fivefold. Taken together, these results strongly support a direct role for Env-W in human trophoblast cell fusion and differentiation.

Nonclassical major histocompatibility complex (MHC) class I human leukocyte antigen E (HLA-E) and HLA-G molecules differ from classical ones by specific patterns of transcription, protein expression, and immunotolerant functions. The HLA-G molecule can be expressed as four membrane-bound (HLA-G1 to -G4) and three soluble (HLA-G5 to -G7) proteins upon alternative splicing of its primary transcript. In this study, we describe a new set of monoclonal antibodies (mAbs) called MEM-G/01, -G/04, -G/09, -G/13, MEM-E/02, and -E/06 recognizing HLA-G or HLA-E. The pattern of reactivity of these mAbs were analyzed on transfected cells by flow cytometry, Western blotting, and immunochemistry. MEM-G/09 and -G/13 mAbs react exclusively with native HLA-G1 molecules, as the 87G mAb. MEM-G/01 recognizes (similar to the 4H84 mAb) the denatured HLA-G heavy chain of all isoforms, whereas MEM-G/04 recognizes selectively denatured HLA-G1, -G2, and -G5 isoforms. MEM-E/02 and -E/06 mAbs bind the denatured and cell surface HLA-E molecules, respectively. These mAbs were then used to analyze the expression of HLA-G and HLA-E on freshly isolated cytotrophoblast cells, on the JEG-3 placental tumor cell line, and on cryopreserved and paraffin-embedded serial sections of trophoblast tissue. These new mAbs represent valuable tools to study the expression of HLA-G and HLA-E molecules in cells and tissues under normal and pathologic conditions.

We report on the preliminary results of a series of 111,292 patients who benefited from a liquid medium sample (CytoRich) for cervical cancer screening. The number of dubious or limited smears was reduced by 0.03% and 0.53% respectively. The junction zone was better explored, and metaplastic changes were observed in 35.71% of the cases. This method improved the identification of low-grade lesions by +56% (2751/111,292; 2.47%) and of high-grade lesions by +75% (860/111,292; 0.77%), with a reduction in the number of ASCUS/AGUS by -44% (2065/111,292; 1.85%). This preliminary study confirms the results already published. The results demonstrating cytohistological correlation should prove to be a decisive factor, enabling the testing of the sensitivity and specificity of this technique. It will then be possible to envisage a future 'new paradigm' for screening cervical cancer as the result of a liquid medium sample, computer-assisted screening and HPV viral identification by Hybrid capture II.

Myometrial coagulation necrosis occurred after LH-RH analogue treatment and Nd:YAG laser reduction of the endometrium. This rare complication occurred in a patient with adenomyosis.

The human helper virus-dependent parvovirus, adeno-associated virus (AAV) has never been associated with disease in humans [Berns et al. (1987): Advances in Virus Research 32:243-306; Siegl et al. (1985): Intervirology 23:61-73]. However, in pregnant mice, infection with AAV induces early abortion [Botquin et al. (1993): Journal of Cancer Research and Clinical Oncology 119:24]. We investigated whether this common human virus may be found in human genital tissue or in curettage material from spontaneous abortion. Using the polymerase chain reaction (PCR) AAV type 2 DNA was amplified in histological sections of 19 of 30 biopsies of the uterine mucosa. In addition, AAV-2 DNA was detected in abortion material during the first trimester of pregnancy (12/30 cases were positive) but not in material of abortion from the second or third trimester (9 cases). Whereas in tissues from the uterus AAV DNA was found only by PCR, large amounts of viral DNA were detectable by Southern blot analysis in abortion material. In situ hybridization revealed DNA of AAV to be present in the villous moiety (trophoblast) of the placenta but not in the embryo or decidua. in the same cells, AAV proteins (including the replication-associated rep proteins) were detected by immunofluorescence analysis. These results suggest (1) that AAV infects the uterine mucosa (possibly persistently) and (2) that it can replicate in trophoblast cells. This might disturb placenta development and may play a role in early miscarriage.(ABSTRACT TRUNCATED AT 250 WORDS)

Localisation of Langerhans' cell histiocytosis (HCL) is rare. In solitary form the prognosis for this pathology is good, if the tumour occurs in a woman of 36 years of age. (In this case the woman's age was 91) The appearances may be misleading clinically. The diagnosis is made by histological examination of P-S 100 positive cells and by finding Birbeck's granules on electron microscopy. Treatment may be surgical or as in our case medical.