Evidence of prevalent genital-type human papillomavirus infections in adults and children

Recombinant proteins encoded by the E2, E7, L1, and L2 open reading frames (ORF) of human papillomavirus (HPV) types 6b, 16, and 18 were used in Western blot assays to detect serum IgG antibodies in women attending a sexually transmitted diseases clinic (n = 92) and in hospitalized children (n = 81). Antibodies to late gene products (L1 or L2 ORF) were more common than antibodies to early gene products (E2 or E7), both in the adults and the children; overall, the antibody prevalences in the children and the sexually active adults were not significantly different. Human sera with high titers of antibodies to the HPV16 E7 recombinant protein immunoprecipitated the genuine HPV16 E7 protein from the cervical carcinoma cell line CaSki. As an independent measure of HPV infection, the polymerase chain reaction was used to detect HPV6b and HPV16 in oral mucosal scrapings from adults (n = 35) and preschool children (n = 21). In adults, HPV6b and HPV16 DNA were detected in 17% and 23% of oral mucosal samples, respectively. In preschool children, HPV6b and HPV16 DNA were found in 24% and 19% of oral samples, respectively.     

Identification of somatostatin in the human placenta

High pressure liquid chromatography (HPLC), gel chromatography and radioimmunoassay (RIA) were applied to the identification of cyclic somatostatin in human placental tissue. Methanol extracts of the placenta were treated with acetic acid and chloroform, purified on an octadecylsilane column, fractionated on HPLC and gel filtration, and assessed by RIA. It is concluded that human placental somatostatin is similar or identical to cyclic somatostatin on other tissue.     

Resistin is expressed in the human placenta

The mechanism for decreased insulin sensitivity in pregnant women is not fully clarified. Resistin, a novel peptide hormone, is specifically expressed in the adipose tissue and decreases insulin sensitivity in rodents. In the present study, we demonstrate resistin gene expression in the human placental tissue, mainly in trophoblastic cells. The resistin gene expression in term placental tissue was more prominent than was seen in the first trimester chorionic tissue. In contrast resistin gene expression in adipose tissue was rather weak and remained unchanged by pregnancy. Thus, resistin is a newly isolated placental hormone in humans which may modulate insulin sensitivity during pregnancy.     

Transferrin receptor expression in the human placenta

Iron transport from the mother to the fetus is mediated by transferrin receptors located at the maternofetal interface of the placenta. Transferrin receptors bind iron-loaded transferrin molecules from the maternal plasma, thus allowing iron uptake by trophoblastic cells which then deliver the metal to the fetal plasma. We have measured the transferrin receptor content in the placentas from 16 normal-term pregnancies and investigated the relationships between transferrin receptor expression and non-haem iron content, as well as maternal and fetal iron status. Transferrin receptor content was evaluated indirectly by determining the transferrin binding capacity of a placenta extract. Transferrin receptor content of the placenta ranged from 20 to 154 micrograms/g of tissue, with a mean value of 96 +/- 37 micrograms/g. The mean non-haem iron content was 78 +/- 11 micrograms/g of tissue, corresponding to 47 +/- 10 mg for the whole placentas. The amount of transferrin receptors in the placenta was found to be inversely related to the amount of non-haem iron (r = 0.64; p less than 0.025). No significant relationship was observed between each of these two parameters and the iron status of either the mother or the fetus. We conclude that placental non-haem iron, which represents a storage form of this element, is likely to play a regulatory role in the expression of transferrin receptors, and consequently in the process of iron uptake by the placenta.     

Haemostatic mechanisms in human placenta

The placenta is a unique organ with dual blood circulation functioning throughout fetal development. The architecture and functions of the placenta, where maternal blood flows into the intervillous space, present haemostatic problems, mainly the risk of haemorrhage. Placental trophoblasts express and produce coagulation components, participating not only in haemostasis but also in placental vascular development and differentiation. The expression of tissue factor, membrane phosphatidylserine and fibrin render the trophoblasts pro-coagulant, thus compromising the risk of bleeding while exposing the placenta to pro-thrombotic risks. Local inhibitory mechanisms-TFPI-1 and TFPI-2, thrombomodulin, annexin V and the fibrinolytic system-limit coagulation activation and fibrin deposition. Pregnancy complications have been associated with abnormalities in the functions of these inhibitors. Haemostatic processes in placental cells change throughout gestation and are affected by the changing requirements of the organ.     

Immunocytochemical localization of the human growth hormone variant in the human placenta

Two monoclonal antibodies (Mab 5B4 and K24) were used for the immunocytochemical localization of human GH (hGH) and human placental GH in the human pituitary and placenta. On the basis of prior selection by RIA, Mab 5B4 was known to be directed to the N-terminal of hGH and was able to detect both pituitary and placental hGH, since their primary amino acid sequences are identical in this domain. Mab K24 was directed to an epitope present in hGH, but not in placental hGH, and was able to detect pituitary hGH only; neither the 5B4 or K24 Mab detected human placental lactogen. Five placentas were studied from women at term after elective cesarean section without labor. The cells of the anterior pituitary gland and the syncytiotrophoblast of the placental villi were stained with Mab 5B4, whereas K24 only stained the pituitary cells; results consistent with the RIA screen. Mab 5B4 specifically stained two different cell types in the placental basal plate. Neither antiserum stained any cell in the amniotic or chorionic membranes or the adherent decidua. The results demonstrate that pituitary hGH and placental hGH are expressed uniquely in the pituitary and fetal placenta, respectively. In addition, the placental hGH gene is also expressed in the placental basal plate, a region of mixed fetal and maternal cells.     

Thyrotropin-releasing hormone activity in the human placenta.

TRH immunological and biological activities were found in extracts of human placentas. Eight term placentas delivered by cesarean section were extracted with 2 N acetic acid, followed by glacial acetic acid. Lyophilized samples were resuspended in phosphate-buffered saline. TRH activity, identified in each placental extract by specific RIA, averaged 19.8 +/- 3.3 pg/mg protein. TRH in the placental extracts was similar to synthetic TRH by four criteria. 1) Serial dilutions of placental extracts defined an immunoassay inhibition curve with a slope (-1.93) identical to synthetic TRH (-1.88). 2) When placental extract or synthetic TRH was chromatographed on Sephadex G-10, TRH immunoreactivity was found in similar fractions of the eluate. 3) Both placental extract and synthetic TRH stimulated TSH release from rat pituitaries in vitro. 4) Human serum degraded placental extract and synthetic TRH in a qualitatively similar manner. Placental minces did not accumulate exogenous [3H]TRH, suggesting that the placental TRH may originate endogenously.     

Cytoadherence of Plasmodium falciparum-infected erythrocytes in the human placenta

In Plasmodium falciparum-parasitized pregnant women, erythrocytes infected by mature stages of the parasite sequester into placental intervillous spaces. The presence of parasites in the placenta causes maternal anaemia and low birth weight of the infant. In-vitro studies suggest placental sequestration may involve the cytoadherence of infected erythrocytes to chondroitin sulphate A (CSA) and/or intercellular adhesion molecule 1 (ICAM-1) expressed by human placental syncytiotrophoblast. We identified P. falciparum receptors expressed on the surface of human syncytiotrophoblast using immunofluorescence of placental biopsies from Cameroon, a malaria-endemic area. In all placentas, a strongly positive staining was observed on the syncytiotrophoblast for CSA, but not for ICAM-1, vascular endothelium cell adhesion molecule-1, E-selectin, nor CD36. The cytoadherence ability of parasites from pregnant women and nonpregnant subjects was assessed on in-vitro cultured syncytiotrophoblast. Parasites from pregnant women bound to the trophoblast via CSA but not ICAM-1. Parasites from nonpregnant hosts either did not bind to the trophoblast culture or bound using ICAM-1. Our data support the idea that placental sequestration may result from cytoadherence to placental trophoblast and that pregnant women are parasitized by parasites that differ from parasites derived from nonpregnant host by their cytoadherence ability.     

Genital human papillomavirus infections

In summary, the development of new techniques to identify HPV DNA in genital secretions and tissue, the recognition of subclinical HPV infection, and the remarkable association between HPV and genital neoplasia have markedly increased the concern of both patients and physicians about genital wart virus infections. The prevalence of this viral STD appears to be increasing and the clinical spectrum of disease appears to be expanding. New methods to diagnose genital HPV infection and techniques to treat these infections more effectively are under development. It is hoped that these techniques will provide the tools to understand and more effectively control this important infection.     

Limited evolutionary conservation of imprinting in the human placenta

The epigenetic phenomenon of genomic imprinting provides an additional level of gene regulation that is confined to a limited number of genes, frequently, but not exclusively, important for embryonic development. The evolution and maintenance of imprinting has been linked to the balance between the allocation of maternal resources to the developing fetus and the mother's well being. Genes that are imprinted in both the embryo and extraembryonic tissues show extensive conservation between a mouse and a human. Here we examine the human orthologues of mouse genes imprinted only in the placenta, assaying allele-specific expression and epigenetic modifications. The genes from the KCNQ1 domain and the isolated human orthologues of the imprinted genes Gatm and Dcn all are expressed biallelically in the human, from first-trimester trophoblast through to term. This lack of imprinting is independent of promoter CpG methylation and correlates with the absence of the allelic histone modifications dimethylation of lysine-9 residue of H3 (H3K9me2) and trimethylation of lysine-27 residue of H3 (H3K27me3). These specific histone modifications are thought to contribute toward regulation of imprinting in the mouse. Genes from the IGF2R domain show polymorphic concordant expression in the placenta, with imprinting demonstrated in only a minority of samples. Together these findings have important implications for understanding the evolution of mammalian genomic imprinting. Because most human pregnancies are singletons, this absence of competition might explain the comparatively relaxed need in the human for placental-specific imprinting.     

Serology for human papillomavirus

Difficulties with serology for papillomavirus are associated with the large number of human papillomavirus, cross-reactions between papillomavirus, and to the diversity of lesions and target sites for infection. In addition, the expression of the papillomavirus in the superficial layers of the epithelium gives rise to the weak presentation to immunocompetent cells of viral antigens, which in turn gives rise to a weak serological response. Distinct efforts have been made in previous decades to develop more specific and sensitive serological assays. These former studies use fusion proteins and synthetic peptides, although they remain on the whole uninteresting, due to their lack of sensitivity and specificity. Only in the last few years, and principally due to the advent of various virus-like particles (VLP), have more sensitive and specific assays become available. This paper is available too at: http://www.insp.mx/salud/index.html.     

Gene expression patterns in human placenta

The placenta is the principal metabolic, respiratory, excretory, and endocrine organ for the first 9 months of fetal life. Its role in fetal and maternal physiology is remarkably diverse. Because of the central role that the placenta has in fetal and maternal physiology and development, the possibility that variation in placental gene expression patterns might be linked to important abnormalities in maternal or fetal health, or even variations in later life, warrants investigation. As an initial step, we used DNA microarrays to analyze gene expression patterns in 72 samples of amnion, chorion, umbilical cord, and sections of villus parenchyma from 19 human placentas from successful full-term pregnancies. The umbilical cord, chorion, amnion, and villus parenchyma samples were readily distinguished by differences in their global gene-expression patterns, many of which seemed to be related to physiology and histology. Differentially expressed genes have roles that include placental trophoblast secretion, signal transduction, metabolism, immune regulation, cell adhesion, and structure. We found interindividual differences in expression patterns in villus parenchyma and systematic differences between the maternal, fetal, and intermediate layers. A group of genes that was expressed in both the maternal and fetal villus parenchyma sections of placenta included genes that may be associated with preeclampsia. We identified sets of genes whose expression in placenta was significantly correlated with the sex of the fetus. This study provides a rich and diverse picture of the molecular variation in the placenta from healthy pregnancies.     

16-Dehydrogenase in human placenta.

Human placenta subfractions were incubated with radioactive oestriol and 16-oxo-oestradiol. 16-oxo-oestradiol was identified from the oestriol incubation. Oestriol and 16-epi-oestriol were characterized from the incubation while 16-epi-oestriol were characterized from the incubation with 16-oxo-oestradiol. The 16alpha-dehydrogenase has been located in the soluble fraction (105 000 g supernatant) of the human placenta.     

Evidence for Chlamydia trachomatis as a human papillomavirus cofactor in the etiology of invasive cervical cancer in Brazil and the Philippines.

Chlamydia trachomatis infection was examined as a cause of invasive cervical cancer (ICC) among women with human papillomavirus (HPV) infection. In total, 499 women with incident ICC (ICC patients) and 539 control patients from S?o Paulo, Brazil, and Manila, the Philippines, were included. C. trachomatis antibodies were detected by microimmunofluorescence assay. Presence of HPV DNA in cervical specimens was determined by a polymerase chain reaction-based assay. C. trachomatis seropositivity was associated with sexual behavior but not with HPV infection. C. trachomatis increased the risk of squamous cervical cancer among HPV-positive women (odds ratio, 2.1; 95% confidence interval, 1.1-4.0). Results were similar in both countries. There was a suggestion of increasing squamous cancer risk with increasing C. trachomatis antibody titers. This large study examined C. trachomatis and cervical cancer, taking into account the central role of HPV infection. C. trachomatis infection was found to be a possible cofactor of HPV in the etiology of squamous cervical cancer, and its effect may be mediated by chronic inflammation.