bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the Source of Inhibins at the Time of Conception Provides a Diagnostic Role for Them in Very Early Pregnancy
Authors: Lockwood G.M. , Ledger W.L. , Barlow D.H. , Groome N.P. , Muttukrishna S. 
Published: September 2011

PROBLEM: Early diagnosis of a complicated or poor pregnancy outcome in patients undergoing assisted reproductive technique (ART) fertility treatment could aid their counseling and management. A possible role for the inhibin superfamily as markers of early pregnancy viability was investigated.METHOD OF STUDY: To determine the source of the dimeric glycoproteins inhibin A (α‐βA) in early pregnancy, serial blood samples from women who became pregnant following in vitro fertilization (IVF) with fresh embryo transfer (n = 50), from women who achieved pregnancy with frozen‐thawed embryos (n = 8), and from a control group of women with spontaneous conceptions (n = 7) were analyzed using a two‐site enzyme‐linked immunosorbent assay (ELISA). Gonadotropin‐releasing hormone (GnRH) analogues are routinely used in ART treatment cycles and are recognized to be luteolytic, and hence, periconceptual administration may be deleterious to pregnancy outcome. Serum samples were obtained from 8 IVF patients who conceived during the cycle in which they had inadvertent luteal phase exposure to GnRH analogues.RESULTS: Elevated serum levels of inhibin A were detected in ongoing pregnancies from 4 weeks' gestation and increased to an initial peak at 9–10 weeks' gestation. Significantly higher levels (P < 0.05) were found in the multiple pregnancies, and nonviable clinical pregnancies had very low levels of inhibin A. Inhibin pro‐αC was detectable at levels above normal late luteal values in singleton and multiple pregnancies arising from IVF with fresh embryo transfer. In pregnancies established without corpus luteum activity, frozen‐thaw embryo replacement, the levels of pro‐αC containing inhibins were extremely low, suggesting that the corpus luteum is the major source of the alpha monomer. In pregnancies following inadvertent periconceptual exposure to GnRH analogue, the levels of pro‐αC were statistically significantly higher in successful pregnancies than in early pregnancy failures.CONCLUSIONS: The feto‐placental unit is confirmed as the major source of inhibin A in early pregnancy, and the initially low levels and very rapid decline in inhibin A in pregnancies with embryonic failure suggest a role for this glycoprotein as a monitor of early pregnancy viability. The corpus luteum is demonstrated to be the major source of inhibin pro‐αC in early pregnancy, and very low levels in patients with peri‐implantational exposure are indicative of lytic damage and herald pregnancy failure despite luteal supplementation with progesterone.
Anti‐inflammatory Effects of Interleukin‐4, Interleukin‐10, and Transforming Growth Factor‐β on Human Placental Cells In Vitro
Authors: Goodwin V.J. , Sato T.A. , Mitchell M.D. , Keelan J.A. 
Published: September 2011

PROBLEM: To determine the effects of anti‐inflammatory cytokines on the production of inflammatory mediators by placental cells.METHOD OF STUDY: Cells from term human placentas were isolated and cultured in vitro in the presence of anti‐inflammatory cytokines interleukin (IL)‐4, IL‐10, and transforming growth factor (TGF)‐β. Their effects on the production of IL‐8 and prostaglandin E2 (PGE2) were investigated under basal conditions and after stimulation with IL‐1β and tumor necrosis factor (TNF)‐α.RESULTS: Both IL‐10 and IL‐4 inhibited IL‐1β‐ and TNF‐α‐induced PGE2 production but had no significant effects on the production of PGE2 under basal conditions. TGF‐β1 was without effect in stimulated cells, whereas under basal conditions TGF‐β1 stimulated PGE2 production. Similar trends were seen for IL‐8 production, with the exceptions that TGF‐β1 decreased the TNF‐α‐induced production and IL‐4 decreased basal IL‐8 production.CONCLUSIONS: The anti‐inflammatory effects shown by IL‐4, IL‐10, and (to lesser extent) TGF‐β may play a role in ameliorating the potentially harmful effects of pro‐inflammatory mediators in the feto‐placental unit.
Gestational Age‐Dependent Extravillous Cytotrophoblast Osteopontin Immunolocalization Differentiates Between Normal and Preeclamptic Pregnancies
Authors: Gabinskaya Tatyana , Salafia Carolyn M. , Gulle Veronica E. , Holzman Ian R. , Weintraub Andrea S. 
Published: September 2011

PROBLEM: Normal placentation requires modulation of proliferative cytotrophoblast to an invasive phenotype. Preeclampsia is characterized by failed cytotrophoblast invasion and arterial remodeling. Osteopontin (OPN) is an extracellular matrix protein implicated in cell adhesion, spreading, and invasion.METHOD OF STUDY: To investigate gestational age‐related OPN expression, placental immunostaining was performed. To investigate the role of OPN in uteroplacental vascular pathology, placental immunostaining from pregnancies with preeclampsia (n = 12), fetal growth retardation (FGR) (n = 8), or both (n = 4) was compared with gestational age‐matched controls (n = 24).RESULTS: In non‐preeclamptic pregnancies, OPN immunolocalized to basal plate and intervillous cytotrophoblasts from 24–30 weeks (n = 13). In preeclampsia, OPN immunoreactivity was detected from 24–40 weeks. Cytotrophoblasts from FGR placentas were OPN‐positive until 30 weeks, unless preeclampsia accompanied the FGR. In this case, cytotrophoblasts were OPN‐positive from 24–40 weeks.CONCLUSIONS: The data suggest a role for OPN in cytotrophoblast invasion of the maternal vasculature/extracellular matrix during non‐preeclamptic placentation, and OPN may serve as a marker for placental bed remodeling.
Labor Affects Cytokine Production in Newborns
Authors: Bessler H. , Kuperman A. , Beilin B. , Klinger G. , Gurary N. , Mozes C. , Sirota L. 
Published: September 2011

PROBLEM: To investigate whether the mode of delivery or the drugs given to the mother during labor may affect the newborns' immune system.METHOD OF STUDY: Three groups of term newborns were included: A, spontaneously delivered with i.v. analgesia (n = 37); B, spontaneously delivered with epidural analgesia (n = 26); and C, delivered by cesarean section under general anesthesia (n = 29). Natural killer (NK) cell cytotoxicity, mitogenic response, and the capacity of peripheral blood mononuclear cells (PBMCs) to produce interleukin (IL)‐1β, IL‐2, IL‐3, IL‐6, and tumor necrosis factor (TNF)‐α were examined.RESULTS: NK cell cytotoxicity increased significantly in all three groups of newborns on the second day of life. Decreased IL‐2 production was observed in newborns delivered by cesarean section. Spontaneous IL‐1β secretion was higher in newborns to mothers treated with epidural analgesia. Spontaneous IL‐6 secretion was elevated in infants to mothers undergoing general anesthesia and surgery or epidural analgesia. TNF‐α production was increased in newborns delivered by cesarean section.CONCLUSION: The immune response of the newborn is affected by the mode of delivery and/or drugs given to the mother during labor.
Inhibin A Concentrations in the Sera of Young Women During and After Chemotherapy for Lymphoma: Correlation with Ovarian Toxicity
Authors: Blumenfeld Z. , Ritter M. , Shen‐Orr Z. , Shariki K. , Ben‐Shahar M. , Haim N. 
Published: September 2011

PROBLEM: Inhibin A concentrations in serum may reflect the ovarian granulosa cell compartment. To characterize the correlation between ovarian function after gonadotoxic chemotherapy for Hodgkin's or non‐Hodgkin's lymphoma in young women, the immunoreactive inhibin A concentrations in the sera of these patients was measured before, during, and after the gonadotoxic chemotherapy.METHOD OF STUDY: A prospective clinical protocol was undertaken in 20 cycling women with lymphoma, aged 15–40 years. A monthly injection of depot D‐TRP6 ‐GnRH‐a (Decapeptyl CR, Ferring) was administered from before starting the chemotherapy until its conclusion, up to a maximum of six monthly injections. Most of the patients were treated with the mustargen‐oncovin‐procarbazine‐prednisone (MOPP)/actinomycin D‐bleomycinvincristine (ABV) chemotherapy combination; 13 with and 7 without radiotherapy. A hormonal profile [follicle‐stimulating hormone (FSH), luteinizing hormone (LH), 17‐β‐estradiol (E2), testosterone (T), progesterone (P4), insulin‐like growth factor (IGF)‐1, IGF‐bp3, and prolactin (PRL)] was taken before starting the gonadotropin‐releasing hormone agonist (GnRH‐a)/chemotherapy co‐treatment and monthly thereafter until resuming spontaneous ovulation and menstrual cyclicity. This group of prospectively treated lymphoma patients was compared with a control group of 22 regularly cycling women who had been treated with chemotherapy (mostly MOPP/ABV) with or without radiotherapy for Hodgkin's or non‐Hodgkin's lymphoma. Inhibin A immunoactivity developed by Nigel Groome was measured by an enzyme‐linked immunoadsorbent assay (ELISA) commercial kit (Serotec).RESULTS: Whereas all but one (40 years of age) of the surviving patients in the GnRH‐a/chemotherapy co‐treatment group resumed spontaneous ovulation and menses within 6 months, only one half of the patients in the “control” group (chemotherapy without GnRH‐a co‐treatment) resumed ovarian function and regular cyclic activity (P < 0.05). The remaining 50% experienced premature ovarian failure (POF). Temporarily increased FSH concentrations were experienced by approximately one third of the patients resuming cyclic ovarian function, suggesting a reversible ovarian damage in a larger proportion of women than those experiencing POF. The inhibin A immunoactive concentrations decreased during the GnRH‐a/chemotherapy co‐treatment but increased to normal levels in patients who resumed regular ovarian cyclicity, and/or spontaneously conceived, as compared to low levels in menopausal women and those who had developed POF.CONCLUSIONS: If these preliminary data are consistent in a larger group of patients, inhibin A concentration may serve as a prognostic factor for predicting the resumption of ovarian function, in addition to the levels of FSH, LH, and E2.
Tumor Necrosis Factor‐α mRNA‐Positive Cells in Spontaneous Resorption in Rodents
Authors: Lea Richard G. , McIntyre Susan , Baird Joyce D. , Clark David A. 
Published: September 2011

PROBLEM: It has been proposed that high rates of resorption/spontaneous abortion may result from interaction in the decidua of γ‐interferon‐producing natural killer (NK) cells and tumor necrosis factor (TNF)‐α‐producing macrophages. An increased release of TNF‐α from placental tissue of resorptions has been reported, but macrophages producing TNF‐α have so far not been demonstrated at the feto‐maternal interface. Therefore, we have sought to identify TNF‐α‐producing cells by in situ hybridization at the feto‐maternal interface in two inbred, well‐characterized, and stable strains of laboratory rodents with high and low resorption rates.METHOD OF STUDY: Pregnant DBA/2‐mated CBA/J mice with a resorption rate of 20% to 30% (dependent on NK cells and macrophages) and diabetes‐resistant Bio‐Breeding/ Edinburgh (DR‐BB/E) rats with low resorption rates (presumed to result from chromosomal abnormalities) were studied. AsialoGMl+ cells were detected by immunohistochemistry, and TNF‐α mRNA+ cells were detected by in situ hybridization.RESULTS: TNF‐α mRNA+ cells were detected in DBA/2‐mated CBA/J mice at the time of resorption but only at the trophoblast‐decidual junction. AsialoGM1+ cells were present in decidua, as assessed by immunohistochemistry, but few if any gave a positive signal for TNF‐α. In rat resorptions, TNF‐α mRNA‐positive cells were present within the yolk sac and in contact with the trophoblast, but not at the trophoblast‐decidual junction. In neither species did a significant accumulation of detectable TNF‐α mRNA+ cells occur before the usual time of onset of resorption.CONCLUSIONS: In the DBA/2‐mated CBA/J mouse, the removal of the placenta is associated with removal of a thin rim of adherent decidua similar to the location of the TNF‐α mRNA+ cells detected in this study. Our data suggest that increased TNF‐α in tissues associated with failing feto‐placental units may arise from infiltration/activation of scavenger cells from decidua that are likely to be macrophages. Local TNF‐α production in decidua, which occurs as a prelude to resorption in the CBA x DBA/2 model, could not be detected due to the insensitivity of the TNF‐α probe we used; the release of TNF‐α from decidual tissue left after the removal of the placenta does not differ between resorbing and healthy implant sites. AsialoGM1+ cells did not seem to be major producers of TNF‐α. TNF‐α mRNA+ cells in a low rate of resorption (rat) model were only found on the fetal side of the trophoblast, and they may also represent a macrophage response (to dying embryo tissue) derived from a nondecidual source. The location of TNF‐α mRNA+ cells may identify distinct and different mechanisms of resorption in rodents.
Anti‐Endothelial Cell Antibodies: Another Cause for Pregnancy Loss?
Authors: Roussev Roumen G. , Stern Jaroslav J. , Kaider Brian D. , Thaler Christian J. 
Published: September 2011

PROBLEM: Previous studies demonstrated that unique tissue‐specific antigens expressed on vascular endothelial cells can serve as immunogens, and the apparent association between transplant rejection and antiendothelial cell (EC) antibodies is well established. A common feature of some placentas from women with recurrent pregnancy loss is the diffuse formation of microthrombi associated with changes in thromboresistant properties of endothelial cells, similar to the findings in rejected organs. Therefore, the prevalence of anti‐EC antibodies in patients with recurrent pregnancy loss and the role of these antibodies in cultured human endothelial cells from umbilical cord vein were studied.METHOD OF STUDY: To evaluate the frequency of anti‐EC antibodies, sera from 160 nonpregnant patients with recurrent pregnancy loss after absorption with pooled platelets and pooled leukocytes were tested using cultured human umbilical cord vein endothelial cells (HUVEC) by flow cytometry. To study the role of anti‐EC antibodies, purified anti‐EC IgGs were added to HUVEC cultures and hemostatic, fibrinolytic, and anticoagulation pathway markers (tissue factor, tissue plasminogen activator, palsminogen‐activator inhibitor, thrombomodulin, heparan‐sulfate proteoglican, antithrombin III, von Willebrand factor, CD54, human leukocyte antigens‐DR, and transferin receptor) were detected by specific antibodies and flow cytometry. Immunoblotting analyses were done by using purified anti‐EC IgGs against cell membrane proteins from endothelial cells and leukocytes extracted by detergent solubilization.RESULTS: Thirty‐nine (24%) of the patients were positive for EC antibodies. Antipaternal lymphocyte antibodies were tested as well and were found in 37 (23%) of the patients as 25 sera (15.6%) showed reactivity with both EC and lymphocytes. Certain patient sera were reactive with HUVEC lines from some but not other umbilical cords, which suggests allotype Sera from 70 normal healthy male and nonpregnant female controls did not react with any of the individual HUVEC lines used. The purified anti‐EC immunoglobulin G (IgGs) recognized bands, from HUVEC surface membrane protein preparations, with molecular weights of 120 kDa. Both hemostatic and fibrinolytic pathway markers were found activated in the presence of anti‐EC IgGs, suggesting an altered endothelial cell surface activation state.CONCLUSIONS: The results indicate that anti‐EC antibody is another marker for a subset of recurrent spontaneous aborters who may have activation of hemostasis and fibrinolysis as a mechanism involved in their losses.
The Production of MLR‐Blocking Factors After Lymphocyte Immunotherapy for RSA Does Not Predict the Outcome of Pregnancy
Authors: Peña Ruth Beatriz , Cadavid Angela P. , Botero Jorge H. , García Gloria P. , Gallego María I. , Ossa Jorge E. 
Published: September 2011

PROBLEM: The questions of whether production of mixed lymphocyte reaction‐blocking factors (MLR‐BFs) after immunotherapy with lymphocytes for recurrent spontaneous abortion (RSA) has prognostic value and whether cytotoxic antibodies are also involved were tested.METHOD OF STUDY: A prospective study with 33 patients who had a history of two or more abortions, lacking MLR‐BFs, was carried out. The patients received immunizations with lymphocytes and 6 weeks or later were tested for seroconversion of MLR‐BFs. Seventeen of these thirty‐three patients were evaluated for antipaternal cytotoxic antibodies. The results were correlated with the outcome of the next pregnancy after treatment. RESULTS: Eighty percent of the 33 patients had a live child. Of those patients having success, only 50% produced MLR‐BFs. Of those patients having a new loss, five did and two did not produce MLR‐BF (P > 0.05). Regarding the 17 patients tested for cytotoxic antibodies, 4 of the 5 patients who tested positive had a new abortion, whereas only 1 of 12 whose tests remained negative did not have gestational success (P < 0.01). CONCLUSION: The presence of MLR‐BFs is not a prognostic criterium for the outcome of pregnancy after alloimmunotherapy, and, consequently, it is not a good diagnostic tool for RSA of alloimmune cause.
Soluble Intercellular Adhesion Molecule‐1 Serum Profile in Physiologic and Preeclamptic Pregnancy
Authors: Airoldi Lucia , Gaffuri Barbara , Rossi Gabriele , Iurlaro Enrico , Nozza Arrigo , Vigano Paola , Vignali Mario 
Published: September 2011

PROBLEM: The aim of this study was to determine serum levels of soluble intercellular adhesion molecule (sICAM)‐1, an adhesion receptor that mediates interactions with the immune system, in physiologic and preeclamptic pregnancies. Moreover, we evaluated whether the release of sICAM‐1 during pregnancy correlated to plasma fibronectin concentrations.METHOD OF STUDY: Serum was collected from 18 nonpregnant, control women, from 58 normal pregnant women during the first (n = 13), second (n = 15), and third (n = 30) trimesters, and from 25 preeclamptic patients at 27–39 weeks' gestation. All samples were assayed for sICAM‐1 by a specific enzyme‐linked immunoassay and for fibronectin by a nephelometric system. Serum sICAM‐1 levels in preeclamptic patients were compared to those obtained from gestational‐matched normal pregnant women.RESULTS: Levels of sICAM‐1 were significantly elevated (P < 0.001) in each of the three trimesters of normal pregnancy (I trimester: 390.4 ± 25.7 ng/ml; II trimester: 386.3 ± 15.4 ng/ml; and III trimester: 367.3 ± 15.8 ng/ml) when compared to those of healthy nonpregnant women (263.3 ± 11.6 ng/ml). No significant difference in sICAM‐1 concentrations was observed among the three trimesters. Preeclampsia was associated to a significant decrease (P < 0.01) of sICAM‐1 levels (309.8 ± 11.6 ng/ml) relative to those observed in gestational‐matched pregnant women (367.3 ± 15.8 ng/ml). Fibronectin and sICAM‐1 levels did not correlate.CONCLUSION: The increased levels of sICAM‐1 found in physiologic pregnancies and its reduction in preeclampsia may account for some of the immunologic alterations demonstrated to be associated with pregnancy.
Vaginal Immunization with Recombinant Gram‐Positive Bacteria
Authors: Medaglini Donata , Oggioni Marco R. , Pozzi Gianni 
Published: September 2011

PROBLEM: Many viral and bacterial pathogens enter the body through the genital mucosa. Therefore, one of the major goals of a vaccine against sexually transmitted diseases (STDs) should be to induce an immune response in the genital mucosa capable of controlling the entry of the pathogen. Our approach for the development of vaccines against STDs is based on the use of nonpathogenic Gram‐positive bacteria as live vaccine vectors.METHOD OF STUDY: Recombinant Gram‐positive bacteria expressing vaccine antigens were constructed using genetic systems developed in our laboratory. Balb/c mice and Cynomolgus monkeys were inoculated by the vaginal route and vaginal samples were collected using absorbent wicks. Colonization was evaluated by the presence of recombinant bacteria in the vaginal samples. Local and systemic immune responses were studied.RESULTS: We have developed genetic systems for the expression of heterologous antigens on the surface of the human commensals Streptococcus gordonii and Lactobacillus spp. Both S. gordonii and L. casei stably colonized the murine vagina after a single inoculum. Vaginal colonization of mice with recombinant strains of S. gordonii, expressing human papillomavirus (HPV) and human immunodeficiency virus (HIV) antigens, induced antigen‐specific vaginal immunoglobulin A (IgA) and serum IgG. Local and systemic immune responses also were detected in monkeys immunized intravaginally with recombinant S. gordonii.CONCLUSION: The results obtained indicated that the approach of using colonizing Gram‐positive bacteria as live vectors has a great potential for the development of vaccines against STDs.
Neutralizing Antibodies and Complement‐Mediated, Antibody‐Dependent Enhancement (C'‐ADE) of Human Immunodeficiency Virus Infection in Its Vertical Transmission
Authors: Gras Gabriel , Beyssen Véronique , Tranchot‐Diallo Juliette , Dormont Dominique , Parnet‐Mathieu Françoise , Lasfargues Géraud , Courpotin Christian 
Published: September 2011

PROBLEM: Mother‐to‐child transmission is a major route for the spread of human immunodeficiency virus (HIV) worldwide. Our understanding of its mechanisms and parameters is still limited. Among the factors possibly involved in virus passage determination are the level and quality of antiviral humoral response.METHOD OF STUDY: Anti‐HIV‐1/Lai neutralizing activity in sera from 35 mother‐infant pairs (in which 13 transmission cases occurred) was investigated, as was the complement‐mediated antibody‐dependent enhancement capacity of the same sera.RESULTS: Neutralization titers of 640 or more were found only in four mothers of uninfected children, but this result was not significant. No significant link was obtained with the occurrence of complement‐mediated, antibody‐dependent enhancement.CONCLUSIONS: As suggested by a synthesis of the literature, vertical transmission of HIV is probably the result of multiple active and/or stochastic parameters in the mother, the fetal structures, and the viral population. The precise definition of cellular mechanisms involved in in utero infection would help to better define which immune activity in the mother should be more carefully considered.
Fas‐Fas Ligand System‐Induced Apoptosis in Human Placenta and Gestational Trophoblastic Disease
Authors: Mor Gil , Gutierrez Linda S. , Eliza Mariel , Kahyaoglu Ferahnaz , Arici Aydin 
Published: September 2011

PROBLEM: The low frequency of maternal immune responses to paternally inherited fetal antigens raises the following question: What regulates the immunobiology of pregnancy? Data suggest that this state is the result of peripheral immune‐tolerance, an active process of immune‐regulation in which activated T cells undergo apoptosis. We studied Fas ligand (FasL) expression and apoptosis in normal and pathologic placentas to find out whether the Fas‐FasL‐induced apoptosis takes place during implantation.METHOD OF STUDY: FasL expression in paraffin sections was detected using specific antibodies and confirmed with reverse transcriptase‐polymerase chain reaction of total RNA from frozen placentas. Apoptosis was detected using the terminal deoxy (d)‐UTP nick end‐labeling assay.RESULTS: FasL was found in the normal placenta and in gestational trophoblastic disease. Apoptotic leukocytes were localized to the maternal‐fetal interface corresponding in localization with the distribution of FasL.CONCLUSIONS: We propose that FasL expression in the placenta is a mechanism responsible for the development of maternal immune tolerance specific for paternal alloantigens and operates in pathologic states characterized by trophoblastic invasion/proliferation.