bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Pregnancy on Lymphocytes Within Sheep Uterine Interplacentomal Epithelium
Authors: FOX A. , LEE C.S. , BRANDON M.R. , MEEUSEN E.N.T. 
Published: September 2011

PROBLEM: Previous studies demonstrate increases in the number and granularity of γδ T cells within the sheep uterine interplacentomal epithelium during pregnancy. To further characterize their activation and function, γδ T‐cell receptor (TCR)+ intraepithelial lymphocytes (IELs) from nonpregnant and pregnant uteri were phenotyped extensively. Cytokine mRNA expression in the epithelium and by γδTCR+ IELs isolated from pregnant uteri was also examined.METHOD OF STUDY: Cell suspensions were prepared from the uterine interplacentomal epithelium and from the peripheral blood of nonpregnant and pregnant ewes (120–140 days of gestation). Surface marker expression was determined by two‐color flow cytometry and cytokine expression determined by reverse transcriptase‐polymerase chain reaction.RESULTS: Uterine γδTCR+IELs exhibited increased β1‐integrin expression but decreased leukocyte function associated antigen (LFA)‐1 and major histocompatibility complex class I expression during pregnancy. Major histocompatibility complex class II, CD44, CD2, and LFA‐3 expression was unchanged during pregnancy, whereas CD25, VLA‐4 and L‐selectin were never expressed. The same cytokines were expressed in the pregnant and nonpregnant uterine interplacentomal epithelium with detectable mRNA for interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α, and interleukin (IL)‐1α, but not for IL‐2 or IL‐4. γδTCR+ and CD8+ IEL purified from pregnant uteri expressed mRNA for IFN‐γ, TNF‐α, transforming growth factor‐β, and IL‐10.CONCLUSIONS: γδTCR+ IELs from pregnant uteri have cytoplasmic granules, and express CD8 and cytokines indicative of cytotoxic potential. Phenotypic changes induced during pregnancy differed from those observed after activation of circulating naive cells and may represent further stimulation of fully differentiated effectors. γδTCR+ IELs are present only in interplacentomal areas of pregnant uteri and may control trophoblast invasion within these areas.
Elevated IL‐6 in Midtrimester Amniotic Fluid Is Involved with the Onset of Preeclampsia
Authors: Nakabayashi Masao , Sakura Mari , Takeda Yoshihiko , Sato Kodo 
Published: September 2011

PROBLEM: The primary defect of placental development in preeclampsia is speculated to occur at midtrimester gestation. Abnormal feto‐maternal immune reactions have been considered as factors in such defective placentation.METHOD OF STUDY: Midtrimester amniotic fluid specimens were retrospectively identified as coming from gestations that later had severe preeclampsia develop, gestations with normal outcomes, and gestations measured for cytokines tumor necrosis factor‐α (TNF‐α), interleukin (IL‐1β, IL‐6, and IL‐8). The effect of each cytokine on thrombomodulin levels was tested in cultured trophoblast cells.RESULTS: Among the measured cytokines, IL‐6 and IL‐8 were significantly elevated in the midtrimester amniotic fluid of the future preeclamptic group. Trophoblasts stimulated with TNF‐α plus IL‐6 had significantly decreased levels of cellular thrombomodulin compared to those without cytokine addition.CONCLUSIONS: Elevated cytokines in midtrimester amniotic fluid suggest an abnormal fetomaternal immune response occurring before the clinical manifestation of preeclampsia. Cytokine‐induced suppression of thrombomodulin in trophoblasts may be directly involved in the pathogenesis of preeclampsia.
Why Did Your Mother Reject You? Immunogenetic Determinants of the Response to Environmental Selective Pressure Expressed at the Uterine Level
Authors: Clark David A. , Arck Petra C. , Chaouat Gerard 
Published: September 2011

PROBLEM: Maternal “rejection” of the implanted conceptus is considered to account for a significant proportion of miscarriages (abortions) in both humans and animals. Our understanding of mechanisms has been limited, and hence, explanations for nonrejection have remained largely speculative. Losses, when they occur, could represent either random accidental failure of protective mechanisms or a more purposeful discrimination.METHOD OF STUDY: An analysis of the most recent data.RESULTS AND CONCLUSIONS: The embryo is most akin to a parasite, and pregnancy is most akin to a host‐parasite interaction. If one excludes chromosome abnormalities in the embryo as a cause of death, activation of coagulation mechanisms, leading to vasculitis affecting the maternal blood supply to the implanted embryo, appears to represent a major loss‐causing mechanism—a form of ischemic autoamputation. Proinflammatory T‐helper (Th) 1‐type cytokines trigger this process via upregulation of a novel prothrombinase, fg***12. Th2/3 cytokines, such as interleukin (IL)‐4, IL‐10, and transforming growth factor (TGF)‐β2, may antagonize the processes involved. Cytokine balance is determined by the genetics of the mother, which regulate her response to stress; endotoxin (LPS); and paternal antigens, selectively expressed on the trophoblast of the embryo, via imprinting. Based on studies in abortion‐prone mice, where immunity to paternal alloantigens prevents loss, three distinct gene products in the embryo are proposed to determine the cytokine response of maternal lymphomyeloid cells in the uterus.
Placenta Growth Factor: Potential Role in Pregnancy
Authors: Torry Donald S. , Ahn Henry , Barnes Eva L. , Torry Ronald J. 
Published: September 2011

PROBLEM: In spite of the known requirement for adequate vascularity during placentation, little is known regarding the regulation of angiogenic growth factor production by trophoblast. Placenta growth factor (P1GF) is a recently discovered angiogenic growth factor whose expression is relatively limited to trophoblast.METHOD OF STUDY: Current literature of P1GF was reviewed, with emphasis on its expression, regulation, role in angiogenesis, and potential function(s) at the maternal‐fetal interface.RESULTS: P1GF is abundantly expressed by trophoblast, which implies that it could act in a paracrine manner to modulate vascular development, stability, and/or function within the decidua and placental villi. In addition, expression of the P1GF receptor, fms‐like tyrosine kinase (f***lt‐1) receptor, on trophoblast raises the potential for an autocrine role of P1GF in regulating trophoblast growth and/or function.CONCLUSIONS: The potential for P1GF to influence both vascular endothelial cells and trophoblast suggests that aberrant trophoblast production of P1GF could compromise cellular function during gestation and contribute to the vascular and placental pathologies noted in many obstetric complications.
Immunodiagnostic Evaluation in Women with Reproductive Failure
Authors: Kaider Azadeh S. , Kaider Brian D. , Janowicz Patrick B. , Roussev Roumen G. 
Published: September 2011

Kaider AS, Kaider BD, Janowicz PB, Roussev RG. Immunodiagnostic evaluation in women with reproductive failure. AJRI 1999; 42:335–346 © Munksgaard, CopenhagenPROBLEM: Several immunological factors have been associated with diagnostic subpopulations of reproductive failure. It is important to determine a trend of immunological abnormalities among these subpopulations. The purpose of this study is to assist in the selection of treatment for patients suspected of having specific diagnoses of reproductive failure.METHOD OF STUDY: Blood samples from 591 patients were evaluated for the presence of antiphospholipid (APA), antinuclear (ANA), and antithyroid (ATA) antibodies, as well as for lupus anticoagulant (LA), embryotoxic factors (ETF), and elevated levels of natural killer (NK) (CD56+) cells, and all tests were performed as a panel. The patients were grouped into the following diagnostic categories: recurrent pregnancy loss (n = 302), IVF/ET failure (IVFf, n = 122), unexplained infertility (n = 97), ovarian dysfunction (n = 47), and endometriosis (n = 23). The thresholds for positivity and the prevalence of the tested factors among normal healthy populations have been established by testing 100 or more healthy male and female individuals with each one of the tests used (general population control). All tests as panel were performed on 20 normal fertile female individuals as controls (fertile female controls).RESULTS: Of all patients with reproductive failure, 75.6% had at least one abnormal test. The most frequent abnormal result was found to be the elevation of NK (CD56+) cells (37%), followed by ANA (34%), APA (24%), ATA (19%), and ETF (11%). Of the recurrent pregnancy loss patients, 74.2% had at least one positive abnormal result from all of the tests performed; overall, 70% of women with IVF failure had at least one abnormal test; of patients diagnosed with unexplained infertility, approximately 81% had at least one abnormal result; 74.4% of the patients with ovarian dysfunction and 52% of the patients with endometriosis had at least one abnormal result. From normal fertile controls, 10% showed at least one abnormal test result.CONCLUSION: APA, ANA, ATA, ETF, and elevated NK (CD56+) cells are significantly more prevalent among women experiencing reproductive failure than among the control group and normal healthy individuals.
Hepatocyte Growth Factor in Human Milk and Reproductive Tract Fluids
Authors: Srivastava Maya D. , Lippes Jack , Srivastava B. I. Sahai 
Published: September 2011

Srivastava MD, Lippes J, Sahai Srivastava BI. Hepatocyte growth factor in human milk and reproductive tract fluids. AJRI 1999; 42:347–354 © Munksgaard, CopenhagenPROBLEM: Despite evidence indicating a role for hepatocyte growth factor (HGF) in gastrointestinal and reproductive physiology, the concentration and distribution of HGF in human breast milk (BM) and reproductive tract fluids remain unknown.METHOD OF STUDY: Using enzyme‐linked immunosorbent assay (ELISA), the HGF concentrations were determined in human oviductal fluid (hOF), follicular fluid (FF), amniotic fluid (AF), seminal plasma (SP), and colostrum/milk samples, and expression of HGF mRNA by milk cells and AF cells were examined by reverse transcriptase‐polymerase chain reaction (RT‐PCR).RESULTS: HGF is present at nearly 70‐fold normal serum (0.85 ± 0.15 ng/mL) concentration in FF (n = 3; x = 57 ± 16 ng/mL) and AF (n = 17; x = 57 ± 26 ng/mL), and is also present in hOF (n = 3; x = 4.8 ± 2.3 ng/mL) and CVL (n = 8; x = 0.7 ± 1.1 ng/mL) varying throughout the menstrual cycle. HGF is found at 3‐times serum concentration in BM (n = 24; x = 2.3 ±1.3 ng/mL) with no significant difference between premature and full term or stage of lactation (colostrum, transitional, mature milk). HGF mRNA was detected in BM cells but not in AF cells.CONCLUSIONS: HGF is present in sufficient amounts to profoundly affect gastrointestinal maturation in the fetus via swallowed AF and neonate via BM, and helps to explain the increased rate of necrotizing enterocolitis (NEC) in infants of premature rupture of membrane (PROM)‐complicated pregnancies, and the decreased rate in breast fed neonates. HGF in FF may be necessary for the development and maturation of the oocyte. HGF in hOF, SP, and cervicovaginal lavage (CVL) is likely to enhances epithelial cell integrity and the mucosal barrier. Thus, HGF is widely available in the reproductive tract with functions that remain to be fully elucidated.
The Role of γ/δ T Cell Receptor Positive Cells in Pregnancy
Authors: Polgar B. , Barakonyi A. , Xynos I. , Szekeres‐Bartho J. 
Published: September 2011

PROBLEM: Due to the lack of classical HLA antigens on the trophoblast, fetal antigens are possibly presented in a non major histocompatibility complex (MHC) restricted way. Decidual γδ T cells, which significantly increase in number during pregnancy, might play a role in recognition of fetal antigens and also in determining the quality of the response to these antigens. Our study was aimed at investigating the role of this cell population in progesterone‐dependent immunomodulation.METHOD OF STUDY: Peripheral lymphocytes from healthy pregnant women and from habitual aborters were tested by immunocytochemistry for the presence of γ/δ T cell receptor (TCR) and progesterone receptor. To investigate the effect of treatment with a pan anti γ/δ antibody, lymphocytes were incubated for 3 hr with the antibody, and then interleukin (IL)‐10, IL‐12 and progesterone‐induced blocking factor (PIBF) expression (by immuno‐cytochemistry) as well as natural killer (NK) cell activity were determined.RESULTS: In peripheral blood of healthy pregnant women the percentage of γ/δ TCR + cells was significantly higher (P < 0.001) than in that of recurrent aborters or of non‐pregnant individuals. Ninety‐seven percent of γ/δ TCR + pregnancy lymphocytes expressed progesterone receptor. Binding of a specific antibody to the γ/δ TCR inhibited PIBF‐ as well as IL‐10 production, whereas it increased NK activity and IL‐12 expression.CONCLUSIONS: These data suggest the role of γ/δ TCR‐bearing lymphocytes in progesterone‐dependent immunomodulation.
Antineutrophil Cytoplasmic Antibodies and Other Immunologic Abnormalities in Patients with Habitual Abortion
Authors: Kovács László , Szabó János , Molnár Katalin , Kovács Attila , Pokorny Gyula 
Published: September 2011

PROBLEM: The immunologic mechanisms of pregnancy loss in habitual aborters with antiphospholipid and antinuclear antibodies have not been fully clarified. The possible association of antineutrophil cytoplasmic antibodies (ANCAs) with recurrent miscarriage was examined.METHOD OF STUDY: In a prospective, controlled trial of 59 women with recurrent abortion, the prevalence of pANCA (antimyeloperoxidase), cANCA (antiproteinase‐3), and immunoserologic abnormalities of systemic lupus erythematosus (SLE)—anti‐double‐stranded DNA, anti‐SSA, anti‐SSB, anti‐UIRNP, anti‐Sm, anticardiolipin and antinuclear antibodies, LE‐cell, lupus anticoagulant, and complement‐3—were investigated.RESULTS: pANCA occurred in 2, and cANCA in 6 of 59 case patients, but neither was observed in the controls (P = 0.09 for cANCA). cANCA levels were significantly higher in patients than in controls (P = 0.028). Six recurrent aborters were identified as having a group of immunoserologic abnormalities characteristic of SLE.CONCLUSIONS: Immunologic mechanisms detectable in SLE may operate in a subgroup of habitual aborters with suspected immunologic cause. ANCAs occur more frequently in patients with recurrent miscarriage than in controls.
Heparin Plus Aspirin as a “Single” Therapy for Recurrent Spontaneous Abortion Associated with both Allo‐ and Autoimmunity
Authors: Cadavid Angela , Peña Beatriz , García Gloria , Botero Jorge , Sánchez Fabio , Ossa Jorge , Beer Alan 
Published: September 2011

PROBLEM: The aim of this study was to contribute to the study of the pathogenesis and the treatment of recurrent spontaneous abortion (RSA) associated with immune alterations.METHOD OF STUDY: This is a prospective clinical trial with 11 patients with RSA associated with allo‐ and autoimmunity not receiving lymphocyte immunizations but only heparin and aspirin preconceptionally and through pregnancy. A concurrent group of 8 patients receiving a complete therapy (lymphocyte immunizations, heparin, and aspirin) but not receiving heparin and aspirin preconceptionally is also included in this report.RESULTS: The rate of pregnancy success in these patients was 90.9% (10/11), and the rate of success of the concurrent group was 75.0% (6/8).CONCLUSIONS: The results are in agreement with the working hypothesis regarding the possible final common mechanism in the pathogenesis of abortion associated with allo‐ and autoimmunity. The “single” therapy with heparin and aspirin was effective, less costly, and logistically simpler to provide than a complete therapy including lymphocyte immunizations.
Quantitative Assessment of Human Leukocyte Antigen‐G Protein in Amniotic Fluid by a Double‐Determinant Enzyme‐Linked Immunosorbent Assay Using Anti‐Human Leukocyte Antigen‐G‐Specific Antibody ‘87G’
Authors: Hamai Yoko , Fujii Tomoyuki , Miki Akinori , Geraghty Daniel E. , Harada Ikuko , Takai Yasushi , Kozuma Shiro , Tsutsumi Osamu , Taketani Yuji 
Published: September 2011

PROBLEM: The objective of this study was to establish an enzyme‐linked immunosorbent assay (ELISA) system, in an attempt to quantify the amount of human leukocyte antigen (HLA)‐G protein in amniotic fluid.METHOD OF STUDY: We established a double‐determinant ELISA system using the anti‐HLA‐G‐specific mouse monoclonal antibody ‘87G’ as a capture antibody and the horseradish‐peroxidase‐labeled rabbit anti‐human β2‐microglobulin antibody as a detection antibody. We then measured the concentration of HLA‐G protein in amniotic fluid samples from nine normal second‐trimester pregnant women and in serum samples from eight normal males.RESULTS AND CONCLUSION: HLA‐G protein was detected in amniotic fluid at a concentration of 275 ng/ml (197–343 ng/ml) (median value and 95% confident range), whereas the concentration of HLA‐G protein in male serum was below the minimum detection level.
Immunoadsorption Plasmapheresis as a Treatment for Pregnancy Complicated by Systemic Lupus Erythematosus with Positive Antiphospholipid Antibodies
Authors: Nakamura Yasushi , Yoshida Koyo , Itoh Shigeru , Kanai Yoshinori , Tsuda Hiroshi , Hashimoto Hiroshi , Mitsuhashi Naoki , Kuwabara Yoshinori 
Published: September 2011

PROBLEM: Our purpose was to study the effect of maternal immunoadsorption plasmapheresis (IA) on the outcome of pregnancies complicated by systemic lupus erythematosus (SLE) with positive antiphospholipid antibodies, which were known to have a strong correlation with abortion or stillbirth.METHOD OF STUDY: Eight pregnancies in 7 patients with SLE were treated according to our protocol. They were all positive for the lupus anticoagulant. The treatments provided in these cases were as follows: an oral low‐dose steroid; oral low‐dose aspirin; and IA. The outcomes of the pregnancies were then studied.RESULTS: Of eight pregnancies, seven resulted in preterm deliveries, and cesarean sections were performed at 26–36 weeks of gestation. In one case, intrauterine fetal death occurred at 24 weeks of gestation. The other seven pregnancies resulted in live births (survival rate of 87.5%).CONCLUSION: IA improves the outcome of pregnancy complicated by SLE with positive antiphospholipid antibodies, without increasing steroid dosage.
A Possible Role for Activated Complement Component 3 in Phagocytic Activity Exhibited by the Mouse Trophoblast
Authors: Albieri A. , Kipnis T. , Bevilacqua E. 
Published: September 2011

PROBLEM: To determine whether any blood plasma factor may play a regulatory role in trophoblast phagocytosis in rodent early pregnancy.METHOD OF STUDY: The effects of alloplasma on the phagocytosis of cultured mouse trophoblast cells (TCs) were evaluated using erythrocytes as target cells, in the presence of 10% fresh, normal plasma; 10% heat‐inactivated plasma; 10% component 3 (C3)‐depleted plasma; or medium alone. The possible activation of C3 complement, the phagocytosis of zymosan bound or unbound to C3b, and immunoreactivity to C3b receptor were also estimated. Phagocytic activity was expressed as the percentage of phagocytic TCs, and as the number of phagosomes/TCs.RESULTS: The use of complement sufficient plasma significantly enhanced the phagocytosis of the TCs while the use of heat‐inactivated plasma eliminated the erythrophagocytosis. Very low levels of phagocytic activity were seen when the plasma was C3‐complement deficient. Phagocytosis of C3b‐bound zymosan was remarkable in comparison to zymosan alone, and immunoreactivity to C3b‐receptors was seen on the TCs.CONCLUSION: These results indicate the participation of thermosensitive molecules mediating the phagocytosis of TCs and suggest, as in macrophages, a role for C3‐C3b in this process.
Mouse Granulated Metrial Gland Cell Cytotoxicity of Wehi 164 Cells: Is There a Role for Interleukin‐3 and Tumour Necrosis Factor‐α?
Authors: Stewart I.J. , Peel S. 
Published: September 2011

PROBLEM: Mouse granulated metrial gland (GMG) cells are maternal, cytotoxic cells found in the uterine wall in pregnancy. In vivo, they are cytotoxic to layer 1 labyrinthine placental cells. In an in vitro system, granulated metrial gland cells are highly cytotoxic to Wehi 164 fibrosarcoma cells. In this study the role of interleukin (IL)‐3 and tumour necrosis factor (TNF)‐α in granulated metrial gland cell cytotoxic activity was investigated.METHOD OF STUDY: Chromium‐release cytotoxicity assays using mouse metrial gland effector cells and Wehi 164 target cells with the addition of IL‐3 or an antibody to TNF‐α.RESULTS: An antibody to TNF‐α reduced the level of cytotoxic activity. IL‐3 had no effect on the level of cytotoxicity.CONCLUSION: Mouse granulated metrial gland cells kill using a TNF‐α mediated mechanism which is independent of IL‐3 stimulation.
Localization of the Th2 Cytokines IL‐3, IL‐4, IL‐10 at the Fetomaternal Interface During Human and Murine Pregnancy and Lack of Requirement for Fas/Fas Ligand Interaction for a Successful Allogeneic Pregnancy
Authors: Chaouat Gerard , Cayol Veronique , Mairovitz Valarie , Dubanchet Sylvie 
Published: September 2011

PROBLEM: Th2 cytokines and Fas/Fas ligand interactions are proposed to be part of the placental barrier that contribute to the success of allogeneic pregnancy. To fully understand the role regulation of Th2 cytokines, we must isolate and identify the cells that produce them. We also need to assess the requirement for Fas/Fas ligand interaction in facilitating a successful allogeneic pregnancy.METHOD OF STUDY: To assess the site of production of Th2 cytokines, we used immunohistochemistry sections from placental and decidual tissue obtained at various stages of gestation in mice and humans. We used mice that are genetically deficient in Fas/Fas ligand interactions and raised specific anti‐paternal CTLs by anti‐paternal immunization of the mother before mating.RESULTS: The detailed results show that in both species the bulk of Th2 production may come from non‐lymphoid tissues in the placenta and decidua, with a major role for trophoblasts. This raises questions about the mechanism(s) by which alloimmunization enhances local Th2 cytokine production. This issue is discussed.CONCLUSIONS: The success of allopregnancy in mice with circulating anti‐paternal CTLs and deficient Fas/Fas ligand interactions rules out a mandatory role for such a mechanism in ensuring the success of allogeneic pregnancy.
Modulation of Perforin Expression in the Decidual and Peripheral Blood Cytotoxic Lymphocytes in Culture
Authors: ŠTrbo N. , Laškarin G. , Sotošek V. , Randić L.J. , Podack E.R. , Rukavina D. 
Published: September 2011

PROBLEM: Perforin (P) is a cytolytic molecule located in intracellular granules of cytotoxic lymphocytes both in the peripheral blood and decidua of pregnancy. The aim was to analyze the kinetics of P expression during in vitro culture and modulation of P expression by adherent cells, their supernatants and mitogen (PHA) stimulation.METHOD OF STUDY: P (intracellular antigen) was detected by flow cytometry in the suspension of first trimester pregnancy peripheral blood lymphocytes (PBL) and decidual lymphocytes (DL).RESULTS: A decrease of the percentage of P+ cells was obtained after 1 hr incubation and was prevented by addition of 30% of decidual adherent cells (DAC) or their supernatants. Upregulation of P expression was obtained when, in addition to adherent cells, DL and PBL were stimulated by PHA. DAC present in the culture in physiological concentrations prevent downregulation of P expression.CONCLUSION: DAC located in the vicinity of decidual cytotoxic lymphocytes, owing to their unique ability to produce a wide range of substances on demand, contribute to the high level of P expression in the decidua of pregnancy.