bluuebunny/crossref_metadata_2025_split huggingface dataset:
Granulocyte Macrophage‐Colony Stimulating Factor Production by Autologous Endometrial Co‐Culture Is Associated with Outcome for In Vitro Fertilization Patients with a History of Multiple Implantation Failures
Authors: Spandorfer S.D. , Barmat L.I. , Liu H.‐C. , Mele C. , Veeck L. , Rosenwaks Z. 
Published: September 2011

PROBLEM: To determine whether granulocyte macrophage (GM)‐colony stimulating factor (CSF) produced by autologous endometrial co‐culture was associated with outcome in 53 patients with a history of multiple in vitro fertilization failures.METHOD OF STUDY: The conditioned media from endometrial co‐culture cells exposed or non‐exposed to human embryos was analyzed for GM‐CSF.RESULTS: Exposure or non‐exposure to an embryo did not result in an enhancement of GM‐CSF production. Insignificant levels of GM‐CSF were determined from media alone. ROC analysis revealed that levels of GM‐CSF from supernatants of endometrial co‐culture exposed to embryos that measured below 130 pg/ml reflected a diminished prognosis (5/17 had a positive pregnancy vs. 21/36 with GM‐CSF levels greater than 130 pg/ml; P < 0.05).CONCLUSIONS: The improved outcome associated with GM‐CSF values greater than 130 pg/ml may reflect: 1) a direct positive effect of GM‐CSF; 2) an embryotrophic factor upregulated by GM‐CSF; or, 3) that GM‐CSF functions as a marker for the importance of the glandular component in endometrial co‐culture systems.
Review: Analogies Between Trophoblastic and Malignant Cells
Authors: Mullen Catherine A. 
Published: September 2011

PROBLEM: The question of how trophoblastic and malignant cells evade immunologic recognition and rejection by their host was studied. METHOD OF STUDY: A literature review was conducted.RESULTS: Trophoblastic and malignant cells share a number of similarities. These include a lack of major histocompatibility complex antigen expression, resistance to lysis by natural killer cells, T‐helper cell‐2 (TH2)‐biased response, prostaglandin E production, and response to transforming growth factor beta. In addition, the analogies between trophoblastic and malignant cells extend into immunotherapy in which anti‐idiotype therapy has a viable role in the prevention of pregnancy loss and the treatment of cancer. CONCLUSIONS: Trophoblastic and malignant cells use a number of similar mechanisms to resist rejection by their host. By using similar strategies these cells are able to successfully co‐exist in an immunologically hostile environment.
The Role of Placental Trophoblast in the Pathophysiology of the Antiphospholipid Antibody Syndrome
Authors: Rote Neal S. , Vogt Elizabeth , Devere Gabrielle , Obringer Amy R. , Ng Ah‐Kau 
Published: September 2011

PROBLEM: The antiphospholipid (aPL) antibody syndrome is characterized by severe pregnancy complications, the cause of which remains unknown. We hypothesized that the placental trophoblast is a target for aPLs.METHOD OF STUDY: The effects of monoclonal aPLs on trophoblast function, including the invasion of JAR into matrigel‐coated filters and the effects of annexin V expression on BeWo, were investigated using choriocarcinoma models.RESULTS: aPLs against phosphatidylserine (PS) significantly (P < 0.001) decreased the migration of JAR across the membrane. In the annexin V studies, undifferentiated BeWo did not express surface annexin V. After differentiation, BeWo expressed surface annexin V, which was removed in the presence of aPLs, resulting in increased binding of prothrombin.CONCLUSIONS: PS is expressed on the trophoblast surface during differentiation and invasion of extracellular matrix. Our data suggest that aPLs against PS can directly affect trophoblast function by limiting the depth of decidual invasion and by concurrently creating a procoagulant surface on trophoblast exposed to the maternal circulation.
The Peritoneal Fluid Levels of Interleukin‐12 in Women with Endometriosis
Authors: Zeyneloglu Hulusi B. , Senturk Levent M. , Seli Emre , Bahtiyar Ozan M. , Olive David L. , Arici Aydin 
Published: September 2011

PROBLEM: Interleukin‐12 (IL‐12) is produced mainly by monocytes/macrophages, and it induces proliferation and cytotoxicity of T‐cells and natural killer cells. In women with endometriosis, natural killer cell activity in the peritoneal fluid is significantly decreased. We aimed to measure the peritoneal fluid level of IL‐12 in endometriosis.METHOD OF STUDY: We measured IL‐12 levels in peritoneal fluid samples from women with or without endometriosis and in supernatants from endometrial stromal, ovarian stromal, and mesothelial cell cultures, using a high‐sensitivity enzyme‐linked immunosorbent assay.RESULTS: The median concentration of IL‐12 in the peritoneal fluid of women with endometriosis was 1.1 pg/ml (range, 0.2–5.5) and was 1.6 pg/ml (range, 0.4‐2.8) in women without endometriosis, not a statistically significant difference. IL‐12 was not detected in the supernatants of endometrial stromal, ovarian stromal, and mesothelial cell cultures. CONCLUSION: Concentrations of IL‐12 in the peritoneal fluid of women with or without endometriosis are low, but they are detectable and are not affected significantly by the presence of endometriosis.
Multivariant Analysis of Men from Infertile Couples With and Without Antisperm Antibodies
Authors: Gubin David A. , Dmochowski Roger , Kutteh William H. 
Published: September 2011

PROBLEM: Research studies in animal and human systems have demonstrated conclusively that antisperm antibodies can interfere with fertilization. In the male, autoantibodies to sperm can be detected both in the sera and seminal plasma.METHOD OF STUDY: Ninety‐seven men who were tested for antisperm antibodies as a part of an infertility evaluation were identified. Complete medical history was obtained, including information related to events suspected of being associated with antisperm antibodies. History of surgery (varicocele repair, hernia repair, and vas reversal) and infection (epididymitis, sexually transmitted disease, and orchitis) were compared with semen parameters (motility less than 60%, concentration less than 20 times 106, and volume less than 2 cc). These were compared to antisperm antibody results of mixed agglutination reaction (MAR) and direct immunobead binding test (IBT) for immunoglobulin G (IgG). Statistical analysis was performed using Fishers exact two‐tailed test.RESULTS: As expected, prior vas reversal was significantly associated with the presence of antisperm antibodies (P = 0.0002) by MAR or IBT with a fivefold increased relative risk (95% confidence interval, 1.97‐12.38). Other surgeries manipulating the cord structures independent of vas reversal were not associated with antisperm antibodies (P = 0.09). Prior infections, independent of vas reversal, were significantly associated with antisperm antibodies by MAR (P = 0.04) with a 3.8‐fold increased relative risk (95% confidence interval, 1.06–13.87) but not by IBT. Sperm concentration less than 20 times 106, motility less than 60%, and a volume less than 2 cc were not associated with antisperm antibodies by MAR or IBT. CONCLUSION: These findings suggest that manipulation of the cord structures excluding the vas were not associated with antisperm antibodies; however, vas reversal and prior infection are significant risk factors for the development of antisperm antibodies.
Complement Regulatory Proteins on the Sperm Surface: Relevance to Sperm Motility
Authors: Jiang Haixiang , Pillai Subbi 
Published: September 2011

PROBLEM: To determine whether complement regulatory proteins are present on human spermatozoa and whether antibodies to these proteins adversely affect sperm motility.METHOD OF STUDY: Human sperm membrane proteins were solubilized and subjected to Polyacrylamide gel electrophoresis followed by Western blot analysis against antibodies to complement component 1 inhibitor (C1‐INH), decay‐activating factor (DAF; CD55), membrane cofactor protein (MCP; CD46), and homologous restriction factor (HRF; CD59). Spermatozoa, obtained by a swim‐up technique, were incubated in medium (control 1) and medium supplemented with antibodies to human albumin (control 2) and antibodies to these complement regulatory proteins. We used a computerized sperm motion analysis to determine the effect of these antibodies on sperm motion characteristics.RESULTS: Complement regulatory proteins such as C1‐INH, CD55, CD46, and CD59 were found in the sperm extracts as shown by Western blot analysis. The heat‐treated (56°C, 30 min) IgG fraction of antibodies to these proteins significantly reduced sperm motility in general and other motion parameters. Addition of complement did not affect these results except in the antibodies to CD46 in which the reducing action was further amplified.CONCLUSIONS: Our data suggest that C1‐INH, CD55, CD46, and CD59 are present on the sperm surface. These proteins may have biological functions, such as affecting sperm motility, besides the complement regulatory functions. In infertile men and women with antibodies that recognize one or more of these complement regulatory proteins, there may be problems related to poor sperm motility and survival in the reproductive tracts.
Identification of a Unique Form of p53 in Human Cord Blood Associated with the Development of Maternal Autoantibodies
Authors: Yashar Catheryn M. , Gercel‐Taylor Cicek , Gibb Randall K. , Weeks Jonathan W. , Taylor Douglas D. 
Published: September 2011

PROBLEM: The possible link between p53‐reactive antibodies in multiparous women and exposure to a unique p53 protein during pregnancy was examined.METHOD OF STUDY: p53‐reactive antibodies were evaluated in sera from nulligravid and multiparous women and patients with ovarian cancer by Western immunoblot. Furthermore, the presence of p53 protein was assayed in cord blood by enzyme‐linked immunosorbent assay. Cord blood‐derived p53 was compared structurally by protein fingerprinting and functionally by gel mobility shift assay to other isolates of p53.RESULTS: Antibodies reactive with wild‐type p53 were observed in 92% of multiparous women and 42% were reactive with one tumor‐derived p53 protein. p53 protein was detected in 27 of 154 samples of cord blood. Structural analysis indicated that the fetal p53 resembled the UL‐1 p53. Functionally, the fetal and UL‐1 proteins failed to bind DNA.CONCLUSIONS: Fetal p53 protein seems to be distinct from wild‐type p53, characterized by enhanced stability, structural differences and inability to bind DNA, analogous to alternatively spliced variants. Exposure to fetal p53 protein may form the basis for immunologic protection against cancer induced by multiparity.
Gonadotropins Induce the Release of Interleukin‐1β, Interleukin‐6 and Tumor Necrosis Factor‐α from the Human Preovulatory Follicle
Authors: de Mola J. Ricardo Loret , Goldfarb James M. , Hecht Bryan R. , Babbo C. Jan , Baumgardner Gavin P. , Friedlander Miriam A. 
Published: September 2011

PROBLEM; The effects of exogenous gonadotropin administration and steroid levels on the release of various cytokines into the human follicular fluid (FF) were studied.METHOD OF STUDY: Forty patients were included in two groups, those undergoing controlled ovarian hyperstimulation (COH) (n = 33) and natural cycles (n = 7). FF transvaginal aspirations were performed 36 hr after administration of human chorionic gonadotropin or a spontaneous surge of luteinizing hormone, respectively. FF cytokine measurements were performed with sensitive immunoassays.RESULTS: FF cytokine levels were higher after COH [interleukin (IL)‐1β, 6.6 ± 0.32 pg/ml; IL‐6, 18.7 ± 2.1 pg/ml; and tumor necrosis factor (TNF)‐α, 32.5 ± 4.9 pg/ml] than in natural unstimulated cycles (0.52 ± 0.1 pg/ml, P < 0.001; 8.9 ± 1.2 pg/ml, P < 0.01; and 13.2 ± 2.6 pg/ml, P < 0.001, respectively). FF estradiol (E2) and progesterone levels were not statistically different between groups, despite the higher serum E2 levels observed in patients after COH.CONCLUSIONS: Gonadotropins might regulate ovarian secretion of cytokines, because FF IL‐1β, IL‐6, and TNF‐α levels after COH were higher than during natural cycles.
Immunodetection of Cell Adhesion Molecules in Rat Sertoli Cell Cultures
Authors: Lustig Livia , Casanova Marta B. , Vianello Sergio E. , Denduchis Berta , Meroni Silvina , Cigorraga Selva 
Published: September 2011

PROBLEM: The presence of cell adhesion molecules (CAMs) in Sertoli cells has not been explored extensively. The expression of CAMs involved in cell‐matrix and cell‐to‐cell interactions in Sertoli cell cultures was examined.METHOD OF STUDY: Immunohistochemical and Western blot techniques were applied to rat Sertoli cell cultures using specific antibodies to α3, α5, and α6 integrin subunits; NCAM; and Cadherins.RESULTS: Expression of α3 and α6 integrin subunits (mainly laminin receptors) and lack of expression of α5 integrin subunit (fibronectin receptor) was observed in Sertoli cells by immunohistochemistry. These cells also expressed neural CAM (NCAM) and N‐cadherin. By Western blot analysis, Sertoli cell extracts reacted with antibodies to α3 integrin subunit revealed a band approximately 130 kDa, whereas no expression of α5 integrin subunit was detected. Cell extracts incubated with antibodies to pan Cadherin exhibited a band approximately 120 kDa, whereas bands of 180, 140, and 120 kDa were observed with antibodies to NCAM.CONCLUSION: New data about the expression of receptors for extracellular matrix proteins (α3 and α6 integrin subunits) as well as cell‐to‐cell adhesion molecules (NCAM and Cadherins) are reported in rat Sertoli cell cultures.
Cell‐Mediated Immunity to Human and Escherichia coli 60‐kDa Heat Shock Protein in Women: Association with A History of Spontaneous Abortion and Endometriosis
Authors: KLIGMAN ISAAC , JEREMIAS JAN , ROSENWAKS ZEV , WITKIN STEVEN S. 
Published: September 2011

PROBLEM: Heat shock proteins are expressed during early pregnancy and in peritoneal fluids from women with endometriosis. The relationship between a cell‐mediated immune response to human 60‐kDa heat shock protein (hsp60), spontaneous abortion, and endometriosis was examined.METHOD OF STUDY: Peripheral blood mononuclear cells (PBMCs) from 110 female partners of infertile couples undergoing in vitro fertilization and 41 fertile control subjects were incubated with human hsp60 or Escherichia coli hsp60. PBMC proliferation was measured by [3H]thymidine incorporation, and a stimulation index was calculated.RESULTS: Lymphocytes from 21.8% of the infertile women, as opposed to 7.3% of the fertile women, proliferated in response to human hsp60 (P = 0.05). In contrast, proliferation in response to the E. coli hsp60 was equivalent in both groups. Within the infertile group, the response to human hsp60 was 40.7% among women with a history of spontaneous abortion and only 12% in those with no history of spontaneous abortion (P = 0.003). There was no association between immunity to E. coli hsp60 and spontaneous abortion or between immunity to human hsp60 and therapeutic abortion or the cause of infertility. Immunity to the E. coli hsp60 was associated with endometriosis.CONCLUSIONS: A cell‐mediated autoimmune response to human hsp60 is associated with a history of spontaneous abortion, whereas immunity to E. coli hsp60 was most prevalent in women with endometriosis.
Inhibin‐ A and Pro‐αC Are Elevated in Preeclamptic Pregnancy and Correlate with Human Chorionic Gonadotropin
Authors: FRASER ROBERT F. , MCASEY MARY E. , CONEY PONJOLA 
Published: September 2011

PROBLEM: Serum concentrations of the heterodimeric glycoprotein inhibin‐A (α‐βA) and its α‐subunit increase during pregnancy. The placenta is the predominant source of inhibin during pregnancy, and a paracrine role in the trophoblast has been suggested. Elevated serum concentrations of inhibin α‐subunit as well as the glycoprotein human chorionic gonadotropin (hCG) have been described in preeclamptic pregnancy. The objectives of this investigation were to compare serum concentrations of inhibin‐A and inhibin pro‐αC in preeclamptic and normotensive pregnancy, and to examine the relationship of hCG and inhibin‐A in those pregnancies.METHOD OF STUDY: A case‐control design using 32 patients with preeclampsia with a single fetus at 32–40 weeks of gestation and 34 gestation age‐matched normotensive control subjects was used for this investigation. Solid‐phase enzyme‐linked immunosorbent assays were used to measure inhibin‐A and inhibin pro‐αC in sera. An immunoradiometric assay was used to measure intact hCG.RESULTS: Inhibin‐A and inhibin pro‐αC concentrations were significantly elevated in the sera of women with preeclampsia compared with those concentrations in normotensive control subjects (P < 0.05). A relationship of inhibin‐A or pro‐αC with severity of preeclampsia was not observed. There was a significant positive correlation of serum hCG with both inhibin‐A and pro‐αC (P < 0.05).CONCLUSIONS: Levels of inhibin‐A and the subunit pro‐αC are increased in pregnancies complicated by preeclampsia. These findings are potentially the effect of a paracrine role of inhibin‐A in the development and proliferation of the trophoblast.
Differential Gene Expression of TGF‐β Isoforms and TGF‐β Receptors During the First Trimester of Pregnancy at the Human Maternal‐Fetal Interface
Authors: ANDO NORIKO , HIRAHARA FUMIKI , FUKUSHIMA JUN , KAWAMOTO SUSUMU , OKUDA KENJI , FUNABASHI TOSHIYA , GORAI ITSUO , MINAGUCHI HIROSHI 
Published: September 2011

PROBLEM: The transforming growth factor (TGF)‐βs are multifunctional cytokines, and they play a role in the controlled growth of trophoblasts. Moreover they are thought to be important in maternal‐fetal interaction during early gestation.METHOD OF STUDY: Human decidual and villous tissues in the first trimester were Northern blotted and amplified by reverse transcription‐polymerase chain reaction to measure the expression of TGF‐β1, ‐β2, and ‐β3 and their receptors, types I and II, at the first trimester of pregnancy. In addition, their cell‐specific expression at the maternal‐fetal interface was determined by in situ hybridization.RESULTS: Each isoform of TGF‐β was expressed in both decidual and villous tissues. Because most TGF‐β1 gene expression was found in villous tissues, TGF‐β2 mRNA was expressed preferentially in the decidual tissues. TGF‐β3 transcripts were expressed in the nonpregnant endometrium.CONCLUSIONS: The results suggest that each isoform of TGF‐β plays some specific role in decidualization and placentation. Furthermore, it is predicted that they regulate the maternal‐fetal interaction at early gestation.
Maternal Blood B‐Cell (CD19+) Percentages and Serum Immunoglobulin Concentrations Correlate with Breast‐feeding Behavior and Serum Prolactin Concentration
Authors: ZIMMER J. PAUL , GARZA CUTBERTO , BUTTE NANCY F. , GOLDMAN ARMOND S. 
Published: September 2011

PROBLEM: Lactating women recover from pregnancy‐induced immunosuppression while actively secreting immunologically active agents into milk. Few clinical studies have examined changes in postpartum maternal immune status or explored mechanisms.METHOD OF STUDY: We measured blood B‐cell (CD19+) percentages and serum concentrations of immunoglobulin (Ig) G, IgM, and IgA at 1 to 2 weeks, 1 month, and 2 months postpartum in a longitudinal study of seven healthy, lactating women.RESULTS: More frequent or extended breast‐feeding sessions were correlated with lower CD 19+ percentages, reduced serum IgG, and higher serum IgA and IgM concentrations. CD19+ percentages were correlated negatively with serum prolactin concentrations. Blood samples drawn before and 30 min after breast‐feeding did not differ in CD 19+ percentages or serum Ig concentrations.CONCLUSIONS: These findings confirm our previous cross‐sectional study showing a negative correlation between CD 19+ percentages and serum prolactin. Because lactation practices are modifiable, these findings suggest that women can influence the course of lactation‐associated immunologic changes.
The Selective Use of Heparin/Aspirin Therapy, Alone or in Combination with Intravenous Immunoglobulin G, in the Management of Antiphospholipid Antibody‐Positive Women Undergoing In Vitro Fertilization
Authors: Sher Geoffrey , Matzner William , Feinman Michael , Maassarani Ghanima , Zouves Christo , Chong Penny , Ching Wendell 
Published: September 2011

PROBLEM: The effect of mini‐dose heparin/aspirin (H/A) alone vs. combined intravenous immunoglobulin G (IVIg) and H/A on in vitro fertilization (IVF) birthrates in women who test seropositive for antiphospholipid antibodies (APA+) was evaluated, as was the question of whether outcome is influenced by the gammaglobulin isotype(s) or the phospholipid (PL) epitope(s) to which the APAs are directed.METHOD OF STUDY: A case‐control study was conducted in three phases, spanning a 4‐year period, in a multicenter clinical research environment. Six hundred eighty‐seven APA+ women, who were younger than 40 years and who each, completed up to three consecutive IVF/embryo transfer cycles within a 12‐month period, were given either H/A alone or H/A in combination with IVIg. Birthrates relative to the type of immunotherapy (i.e., H/A alone and H/A with IVIg) and APA profile were the main outcome measurements.RESULTS: In phase I, 687 women who tested APA+ to one or more PL epitopes underwent two or fewer IVF attempts for a total of 1050 IVF cycles. Four hundred seventy‐seven (46%) births occurred in 923 IVF cycles in which H/A alone was administered. Twenty‐two (17%) births occurred after 127 IVF cycles in which H/A was not administered. In phase II, 322 of 687 women tested positive for a single APA subtype. These subjects underwent up to two consecutive IVF attempts for a total of 521 IVF cycles while receiving H/A alone. The birthrate was significantly lower for women whose APAs were directed toward phosphatidylethanolamine (PE) or phosphatidylserine (PS) involving IgG or IgM isotypes than for women who had any other APA (17% vs. 43%). In phase III, 121 women who did not achieve live births after two consecutive IVF attempts in which H/A alone was administered received IVIg in combination with H/A during their third consecutive IVF cycle. The birth rate was 41% after these IVF cycles when anti‐PS or anti‐PE involving IgG or IgM isotypes were present, as compared with 17% when H/A alone was administered. The IVF outcome did not improve when IVIg was administered in association with any other single APA.CONCLUSIONS: The treatment of APA+ women with H/A alone improves IVF birthrates. This benefit is selective in that it does not apply in cases in which IgG‐ or IgM‐related APAs are directed against PE or PS. In such cases, the addition of IVIg significantly improves the outcome.
HLA‐G Polymorphisms: Ethnic Differences and Implications for Potential Molecule Function
Authors: VAN DER VEN K. , SKRABLIN S. , OBER C. , KREBS D. 
Published: September 2011

PROBLEM: Human leukocyte antigen (HLA)‐G is uniquely expressed on extravillous cytotrophoblasts of the placenta and is postulated to be a mediator of maternal immune tolerance. Although it was originally considered to be nonpolymorphic, variations of the HLA‐G DNA sequence have been reported, and a limited number of HLA‐G alleles been defined.METHOD OF STUDY: The HLA‐G wild‐type sequence was compared with HLA‐A2 with regard to the conservation of functionally essential parts of classical HLA‐I molecules. HLA‐G polymorphisms were analyzed under the aspect of ethnic differences, site, and consequences for postulated molecule functions.RESULTS: HLA‐G exhibits a high degree of conservation relative to HLA‐A2 in functionally relevant sites of HLA‐class I molecules. However, polymorpahic sites in HLA‐G and classical HLA loci are not congruent.CONCLUSION: The type and localization of HLA‐G polymorphisms suggest that different parts of the HLA‐G molecule underlie different selective constraints.