bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrent Spontaneous Abortion: Histocompatibility Between Partners, Response to Immune Therapy, and Subsequent Reproductive Performance
Authors: VAN IDDEKINGE B. , HOFMEYR G.J. , BEZWODA W.R. , WADEE A.A. , VAN ROOY P. 
Published: May 2013

PROBLEM: Immunological factors may account for previously unexplained cases of recurrent abortion.METHOD: After screening 76 couples for causes of recurrent spontaneous abortion and measuring maternal antipaternal immunity, 23 primary spontaneous recurrent aborters were immunized once with their husbands' leukocytes. Testing for antipaternal cytotoxicity was repeated in 21 couples. Seroconversion was significantly less frequent in couples who shared more than one human leukocyte antigen [one of five (20%) versus 13 of 16 (81%), P < .02].RESULTS: Twelve of 16 women (75%) who became pregnant had live children and five of those have had a second live child. All 12 women who achieved successful pregnancies had become antipaternal cytotoxic antibody‐positive after immunization, whereas all four patients who had repeat abortions had failed to seroconvert (P < .001). However, this relationship is not necessarily causative, as the successful group also tended to have fewer previous abortions and less human lymphocyte antigen sharing.CONCLUSION: Except for transient illness after immunization, one moderately small for gestational age baby and one premature labor at 32 wk, no complications were observed after immunization.
Endometrial Expression of mRNA Encoding Epidermal Growth Factor Receptor in Normal and Leiomyomatous Uteri Throughout the Menstrual Cycle
Authors: HEINER JAMES S. , WANG L. , RUTGERS J.K.L. , WAN Y.‐J.Y. , CAI L. , WU T.‐C.J. 
Published: May 2013

PROBLEM: To investigate the relationship between the histologic phase and the quantitative expression of epidermal growth factor receptor (EGFR) mRNA in the endometrium of normal and leiomyomatous uteri.METHODS: To test this relationship, endometrium was collected at hysterectomy from 38 women with a history of regular cycles. Total RNA (20 μg) was isolated and analyzed by Northern blot using a human EGFR‐specific 32P labeled cDNA probe. The hybridization signals were quantified by densitometry, standardized, and reported in densitometry signal units. Separate portions of the same endometrial specimens were simultaneously prepared for histologic evaluation. The differences between menstrual phases were evaluated by Student's t‐test.RESULTS: EGFR mRNA was expressed in all endometrial tissues tested. Levels were higher in the midproliferative phase than in all other phases for both myomatous and nonmyomatous uteri (P <.05). Myomatous uteri showed lower expression than nonmyomatous uteri in the early and late proliferative phase (P <.05). Age did not appear to alter endometrial EGFR mRNA expression.CONCLUSION: This data suggest that endometrial EGFR mRNA expression varies in association with the histologic changes of the normal menstrual cycle, and may be associated with the presence of leiomyomata uteri.
Immunocytochemical Localization of Transforming Growth Factor‐α and Epidermal Growth Factor Receptor in Human Fallopian Tubes and Cumulus Cells
Authors: EL‐DANASOURI I. , FRANCES A. , WESTPHAL L.M. 
Published: May 2013

PROBLEM: Transforming growth factor‐a (TGF‐α) has been shown to be a potent stimulant of oocyte maturation and embryonic development. The role of maternal growth factors and their mechanism of action in early mammalian development is not well understood.METHOD: In this study, the presence of TGF‐α and epidermal growth factor receptor (EGF‐R) in human cumulus cells and fallopian tubes was investigated by immunocytochemical techniques.RESULTS: The fallopian tube showed intense staining for TGF‐α in the apical region of the epithelial cells, and the cumulus cells showed intense staining for EGF‐R on cell membranes.CONCLUSION: The presence of TGF‐α in the fallopian tube epithelium and its receptor on cumulus cells suggest a paracrine mechanism between maternal growth factors and the developing embryo.
Absence of Immunoreactive Cytokines in Supernatants of Individual Preimplantation Human Embryos
Authors: SEIFER DAVID B. , ROMERO ROBERTO , BERLINSKY DAVID , HANING RAY V. 
Published: May 2013

PROBLEM: The purpose of this study was to determine if it was possible to use commercially available enzyme‐linked immunosorbent assay (ELISA) kits to quantitate specific cytokine production from individual embryos.METHODS: We examined the supernatants of individual two to six cell preimplantation human embryos using commerically available kits for IL‐1 alpha, IL‐1 beta, IL‐6, and LIF.RESULTS: Cytokines were undetectable in all media samples analyzed.CONCLUSION: While it is possible that individual preimplantation embryos may produce cytokines, we believe these concentrations are below the detectable limits of the commercial assays used in this study.
Antisperm Antibody Binding to Human Sperm Inhibits Capacitation Induced Changes in the Levels of Plasma Membrane Sterols
Authors: BENOFF SUSAN , COOPER GEORGE W. , HURLEY IAN , MANDEL FRANCINE S. , ROSENFELD DAVID L. 
Published: May 2013

PROBLEM: Human spermatozoa express mannose ligand receptors (MLRs) over the entire head when incubated under conditions that promote loss of free cholesterol. Binding of IgA, IgG. and/or IgM head‐directed anti‐sperm antibodies (ASAs) to freshly isolated sperm blocks MLR expression in a dose dependent manner.METHODS: Comparison of Western blots of immunoprecipated glycoproteins from fresh sperm exposed to ASAs from women with those of sperm membrane proteins isolated from capacitated sperm probed with a goat anti‐human macrophage MLR antiserum showed that ASAs do not react with human sperm MLRs of 48 and 61 kd apparent molecular weight.RESULTS: The direct effect of ASA binding was to increase membrane free cholesterol content which remained greater than 0.005 μmol/109 sperm after 18 h incubations, whereas the sterol content of controls decreased to less than 0.001 μmol/109 sperm. Cholesterol addition to sperm inhibited MLR expression in a manner analogous to ASA binding, while increasing temperatures up to the crystalline/liquid‐crystalline phase transition for sperm membranes; less than 45°C failed to promote the appearance of MLRs on the surface of fresh sperm.CONCLUSIONS: We conclude that ASA effects on membrane cholesterol content prevent the membrane fluidity changes needed for MLR expression.
Differential mRNA Expression and Production of Interleukin‐6 in Placental Trophoblast and Villous Core Compartments
Authors: KAUMA S.W. , HERMAN K. , WANG Y. , WALSH S.W. 
Published: May 2013

PROBLEM: Interleukin‐6 (IL‐6) is a plieotrophic protein that functions as an immunoregulatory peptide, growth factor, and endocrine hormone. IL‐6 has been shown to be produced in whole placental tissue and isolated trophoblast (TC). In addition, the villous core (VC) compartment of the placenta contains cell types (fibroblasts, macrophages) capable of IL‐6 production. Consequently, the present study was designed to determine the relative contribution of the TC and VC compartments to placental IL‐6 production.METHOD: The VC and TC compartments from term pregnancies were separated using CR‐Dispase digestion and Percoll density gradient centrifugation. The VC, TC, and whole placental tissues were cultured in Dulbecco's modified Eagle's medium over a 28‐h period. Relative IL‐6 mRNA expression was determined by dot blot analysis and secreted IL‐6 protein was determined by enzyme‐linked immunosorbent assays.RESULTS: All three tissues demonstrated linear production of IL‐6 protein over the culture period. At 28 h, whole placental tissue produced the most IL‐6 (5.1 ng ± 0.8 ng/μg protein) followed by TC (4.0 ng ± 1.3 ng/μg) and VC (0.55 ng ± 0.24 ng/μg). Although production rates of IL‐6 were 8.4‐fold higher in TC compared to VC (P<.05), steady‐state IL‐6 mRNA expression was 3.5‐fold higher in freshly isolated VC compared to TC (P<.0001) and 13‐fold higher in VC compared to TC (P<.01) after 24 h in culture.CONCLUSIONS: These results demonstrate that: (1) the placenta can produce large quantities of immunoreactive IL‐6 in vitro, (2) TC produce significantly more IL‐6 than VC although both compartments contribute to placental IL‐6 production, (3) placental IL‐6 production and secretion are probably posttranscriptionally regulated since steady‐state IL‐6 mRNA expression in VC and TC compartments did not correlate with IL‐6 production.
Ultrastructural Localization of Insulin Receptors in Human Placenta
Authors: JONES CAROLYN J.P. , HARTMANN MICHAELE , BLASCHITZ ASTRID , DESOYE GERNOT 
Published: May 2013

PROBLEM: Investigations to date on localization of placental insulin receptors (IR) at the ultrastructural level focused on the maternal facing side of the placenta but did not allow localization of IRs to intracellular compartments.METHOD: The ultrastructural localization of IR in placentae from early and term gestation was studied using the immunogold technique and a monoclonal antibody against the external domain of the IR (clone MA20).RESULTS: At 10 wk gestation, there were high levels of IR in both cytotrophoblast and syncytiotrophoblast, with sparse microvillous labeling. Fetal vessels contained various amounts of IR while stromal cells were also labeled. By 13 wk, this pattern was unchanged; however, at term, fewer IR were present in the syncytiotrophoblast, with more label on microvilli than before. Fetal vessels were well labeled, while stromal cells appeared unchanged. Intense labeling of fetal erythrocytes provided an internal positive control, while omission of the primary antiserum produced loss of binding.CONCLUSION: The data suggest a spatiotemporal alteration in placental IR distribution during pregnancy, possibly reflecting a shift in control of placental growth and metabolism from mother to fetus.
Evidence for a Common Mechanism of Action of Interleukin‐1β, Tumor Necrosis Factor‐α, and Epidermal Growth Factor on Prostaglandin Production in Human Chorion Cells
Authors: POLLARD J.K. , THAI D. , MITCHELL M.D. 
Published: May 2013

PROBLEM: Although chorion produces prostaglandins in response to interleukin‐1β (IL‐1β), tumor necrosis factor alpha (TNFβ), and epidermal growth factor (EGF), little attention has been given to the mechanisms of action of prostaglandin biosynthesis in this tissue.METHODS: IL‐1β, TNFβ, and EGF induced a concentration‐related stimulation of prostaglandin E2 (PGE2) biosynthesis in human chorion cells, and this stimulation was enhanced by the addition of exogenous arachidonic acid.RESULTS: Protein synthesis inhibition with cycloheximide or actinomycin D resulted in complete abrogation of the stimulation of PGE2 production by IL‐1β, TNFα, and EGF. Finally, all three stimulants induced a more rapid recovery of PGE2 production in chorion cells after ace‐tylsalicylic acid pretreatment than controls.CONCLUSIONS: It is suggested that IL‐1β, TNFα, and EGF all act to stimulate human chorion PGE2 production primarily via induction of prostaglandin endoperoxide synthase activity.
Cyclosporin A Attenuates Increased Prostaglandin and Thromboxane Production in Response to Various Stimuli in Human Decidua
Authors: EDWIN S.S. , BRANCH D.W. , SCOTT J.R. , SILVER R.M. , MITCHELL M.D. 
Published: May 2013

PROBLEM: This study was undertaken to evaluate the effects of cyclosporin A on prostanoid (prostaglandin and thromboxane) production by human decidua.METHOD: Decidual cells were isolated from term placentae obtained at elective cesarean section before the onset of labor. Cells were grown to confluence and then incubated for 16 h with cyclosporin A (0.1–100 ng/ml) in the presence and absence of interleukin 1β (IL‐1β, 10 ng/ml), phorbol 12‐myristate 13‐acetate (PMA, 10−7M) and ionomycin (0.5 μm). Prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) were measured by radioimmunoassay, and cellular protein was determined.RESULTS: IL‐1β, PMA, and ionomycin all stimulated decidual PGE2 and TXB2 production as expected. However, these stimulatory actions were attenuated by 20% when cells were coincubated with cyclosporin A (100 ng/ml). All concentrations of cyclosporin A tested were within the therapeutic range.CONCLUSIONS: Our results indicate that cyclosporin A does not stimulate decidual prostanoid production and is probably unrelated to preterm labor and delivery in allograft recipients.
Evidence of Participation of the Soluble Tumor Necrosis Factor Receptor I in the Host Response to Intrauterine Infection in Preterm Labor
Authors: BAUMANN PETER , ROMERO ROBERTO , BERRY STANLEY , GOMEZ RICARDO , MCFARLIN BARBARA , ARANEDA HERIBERTO , COTTON DAVID B. , FIDEL PAUL 
Published: May 2013

PROBLEM: This study was conducted to determine whether: (1) the soluble tumor necrosis factor receptor I (sTNF‐r I) is present in human amniotic fluid, neonatal urine, and the feto‐maternal plasma; (2) there are changes in the concentration of the sTNF‐r I in amniotic fluid with gestational age; and (3) microbial invasion of the amniotic cavity (in term and preterm parturition) is associated with changes in amniotic fluid sTNF‐r I concentrations.METHOD: Amniotic fluid was retrieved by amniocentesis from 185 women classified into 11 groups according to gestational age (midtrimester, preterm gestation, and term), the presence or absence of labor, spontaneous rupture of membranes and microbial invasion of the amniotic cavity. sTNF‐r I was assayed with a sensitive and enzyme‐linked immunosorbent assay (ELISA) validated for amniotic fluid. In addition, sTNF‐r I concentrations were determined in fetal blood obtained by cordocentesis in preterm gestations (N = 24) or at the time of delivery after spontaneous labor at term (N = 10). sTNF‐r I concentrations were also measured in maternal venous and cord blood and neonatal urine (n = 13).RESULTS: sTNF‐r I was found to be present in all amniotic fluid samples, maternal blood and fetal blood and neonatal urine samples; sTNF‐r I concentrations were higher in the midtrimester than at term (mean ± SD:36.2 ± 12.2 ng/ml versus mean ± SD:5.56 ± 5.72ng/ml [P < .05]); patients with preterm labor and microbial invasion of the amniotic cavity (with intact or with ruptured membranes) had significantly higher amniotic fluid concentrations of sTNF‐r I than patients without microbial invasion; in the absence of microbial invasion, parturition (both term and preterm) was not associated with changes in amniotic fluid concentrations of sTNF‐r I; neonatal urine contained the highest concentrations of sTNF‐r I of all biological fluids assayed including maternal and neonatal/fetal blood and amniotic fluid.CONCLUSIONS: It was concluded that sTNF‐r I is a physiologic constitutent of amniotic fluid, as well as of the fetal and maternal plasma; that amniotic fluid sTNF‐r I concentrations decrease as a function of gestional age and increases in the concentration of the sTNF‐r I are part of the host response to intrauterine infection in preterm parturition.
Dysfunction of Monocytes and Dendritic Cells in Patients With Premature Ovarian Failure
Authors: HOEK ANNEMIEKE , VAN KASTEREN YVONNE , DE HAAN‐MEULMAN MEENY , SCHOEMAKER JOOP , DREXHAGE HEMMO A. 
Published: May 2013

PROBLEM: Due to the presence of ovarian antibodies it has been suggested that premature ovarian failure (POF) belongs to the autoimmune endocrinopathies. Monocytes and the monocyte‐derived dendritic cells play a prominent role in the initial stages of endocrine autoimmune reactions: the accumulation of monocytes/dendritic cells and the clustering of dendritic cells in endocrine organs is one of the first phenomena of an autoimmune endocrinopathy.METHOD: This report describes a study on (1) the chemotactic responsiveness of blood monocytes, and (2) the cluster capability of blood dendritic cells in POF patients. The monocyte chemotaxis was determined using the cell's capability to polarize (changes in shape determined by light microscopy) under the influence of the chemoattractant, N‐formyl‐methionylleucyl‐phenylalanine (fMLP). The cluster capability of dendritic cells was tested by allowing the dendritic cells to form aggregates with allogenic lymphocytes in vitro.RESULTS: The blood monocytes of 46% of a total of 28 POF patients showed a decreased fMLP induced monocyte polarization in comparison to healthy control values. None of the young female controls (N = 28) and postmenopausal women (N= 17), showed such a defective monocyte polarization. The blood dendritic cells of 36% of the POF patients showed a decreased cluster capability. Defects in monocyte polarization and dendritic cell clustering were not affected by therapies aimed at changes in the estrogen levels or gonadotropin levels of the patients [using estrogen substitution therapy, gonadotropin‐releasing hormone (GnRH) analog, follicle‐stimulating hormone (FSH)].CONCLUSIONS: A redistribution of active monocytes and of active dendritic cells from the peripheral blood to the ovaries may be the cause of the described abnormalities. Since similar abnormalities in monocyte function and dendritic cell function have been described in Graves' disease and type I diabetes, the data strengthen the view that POF is one of the endocrine autoimmune diseases.
Differences Between Human Sperm and Somatic Cell DNA in CpG Methylation Within the HLA Class I Chromosomal Region
Authors: GUILLAUDEUX THIERRY , D'ALMEIDA MARTA , GIRR MARYSE , RODRIGUEZ ANNE‐MARIE , PONTAROTTI PIERRE , FAUCHET RENEE , BOUTEILLER PHILIPPE LE 
Published: May 2013

PROBLEM: We investigated the possible negative regulatory mechanisms that repress classical human leukocyte antigen (HLA) class I gene expression in human spermatozoa and searched for novel testis‐specific coding sequences that might be present in the MHC class I chromosomal region.METHOD: We performed a comparative DNA methylation analysis of this genomic region in both purified human spermatozoa and mononuclear blood cells from the same donors, using methylation‐sensitive restriction enzymes followed by classical or pulsed field gel electrophoresis and hybridization with HLA class I locus‐specific probes.RESULTS: Unmethylated CpG sites were detected in the 3′ part of HpaII tiny fragments of the HLA‐F and HLA‐G genes in spermatozoal DNA. In contrast, no difference was observed in the methylation status of the HLA‐B, HLA‐C, and HLA‐E genes between germ and somatic cells. CpG unmethylation events were also detected in several parts of this chromosomal region (outside the known loci) in spermatozoal DNA.CONCLUSIONS: These results suggest that this genomic region undergoes changes in its DNA methylation pattern during the developmental process. We hypothesize that these dynamic changes have functional importance, including a possible transcriptional activity of nonclassical class I genes and/or as yet undescribed testis‐specific coding sequences.
Immunoneutralization of Heterodimeric FSH Using FSH Beta Subunit as the Immunogen
Authors: BUTTERSTEIN G.M. , SACHAR D. , DIAS J.A. 
Published: May 2013

PROBLEM: Immunization with beta subunit of gonadotropin may elicit antibody formation to endogenous heterodimeric gonadotropin and result in reproductive unresponsiveness. The objectives of this study were to determine if antibodies produced in rats following immunization with human follicle stimulating hormone beta‐subunit (hFSH‐β) could bind to and immunoneutralize heterodimeric FSH, and to elucidate the immunoneutralizing epitope.METHOD: Mature female Sprague‐Dawley rats received subcutaneous injections of 10 μg of hFSH‐β emulsified in complete Freund's adjuvant, while control animals received only adjuvant. Animals received 10 μg hFSH‐β booster injections emulsified in incomplete Freund's adjuvant 2,4, 11, and 21.5 wk after the initial immunization.RESULTS: Immunization with hFSH‐β produced appreciable antibody titers against human FSH (hFSH) as measured in enzyme‐linked immunosorbant assays (ELISA) of immunized rat sera. A more modest titer to rat (rFSH) and no antibody response to rat Luteinizing Hormone (rLH) was observed, thus confirming the specificity of the immune response. Titers against hFSH increased throughout the study. Rat anti‐hFSH‐β sera was tested to determine its ability to inhibit binding (immunoneutralizing) of 125I‐hFSH to the FSH receptor. Continued immunization resulted in all animals producing immunoneutralizing antibodies. Immunization of rats also resulted in disrupted estrous cycles, but only animals with subsequent titers high enough to completely block binding of FSH to its receptor failed to conceive.In order to assess the immunoneutralizing epitope, antisera were tested in a peptide ELISA. Peptides used in the ELISA corresponded to amino acids that spanned the entire hFSHB sequence. It was found that antibodies from all rats immunized with hFSHβ bound to amino acids within hFSH‐β 33–53.CONCLUSIONS: Collectively, these data suggest that amino acids within hFSH‐β 33–53 are necessary but not sufficient to confer immunocontraception. Amino acids within this linear sequence appear in a variety of epitopes of hFSH‐β and hFSH, only some of which are immunoneutralizing.
Assessment of Circulating Agglutinating Anti‐Sperm Antibodies in Buffalo Cows With Unexplained Infertility and an Attempt to Identify Buffalo Sperm Isoantigens
Authors: KANCHEV LUBOMIR , PAVLOVA SOPHIA , DANEV ATANAS 
Published: May 2013

The presence of circulating agglutinating anti‐sperm antibodies as cause for unexplained infertility of artificially inseminated buffalo cows was assessed. An attempt to identify buffalo sperm isoantigens was also made. The following methods were applied for that purpose: the tray agglutination test (TAT), SDS‐polyacrylamide gel electrophoresis, and immunoblotting. The results obtained showed that three of 90 sera from buffalo cows with unexplained infertility were positive in TAT (3.3%) and their titers were low. A total of 27 spermatozoal polypeptides reacted positively with the IgG‐isoantibodies of one of the sperm agglutinating sera in immunoblotting. Of the control sera 12 also revealed individual variations in the number of positive fractions on the blots. On the basis of comparing the blot with the positive sperm agglutinating serum to the blots of the positive controls, two buffalo sperm isoantigens were identified, with the respective molecular weights of 40 kDa and 120kDa.In conclusion, circulating agglutinating anti‐sperm antibodies are very rarely detected in buffalo cows with unexplained infertility after several artificial inseminations.