bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transport of Proteins Across the Human Placenta
Authors: Malek Antoine , Sager Ruth , Schneider Henning 
Published: September 2011

PROBLEM: The transport of various proteins across the human placenta was investigated by comparing maternal and fetal concentrations of tetanus antigen (TT‐AG), anti‐tetanus (TT)‐immunoglobulin G (IgG) (following maternal vaccination), IgA, human chorionic gonadotropin (hCG), human placental lactogen (hPL), and alpha‐fetoprotein (AFP) at term.METHOD OF STUDY: The concentrations of the six proteins were determined using enzyme‐linked immunosorbent assay in serum of maternal venous and umbilical (fetal) vein samples obtained at delivery from uncomplicated term pregnancies (n = 16).RESULTS: The ratios (mean ± standard deviation) of fetal (umbilical) to maternal level were 1.41 ± 0.33 (anti‐TT‐IgG), 0.91 ± 0.37 (TT‐AG), 0.002 ± 0.001 (IgA), 0.003 ± 0.001 (hCG), and 0.008 ± 0.004 (hPL), while the maternal:fetal concentration ratio of AFP was 0.002 ± 0.002. IgA, hCG, hPL, and AFP showed a close correlation between maternal and fetal levels varying between r2 = 0.47 to 0.73 (P < 0.004–0.0001). Because AFP is produced by the fetus while IgA originates in the mother, the appearance of small amounts of these two proteins in the maternal or fetal compartment, respectively, suggests a slow rate of diffusion following a high concentration gradient. The detection of hCG and hPL in fetal serum is also interpreted as diffusion from the maternal into the fetal blood. Anti‐TT‐IgG has a significantly higher concentration in the fetal as compared with the maternal serum, which is in line with the well‐documented active transfer of IgG. Fetal TT‐antigen levels were similar to maternal concentrations, showing a close correlation (r2 = 0.74, P < 0.0001) between the two proteins.CONCLUSIONS: The correlation between maternal and fetal concentrations of various proteins like IgA (150,000 Da), hCG (42,000 Da), and hPL (21,000 Da) suggests passive diffusion of these macromolecules across the placenta from the maternal to the fetal side, albeit at a slow rate. A similar process is postulated for AFP (70,000 Da) diffusing in the opposite direction from the fetus to the mother. There was no significant difference between the transplacental fetomaternal gradient of IgA and hCG and the maternal‐fetal gradient of AFP. In view of the substantially larger volume of circulating maternal as compared with fetal blood, a significantly higher rate of crossing of AFP as compared with the other proteins must be assumed. It is uncertain whether a difference in the rate of transplacental transfer in the two directions or an additional source of AFP production in the maternal compartment explains the high maternal level. Anti‐TT‐IgG concentration is significantly higher in fetal than in maternal serum suggesting active transfer from the mother to the fetus. Furthermore, there is considerable transfer of TT‐AG and a close correlation of fetal:maternal ratios of anti‐TT‐IgG (150,000 Da) and TT‐AG (150,000 Da) could be an indication for a specific transfer of the antigen antibody complex.
Endothelin‐1: Expression and Role in Human Corpus Luteum
Authors: Apa Rosanna , Miceli Fiorella , Feo Daniela De , Pierro Emilia , Ayala Gianfranco , Mancuso Salvatore , Napolitano Maddalena , Lanzone Antonio 
Published: September 2011

PROBLEM: Several recent data suggest an involvement of endothelin (ET)‐1, a powerful vasoconstrictor peptide, in reproductive function. This study was designed to investigate the presence and role of ET‐1 in human corpus luteum.METHOD OF STUDY: Purified luteal cells were incubated for different times with ET‐1 or ET‐3 alone or associated with human chorionic gonadotropin. In another set of experiments cells were treated with ET‐1 and BQ485, an ET‐A receptor antagonist, or with phorbol 12‐myristate‐13 acetate (PMA), an activator of protein kinase C.RESULTS: ET‐1 reduced both basal and human chorionic gonadotropin‐induced progesterone production at all examined times, similarly PMA inhibited basal progesterone synthesis. BQ485 prevented the inhibitory effect of ET‐1, while no effect was observed with ET‐3. Finally, ET‐1 mRNA was detected in the luteal cells.CONCLUSION: ET‐1 is expressed by human luteal cells and reduces basal and human chorionic gonadotropin‐induced progesterone synthesis through the ET‐A receptors and the protein kinase C pathway. Conversely, ET‐3 does not affect luteal steroidogenesis.
Incidence of Rat‐Soluble Placental Factors on IgE and IgG2a Synthesis
Authors: Gentile Teresa , Dokmetjian Jose , Garrido Delia , Margni R.A. 
Published: September 2011

PROBLEM: The in vivo effect of soluble factors present in placental culture supernatants (PCSs) on the synthesis of rat immunoglobulin E (IgE) and IgG2a isotypes was investigated.METHOD OF STUDY: Batches of Wistar SPF rats immunized with a 10‐μg dose of ovalbumin and Al(OH)3 were used: group I, consisted of virgin rats; group II, virgin females injected simultaneously with PCSs; and group III, pregnant females. As controls, nonimmunized batches were included. Serum samples were collected at days 0 (basal) and 10 after antigen challenge, determining levels of total and specific antiovalbumin of both IgE and IgG2a by enzyme‐linked immunoadsorbent assay (ELISA).RESULTS: In vivo and at least at the doses administered, PCSs exert an inhibitory effect on the synthesis of specific and total anti‐ovalbumin IgE during the course of immune response to such challenge. However, PCSs did not modify serum values of total and specific IgG2a.CONCLUSIONS: These results suggest that PCSs exert selective influence on the synthesis of diverse immunoglobulin isotypes during immune response, through the balance of cytokines synthesized by placental cells.
Human Lymphocytes Obtained from Decidual Tissue Express Killer Activatory Receptors as Well as Killer Inhibitory Receptors: Analysis Using a Single Strand Conformation Polymorphism Method
Authors: Miki Akinori , Ishikawa Yoshihide , Yabe Toshio , Furukawa Hiroshi , Fujii Tomoyuki , Tokunaga Katsushi , Akaza Tatsuya , Tadokoro Kenji , Taketani Yuji , Juji Takeo 
Published: September 2011

PROBLEM: The objective was to clarify whether lymphocytes in decidual tissue express only killer inhibitory receptors (KIRs) or both KIRs and killer activatory receptors (KARs).METHOD OF STUDY: A polymerase chain reaction (PCR)‐single strand conformation polymorphism (SSCP) analysis method, using cDNA as a template, was applied to detect as many natural killer receptors (NKRs) expressed on natural killer (NK) cells as possible and to distinguish between KIRs and KARs. Using this method, we analyzed NKRs on lymphocytes in decidual tissue and maternal peripheral blood mononuclear cells (PBMCs) (n = 10) from the same individuals.RESULTS: More than 20 SSCP bands were detected for NKRs on both the lymphocytes in decidual tissue and the maternal PBMCs. The SSCP band patterns were different for each individual. KARs mRNA was detected in lymphocytes in decidual tissue according to the SSCP analysis results.CONCLUSION: Lymphocytes in decidual tissue express not only KIRs but also KARs; this finding suggests their roles in placentation and the maintenance of pregnancy.
Early Recognition of Pregnancy by the Maternal Immune System
Authors: Kelemen K. , Szekeres‐Bartho Julia , Paldi A. , Tinneberg H. , Torok A. 
Published: September 2011

PROBLEM: Immunologic recognition of pregnancy is important for normal gestation. Successful pregnancy is characterized by a Th2 dominance, whereas there is a Th1 dominance in failed pregnancies. We assume that a signal given by the fertilized ovum induces a Th2 shift, necessary for a normal outcome. In vitro fertilization provides a tool for testing this possibility.METHOD OF STUDY: Phytohemagglutinin‐stimulated lymphocytes were incubated for 48 hr in the presence of culture media from in vitro fertilized eggs, as well as in follicular fluid (FF) and control supernatants. Total RNA was isolated from the lymphocytes by the guanidine‐isothiocyanate method and interleukin (IL)‐10 mRNA expression was detected by reverse transcription‐polymerase chain reaction.RESULTS: Ten percent of the activated lymphocytes incubated with FF expressed IL‐10 mRNA, whereas 88% of the lymphocytes activated with supernatants of sperm + oocytes gave a positive signal. Significantly (P < 0.05) fewer (50%) lymphocytes stimulated in the presence of control supernatants also expressed mRNA for IL‐10.In supernatants of activated lymphocytes incubated with the culture medium of spermia + oocytes, the concentration of IL‐10 was significantly higher than in the lymphocytes incubated with FF.CONCLUSION: These data suggest that the presence of the fertilized ovum induces a Th2 shift, which enables pregnancy to proceed to term.
Plasma Interleukin‐12 Is Elevated in Patients with Preeclampsia
Authors: Daniel Yair , Kupferminc Michael J. , Baram Amiram , Jaffa Ariel J. , Fait Gideon , Wolman Igal , Lessing Joseph B. 
Published: September 2011

PROBLEM: Abnormal immune activation has been suggested as a contributor to the development of preeclampsia. We hypothesized that intact interleukin (IL)‐12 directly, or through its main mediator, interferon (IFN)‐γ, contributes to the altered immune response observed in preeclampsia.METHOD OF STUDY: Plasma samples were collected from 20 patients with preeclampsia and 20 normotensive patients with uncomplicated pregnancies who were matched with the preeclamptic patients by age, gestational age, and parity. Samples were collected before the onset of labor, induction, or medical intervention. The samples were assayed for IL‐12 and IFN‐γ by specific enzyme‐linked immunoassays.RESULTS: IL‐12 was detected in 35% of the preeclamptic patients and in 5% of the patients with normal pregnancies (P < 0.01). The detection rate and mean concentration of IFN‐γ were comparable in both groups.CONCLUSION: Intact plasma IL‐12 is detected more frequently in preeclamptic patients, suggesting the involvement of this cytokine in the enhanced immune response observed in preeclampsia.
A Rational Basis for the Use of Combined Heparin/Aspirin and IVIG Immunotherapy in the Treatment of Recurrent IVF Failure Associated with Antiphospholipid Antibodies
Authors: Sher Geoffrey , Zouves Christo , Maassarani Ghanima , Feinman Michael , Matzner William , Chong Penny , Ching Wendell 
Published: September 2011

PROBLEMS: 1) Does the administration of heparin and aspirin (H/A) in combination with intravenous immunoglobulin G (IVIG) improve in vitro fertilization (IVF) implantation and birth rates in patients with recurrent IVF failures? 2) Is the effect of such treatment related to the antiphospholipid antibody (APA) status of the patients concerned?METHOD OF STUDY: Subjects consisted of 89 women younger than 36 years of age whose infertility was a result of causes other than male infertility and who had experienced four or more failed IVF/embryo transfer procedures. Fifty‐two women were APA+ (group A), and 37 were APA‐ (group B). All patients, regardless of their APA status, received H/A (5000 U sq bid), aspirin (81 mg po qd) from the inception of menotropin therapy along with IVIG (20 g) through a single infusion 3 to 10 days before egg retrieval.RESULTS: Twenty‐two (42%) of group A and 7 (19%) of group B patients achieved live births (P = 0.020).CONCLUSIONS: IVF outcome is significantly improved when H/A and IVIG are administered to APA+ women with repeat IVF failures. APA‐ women do not seem to benefit from such treatment.
Presence of Leukemia Inhibitory Factor and Interleukin‐12 in Human Follicular Fluid During Follicular Growth
Authors: Coskun Serdar , Uzumcu Mehmet , Jaroudi Kamal , Hollanders Johannes M.G. , Parhar Ranjit S. , Al‐Sedairy Sultan T. 
Published: September 2011

PROBLEM: Cytokines have been shown to be present in human follicular fluid and have regulatory functions on follicular maturation. The presence of leukemia inhibitory factor (LIF) and interleukin (IL)‐12 in human follicular fluid obtained at different stages of maturation was investigated.METHOD OF STUDY: Follicular fluids and granulosa cells were obtained from preovulatory and immature follicles. Follicular fluids from both groups were assayed for IL‐12 and LIF by enzyme‐linked immunosorbent assay. Granulosa cells from preovulatory and immature follicles were treated with human chorionic gonadotropin (hCG) in vitro and subsequent LIF and IL‐12 production were measured.RESULTS: The average concentration of LIF was significantly higher in preovulatory follicles (7.6 ± 1.3 pg/ml, n = 24) than in immature follicles (2.0 ± 1.3 pg/ml, n = 6). The concentration of IL‐12 was significantly higher in follicular fluid obtained from immature follicles (10.9 ± 5.0 pg/ml) than in preovulatory follicles (1.3 ± 0.4 pg/ml). hCG only stimulated LIF production from mature granulosa cells; it had no effect on IL‐12 production.CONCLUSIONS: IL‐12 and LIF are present in follicular fluid and their levels are regulated differently during follicular maturation. hCG stimulates LIF production from granulosa cells in vitro.
Interferon‐α is a Potent Inhibitor of Basic Fibroblast Growth Factor‐Stimulated Cell Proliferation in Human Uterine Cells
Authors: LEE BYUNG‐SEOK , STEWART ELIZABETH A. , SAHAKIAN MARINE , NOWAK ROMANA A. 
Published: September 2011

PROBLEM: Abnormal uterine bleeding is a significant health problem for many women and is the number‐one reason for performing hysterectomy in the United States. Leiomyomas (uterine fibroids) are benign neoplams that are a frequent cause of abnormal uterine bleeding. The goal of this study was to assess the effects of the anti‐angiogenic cytokine, interferon (INF)‐α, on the proliferation of both leiomyoma and normal uterine cells.METHOD OF STUDY: Primary cultures of leiomyoma, myometrial, and endometrial stromal cells were established for in vitro study. The effects of INF‐α (10, 100, and 1000 U/ml) were tested on serum‐stimulated and basic fibroblast growth factor‐stimulated cell proliferation using the [3H]thymidine incorporation assay.RESULTS: INF‐α was a potent inhibitor of cell proliferation for all three cell types, with endometrial stromal cells showing the greatest sensitivity. The antiproliferative effect did not appear to result from toxic effects on the cells.CONCLUSION: INFs may prove to be useful therapeutic agents for the treatment of leiomyoma‐related abnormal uterine bleeding.
H‐Y Antigen Expression Patterns in Human X‐ and Y‐Chromosome‐Bearing Spermatozoa
Authors: SILLS E. SCOTT , KIRMAN IRENA , COLOMBERO LILIANA T. , HARIPRASHAD JUNE , ROSENWAKS ZEV , PALERMO GIANPIERO D. 
Published: September 2011

PROBLEM: Restricted expression of H‐Y antigen on Y‐chromosome‐bearing sperm has been reported in some species, although such preferential expression for H‐Y antigen in human sperm has yet to be described. In this study, an immunomagnetic approach was used to characterize antigen expression patterns as a function of sex‐chromosome content.METHOD OF STUDY: Human sperm was treated with monoclonal immunoglobulin (Ig) M antibodies directed against H‐Y antigen. This preparation then was incubated with sheep antimouse IgM antibody affixed to paramagnetic beads, which then were exposed to a magnetic field and sorted. X‐ and Y‐chromosome frequencies in the two subgroups of sperm were assayed by multiprobe fluorescent in situ hybridization (FISH).RESULTS: Sperm were immunomagnetically separated into two populations: a reactive group (presumably, H‐Y Ag+); and a nonreactive group (presumably, H‐Y Ag‐). Triple‐color FISH analysis of 1,600 spermatozoa (800 in each group) showed the antigen's expression to be somewhat more prevalent among Y‐chromosome‐bearing sperm (54.1%), but a large proportion of Y‐chromosome‐bearing sperm (49.0%) did not express this antigen. The difference was not significant (P = 0.43).CONCLUSIONS: The expression of H‐Y antigen has a slightly higher frequency in human sperm containing the Y‐chromosome, but its expression among X‐chromosome‐bearing sperm also is considerable. Current immunologic techniques relying on this antigen are unlikely to effect the sex selection of human sperm.
Secretion of Interleukin‐2 from Unstimulated Peripheral Blood Mononuclear Cells Is a Possible Pathogenic Mechanism in Recurrent Abortion
Authors: HAMAI YOKO , FUJII TOMOYUKI , KOZUMA SHIRO , SHIBATA YOICHI , TAKETANI YUJI 
Published: September 2011

PROBLEM: The objective of this study was to evaluate the activated status of helper T cells in women with recurrent abortion.METHOD OF STUDY: The spontaneous secretion of interleukin (IL)‐2 from peripheral blood mononuclear cells (PBMCs) obtained from 12 women with primary partner‐specific recurrent abortion and 7 normal females and 10 normal males was measured.RESULTS: IL‐2 concentrations in medium conditioned with PBMCs from the recurrent abortion group were 1.44 ± 0.32 (mean ± standard deviation) U/ml, whereas those from the normal female and male groups were below the minimum detectable concentration.CONCLUSION: The fact that PBMCs from recurrent aborters spontaneously secrete IL‐2 suggests that helper T cells are activated in recurrent aborters.
Levels of Antibodies to Transferrin and Alpha 2‐HS Glycoprotein in Women With and Without Endometriosis
Authors: Mathur Subbi Pillai , Rust Philip F. , Holt Victoria L. , Jiang Haixiang , Lee Jong H. 
Published: September 2011

PROBLEM: To establish an enzyme‐linked immunosorbent assay (ELISA) for determining the levels of antibodies to transferrin and alpha 2‐HS glycoprotein in the serum of women with and without endometriosis.METHOD OF STUDY: Serum samples were obtained from 105 normal women, who were randomly selected for a population‐based epidemiologic study, and 123 patients with active endometriosis. An ELISA using transferrin and alpha 2‐HS glycoprotein as antigens was established.RESULTS: The levels of antibodies to transferrin and alpha 2‐HS glycoprotein in the serum of patients with endometriosis were approximately 21 times higher than those in the serum of control subjects without endometriosis. Only 2% of control subjects had false positive levels of these antibodies, and 5% of patients with endometriosis had false negative levels of these antibodies (specificity, 98.1 and 98.1, respectively, for anti‐transferrin and anti‐alpha 2‐HS glycoprotein; sensitivity, 95 and 96.7, respectively, for anti‐transferrin and anti‐alpha 2‐HS glycoprotein).CONCLUSIONS: Patients with endometriosis have significantly higher levels of antibodies to transferrin and alpha 2‐HS glycoprotein than control subjects. Testing women for antibodies to transferrin and alpha 2‐HS glycoprotein will provide a specific noninvasive diagnosis of endometriosis.
Fertility‐Disrupting Potential of Synthetic Peptides Derived from the β‐Subunit of Follicle‐Stimulating Hormone
Authors: FERRO VALERIE A. , STIMSON WILLIAM H. 
Published: September 2011

PROBLEM: Hormone immunoneutralization is hampered by immunologic cross‐reactivity caused by close‐sequence homology between related molecules. One solution is to use smaller fragments to induce antibodies of greater specificity.METHOD OF STUDY: A number of peptides selected from β‐follicle‐stimulating hormone (FSH) were conjugated to tetanus toxoid and were used to immunize female rats. The antis‐era were examined for FSH cross‐reactivity by immunoassays and in an in vitro bioassay.RESULTS: In the immunoassays, the antisera did not react with FSH but did react with their respective peptides. In the bioassay, sera from VYKDPARPC‐ and CDSLYTYP‐immunized animals inhibited FSH‐receptor interaction by 73% and 68%, respectively. These animals also showed reduced estradiol levels. Sequences were synthesized around VYKDPARPC and were tested on a FSH‐receptor‐bearing Chinese hamster ovary cell line. LVYKDPARPC, VYKDPARPC, YKDPARPIC, CLVYKDPARP, and LVYKDPARP inhibited FSH‐receptor interaction by greater than 50%. In female mice, TRDLVYKDPARPKI and LVYKDPARP disrupted estrous cycling in all animals; LVYKDPARPC and CLVYKDPARP disrupted cycling in three of five animals, whereas VYKDPARPC disrupted cycling in one of four animals.CONCLUSIONS: Peptides from two areas of β‐FSH (VYKDPARP and DSLYTYP) were shown to raise FSH‐neutralizing antibodies, which were able to suppress estradiol levels. An additional leucine residue to VYKDPARP greatly enhanced the peptide's ability to inhibit FSH‐receptor binding and caused fertility disruption in vivo.
Evaluation of the Contraceptive Potential of Recombinant Human ZP3 and Human ZP3 Peptides in a Primate Model: Their Safety and Efficacy
Authors: PATERSON MARGARET , WILSON MARTIN R. , MORRIS KEITH D. , VAN DUIN MARCEL , AITKEN R. JOHN 
Published: September 2011

PROBLEM: The unique recognition events that result in the avid binding of mammalian spermatozoa to the surface of the zona pellucida (ZP) are being exploited in the development of contraceptive vaccines. In this study, the safety and efficacy of a vaccination strategy based on the induction of active immunity against purified, glycosylated, recombinant human ZP3 (rhZP3) has been evaluated in a primate model, Callithrix jacchus.METHOD OF STUDY: Long‐term infertility was established after immunization with rhZP3 and the resulting immune sera reacted with rhZP3 on an enzyme‐linked immunosorbent assay (ELISA) and immunolocalized exclusively to the outer surface of native ZP on marmoset ovarian sections. However, this contraceptive effect was inevitably associated with the eventual appearance of an ovarian pathology characterized by a depletion of primordial follicles. In an attempt to circumvent this side effect, human ZP3 (hZP3) was epitope mapped and four continuous, immunodominant B‐cell epitopes (hZP345–64, hZP393–110, hZP3172–190 and hZP3341–360) were evaluated for contraceptive efficacy in vivo. Using peptide‐tetanus toxoid (TT) conjugates to enhance immunogenicity, antipeptide antibodies were raised against these immunogens, which also cross‐reacted with rhZP3 on ELISA. In addition, antibodies against hZP345–64 and hZP3172–190 recognized native ZP on marmoset ovarian sections when a microwave technique was used to enhance epitope presentation.RESULTS: No ovarian pathology was observed after the long‐term administration of these peptide immunogens, and fertility was suppressed when compared with TT controls but could not be correlated to the antibody titer.CONCLUSION: Clearly, further research is required to identify optimal B‐cell epitopes that will reliably induce infertility, free from any ovarian pathology.
Increased Mast Cell Density in Peritoneal Endometriosis Compared with Eutopic Endometrium with Endometriosis
Authors: MATSUZAKI SACHIKO , CANIS MICHEL , DARCHA CLAUDE , FUKAYA TAKAO , YAJIMA AKIRA , BRUHAT MAURICE A. 
Published: September 2011

PROBLEM: Factors regulating fibrosis in peritoneal endometriosis are poorly understood. We hypothesized that mast cell proteases may play a role in the process of fibrosis in peritoneal endometriosis. As the first step in examining the possible contribution of mast cells to fibrosis, we investigated their distribution in peritoneal endometriosis lesions according to their macroscopic appearance.METHOD OF STUDY: Mast cells were identified by immunohistochemistry using monoclonal antibody against mast cell tryptase on formalin‐fixed, paraffin‐embedded sections. Mast cell density (mean mast cell count per 0.13 mm2 of stroma) was measured using a computerized image analysis system.RESULTS: Mast cell density was significantly increased in black peritoneal lesions compared with red peritoneal lesions in endometriosis.CONCLUSIONS: Mast cells may be involved in the pathogenesis of peritoneal endometriosis.