bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anthropological Considerations Relevant to the Maturation of the Immune Response in Humans
Authors: GILL THOMAS J. 
Published: May 2013

PROBLEM: The reason for the postnatal maturation of the immune response in humans was explored from the anthropological standpoint in order to gain some insight into how development in modern humans evolved and how it might have affected the immune system.METHOD: The estimation of the length of gestation in modern humans if it had followed the same developmental pattern as in the other hominids and the higher primates was calculated by extrapolation from the lengths of gestation and the physical characteristics of these other primates compared to those of modern humans.RESULTS: These calculations show that the gestation time of modern humans would be 3–18 months longer than the 9 months that it is if modern humans had followed a linear evolutionary development comparable to that of the other primates. The key difference between modern humans and the other primates is the rapid and extensive development of the brain that occurs in utero and in the first 12–18 months postnatally in modern humans.CONCLUSION: The first 12–18 months postnatally in humans follows the embryonic/fetal pattern of development, whereas that of other primates does not. The maturation of the immune response in humans occurs during both the intrauterine and extrauterine phases of the embryonic/fetal pattern of development.
Prevention of Human Recombinant Intei leukin‐1β (rhIL‐1β) Embryolethality with Progesterone or Indomethacin
Authors: MARKS THOMAS A. , TRACY DANIEL E. 
Published: May 2013

PROBLEM: Bropirimine and tilorone were found in earlier studies to be embryolethal when administered to Crl:TUC(SD)spf (TUC) rats on gestation day 10. Progesterone or indomethacin could, at least partially, prevent this effect. The immunomodulators appeared to mimic the luteolytic effects of PGF2α, resulting in a shutdown in progesterone release by the corpora lutea, followed by a disruption in maternal support to the pregnant uterus and embryolethality. Since bropirimine has been shown to induce interleukin‐1, and since this cytokine has been found to increase PGF2α levels in human decidual cells, the decision was made to investigate whether human interleukin‐1β might act in an analogous manner to bropirimine and tilorone.METHOD: Bropirimine (400 mg/kg, p.o.) or rhIL‐1β (20, 30, or 40 μg/kg, s.c.) was administered on gestation day 10 to Crl:CD[BR] (CD) or TUC rats, alone and in combination with progesterone (2 mg/kg/day, s.c.) or indomethacin (0.6 mg/day, s.c, days 9–11). On gestation day 14 the dams were killed and their uterine contents examined.RESULTS: rhIL‐1β (30–40 μg/kg) was embryolethal when administered to CD or TUC rats on gestation day 10. Progesterone or indomethacin coadministration prevented, at least partially, the embryolethality seen when rhIL‐1β was administered (30 μg/kg) to TUC rats.CONCLUSION: Evidence was obtained in support of the hypothesis that interleukin‐1 is involved in the embryolethal actions of the immunomodulators bropirimine and tilorone.
Immunohistochemical Studies of the Adult Human Ovary: Possible Contribution of Immune and Epithelial Factors to Folliculogenesis
Authors: BuKOVSKý ANTONÍN , KEENAN JEFFREY A. , CAUDLE MICHAEL R. , WIMALASENA JAY , UPADHYAYA NIRMALA B. , VAN METER STUART E. 
Published: May 2013

PROBLEM: Formation of primordial follicles in adult ovaries could be a cryptic process limited to relatively small areas of the ovarian cortex and occurring during a certain stage of the menstrual cycle. Such an event may require a specific milieu provided by factors involved in developmental processes, i.e., morphoregulatory molecules and macrophages.METHOD: Adult human ovaries were investigated by immunohistochemistry for surface epithelium and granulosa cell markers (cytokeratin 18 and MHC class I), immune system‐related morphoregulatory molecules (Thy‐1 glycoprotein and N‐CAM), and macrophage phenotypes (CD14, CD68, and MHC class II).RESULTS: In some ovaries 300–500 μm areas of surface epithelium were overgrown by tunica albuginea, descended into the stroma, and apparently fragmented into individual small (20–40 μm) follicle‐like cell nests. Differentiation of the surface epithelium was accompanied by macrophages and Thy‐1 glycoprotein. Small segments of surface epithelium showed N‐CAM and a lacked MHC class I expression. In such segments, clear spherical germ‐like cells migrated into the deeper stroma, associated with the microvasculature, and eventually aggregated with follicle‐like cell nests.CONCLUSIONS: Our data suggest that surface epithelium may be involved in the formation of some primordial follicles in adult ovaries. This process, and further follicular fate, may require a precise interplay of immune system related morphoregulatory molecules and macrophages.
Detection of Antibodies Toward Epididymal Sperm Antigens—An Obligatory Step in Evaluation of Human Immunologic Infertility?
Authors: FICHOROVA R.N. , DIMITROVA E. , NAKOV L. , TZVETKOV D. , PENKOV R. , TASKOV H. 
Published: May 2013

PROBLEM: To test the relative impact of epididymal versus ejaculated sperm in immunologic infertility.METHOD: Human antibody binding to epididymal and ejaculated spermatozoa was compared by flow cytometry (FCM) since it allows quantitative analysis of viable sperm while ignoring nonsperm cells. To select sera for FCM, GAT, TAT, and ELISA were applied on 145 sera from fertile men, idiopathically infertile and varicocele patients.RESULTS: All GAT/TAT‐positive infertile patients, a representative group of varicocele patients and the fertile control, were assessed by FCM. Higher reactivity toward epididymal sperm revealed 18/22 sera while only four out of them bound to ejaculated sperm stronger than the control. All varicocele sera were positive against epididymal while negative against ejaculated spermatozoa.CONCLUSIONS: Epididymal sperm antigens may play a predominant role in some cases of immunologic infertility. Such patients might not be adequately diagnosed and respectively treated due to the limitations of diagnostic procedures applying only ejaculated spermatozoa.
Presence of Activated Macrophages in a Murine Model of Early Embryo Loss
Authors: DUCLOS ALAIN J. , HADDAD ELIAS K. , BAINES MALCOLM G. 
Published: May 2013

PROBLEM: Even though our knowledge of the phenomenon at play at the fetoplacental interface has greatly advanced during the past years, a complete understanding of the reasons why the developing embryo is not rejected by maternal immune effector cells remains largely unknown.METHODS: We have used immunohistochemistry with the macrophage‐specific markers F4/80 and MHC II to study the relationship between decidual infiltration and resorption in murine models of embryo loss between days 6 and 10 of gestation.RESULTS: Analysis of day 8 CBA/J × DBA/2 pregnancies has revealed 2 distinct populations of embryos. The majority (69.4%) expressed low levels of F4/80+ cells, but a minority (30.6%) expressed much higher level of the macrophage marker. In CBA/J × BALB/c, most embryos (91.7%) expressed low numbers of F4/80+ cells. As earlier experiments established that products of activated macrophages (TNF‐α and nitric oxide) were implicated in embryo loss in this model, the activation status of the F4/80+ macrophages was assessed through the cell surface expression of MHC II. Again, a similar association was established: 30.6% of the CBA/J × DBA/2 embryos were infiltrated by significantly more MHC II+ cells than the control CBA/J × BALB/c mating. Finally, when coordinate expression of F4/80, MHC II and CD11b was assessed, it was found that an embryo significantly infiltrated by cells bearing one of the 3 markers was also heavily infiltrated by cells bearing the 2 other markers.CONCLUSIONS: This study has shown that the augmented infiltration of the deciduum with maternal macrophages is an early event which precedes spontaneous abortion of the early embryo.
Identification of the Complement Regulatory Proteins CD46, CD55, and CD59 in Human Fallopian Tube, Endometrium, and Cervical Mucosa and Secretion
Authors: JENSEN TONE SKEIE , BJØRGE LINE , WOLLEN ANNE‐LONE , ULSTEIN MAGNAR 
Published: May 2013

PROBLEM: Complement lytic activity has been demonstrated, and a potential for its activation is present in human cervical and tubal secretions and in the endometrium. This necessitates the presence of regulatory mechanisms for protection of the sperm and the implanting allogeneic conceptus in the female genital tract. Complement regulatory proteins demonstrated on sperm and in seminal fluid have been attributed such a role. It is however likely that additional protection is required for a successful conception and implantation to take place. This lead us to investigate the distribution of the complement regulatory factors in cervical mucus and mucosa, uterine endometrium, and fallopian tube.METHOD: Endometrium and cervical mucosa were obtained from patients undergoing hysterectomy for benign conditions, and specimens were selected from different stages of the menstrual cycle. Fallopian tubes were obtained from patients submitted for sterilization, while cervical mucus was aspirated from volunteers undergoing gynecological examination. Immunohistochemistry was performed on all tissue samples, using monoclonal antibodies to membrane cofactor protein (MCP), decay accelerating factor (DAF), CD59 and complement receptor 1 (CR1). Western blot analysis was performed on cervical mucus under nonreducing conditions.RESULTS: MCP, DAF, and CD59 were found to be expressed in human endometrium and fallopian tube. No variation in expression was detected throughout the menstrual cycle. CR1 was not expressed. Soluble forms of DAF and CD59 were found to be present in cervical mucus.CONCLUSION: The complement regulatory proteins MCP, DAF, and CD59 are expressed throughout the female genital tract, and may thus play an important role in protecting the traversing sperm and implanting blastocyst from complement mediated damage.
Evidence for a Leukocyte Adhesion Factor Produced by the Early Embryo
Authors: CHECK JEROME H. , BOLLENDORF ANIELA , ASKARI H. ALI 
Published: May 2013

PROBLEM: To determine if the embryo may induce adhesive molecules needed for implantation.METHOD: Determination of whether platelet rosetting around lymphocytes might occur when exposed to sera from pregnant, but not nonpregnant patients and from culture fluid from embryos but not oocytes.RESULTS: 90.2% of women with positive sera beta human chorionic gonadotropin (P‐hCG) levels taken at least 12 days postovulation demonstrated platelet rosette factor (PRF) vs only 18.7% when β‐hCG was negative. Using mid‐luteal phase sera in women receiving hCG injection 1 wk before, 64.7% had positive PRF when serial β‐hCG levels were positive as did 100% of samples taken from in vitro fertilization (IVF) patients; however, only 15.3% were positive with negative serial hCG levels. Culture media from fertilized oocytes and embryos tested positive for PRF, but follicular fluid and media from unfertilized oocytes were negative.CONCLUSION: The early embryo secretes a factor(s) that gains access to maternal serum and promotes increased lymphocyte/platelet adhesiveness.
Preimplantation Factor (PIF) Predicts Subsequent Pregnancy Loss
Authors: COULAM CAROLYN B. , ROUSSEV ROUMEN G. , THOMASON EDWARD J. , BARNEA EYTAN R. 
Published: May 2013

PROBLEM: To evaluate the ability of preimplantation factor (PIF) measured in the lymphocyte/platelet binding assay (LPBA) to predict subsequent spontaneous abortion.METHOD: Serum from 57 women experiencing first trimester pregnancy losses were studied using the LPBA (46 women conceived after in vitro fertilization and embryo transfer for treatment of infertility and 11 with a history of unexplained recurrent spontaneous abortion conceived spontaneously). The assay employs a combination of heat inactivated sera with donor O+ lymphocytes and platelets, complement and an antibody against CD2. Chromosome analysis was performed on 32 of the abortuses. Results of PIF assay were compared between karyotypically normal and abnormal abortuses.RESULTS: PIF assay was negative in all 57 women at the time of abortion. Among 12 karyotypically normal abortuses only 1 woman (8%) had an initial positive PIF, 11 (92%) had negative PIF. Serial PIF assays were performed on 15 women. PIF assay became negative a minimum of two weeks prior to demonstration of intrauterine demise at a time when hCG concentrations remained elevated. A trend to subnormal was seen in women with normal when compared to those with abnormal abortus karyotype, but the numbers were too small to reach statistical significance (P = 0.09).CONCLUSION: Measurement of PIF throughout the first trimester of pregnancy predicts subsequent pregnancy loss.
Can the Immunobead Assay for Detecting Sperm Antibodies in Fresh Samples Be Reproduced in Cryopreserved/Thawed Human Spermatozoa?
Authors: MELO‐ABREU SUNDAR , BATTISH SARITA , BROWN KIMBERLY , TURECK RICHARD , HEYNER SUSAN , BLASCO LUIS 
Published: May 2013

PROBLEM: To evaluate the reproducibility of the Immunobead Assay (IBA) on sperm samples before and after cryopreservation.METHOD: Sperm samples (fresh and post‐thaw) from known antibody negative donors (N=20) were evaluated for percent immunobead binding by IBA following incubation with known antibody‐positive serum.RESULTS: In both fresh and thawed negative samples, the mean sperm head binding was 0.5% ± 0.5, the mean sperm tail binding was 2.0% ± 2.0 and the mean sperm head‐tail binding was 3.0% ± 2.0 for IgG, IgA and IgM type antibodies, respectively. The same samples exposed to positive sera showed 40.0% ± 10.0 mean head binding, 7.0% ± 8.0 mean tail binding and 47.0% ± 11.0 mean head‐tail binding.CONCLUSIONS: IBA is highly reproducible for detecting sperm antibodies in both fresh and cryopreserved/thawed samples of human spermatozoa.
Circulating Tumor Necrosis Factor (TNF)‐α in Normally Cycling Women and Patients with Premature Ovarian Failure and Polycystic Ovaries
Authors: NAZ RAJESH K. , THURSTON DEBORAH , SANTORO NANETTE 
Published: May 2013

PROBLEM: The purpose of this study was to investigate the levels of tumor necrosis factor (TNF)‐α in sera of infertile patients having premature ovarian failure (POF) and polycystic ovaries (PCO), and to compare the levels with those in age‐matched normally cycling women.METHOD: Levels of TNF‐α, luteinizing hormone (LH), follicle‐stimulating hormone (FSH), and estradiol (E2) were measured in the sera of infertile and normal women by the enzyme linked immunosorbent assay (ELISA), fluorescent immunoassay and radioimmunoassay (RIA), respectively. Multiple groups comparisons were performed using Dunnet's test. Post‐hoc analysis was performed using a Tukey‐Kramer test. P < 0.05 was considered statistically significant.RESULTS: TNF‐α levels were significantly (P = 0.003 to < .0001) lower in the sera of patients with POF compared to sera of controls and patients with PCO.CONCLUSIONS: TNF‐α may have a role in ovarian function. Derangement in follicular development, luteal function and atresia results in a change of circulating TNF‐αa levels.
Constitutive Secretion of Interleukin‐6 by Human Decidual Stromal Cells in Culture. Regulatory Effect of Progesterone
Authors: MONTES M. JOSÉ , TORTOSA CARMEN G. , BORJA CONCEPCIÓN , ABADÍA ANA C. , GONZÁLEZ‐GÓMEZ FRANCISCO , RUIZ CONCEPCIÓN , OLIVARES ENRIQUE G. 
Published: May 2013

PROBLEM: Although several studies have demonstrated that decidual stromal cells (DSC) can secrete cytokines in culture, none of these studies documented the purity of the cultures. Since other cells of the decidua, such as macrophages and epithelial cells, also produce cytokines, it is important to ensure purity of the culture so that cytokine production can be ascribed with confidence to DSC.METHOD: DSC from early human pregnancies were highly purified and maintained in culture. Basal secretion by these cells of IL‐6, together with other cytokines considered critical for pregnancy (IL‐1β, TNFα and IFNγ), was measured with immunological techniques.RESULTS: We found that DSC in culture produce insignificant quantities of IL‐1β, TNFá and IFNΓ, but appreciable amounts of IL‐6. The production of this later cytokine was, however, inhibited by the effect of progesterone.CONCLUSIONS: Basal production of IL‐6 by DSC may be involved in physiological functions at the maternal‐fetal interface. Nevertheless, the secretion of this cytokine is regulated by progesterone, probably to prevent excessive production of this cytokine from triggering an inflammatory response that might compromise pregnancy.
Effect of RU‐486 and Related Compounds on the Proliferation of Cultured Macrophages
Authors: ROBERTS C.P. , PARTHASARATHY S. , GULATI R. , HOROWITZ I. , MURPHY A.A. 
Published: May 2013

PROBLEM: Macrophages are implicated in the pathophysiology of endometriosis and are influenced by anti‐inflammatory steroids as well as anti‐oxidants.METHODS: We tested the effect of RU‐486, an antiprogesterone, antiglucocorticoid and an antioxidant, on the proliferation of RAW macrophages.RESULTS: The incorporation of 3H‐thymidine was significantly inhibited by both progesterone and RU‐486. Progesterone and RU‐486, in combination, synergistically inhibited macrophage growth. In contrast, dexamethasone‐stimulated growth was antagonized by RU‐486 in a dose dependent manner. ZK 112,993 which is structurally related to RU‐486 but lacks antioxidant properties, also inhibited thymidine incorporation. The synergistic effect of RU‐486 and ZK 112,993 with progesterone implicate a mechanism of action separate from receptor bound antagonists. A cell permeable antioxidant, pyrrolidine dithiocarbamate was very effective in inhibiting the incorporation of 3H‐thymidine into cells.CONCLUSIONS: These results suggest novel therapeutic modalities in the management of endometriosis via antiglucocorticoid as well as antioxidant mechanisms.
Hematopoietic Stem Cell Antigen‐1 (Sca‐1) Expression in Different Lymphoid Tissues of Female Mice Treated With GnRH Agonist
Authors: RAO L. V. , CLEVELAND R.P. , KIMMEL R.J. , ATAYA K.M. 
Published: May 2013

PROBLEM: Our earlier studies have demonstrated a general suppression of leukocyte maturation upon GnRH agonist treatment in mice and suggested a potential effect at an early stem cell stage of leukocyte development.METHOD: Three‐week old Balb/c and C57BL/6 female mice received 50 μlg injections of Lupron depot or placebo. Sequential changes in Sca‐1+ cells in the bone marrow, thymus, blood and spleen were studied by flow cytometry.RESULTS: In bone marrow, the absolute numbers of Sca‐1+ cells were significantly decreased at 2 weeks in C57BL/6 mice whereas a decreasing trend was noted in Balb/c mice following agonist administration. Concomitantly, thymocytes expressing Sca‐1+ cells were significantly increased at 2 weeks in C57BL/6 mice, but were significantly decreased in Balb/c mice. Significant decreases in Sca‐1+ cells were also observed in spleen and blood in Balb/c mice whereas no significant differences were observed in C57BL/6 mice.CONCLUSIONS: These data suggest GnRH agonists affect hematopoietic stem cell development in mice. The effects observed vary with different genetic backgrounds. In Balb/c mice these effects are more pronounced, and appear to result in the inhibition of stem cell maturation. In contrast, GnRH agonist enhances stem cell maturation in C57BL/6 mice.
Decidual Natural Killer Cytotoxicity Decreased in Normal Pregnancy but Not in Anembryonic Pregnancy and Recurrent Spontaneous Abortion
Authors: CHAO KUANG‐HAN , YANG YU‐SHIH , HO G‐NERNG , CHEN SHEE‐UAN , CHEN HSIN‐FU , DAI HUI‐JU , HUANG SU‐CHENG , GILL THOMAS J. 
Published: May 2013

PROBLEM: The natural killer (NK) cell activity is depressed in the decidua of early normal pregnancy. Recently Morii et al. (Am J Reprod Immunol 1993;29:1–4) found that all early intradecidual CD3+ T cells expressed either T cell receptor (TCR) α/β or γ/δ but that the expression of the CD3+/TCR complex was down‐regulated.METHOD: To test whether these changes in decidual cellular immunity are different among normal pregnancy, anembryonic pregnancy and recurrent spontaneous abortion, we examined the immune cell subpopulations in the decidua from these three types of pregnancy using flow cytometry and an NK cytotoxicity assay.RESULTS: Intradecidual CD3+ T cells expressed either TCR α/β or γ/δ, and the level of expression of the CD3/TCR complex was down‐regulated in normal pregnancy, anembryonic pregnancy, and recurrent spontaneous abortion. Although the relative proportion of decidual NK cells was increased to approximately the same extent in all three types of pregnancy, decidual NK activity was higher in anembryonic pregnancies and in recurrent spontaneous abortions than it was in normal pregnancies.CONCLUSION: Decidual NK cell responses are different in anembryonic pregnancies and in recurrent spontaneous abortions than in normal pregnancies. Whether this difference is pathogenic or is the response to a dead embryo remains to be elucidated.
Differential Expression of VLAβ1 (CD29) on Monocytes From Patients With Endometriosis
Authors: GEBEL HOWARD M. , RANA NASSIR , BRAUN DONALD P. , DMOWSKI W. PAUL 
Published: May 2013

PROBLEM: Previous studies have established that in vitro proliferation of endometrial cells is enhanced by peripheral blood monocytes (PBM) and suppressed by peritoneal macrophages (PM) from patients with endometriosis but only suppressed by PBM and PM obtained from normal subjects. The functional activity of PBM and PM is influenced by the engagement of numerous cell surface receptors with their respective physiological ligands.METHOD: In this study, PBM and PM from fertile women (Group 1), women with unexplained infertility (Group 2), and women with limited (Group 3) or severe (Group 4) endometriosis were isolated in order to analyze these cells for the expression of CD54, CD58 and HLA‐DR (immunoglobulin supergene antigens) CD18 and CD29 (integrins) and CD44 (an addresin). These cell surface antigens are involved in monocyte/macrophage trafficking, activation, signal transduction and/or adhesion.RESULTS: No differences were detected in the percentage of PBM expressing CD18, CD44, CD54, CD58, or HLA‐DR among the four groups of subjects. Furthermore, the density of these antigens expressed on PBM was identical in patients and control subjects. In contrast, the percentage of PBM expressing CD29 (also known as VLAβ1) and the density of CD29 expressed per cell were significantly reduced (P < 0.01) in patients with limited endometriosis compared to controls and patients with severe disease. Interestingly, although the percentage of CD29+ PBM from women with severe endometriosis was not statistically different from the percentage of CD29+ PBM from controls, the density of CD29 expressed per cell was significantly elevated among patients with severe disease. Analysis of PM from the four subject groups revealed no differences in CD29 expression or density. However, the percentage of PM expressing CD18 was significantly decreased in patients with limited (but not severe) endometriosis.CONCLUSION: Since both CD18 and CD29 play a role in cell trafficking and/or adhesion, alterations in their expression among patients with endometriosis suggest that these integrin β chains may play a role in the pathogenesis of the disease.