bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Leukocytic Reaction of the Human Uterine Cervix
Authors: THOMPSON L.A. , BARRATT C.L.R. , BOLTON A.E. , COOKE I.D. 
Published: May 2013

PROBLEM: Sperm interaction with the immune system of the human cervix is poorly understood.METHOD: The leukocytic response of the human cervix to sperm was examined in a closely monitored patient population (N = 10), using monoclonal antibody cell identification techniques. Baseline data were collected from both cervical mucus and smears sampled before treatment by donor insemination. Donor insemination was timed to coincide with ovulation by monitoring plasma LH concentrations twice daily. Following insemination the numbers of leukocytes were recorded in cervical mucus and smear samples taken over a 24‐h period relative to the time of treatment. Controls treated with “pure sperm,” seminal plasma, cryopreservative, and cervical smearing alone were also included in the study.RESULTS: Only those women treated with sperm cells exhibited substantial elevations in leukocyte numbers following inseminations. Additionally, serial cervical smearing induced an inflammatory response of the cervix. In all the women, the neutrophil was the predominant leukocyte of the cervix both during the baseline and treatment periods (median values ranged from 77 to 86%). Macrophages, T‐helper lymphocytes, and T‐suppressor lymphocytes were also detected, but only in low numbers (2–10.6%). Two patients and one control (“pure sperm”) became pregnant during their study cycle.CONCLUSIONS: We conclude that the leukocytic reaction is a physiological response of the cervix to sperm, the function of which remains to be established.
Immunotherapy of Habitual Abortion
Authors: CARP H.J.A. , TODER V. , MASHIACH S. 
Published: May 2013

ABSTRACT: Many cases of habitual abortion have been assumed to be due to hyporesponsiveness to the spouse's antigens encountered in pregnancy. Immunization by paternal leukocytes has been used to potentiate the immune response and prevent further miscarriages. This treatment has been highly controversial in terms of efficacy, mode of action, and side effects. More recently immunoglobulin has been used as passive immunization for similar indications.In our experience immunotherapy is effective; 80% of patients have subsequent live births. The most significant results are seen in patients with five or more abortions, in whom 66% of subsequent pregnancies develop normally compared to 20% in a control group. We have used antipaternal complement‐dependent antibody (APCA) production after immunization as a marker of immune response. APCA correlates with beneficial outcome in the next pregnancy. APCA may also be associated with cytokines, which may enhance embryonic and trophoblast development. Immunoglobulin may similarly provide the relevant antibodies or cytokines. At present a large scale meta‐analysis is being performed to confirm or refute the efficacy of this treatment This meta‐analysis may resolve the controversy.
Stable Production of Recombinant Human Sperm Immobilizing Antibody Using cDNA Expression Vectors
Authors: SAWAI HIDEAKI , YAMASAKI NORIYUKI , KOMORI SHINJI , KARASUYAMA HAJIME , ISOJIMA SHINZO 
Published: May 2013

PROBLEM: Sperm immobilizing antibodies present in sterile women may be one of the principal causes of immunological infertility. We already established cell lines that secrete recombinant human IgG sperm immobilizing antibody using class‐switched (from IgM to IgG) genomic immunoglobulin genes. However, these transfectants produced a small quantity of antibody and required continuous use of a medium with selective reagents. We have now constructed cell lines that stably secrete the antibody in large quantities using immunoglobulin cDNAs and cDNA expression vectors.METHOD: The immunoglobulin heavy chain cDNA was cloned from transfectants that secrete the class‐switched human IgG sperm immobilizing antibody. The light chain cDNA, which had already been cloned, and the heavy chain cDNA were inserted into the modified bovine papilloma virus‐based cDNA expression vectors BCMGSNeo and BCMGSHyg, respectively. These constructs were sequentially transfected into a mouse myeloma cell line by electroporation.RESULTS: The established transfectants produced recombinant antibody that retained human sperm immobilizing activity in nonselective medium for at least 30 days. Moreover, the production of the antibody was increased three times over that of the previous cell lines.CONCLUSION: We have established an unique method that improves the production of sperm immobilizing antibody stably and in large quantities.
Antiendometrial Autoantibodies Are Generated in Patients With Endometriosis
Authors: GORAI ITSUO , ISHIKAWA MASAHIKO , ONOSE RYO , HIRAHARA FUMIKI , MINAGUCHI HIROSHI 
Published: May 2013

PROBLEM: Our aim was to investigate endometrial antigens involved in the autoimmunity of endometriosis.METHOD: We detected endometrial antigens against which autoantibodies directed with Western blotting.RESULTS: Thirteen (72.2%), 14 (77.8%), and 15 (83.3%) of 18 serum samples from endometriosis patients had antibodies reactive against endometrial antigen wtih MW of 26 kd, 34 kd, and 42 kd, respectively, while 6 (33.3%), 8 (44.4%), and 8 (44.4%) of 18 samples from normal control women reacted against these antigens, respectively. The frequencies of antibodies to the endometrial antigens were significantly (P < 0.05) higher in the endometriosis patients than in the normal control women. Antibodies in peritoneal fluid (PF) reacted against antigens with MW of 26, 34, 38, 42, and 64 kd, while those from the normal control reacted against antigens wtih MW of 38, 42, and 64 kd. Serum samples from normal fertile males did not show any reactivity against these endometrial antigens.CONCLUSIONS: Our results show that autoantibodies reactive against endometrial antigens are present in patients with endometriosis.
Mitogen Induced Production of Polyclonal IgG is Decreased in Women With Severe Endometriosis
Authors: GEBEL HOWARD M. , BRAUN DONALD P. , ROTMAN CARLOS , RANA NASIR , DMOWSKI W. PAUL 
Published: May 2013

PROBLEM: The etiology and/or pathogenesis of endometriosis may involve aspects of both humoral and cellular immunity.METHOD: In this investigation, we analyzed the ability of B lymphocytes from distinct patient groups for production of IgGl, IgG2, and IgG3 following in vitro stimulation with polyclonal B‐cell mitogens (pokeweed mitogen and Staphylococcus aureus Cowan strain I) after in vitro stimulation with polyclonal B‐cell activators.RESULTS: We observed that the in vitro production of IgGl, IgG2, and IgG3 was identical among fertile controls (no endometriosis; N = 22), infertile women without endometriosis (N = 22), infertile women without endometriosis (N = 20) and patietns with stage 1 or 2 endometriosis (N = 31). In contrast, in vitro IgG2 production was significantly reduced among women with stage 3 or 4 endometriosis (N = 11) compared to controls (P < 0.001).CONCLUSION: Since the number of circulating B cells was similar in each patient group studied, the reduced production of IgG2 in patients with stage 3 or 4 disease was not merely due to fewer antibody producing cells in those subjects, and we speculate that the observed decrease in polyclonal IgG2 production among these patients is due to a primary defect. In additional studies, we observed that polyclonal IgG2 production was normal among stage 3 or 4 patients treated with danazol (N=ll), but significantly reduced in patients treated with gonadotropin releasing hormone agonists (N = 8). Although not conclusive, these data suggest that danazol may have the capacity to correct the defective production of polyclonal IgG2 in patients with severe endometriosis.
A Solid‐Phase Assay for the Detection of Anti‐Sperm Antibodies
Authors: OKADA HIROSHI , KAMIDONO SADAO , OWENS GEORGE R. , NAGAMATSU R. GEORGE , ADDONIZIO JOSEPH C. 
Published: May 2013

PROBLEM: ELISA is an ideal assay method for a large‐scale screening of anti‐sperm antibodies among a large number of infertile males. However, conventional ELISA with whole spermatozoa needs time‐consuming steps of centrifugation.METHOD: A solid‐phase assay used for detecting anti‐sperm antibodies was established. This assay is suitable not only for detecting circulating anti‐sperm antibodies of IgG, IgM, and IgA subclass simultaneously but also for screening hybridomas secreting anti‐sperm monoclonal antibodies (mAbs). The microtiter plates, on which solubilized sperm antigens are fixed, can be stored at − 80°C for up to six months without losing reactivity with anti‐sperm antibodies.RESULTS: Using this assay, 53 sera (13 were proven positive and 40 were proven negative for sperm agglutination antibody) were tested. Although the false‐negative rate was 0%, the false‐positive rate was 32%. One thousand one hundred sixty‐five supernatants from hybridomas constructed with splenocytes of mice who were hyperimmunized with human sperm and nonsecreting myeloma cells were tested by this solid‐phase assay and two anti‐sperm mAb secreting clones were selected and established.CONCLUSIONS: It is recommended that for research work this assay could be used for the first screening of the hybridoma secreting anti‐sperm mAb, and for clinical use this assay might be suitable for the first screening of sera of infertile patients. However, conventional bioassays should follow to confirm the biological meaning of the positivity.
Cytokine‐Initiated Signal Transduction in Human Myometrial Cells
Authors: HERTELENDYM FRANK , ROMERO ROBERTO , MOLNÁR MIKLÓS , TODD HERBERT , BALDASSARE JOSEPH J. 
Published: May 2013

PROBLEM: The objectives of this study were to evaluate interleukin‐1 (IL‐1) binding and some postreceptor actions of this cytokine and tumor necrosis factor (TNF) in human myometrial cells (HMC).METHOD: Monolayer cultures of HMC were used to characterize binding and to measure cyclic (c)AMP, prostaglandin (PG)E2, and PGI2 production. Membrane preparations were used to assess ADP‐ribosylation and for immunoblotting.RESULTS: HMC were found to specifically bind [125I]IL‐1 with an apparent Kd of 2 × 10−10M. Incubation of HMC with IL‐1 or TNF caused a time‐dependent and dose‐dependent accumulation of cAMP, as well as a significant potentiation of forskolin‐promoted cAMP production. These cytokines also increase PGE2 and PGI2 output, independently of the activation of adenylyl cyclase. IL‐1 treatment had no measurable effect either on cholera toxin‐mediated and pertussis toxin‐mediated ADP‐ribosylatidn, or on the amount of Gi proteins, as assessed by immunoblotting using a polyclonal antibody.CONCLUSIONS: It is suggested that IL‐1 and TNF may activate one or more isoforms of the catalytic component of adenylyl cyclase, raising intracellular cAMP.
Hormonal Regulation of Complement Factor B in Human Endometrium
Authors: HASTY LISA A. , BROCKMAN WENDY W. , LAMBRIS JOHN D. , LYTTLE C. RICHARD 
Published: May 2013

PROBLEM: Recent investigations have demonstrated the presence of complement components in human endometrium in a cycle‐specific manner. Luteal phase endometrium has been shown to synthesize complement C3 de novo, whereas proliferative endometrium produces little or no C3. Likewise factor B. which is critical to the activation of the alternative pathway of complement, has been shown to be present only in the glandular epithelium of luteal phase endometrium. This investigation was designed to determine if factor B is present in the endometrium in a high progesterone state such as pregnancy or with exogenous progesterone treatment.METHOD: Endometrial biopsies were obtained from patients on progesterone therapy. The endometrium of early pregnancy was evaluated by obtaining biopsies from patients with ectopic pregnancies as well as from patients undergoing therapeutic termination. Immunohistochemistry was performed on each biopsy using monoclonal antibodies to factor B.RESULTS: Our results demonstrate the presence of factor B in the glandular epithelial cells of the endometrium of patients treated with exogenous progesterone therapy. Additionally. factor B was localized to the glandular compartment of the endometrium from patients with ectopic gestations. Interestingly, the evaluation of an implantation site from an early gestation demonstrated factor B in the maternal decidua only; trophoblast did not exhibit the presence of factor B.CONCLUSION: Factor B exists in the endometrium in a hormone‐dependent manner and is not expressed in fetal tissue in early gestation.
Association Between Maternal‐Fetal HLA‐DR Relationships and Fetal Growth
Authors: HOFF CHARLES , PEEVY KEITH J. , SPINNATO JOSEPH A. , GIATTINA KATHERINE , PETERSON RAYMOND D.A. 
Published: May 2013

PROBLEM: To determine whether maternal‐fetal human leukocyte antigen (HLA) antigenic relationships are associated with differential fetal growth in weight.METHOD: A cohort of 659 primigravid women were enrolled in this study in the prepartum period and their neonates were subsequently examined. Anthropometric, maternal cigarette smoking behavior, health, pregnancy, and delivery data were collected; serogenetic typing was conducted on maternal and cord bloods to determine maternal and neonatal HLA antigenic phenotypes. Women and their neonates were assigned to one of the four different types of maternal‐fetal relationships existing at each of the HLA‐A, B, DR, and DQ loci. Birthweights were treated quantitatively and qualitatively (neonates classified as growth‐retarded or normal).RESULTS: After controlling for other factors influencing birthweight (e.g., smoking, maternal body size), significantly lower birthweight trends (P < .01) were found when neonates expressed a single HLA‐DR antigen and their mothers expressed a second HLA‐DR antigen that was foreign (allogeneic) to their neonate.CONCLUSION: Our finding supports the hypothesis that lack of maternal immune exposure to fetal HLA antigens is associated with a slowing of fetal growth. However, in this situation slowed fetal growth is most likely to occur when the fetus is potentially exposed to maternal HLA‐DR alloantigens. We believe this sheds new light on immunologic events at the maternal‐fetal interface influencing fetal growth. We present one possible explanation to account for this finding.
Membrane‐Spanning Fcγ Receptor III Isoform Expressed on Human Placental Trophoblasts
Authors: NISHIKIORI NAOKO , KOYAMA MASAYASU , KIKUCHI TOMOYUKI , KIMURA TOSHIO , OZAKI MASAMI , HARADA SHIGENORI , SAJI FUMITAKA , TANIZAWA OSAMU 
Published: May 2013

PROBLEM: Fc receptor for immunoglobulin (FcγR) is an important mediator of immunological functions in the feto‐maternal relationship. We have demonstrated by immunohistochemical means that three distinct classes of FcγRS are expressed in the different cell components of the human placenta.METHOD: In this study, FcγRIII isoform expressed on placental trophoblasts (PTs) was investigated by indirect immunofluorescence and cDNA cloning. PTs, isolated from human term placenta by digestion with proteolytic enzyme, were reacted with monoclonal antibodies (MAb) against the Fc‐γRs and other surface markers of leukocytes and subjected to flow cytometric analysis.RESULTS: PTs were positively stained with 3G8 and Leul lb against FcγRIII, partially stained with MAb against MHC class I, but not with 32.2 (FcγRI), IV3 (FcγRII), or MAbs against CD4, CD19, or CD56, indicating that only low affinity receptor, FC7RIII, is γexpressed on PTs. The DNA sequence of cloned FcγRIII CDNA from PTs by PCR was identical to that of natural killer (NK) cell isoform, including the position of the stop codon that differs from the granulocyte isoform by several nucleotide substitutions. We further analyzed the susceptibility of PTs against phosphatidylinositol specific phospholipase C (PI‐PLC) to determine the structural topology of PT isoform. While the reactivity with 3G8 on PTs was not influenced by treatment with PI‐PLC, that on granulocytes was significantly diminished with PI‐PLC.CONCLUSIONS: This result confirmed that FcγRIII on PTs is a membrane‐spanning molecule, and that it is distinctive from PI anchoring FcγRIII on granulocytes.
Natural Killer Cell Activity of Lymphocytes Exposed to Ovine, Type I, Trophoblast Interferon
Authors: TUO WENBIN , OTT TROY L. , BAZER FULLER W. 
Published: May 2013

PROBLEM: A member of newly described interferon (IFN) family, ovine trophoblast protein one (oTP‐1, now named as ovine type I trophoblast interferon, oTIFN), is a major secretory product of sheep conceptuses during days 11–21 of pregnancy. Type I trophoblast IFN shares high amino acid and nucleotide sequence homology with other mammalian IFN‐αs and has functional characteristics of IFNs such as antiproliferative, immunosuppressive, and antiviral activities. Moreover, oTIFN is responsible for the antiluteolytic signaling for early pregnancy recognition in sheep. It has been reported that natural killer (NK) cells are recruited to the pregnant uterus and contribute para‐immunotrophic effects on growth and differentiation of the conceptus (embryo/fetus and associated membranes). Because IFNs are potent modulators of NK cell activity, the present study examined interactions between oTIFN and sheep and pig NK cells.METHODS: A 51Cr release assay was used to evaluate the effects of various concentrations of oTIFN and IFN‐α on sheep and pig NK cell activity against K562 and HeLaS3 cells in vitro. Dosages were tested at four effector to target cell ratios.RESULTS: These data provide the first evidence that oTIFN is a potent NK cell activator in vitro. Recombinant human IFN‐α, (rhIFN‐α) and oTIFN increased (P < 0.01) ovine NK cell cytotoxicity for K562 cells at very low dosages (50 antiviral units (AVU)/ml). Lower doses of oTIFN (15 AVU/ml) were sufficient (P < 0.01) to enable sheep NK cells to kill ovine NK resistant cells, HeLa S3, in a dose‐dependent fashion. However, much higher concentrations (>400 AVU/ml) of oTIFN were needed to increase (P < 0.01) porcine NK cell cytotoxicity. This suggests that oTIFN has some species specificity in activating NK cells. The augmentation of NK cell activity by 100 AVU/ml of oTIFN was effectively neutralized by an anti‐oTIFN monoclonal antibody (HL‐98) at a dilution of 1:800.CONCLUSIONS: Results of the present study clearly indicate that oTIFN is as active as rhIFN‐α, for activating NK cells in vitro. Immune cells, especially those recruited to the pregnant uterus by conceptus secretory products,−may be stimulated/activated by trophoblast IFNs. However, the function of activated NK cells during early pregnancy remains to be determined.
Is an Additional Vaccination Necessary for a Successful Second Pregnancy in Unexplained Recurrent Aborters Who Were Successfully Immunized With Their Husband's Lymphocytes Before the First Pregnancy?
Authors: TAKAKUWA KOICHI , HIGASHINO MASAHIKO , YASUDA MASAKO , ISHII SHIRO , UEDA HIROYUKI , ASANO KENSAKU , KAZAMA YOSHIKI , TANAKA KENICHI 
Published: May 2013

PROBLEM: Is an additional immunotherapy necessary or not for patients who have obtained successful results after initial immunotherapy?METHODS: The successive pregnancy outcome was analyzed in 22 patients out of 29 unexplained recurrent aborters who had undergone immunotherapy with their husband's lymphocytes according to our previously reported protocol (Takakuwa et al., Am J Reprod Immunol Microbiol. 10:1–9, 1986; Takakuwa et al., Am J Reprod Immunol. 23:37–41, 1990) and had obtained successful outcome between January 1983 and December 1989. In addition, the alteration of blocking antibodies (BAbs), which was evaluated by a one‐way mixed lymphocyte culture reaction (MLR) blocking assay between the spouses, was analyzed in 26 patients out of 29.RESULTS: None of the 22 patients underwent further immunotherapy because a significantly high titer of MLR‐BAbs had been detected before the new pregnancy. In 19 out of the 21 patients (90.5%), pregnancy was successful.CONCLUSION: Additional immunotherapy is not necessary for patients who have obtained successful results after the initial immunotherapy and are positive for MLR‐BAbs after their first delivery.
Does Endothelin‐1 Affect Human Spermatozoa Function?
Authors: Kamada Shusaku , Oehninger Sergio , Mahony Mary C. , Blackmore Peter F. , Lanzendorf Susan E. , Hodgen Gary D. 
Published: May 2013

PROBLEM: It has been reported that massive amounts of immunoreactive endothelins (ETS) exist in human seminal plasma. However, the physiological role of ETS in seminal plasma remains to be determined. We speculated that ETS might affect sperm function.METHOD: The present study was designed to investigate the effect of endothelium‐1 (ET‐1) on: (a) sperm motion parameters, (b) hyperactivated motility, (c) sperm‐zona pellucida‐binding capacity, (d) sperm‐oocyte penetration capacity, (e) acrosome reaction and its prerequisite, an increase in intracellular Ca2+ concentration ([Ca2+]i), and to examine (f) the presence of binding sites for ET‐1 in human sperm. Forty‐six semen ejaculates from 14 fertile men were assessed under capacitating conditions after separation of the motile sperm fraction by wash and swim‐up.RESULTS: ET‐1 (1 (μm) exhibited significant stimulatory effects on sperm velocity at 30 min (P = 0.01), amplitude of lateral head displacement (ALH)max (P = 0.05), and ALHmean at 60 min (P = 0.04) in some samples (n = 10). However, these effects were not observed in experiments using a larger number of samples (n = 39). ET‐1 had no effect on hyperactivated motility of sperm at 30 min to 24 h. Neither ET‐3 nor IRL 1620, a selective ETB receptor agonist, affected sperm motion parameters or hyperactivated motility. ET‐1 did not affect sperm‐zona‐binding capacity, sperm‐oocyte penetration capacity, acrosome reaction, or [Ca2+]i of sperm. Specific binding sites for ET‐1 were not detected on the cell surface of human sperm.CONCLUSIONS: Although ET‐1 is present in massive amounts in human seminal plasma and may have the capacity to alter the quality of motile sperm in some samples, a physiological role of ET‐1 in the modulation of the function of mature, ejaculated sperm still remains unknown.
Direct Ovarian Effect of Growth Hormone in the Rabbit
Authors: Ando Motomu , Yoshimura Yasunori , Iwashita Mitsutoshi , Oda Takahisa , Karube Masataka , Ubukata Yoshinobu , Jinno Masao , Nakamura Yukio 
Published: May 2013

PROBLEM: This study was undertaken to assess whether growth hormone (GH) can stimulate follicle growth and ovarian steroidogenesis via putative GH receptors.METHOD: In vitro perfused rabbit ovary.RESULTS: Ovulation occurred in neither the control ovaries nor experimental ovaries treated with 100 ng/ml of GH, whereas all ovaries exposed to 50 IU of human chorionic gonadotropin (hCG) ovulated. The addition of GH to the perfusate significantly stimulated the follicle growth in the absence of gonadotropin. The percent change in follicle diameter in GH‐treated ovaries did not differ significantly from that in hCG‐treated ovaries. Exposure to GH significantly stimulated the meiotic maturation in the follicular oocytes, as compared with the contralateral control ovaries. Although the concentration of progesterone in the perfusate did not differ significantly between GH‐treated and control ovaries, GH stimulated estradiol production by the perfused rabbit ovaries. Rabbit ovary membranes exhibited high affinity binding sites of hGH (Kd = 6.1 × 10−9M).CONCLUSION: GH acts on the rabbit ovary to stimulate the follicle growth, oocyte maturation, and ovarian estradiol production by interacting with the specific receptors located in ovarian plasma membranes.