bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward Regulation of Gonadal Function by a Synthetic Hybrid Molecule Composed of Gonadotropin and Fc Fragment of Immunoglobulin G
Authors: JOHNSON G.A. , WILKEN C. , VAN KIRK E.A. , BELDEN E.L. , MURDOCH W.J.
Published: May 2013

ABSTRACT: A conjugate of human chorionic gonadotropin (HCG) and Fc fragment of immunoglobulin G was prepared by covalent cross‐linking using the heterobifunctional reagent, N‐succini‐midyl 3‐(2‐pyridyldithio) propionate. Mouse Leydig tumor cells expressing receptors for luteinizing hormone were specifically lysed in vitro as a consequence of complement fixation via the Fc component of the hybrid molecule. Furthermore, administration of HCG‐Fc to rams caused an acute depression in circulatory testosterone. This novel concept of targeted inhibition of gonadal function could prove to have future applications in control of reproductive processes.
Maternal‐Fetal Interactions on the Regulation of the Autoimmune Response
Authors: YRANZO‐VOLONTÉ NORA , RIERA CLELIA M.
Published: May 2013

ABSTRACT: Adult female rats were immunized with 5 mg or 25 mg of modified rat male accessory glands (MRAG) incorporated to complete Freund's adjuvant (CFA) before, during, and after pregnancy. The mothers and litters were exchanged between the experimental and normal groups. The offspring were brought up to 20 days of age and immunized with 5 mg of MRAG‐CFA and 5 mg of human serum albumin (HSA)‐CFA. Anti‐MRAG antibodies were detected in the offspring brought up by the immunized mothers and the titers were similar to those of the foster mothers whereas in the offspring of the experimental group fostered by normal mothers antibodies to MRAG were not detected. The DTH performed in the offspring 13 days after the immunization was significantly diminished in male and female offspring from the 5 mg and 25 mg experimental group fostered by normal mothers (P<0.0005 for all groups). Similar results were found when the offspring from normal mothers were suckled by mothers immunized with MRAG‐CFA.

To assess whether MRAG or HSA administered to female rats reached the offspring via the placenta or the milk, female rats were immunized with 3 mg of 125I‐MRAG‐CFA or with 3 mg of 125I‐HSA‐CFA. When radioactivity was measured in neonates (n=ll) that were suckled by the 125I‐MRAG‐CFA immunized mothers, the specific activity was 116 in stomach (0.4 μg of MRAG) and 940 in the total organs (3.8 μg of MRAG). In the litters that were killed before suckling (n= 18) had started, the radioactivity was not observed in stomach and was lower in the total organs. The radioactivity found in the offspring of 125I‐HSA‐CFA immunized mothers was similar for both the suckling and the non‐suckling pups. We can conclude that there is an immunoregulation of the immune response to self‐antigens through the placenta and the milk.
Effect of Human Seminal Plasma on the Lytic Activity of Natural Killer Cells and Presumptive Identification of Participant Macromolecules
Authors: ABLIN RICHARD J. , BARTKUS JOHN M. , POLGÁR JANOS
Published: May 2013

ABSTRACT: Using the lytic activity of natural killer (NK) cells as an in vitro parameter, the immunoregulatory properties of human seminal plasma (SeP1) and participant macromolecules have been investigated. Significant (P < 0.05) suppression of NK cell activity by SeP1 and chromatographically separable fractions was demonstrated in association with high and low molecular weight (Mr) macromolecules. SePl suppression was retained after heating to 56°C for 30 min, and appeared to function at the level of the effector, rather than target cell. Physicochemical characterization of high and low Mr fractions provided presumptive identification of the participation of transglutaminase and prostaglandins as the principal molecules contributory to SeP1 immunosuppression.
Reduction of lnterleukin‐2‐Receptor Expression on Retroplacental Blood Lymphocytes in Human Pregnancy
Authors: YOSHIDA MASUMI , KANZAKI HIDEHARU , KARIYA MASATOSHI , EMI NOBUYUKI , IMAI KIMITOSHI , OKAMOTO NORIHIKO , UCHIDA ATSUSHI , KASAKURA SHINPEI , MORI TAKAHIDE
Published: May 2013

ABSTRACT: Retroplacental blood lymphocytes (RPL) in human pregnancy were studied for proliferative response induced by recombinant interleukin‐2 (rIL‐2) and anti‐Tac positive cells before and after PHA stimulation for 24 hr and compared with peripheral blood lymphocytes (PBL) of the same donor. Proliferation of RPL induced by IL‐2 was significantly lower than that of PBL in all of six cases. In addition, flow cytometry analysis of IL‐2 receptors (IL‐2R) revealed that IL‐2R expression of RPL after stimulation with PHA for 24 hr was significantly less than that of PBL in three of four cases and that RPL showed significantly fewer IL‐2R than PBL even at resting state in one case. These results suggest that RPL seem likely to be composed of reduced numbers of lymphocytes bearing IL‐2R of non‐Tac protein and to have impaired capacity for the acquisition of high‐affinity receptors for IL‐2.
Detection of Early Pregnancy Factor‐Like Activity in Human Amniotic Fluid
Authors: ZHEN‐QUN ZHENG , ZHIHAI QIN , AIYING MA , CHANGXIN QIAO , HOUNG WANG
Published: May 2013

ABSTRACT: Early pregnancy factor (EPF), an immunosuppressive substance, appears in mammalian maternal serum at a very early stage after fertilization. To investigate the normal distribution of EPF in the human body, the rosette inhibition test has been used to detect EPF in human amniotic fluid. The mean value of rosette inhibition titer (RIT) was significantly higher (5.93 × 0.43 SE) in 52 amniotic fluid samples (16–30 weeks' gestation) than in 23 nonpregnant sera (3.54 × 0.11), indicating that something in amniotic fluid inhibits rosette formation. This inhibitory factor is recognized as EPF or EPF‐like substance for its activity significantly correlated with that of EPF in serum from the same donor (r = 0.756: P<10−6). The immunological significance of the EPF‐like substance in amniotic fluid may be important to the survival of semiallogeneic conceptus.
Paternal Mononuclear Cell Immunization Therapy for Repeated Miscarriage: Predictive Variables for Pregnancy Success
Authors: COWCHOCK F. SUSAN , SMITH J. BRUCE , DAVID SAMI , SCHER JONATHAN , BATZER FRANCES , CORSON STEPHEN
Published: May 2013

ABSTRACT: Pregnancy outcomes for 125 women with unexplained recurrent abortion conceiving after immunologic testing for possible paternal leukocyte immunization were analyzed. Pregnancy success was related to the number of previous miscarriages (relative risk 0.36 for each additional miscarriage after 3), a history of a late pregnancy loss (relative risk 0.18), any other relevant treated or untreatable diagnosis (relative risk 0.27), immunization with paternal mononuclear cells (relative risk 5.6), and time in weeks from test date to LMP of the next pregnancy (relative risk 0.93 for each additional week). The significant difference in pregnancy outcomes between women given a single immunization and nonimmunized women reflected a larger difference between those in each group conceiving within 12 weeks of initiating tests for inclusion in the treatment program. The latter observation suggests that any effect from a single immunization in prevention of recurrent miscarriage is of relatively short duration.
Active Immunization Against LHRH: I. Effects of Conjugation Site and Dose
Authors: LADD A. , TSONG Y‐Y. , LOK J. , THAU R.B.
Published: May 2013

ABSTRACT: Active immunization against LHRH is a promising method of contraception for men. In order to be acceptable, sufficient amounts of anti‐LHRH antibodies must be induced rapidly after vaccination. In previously reported animal studies, we found that it took considerable time (up to 5 months) to obtain antibody titers (AT) that were sufficiently high for complete suppression of spermatogenesis. The possibility of accelerating the immune response to LHRH by increasing the dose of immunogen was investigated in the male rat. Six doses of LHRH conjugated to tetanus toxoid (TT) in the 10 position (LHRH10‐TT), ranging from 2.5 to 612 μg, and three doses of LHRH1‐TT (50 to 612 μg) were tested. The magnitude of the immune response did not depend on the dose of the antigen, provided a threshold dose had been surpassed. Antigenicity of LHRH conjugated to TT at either the 1‐, 6‐, or 10‐position was compared in rats and rabbits. In both species LHRH1‐TT induced sufficient antibody concentrations to suppress pituitary gonadotropins (LH and FSH) and, subsequently, serum testosterone (T) levels faster than either the 6‐ or 10‐conjugates. Only materials permitted for use in humans were utilized in these experiments. Conclusion: Active immunization against LHRH conjugated to TT at the 1‐position has potential as a fast, convenient method of male contraception.
Delineation Between T and B Suppressive Molecules From Human Seminal Plasma: II. Spermine is the Major Suppressor of T‐Lymphocytes in Vitro
Authors: QUAN CANH P. , ROUX CHRISTOPHE , PILLOT JACQUES , BOUVET JEAN‐PIERRE
Published: May 2013

ABSTRACT: The nature of the human semen T‐sup‐pressor was investigated in vitro on human lymphocyte proliferations induced by phytohemagglutinin (PHA) or by alloantigens. Purification by ion‐exchange chromatography, followed by butanol extraction, showed this factor to be present only in the polyamine‐containing fractions. The purified product, obtained by preparative thin‐layer electrophoresis, contained almost exclusively spermine and exhibited the same suppressive activity as this polyamine. Human T‐lymphocyte suppression occurred in the presence of fetal calf serum, but it did not occur in a serum‐free medium. No suppression was observed after preincubation of the fetal calf serum with hydroxylamine, a spermine oxidase inhibitor, whereas a nondialyzable fraction, from normal human serum, decreased the suppression. The semen factor did not act by direct cytotoxicity, as there was no effect of preincubation and suppression could be induced only within the first 6 hr of mitogen activation. These data demonstrate that the in vitro T‐suppressive activity of semen can be assigned mainly to spermine and show that in vivo this suppression must require locally the presence of a spermine oxidase or related enzyme.
Nonspecific Immunopotentiators and Pregnancy Loss: Complete Freund Adjuvant Reverses High Fetal Resorption Rate in CBA × DBA/2 Mouse Combination
Authors: TODER V. , STRASSBURGER D. , IRLIN Y. , CARP H. , PECHT M. , TRAININ N.
Published: May 2013

ABSTRACT: CBA/J female mice mated with DBA/ 2J males show a high incidence of fetal resorptions. This paper presents data demonstrating that nonspecific immunopotentiation by complete Freund adjuvant (CFA) reversed pregnancy loss in CBA/J mothers. Immunization of more than 70 CBA/J females mated with DBA/2J males with CFA reduced the incidence of fetal resorption from 27.3 ± 1.9 to 7.9 ± 1.5%. The injection of Thymus Humoral Factor known to be a potent T cell stimulator did not reduce the number of fetal resportions. The route of CFA distribution was found to be important—only foot pad injections were effective in fetal protection, whereas i.p. treatment did not reduce fetal resorptions. Fetal protection could be transferred by splenocytes of CFA‐injected CBA/J mothers (9.6 ± 5.0% fetal resorptions). Sera from treated CBA/J mice could not cause such an effect (17.6 ± 4.6 vs. 21.3 ± 6.1 in control animals). Thus, stimulation of the maternal immune system by nonspecific immunopotentiators can improve reproductive performance of this mouse combination which has an increased rate of pregnancy loss. Possible mechanisms of this fetal protection are discussed.
Epidemiology of Recurrent Spontaneous Abortion
Authors: COULAM CAROLYN B.
Published: May 2013

ABSTRACT: With recent scientific advances leading to better understanding of the immunobiology of recurrent spontaneous abortion (RSA), interest has now focused upon the epidemiology of RSA. A cohort of 214 couples with a history of two or more consecutive abortions were studied for the prevalence of etiologic factors and association with other reproductive failures. The prevalence of causes of RSA in this cohort was compared with etiologic factors among 179 couples with a history of three or more consecutive abortions. The obstetrical histories of 214 women with RSA were analyzed for the total number of pregnancies, live births, stillbirths, spontaneous abortions, ectopic pregnancies, and hydatidiform moles. These numbers were compared with the expected frequency of each in the general population. The prevalence of etiologies among 214 with RSA were as follows: chromosomal—6%, anatomic—1%, hormonal—5%, immunologic—65%, and unexplained—23%. No differences in the prevalence of etiologic factors exist when couples with a history of two or more abortions are compared with three or more abortions. When the number of ectopic pregnancies, molar pregnancies, and stillbirths among 214 women with RSA were compared with the expected numbers, the odds ratios were 2.2 for ectopic pregnancies, 6.0 for molar pregnancies, and 2.3 for stillbirths. These data indicate that no difference in the prevalence of etiologies of RSA exist when couples with two or more abortions are compared with three or more and a comorbidity between RSA and other types of reproductive failure exists.
Autoantibodies and Pregnancy Wastage
Authors: COWCHOCK SUSAN
Published: May 2013

ABSTRACT: The established association between a relatively specific group of autoantibodies binding negatively charged phospholipids and poor pregnancy outcome has advanced treatment options for women with this diagnosis. Evidence for an association between systemic autoimmune disorders and otherwise unexplained obstetric complications, in the absence of a documented antiphospholipid antibody(s), is reviewed. The existence of autoantibodies with other specificities that could be related to fetal wastage has been suggested by associations between poor obstetric histories and nonspecific serologic abnormalities observed in women with no clinical signs of an autoimmune disorder. Because signs and symptoms of vasospasm such as Raynaud's phenomenon or placental infarction have been observed in women with a history of unexplained fetal demise, a search for autoantibodies recognizing antigens common to trophoblastic and vascular cell surfaces is suggested.
Inhibition of Antigen‐ and Mitogen‐Induced Activation of Mouse Splenocytes by Uterine Secretions From Pregnant and Progesterone‐Treated Ewes
Authors: STEPHENSON DAVID C. , HANSEN PETER J. , ISAAK DALE D.
Published: May 2013

ABSTRACT: Pregnant and progesterone‐treated, ovariectomized ewes accumulate secretory products in the uterus that are immunosuppressive in mitogen‐stimulated and mixed lymphocyte sheep cell cultures. In this study, uterine secretions from pregnant (Preg‐UTM) and progesterone‐treated, ovariectomized (P‐UTM) ewes were equally effective in suppressing 3H‐Tdr incorporation in mouse spleen cells stimulated with PHA. P‐UTM inhibited PHA‐stim‐ulated, purified T‐cells and separated L3T4+ and Lyt2+ T‐cell subpopulations more than Preg‐UTM, however. Both fluids were slightly inhibitory to conA‐stimulated mouse spleen cells, enriched T‐cells, and Lyt2+ T‐cells but neither inhibited L3T4+ T‐cells. For LPS‐stimulated cells, P‐UTM caused more suppression than Preg‐UTM of enriched B‐cells; however, suppression was similar for the two fluids on unseparated splenic cells. In antigen‐stimulated mouse spleen cell cultures, both fluids inhibited antibody‐forming cell responses to sheep erythrocytes, a thymus‐dependent antigen, but neither suppressed antibody‐forming cell responses to TNP‐Ficoll, a thymus‐independent antigen. These data indicate that uterine secretions in the ewe produced under the influence of progesterone or pregnancy contain immunoregulatory molecule(s) which modulate the activity of both homologous sheep and unrelated mouse lymphocytes. These studies establish the mouse as a useful in vivo model for studying the biological actions of these molecules.
Epstein‐Barr Virus Activating Principle in Husbands' Semen of Cervical Cancer Patients
Authors: IDA KENJI , TOKUDA HARUKUNI , KANAOKA TOSHIO , KANZAKI HIDEHARU , NODA YOICHI , YOSHIDA OSAMU , ITO YOHEI , MORI TAKAHIDE
Published: May 2013

ABSTRACT: A short‐term in vitro assay for detecting tumor promotor activity has been cultivated utilizing the induction of Epstein‐Barr virus early antigen (EBV‐EA) in EBV genome‐carrying human lymphoblastoid cell line (Raji cell) system. By using this system, we found that some of human semen samples possessed a marked capacity to induce EBV‐EA, suggesting possible tumor promotor activity of semen. In the present study, 60 semen samples obtained from husbands of cervical cancer patients and 90 control samples were incubated with Raji cells for 48 h, and EBV‐EA‐expressing cells detected by indirect immunofluorescence were counted. The percentages of EBV‐EA‐positive cells treated with semen of cervical cancer patients' husbands (8.17±5.43%) were significantly higher than those of controls (5.23 ± 5.91%). Since most of EBV‐EA expressing effect on Raji cells show overlapping with tumor promotor activities, our present results implies the circumstantial association of seminal EBV‐EA inducing activity with occurrence of human cervical cancer.
Treatment of Recurrent Aborters by Immunization With Paternal Cells—Controlled Trial
Authors: CAUCHI M.N. , LIM D. , YOUNG D.E. , KLOSS M. , PEPPERELL R.J.
Published: May 2013

ABSTRACT: A paired sequential trial was undertaken to establish whether paternal mononuclear cells improved the prognosis in couples with recurrent abortions. For this purpose, 107‐108 cells obtained from the blood of partners were injected intravenously, subcutaneously, and intra‐dermally into women who had had three or more consecutive miscarriages with the same partner. Control women were given normal saline, injected in the same manner. The result of the sequential analysis showed that there was no significant beneficial effect of the cells compared to control. The overall success rate was 70% (32/46 couples). The success rate in patients given cells was 62% (13/21), while in those given saline it was 76% (19/25). While the overall success rate in this study compares with a number of other studies, we find an equally high success rate with non‐immunized patients. We conclude that the value of immunization for the prevention of recurrent miscarriage has not been established.
HLA Antigen‐Sharing in Couples With Repeated Spontaneous Abortions and the Birthweight of Babies in Successful Pregnancies
Authors: REZNIKOFF‐ETIEVANT M.F. , BONNEAU J.C. , ALCALAY D. , CAVELIER B. , TOURÉ C. , LOBET R. , NETTER A.
Published: May 2013

ABSTRACT: Previously, several groups reported an increase in HLA antigen‐sharing in couples suffering from unexplained repeated spontaneous abortions. It was felt necessary to find out if HLA sharing could have any effect on children born after a successful pregnancy. The birthweight figures of children of 76 couples with repeated spontaneous abortions were analyzed. The results show a significantly lower birthweight in babies born from those couples, presenting a high incidence of HLA antigen‐sharing, particularly concerning class II antigens.
Occurrence of Other Reproductive Failures Among Women With Recurrent Spontaneous Abortion
Authors: COULAM CAROLYN B. , WAGENKNECHT DAWN , MCINTYRE JOHN A. , FAULK W. PAGE , ANNEGERS J.F.
Published: May 2013

ABSTRACT: We have previously reported an association between recurrent spontaneous abortion and ectopic pregnancy. We now report that not only ectopic pregnancy, but also other reproductive failures including hydatidiform moles, preterm births, and stillbirths are also associated with recurrent spontaneous abortion. The obstetrical histories of 455 women who had experienced two or more consecutive spontaneous abortions were studied for the occurrence of term births, preterm births, stillbirths, spontaneous abortions, ectopic pregnancies, and hydatidiform moles. The observed frequencies of these reproductive outcomes were compared with the expected frequencies of 920 term births, 80 preterm births, five stillbirths, 150 spontaneous abortions, 14.5 ectopic pregnancies and 0.5 molar pregnancies per 1,000 livebirths. The 455 women had experienced 1,968 pregnancies of which 184 were term births, 30 were preterm births, 16 were stillbirths, 1,669 were spontaneous abortions, 63 were ectopic pregnancies, and six were molar pregnancies. The ratio of observed to expected values was term births 0.1, preterm births 1.6, stillbirths 14.0, spontaneous abortion 6.6, ectopic pregnancy 2.6, and molar pregnancy 7.1. The gravid specific proportions of reproductive outcomes were constant suggesting comorbidity or common cause(s). The commonality that links these types of reproductive failure will provide insight into the mechanisms of reproductive wastage.
The Clinical Potential of Recombinant Human Interleukin 4 and Alfa‐2b Interferon
Authors: TROTTA PAUL P.
Published: May 2013

ABSTRACT: Recombinant human interleukin 4 and alfa‐2b interferon (Intron A) exhibit multiple biological effects on cells of diverse origin. Interleukin 4 can affect the growth, differentiation and functional activity of lymphoid and myelomonocytic cells. Alfa‐2b interferon expresses a broad spectrum of antiviral, immunomodulatory, and antiproliferative activities. These properties suggest a broad clinical application for both cytokines.
Evaluation of a Monoclonal Antibody, BC‐1, Which Identifies an Antigen Expressed on the Surface Membrane of Human Extravillous Trophoblast
Authors: LOKE Y.W. , HSI B.‐L. , BULMER JUDITH N. , GRIVAUX CATHERINE , HAWLEY SASHA , GARDNER LUCY , KING ASHLEY , CARTER N. P.
Published: May 2013

ABSTRACT: This paper describes a new Mab BC‐1 which is directed at a cell surface antigen expressed by extravillous cytotrophoblast and not by villous cytotrophoblast, so it is useful for distinguishing between the two populations. The antigen recognised by BC‐1 is trypsin‐resistant, which allows it to be used for flow cytometric analysis of living trophoblast isolated by enzymic disaggregation. However, BC‐1 is not trophoblast‐specific but cross‐reacts with some other tissues, in particular endothelial cells and peripheral blood monocytes. The nature of this antigen has not been established.
Preliminary Communication: Possible Role of Reactive Nitrogen Intermediates in Leucocyte‐Mediated Sperm Dysfunction
Authors: TOMLINSON M.J. , EAST S.J. , BARRATT C.L.R. , BOLTON A.E. , COOKE I.D.
Published: May 2013

ABSTRACT: This preliminary study was designed to examine whether nitric oxide, a reactive nitrogen intermediate produced by leukocyte metabolism of L‐arginine, could reduce sperm motility. Increasing doses (10−6‐10−4M) of the nitric oxide‐generating drug, sodium nitroprusside (SNP) were added to motile sperm preparations and incubated over 20 hr. Quantitative sperm motility measurements were made using a computer‐assisted motility analyzer in each treated sample and controls over this time period.

The percentage of motile sperm, progressive motility, and concentration of motile cells were all significantly reduced with all doses of SNP. This effect was not observed in preparations treated with oxyhaemoglobin (HbO2). Mean path velocity was unaltered. Sperm viability in SNP treated sperm did not differ significantly from that of control sperm over the same time period.

We conclude that further experiments are required to determine whether the production of nitric oxide/reactive nitrogen intermediates in vivo by activated leukocytes could be a contributory factor in the development of immunologic infertility.
Microvascular Perturbations in Human Allografts: Analogies in Preeclamptic Placentae
Authors: LABARRERE CARLOS A. , FAULK W. PAGE
Published: May 2013

ABSTRACT: The thromboresistance of endothelium is maintained as long as natural anticoagulant pathways are functionally present on endothelial plasma membranes. The principal anticoagulant pathways in human hearts and kidneys are thrombomodulin (TM) and heparan sulfate proteoglycan‐antithrombin III (HSPG‐ATIII). The downregulation of TM or the loss of ATIII is associated with fibrin deposition. This sequence of events occurs when stable allografts of hearts or kidneys become unstable or rejected. Human placentae do not contain the HSPG‐ATIII natural anticoagulant pathway, but the TM system is uniformly represented on endothelium of normal chorionic villi. However, many villi in placentae from preeclamptic pregnancies contain thrombomodulin‐negative endothelium, and these vessels contain fibrin thrombi. These thrombi compromise blood flow through the placental microcirculation and are associated with ischemic changes either with or without the presence of cellular infiltrates.
Angiogenesis in the Uterus: Potential Regulation and Relation to Tumor Angiogenesis
Authors: TORRY RONALD J. , RONGISH BRENDA J.
Published: May 2013

ABSTRACT: Except under certain pathological conditions such as wound healing and solid tumor growth, angiogenesis is a relatively rare event in the adult. One exception, however, is the angiogenesis that occurs during the cyclical changes in the female reproductive tract. Many factors, chemical as well as mechanical, have been shown to be capable of promoting or inhibiting angiogenesis in vivo and in vitro. However, despite intense research efforts, the mechanisms involved in the regulation of angiogenesis in vivo are not fully understood. In this article we briefly review the basic steps involved in angiogenesis and present examples of factors and conditions that may serve as potential regulators of angiogenesis in the nonpregnant uterus. Finally, we discuss some of the architectural, anatomical, and physiological differences between the microcirculatory beds established during normal, self‐limited vessel growth and that associated with the uncontrolled, pathological vascular growth that accompanies tumor growth and metastasis.
Cytokines Considered Critical in Pregnancy
Authors: HILL JOSEPH A.
Published: May 2013

ABSTRACT: Cytokines considered critical in pregnancy include interleukin‐1 (IL‐1), tumor necrosis factor alpha (TNF‐α), interferon gamma (IFN‐γ, granulocyte‐macrophage colony stimulating factor (GM‐CSF), and colony stimulating factor (CSF‐1). They affect blastocyst attachment, trophoblast outgrowth, implantation, proliferation of cells isolated from placentas, proliferation of trophoblast cell lines, and percent fetal resorption in spontaneously aborting mice. Cytokines also affect chorionic gonadotrophin and progesterone production by trophoblast. Cytokine effects vary with concentration, route of administration, and timing of secretion.
Glucocorticoid Therapy for Rheumatic Diseases: Maternal, Fetal, and Breast‐Feeding Considerations
Authors: RAYBURN WILLIAM F.
Published: May 2013

ABSTRACT: Glucocorticoids form the mainstay of therapy for many rheumatic diseases, especially systemic lupus erythematosus (SLE). Prednisone is the drug of choice, because it has been well described during pregnancy and is the primary drug for maintenance therapy or to induce a remission. Principles for prescribing glucocorticoids would apply during pregnancy, recognizing that many effects of rheumatic disease and long‐term therapy are similar to physiologic changes of pregnancy. Particular attention should be placed on screening for pregnancy‐induced glucose intolerance, hypertension, and delayed fetal growth. Although animal studies suggest an increased risk of oral clefts associated with glucocorticoids, several human studies have failed to demonstrate teratogenic or toxic effects. Nevertheless, rare cases of transient fetal adrenal suppression have been reported, so all infants should be monitored in the nursery. Breastfeeding is safe, with clinically insignificant amounts of the drug being concentrated in breast milk.
The Use of Low Dose Aspirin in Pregnancy
Authors: SCHIFF EYAL , MASHIACH SHLOMO
Published: May 2013

ABSTRACT: Pregnancy‐induced hypertension (PIH) in general and preeclampsia in particular are major causes of maternal and perinatal morbidity. Data from our studies and from a number of prospective controlled trials have suggested that aspirin in doses of 60–150 md/day during the second and third trimester reduces the risk of PIH and improves maternal and neonatal outcomes. The number of patients enrolled in these studies is relatively small. However, metaanalysis of existing trials suggests that low dose aspirin reduces the risk of PIH and severe low birth weight. Although no maternal or neonatal adverse effects associated with aspirin were observed, the use of aspirin in the third trimester has been reported to cause hemostatic abnormalities in both mother and neonate. Other complications associated with prostaglandin synthetase inhibitors include premature closure of the ductus and neonatal primary pulmonary hypertension. The use of aspirin in the first trimester is not associated with increased risk of structural malformations. On the basis of these findings and pending the results of ongoing large‐scale randomized multicenter trials, we suggest that daily low dose aspirin (1 to 2 mg/kg/day) be recommended only for select women at high risk for developing PIH and its associated complications.
The Effect of Cyclophosphamide Pulses on Fertility in Patients With Lupus Nephritis
Authors: LANGEVITZ PNINA , KLEIN LIORA , PRAS MORDECHAI , MANY AMIRA
Published: May 2013

ABSTRACT: The effect of cyclophosphamide pulse therapy given in relatively small doses (10 mg/kg per pulse) in 17 females with lupus nephritis has been studied. Four females developed menopause; in one transient amenorrhea occurred. No changes in menstrual cycle were noted in the other 11 females, four of whom subsequently delivered five normal babies. These data suggest the relative safety of small doses of cyclophosphamide pulse therapy on gonadal function in females under age 40 years.
Overview of Lupus Pregnancies
Authors: LOCKSHIN MICHAEL D.
Published: May 2013

ABSTRACT: Pregnancy in patients with systemic lupus erythematosus (SLE) requires consideration of 5 major issues: (1) What is the risk to the mother? (2) What is the risk to the fetus? (3) What is the effect and treatment of antiphospholipid antibody? (4) What is the risk of neonatal lupus? (5) Stability of the family unit, particularly in the events of maternal disability or death, should be discussed by all parties when a pregnancy is planned. Consistency of measurement criteria, standardized treatment protocols, and long‐term follow‐ups are needed in the future.
The Hopkins Lupus Pregnancy Center: 1987–1991 Update
Authors: PETRI MICHELLE , HOWARD DENISE , REPKE JOHN , GOLDMAN DANIEL W.
Published: May 2013

ABSTRACT: The course of pregnancy in patients with systemic lupus erythematosus is not known. The Hopkins Lupus Pregnancy Center has followed 64 patients (74 pregnancies) prospectively since 1987. Patients are seen monthly and clinical and pregnancy‐related data collected, with particular emphasis on the occurrence of lupus flare. Flare rate during pregnancy was 1.63 per person‐year, compared to 0.64‐0.65 after delivery or in non‐pregnant patients. Flare did not influence pregnancy outcome. Low serum C3 or C4 and high anticardiolipin antibody predicted pregnancy loss, and prednisone dose, aspirin use, diastolic second trimester blood pressure, C3 at first visit, and race predicted preterm birth. Maternal flare and preterm birth are important risks in lupus pregnancy. The latter can be predicted from maternal pregnancy data.
Previous Pregnancy Outcome Is an Important Determinant of Subsequent Pregnancy Outcome in Women With Systemic Lupus Erythematosus
Authors: RAMSEY‐GOLDMAN ROSALIND , KUTZER JOAN E. , KULLER LEWIS H. , GUZICK DAVID , CARPENTER A. BETTS , MEDSGER THOMAS A.
Published: May 2013

ABSTRACT: Women with systemic lupus erythematosus (SLE) have increased adverse pregnancy outcomes. The reasons for these problems include maternal disease, clinical or serologic activity, medication use, and residual organ impairment from prior disease flares. In retrospective studies, pregnancy data are often treated cross‐sectionally, with births rather than mothers as the unit of analysis. Multiple pregnancies from the same mother may be highly correlated with each other.

In an unmatched retrospective study, the first two pregnancy outcomes in lupus patients with anticardiolipin antibody (anti‐CL IgG or IgM isotype) (cases N = 47) and without anticardiolipin antibody (controls, N = 125) were assessed according to birth order. A good outcome was defined as a full‐term (> 38 weeks) live birth without neonatal complications. All other pregnancy outcomes were considered adverse outcomes. Therapeutic abortions and ectopic or molar pregnancies were excluded. Both cases and controls with an adverse outcome in their first pregnancy had at least a 50% chance of another adverse outcome in their second pregnancy. Cases with a late miscarriage (fetal loss at 14 to 20 weeks' gestation) in their first pregnancy had the highest risk, 80%, of an adverse outcome in their second pregnancy. Both previous pregnancy loss and anti‐CL antibody status should be considered in the analysis of pregnancy outcomes in women with SLE.
The Effect of Systemic Lupus Erythematosus on Pregnancy and Pregnancy Outcome
Authors: HAYSLETT JOHN P.
Published: May 2013

ABSTRACT: This review provides an analysis of reports published since 1980 on the effect of systemic lupus erythematosus (SLE) on pregnancy and pregnancy outcome. The question whether pregnancy increases clinical flares and the severity of flares in patients with SLE during pregnancy has not been resolved because of difficulty in defining exacerbations of SLE and of preeclampsia. An analysis of major detailed reports indicates that maternal complications are reduced in patients who are in clinical remission prior to the onset of pregnancy compared with women with persistent disease activity. Complications are observed in 30%–50% of patients with inactive disease at onset of gestation. After exclusion of spontaneous abortions during the first trimester, fetal survival was 85%–90% in most reported case series. The best outcomes were reported in patients with inactive disease at onset of pregnancy. It seems likely that some maternal complications and fetal wastage in this population are related to anticardiolipin antibodies.
Pregnancy Course and Complications in Patients with Systemic Lupus Erythematosus
Authors: RUBBERT A. , PIRNER K. , WILDT L. , KALDEN J.R. , MANGER B.
Published: May 2013

ABSTRACT: Among 165 patients with systemic lupus erythematosus (SLE), we observed 21 pregnancies in 19 patients since 1987. The mean duration of disease at the time of pregnancy was 4.5 ± 3 years. All but three patients required immunosuppressive treatment before and during pregnancy. The effect of pregnancy on the course of SLE was studied. Severe disease exacerbations were rare and largely confined to patients with renal involvement. Most patients showed elevated titers of dsDNA antibodies during pregnancy but clinical activity of disease was usually mild. Complement C3 decrease appeared to be the most sensitive marker for pregnancy‐related complications. The detection of antibodies to phospholipids was frequent during pregnancy in contrast to a low prevalence before and after pregnancy. Their presence could be associated with intrauterine growth retardation. Preterm delivery before the 37th week of pregnancy had to be performed in the majority of patients. None of the patients experienced abortion although three patients had to be delivered in the 29th week of pregnancy because of increasing symptoms of preeclampsia. Two of these children died and the third child suffered from intracranial hemorrhage in the early postpartum period. Our data demonstrate that successful pregnancy outcome was related to a gestational age of more than 32 weeks, making careful monitoring and appropriate therapeutic management necessary.
Antiphospholipid Antibodies: Method of Detection
Authors: HARRIS E. N. , PIERANGELI S.
Published: May 2013

ABSTRACT: Antiphospholipid antibody, measured by enzyme‐linked immunosorbent assy (ELISA) or by radioimmunoassay, and the lupus anticoagulant, represent similar but different tests. The ELISA is now well standardized. It is at least partly, and possibly primarily, dependent on the presence of a cofactor, β2‐glycoprotein I. Tests for both antiphospholipid antibody by ELISA and lupus anticoagulant should be performed in patients suspected of having this syndrome.
Antiphospholipid Antibodies: Proposed Mechanisms of Action
Authors: TRIPLETT DOUGLAS A.
Published: May 2013

ABSTRACT: Antiphospholipid antibodies (APA) are a family of immunoglobulins that react with anionic phospholipids, or anionic phospholipids‐protein complexes. Recent evidence would support the latter definition. Lupus anticoagulants (LA) inhibit in vitro phospholipid dependent coagulation tests [e.g., activated partial thromboplastin time (APTT), prothrombin time (PT), and dilute Russell viper venom time (dRVVT)]. This inhibition appears to be specific for reagent phospholipids. The addition of freeze‐thawed platelets or activated platelets will result in correction of the LA‐induced abnormality. Anticardiolipin antibodies (ACA) are related to LA but appear to be distinct. ACA are detected by solid phase assays (ELISA, RIA) and require a plasma cofactor: β2 Glycoprotein‐I (β2 GPI). ACA and LA activities can be separated in individual patient plasmas by affinity chromatography. In some instances they are of differing isotypes. Preliminary evaluation of β2 GPI in coagulation assays suggests it may function as a cofactor for LA activity. Recent work also suggests human prothrombin may represent a necessary cofactor for in vitro LA activity. Paradoxically, patients with LA/ACA may sustain thromboembolic events involving both venous and arterial sites. The prothrombotic properties of LA/ ACA have not been satisfactorily characterized. A number of proposals have been reported, including inhibition of prostacyclin (PGI2) generation by endothelial cells, decreased activity of the protein C system, impaired fibrinolysis, and inhibition of β2 GPI. Among these various hypotheses, down regulation of the protein C system appears most plausible. Also, LA/ACA may interfere with the phospholipase A2‐phospholipid substrate complex involved in the generation of arachidonic acid from membrane phospholipids.
Induction of Experimental Primary and Secondary Antiphospholipid Syndromes in Naive Mice
Authors: SHOENFELD YEHUDA
Published: May 2013

ABSTRACT: In the current series of experimental studies we show that anticardiolipin antibodies (ACA) are pathogenic: Infusion of serum ACA to the tail vein of naive mice induces experimental antiphospholipid syndrome (APLS) characterized by thrombocytopenia, prolonged aPTT, and recurrent fetal resorptions. Similar experimental APLS is induced by active immunization with serum as well as with natural human monoclonal ACA. APLS is also associated with low fecundity rate. The experimental APLS models were employed to demonstrate the efficacy of aspirin, low molecular heparin, and interleukin‐3 preventing recurrent fetal loss. In another experiment, immunization with human monoclonal anti‐DNA antibody was followed by the induction of APLS secondary to experimental systemic lupus erythematosus (SLE). In all studies, IgGs were found to be more pathogenic than IgMs ACA. These studies confirm the autoimmune nature of APLS.
The Effect of Pregnancy on Renal Function in Amyloidosis of Familial Mediterranean Fever
Authors: CABILI SHALTIEL , LIVNEH AVI , ZEMER DEBORAH , RABINOVITCH OSVALDO , PRAS MORDECHAI
Published: May 2013

ABSTRACT: The effect of pregnancy on kidney function was studied in 29 pregnancies of 17 patients with familial Mediterranean fever (FMF) and amyloidosis. Pregnancy associated deterioration of renal function occurred in seven patients who had advanced renal disease at conception, marked by serum creatinine ≥ 1.5 mg/dl or urine protein ≥ 2 g/24 h. This finding suggests that the severity of renal disease at conception may predict the fate of kidney function during pregnancy and puerperium.
Diffuse Infiltrative Lymphocytosis Syndrome in Children and Adults Infected With HIV‐1: A Model of Rheumatic Illness Caused by Acquired Viral Infection
Authors: ITESCU SILVIU
Published: May 2013

ABSTRACT: Certain maternal/infant pairs, as well as other high‐risk adults, develop a host‐response HIV‐1 infection characterized by circulating and tissue infiltrative CD8 T‐cell lymphocytosis, termed Diffuse Infiltrative Lymphocytosis Syndrome (DILS). DILS primarily occurs in the salivary glands, lungs, renal interstitium, and gastrointestinal tract. DILS differs from Sjogren's syndrome in the degree of salivary gland enlargement, high frequency of extra‐glandular manifestations, paucity of autoantibodies, and distinct immunogenetic associations. Salivary gland B‐cell lymphoma is a complication common to both conditions. The circulating CD8 T cells in DILS have a memory phenotype. Egress into target tissues involves adhesion molecule receptor‐ligand interactions, apparently in response to the local presence of HIV‐1. Immunogenetic predisposition involves interaction between both MHC classes I and II loci. This disease appears to reflect a specific host response that leads to persistence of monocyte‐tropic, rather than T‐cell‐tropic, HIV‐1 strains, in an analogous fashion to Visna Maedi virus disease in sheep. The development of DILS in children appears to be regulated in a dominant fashion by maternally or paternally inherited MHC class II alleles in response to transplacentally or perinatally acquired maternal HIV‐1 strains.
Antigenic Stimulation and Blocking of Pregnancy in Mice by an Anti‐Idiotypic Antibody to Progesterone
Authors: KHOLE VRINDA , HEGDE UMASHASHI C.
Published: May 2013

PROBLEM: The present study was carried out to see if the anti‐idiotypic (anti‐Id) antibody (Ab2) to progesterone could mimic the immunogenicity of the steroid hormone by giving rise to antiprogesterone antibodies (Ab3) and whether these antiprogesterone antibodies (Ab3) were biologically active.

METHOD: Twenty virgin female Balb/C mice were actively immunized with the anti‐Id antibody (Ab2). The antiprogesterone antibody (Ab3) titres in the serum were determined and the animals were used for fertility studies. In the passive immunization studies Balb/C female mice were injected i.p. with 100 μg of anti‐Id antibody to see its effect on pregnancy. RESULTS: The actively immunized animals when mated showed 80% reduction in their fertility rate. The duration of infertility (20–121 days) in these animals could be directly correlated with the concentration of antiprogesterone antibody (Ab3). The anti‐Id antibody (Ab2) blocked pregnancy in 80% of the passively immunized mice.

CONCLUSION: The studies show that anti‐Id antibody to progesterone could mimic the immunogenicity of progesterone and give rise to antiprogesterone antibodies (Ab3). The anti‐Id antibody successfully blocked pregnancy in mice both after active and passive immunization.
A Study of Early Pregnancy Factor Activity in the Sera of Patients With Unexplained Spontaneous Abortion
Authors: SHU‐XIN HU , ZHEN‐QUN ZHENG
Published: May 2013

PROBLEM: Seventy‐seven sera samples obtained from 51 patients (6–20 wk gestation) with unexplained spontaneous abortions including 20 threatened abortions (TA), 13 inevitable abortions (IA), and 18 intrauterine fetal growth retardation (IFGR), as well as 9 sera from 9 patients (6–20 wk gestation) with hydatidiform mole (HM), were detected for early pregnancy factor (EPF) by rosette inhibition assay. Rosette inhibition titer (RIT) was used to express EPF activity.

RESULTS: The RIT value of EPF was 5.95 ± 0.69(mean ± SD) in the TA group; 4.06 ± 0.93 in the IA group; 3.50 ± 0.71 in the IFGR group, and 4.00 ± 0.71 in the HM group. Except for the TA group, in which the mean RIT was in normal pregnancy range, the RIT in the other three groups was significantly lower (P < 0.01) then that of the normal pregnancy group (5.81 ± 0.68).

CONCLUSIONS: These results suggest that measurement of EPF is a sensitive method for judging survival of the embryo. It may be used to predict the prognosis of the patient with unexplained spontaneous abortion.
Influence of Immunotherapy on Antisperm Antibody Titer in Unexplained Recurrent Aborters
Authors: SUGI TOSHITAKA , MAKINO TSUNEHISA , MARUYAMA TETSUO , NOZAWA SHIRO , IlZUKA RIHACHI
Published: May 2013

PROBLEM: The mechanism of the beneficial effect of immunotherapy for human reproductive wastage remains to be elucidated. Because some women with unexplained recurrent spontaneous abortion are immunized with their partner's lymphocytes, it is important to determine whether such immunization results in elevation or enhancement of immunity to spermatozoa, because antigenic cross‐reactivity between lymphocytes and spermatozoa has been reported.

METHOD: The present study was initiated to evaluate the changes in antisperm antibody titer and lymphocyte subsets after immunotherapy as compared to before immunotherapy. Antisperm antibody detection was performed by SpermCheck Assay, which is based on a modification of the immunobead test. Maternal lymphocyte subsets were analyzed in two‐color flow‐cytometric experiments.

RESULTS: The percentage of antibody‐positive sperm decreased significantly (P = 0.0008) after immunotherapy. The percentage of B(CD19 +) cells (P = 0.0003), cytotoxic T(CD8 + and CD11 b ‐) cells (P = 0.02) and the Th/Ts ratio (P = 0.005) decreased significantly, while suppressor T(CD8 + and CD 11b +) cells increased significantly (P = 0.0002) after the immunotherapy. This suggests that cell‐mediated immunosuppression was induced by immunotherapy.

CONCLUSION: The data of the present study suggest that antisperm antibodies have potential for use as a marker for a deficiency in maternal genital tract immunosupressor mechanisms and that immunotherapy could be an effective treatment for women with antisperm antibodies who have unexplained recurrent abortions.
Treatment of Recurrent Spontaneous Abortions by Immunization With Paternal Lymphocytes Induces Immunosuppression by Placental Isoferritin
Authors: MOROZ CHAYA , LIVNI ELLA , SEGAL JACOB
Published: May 2013

PROBLEM: The immunological mechanism leading to an effective vaccination of unexplained habitual aborters with paternal lymphocytes is not yet elucidated. Since previous studies revealed that immunosuppression by placental isoferritin (PLF) may play an important role in the down regulation of the immune system during pregnancy, it was of interest to investigate whether alloimmunization activates immunosuppression by PLF.

METHOD: The immunosuppressive effect of PLF or anti‐PLF CM‐H‐9 monoclonal antibody (MAb) was studied by a one‐way mixed lymphocyte reaction (MLR) of alloimmunized women and their husbands.

RESULTS: It was found that vaccination of the women with paternal lymphocytes resulted in in vitro immunosuppression by PLF as well as by CM‐H‐9 MAb, reaching the highest effect after three vaccinations (38 ± 8 and 42 ± 10%, respectively). The increase in PLF immunosuppressive effect was accompanied by the appearance of serum antipaternal human leukocyte antigen cytotoxic antibodies. However, there was no correlation between the degree of suppression and titer of antibodies. The study group was too small to reach a significant correlation between degree of immunosuppression and pregnancy outcome.

CONCLUSION: Although it may be of value to measure the inhibitory effect of PLF in one‐way MLR as an index of immunosuppression, further studies are needed to establish whether it is a relevant predictor of a successful pregnancy.