bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is Immunotherapy for Habitual Aborters an Immunologically Hazardous Procedure for Infants?
Authors: TAKAKUWA KOICHI , GOTO SHIGENORI , HASEGAWA ISAO , UEDA HIROYUKI , MARUHASHI TOSHIHIRO , KAJINO TORU , YOSHIZAWA HIROSHI , KANAZAWA KOJI , TAKEUCHI SHOSHICHI 
Published: May 2013

ABSTRACT: Physical development and tests of immunologic function are reported from the first year of life for 13 infants born to mothers who were habitual aborters and who had undergone subcutaneous vaccination with their husband's lymphocytes. The mean weight of the infants at birth was 2,975 ± 540 g, including one infant who was small for dates. Physical development parameters for the first year were all within normal range.Immunologic studies were performed at ages 0, 1, 3, 6, 9, and 12 months. The studies included the following: (1) serum levels of immunoglobulins and complement components; (2) the number of peripheral blood lymphocytes (PBL) and their subpopulations; and (3) proliferative responses by PBL against unrelated lymphocytes and some mitogens (pokeweed, phytohemagglutinin, and concanavalin A). All were normal when compared with studies of infants of nonimmunized mothers.These observations suggested that subcutaneous vaccination of women with their husband's lymphocytes did not result in any adverse effects on their infants' physical or immunologic development.
New Antibody in Severe Rhesus Incompatible Pregnancies: IgG‐Kappa Antiplacental Alkaline Phosphatase
Authors: BRISSON‐LOUGARRE A , VERGNES H. , GROZDEA J. , ALIE‐DARAM S. , FONTANILLES A.M. , BIERME R. 
Published: May 2013

ABSTRACT: As already found in other various diseases, a macromolecular alkaline phosphatase complex (HMW‐AP) was also found in sera of two severe Rhesus‐incompatible pregnancies complicated by ascitis and fetal hydrops at delivery.This atypical complex was detected and isolated by agarose gel electrophoresis. Immunoelectrophoresis and heat inactivation of this HMW‐AP complex revealed that it consisted of IgG of the kappa type and placental AP isoenzyme. The transitory presence of this immuncomplex is discussed. However, in all women with Rhimmunized complicated pregnancies, significant variations of neutrophil and serum AP activities were observed.A fall in AP activity and the presence of an antiplacental AP antibody in serum of women with complicated Rh immunization should be of value in assessing the prognosis of the disease.
Alteration of Lymphocyte Reactivity in Pregnant Women Treated With the Progesterone Receptor Inhibitor ZK 98734
Authors: SZEKERES‐BARTHO JULIA , SZABO J. , KOVACS L. 
Published: May 2013

ABSTRACT: Thirteen women during the 5th and 6th weeks of gestation were treated with a progesterone receptor blocker (ZK 98734) for pregnancy termination. Five patients received 100 mg/day of the compound, and eight patients received 50 mg/ day for 4 days. Daily blood samples were obtained during the treatment period as well as on days 8 and 15 after the beginning of drug administration, and cytotoxic activity, progesterone sensitivity, and progesterone binding capacity of the lymphocytes were determined. Determination of SP‐1 concentrations monitored the saturation state of trophoblastic progesterone receptors.High and low responders to the progesterone antagonist were identified. Lymphocytes of high responders treated with the 100 mg/day dose demonstrated a rapid increase of cytotoxicity, with a concomitant fall in progesterone sensitivity and progesterone binding capacity. Vaginal bleeding began as early as the 2nd day of treatment, and pregnancy was terminated by the 8th day of the treatment.Low responders receiving 100 mg/day demonstrated similar but attenuated changes. Low responders did not bleed during the first 4 days of treatment, and termination of pregnancy occurred later compared to high responders. Lymphocytes of high responders treated with 50 mg/ day behaved similarly to those obtained from the low responders treated with 100 mg/day, and abortion was not completed before the 25th day after the beginning of the treatment. Lymphocytes function of low responders treated with 50 mg/day did not change significantly, the SP‐1 concentration did not decline, and pregnancies continued. We conclude that a difference in sensitivity to the progesterone receptor blocker explains the selective block at trophoblastic binding sites only and the inability to block those in the lymphocytes. Progesterone receptor blocker apparently discriminates between lymphocytic and trophoblastic binding sites. Lymphocytes progesterone binding sites block correlates better than does trophoblastic receptors block in the prediction of successful interruption of early pregnancies with ZK 98734.
Study on Nonspecific Immunity in Pregnant Women: II. Effect of Hormones on Chemiluminescence Response of Peripheral Blood Phagocytes
Authors: SHIBUYA TAKAHIRO , IZUCHI KUNIO , KUROIWA ATARU , HARADA HIROYUKI , KUMAMOTO ARIHIRO , SHIRAKAWA KOICHI 
Published: May 2013

ABSTRACT: To analyze the mechanisms of increased nonspecific immunity in pregnant women, the effect of various hormones on the phagocytic activity was estimated by a luminol‐dependent chemiluminescence (CL) response during phagocytosing opsonized zymosan. The CL response of whole blood supplemented with exogenous human chorionic gonadotropin (hCG) increased significantly in all the male and female subjects and pregnant women. An approximate two‐ to fourfold increase was observed in comparison with the unsupplemented control in each subject at concentrations ranging from 1 to 1,000 IU/ml after 48 h of incubation (P < 0.05). Progesterone slightly stimulated the CL response in female subjects only, but had no effect on male and pregnant women. Estradiol (E2) did not stimulate the CL response in any subject.The expression of Fc and C3b receptors on the surface of polymorphonuclear leucocytes (PMNL) in pregnant women was also investigated by measuring the immunofluorescence stained with monoclonal antibody to Fc and C3b receptors, respectively. The relative numbers of Fc receptors increased significantly in the third trimester compared to those of female control (P < 0.05). Those of C3b receptor also increased in the second and third trimester (P < 0.005).These results suggested that the nonspecific immunity represented by phagocytic activity in pregnant women increased with both oxidative metabolic responsiveness and the expression of membrane receptors. Besides, the increased phagocytic activity of the maternal host is probably due to the stimulatory effect of both endogenous and exogenous hCG on their peripheral blood phagocytes.
Detection of Sperm Antibodies on Unwashed Spermatozoa With the Immunobead Test: A Comparison of Results With the Routine Method and Seminal Plasma TAT Titers and SCMC Test
Authors: MENKVELD R. , KRUGER T.F. , KOTZE T.J.v.W. , WINDT M‐L. , PRETORIUS E. 
Published: May 2013

ABSTRACT: This study investigated whether the immunobead test (IBT) could, for the purposes of simplicity and saving time, be applied directly on an unwashed semen sample instead of washed spermatozoa. These two methods were performed simultaneously on the semen samples of 15 men with a positive MAR test and 10 men with a negative MAR test. A possible association was found between the unwashed samples, showing positive IB binding (>20%) on the tail and/or head and the seminal plasma TAT titers (P < .00001, Fisher's exact test). In all cases with IB binding of ≥20% on unwashed spermatozoa, positive seminal plasma TAT titers (≥32) and SCMC tests (≥50%) were found.In all cases where the binding of the beads was mainly located on the tailtips of the washed or unwashed spermatozoa, negative seminal plasma TAT titers and SCMC tests were found. Coating of the head and/or upper tail regions in both methods was always associated with high TAT titers and a strong‐positive SCMC test.It is concluded that the IBT for IgA, but not for IgG, can be performed directly on unwashed semen and that the position of IB binding on the spermatozoa is of prognostic importance with regard to the expected outcome of the SCMC test and seminal plasma TAT titers.
The Effect of Peritoneal Macrophage‐Derived Factor(s) on Ovarian Progesterone Secretion and LH Receptors: The Role of Calcium
Authors: CHEN THOMAS T. , LANE TERESA A. , DOODY MICHAEL C. , CAUDLE MICHAEL R. 
Published: May 2013

ABSTRACT: Macrophages and their secretory products, cytokines, play an integral role in many reproductive processes. In this study we examined the effect of conditioned media from cultured human peritoneal macrophages on progesterone production by granulosa cells and the role of calcium in this process.Macrophages were pretreated with various concentrations of a calcium channel blocker (verapamil) or a calcium ionophore (A23187). Macrophage‐conditioned media (MCM) or cell‐free media that contained calcium channel modifiers were added at three dose levels to cultured porcine granulosa cells. Progesterone production and LH receptor content were determined.Macrophage‐conditioned media alone elevated basal progesterone production, but significantly attenuated granulosa cell LH receptor content. These effects were neither potentiated nor suppressed by pretreating macrophages with verapamil. However, production of the LH receptor lowering factor(s) appeared to be suppressed by calcium ionophore.We conclude that (1) one or more factors produced by macrophages have a net stimulatory effect on basal progesterone production and these factor(s) may not be calcium‐dependent and (2) macrophage‐derived secretory products reduce granulosa cell LH receptor content. The production of these factor(s) may be calcium‐dependent.
Immunosuppression by Human Seminal Plasma&—Extracellular Organelles (Prostasomes) Modulate Activity of Phagocytic Cells
Authors: SKIBINSKI G. , KELLY R.W. , HARKISS D. , JAMES K. 
Published: May 2013

PROBLEM: Prostasomes are trilamellar to multilamellar vesicles produced by the acinar cells of the human prostate and are present in appreciable amounts in normal human semen. The aim of this work was to study the effect of prostasomes on human polymorphonuclear cell and monocyte function.METHODS: Functional activity of human neutrophils and monocytes was studied after incubation with prostasomes isolated from normal human seminal plasma. The following functional tests were employed: ability to ingest latex particles and opsonized bacteria (St. aureus) and ability to generate superoxide anion in response to PMA and FMLP. The latter was determined by measuring the super‐oxide‐dismutase inhibitable reduction of ferricytochrome c to ferrocytochrome c at 550 nm. Expression of cell surface markers and interactions of prostasomes with cells were studied by cytofluorimetry.RESULTS: We show that prostasomes bind rapidly to the leukocyte cell membrane followed by internalization of adsorbed material. Interactions of prostasomes with neutrophils and monocytes inhibits their ability to phagocytose latex particles. The ability to ingest opsonized bacteria is, however, not impaired. Our results also show that incubation of leukocytes with prostasomes effectively inhibits superoxide anion generation in response to activation by PMA and FMLP.CONCLUSIONS: Prostasomes may play a complementary role to other immunosuppressive factors contained in the human semen. They may protect sperm cells from deleterious effects of phagocytosing cells, prolong their life, and consequently enhance the chance of conception. At the same time prostasomes may have a permissive effect on sexually transmitted diseases.
Etiological Implication of Autoantibodies to Zona Pellucida in Human Female Infertility
Authors: KAMADA MASAHARU , DAITOH TOSHIFUMI , MORI KAZUMASA , MAEDA NOBUHIKO , HIRANO KOHIKO , IRAHARA MINORU , AONO TOSHIHIRO , MORI TAKAHIDE 
Published: May 2013

PROBLEM: Autoantibodies to zona pellucida (ZP) have been implicated as a cause of infertility in woman by three lines of clinical and laboratory evidence.METHOD: First, positive anti‐zona activities, as assessed by the passive hemagglutination reaction (PHAR) using bovine red blood cells sensitized with porcine zona antigen, were detected in 45 of 1,872 serum samples collected from infertile women, but in only three (two nonpregnant and one pregnant) of 592 serum samples from control subjects. Their incidence in 320 women with unexplained infertility (5.6%) was much higher than that in 1,552 women with infertility of known cause (1.7%, P < 0.01), which was comparable to the incidence observed in 193 age‐matched fertile nonpregnant and pregnant women (1.5%, P < 0.05). None of the serum samples from 292 age‐matched adult men and 100 children of between 5 and 10 years old gave a positive PHAR. Second, follow‐up study for a minimum of 2 years with treatment revealed that no pregnancy occurred in 11 infertile women with a consistently positive PHAR, and only three pregnancies in 19 infertile women with a fluctuating positive PHAR. Third, three of seven serum samples from women who gave a consistently positive PHAR produced strong immunofluorescence reactions on human ZP even after adsorption with porcine and human AB blood cells. Pre‐exposure of human ZP to the sera showing positive immunofluorescence, including that of one patient undergoing an in vitro fertilization program, greatly diminished the number of spermatozoa of normal quality that bound to and penetrated across human ZP.CONCLUSIONS: The observed high incidence of anti‐zona activities and long‐term resistancy to treatment in women with unexplained infertility may be closely correlated with inhibition of sperm‐egg interaction by anti‐zona autoantibodies produced in these women.
NSAIDs: Maternal and Fetal Considerations
Authors: SCHOENFELD ALEX , BAR YACOB , MERLOB PAUL , OVADIA YARDENA 
Published: May 2013

ABSTRACT: Nonsteroidal anti‐inflammatory drugs (NSAIDs) gained popularity in the late 1970s. Inhibition of prostaglandin synthesis with indomethacin has been reported to be effective for prevention of labor and for treatment for symptomatic polyhydramnios. Concern about its possible constrictive effect on the fetal ductus arteriosus has limited its use in pregnancy. Maternal indomethacin therapy has also been associated with reduction in urine production in the fetus and with oligohydramnios.Obstetricians have discouraged pregnant women from taking analgesic doses of aspirin, mainly because of the availability of paracetamol (acetaminophen), which causes less gastric irritation, but also because of fear of maternal and fetal hemorrhage and of possible premature closure of the ductus. These fears largely derive from studies on patients taking large doses and from extrapolation from other NSAIDs. The likelihood that treatment with 60–75 mg/day of aspirin markedly reduces the incidence of preeclampsia and fetal intrauterine growth retardation makes it important to reexamine its use.This review describes the pharmacology and pharmacokinetics of aspirin with particular reference to pregnancy and considers teratogenesis, prolongation of pregnancy and labor, maternal bleeding, fetal and neonatal bleeding, possible effects on the ductus arteriosus and pulmonary circulation, and possible nonspecific effects on intelligence and breast feeding and acute toxicity in the neonate.
Target Antigens of the SSA/Ro and SSB/La System
Authors: BEN‐CHETRIT E. 
Published: May 2013

ABSTRACT: The SSA/Ro and SSB/La antigens are polypeptides which serve as autoantigens in systemic lupus erythematosus and Sjogren's syndrome. The SSA/Ro contains two major isoforms of 60 kD and 52 kD. The former is the main native antigen while the latter is a major autoantigen in its denatured form. The SSB/La is a single phosphorylated protein of 48 kD. Recently a new protein of 46 kD, termed calregulin, was suggested as an additional component of the SSA/Ro antigens. However, extensive investigations failed to confirm its relation to the SSA/Ro system.Based on molecular techniques and cDNA cloning of these antigens, it was demonstrated that the 60 kD protein is capable of binding RNA and DNA molecules, suggesting a regulatory role in transcription for this antigen. The 52 kD polypeptide contains multiple zinc finger motifs and its sequence is homologous to the mouse rptl protein, which is a T‐cell regulating peptide. The SSB/La is associated with precursors of 5S RNA and tRNA, implying that it has a role in the synthesis and maturation of RNA polymerase III transcripts.The 60 kD and 52 kD SSA/Ro components may be associated within the cell. The SSA/Ro and SSB/La may also be in complex in some points of the cell cycle.
Autoantibodies in Normal and Abnormal Pregnancy
Authors: GLEICHER NORBERT 
Published: May 2013

ABSTRACT: Abnormal autoimmune function has been associated with reproductive failure for decades. In fact, all medical conditions historically associated with pregnancy loss (and on occasion infertility) are now recognized to have an autoimmune etiology. It is therefore quite surprising that only less than a decade ago a correlation between the presence of abnormal autoantibodies and pregnancy loss was reported for the first time. Since reproductive failure, similar to other abnormal autoimmune states, is not a monoclonal event, we have established that affected patients demonstrate polyclonal autoantibody abnormalities including a variety of nonorganospecific as well as organspecific autoantibody groupings. For example, patients with repeated pregnancy loss will exhibit abnormal levels of anti‐phospholipid antibodies (PA).In normal pregnancy natural autoantibodies do not follow the standard immunoglobulin (Ig) pattern, characterized by a decrease in levels despite a probably mild increase in production, which is excessively compensated by the vasodilatation of pregnancy. PA, especially, demonstrate a mild increase during pregnancy, though levels only in the peripartal period may reach abnormally high titers (in comparison to nonpregnant controls). This dichotomy between total Ig and natural autoantibodies is interesting since it suggests that autoantibodies may be under distinct control. In fact, we have suggested that this observed elevation of autoantibodies may be the result of an antigenic stimulus by self‐like antigen, represented by the maternal growth of the parasitic fetus.In abnormal pregnancies, especially those associated with maternal hypertension and fetal growth retardation (IUGR), autoantibody levels do reach highly abnormal levels. We have reported that in both of these conditions significant abnormalities especially in IgG‐PA can be detected, which stand in direct correlation with severity of disease (though autoimmune hemolytic anemia (AHA) can also be found). This is an interesting observation because both of these conditions have been associated with an imbalance between thromboxane and prostacyclin in favor of the platelet aggregating and vasoconstrictive thromboxane. This is exactly the imbalance reported in women with habitual abortions, which is assumed to be PA‐induced. Aspirin, recently widely reported as being successful in the prevention of pregnancy‐induced hypertension (PIH) and IUGR, has also been recommended as treatment for habitual aborters. Lastly, habitual aborters who are successfully treated and reach viability in a subsequent pregnancy, experience a highly increased incidence of PIH and IUGR. All of these observations strongly suggest that PIH, IUGR, and repeated pregnancy loss may have a common pathophysiology. It is tempting to speculate that it is autoantibody—and especially PA—related.
Specific Antiphospholipid Antibodies as a Predictive Variable in Patients With Recurrent Pregnancy Loss
Authors: AOKI KOJI , HAYASHI YAYOI , HlRAO YUKIE , YAGAMI YOSHIAKI 
Published: May 2013

PROBLEM: Antiphospholipid antibodies (APLs) consist of very heterogenous autoantibodies. It has not been fully explored what kind of specificities are most relevant to recurrent pregnancy loss. Thus, we investigated the effects of specific APLs on recurrent aborters.METHOD: IgG and IgM antibodies against PE (treated with 1% acetic acid) and five negatively‐charged phospholipids were measured by ELISA among 334 recurrent aborters without autoimmune disease. The relationships between APL specificities and subsequent pregnancy outcome were prospectively investigated in 38 recurrent aborters with positive APL who did not receive treatment with prednisolone and aspirin. Antibody levels exceeding the 99th percentile of 280 healthy women were considered positive.RESULTS: Positive IgG and/or IgM APLs were detected in 14%, IgG APLs in 12%, and IgG antibodies against PA, PG, PI, PS, CL and PE, respectively, in 9%, 7%, 7%, 7%, 8%, and 8%. In a prospective study of the 38 untreated patients, fetal loss recurred in 82% of the 33 IgG APL‐positive patients, but in 40% of the five patients positive for only IgM APLs. The incidence of fetal loss in the next pregnancy of patients with IgG specific APL‐positive against PE, PI, PS, or CI was even higher at 90% and over, and fetal loss recurred in all of 21 patients with two or more IgG APL‐positive against PE, PI, PS, or CL.CONCLUSION: These results suggest the possibility that two or more IgG APL‐positive value against treated PE, PI, PS, or CL, may be more accurate as a predictive variable than that of only one IgG APL‐positive in patients with recurrent pregnancy loss.
Treatment of Recurrent Spontaneous Abortion by Immunization With Paternal Lymphocytes: Results of a Controlled Trial
Authors: GATENBY PAUL A. , CAMERON KAYE , ADELSTEIN STEPHEN , SIMES R. JOHN , BENNETT MICHAEL J. , JANSEN ROBERT P.S. , SHEARMAN RODNEY P. , STEWART GRAEME J. , WHITTLE MELANIE , DORAN TREVOR J. 
Published: May 2013

PROBLEM: It remains unclear whether maternal immunization with paternal lymphocytes prior to conception improves the reproductive outcome in women with recurrent abortion in whom all secondary causes have been excluded.METHOD: A double‐blind placebo controlled trial was instituted in women with unexplained recurrent spontaneous abortion, comparing immunization with 400 million paternal to 400 million maternal (autologous) lymphocytes. The groups were compared in a paired sequential trials chart, by logistic regression, and, in addition, a meta‐analysis of this and other published trials was carried out.RESULTS: The live birth rate among pregnancies in paired couples with paternal lymphocyte immunization was 68% compared to 47% in the women who received their own cells. The results bordered on, but did not achieve, statistical significance. The women in each group were thoroughly investigated to exclude known causes of recurrent pregnancy loss and appeared to have been well matched in all variables. Women with lymphocytotoxic antibodies against paternal lymphocytes were excluded. Unlike our previous study there was not association between the time to conception and the chance of a successful outcome. Indeed, the time to conception was relatively short, 12 wk in all groups. The meta‐analysis supported an overall modest favorable experience with paternal cells.CONCLUSION: The study is consistent with a general trend favoring paternal over maternal lymphocyte immunization but reinforces the need for larger multicenter controlled trials as well as more detailed biological study in humans to understand the nature of the maternal‐fetal interface and its breakdown.