bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibin‐ A and Pro‐αC Are Elevated in Preeclamptic Pregnancy and Correlate with Human Chorionic Gonadotropin
Authors: FRASER ROBERT F. , MCASEY MARY E. , CONEY PONJOLA
Published: September 2011

PROBLEM: Serum concentrations of the heterodimeric glycoprotein inhibin‐A (α‐βA) and its α‐subunit increase during pregnancy. The placenta is the predominant source of inhibin during pregnancy, and a paracrine role in the trophoblast has been suggested. Elevated serum concentrations of inhibin α‐subunit as well as the glycoprotein human chorionic gonadotropin (hCG) have been described in preeclamptic pregnancy. The objectives of this investigation were to compare serum concentrations of inhibin‐A and inhibin pro‐αC in preeclamptic and normotensive pregnancy, and to examine the relationship of hCG and inhibin‐A in those pregnancies.

METHOD OF STUDY: A case‐control design using 32 patients with preeclampsia with a single fetus at 32–40 weeks of gestation and 34 gestation age‐matched normotensive control subjects was used for this investigation. Solid‐phase enzyme‐linked immunosorbent assays were used to measure inhibin‐A and inhibin pro‐αC in sera. An immunoradiometric assay was used to measure intact hCG.

RESULTS: Inhibin‐A and inhibin pro‐αC concentrations were significantly elevated in the sera of women with preeclampsia compared with those concentrations in normotensive control subjects (P < 0.05). A relationship of inhibin‐A or pro‐αC with severity of preeclampsia was not observed. There was a significant positive correlation of serum hCG with both inhibin‐A and pro‐αC (P < 0.05).

CONCLUSIONS: Levels of inhibin‐A and the subunit pro‐αC are increased in pregnancies complicated by preeclampsia. These findings are potentially the effect of a paracrine role of inhibin‐A in the development and proliferation of the trophoblast.
Differential Gene Expression of TGF‐β Isoforms and TGF‐β Receptors During the First Trimester of Pregnancy at the Human Maternal‐Fetal Interface
Authors: ANDO NORIKO , HIRAHARA FUMIKI , FUKUSHIMA JUN , KAWAMOTO SUSUMU , OKUDA KENJI , FUNABASHI TOSHIYA , GORAI ITSUO , MINAGUCHI HIROSHI
Published: September 2011

PROBLEM: The transforming growth factor (TGF)‐βs are multifunctional cytokines, and they play a role in the controlled growth of trophoblasts. Moreover they are thought to be important in maternal‐fetal interaction during early gestation.

METHOD OF STUDY: Human decidual and villous tissues in the first trimester were Northern blotted and amplified by reverse transcription‐polymerase chain reaction to measure the expression of TGF‐β1, ‐β2, and ‐β3 and their receptors, types I and II, at the first trimester of pregnancy. In addition, their cell‐specific expression at the maternal‐fetal interface was determined by in situ hybridization.

RESULTS: Each isoform of TGF‐β was expressed in both decidual and villous tissues. Because most TGF‐β1 gene expression was found in villous tissues, TGF‐β2 mRNA was expressed preferentially in the decidual tissues. TGF‐β3 transcripts were expressed in the nonpregnant endometrium.

CONCLUSIONS: The results suggest that each isoform of TGF‐β plays some specific role in decidualization and placentation. Furthermore, it is predicted that they regulate the maternal‐fetal interaction at early gestation.
Maternal Blood B‐Cell (CD19+) Percentages and Serum Immunoglobulin Concentrations Correlate with Breast‐feeding Behavior and Serum Prolactin Concentration
Authors: ZIMMER J. PAUL , GARZA CUTBERTO , BUTTE NANCY F. , GOLDMAN ARMOND S.
Published: September 2011

PROBLEM: Lactating women recover from pregnancy‐induced immunosuppression while actively secreting immunologically active agents into milk. Few clinical studies have examined changes in postpartum maternal immune status or explored mechanisms.

METHOD OF STUDY: We measured blood B‐cell (CD19+) percentages and serum concentrations of immunoglobulin (Ig) G, IgM, and IgA at 1 to 2 weeks, 1 month, and 2 months postpartum in a longitudinal study of seven healthy, lactating women.

RESULTS: More frequent or extended breast‐feeding sessions were correlated with lower CD 19+ percentages, reduced serum IgG, and higher serum IgA and IgM concentrations. CD19+ percentages were correlated negatively with serum prolactin concentrations. Blood samples drawn before and 30 min after breast‐feeding did not differ in CD 19+ percentages or serum Ig concentrations.

CONCLUSIONS: These findings confirm our previous cross‐sectional study showing a negative correlation between CD 19+ percentages and serum prolactin. Because lactation practices are modifiable, these findings suggest that women can influence the course of lactation‐associated immunologic changes.
The Selective Use of Heparin/Aspirin Therapy, Alone or in Combination with Intravenous Immunoglobulin G, in the Management of Antiphospholipid Antibody‐Positive Women Undergoing In Vitro Fertilization
Authors: Sher Geoffrey , Matzner William , Feinman Michael , Maassarani Ghanima , Zouves Christo , Chong Penny , Ching Wendell
Published: September 2011

PROBLEM: The effect of mini‐dose heparin/aspirin (H/A) alone vs. combined intravenous immunoglobulin G (IVIg) and H/A on in vitro fertilization (IVF) birthrates in women who test seropositive for antiphospholipid antibodies (APA+) was evaluated, as was the question of whether outcome is influenced by the gammaglobulin isotype(s) or the phospholipid (PL) epitope(s) to which the APAs are directed.

METHOD OF STUDY: A case‐control study was conducted in three phases, spanning a 4‐year period, in a multicenter clinical research environment. Six hundred eighty‐seven APA+ women, who were younger than 40 years and who each, completed up to three consecutive IVF/embryo transfer cycles within a 12‐month period, were given either H/A alone or H/A in combination with IVIg. Birthrates relative to the type of immunotherapy (i.e., H/A alone and H/A with IVIg) and APA profile were the main outcome measurements.

RESULTS: In phase I, 687 women who tested APA+ to one or more PL epitopes underwent two or fewer IVF attempts for a total of 1050 IVF cycles. Four hundred seventy‐seven (46%) births occurred in 923 IVF cycles in which H/A alone was administered. Twenty‐two (17%) births occurred after 127 IVF cycles in which H/A was not administered. In phase II, 322 of 687 women tested positive for a single APA subtype. These subjects underwent up to two consecutive IVF attempts for a total of 521 IVF cycles while receiving H/A alone. The birthrate was significantly lower for women whose APAs were directed toward phosphatidylethanolamine (PE) or phosphatidylserine (PS) involving IgG or IgM isotypes than for women who had any other APA (17% vs. 43%). In phase III, 121 women who did not achieve live births after two consecutive IVF attempts in which H/A alone was administered received IVIg in combination with H/A during their third consecutive IVF cycle. The birth rate was 41% after these IVF cycles when anti‐PS or anti‐PE involving IgG or IgM isotypes were present, as compared with 17% when H/A alone was administered. The IVF outcome did not improve when IVIg was administered in association with any other single APA.

CONCLUSIONS: The treatment of APA+ women with H/A alone improves IVF birthrates. This benefit is selective in that it does not apply in cases in which IgG‐ or IgM‐related APAs are directed against PE or PS. In such cases, the addition of IVIg significantly improves the outcome.
HLA‐G Polymorphisms: Ethnic Differences and Implications for Potential Molecule Function
Authors: VAN DER VEN K. , SKRABLIN S. , OBER C. , KREBS D.
Published: September 2011

PROBLEM: Human leukocyte antigen (HLA)‐G is uniquely expressed on extravillous cytotrophoblasts of the placenta and is postulated to be a mediator of maternal immune tolerance. Although it was originally considered to be nonpolymorphic, variations of the HLA‐G DNA sequence have been reported, and a limited number of HLA‐G alleles been defined.

METHOD OF STUDY: The HLA‐G wild‐type sequence was compared with HLA‐A2 with regard to the conservation of functionally essential parts of classical HLA‐I molecules. HLA‐G polymorphisms were analyzed under the aspect of ethnic differences, site, and consequences for postulated molecule functions.

RESULTS: HLA‐G exhibits a high degree of conservation relative to HLA‐A2 in functionally relevant sites of HLA‐class I molecules. However, polymorpahic sites in HLA‐G and classical HLA loci are not congruent.

CONCLUSION: The type and localization of HLA‐G polymorphisms suggest that different parts of the HLA‐G molecule underlie different selective constraints.
Placental Transport of Maternal Immunoglobulin G in Pregnancies at Risk of Rh (D) Hemolytic Disease of the Newborn
Authors: Palfi Miodrag , Hildén Jan‐Olof , Gottvall Tomas , Selbing Anders
Published: September 2011

PROBLEM: The following questions were addressed: Is the placental transport of immunoglobulin (Ig)G, IgG1, and IgG3 diminished in pregnancies at risk of hemolytic disease of the newborn? Is the placental transport of IgG, IgG1, and IgG3 correlated with the hemoglobin concentration in the fetus and AutoAnalyzer (AA) quantitations of maternal anti‐D?

METHOD OF STUDY: IgG concentrations were determined retrospectively in 41 paired fetal/maternal (f/m) samples in 31 Rh (D) alloimmunized pregnancies. IgG1 and IgG3 concentrations were determined in those 23 cases in which the results of fetal hemoglobin concentration and quantitations of maternal anti‐D were available. The results were compared with values found in normal pregnancy and correlated with maternal anti‐D AA quantitations and fetal hemoglobin concentrations.

RESULTS: Fetal IgG, IgG1, and IgG3 concentrations, and the corresponding fetomaternal ratios in Rh (D) alloimmunized pregnancies, increased with gestational age according to the following formulas (obtained by simple regression): Fetal IgG = −8.846 + 0.491.gestational age (GA), (R2 = 0.544); fetal IgG1 = −10.021 + 0.46GA, (R2 = 0.463); fetal IgG3 = −0.865 + 0.039GA, (R2 = 0.327); f/m IgG = −1.006 + 0.054−GA, (R2 = 0.557); f/m IgG1 = −1.876 + 0.085GA, (R2 = 0.654); f/m IgG3 = −0.199 + 0.026GA, (R2 = 0.146).

CONCLUSIONS: The placental transport of IgG, IgG1, and IgG3 in women with Rh (D) immunizations is not diminished compared with normal pregnancy. However, AA quantitations of anti‐D are inversely correlated with f/m IgG ratio, f/m IgG1 ratio, and fetal IgG and IgG1 concentrations (P = 0.002, P = 0.004, P = 0.02, and P = 0.02 respectively).

The placental transport of IgG3 is significantly higher in pregnancies at risk of hemolytic disease of the newborn compared with IgG3 concentrations in normal pregnancy.
Fas and Fas‐Ligand Are Expressed in the Uteroplacental Unit of First‐Trimester Pregnancy
Authors: Hammer Astrid , Blaschitz Astrid , Daxböck Christine , Walcher Wolfgang , Dohr Gottfried
Published: September 2011

PROBLEM: Fas and Fas‐ligand (FasL) are thought to provide a strategy for reducing graft rejection in immunologically ‘privileged’ tissues by controlling injurious lymphocyte reactions. As the uteroplacental unit is often defined as an immune‐privileged site, we investigated the expression of Fas and FasL in this tissue in the first trimester of pregnancy.

METHOD OF STUDY: Western blotting, immunohistochemistry, and double immunofluorescence were used for this examination.

RESULTS: Western blotting with purified first‐trimester trophoblast cells revealed one specific band for FasL. The presence of FasL on different trophoblast populations could be confirmed by immunohistochemistry and double immunofluorescence. In the villous part of the placenta, FasL is mostly located on cytotrophoblast cells with no access to maternal blood flow, whereas in trophoblast‐invaded uterine tissue, interstitial trophoblast cells, which are in close contact with maternal leukocytes, revealed a strong signal for FasL, but no staining for Fas on these cells. However, Fas was found on CD45+ maternal leukocytes.

CONCLUSION: Based on our experimental findings, we speculate that the abundant presence of FasL on trophoblast cells within the maternal decidua may play an important role in the maintenance of immune privilege in the pregnant uterus by endowing fetal trophoblast cells with a defense mechanism against activated maternal leukocytes, whereas in the villous part of the placenta, the Fas/FasL system seems to be involved in the regulation of placental growth.
First‐Trimester Human Chorionic Villi Express Both Immunoregulatory and Inflammatory Cytokines: A Role for Interleukin‐10 in Regulating the Cytokine Network of Pregnancy
Authors: Bennett William A. , LagooDeenadayalan S. , Whitworth N.S. , Stopple J.A. , Barber W.H. , Hale E. , Brackin M.N. , Cowan B.D.
Published: September 2011

PROBLEM: T‐helper 2 (TH2)‐type cytokines [i.e., interleukin (IL)‐6. IL‐10, and IL‐13] and transforming growth factor (TGF)‐β are expressed by the murine decidua and/or placenta and are likely to suppress inflammatory cytokine [i.e., IL‐2, interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α, IL‐1α, and IL‐1β] production at the maternal‐fetal interface. In addition, class I IFNs may protect the fetus from immunologic rejection and viral infections. This study examines the expression of inflammatory/immunoregulatory cytokines and IL‐10 production by first‐trimester chorionic villi.

METHOD OF STUDY: Gestational tissues (n ? 5) were obtained following elective terminations performed between 7 and 9 weeks of gestation. Chorionic villous tissues were separated from fetal membranes and decidua, and total RNA was extracted. Cytokine expression was assessed by a reverse transcriptase‐polymerase chain reaction technique. Chorionic villi (n = 9; 6–12 weeks gestation) were maintained in organ culture, and human chorionic gonadotropin (hCG) and IL‐10 levels were determined by immunoradiometric and enzyme‐linked immunosorbent assays, respectively.

RESULTS: IFN‐γ and IL‐2 were generally not expressed by first‐trimester chorionic villi. Low to moderate levels of expression were noted for IL‐1α, IL‐1β, and TNF‐α. High levels of mRNA were noted for IFN‐α and IFN‐β, but IFN‐τ was not expressed. In all tissues. TGF‐β1 and IL‐13 were either weakly expressed or not expressed. In contrast, moderate to high levels of IL‐6 and IL‐10 mRNA were detected in each chorionic villous sample. In chorionic villous explants obtained at 6–11 weeks gestation, production of hCG and IL‐10 was greatest during the first 24 hr ([hCG] ? 6961 ± 815 mIU/mL, [IL‐10] = 92 ± 11 pg/mL) and then declined through 72 hr.

CONCLUSIONS: TH1‐type cytokines (IL‐2, IFN‐γ) are not expressed by first‐trimester chorionic villous tissues: This is possibly due to local production of IL‐10. In contrast, macrophage‐associated cytokines (IL‐1β and TNF‐α) are expressed and their regulation may be critical for fetal survival. Finally, class I IFNs expressed by early chorionic tissues may protect the fetus from maternal rejection and viral transmission.
Immunoglobulins of the Human Amniotic Fluid
Authors: Quan Canh P. , Forestier François , Bouvet Jean‐Pierre
Published: September 2011

Quan CP, Forestier F, Bouvet J‐P. Immunoglobulins of the human amniotic fluid. AJRI 1999; 42:219–225 © Munksgaard, Copenhagen

PROBLEM: Except for the description of a secretory immunoglobulin (S‐Ig) of a low size, no recent study has investigated the molecular status of antibodies in the human amniotic fluid.

METHOD: After separation with a high performance chromatography, we analyzed the different isotypes of amniotic Igs by immunoblotting and ELISA.

RESULTS: IgG is found to be the major isotype and to contain mother‐derived tetanus antitoxins. IgA is much less abundant, whereas no IgM can be detected. IgA is monomeric, with a low level of secretory IgA and with various amounts of free secretory component (SC). The presence of a low level of SC‐containing immunoglobulin of a low size is confirmed during the last trimester of pregnancy. This molecule contains no α chain but includes a Fabγ fragment noncovalently associated with SC. IgG, IgA, and SC are detected in the fetal urine and, therefore, can reach the amniotic fluid by this route.

CONLUSION: In addition to the predominant maternal IgG, the amniotic fluid contains different molecular forms of fetal immunoglobulins. Their function as an immune barrier against infection and against mother‐derived autoantibodies is discussed.
Fetal Treatment of Congenital Heart Block Ascribed to Anti‐SSA Antibody: Case Reports with Observation of Cardiohemodynamics and Review of the Literature
Authors: Yamada Hideto , Kato Emi H. , Ebina Yasuhiko , Moriwaki Masashi , Yamamoto Ritsu , Furuta Itsuko , Fujimoto Seiichiro
Published: September 2011

Yamada H, Kato EH, Ebina Y, Moriwaki M, Yamamoto R, Furuta I and Fujimoto S. Fetal treatment of congenital heart block ascribed to anti‐SSA antibody: case reports with observation of cardiohemodynamics and review of the literature. AJRI 1999; 42:226–232 © Munksgaard, Copenhagen

PROBLEM: Maternal anti‐SSA(B) antibody crosses the placenta and causes fetal myocarditis, congenital heart block (CHB), hydrops fetalis, and intrauterine fetal death. The aim of this study was to evaluate corticosteroids' efficacy as a treatment for CHB.

METHOD OF STUDY: One fetus with complete CHB and one fetus with incomplete CHB due to anti‐SSA(B) antibody received maternal prednisolone (PSL) and dexamethasone (DEXA) treatments. Heart rate, cardiothoracic ratio (CTR), left ventricular fractional shortening (FS), and preload index (PLI) were longitudinally measured by serial fetal echocardiograms.

RESULTS: In the former case, after maternal PSL/DEXA administration, improvement of cardiohemodynamics, i. e., the reduction of PLI from 1.7 to 0.4, CTR from 70 to 52%, and FS from 63 to 54% were observed. In the latter case, second degree 2:1 block was converted to 3:2 block/sinus rhythm, resulting in the increase of the fetal heart rate from 65 to 116 beats per minute (bpm).

CONCLUSIONS: We disclosed for the first time the beneficial effects of corticosteroids in the fetal cardiohemodynamics and conduction system of affected fetuses with the presence of maternal anti‐SSA(B) antibodies.
Distribution of Th1, Th2, and Th0 and the Th1/Th2 Cell Ratios in Human Peripheral and Endometrial T Cells
Authors: Saito S. , Tsukaguchi N. , Hasegawa T. , Michimata T. , Tsuda H. , Narita N.
Published: September 2011

Saito S, Tsukaguchi N, Hasegawa T, Michimata T, Tsuda H, Narita N. Distribution of Th1, Th2, and Th0 and the Th1/Th2 cell ratios in human peripheral and endometrial T cells. AJRI 1999; 42:240–245 © Munksgaard, Copenhagen

PROBLEM: To examine whether normal pregnancy involves type 2 T‐helper (Th2) immune condition or not.

METHOD OF STUDY: We measured the percentage of Th0, Th1, and Th2 and the Th1/Th2 cell ratios of human peripheral blood and endometrial T cells using flow cytometry, which can analyze both the surface marker CD3, and intracellular cytokines, interleukin 4 (IL‐4) and interferon γ (IFNγ).

RESULTS: No significant differences were found in the percentages of Th1, Th2, and Th0 and the Th1/Th2 cell ratios in the peripheral blood T cells of nonpregnant women and women in early pregnancy. On the other hand, the percentage of Th1 cells was highest during the proliferative phase of the endometrium, followed by the secretory phase and early pregnancy decidua. The percentage of Th2 cells was highest in early pregnancy decidua and lowest during the proliferative phase of the endometrium. The Th1/Th2 ratio was 147.48 ± 96.68 during the proliferative phase of the endometrium, 37.74 ± 21.33 during the secretory phase, and 1.31 ± 0.48 in the early pregnancy decidua.

CONCLUSIONS. These data indicate that Th1 cells predominate in the nonpregnant endometrium, especially during the proliferative phase, while Th2 cells predominate in early pregnancy decidua.
Spontaneous Accumulation of Eosinophils and Macrophages Throughout the Stroma of the Epididymis and Vas Deferens in Alymphoplasia (aly) Mutant Mice: I. A Histological Study
Authors: Itoh Masahiro , Miyamoto Kensaku , Ooga Takuji , Iwahashi Kazuhiko , Takeuchi Yoshiki
Published: September 2011

Itoh M, Miyamoto K, Ooga T, Iwahashi K, Takeuchi Y. Spontaneous accumulation of eosinophils and macrophages throughout the stroma of the epididymis and vas deferens in alymphoplasia (aly) mutant mice: I. A histological study. AJRI 1999; 42:246–253 © Munksgaard, Copenhagen

PROBLEM: The alymphoplasia (aly) mutation of mice causes the systemic absence of lymph nodes and Peyer's patches. Histopathological analysis has revealed that lymphocytes accumulate in some organs such as the salivary glands, lungs, kidneys, liver, and pancreas of homozygotes (aly/aly) but not heterozygotes (aly/+). However, the presence of lymphocytic accumulation in male reproductive tissues of aly/aly mice has not been reported.

METHOD OF STUDY: The male reproductive organs of homozygous aly/aly, heterozygous aly/+, and other immunodeficient mice bred in a specific pathogen‐free state were histologically investigated.

RESULTS: Testes, ductuli efferentes, prostates, coagulating glands, and seminal vesicles of homozygous aly/aly mice were free from any pathological accumulation of leukocytes. However, their epididymides and vasa deferentia exhibited massive infiltration by leukocytes, which were composed of eosinophils and macrophages. In all homozygotes examined, both eosinophils and macrophages were extensively observed throughout the stroma of the epididymis and vas deferens, but never within the epithelium or lumen of the ducts, with no parenchymal tissue damage. The accumulation of eosinophils was never found in nonreproductive organs. In aly/+ heterozygous mice and other immunodeficient mice, no pathological accumulation of leukocytes were noted.

CONCLUSIONS: The accumulation of eosinophils and macrophages is specific to the epididymides and vasa deferentia of immunodeficient aly/aly homozygotes, although the pathogenesis remains unknown.
Novel Hyperactive Mitogen to Endothelial Cells: Human Decidual NKG5
Authors: Langer Noga , Beach Dvora , Lindenbaum Ella S.
Published: September 2011

Langer N, Beach D, Lindenbaum ES. Novel hyperactive mitogen to endothelial cells: human decidual NKG5. AJRI 1999; 42:263–272 © Munksgaard, Copenhagen

PROBLEM: The purpose of this study was the isolation and characterization of decidual extract proteins that exhibit mitogenicity on endothelial cells.

METHOD OF STUDY: A partially purified extract (F1 fraction) was obtained from human decidua of the first trimester of pregnancy. F1 was separated by heparin‐sepharose column and showed significant mitogenicity on bovine brain capillary endothelial (BBCE) cells in vitro, using methylene blue stain nuclear assay. Sodium‐dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) revealed four fractions with MW less than 30 KDa.

RESULTS: Mitogenic fraction, E11–12 (eluted at 1.5 M NaCl) was identified as basic fibroblast growth factor (bFGF). Vascular endothelial growth factor (VEGF) and acidic (a)FGF were not identified as one of the mitogenic fractions. However, fractions E5–6 and E7–8 induced statistically significant mitogenicity at concentration of 1 pg/mL, which is 103 times lower than bFGF. Sequencing of E5–6 fraction identified NKG5 protein, a putative secreted polypeptide derived from human natural killer (NK) cells and activated T cells of unknown function.

CONCLUSION: This work demonstrates that NKG5 stimulates mitogenicity of endothelial cells and may be involved in angiogenesis.
Natural Killer Cell Activity and Cytokine Production after In Vitro Immunoglobulin Treatment of Lymphocytes Derived from Pregnant Women with or without Risk for Spontaneous Abortion
Authors: Szereday L. , Späth P. , Szekeres‐Bartho J.
Published: September 2011

Szereday L, Späth P, Szekeres‐Bartho J. Natural killer cell activity and cytokine production after in vitro immunoglobulin treatment of lymphocytes derived from pregnant women with or without risk for spontaneous abortion. AJRI 1999; 42:282–287 © Munksgaard, Copenhagen

OBJECTIVE: To investigate the possible mechanism of action effective in immunoglobulin G (IgG) treatment of recurrent spontaneous abortion (RSA). The effect in vitro of a commercially available intravenous immunoglobulin (IvIg) on the rate of interleukin (IL)‐10 and IL‐12 positive cells (Th1/Th2 balance) and on natural killer (NK) cell activity in populations of peripheral lymphocytes of healthy pregnant women and women at risk for premature pregnancy termination was studied. Primary habitual aborters as well as women showing clinical symptoms (bleeding or regular uterine contractions) of threatened premature pregnancy termination were included.

METHODS: Lymphocytes of 20 pregnant women were tested. Five different batches of an IvIg with reported immunomodulatory potential were used at a concentration of 10 mg/mL. Cytokine profiles of the lymphocytes were determined by immunocytochemistry. For testing of NK cell activity, the 4 hr single cell cytotoxicity assay was used.

RESULTS: Incubation with IgG of lymphocytes from recurrent spontaneous aborters concomitantly and significantly decreased the rate of IL‐12 positive cells (P < 0.01) and increased the rate of IL‐10 positive cells (P < 0.01), whereas such treatment had no significant effect on lymphocytes of pregnant women not at risk of abortion. Dialysis or heat treatment (56°C, 30 min) of the IgG preparations did not modify the effect. Elevated NK cell activity of women at risk for premature pregnancy termination significantly decreased after IgG incubation of cells in all cases, whereas NK cell activity of normal pregnancy lymphocytes was not altered.

CONCLUSION: This study suggests that incubation of peripheral lymphocytes from RSA patients with polyclonal polyspecific IgG alters cytokine profiles and NK activity while the same treatment does not affect lymphocytes of healthy pregnant women. These data might add to the understanding of mechanisms of action of IvIg in prevention of recurrent pregnancy loss.
The Possible Role of Antiovary Antibodies in Repeated In Vitro Fertilization Failures
Authors: Geva Eli , Fait Gideon , Lerner‐Geva Liat , Lessing Joseph B. , Swartz Tamar , Wolman Igal , Daniel Yair , Amit Ami
Published: September 2011

Geva E, Fait G, Lerner‐Geva L, Lessing JB, Swart: T, Wolman I, Daniel Y, Amit A. The possible role of antiovary antibodies in repeated in vitro fertilization failures. AJRI 1999; 42:292–296 © Munksgaard, Copenhagen

PROBLEM: The study was conducted to investigate the possible role of circulating ovarian autoantibodies (ov‐ab) in patients with repeated in vitro fertilization‐embryo transfer (IVF‐ET) failure and to evaluate the effectiveness of immunosuppression treatment in these patients.

METHOD OF STUDY: The study group comprised 80 IVF patients who had five or more failed treatment cycles (mean 10.2; range 7–22). The presence of ov‐ab was compared between these women and 1) 50 IVF patients who conceived during the first three treatment cycles; 2) 50 healthy nulligravidae. All participants were seronegative to nonorgan‐specific and antithyroid autoantibodies. Patients in the study group who were positive for ov‐ab were treated with 10 mg/day prednisone starting 1 month before ovulation induction. Embryo grading was compared in the IVF cycles before and after treatment.

RESULTS: Ov‐ab were found in ten patients (12.5%) in the study group, compared to none in the control groups (P = 0.01). Nine of the patients positive for ov‐ab were treated with prednisone for their following cycle. A statistically significant improvement in embryo grading was noted. Three patients conceived after treatment (33%), with a take‐home baby rate of 22%, compared to only six patients (8.6%) who conceived among the rest of the seronegative study group, with a take‐home baby rate of 7.1% (P = 0.05).

CONCLUSIONS: Ov‐ab are a possible marker of an autoimmune disorder that may be one of the causes of repeated IVF failures. Immunosuppression treatment may prove efficient in ov‐ab seropositive patients with repeated IVF failures by improving embryo grading and pregnancy rate.
The Expression of Granulocyte Macrophage‐Colony Stimulating Factor (GM‐CSF) and Receptors in Human Endometrium*
Authors: Zhao Yong , Chegini Nasser
Published: September 2011

Zhao Y, Chegini N. The expression of granulocyte macrophage‐colony stimulating factor (GM‐CSF) and receptors in human endometrium. AJRI 1999; 42:303–311 © Munksgaard, Copenhagen

PROBLEM: To determine the temporal and spatial expression of granulocyte macrophage‐colony stimulating factor (GM‐CSF) and GM‐CSF α and β receptor mRNA and protein in human endometrium.

METHOD OF STUDY: The endometrial expression of GM‐CSF and GM‐CSF receptor mRNA and protein was determined using competitive quantitative reverse transcription polymerase chain reaction (Q‐RT‐PCR), in situ hybridization, and immunohistochemistry.

RESULTS: Endometrium expresses GM‐CSF and GM‐CSF α receptor mRNA with maximal expression occurring during the mid‐secretory phase (21.1 ±4.2 and 32.2 ± 7.7 × 106 mRNA copies/μg total RNA) compared to the proliferative phase (1.46 ± 0.4 and 7.5 ± 0.5 × 106 copies) of the menstrual cycle, with a significant reduction (0.67 ± 0.1 and 1.7 ± 0.2 × 106 mRNA copies) during the post‐menopausal period (P < 0.05). The endometrium expresses a significantly lower level of GM‐CSF β receptor mRNA (≈ 0.01 × 105 mRNA copies). Endometrial luminal and glandular epithelial cells are the primary site of GM‐CSF mRNA and protein expression, while arteriole endothelial, stromal, and inflammatory cells are the primary site of GM‐CSF α receptor protein. GM‐CSF β receptor protein has a similar cellular distribution as GM‐CSF.

CONCLUSION: Temporal and spatial expression of GM‐CSF and GM‐CSF receptors in human endometrium during the menstrual cycle suggests that epithelial‐derived GM‐CSF in an autocrine/paracrine manner may influence various endometrial biological activities, local inflammatory response, and macrophage survival.
Progesterone Directly and Indirectly Affects Perforin Expression in Cytolytic Cells
Authors: Laškarin G. , Faust Zs. , ŠTrbo N. , Sotošek V. , Szekeres‐Bartho J. , Podack E. R. , Rukavina D.
Published: September 2011

Laskarin G, Faust Zs, Štrbo N, SotoŠek V, Szekeres‐Bartho J, Podack ER, Rukavina D. Progesterone directly and indirectly affects perforin expression in cytolytic cells. AJRI 1999; 42:312–320 © Munksgaard, Copenhagen

PROBLEM: Decidual lymphocytes (DL) expressing the cytolytic molecule perforin represent approximately 55% of DL in the first trimester of human pregnancy. Progesterone dominates this phase of pregnancy and controls the production of uterine cytokines and growth factors. The aim of this study was to investigate the role of progesterone and progesterone‐induced blocking factor (PIBF) on perforin expression in DL and peripheral blood lymphocytes (PBL).

METHOD OF STUDY: Perforin expression was analyzed in PBL and DL incubated either in culture medium or with decidual adherent cells (DAC) and peripheral blood adherent cells (PBAC) and their supernatants with or without progesterone or PIBF. Perforin was detected by flow cytometry in PB and in decidual first trimester pregnancy lymphocytes.

RESULTS: Progesterone in high concentrations directly affects perforin expression in DL but not in PBL. Progesterone in a concentration dependent manner indirectly blocks perforin expression in DL and PBL cultured with adherent cells or their supernatants. PIBF blocked upregulation of perforin expression of DL cultured with DAC, but none of those cultured with PBAC. Similarly, PIBF was inefficient when PBL or DL were cultured with PBAC.

CONCLUSION: Progesterone present in a high concentration locally at the maternal‐fetal interface modulates perforin expression in the first trimester pregnancy DL.
F4/80‐Positive Cells Rapidly Accumulate Around Tubuli Recti and Rete Testis Between 3 and 4 Weeks of Age in the Mouse: An Immunohistochemical Study
Authors: Itoh Masahiro , Xie Qiang , Miyamoto Kensaku , Takeuchi Yoshiki
Published: September 2011

Itoh M, Xie Q, Miyamoto K, Takeuchi Y. F4/80‐positive cells rapidly accumulate around tubuli recti and rete testis between 3 and 4 weeks of age in the mouse: an immunohistochemical study. AJRI 1999; 42:321–326 © Munksgaard, Copenhagen

PROBLEM: Previous studies demonstrated that F4/80 antigen (murine macrophage‐specific antigen)‐positive cells in testes of normal adult mice accumulate particularly in the interstitium adjacent to the tubuli recti and rete testis (i. e., the central region). However, it remains unknown whether this accumulation is a congenital or acquired phenomenon.

METHOD OF STUDY: The distribution of F4/80‐positive cells on frozen sections of testes obtained from various aged mice was immunohistochemically examined to determine when the positive cells specifically accumulate in the central region.

RESULTS: F4/80‐positive cells were homogeneously distributed throughout the testicular interstitium with no specific accumulation until 2 weeks of age. However, at 3 weeks of age, the density of positive cells in the central region became slightly, but significantly, higher than that in the interstitium between the seminiferous tubules. Between 3 and 4 weeks of age, the cell density in the central region increased rapidly, the density at 4 weeks of age reaching the level of the mature testes of 8‐week‐old mice.

CONCLUSION: These results demonstrate that the specific accumulation of F4/80‐positive cells in the central region is an acquired phenomenon, which starts and ends before puberty.
Proportion of CD56+ 3+ T Cells in Decidual and Peripheral Lymphocytes of Normal Pregnancy and Spontaneous Abortion With and Without History of Recurrent Abortion
Authors: Yamamoto Tatsuo , Takahashi Yuko , Kase Namiko , Mori Hiroyuki
Published: September 2011

Yamamoto T, Takahashi Y, Kase N, Mori H. Proportion of CD56+ 3+ T cells in decidual and peripheral lymphocytes of normal pregnancy and spontaneous abortion with and without history of recurrent abortion. AJRI 1999; 42:355–360 © Munksgaard, Copenhagen

PROBLEM: The present study investigated the proportion of CD56+ 3+ T cells in maternal peripheral and decidual lymphocytes in normal pregnancy and spontaneous abortion with and without history of recurrent spontaneous abortion (RSA).

METHOD OF STUDY: Maternal peripheral blood and decidua were taken from normal pregnancies and missed abortions with and without RSA. Decidual lymphocytes were prepared from decidual tissue and analyzed by flow cytometry.

RESULTS: In normal pregnancy, the percentages of CD56+ 3+ T cells in decidual lymphocytes did not differ from those in the peripheral blood. However, the proportion of CD56+ 3+ T cells in decidual CD3+ T cells increased higher than that in the peripheral CD3+ T cells. The percentages of decidual CD56+ 3+ T cells in missed abortions with and without RSA were lower than those in normal pregnancies.

CONCLUSION: CD56+ 3+ T cells may play a role in the maintenance of pregnancy. The phenomenon, where the proportion of CD56+ 3+ T cells in decidual lymphocytes decreases, may be due to an immunologic event leading to missed abortion.
Increased T‐Helper‐1‐Type Immunity and Decreased T‐Helper‐2‐Type Immunity in Patients with Preeclampsia
Authors: Saito Shigeru , Umekage Hideshi , Sakamoto Yoshiharu , Sakai Masatoshi , Tanebe Kyoko , Sasaki Yasushi , Morikawa Hajime
Published: September 2011

PROBLEM: To examine whether preeclampsia involves type‐1 T‐helper (Th1) immune hyperactivity.

METHOD OF STUDY: Expression of HLA‐DR, a cell‐surface marker of activation, was analyzed on CD3+, CD4+, and CD8+ T cells in 15 preeclamptic patients and 15 normal pregnant women using flow cytometry. Additionally, peripheral blood mononuclear cells from preeclamptic patients and normal pregnant women were cultured with or without phytohemagglutinin (PHA) stimulation, and interleukin (IL)‐2, IL‐4, interferon (IFN)‐Γ, and tumor necrosis factor (TNF)‐α concentrations were determined in the supernatant by immunoassays.

RESULTS: HLA‐DR antigen was expressed more strongly on CD3+ T cells in preeclamptic patients than in normal subjects. In preeclampsia, HLA‐DR was expressed more strongly in CD8+ T cells than in CD4+ T cells. More TNF‐α, IL‐2, and IFN‐γ were produced by unstimulated and stimulated cultured peripheral blood mononuclear cells from preeclampsia patients than by those from normal subjects. TNF‐α/IL‐4, IL‐2/IL‐4, and IFN‐γ/IL‐4 ratios were higher in preeclamptic patients than in the normal group. Significant positive correlations were observed between mean blood pressure and concentrations of the Th‐1 type cytokines IL‐2, IFN‐γ, and TNF‐α.

CONCLUSION: Up‐regulation of Th1 responses and down‐regulation of Th2 responses occur in preeclampsia.
Interleukin‐12 Augments Cytolytic Activity of Peripheral and Decidual Lymphocytes Against Choriocarcinoma Cell Lines and Primary Culture Human Placental Trophoblasts
Authors: Hayakawa Satoshi , Nagai Nobuhisa , Kanaeda Takashi , Karasaki‐Suzuki Miki , Ishii Maki , Chishima Fumihisa , Satoh Kazuo
Published: September 2011

PROBLEM: Human trophoblasts are tolerant to the maternal immune system, but susceptible to interleukin (IL)‐2‐activated lymphocytes. IL‐12 is also a key cytokine in the induction of cytotoxic responses. We administered IL‐12 to peripheral blood lymphocytes (PBLs) and to decidual lymphocytes (DLs) and studied resulting cytotoxicity against trophoblasts.

METHOD OF STUDY: PBLs and DLs were stimulated with rIL‐2 and/or rIL‐12 for 48 hr in vitro. Cytotoxicity against the choriocarcinoma cell line JEG‐3, JAR, and primary culture trophoblasts were examined by LDH release assay. The proliferative response was estimated by MTT assay. Expression of cytotoxic factors was studied by reverse transcriptase‐polymerase chain reaction (RT‐PCR).

RESULTS: Whereas IL‐12 alone produced a modest enhancement in cytotoxicity of PBLs and DLs, the combination of IL‐2 and IL‐12 was most effective in trophoblast cell lysis. IL‐12 enhanced the mRNA expression of T‐cell specific serine protease (TSP, granzyme B) and FasL in DLs, but the expression of perforin was unchanged. Expression of these cytotoxic factors in PBLs was up‐regulated by IL‐12.

CONCLUSION: Our findings indicate critical roles of IL‐12 in the activation of maternal lymphocytes, which could possibly result in pregnancy failure syndromes.
Quantification of C3 and C4 in Infertile Men with Antisperm Antibody in Their Seminal Plasma
Authors: Rahimi Azita , Sepehri Houri , Pakravesh Jalil , Bahar Kamal
Published: September 2011

PROBLEM: Previous studies showed that some infertilities are caused by antisperm antibodies (ASAs). It was shown that some major complement (C) components are present in seminal fluid. Due to the role of C in the pathogenesis of ASAs, the existence and amount of two key C components (C3 and C4) were investigated in seminal plasma (SP).

METHOD OF STUDY: Single radial immunodiffusion assay and a sandwich‐type enzyme‐linked immunosorbent assay (ELISA) were used for C3 and/or C4 quantification, respectively, in serum and SP, and the tray agglutination test was used for ASA detection in 12 fertile and 53 infertile men (18 ASA‐positive [ASA +] and 35 ASA‐negative [ASA —] men).

RESULTS: Of the 18 ASA+ infertile men, 61.11% had positive C3, whereas 27.77% showed positive C4 levels. ASA+ infertile men showed significant differences in seminal plasma C3 mean values compared with ASA — infertile (P < 0.01) and fertile (P < 0.05) men, but the seminal plasma C4 values only showed differences compared with ASA — infertile men (P < 0.05). No significant differences were observed in serum C3 and/or C4 levels of ASA + infertile men compared with other groups. No significant correlation was found between ASA titer and C3 and C4 levels in SP. A significant correlation existed between SP and serum C3 levels of ASA + (r = 0.522, P < 0.01) and ASA— (r = 0.451, P < 0.01) infertile men, but no correlation was observed between C4 levels.

CONCLUSIONS: In the presence of ASAs, the C system has no definitive activity in blood serum or outside the male genital tract. In SP, and in association with ASAs, C has no lytic activity by the classical pathway. The excess of C3 in SP of ASA + infertile men may participate in other C‐mediated activities in the male reproductive tract.
Decidual Natural Killer Cells in Recurrent Spontaneous Abortion with Normal Chromosomal Content
Authors: Yamamoto Tatsuo , Takahashi Yuko , Kase Namiko , Mori Hiroyuki
Published: September 2011

PROBLEM: The maternal local immune responses in unexplained recurrent spontaneous abortion (RSA) are not yet well known. Maternal peripheral and decidual natural killer (NK) cells were evaluated in RSA with normal chromosomal content.

METHOD OF STUDY: Maternal peripheral blood, villous trophoblast, and decidua were taken from 15 normal pregnancies and 9 RSA patients with normal chromosomes. The NK cells in decidual lymphocytes were evaluated by flow cytometry using monoclonal antibodies for CD56, CD16, and CD3.

RESULTS: The percentages of CD56 + CD16—CD3— cells in decidual lymphocytes in RSA were lower than in normal pregnancies (P < 0.002). The CD56+ CD16+ / CD56+ CD16— cells ratio in RSA was higher than in normal pregnancies (P < 0.02). CONCLUSION: The lower percentages of CD56+ CD16—CD3— cells in RSA cases may show an inappropriate accumulation of NK cells in the decidua, and this finding may be a factor involved in RSA.
The Emerging Role of Immunoregulation of Fibrinogen‐Related Procoagulant Fgl2 in the Success or Spontaneous Abortion of Early Pregnancy in Mice and Humans
Authors: Clark David A. , Ding Jin‐Wen , Chaouat Gerard , Coulam Carolyn B. , August Carey , Levy Gary A.
Published: September 2011

PROBLEM: Abortion of chromosomally normal embryos in the CBA X DBA/2 mating combination is triggered by release of Th1 cytokines (tumor necrosis factor [TNF]‐α, interferon [IFN]‐γ, and interleukin [IL]‐1), which cause abortion via a novel prothrombinase, fgl2, and polymorphonuclear leukocytes. The site of activation may be maternal vascular endothelium on arteries and veins nourishing the placenta. Activation of coagulation is also prominent in spontaneous abortion of chromosomally normal human embryos. We asked where is fgl2 up‐regulated in the uterus in murine abortions, and if similar fgl2 expression occurs in human pregnancy failure.

METHODS: Control CBA X DBA/2 pregnant mice, or from mice injected with TNF‐α + IFN‐γ on day 7.5 of gestation, were removed on day 8.5, fixed, sectioned, and subject to in situ hybridization for fgl2. Sections were also stained for fibrin. Elective first trimester termination samples or biopsies taken early in the course of a recurrent miscarriage were similarly fixed, sectioned, and analyzed by in situ hybridization. Control and cytokine‐treated mice were anticoagulated with heparin, an activator of antithrombin III, and/or the direct anti‐thrombin inhibitor hirudin.

RESULTS: Low level fgl2 expression localized to basal decidua remote from the embryo was noted in control mice; cytokine treatment, which causes greater than 80% of abortions, produced a striking up‐regulation in this area as well as in a band at the junction of decidua and myometrium. Trophoblast also became strikingly positive. Fgl2 expression was associated with increased fibrin staining. Anticoagulation significantly protected against abortions, but doses were limited by the complication of retroplacental hemorrhage. In tissue from normal first trimester pregnancy, minimal fgl2 positivity was seen in some villous syncytiotrophoblast, in villous stroma, cytotrophoblast, and in some cells in decidua. In spontaneous abortion of normal embryo, striking fgl2 positivity was seen in syncytiotrophoblast and extravillous cytotrophoblast, in association with areas of thrombus formation.

CONCLUSIONS: Fgl2 appears to be physiologically expressed and may protect against the internal danger of maternal and/or fetal bleeding during pregnancy and at parturition; a role in inhibiting transplacental traffic is also possible. External dangers in the form of stress, endotoxin, and antigens eliciting Th1 cytokine responses upregulate fgl2 prothrombinase in trophoblast as well as in decidua, which results in spontaneous abortion of immunogenetically “weaker” embryos.
Pregnancy‐Specific Glycoprotein Gene Expression in Recurrent Aborters: A Potential Correlation to Interleukin‐10 Expression
Authors: Arnold Lori L. , Doherty T. Mark , Flor Armando W. , Simon James A. , Chou Janice Y. , Chan Wai‐Yee , Mansfield Brian C.
Published: September 2011

PROBLEM: The expression of the pregnancy‐specific glycoprotein (PSG) genes in the uterine endometrium of women experiencing recurrent first‐trimester abortions, and potential correlations to cytokine expression were examined.

METHOD OF STUDY: Endometrial RNA, isolated from women with a history of either repetitive first‐trimester pregnancy losses or uncomplicated pregnancies, was isolated and analyzed for PSG transcripts by the reverse transcriptase‐polymerase chain reaction method. PSG genes showing different patterns of expression were expressed in baculovirus, and the purified proteins examined for their effects on cytokine expression.

RESULTS: The expression of PSG11 in the endometria of recurrent aborters was significantly lower than in that of controls (P < 0.01). When tested on monocytes, PSG11 stimulated secretion of interleukin (IL)‐10.

CONCLUSIONS: The level of expression of the PSG11 gene in the uterine endometrium, during the peri‐implantation period, correlates with the risk of pregnancy loss in some women experiencing recurrent spontaneous abortions. The ability of PSG 11 to influence the secretion of IL‐10 suggests that PSG11 may contribute to the local modulation of the inflammatory T helper‐1 response seen in the endometrium of these women.
Comparison of soymilk, powdered milk, Hank’s balanced salt solution and tap water on periodontal ligament cell survival
Authors: Moazami Fariborz , Mirhadi Hosein , Geramizadeh Bita , Sahebi Safoura
Published: September 2011

Abstract –  The purpose of this study was to evaluate the ability of soymilk, powdered milk, and Hank’s balanced salt solution (HBSS) to maintain human periodontal ligament (PDL) cell viability in vitro. PDL cells were obtained from extracted healthy third molars and cultured in Dulbecco’s modified Eagles medium (DMEM). The cultures were exposed for 1, 2, 4, and 8 h to experimental solutions (tap water served as negative control and DMEM as positive control) at 37°C. The viable cells were then counted using the trypan blue exclusion technique. Data were analyzed by using one‐way anova, post hoc Scheffe and two‐way anova test. Statistical analysis showed that HBSS, powdered baby formula, and soymilk maintain cell viability equally well in different periods of times. Tap water cannot keep cells viable as well as other solutions. Soymilk and powdered baby formula can be recommended as suitable storage media for avulsed teeth for up to 8 h.
SHOP‐FLOOR LABOR ORGANIZATION IN ARGENTINA FROM EARLY PERONISM TO THE “PROCESO” MILITARY DICTATORSHIP
Authors: Basualdo Victoria
Published: September 2011

This article focuses on a crucial aspect of the Argentine labor movement that, in spite of its importance, has not been adequately examined by the existing historiography: the high degree of union structure penetration at the shop‐floor level through means of shop‐stewards and comisiones internas (CI). First, it provides a basic definition of shop‐stewards and CI for the Argentine case. Second, it briefly analyzes the history of these bodies from the early 1940s to the early 1980s, taking into account the most important structural transformations during this period, in particular the transition from an economic model driven by import‐substituting industrialization from the 1930s to the mid‐1970s to a process of deindustrialization from that moment onward. Third, it contends that these shop‐stewards and CI experienced tensions and contradictions, some of which were related to those present within the Argentine industrial working class. Finally, it underlines the importance of taking into account this rich history of shop‐floor organization to understand the strength of the Argentine labor movement in this period.