bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct Subsets of Stromal Cells Confined to Unique Microenvironments in Human Endometrium Throughout the Menstrual Cycle
Authors: TABIBZADEH S.
Published: May 2013

ABSTRACT: Human endometrial stroma exhibits rather uniform morphology throughout the endometrium. However, predecidualization develops characteristically around vessels and subsequently around glands and under surface epithelium, demonstrating existence of regional differences among stromal cells. Immunoreactivity of stromal cells in endometrial tissues from various phases of the menstrual cycle, as elucidated by employing monoclonal antibodies to cytokeratin, vimentin, very late anti‐gen‐1 (VLA‐1), Ber‐EP4, and HLA‐DR, revealed presence of phenotypically distinct subsets of stromal cells confined to unique microenvironments throughout the menstrual cycle. All stromal cells strongly expressed vimentin and weakly expressed cytokeratin. However, Ber‐EP4 positive stromal cells were distinctly confined around glands and to the sub‐luminal regions of the surface epithelium. The intervening stromal cells were Ber‐EP4 negative. The HLA‐DR positive stromal cells were characteristically present in three different locations: around glands and under surface epithelium, around blood vessels and around HLA‐DR positive lymphoid cells. From all antigens studied, only expression of VLA‐1 in the stromal cells showed a characteristic change throughout the menstrual cycle. Stromal cells in the proliferative and early secretory phases were VLA‐1 negative. However, VLA‐1 characteristically developed initially in the HLA‐DR positive cells around vessels and then in HLA‐DR/Ber‐EP4 positive cells around glands and under surface epithelium. Eventually, all stromal cells in the upper functionalis expressed VLA‐1 in the late secretory phase of the menstrual cycle. These data underscore a heterogeneity in stromal cells not exemplified by their morphology. Also, they provide a basis for understanding the differences that the stroma exhibits in morphologic and functional differentiation throughout the menstrual cycle.
Fertility Impairment and Improved Fetal Survival Induced by a Tumor Cell Line in Mice
Authors: BROSH NAAMA , LOTAN MIRIT , EISENBACH LEA , BROCKE STEFAN , TARTAKOVSKY BORIS
Published: May 2013

ABSTRACT: The BL6‐T2 tumor, a regressor melanoma line in C57BL/6J mice shown by us previously to be abortifacient, has been cloned in vitro. Clones obtained have been tested in vivo for tumorigenicity and effect on gestations, in order to correlate the immunogenicity of the tumor and its effect on fetal survival. Results demonstrate that high immunogenicity and impairment of fertility do not occur in the same tumor clones. We also show that this tumor produces and secretes GM‐CSF and CSF‐1 and that trophoblast cells express in situ mRNA encoding for the CSF‐1 receptor. We consequently hypothesize that this tumor exerts its abortifacient effect not via its strong immunogenicity but via cytokines it secretes.
Expression of CD4‐Like Structure on Murine Egg Vitelline Membrane and Its Signal Transductive Roles Through p56lck in Fertilization
Authors: MORI TSUNEATSU , WU GUO MAO , MORI ETSUKO
Published: May 2013

ABSTRACT: Expression of CD4‐like molecule on vitelline membrane of murine eggs was demonstrated by indirect immunofluorescence (IIF) test and immunoprecipitation corresponding to the expression of major histocompatibility complex (MHC) class II molecule on murine sperm detected by immunoblotting. This molecule showed slightly larger size than that of the authentic CD4 molecule from T‐cells on SDS‐PAGE. This molecule was suggested to bind to MHC class II structure on sperm during fertilization because anti‐CD4 monoclonal antibody (mAb) blocked in vitro fertilization (IVF). In addtion, src‐related tyrosine protein kinase (p56lck) was demonstrated in the inner vitelline membrane of eggs by means of IIF with anti‐p56lck mAb and immune‐complex kinase assay. This molecule was suggested to be associated with CD4‐like molecule.
Expression of Transferrin Receptor on Human Maternal and Neonatal Peripheral Blood Lymphocytes
Authors: KOMLOS LUISE , LANDMANN JACOB , NOTMANN JAFFA , DULITZKY FREDERIKA , HART JACOB , HALBRECHT ISAAC , GLOBERSON AMIELA
Published: May 2013

ABSTRACT: The levels of peripheral blood lymphocytes expressing the receptor for transferrin (TSR) on untreated and phytohemagglutinin (PHA)‐stimulated cell samples from maternal‐neonate pairs were evaluated 4–12 h postpartum. Significantly increased levels of TSR+ cells were observed on fresh, unstimulated neonatal and maternal cells, as compared to control cells from young adult males and females, and the values seemed to correlate with the sex of the neonate and with birth order. The level of TSR+ cells in culture was found to be increased on neonatal cells and decreased on maternal cells.
Analysis of the Expression and Immunostimulatory Capacity of Class I Major Histocompatibility Antigens on Rat Trophoblast Cell Lines
Authors: HUNT JOAN S. , YANG YAPING , WHEATON DAVID , KUNZ HEINZ W. , GILL THOMAS J.
Published: May 2013

ABSTRACT: In rat strains expressing the a and other major histocompatibility complex (MHC) haplotypes, subpopulations of placental trophoblast cells synthesize the nonclassical class I Pa antigen in preference to the classical RT1.Aa antigen. In this study, a rat trophoblast cell line, R8RP.3, which was derived from midgestation placentas of PVG.R8 (RT1.Aa) rats, was shown to express class I antigens similarly to those of trophoblast cells in situ. Both unstimulated and IFN‐γ‐exposed metabolically labeled R8RP.3 cells synthesized more Pa than RT1.Aa antigen. The reverse was true for labeled spleen cells from PVG.R8 rats. The R8RP.3 cells failed to stimulate allogeneic lymphocyte proliferation even when high levels of both classical and nonclassical class I MHC antigens were expressed on their membranes after incubation with IFN‐γ. These experiments thus supply the first evidence that the inductive phase of the immune response is not promoted by trophoblast cell class I MHC antigens, which could explain the failure of mothers to mount immune responses to class I MHC positive trophoblast cells.
Anti‐idiotypic IgM Antibodies to Anti‐HLA Class I Antibodies in Habitual Abortion
Authors: BEHAR ESTHER , CARP HOWARD , LIVNEH AVI , GAZIT EPHRAIM
Published: May 2013

ABSTRACT: In order to investigate the role of the idiotypic network in miscarriages, sera from 28 habitually aborting women undergoing paternal leukocyte immunization were studied for the presence of HLA antibodies and related anti‐idiotypes. Sixty‐eight percent of sera from preimmunized patients which did not contain anti‐lymphocyte antibodies inhibited the activity of antibodies to the HLA class I antigens expressed by the spouse.

This inhibitory activity could be assigned to IgM antibodies, which cross‐inhibit antibodies of similar specificity. This suggests that they are antiidiotypes for the binding site of HLA antibodies. Immune sera of successfully treated patients exhibited both cytotoxic IgG anti‐HLA antibodies and inhibitory IgM anti‐idiotypic antibodies. A possible role for an intact idiotypic network in maintaining pregnancy is suggested.
Immunosuppressive Factor in Cow Follicular Fluid
Authors: VESELSKÝ LEOPOLD , DOSTÁL JAROMÍR , LANDA VLADIMÍR , STANĚK ROSTISLAV , VINTER PETR
Published: May 2013

ABSTRACT: The activity of the immunosuppressive fraction and proteinase inhibitor isolated from cow follicular fluid was investigated. The immunosuppressive factor was separated from the accompanying proteinase inhibitor by Sepharose 6B and Sephacryl S‐200 column chromatography.

In vitro, the fraction significantly reduced mitogen‐induced lymphocyte proliferation. In vivo, the fraction inhibited mouse plaque formation. However, the factor had no effect on the development of intact or zona free embryos. The active components have a molecular mass of about 110,000.
A Functionally Active Complement System Is Present in Uterine Secretion of the Mouse Prior to Implantation
Authors: JIN MEISHAN , LARSSON ANDERS , NILSSON B. OVE
Published: May 2013

ABSTRACT: Sephadex beads were placed carefully in the uterus on days 2 and 3 and left for 6 to 8 h to absorb uterine secretion. The beads were then removed with volatile silicon oil and mounted on small pieces of nitrocellulose paper. Immunostaining of these bead blots showed they contained the complement components C1q, C3, C4, and C5. We demonstrated that complement component C3 in the uterine secretion could be activated and deposited on model immune complexes, and also that antibody‐coated erythrocytes were lysed in utero, that is, a membrane attack complex was produced. Thus, the mouse uterine secretion at the preimplantation stage contains a functionally active complement system.
Complete Freund Adjuvant Treatment of Pregnant Females Influences Resorption Rates in CBA/J × DBA/2 Matings via Progesterone‐Mediated Immunomodulation
Authors: SZEKERES‐BARTHO JULIA , KINSKY R. , KAPOVIC M. , CHAOUAT G.
Published: May 2013

ABSTRACT: Treatment of pregnant CBA/J females with CFA at day 0.5 and 7.5 of pregnancy significantly reduced the fetal resorption rates from 45% to 29% (P < 0.05). Supernatants of progesterone‐treated spleen cells from CFA treated CBA/J females pregnant of DBA/2 males significantly reduced natural cytotoxicity, while those of untreated identically pregnant mice had no effect. Supernatants of CFA‐treated virgin mice blocked natural cytotoxicity to the same extent as those of CFA‐treated pregnant mice. These data suggest that nonspecific immunostimulation induces progesterone receptors in spleen cells of CBA mice and that these receptors allow a progesterone dependent suppressive pathway to exert an antiresorptive effect.
Immunotherapy for Recurrent Spontaneous Abortions in a Chinese Population
Authors: HO HONG‐NERNG , GILL THOMAS J. , HSIEH HON‐JOU , JIANG JENG‐JIER , LEE TZU‐YAO , HSIEH CHANG‐YAO
Published: May 2013

ABSTRACT: The efficacy of immunotherapy for the treatment of recurrent spontaneous abortions was tested in patients selected from the same ethnically homogeneous population of Chinese in Taiwan in whom the immunogenetics of gestational trophoblastic tumors and of recurrent spontaneous abortion had been studied. The patients, who included both primary and secondary aborters, were randomly assigned to three groups: those who were immunized with their own lymphocytes (controls) (49); those who were immunized with their husbands' lymphocytes (39); and those who were immunized with third party lymphocytes (11). The data were analyzed individually for the primary and secondary aborters and collectively for both groups combined. The number of babies born, the number of current pregnancies, and the number of recurrent abortions were not statistically significantly different between the control and the immunized groups, and a similar small number of congenital abnormalities (4–9%) occurred in both the control and immunized groups. The increase in the blocking effect for the mixed lymphocyte reaction was not related to the success of the postimmunization pregnancies. Thus, this study does not show any significant improvement in the rate of livebirths in women immunized with their husbands' lymphocytes or with third party lymphocytes compared to that in a placebo‐controlled group of women.
Polyclonal Activation of IgM Antibodies to Phospholipids in Patients With Idiopathic Fetal Growth Retardation
Authors: KAJINO TORU
Published: May 2013

ABSTRACT: Phospholipid fractions and antibodies to phospholipids in the sera of normal pregnant women and patients with intra‐uterine growth retardation (IUGR) were examined. Significant elevation of serum phospholipids were observed in the second and third trimesters of normal pregnancy. Serum concentration of phosphatidylserine and sphingomyeline was significantly lower in the third trimester in patients with IUGR than in normal pregnant women. Remarkable concentrations IgG and IgA antibodies to phospholipids were not observed in the patients or in normal pregnant women. Polyclonal activation of IgM antibodies was detected in normal pregnant women in the first and second trimesters but less so in the third. The activation of IgM antibodies was not observed in patients with IUGR induced by severe preeclampsia, but significant levels of IgM antibodies were detected in the third trimester in patients with idiopathic IUGR. It is suggested that antibody formation to phospholipids in normal pregnant women is induced by elevation of phospholipids and is down‐regulated in the third trimester. Failure to down‐regulate IgM antibodies may be related to the pathogenesis of idiopathic IUGR.
Lymphocyte Subsets in the Lymph Nodes of Rats With Autoimmune Orchitis
Authors: DONCEL GUSTAVO F. , LUSTIG LIVIA
Published: May 2013

ABSTRACT: We determined temporal variations of cell subpopulations in the immunization draining lymph nodes during the development of an experimental autoimmune orchitis (EAO) induced in Wistar rats. A phenotypic characterization of T cells and their subsets (CD4+ and CD8+), B, and Ia+ cells was performed by immunofluorescent technique. At the end of the immunization period (30 days), rats injected with testicular homogenate plus adjuvants presented a considerable increase in absolute cell number but normal lymphocyte subset percentages. Testicular damage became evident at 50 days after the first immunization and increased its severity at 80 days: animals that developed EAO presented a lower number of CD8+ cells as compared with undamaged rats. This latter group showed a low CD4/CD8 ratio due to the high proportion of CD8+ cells, which could probably have a suppressor function. At 80 days massive testicular infiltration and decreased absolute cell number in lymph nodes suggest the possible migration of specific lymphocytes to the target organ.
Book Review: Pregnancy, Autoimmunology, and Connective Tissue Disorders
Authors: Shoenfeld Yehuda
Published: May 2013

Book reviewed in this article:

Pregnancy, Autoimmunology, and Connective Tissue Disorders, Edited By JS Scott and HABird
HIV Proteins in Normal Human Placentae
Authors: FAULK W. PAGE , LABARRERE CARLOS A.
Published: May 2013

ABSTRACT:Cryostat sections of human normal term placentae were studied for evidence of immunopathology by using antibodies to lymphocytes, macrophages, platelets, and coagulation factors. Areas of so‐called chronic villitis of unestablished etiology were identified in all placentae. The same tissues were examined for HIV protein antigens gp120, p17, p24, and gp41. No evidence for gp41 was found. Antigens gp120 and p17 were identified in normal chorionic villi in vimentin‐positive fibroblast‐like cells and in endothelium, respectively. Antigen p24 was localized to HLA‐DR positive cells that morphologically resembled macrophages in areas of villitis. The distribution of gp120 and p17 was similar to that observed for tissue factor. These findings prompted speculation that retroviral proto‐oncogenes that are known to encode for certain placental receptors could be involved in the presentation of tissue factor, and that gp120 may be a hitherto unrecognized immunobiological mechanism for the blockade of CD4 on maternal lymphocytes if and when such cells gain entrance to chorionic villi.
Preeclamptic Sera Stimulate Increased Platelet‐Derived Growth Factor mRNA and Protein Expression by Cultured Human Endothelial Cells
Authors: TAYLOR ROBERT N. , MUSCI THOMAS J. , RODGERS GEORGE M. , ROBERTS JAMES M.
Published: May 2013

ABSTRACT: Monolayer cultures of human endothelial cells were incubated with pre‐ and postdelivery sera from five women with preeclampsia and four matched, normal pregnancies. Conditioned media collected from endothelial cells pretreated in vitro with prepartum sera from preeclamptic women contained greater mitogenic activity and elevated levels of platelet‐derived growth factor (PDGF)‐like peptides than cells exposed to normal pregnancy sera or postpartum preeclamptic sera. Under the same experimental conditions, predelivery preeclamptic sera stimulated greater expression of endothelial cell PDGF‐B‐chain mRNA than that accumulated in the presence of matched postdelivery sera. By contrast, no differences in endothelial cell PDGF‐B mRNA levels were noted when pre‐ and postdelivery sera from normal parturients were tested. The results suggest that a factor(s) in the blood of preeclamptic women can stimulate the synthesis and release of a potent growth factor and vasoconstrictor from human endothelial cells.
Peptide Growth Factors: The Parallel Between Fetal Development and Malignant Transformation
Authors: MYERS CHARLES
Published: May 2013

ABSTRACT: Normal embryonic development and tissue homeostasis depend upon cell‐to‐cell and tissue‐to‐tissue communication. Much of this depends upon the production and release of peptide growth regulators such as fibroblast growth factor, epidermal growth factor, etc. As the molecular basis of malignant transformation has been documented, it is apparent that a common means by which a tumor becomes autonomous of external control is by becoming independent of the need for external growth factor stimulation. This can occur through the cell producing and releasing the growth factors needed for its own growth. A similar end result can occur with growth factor receptor mutants in which the receptor gives a positive signal even when no growth factor is bound to the receptor. One potential therapeutic strategy is to interfere with this autocrine loop. Suramin is presented as an example of a drug capable of blocking such autocrine loops. This drug also reverses malignant transformation due to Platelet Derived Growth Factor and K‐fgf/hst oncogenes on this basis. Another potential mechanism to accomplish the same end is through the use of monoclonal antibodies to either the growth factor or its receptor. Examples of this are available for TGF‐alpha. We have discussed a range of practical issues involved in developing monoclonal antibodies as therapeutic agents.
Cytokines: An Overview
Authors: TROTTA PAUL P.
Published: May 2013

ABSTRACT: Cytokines are a broad, heterogeneous group of proteins and polypeptides that regulate intercellular communication. Examples of cytokines include interleukins, interferons, colony‐stimulating factors, and a variety of growth factors. The preparation of large quantities of highly purified recombinant cytokines has provided a basis for their biological and physicochemical characterization. The pleiotropic biological effects of these factors are expressed through binding to specific, high‐affinity cell‐surface receptors. Although they are different in amino acid sequence, cytokines have a number of biological and physicochemical properties in common.
Failure to Detect Integrins of the Beta‐2 Subclass on the Human Sperm Surface
Authors: FUSI FRANCESCO , BRONSON RICHARD A.
Published: May 2013

ABSTRACT: Several cell‐to‐cell recognition systems utilize the tripeptide Asp‐Gly‐Arg (RGD) as a cell surface signaling sequence. Mac‐1, a member of the integrin subfamily defined by the beta‐2 subunit, recognizes C3bi by means of an RGD sequence. Because C3 complement components have been detected on the gamete surfaces and RGD has been demonstrated to be involved in sperm‐egg interaction, we explored the possibility that a member of the b2 integrin subfamily was present on the sperm surface and involved in egg recognition. Two methods were utilized to detect integrins on the sperm surface. Sperm were exposed to Mabs directed against different epitopes of each member of this integrin subfamily; and spermatozoa were tested for their ability to bind zymosan or yeast, since Mac‐1 bearing cells possess this property. Both methods failed to demonstrate such integrins on the sperm surface, suggesting that another RGD receptor is involved in gamete recognition.
Regulation of Bovine Endometrial Secretion of Prostaglandins and Synthesis of 2′,5′‐Oligoadenylate Synthetase by Interferon‐α Molecules
Authors: BARROS C.M. , PLANTE C. , THATCHER W.W. , HANSEN P.J.
Published: May 2013

ABSTRACT: Experiments were performed to (1) verify the inhibitory effect of bovine trophoblast protein‐1 (bTP‐1) on uterine prostaglandin synthesis, (2) evaluate whether other interferon‐α (IFN‐α) molecules also inhibit prostaglandin secretion, and (3) test whether the enzyme 2′,5′‐oligoadenylate synthetase (2‐5A synthetase) can be induced in endometrium by interferon‐α. In experiment 1, all interferon molecules (bTP‐1, oTP‐1, bIFN‐α and hIFN‐α) equally inhibited secretion of PGF and PGE2 from endometrial explant cultures obtained at day 17 of the estrous cycle. In experiment 2, endometrial explants obtained from day 17 of the cycle were cultured with and without bovine serum albumin (BSA; 50 μg/ml) and bIFN‐α (0, 0.84, 4.2, and 42 nM). Addition of BSA to the culture medium greatly enhanced the accumulation of PGF into the medium. The bIFN‐α inhibited accumulation of PGF and PGE2 in both the presence or absence of BSA by 12 h. All three concentrations of bIFN‐α were equally effective in inhibiting prostaglandin accumulation. Additionally, all concentrations of bIFN‐α increased the amounts of 2‐5A synthetase in endometrium. In conclusion, these results confirm the inhibitory effect of bTP‐1 on PGF release from endometrium and demonstrate that bTP‐1 can also inhibit PGE2 secretion. Furthermore, other interferon‐α molecules, including bIFN‐α, hIFN‐α, and oTP‐1, also reduced PGF and PGE2 secretion in culture. It is likely, therefore, that conceptus and other interferon‐α molecules exert similar effects on endometrium in vitro and that the antiluteolytic effects of bIFN‐α in vivo are mediated in part by changes in endometrial prostaglandin synthesis.
Leukocyte Distribution in the Pseudopregnant Mouse Uterus
Authors: CHOUDHURI RAJANI , WOOD GARY W.
Published: May 2013

ABSTRACT: Pseudopregnancy, induced by mating females with vasectomized males, is a frequently used model for studying pregnancy‐like uterine changes in the absence of an embryo. Leukocytes make a significant contribution to uterine cellularity during pregnancy. The present study was designed to determine whether changes in numbers and distribution of leukocytes in the uterus during pseudopregnancy and following intraluminal injection of a deciduogenic stimulus parallel changes observed during the first eight days of pregnancy. Common leukocyte antigen positive (CLA +) cells, macrophages (F4/80+ cells), and granulocytes were assessed between days 1 and 8 of pseudopregnancy using qualitative and quantitative immunohistochemistry. High numbers of CLA+ leukocytes were present on days 1 and 2. Those were comprised primarily by macrophages, polymorphonuclear leukocytes, and eosinophils. High concentrations of leukocytes were detected in the endometrium, and some granulocytes were observed migrating through the luminal epithelium. Leukocytes, principally macrophages, were reduced in number and were distributed throughout the endometrium on days 3 and 4. Introduction of oil to the uterine lumen on day 4 stimulated primary decidualization. Decidual cells were CLA − and F4/80, − and, as decidualization proceeded, CLA+ and F4/80+ cells decreased in number in the anti‐mesometrial uterus and were detected primarily in the deep endometrium. Later, a secondary decidualization zone developed in the mesometrial aspect of the uterus. Unlike the initial decidual reaction, which was relatively free of leukocytes, the secondary decidual zone contained very high numbers of CLA+ and F4/80+ cells. The uninjected uterine horn remained relatively unchanged from days 3 through 8. The quantitative and distributional changes observed in the leukocyte populations during pseudopregnancy were similar to those which have been observed during pregnancy.
Functional Alterations of Murine Peritoneal Macrophages During Pregnancy
Authors: BARAÑAO ROSA INÉS , TENENBAUM ANNAT , SALES MARIA ELENA , RUMI LILIA S.
Published: May 2013

ABSTRACT: We have studied some functional characteristics of murine peritoneal macrophages (MOp) related to hormonal changes produced during pregnancy. Maximal expression of Ia antigen and release of interleukin 1 (IL1) were observed during the first week of pregnancy (implantation), when the highest peak of estradiol was produced. Both Ia antigen expression and IL1 levels progressively decreased as gestation advanced. Inversely, MOp capability to phagocyte and reduce nitro blue tetrazolium (NBT) was diminished at the beginning of pregnancy but returned to normal values in the last week. Sexual steroid levels (estradiol and progesterone) were inversely related, and the release of prostaglandin E2 (PGE2) by MOp decreased when progesterone levels increased. Although PGE2 production had no evident relation with Ia antigen expression and IL1 activity during the first and second weeks of pregnancy, the increment in PGE2 values and percentages of NBT+ cells could indicate a different stage of macrophage activation. These results suggest a possible hormonal regulation of macrophage functionality.
Fetal Stem Vessel Endothelial Changes in Placentae From Normal and Abnormal Pregnancies
Authors: LABARRERE C. A. , FAULK W. PAGE
Published: May 2013

ABSTRACT: Areas of immunocytochemically defined immunopathology are common in placentae from secondary recurrent spontaneous aborters. Endothelial cells of affected villi were found to be negative for the thrombomodulin natural anticoagulant pathway, and these cells were reactive with monoclonal antibodies to tissue factor and fibrin. Endothelial cells of normal villi adjacent to affected villi also were negative for thrombomodulin and positive for tissue factor and fibrin, but endothelium of normal villi distant to affected villi were thrombomodulin‐positive, tissue factor‐negative, and did not contain deposits of fibrin. These findings indicate that a loss of endothelial anticoagulant activity precedes the onset of immunopathology. This observation, coupled with the findings that fetal stem vessels normally lack the heparan sulfate proteoglycan‐antithrombin III natural anticoagulant pathway and that normal cord blood contains a heparin‐like anticoagulant, suggest that a failure of endothelial anticoagulation may be a primary event in the development of placental immunopathology.
Interleukin‐1α and Interleukin‐1 β in Preterm and Term Human Parturition
Authors: ROMERO ROBERTO , MAZOR MOSHE , BRANDT FRANCISCO , SEPULVEDA WALDO , AVILA CECILIA , COTTON DAVID B. , DINARELLO CHARLES A.
Published: May 2013

ABSTRACT: Interleukin‐1 (IL‐1) has been implicated in the mechanism of human parturition in the setting of infection. The purpose of this study was to determine the effect of labor (term and preterm) and microbial invasion of the amniotic cavity on amniotic fluid (AF) concentrations IL‐1 α and IL‐1 β. AF was retrieved by transabdominal amniocentesis from the following groups of women: midtrimester genetic amniocentesis (16 to 18 wk) (N = 15), preterm labor with intact membranes (21 to 36 wk) with or without infection (N = 72), preterm premature rupture of membranes (PROM) (N = 88), and term not in labor or in active labor with or without infection (N = 58). AF was cultured for aerobic and anaerobic bacteria as well as Mycoplasmas. IL‐1 was measured with a commercially available immunoassay validated for AF (sensitivity: IL‐1α, 157 pg/ml; IL‐1β, 50 pg/ml). All women at midtrimester had undetectable AF IL‐1α and IL‐1 β. Among women in preterm labor with positive AF cultures, IL‐1α and IL‐1 β were detectable in the AF in 86.6% (13/15) and 100% (15/15), respectively. In contrast, all women with negative AF cultures without labor (N = 36) had undetectable AF IL‐1α concentrations and 52.7% (19/36) had undetectable AF IL‐1β concentrations. Histopathological chorioamnionitis was present in 92.8% (13/14) of patients who had positive AF cultures and detectable IL‐1 in the AF. IL‐1 was significantly higher in patients with preterm PROM, labor, and positive AF cultures than in the other subgroups of patients with preterm PROM. Among women at term who were not in labor, 26.3% (5/19) had detectable IL‐1α and 19.8% (3/19) had detectable IL‐1β in the AF. Among those in active labor with positive AF cultures, 44.4% (4/9) had detectable IL‐1α and 88.8% (8/9) had detectable IL‐1β in the AF. IL‐1β was detected more frequently in patients at term with positive AF cultures than in those with negative AF cultures (88.8% [8/9] vs. 38.7% [19/49]; P = 0.0088). We conclude that AF IL‐1 concentrations are elevated in women with preterm labor an microbial invasion of the amniotic cavity and in women with spontaneous parturition at term.
Evaluation of Immunological Infertility
Authors: COULAM CAROLYN B. , STERN J. JAROSLAV
Published: May 2013

ABSTRACT: To evaluate the frequency with which immunological factors are associated with infertility, 92 couples with unexplained infertility were studied by using assays to detect anti‐sperm antibodies (ASA), human leukocyte antigen tissue types (HLA), lymphocytotoxic antibodies (LCA), and inhibitors of mixed lymphocyte culture (MLC) and mouse blastocyst assay (MBA). Seventy‐three of the women had blood assayed for antiphospholipid antibodies (APA). The frequencies of APA, ASA, LCA, inhibitors of MLC and MBA, as well as HLA associations previously reported to be related to infertility (B locus blanks, single DQ locus in offspring, >1 DR sharing between mates) among 92 infertile couples were compared with those observed among 41 fertile control couples. No significant differences in the frequencies of APA, ASA, MBA, and HLA associations between fertile and infertile couples were observed. Fertile couples demonstrated the presence of wife anti‐husband LCA and MLC inhibitors more frequently than did infertile couples (51% vs. 8%, P = 0.0001 and 29% vs. 4%, P = 0.002, respectively). While APA, ASA, HLA tissue typing, LCA, and MLC and MBA have been previously reported as being markers of autoimmune and alloimmune responses relating to reproductive outcome, the current data suggest that more specific markers are necessary to diagnose immunological components of intertility.
New Concepts in Ovarian Regulation: An Immune Insight
Authors: STERN JAROSLAV , COULAM CAROLYN B.
Published: May 2013

ABSTRACT: The purpose of the ovary is to produce eggs. In the human, oocyte production occurs cyclically at monthly intervals. The control of egg production is provided by both the endocrine and immune systems. Successful oocyte production is the result of sophisticated communication between the two systems. These interactions allow adaptive processes necessary for continuation of the species.
The Complement System in Human Reproduction
Authors: VANDERPUYE OLUSEYI A. , LABARRERE CARLOS A. , McINTYRE JOHN A.
Published: May 2013

ABSTRACT: Regulation of the complement system in reproduction is unique inasmuch as reproductive tissues represent the only condition where allogeneic interactions occur naturally. Both allogeneic extraembryonic membranes and semen that contact and interact with maternal cells and tissues must avert complement‐mediated damage to ensure reproductive success. Several regulators of complement activation exist. Membrane cofactor protein (MCP) and decay accelerating factor (DAF) inactivate C3 and C5 convertases on cell surfaces. In addition, CD59 inhibits the membrane attack complex (MAC) of the complement cascade. Strong expression of these membrane glycoproteins by trophoblast and amniotic epithelium has been observed. MCP, DAF, and CD59 likely safeguard extraembryonic tissues from complement damage originating from maternal and fetal blood or amniotic fluid.

Different reproductive tract fluids vary in complement levels. With the exception of ovarian follicular fluid, these levels are generally much less than those in blood. Endometrial and cervical content of C3 appear to be regulated by hormones. These observations suggest that the effects of complement activation may vary in reproductive tissues. MCP is absent from the surfaces of oocytes. Sperm express MCP and DAF in discrete areas that would not be associated with the known complement‐regulatory functions of these proteins. Seminal plasma contains MCP and the MAC inhibitor SP‐40,40 but not DAF. SP‐40,40 may exemplify how complement‐regulatory proteins perform alternative functions as it interacts with molecules other than complement components. We have reviewed aspects of the complement system that relate to allogeneic interactions in reproduction and that suggest fruitful areas for further research.
Characterization of the Anti‐Cancer Activity of Transferrin‐Adriamycin Conjugates
Authors: SIZENSKY JOSEPH A. , BARABAS KLARA , FAULK W. PAGE
Published: May 2013

ABSTRACT: The anthracycline anti‐cancer drug adriamycin (Adr) was coupled to human transferrin (Trf) by using a glutaraldehyde technique. The effect of Trf‐Adr conjugates and unconjugated Adr on human cells was determined by using normal peripheral blood mononuclear cells and chronic myelogenous K562 cells. Cytotoxicity was determined by using an assay that measures the conversion of a tetrazolium salt (MTT) into a purple product (formazan) by mitochondrial dehydrogenases in viable cells. We found that free Adr at a concentration of 1 × 10−7 had little effect on K562 cells, while Trf‐Adr conjugates inhibited 75% of cellular activity. When normal peripheral blood mononuclear cells were tested against Trf‐Adr conjugates, the 50% inhibitory concentration was found to be 1.4‐1.7 × 10−6 M, at which concentration >85% of K562 cells were inhibited. Interactions of Trf‐Adr conjugates with plasma membrane energy‐producing systems are the proposed mechanisms of cytotoxicity.
Proto‐Oncogenes and Germ‐Cell Differentiation
Authors: TORRY DONALD S.
Published: May 2013

ABSTRACT: Oncogenes are identified functionally by their ability to induce neoplastic transformation of susceptible cells. The first oncogenes to be characterized were isolated from acutely transforming retroviruses. Subsequently, it was determined that the retroviral oncogenes were formed from normal, progenitor genes. These cellular homologs of the viral oncogenes are termed proto‐oncogenes. The derivation of oncogenes from proto‐oncogenes is the consequence of mutations that remove regulatory constraints from the proto‐oncogene. The ability of oncogenes to induce transformation implies that proto‐oncogenes may function in growth and differentiation pathways in normal cells. Although many proto‐oncogenes have been defined, the normal physiological function of most is not known. Studies of proto‐oncogene expression during normal game‐togenesis have determined that some genes are expressed in a stage‐specific manner. The use of germ cells to provide homogeneous and defined normal cell populations facilitates identifying the roles proto‐oncogenes have in regulating cell growth and differentiation.
Significant Compatibility Does Not Exist at the HLA‐DQB Gene Locus in Couples With Unexplained Recurrent Abortions
Authors: TAKAKUWA KOICHI , HIGASHINO MASAHIKO , UEDA HIROYUKI , YAMADA KIYOSHI , ASANO KENSAKU , YASUDA MASAKO , ISHII SHIRO , KAZAMA YOSHIKI , TANAKA KENICHI
Published: May 2013

ABSTRACT: The polymerase chain reaction‐restricted fragment length polymorphism (PCR‐RFLP) method was used for both examining compatibility at the HLA‐DQB1 gene locus and determining HLA‐DQ antigen polymorphism in spouses of unexplained recurrent abortions. Genomic DNA samples were prepared from peripheral mononuclear cells from patient and control couples. Two hundred and thirty base pair fragments of the second exon of the HLA‐DQB genes were selectively amplified. Amplified DNAs were digested with the restriction endonucleases, Fok I, Hae III, Hha I, Rsa I and Sau3A I, and subjected to electrophoresis in a polyacrylamide gel. The RFLPs showed that habitual aborters and their husbands had neither significantly frequent alleles nor shared common alleles at the HLA‐DQB locus when compared to the control group.

Since significant HLA‐DQB compatibility was not observed between the spouses and unexplained recurrent aborters, in order to determine whether or not HLA compatibility is responsible for the genesis of unexplained recurrent abortions, it is imperative to further examine the compatibility between other HLA gene loci.
Danazol Suppresses Both Spontaneous and Activated Human Lymphocyte‐Mediated Cytotoxicity
Authors: VIGANÓ PAOLA , DI BLASIO ANNA MARIA , BUSACCA MAURO , SABBADINI MARIA GRAZIA , VIGNALI MARIO
Published: May 2013

ABSTRACT: Danazol is an effective drug in the treatment of endometriosis. Previous reports suggest that it can act by influencing the immune system. Thus, in this study we evaluated whether danazol is able to affect the expression of natural and activated cytotoxicity by human peripheral blood lymphoctyes (PBL).

A cytotoxicity assay by 51Cr release was performed to determine the effect of danazol on lymphocyte cytotoxic response toward an erytroleukemic cell line (K562).

A significant suppression of spontaneous cytotoxicity was observed when lymphocytes were pre‐treated for 18 h with danazol at the concentration of 5 × 10−6M. In addition, danazol could significantly inhibit both IL‐2‐ and INFα‐activated cytotoxicity at the concentration of 10−5 M. Following 18 h exposure to danazol, PBL were able to completely recover their spontaneous but not activated cytotoxic potential upon further in vitro incubation (18 h) in absence of the drug. The biological significance of danazol as an inhibitor of immune function under experimentally defined conditions is discussed in relation to its possible role in vivo.
In Vitro Sperm Capacitation to Treat Antisperm Antibodies Bound to the Sperm Surface
Authors: LENZI Dott. A. , GANDINI L. , LOMBARDO F. , MICARA G. , CULASSO F. , DONDERO F.
Published: May 2013

ABSTRACT: Our objective was to study antisperm antibody bound to the acrosome region during in vitro capacitation and to determine whether acrosome‐antibody free sperm can be obtained from previously acrosome‐antibody‐coated sperm.

The spermatozoa from a selected series of 14 patients were tested for sperm antibodies bound to the sperm surface using d‐IBT and focusing on the acrosome positivity. The tests were carried out before the incubation and after 3, 6, 9, and 12 h of incubation in Tyrode's solution with 0.5% human serum albumin as the capacitation medium. Tests to evaluate acrosome region, sperm motion parameters, and zonae binding ability were carried out. In this way we were able to evaluate sperm function during capacitation protocol.

The patients were 14 subjects selected according to good seminal characteristics, good post‐rise sperm parameters, and high percentage of ASA bound to the sperm surface.

In all cases the results showed that antisperm antibodies bound to the acrosome region were shed prior to the acrosome reaction.

During sperm capacitation in human a modification, migration, or shedding of plasma membrane molecules takes place. The presence of antibodies in such an important area of the sperm head could certainly interfere in the fertilization process. Our data indicate that in vitro capacitation could provide an in vitro therapy capable of eluting antibodies from the acrosome region.
Analysis of T‐Lymphocyte Subsets After Phytohemagglutinin Stimulation in Normal and Type 1 Diabetic Mothers and Their Infants
Authors: GIORDANO C. , DE MARIA R. , MATTINA A. , STASSI G. , TODARO M. , PUGLIESE A. , GALLUZZO G. , BOTTA R.M. , GALLUZZO A.
Published: May 2013

Our aim was to investigate the immunological status of diabetic pregnancy, which is an overlap of diabetic immunity abnormalities and the immunological modifications normally occurring during pregnancy.

METHOD: We studied lymphocyte subpopulations and lymphokine production, after 96 h of phytohemagglutinin (PHA) stimulation, from normal and Type I diabetic pregnant women at delivery time and from the respective cord blood.

RESULTS: Peripheral blood mononuclear cells (PBMC) from both normal and Type I diabetic mothers showed an increase in CD8+ and a decrease in CD4+ cells compared to the respective cord blood mononuclear cells (CBMC). Moreover, Type I PBMC showed a lower number of “activated” CD3+DR+cells and a higher number of CD8+CD25+ cells with respect to normal women, which may reflect the dysregulatory pattern due to the autoimmune condition. Type I CBMC showed a big increase in the number of CD4+ Leu8+ cells, a cell subpopulation characterized by inhibitory activity. Finally, as regards lymphokine release in culture supernatants, type I diabetes seemed to be associated with an overproduction of IL1 and IL6, although the latter increase is less evident in CBMC cultures.

CONCLUSIONS: The present study shows that diabetic pregnancy is associated with major alterations of cell‐mediated immunity leading to a state of immunodepression. Moreover, our study suggests that the maternal immunological status influences fetal immunity, as demonstrated by the increase in the number of regulatory cells and by the altered pattern of lymphokine production (IL1 and IL6) by lymphocytes derived from diabetic CBMC. The latter phenomenon perfectly mirrors maternal PBMC characteristics.
Effect of Labor on Lymphocyte Subsets in Full‐Term Neonates
Authors: SAMELSON RENEE , LARKEY DEBORAH M. , AMANKWAH K.S. , MCCONNACHIE PETER
Published: May 2013

PROBLEM: To determine the effect of labor on lymphocyte subsets in full‐term neonates. Method of Study. Cord blood obtained at delivery from full‐term neonates, six born vaginally and six born by elective Cesarean section, was analyzed for lymphocyte subsets. Monoclonal antibodies, immunofluorescence, and flow cytometry were utilized to determine the lymphocyte phenotype frequencies in these neonates. These frequencies were compared by mode of delivery and to adult peripheral blood reference ranges using a two‐tailed Student's t‐test,P<0.05.

RESULTS: A profile of significantly elevated T (CD2, CD3) and helper cells (CD4) and depressed Natural Killer cells (CD16, CD56) is characteristic of term Cesarean section neonates. Significantly depressed frequency of T cells (CD2, CD3) and helper T cells (CD4) and elevated Natural Killer cells (CD16, CD56) is characteristic of vaginally delivered neonates

CONCLUSIONS: The mode of delivery affects the lymphocyte subset frequencies in full‐term neonates.
Polymorphism of the Pa Gene
Authors: VISHTEH ARASH G. , KUNZ HEINZ W. , HASSETT ANDREA L. CORTESE , GILL THOMAS J.
Published: May 2013

PROBLEM: This study was undertaken to identify the number of alleles of the Pa gene at the DNA level and to correlate the presence of the different alleles with the ability of a strain to elicit an anti‐Pa antibody response when mated with a WF female. The Pa gene is present in both Pa + and Pa − strains of rats, but it has unique restriction fragment length polymorphisms (RFLP) in the two types of strains: 1.7 kb in Pa− and 1.8 kb in Pa + Xbal digests using a probe derived from the Pa gene.

RESULTS: Examination of DNA from a variety of strains using different enzymes showed that there were characteristic RFLP patterns for Pa+ and Pa−strains. Strains of the b haplotype, however, had an intermediate RFLP pattern, and all of these strains had a relatively low level of reactivity with anti‐Pa antibody.

CONCLUSIONS: Thus, there are three alleles of the Pa gene based on their level of expression: Paa, high; Pab, low; and Pa−, none.
Development and Distribution of the White Blood Cells Within Various Structures of the Human Menstrual Corpus Luteum Examined Using an Image Analysis System
Authors: PETROVSKÁ MARIANNA , SEDLÁK ROMAN , NOUZA KAREL , PRESL JIRÍ , KINSKÝ RADSLAV
Published: May 2013

PROBLEM: Emerging evidences suggest that immunoendocrine interactions play definitive roles during development and regression of the human menstrual corpus luteum (hmCL). We have studied the distribution of immune cells within individual structures of hmCL during various stages of its development.

METHOD: Immunoperoxidase‐stained ultra‐thin frozen sections were evaluated using light microscopy fitted with an image analysis system.

RESULTS: The results suggest that monocytes/ macrophages and MHC class II positive cells are the most prominent immune cells within the hmCL throughout its whole lifespan. Both cell types are concentrated within the trabeculae. In addition, MHC class II positive cells are abundant also within the granulosa‐luteal layer. T helper/inductor (Th/i) and T cytotoxic/suppressor (Tc/s) cells were detected only in minor amounts within the thecal trabeculae of mature tissue.

CONCLUSIONS: Possible links between the occurrence and functional roles of the immune cells studied are discussed.
Identification of Lymphocyte Subsets in the Human Fallopian Tube
Authors: BOEHME MICHAEL , DONAT HANS
Published: May 2013

PROBLEM: Immunohistochemical investigations for the detection of lymphocyte subsets in the human oviduct have been performed. Knowledge about local immunity especially cell‐mediated immunity, in the fallopian tube has been, up to now, limited. As an essential structure for the human reproduction process, the tubal mucous membrane is exposed to a variety of antigens.

METHOD: A total number of 20 tubal biopsies obtained from fertile women during gynecological operations like tubal ligations or hysterectomy were examined by the immunoperoxidase technique. Seven specimens were obtained during the proliferative phase, ten during the secretory phase and three during a caesarean section with tubal ligations.

RESULTS: It could be established that the presence of lymphocytes in the oviductal mucous membrane is physiological. These cells can be identified by their typical immunohistochemical patterns. There were no significant differences of the type and number of lymphocytes in the mucosa within the phases of menstrual cycle. The dominant cell types in the tubal mucosa were the CD3 + and CD8 + lymphocytes.

CONCLUSIONS: It can be suggested that the lymphocytes in the tubal mucosa may involved in the process of immune tolerance, which could realize the transport of sperms and blastocyst through the oviduct under normal conditions without activation of local immune mechanisms. The lymphoid tissue of the oviduct is a specialized form of mucosal‐associ‐ated lymphoid tissue (MALT).
Quantitative and Qualitative Changes in the Intraepithelial Lymphocyte Population in the Uterus of Nonpregnant and Pregnant Sheep
Authors: LEE C.S. , MEEUSEN E. , GOGOLIN‐EWENS K. , BRANDON M.R.
Published: May 2013

PROBLEM: Previous studies have revealed the presence of a unique population of CD45R + granulated cells in the sheep uterine epithelium. In the present study, dramatic changes in this cell population and in the nongranulated lymphocytes in the uterine and endometrial glandular epithelium of non‐cycling, cycling, pregnant, and postparturient sheep are described. In noncycling and cycling sheep, the granules in the granulated intraepithelial cells were small. From days 55 to 134 of pregnancy, the granules in these cells were large, and there was a significant increase (P < 0.01) in the proportion of this cell population in the uterine epithelium but not in the endometrial glandular epithelium located in the deeper region of the stroma. The number of these cells declined dramatically (P < 0.01) from 2 to 15 days after parturition. Both the tissue distribution and the time of activation of these cells suggests they are different from the granulated lymphocytes described in placentae of mice and man.

CONCLUSIONS: It is concluded that this unique population of granulated cells is derived from lymphocytes, and that these cells become metabolically active from mid‐ to late‐pregnancy and may play a physiological role during pregnancy or birth. In contrast, the number of nongranulated intraepithelial lymphocytes were suppressed throughout pregnancy and they probably do not play a role in pregnancy.