bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular Immunity in Human Milk
Authors: OKSENBERG J.R. , PERSITZ E. , BRAUTBAR C.
Published: December 2015

ABSTRACT: The responses of human milk lymphocytes (MIL) to a variety of immunogenic stimuli were studied and compared to those of peripheral blood lymphocytes (PBL) from the milk donors. MIL showed a decreased proliferative response to mitogens and allogeneic leukocytes in vitro but displayed the ability to stimulate alloreactivity equivalent to PBL. Neither pretreatment with cell‐free autologous milk nor co‐cultured MIL were capable of suppressing the proliferative responses of PBL. Moreover, macrophages isolated from milk and pulsed with soluble antigen or allogeneic cells effectively induced proliferation by peripheral blood T cells whereas the response of milk nonadherent cells to antigen presented by peripheral macrophages was very low. MIL respond better to pathogenic enteric E. coli than PBL but not as well as PBL to Yersinia enterocolitica. Treatment of MIL with monoclonal antibodies cytotoxic for T cells abolished their response to bacterial antigens. Application of an anti HLA class II antigen monoclonal antibody to mixed lymphocyte or lymphocyte‐bacteria cultures resulted in substantial inhibition of the MIL response similarly to that of PBL. The relevance of these data to the immunological needs of the neonate are discussed.
In Vitro Fertilization Results for Women With Sperm Antibodies in Plasma and Follicular Fluid
Authors: CLARKE G.N. , McBAIN J.C. , LOPATA A. , JOHNSTON W.I.H.
Published: December 2015

ABSTRACT: In vitro fertilization (IVF) and embryo transfer results were analyzed for three women with sperm antibodies in their plasma and follicular fluid. These preliminary results suggest that substitution of the patients' serum by replacement serum in the fertilization and embryo growth media may prove to be an effective means of improving IVF' treatment for women with sperm immunity.
Effect of Maternal Parasitic Disease on the Neonate
Authors: STRATTON JOAN A. , MILLER R. DAVID , SCHMIDT PATRICIA
Published: December 2015

ABSTRACT: Parasitic disease is the most common infectious disease complication of pregnancy worldwide, resulting in maternal debilitation and fetal prematurity and low birth weight. The increasing incidence of these diseases in our population led to the present study of 125 patients, 34 of whom were found to be infected with at least one intestinal parasite. In contrast to studies in developing countries, no significant differences in either maternal anemia, or fetal birth weight, or prematurity were found between the infected and non‐infected groups. However, there was a three‐fold increase in the incidence of significant neonatal hyperbilirubinemia in the parasitized group. Parasitic disease complicating pregnancy in our population does not appear to exert the same adverse effect on mother and fetus as that described in other countries. In view of the limited pathology associated with parasitic disease, treatment, other than with iron and vitamin supplementation, is not routinely indicated in pregnancy in populations similar to ours. However, due to the increased incidence of neonatal jaundice and morbidity we would recommend close observation of the neonates in the immediate postpartum period.
The Immunoglobulin Class of anti‐spermatozoal antibodies in Serum
Authors: Clarke G.N. , Stojanoff A. , Cauchi M.N. , Johnston W.I.H.
Published: December 2015

ABSTRACT: The aim of this study was to determine the immunoglobulin class of circulating antisperm antibody using a technique called the indirect immunobead test (IBT). In the IBT sperm bound antibodies are detected using polyacrylamide beads coated with rabbit antihuman immunoglobulin classes IgG, IgA, and IgM. Of the 20 infertile men with serum immobilizins, 100% were found to be positive for sperm‐bound IgG, 50% positive for IgA, and 0% positive for IgM, using the IBT. Similarly, 20 infertile females with serum immobilizins showed 95% positivity for IgG, 60% for IgA, and 15% for IgM. Thus there was a good correspondence between the presence of serum immobilizins as determined by the sperm immobilization test (SIT) and the IBT. This study provides data that indicates that IgG and IgA are the two major immunoglobulin classes of sperm antibody in male and female immune sera as detected by a simple, sensitive immunological technique, the serum IBT.
A Candidate Carrier Protein for β‐Human Cliorionic Gonadotropin: 54,000‐Molecuiar‐Weiglit Fragment of Tetanus Toxin
Authors: COVEY DANA C. , MOORE DONALD E. , CHANG C.C. , LAURENCE KENNETH A.
Published: December 2015

ABSTRACT: As an alternative to intact tetanus toxoid as a carrier for β‐human chorionic gonadotropin (β‐hCG), a fragment of tetanus toxin was sought that had a relatively low molecular weight, yet was highly immunogenic. Purified culture filtrate tetanus toxin was subjected to limited enzymatic digestion with papain, and the resulting fragments separated by column chromatography on Sephadex G‐150. Four fractions were thus identified. Fraction II was found to have a molecular weight of 54,000 by SDS‐polyacrylamide gel electrophoresis. This fragment was covalently linked to the β‐subunit of hCG (β‐hCG‐TTn) using carbodiimide hydrochloride. The ability of β‐hCG‐TTn to stimulate production of anti‐hCG sera in rabbits was measured by 125I‐hCG radioimmunoassay. At sera dilutions of 1:40,000, an average 125I‐hCG binding capacity of 34.7 + 5.86% (mean ± SD) was observed 8 weeks after the final immunization. Tetanus toxin Fragment II has the potential for future application in active immunization studies involving hormone‐carrier conjugates.
Analysis of Antibodies Against Mouse Spermatozoa Using an Enzyme‐Linked Immunosorbent Assay (ELISA)
Authors: ALLEN R.D. , STEVENSON K.L. , ROBERTS T.K.
Published: December 2015

ABSTRACT: Conventional techniques used for the analysis of antisperm antibodies are not suited to the mouse model because of their requirements for relatively large amounts of serum and their inability to handle large numbers of samples. This has inhibited use of the mouse as an experimental model in areas involving antisperm immunity. As the ELISA technique has been successfully applied to analysis of antisperm antibody in human sera, we investigated its use as an assay for screening antisperm antibody in mouse serum. This report describes a simplified version of the ELISA technique that we have found to be successful for this purpose. The assay described can assess levels and classes of antisperm antibody in mouse serum and can also be used as a screening assay for monoclonal antibodies to mouse sperm. It should facilitate use of the mouse in experimental work in areas involving assessment of immunity to sperm.
Effect of Oral Contraceptives on Leukocyte Phagocytic Activity and Plasma Levels of Prostaglandin E2 and Tromboxane B2 in Normal Menstruating Women
Authors: STRATTON JOAN A. , MILLER R. DAVID , KENT DERYCK R. , WEATHERSBEE PAUL S. , THRUPP LAURI D. , RICHARDS CAROL A. , DISAIA PHILIP J.
Published: December 2015

ABSTRACT: Mononuclear and polymorphonuclear cells were isolated from the peripheral blood of normal menstruating women. Four of the subjects were not using oral contraceptives and five were taking various formulations. The women were tested once a week for 12 consecutive weeks. Plasma levels of 6‐keto‐prostaglan‐din F2α (6‐KF), prostaglandin E2 (PGE2), thromboxane B2 (TxB2), estrogen, and progesterone were measured by specific radioimmunoassays. The phagocytic activity of the mononuclear and polymorphonuclear cells isolated from the peripheral blood was measured with a bacterial phagocytosis and killing assay. The phagocytic activity of both types of cells was depressed perimenstrually in both groups of women. However, examination of individuals showed that those subjects not taking oral contraceptives had a worsening of phagocytic activities with approaching menses while the oral contraceptive subjects generally had an improving of these activities at this time. We were unable to correlate the phagocytic activities with either hormone or prostaglandin levels in the plasma of these subjects. However, the subjects on oral contraceptives had significantly lower levels of PGE2 and TxB2 than those women who were not using oral contraceptives.
Spermatogenic Disturbance Induced in Mice by Combined Local Injection of Monoclonal Antibodies to Sertoli Cell and to Basal Lamina of Seminiferous Tubule
Authors: ICHINOHASAMA RYO , HIROKAWA KATSUIKU , HATAKEYAMA SHIGERU
Published: December 2015

ABSTRACT: Two kinds of hybridoma clones, one producing monoclonal antibodies against Sertoli cell (TM‐1) and the other the basal lamina of the seminiferous tubule (TM‐2), were raised by fusion between P3X63Ag8‐653 mouse myeloma cells and spleen cells of BALB/c mice (H‐2d) immunized with testicular homogenate of the same inbred mice. Immunohistochemically, TM‐1 reacted specifically with cytoplasmic component of Sertoli cell and TM‐2 with basal lamina of the seminiferous tubule. Using these monoclonal antibodies, spermatogenic disturbance was induced experimentally in BDF1(H‐2b/d) by intratesticular injection of a set of these two antibodies. Single injection of either TM‐1 or TM‐2 failed to induce the lesion. This fact indicated that TM‐1 antibody could reach the Sertoli cell to impair its function, which was otherwise inaccessible without coincidental action of TM‐2 antibody. TM‐2 antibody appeared to alter the permeability of the basal lamina of the tubule and lower its barrier effect.
Refractoriness of Rhesus Monkeys to Repeated Ovarian Stimulation by Exogenous Gonadotropins is Caused by Nonprecipitating Antibodies
Authors: BAVISTER BARRY D. , DEES CRAIG , SCHULTZ RONALD D.
Published: December 2015

ABSTRACT: Oocytes obtained from superstimulated rhesus monkeys are needed for in vitro fertilization experiments. The animals become refractory to repeated ovarian stimulation by pregnant mare serum gonadotropin (PMSG). Production of antibodies against PMSG was suspected. Antibodies were not detected by gel‐diffusion tests, but were found using ELISA procedures in sera from all monkeys that had been treated with PMSG. Sera from seven of nine treated monkeys had antibodies that cross‐reacted with FSH‐P. An ovarian stimulation test using golden hamsters showed that sera from PMSG‐treated rhesus monkeys completely blocked superstimulation of follicle development and ovarian weight gain by PMSG. This study demonstrates that the refractoriness of rhesus monkeys to repeated ovarian stimulation by PMSG is due to the production of nonprecipitating antibodies to PMSG that effectively block the activity of PMSG on the ovary. Formation of these antibodies may preclude use of other gonadotropin preparations in refractory monkeys. Alternative ovarian stimulation procedures avoiding use of gonadotropin preparations need to be developed to permit repeated treatment of rhesus monkeys for multiple oocyte collection.
Human Cord Blood Suppressor T Lymphocytes II. Characterization of Inducer of Suppressor Cells
Authors: CHENG HENRY , DELESPESSE GUY
Published: December 2015

ABSTRACT: Previously, we reported an antigen nonspecific inducer of T suppressor cell factor (TisF) produced by cord blood mononuclear cells (MNC) in 48‐hr, two‐way mixed lymphocyte cultures (MLC). The target of this factor was a radiosensitive, T4+ (T8−) adult suppressor T cell subset. The cellular origin of this TisF was examined in the present study. IgG production by pokeweed mitogen (PWM)‐stimulated adult MNC was used as an assay for TisF activity. It was found that TisF‐producing cells formed rosettes with sheep erythrocytes (E+) and were independent of adherent cells (AC) in the production of TisF. They were resistant to irradiation (2500 rads) and phenotypic characterization with T cell reactive monoclonal antibodies indicated that they resided in the T8− (T4+) population. Furthermore, both TQ1− and TQ1+ cells were required for the production of TisF activity and such activity could not be reconstituted by supernatants from TQ1− MLC and TQ1+ MLC. These results indicate that the production of TisF is dependent upon interactions between radioresistant E +, T8−, TQ1− and radioresistant E +, T8−, TQ1+ cells.
The Relationship Between the Immunosuppressive and Cytotoxic Effects of Human Seminal Plasma
Authors: ALLEN R.D. , ROBERTS T.K.
Published: December 2015

ABSTRACT: This report describes the cytotoxic properties of human seminal plasma and demonstrates that the inhibition of response to mitogens shown by murine lymphocytes in the presence of whole human seminal plasma can be attributed largely to an effect of seminal components on lymphocyte viability. It is hypothesised that the cytotoxic effect of seminal plasma arises as a result of the oxidation of spermine in seminal plasma by an amine oxidase enzyme present in fetal calf serum. In support of this hypothesis, it was found that seminal plasma cytotoxicity is serum dependent and is inhibited in the presence of the amine oxidase inhibitor hydroxylamine
Suppression of Post‐vasectomy Cytotoxic Sperm Antibody Formation in Rats by a Short‐term Pretreatment With Cyclosporine
Authors: LOVETT JOHN , NYBERG LEROY M. , BROWN SUSAN , MATHUR SUBBI
Published: December 2015

ABSTRACT: The effect of a short pulse therapy with cyclosporine on the production of vasectomy‐induced cytotoxic sperm antibodies was studied in Lewis rats. Cyclosporine at a dose of 10 mg/kg was administered once daily for 7 days before and 7 days after vasectomy (group A), for 7 days before vasectomy (group B), and for 7 days after vasectomy (group C). Ten rats were studied in each group for a period of 5 weeks. Ten rats were vasectomized and untreated with cyclosporine (group U). All animals in this group developed high titers of cytotoxic sperm antibodies at the end of the first week after vasectomy (primary antibody response). In contrast, all the treated rats of groups A, B, and C had a normal range of sperm antibody titers. By the third week, six of nine rats in the post‐treated group C had significant cytotoxic sperm antibody titers, while the other groups had normal antibody titers. In the fourth week, all the rats of groups A and B continued to have normal sperm antibody titers of ≤16, while most animals in groups C (78%) and U (63%) had significant cytotoxic sperm antibody titers. It is concluded that prevasectomy treatment with cyclosporine may significantly reduce or delay the production of cytotoxic sperm antibodies in Lewis rats.
Production of Immunosuppressor Factor(s) by Preimplantation Human Embryos
Authors: DAYA SALIM , CLARK DAVID A.
Published: December 2015

ABSTRACT: Embryonic loss prior to implantation appears to be a significantly frequent phenomenon and this is further reinforced by the very low pregnancy rates reported by in vitro fertilization and embryo transfer programs. Implantation failure may possibly be the result of rejection of the antigenic embryo by the hostile maternal immune system. The mechanism by which embryos in successful pregnancies escape these rejection responses may depend upon their ability to produce factor(s) that suppress in vitro mitogen‐induced lymphocyte proliferation. Only 43% of cleaved embryos demonstrated this ability. We postulate that successful pregnancies are dependent upon the production by embryos of immunosuppressor factor(s) that has a direct suppressive effect on the maternal immune response.
Antisperm Antibodies and Circulating Immune Complexes of Vasectomized Men With and Without Coronary Events
Authors: ALEXANDER NANCY J. , FULGHAM DAVID L. , PLUNKETT EARL R. , WITKIN STEVEN S.
Published: December 2015

ABSTRACT: We compared antisperm antibody and circulating immune complex (CIC) levels in serum samples from 101 vasectomized and 101 normal age‐matched nonvasectomized men; 31 of each group had histories of coronary heart disease (CHD). Vasectomy and CHD status were treated as categorical independent variables in the two‐way analysis of variance. Elevations of both systolic and diastolic blood pressures were significantly associated with age and body mass index but not vasectomy. Antisperm antibodies (immobilizing and agglutinating) were significantly associated with vasectomy (P ≤ .001); the incidences were similar in men with and without CHD.

The CICs were significantly associated with vasectomy in a Staphylococcus aureus (FcSa) CIC assay (P ≤ .001) and a Raji cell CIC assay (P ≤ .05). A third CIC assay, the Clq binding asssay, did not reveal a difference between any subgroups. Generally, CICs occurred more frequently in the CHD group by the FcSa assay and particularly the Raji cell assay (P ≤ .001). In summary, vasectomized men had a higher incidence and higher levels of circulating antisperm autoantibodies and CICs than did age‐matched controls.
Graft‐vs‐Host Reaction Induced by Para‐aortic Lymph Nodes During Estrous and Diestrous Stages
Authors: DE BONAPARTE YOLANDA P. , COLOMBO LUCAS L. , KLEIN SLOBODANKA , D'ELIA ISABEL S. , DIAMENT MIRIAM
Published: December 2015

ABSTRACT: Mouse uterine draining lymph node (UDLN) cells, or soluble factors released by them in both phases of the estrous cycle were examined in the graft‐vs‐host (GVH) assay. The immune response during the estrous phase was significantly decreased as compared with diestrous phase; 24‐hour culture supernatant of UDLN cells was also able to decrease GVH activity mounted in F1 hybrids. This difference in reactivity was not found when peripheral nodes (PN) or spleen cells were tested. These results show that in physiological conditions it is possible to detect an hormonal influence on T lymphocyte function and would suggest that a nonspecific immunosuppression would appear even during the estrous phase.
Implication of Prostaglandin E2 in Soluble Factor‐Mediated Immune Suppression by Murine Decidual Cells
Authors: TAWFIK OSSAMA W. , HUNT JOAN S. , WOOD GARY W.
Published: December 2015

ABSTRACT: Cells from the uteri of pregnant mice mediate profound nonantigen‐specific and nonmajor histocompatibility complex‐restricted immune suppression in vitro. In part, those cells accomplish suppression by releasing soluble suppressor factors. The purpose of the present study was to initiate identification of uterine cell suppressor factors. Immune suppression was assayed by the effect of decidual cells or in vitro generated supernatants of decidual cells on mixed lymphocyte reactions (MLR). The following findings support the designation of prostaglandin E2 (PGE2) as a primary suppressor molecule originating with decidual cells: (1) Suppression mediated by supernatants of decidual cells was relieved by removal of lipids but not proteins; (2) indomethacin, an inhibitor of prostaglandin synthesis, produced partial relief of suppression mediated by uterine cells and totally inhibited soluble suppressor factor generation by those cells; (3) decidual cells produced high levels of both PGE2 and PGF2a; (4) the addition of exogenous PGE2 at levels comparable to those found in the decidual cell supernatants restored suppression by decidual cells and their supernatants whereas the addition of PGF2a had no effect; (5) inhibition of the lipoxygenase pathway of arachidonate metabolism had no effect on cell or supernatant mediated suppression; (6) nonspecific suppressor mechanisms, such as arginine depletion and peroxide generation, were excluded as possible mediators of MLR suppression by decidual cells and their supernatants. Fractionation of decidual cells revealed at least three indomethacin‐sensitive cell types: small, lymphocytelike cells, macrophages, and a third population of large decidual cells that was not identified by specific markers. The data strongly suggest that prostaglandins, primarily PGE2, are involved in immunosuppression by cells from the uteri of pregnant mice.
Role of Spermine in the Cytotoxic Effects of Seminal Plasma
Authors: ALLEN R.D. , ROBERTS T.K.
Published: December 2015

ABSTRACT: This report further characterizes the cytotoxic properties of seminal plasma and provides evidence for a role of spermine oxidation in the generation of seminal plasma cytotoxicity. Addition of spermine to lymphocyte cultures was found to result in a cytotoxic effect similar to that observed upon addition of seminal plasma. Furthermore, although seminal plasma is not cytotoxic in serum‐free medium, addition of monoamine oxidase was sufficient to result in the generation of seminal plasma‐associated cytotoxicity. Analysis of 73 individual seminal plasma samples indicated that all were cytotoxic, suggesting that this is an intrinsic property of seminal plasma. These results support a mechanism for seminal plasma cytotoxicity in which oxidation of spermine in seminal plasma by the amine oxidase of fetal calf serum results in generation of a cytotoxic product. It is hypothesized that this product plays a significant role in the phenomenon of seminal plasma immunosuppression. The general application of this principle to other fluids and tissues is discussed.
Detection of Early Pregnancy Factor in Human Sera
Authors: ZHIHAI QIN , ZHEN‐QUN ZHENG
Published: December 2015

ABSTRACT: The rosette inhibition titers (RIT) for sera from 94 women at various stages of gestation were detected with a standardized rosette inhibition test. The results showed that an immunosuppressive substance, named early pregnancy factor (EPF), did exist in the pregnancy sera. We confirmed that the EPF activity was very high in the early pregnant stage (the mean RIT = 6.30), gradually decreased with the continuance of gestation, and disappeared at 8 weeks before delivery when the mean RIT for sera (<4) had fallen in the RIT nonpregnant range. In addition, observations for the EPF dynamic changes before and at varying stages after the induced abortion in 21 pregnant women showed that the mean RIT was 5.9 ± 0.25 (SE) before the abortion and dropped below 4 (EPF activity could not be detected) at 3–5 days after the abortion.
Natural Killer Cell Cytotoxicity and Antibody‐Dependent Cellular Cytotoxicity to Herpes Simplex Virus‐Infected Cells in Human Pregnancy
Authors: GONIK BERNARD , LOO LIAM S. , WEST STEWART , KOHL STEVE
Published: December 2015

ABSTRACT: Natural killer cell (NKC) cytotoxicity and antibody‐dependent cellular cytotoxicity (ADCC) represent the ability of human leukocyte effector cells to destroy target cells in the absence and presence of antibody, respectively. Since these immune systems play a pivotal role in the body's primary lines of defense against a variety of pathogens including herpes simplex virus (HSV), a study was undertaken to evaluate the influence of pregnancy on these systems. Eleven uncomplicated gravidas were followed serially through each trimester and compared to 11 nonpregnant female controls. Mononuclear cells were acquired by Ficoll‐Hypaque centrifugation of heparinized blood. Chang liver cells infected with HSV‐I were utilized as target cells in a 51Cr release assay. Mean NKC values in the pregnant patients were uniformly lower than in the controls. No similar decreases in ADCC activity were observed in a comparison between the two study populations. These data support previous observations suggesting that pregnancy represents a relatively immunocompromised state. Differences apparently exist between NKC and ADCC effector cell populations with regard to the influence of pregnancy. Although these physiologic alterations in immunoregulation may help support the fetoplacental allograph, detrimental conditions may exist regarding susceptibility to various pathogens such as HSV.
Antigenic Analysis of Human Trophoblast Membrane: Detection of a Lymphocyte Cross‐Reactive Antigen
Authors: KIM IN C. , SABOURIN CAROL L.K.
Published: December 2015

ABSTRACT: The antigenicity of human syncytiotrophoblast membrane (TM) was analyzed using rabbit antiserum raised against TM. From immunoblot analysis, about ten protein bands in TM were recognized by the anti‐TM. These included placental alkaline phosphatase and TM‐bound albumin. From limited antigenic specificity studies, these antigens, with the exception of albumin, were not detectable in membranes of liver, kidney, heart, and erythrocyte, or in human normal serum. Therefore, these antigens appear to be placental membrane specific.

Analysis of lymphocyte membrane by Immunoelectrophoresis, crossed Immunoelectrophoresis, and immunoblot techniques revealed that a single protein band, designated “40 kDa,” was cross‐reactive with the anti‐TM antiserum, indicating that this antigen is shared commonly between placenta and lymphocyte membranes. Experimental evidence suggesting that the 40‐kDa membrane antigen is probably a unique trophoblast‐Iymphocyte cross‐reactive antigen is based on the following observations: 1) the 40‐kDa antigen was not detectable in liver, heart, and kidney membrane; 2) γ2‐microglobulin (12,000 daltons) was not detectable in our TM preparation; and 3) the lymphocyte membrane showed only a single protein band at 40,000 daltons, not at 12,000 for γ‐microglobulin.
Epithelial Localization of Antiendometrial Antibodies Associated With Endometriosis
Authors: WILD ROBERT A. , SATYASWAROOP PONDICHERY G. , SHIVERS ALEX C.
Published: December 2015

ABSTRACT: Antiendometrial antibodies have been demonstrated in patients with endometriosis. As a further step in understanding the immunological alterations against the endometrium, isolated glandular and stromal monolayer endometrial cell preparations and endometrial, breast, and ovarian carcinoma cell lines were tested by indirect immunofluorescence assay utilizing sera of patients with endometriosis previously shown to have antibodies against endometrium. In dilutions of serum of 1:1 to 1:16, significant fluorescence staining was noted only in the glandular (epithelial) component and not in the stromal component of normal endometrium without regard to phase of the menstrual cycle. The significance of this finding as it relates to the pathophysiology of endometriosis awaits further study.
Enhancement of Human Monocyte and Peritoneal Macrophage Chemiluminescence Activities in Women With Endometriosis
Authors: ZELLER JANICE M. , HENIG ISRAEL , RADWANSKA EWA , DMOWSKI W. PAUL
Published: December 2015

ABSTRACT: Preliminary reports indicate that products of human mononuclear phagocytes may contribute to the infertility associated with endometriosis. To determine whether the generation of reactive oxygen metabolites by blood monocytes and peritoneal macrophages is altered in women with endometriosis, the present study evaluated luminol‐enhanced chemiluminescence (CL) in cells at rest and following stimulation with phorbol myristate acetate (PMA) or serum‐opsonized zymosan (SOZ). Peripheral venous blood and peritoneal fluid samples were collected from 60 infertile women undergoing diagnostic laparoscopy at midluteal phase and mononuclear phagocytic cell fractions were obtained by density gradient centrifugation. Whereas there was no significant difference between resting CL values in peripheral blood monocytes collected from women with and without endometriosis, PMA‐ and SOZ‐stimulated monocyte CL was significantly greater in endometriosis patients. In contrast, there was a significant elevation in resting CL values when peritoneal macrophages from endometriosis patients were compared with macrophages obtained from patients with normal pelvic organs. It appears that chronic stimulation of macrophages in the peritoneal cavity provokes constitutive release of large quantities of reactive oxygen products in women with endometriosis. This may occur secondary to the accumulation of activated monocytes into the peritoneal cavity.
Antigenic and Cytochemical Characterization of Cells Adhering to Intrauterine Contraceptive Devices
Authors: ENNAS MARIA G. , LACONI SERGIO , MANCONI PAOLO E. , MARCELLO COSTANTINO , PARODO GIUSEPPINA , PULIGHEDDU PAOLA , LECCA UMBERTO
Published: December 2015

ABSTRACT: Eighteen copper intrauterine devices (IUDs), removed after 25 months of use, were examined to evaluate cells adhering to them (IAC). By means of monoclonal antibodies, the antigenic phenotype of IAC was studied, along with some IAC cytochemical properties. Sixty percent of IAC were identified as granulocytes based on morphological, cytochemical, and antigenic characteristics. A small proportion of IAC were shaped like large foreign‐body macrophages, with multiple picnotic nuclei, and diffused alpha naphtyl acetate esterase (ANAE) activity. Some IAC identified as macrophages from a morphological view point also showed dipeptidil‐diaminopeptidase IV (DAPIV) reactivity, previously described only in T‐helper lymphocytes. Most IAC identified as macrophages reacted with the monoclonal antibodies OKM1 and HLA‐DR, and showed ANAE activity in the form of small multiple granules.

The hypothesis that IUD‐adhering macrophages with an ANAE +, DAPIV+, OKM1 +, and HLA‐DR + phenotype could play a role in the inactivation of spermatozoa can be proposed.
Effects on Fertility of Rabbits After Active Immunization With Rat Testicular Cytochrome ct
Authors: KIM IN C.
Published: December 2015

ABSTRACT: A Male rabbit was immunized with rat testicular cytochrome (Cyt) ct and mated with normal, unimmunized females. The matings resulted in abnormal pregnancies: no offspring or stillborn or undersized liveborn offspring weighing 25–30 gm each. Another unusual observation was that fur‐pulling behavior, normally exhibited by pregnant female rabbits at the end of the gestational period, was absent in all of these pregnancies. Therefore, immunization of a normal rabbit with testicular cyt ct appeared to interfere with physiological and behavioral aspects of pregnancy in normal female rabbits. The immunological basis of these findings remains to be determined.
Mechanistic Studies of Early Pregnancy Associated Thrombocytopenia (EPAT) in the Mouse
Authors: ADAMSON LOUISE M. , SMART Y. CHENG , STANGER JAMES D. , MURDOCH RAYMOND N. , ROBERTS TIMOTHY K.
Published: December 2015

ABSTRACT: The preimplantation period of uterine pregnancy is associated with the transient (first 4 days of gestation) expression of a state of early pregnancy‐associated thrombocytopenia (EPAT), a phenomenon shown to be mediated by the embryo‐derived EPAT factor, which presumably causes platelet activation and subsequent removal. We previously investigated the time course of production of EPAT factor in mouse embryo culture medium and found a correlation between the production of this factor and the in vivo platelet alterations in pregnant mice. The present paper supports the postulation that the EPAT factor and PAF‐acether (a phospholipid platelet‐activating factor) are related by providing data showing that PAF‐acether may be responsible for the thrombocytopenia. Finally, data are presented to suggest that platelet activation, though not affecting the rate of ovulation, is important for successful ongoing pregnancy. Results suggest that the EPAT factor, produced by the fertilized egg, might act to signal uterine decidualization and/or modulate maternal immunological rejection of the implanting conceptus.
Effects of Sperm‐Reactive Monoclonal Antibodies on the Cervical Mucus Penetrating Ability of Human Spermatozoa
Authors: BRONSON RICHARD A. , COOPER GEORGE W.
Published: December 2015

ABSTRACT: A group of monoclonal antibodies (Mabs) was tested by immunobead binding and indirect immunofluorescence to determine its reactivity with antigenic moieties present either on the surface of motile human spermatozoa or internally. Those Mabs reactive with the surface of motile spermatozoa impaired their ability to penetrate cervical mucus in vitro, while Mabs solely reactive with freeze‐thawed, nonmotile sperm (presumptive subsurface epitopes) were without effect on sperm function.
A Potential Anti‐Pregnancy Vaccine Built by Conjugation of the β‐Subunit of Human Chorionic Gonadotropin to Adjuvant‐Active Muramyl Peptide
Authors: SCHUTZE M.P. , LECLERC C. , JOLIVET M. , DERIAUD E. , AUDIBERT F. , CHANG C.C. , CHEDID L.
Published: December 2015

ABSTRACT: The β‐subunit of human chorionic gonadotropin (hCG) conjugated to tetanus toxoid is being investigated as a vaccine for human fertility control. Initial clinical trials indicated that the level of antibody response induced by such an immunogen was not always sufficient to prevent pregnancy. Therefore, efforts are being made to evaluate new carriers for the β‐subunit and to select adjuvants to yield a more efficient vaccine. In the present report, we demonstrate that conjugates of the β‐subunit of hCG with muramyl di‐peptide (MDP), or its nonpyrogenic derivative murabutide, may have potential as an effective antipregnancy vaccine. The copolymer of βhCG and MDP administered with Al(OH)3 to mice induced a high anti‐βhCG response, better than that induced by the conjugate of βhCG to tetanus toxoid given with Al(OH)3. Moreover, the antibodies induced by such an immunogen were competent for neutralizing the biological activity of hCG in vivo. Even more interesting, a copolymer of βhCG and of murabutide induced high levels of biologically active antibodies. This immunogen may represent a promising candidate for the development of an efficient vaccine for human fertility control.
Suppression of Reproductive Function in Autoimmune NZB/W Mice: Effective Doses of Four Contraceptive Steroids
Authors: KEISLER LYDIA W. , WALKER SARA E.
Published: December 2015

ABSTRACT: Oral contraceptives have been implicated in causing flares of systemic lupus erythematosus in humans, and studies of these agents in the NZB/W mouse model of lupus may help to elucidate mechanisms responsible for disease activation. To define doses which effectively suppress reproductive function in NZB/W mice, we implanted groups of NZB/W females with Silastic capsules containing increasing doses of four compounds: norethindrone (NE) 0.5‐5.0 mg, norgestrel (NG) 1.0–7.5 mg, medroxyprogesterone (MP) 0.5–20.0 mg, and ethinyl estradiol (EE) 0.5‐5.0 mg. Controls received empty implants. Serum concentrations of LH and FSH, uterine weight, endometrial proliferation, and luteal tissue were assessed after 3 weeks of treatment. Based upon these parameters, we determined that effective doses were 5.0 mg NE, 7.5 mg NG, and 0.5 mg EE given as single implants and 10.0 mg MP given in two 5.0‐mg implants. This is the first dosing study of contraceptive steroids in a murine model of lupus. Effective, nontoxic doses of these drugs can now be employed in studies of interactions between gonadal hormones and autoimmunity.
In Vivo and In Vitro Immunosuppressions in Mice by a 100–110‐Kd Fraction From Boar Seminal Plasma
Authors: BOUVET JEAN‐PIERRE , COUDERC JACQUES , PILLOT JACQUES
Published: December 2015

ABSTRACT: The activity of a 100–110‐Kd immunosuppressive fraction (ISF), isolated from boar seminal plasma, was investigated in mice. In vitro, this fraction was found to inhibit a unidirectional mixed lymphocyte response and cell‐mediated lymphocytotoxicity, as well as antisheep red blood cells (T‐dependent) and antitrinitrophenylated lipopolysaccharide (T‐independent) responses. The ISF also inhibited the macrophage phagocytosis of erythrocytes coated with IgG antibodies, but it did not suppress the natural killer activity. In vivo, ISF was found to lower both the primary responses to T‐dependent and to T‐independent antigens.

Trypsin or pronase digestion of ISF provided active molecules of 30 Kd or 2–5 Kd respectively, thus showing that the activity is due to a protein.

This ISF factor, capable of suppressing a wide variety of immune functions and remaining active after cleavage by proteases, could play a role in the lack of immune response against the spermatozoa present in the sow genital tract after intercourse. The use of this factor as a therapeutic agent in humans could eventually be considered after further molecular characterization.
Immunohistologic Study of the Leukocytic Infiltrate in Maternal Uterine Tissues in Normal and Preeclamptic Pregnancies at Term
Authors: KHONG T.Y.
Published: December 2015

ABSTRACT: The leukocytic infiltrate in maternal uterine tissues at term in normal and preeclamptic pregnancies was studied immunohistologically using a number of monoclonal antibodies. No differences in the quantity and type of infiltrate are apparent between normal and preeclamptic pregnancy tissues. A large population of macrophages has been identified. Suppressor/cytotoxic T lymphocytes expressing major histocompatibility complex (MHC) class II products but lacking interleukin‐2 receptor expression constitute the other component of the bone marrow‐derived cell population. The suppressor/cytotoxic cells are seen around both arteries with and without physiologic changes and are seen also in acute atherosis. While it is suggested that the maternal macrophages serve to down‐regulate maternal immune response, further functional studies of these leukocytes are required to define their role in normal pregnancy.
Rectal Infusion of Semen Results in Transient Elevation of Blood Prostaglandins
Authors: ALEXANDER NANCY J. , TARTER THOMAS H. , FULGHAM DAVID L. , DUCSAY CHARLES A. , NOVY MILES J.
Published: December 2015

ABSTRACT: Repeated semen deposition in the gut may be linked to the development of viral infections in homosexual men. Other investigators have suggested that rectal insemination may diminish immune responsiveness. We approximated conditions of human insemination by infusing 2 ml of pooled human seminal plasma (SP) into the rectum and/or vagina of rhesus monkeys. This resulted in increased blood plasma concentrations of the bicycloderivative of prostaglandin E (PGEM‐II) which reached peak concentrations 2 h after rectal SP instillation in seven of eight test monkeys, but not the controls. The rate of PGE2 diffusion appeared to occur more rapidly across vaginal than rectal mucosa. Suppression of peripheral cellular immune functions was not demonstrated after the single exposure of this study, although persistent and repeat exposures could lead to local or generalized suppression of host defense mechanisms. Absorption of PGE's from the gut may be a cofactor in the development of sexually transmitted viral diseases.
EBV Transformation and Microfusion as the Potential Source of Human Monoclonal Antisperm Antibodies
Authors: KURPISZ MACIEJ , SIMON LAUREL L. , ALEXANDER NANCY J.
Published: December 2015

ABSTRACT: Peripheral blood lymphocytes were obtained from vasectomized men with high serum titers of anti‐sperm antibodies. An Epstein‐Barr virus (EBV) transformation was performed either with B cells or mononuclear leukocytes. The effect of feeder cells (irradiated umbilical cord blood lymphocytes), cyclosporin A, and in vitro stimulation of lymphocytes with sperm extract on EBV transformation was evaluated. Antibody‐producing cells were screened for specificity against human sperm by an enzyme‐linked immunosorption assay (ELISA) one to six weeks after transformation. Using B cells or leukocyte mononuclear cells, we found that the percentage of wells containing antibody reactive against human sperm was greatest two weeks after transformation (range 3% to 7.5% positive wells).

To increase and maintain antibody synthesis by these transformed cells, microfusions were performed in those wells positive for antisperm antibody using the UC 729‐6 lymphoblastoid cell partner. Then resultant hybridomas were expanded, subcloned, and preliminarily characterized.
Long‐Term Immunization Against the β‐Subunit of Ovine Luteinizing Hormone (oLHβ) Has No Adverse Effects on Pituitary Function in Rhesus Monkeys
Authors: THAUd R.B. , WILSON C.B. , SUNDARAM K. , PHILLIPS D. , DONNELLY T. , HALMI N.S. , BARDIN C.W.
Published: December 2015

ABSTRACT: One postulated safety hazard of contraceptive methods based on immunization against gonadotropic hormones is the possibility that circulating antibodies which crossreact with pituitary hormones may impair pituitary function through the deposition of immunoglobulin and/or complement suggesting immune complexes. In order to evaluate this possibility in rhesus monkeys actively immunized against the β‐sub‐unit of ovine luteinizing hormone (oLHβ), we used three approaches to study the effects of long‐term immunization on pituitary function: a) evaluation of pituitary responsiveness to challenge with a GnRH‐agonist; b) examination of pituitary histology and immunostaining with gonadotropin antisera; and c) examination of pituitary cells for deposition of immune complexes. Our results indicate that circulating anti‐oLHβ antibodies did not result in significant impairment of pituitary function in rhesus monkeys.
Seminal Plasma Immunosuppressive Factors in the Spouse of a Woman With Seminal Fluid Allergy
Authors: WASSON ANN W. , COY ELIZABETH A. , KOOISTRA J. BRENT , YUNGINGER JOHN W.
Published: December 2015

ABSTRACT: Women who are allergic to human semen may become sensitized because their sexual partners lack normally occurring immunosuppressive facto(s) in their seminal plasma. To investigate this possibility, we tested whole seminal plasma from the husband of a sensitized woman for its ability to inhibit in vitro phytohemagglutinin‐induced stimulation of peripheral blood mononuclear cells from a nonatopic donor. However, the immunosuppressive activity exhibited by the husband's seminal plasma did not differ from that in seminal plasmas from three other donors.
Editorial: Preterm Birth and Infection: Pathogenic Possibilities
Authors: McGREGOR JAMES A. , FRENCH JANICE I. , LAWELLIN DAVID , TODD JAMES K.
Published: December 2015

ABSTRACT: Preterm delivery remains the preeminent problem in perinatal care worldwide. Recent data suggest that cervical/vaginal microflora, and/or the inflammatory responses they engender, produce factors which can cause or predispose to preterm labor and rupture of membranes. Microorganisms mediating such processes may not be “recognized pathogens” and are often considered normal flora. These microorganisms may act singly, additively, or synergistically with host factors released during an induced inflammatory response. Both qualitative and quantitative aspects of cervical/vaginal microflora are likely important. Multiple cervical/vaginal microorganisms produce IgA proteases, neuraminidases, and mucinases which may facilitate passage of these and other agents past cervical barriers and into the lower uterine segment. Multiple microflora also produce phospholipases A2 and C, each of which can locally augment production of eicosanoids within the uterus which are important in cervical ripening and labor. Similar microflora produce various proteases, including collagenase, which can locally weaken the amniochorion and predispose to premature rupture of membranes and cervical ripening. Intrauterine microorganisms induce inflammatory reaction and may engender local release of similar proteases, phospholipases, oxygen radicals, as well as platelet activating factor (PAF), and lymphokines which can also initiate or further potentiate labor‐inducing mechanisms. Roles for uteroplacental or systemic release of tumor necrosis factor (TNF) and various interferons are beginning to be understood. Recognition of microbe‐induced pathogenesis of some cases of preterm birth offers the hope of specific treatment and prophylaxis. In recent studies, administration of erythromycin and tocolytic agents was associated with an improved outcome in selected women. “Just why so many gravidas go into labor prematurely and hence give birth to infants who often are unable to cope with extrauterine conditions is one of the great unsolved problems of obstetrics.”
T and B Lymphocyte Populations in Uterus Draining Lymph Nodes at Estrus and Diestrus in Wistar Rats
Authors: COLOMBO LUCAS L. , LÓPEZ MARÍA DEL C. , HERKOVITS JORGE , ROUX MARÍA E.
Published: December 2015

ABSTRACT: In this paper, data are presented on the characterization of uterous draining lymph nodes (UDLN) B and T lymphocytes of virgin rats at estrus (E) and diestrus (D). We established that the T/B lymphocyte relationship in the UDLN is less than one at estrus and more than one at diestrus. This is due to a decrease in the percentage and in the total number of mature T cell population in association with a decrease in the percentage of the OX8 subset in the UDLN at estrus. This situation may be related to an increase in estrogens known to produce thymic involution. These changes were not observed when we studied peripheral (popliteal) lymph nodes. The changes observed in the UDLN T cell population at estrus could be under hormonal control and we think that this condition may be important to prepare the immune system for an eventual pregnancy.
Vaccination Against Spontaneous Abortion in Mice by Preimmunization With an Anti‐diotypic Antibody
Authors: CHAOUAT G. , LANKAR D.
Published: December 2015

ABSTRACT: CBAE/J females mated with DBA/2 display a high level of fetal wastage which can be corrected by anti‐Balb/c vaccination. A batch of CBA/J anti‐(CBA/J anti‐Balb/c) antiserum was raised. This serum was characterized as anti‐idiotypic by various techniques, including a solid‐phase radioimmunoassay. Such a serum proved to confer protection against resorbtions when injected into CBA/J mice mated with DBA/2. However, the kinetics of the effect pointed to the need for administration in early pregnancy for successful protection. The significance of these data, and the possible mechanism(s) by which the serum acts, are discussed.
Evidence for Active Immunological Regulation in Prevention of Testicular Autoimmune Disease Independent of the Blood‐Testis Barrier
Authors: MAHI‐BROWN CHERRIE A. , YULE TERECITA D. , TUNG KENNETH S.K.
Published: December 2015

ABSTRACT: It has long been considered that autoimmune disease of the testis is prevented by sequestration of testis‐specific autoantigens on germ cells behind the blood‐testis (BT) barrier. However, we now have evidence that not all such antigens are sequestered. Some appear to reside on germ cells in the basal compartment of the seminiferous tubule where they are accessible to antibodies and to circulating activated T cells. Mice immunized with syngeneic testis homogenate are found to have immunoglobulin G (IgG) bound to cells in the basal compartment before onset of orchitis. This IgG is absorbed from circulation by the testis and, therefore, found only in the serum of mice orchiectomized before immunization. When the IgG is eluted from the testis, it is found to react preferentially with testicular cells enriched in preleptotene spermatocytes. T cells from mice immunized with testis can be transferred to naive syngeneic mice where they infiltrate the testis to cause orchitis. This implies that the BT barrier does not need to be breached directly for specific T cells to have access to testicular autoantigens on antigen presenting cells. Thus, active systemic and/or local immunoregulatory mechanisms must operate to prevent testicular autoim‐
Bacteriology of the Cervix in Cases of Infertility: Effect on Human and Animal Spermatozoa and Role of Elastase
Authors: KAUR MOHINDER , TRIPATHI K.K. , BANSAL M.R. , JAIN P.K. , GUPTA K.G.
Published: December 2015

ABSTRACT: Microorganisms such as Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans isolated from cervices of infertile human females inhibited motility and agglutinated human, cow bull, buffalo bull, and rat spermatozoa in vitro. Fifty percent of the infertile females studied carried elastase‐positive microorganisms. Cell‐free culture supernatants of 72‐hr‐old elastase‐positive cultures were spermicidal within 60 min of contact with sperm, while elastase‐negative cultures were spermicidal in 4–6 hr. Cultures of all the cervical isolates were spermicidal and agglutinated human, cow bull, buffalo bull, and rat spermatozoa, and these activities increased with age of the culture. Human sperm showed only tail‐to‐tail agglutination, while cow bull, buffalo bull, and rat spermatozoa showed mainly head‐to‐head agglutination. Spermicidal activity was also attributable to elastase, which was present more in 72‐hr‐old cultures than in 24‐hr‐old cultures.