bluuebunny/crossref_metadata_2025 huggingface dataset:
Carcinoembryonic Antigen as a Monitor in Breast Cancer
Authors: CILLARI ENRICO , BELLAVIA ANGELO , ROMANO GIUSEPPINA COLONNA , DI GESU GIUSEPPE , PALMERI SERGIO , NORATO ARCANGELO , SALERNO ALFREDO , VOTI PIETRO LI
Published: May 2013

ABSTRACT: Carcinoembryonic antigen (CEA) levels were serially determined in 125 patients with breast cancer in order to study the diagnostic and prognostic use of serum CEA levels before and/or after surgery and during treatment with hormonal and chemotherapy. Serum CEA levels were elevated in 15.5% of nonmetastatic patients. Carcinoembryonic antigen increased according to stage (TNM classification); and a direct relationship between positive CEA levels and subsequent recurrence was found. After a three‐year postoperative interval a 50% survival rate was exhibited in CEA‐positive patients vs an 88% survival rate in those patients found to be CEA negative.

There is a definite correlation between the trend of serial CEA values and the response to therapy and the development of metastases despite the fact that metastases occurred in CEA‐negative patients.

Therefore CEA assay is a useful and simple adjuvant test of monitoring metastatic and nonmetastatic breast cancer.
Acrosin‐Dependent Solubilization of Antigenic Peptides From Human Spermatozoa*
Authors: CZUPPON A.B. , METTLER L.
Published: May 2013

ABSTRACT: Human spermatozoal polypeptides have been solubilized by incubation of spermatozoa in phosphate‐buffered saline. Inhibition of peptide release by the acrosin inhibitor N‐α‐tosyl‐L‐lysin‐chloromethyl suggests the direct involvement of the acrosomal enzyme in the liberation of the peptides. The peptides were coupled to activated Sepharose 4B gel and the peptide‐absorbed antibody of antispermatozoal antisera was detected with the aid of 125I‐protein‐A tracer. The occurrence of three types of peptides became evident: one that binds to both sperm‐agglutinating and sperm‐immobilizing antibodies, one that binds to sperm‐immobilizing antibodies, and another that binds to sperm agglutinating antibodies only. The peptides might be of interest from an immunological point of view, because the relatively mild procedure of their solubilization could also prevail under physiological conditions, resulting in release of immunogenic peptides from spermatozoa in the genital tracts.
Antibody Transfer Mechanisms From Mother to Fetus Across Rat Yolk Sac Endoderm*
Authors: LALIBERTÉ F. , MUCCHIELLI A. , AYRAUD N. , MASSEYEFF R.
Published: May 2013

ABSTRACT: The rat yolk sac, like the human placenta, has been shown to be the transport route of passive immunity from mother to fetus. Different hypotheses deal with the transfer mechanisms of antibodies.

To investigate this mechanism, female rats were immunized with horseradish peroxidase (HRP). After mating, 16‐to 18‐day pregnant rats were sacrificed, yolk sac removed, and autologous anti‐HRP antibodies were detected.

The IgG was detected on the apical plasma membrane, in clusters forming from this membrane, in coated vesicles, and in intercellular spaces.

These structures were never implicated in experiments where monospecific anti‐HRP Fab fragments or free HRP were injected into pregnant rats before sacrifice.

The sole common structures implicated in IgG, Fab fragments, and free HRP transfer, were dense reaction product‐filled vesicles. From the comparison of these experiments, a selective uptake and transport system functioning alongside a nonselective system was hypothesized. The IgG transfer from mother to fetus could be a result of this specific mechanism.
Fetal Cytotoxic Antibodies to Maternal T Lymphocytes: A Possible Mechanism for Maternal Tolerance of the Fetal Allograft*
Authors: MATHUR SUBBI , FUDENBERG H. HUGH , KEANE MOULTON , RUST PHILIP F. , WILLIAMSON H. OLIVER
Published: May 2013

ABSTRACT: The absolute numbers of B lymphocytes and of total and “active” T lymphocytes in peripheral venous blood (Mv) from 15 females at the time of normal term deliveries were found to be significantly less (p< 0.001) than in the fetal umbilical vein (Uv) or artery (Ua) or in the peripheral blood of 75 normal nonpregnant controls (Cv), suggesting that maternal cellular immunity at term is lowered. In 19 umbilical artery samples, titers of lymphocytotoxic antibodies (Cyt), expressed as the mean log of reciprocal titer values, were significantly higher (p< 0.01 in each case) than in matched maternal samples, against the following cell types: Maternal T cells (7.1 in Ua vs 1.21 in Mv sera); maternal B cells (3.23 vs 1.58); T cells (4.41 vs 1.38) but not B cells from other females at delivery; autologous T cells (2.9 vs 1.0); autologous B cells (1.88 vs 0.69); T (5.39 vs 0.81) and B (2.89 vs 1.25) cells from the paired Uv; T (3.78 vs 0.62) and B (2.64 vs 0.77) cells from the Uv of other newborn infants; and T (4.19 vs 2.0) but not B cells from controls (Cv). The highest Cyt titers in the umbilical artery samples were against maternal T lymphocytes. Immunofluorescence studies indicated that the Cyt antibodies were primarily IgG. Absorption of 13 other Ua sera with maternal T cells eliminated Cyt activity against both Mv and Cv T cells; absorption with Cv T cells eliminated the reaction against Cv T while reducing Cyt titers to Mv T lymphocytes. We conclude that the fetus produces lymphocytotoxic antibody specifically directed against maternal T lymphocytes, in addition to antibody against T lymphocytes of other adults.
Effect of Anti‐HCG Sera on Purified Syncytiotrophoblast From Full‐Term Human Placenta
Authors: PAUL SUDHIR , JAILKHANI BANSI L.
Published: May 2013

ABSTRACT: Heterologous anti‐HCG and anti‐β‐HCG sera failed to effect complement‐dependent lysis of purified 51chromium‐labeled syncytiotrophoblast in vitro. The progesterone synthetic activity of syncytiotrophoblast was also preserved in the presence of the anti‐HCG sera. Binding of the anti‐HCG antibodies to the syncytiotrophoblast was demonstrated in an immunofluorescence test. The potential of the anti‐HCG sera to participate in complement‐dependent lysis of other HCG‐bearing cell types was revealed using BeWo cells as the targets; 53%‐68% of the latter were killed by exposure to anti‐HCG sera and complement.

The possible mechanism(s) whereby syncytiotrophoblast resists damage by the anti‐HCG sera are considered.
Zona Pellucida Antibodies in a Group of Women With Idiopathic Infertility*
Authors: BOUSQUET D. , ST‐JACQUES S. , ROBERTS K.D. , CHAPDELAINE A. , BLEAU G.
Published: May 2013

ABSTRACT: The presence of zona pellucida antibodies was sought in a group of ten women with infertility of unknown cause. The reaction of these sera with ova was compared to the reaction obtained with a control antizona pellucida serum produced by the immunization of a rabbit with 8,000 solubilized hamster zonae pellucidae. This antiserum reached a maximum titer of 1 in 256 as measured by an immunoprecipitation assay and of 1 in 1,024 as measured by indirect immunofluorescence. It is tissue‐specific but is not species‐specific.

With the indirect immunofluorescence technique on ova obtained from different species, the sera of eight of the ten patients gave a positive reaction with at least one type of test ova: three patients gave a positive reaction with hamster ova, six with porcine ova, and two with monkey ova. One infertile woman presented a positive reaction on hamster ova and another on pig ova as detected with all three types of γ‐globulins. Two other patients presented a positive reaction with the anti‐IgG and ‐IgM on porcine ova. The titer of the reaction never rose above one in four in any of the positive cases.

Adsorption of the sera with fresh erythrocytes from human, hamster, and porcine blood did not change the titer or the intensity of the fluorescent reaction on ova. This indicates that the positive reactions are not due to nonspecific heteroagglutinins. Adsorption of the sera with formalin‐fixed erythrocytes from human and porcine blood completely abolished the fluorescent reaction. However, the latter treatment, applied to a dihydrotestosterone antiserum and a β‐hCG antiserum also greatly diminished the binding of hormones to these antisera; fresh erythrocytes did not adsorb the antibodies in these two antisera. This demonstrates that formalin‐fixed erythrocytes are not suited for adsorption of sera before testing for specific autoantibodies to the zona pellucida in infertile women.

None of the sera from the infertile women gave a positive reaction with human pre‐ovulatory or post‐ovulatory ova or with frozen sections of human ovary. None of the sera produced an inhibition of in vitro fertilization of hamster ova. On the contrary, the control zona pellucida antiserum completely blocked in vitro fertilization. Furthermore, in a group of pregnant women, 2 of 11 exhibited a positive reaction with hamster ova while 6 of 28 showed a positive reaction with porcine ova.

These results suggest the presence of low titer zona pellucida antibodies in 8 of the 10 infertile women. The importance of these antibodies in their infertility remains to be established.
Stimulation of Lymphocytes by Spermatozoa‐Stimulated Cells*
Authors: KURPISZ MACIEJ , SZYMCZYNSKI GRZEGORZ A.
Published: May 2013

ABSTRACT: The mechanism of spermatozoalymphocyte interaction was studied using spermatozoa and lymphocytes obtained from 11 healthy individuals and from 2 patients with spermatocoele. The lymphocytes activated by spermatozoa in 3‐day cultures were used as inducers of fresh, unstimulated autologous or allogeneic lymphocytes. In 9 cases of 13 tested sperm samples, a slight proliferative response of lymphocytes stimulated by spermatozoa‐induced lymphocytes was observed. The final effect did not depend on whether an autologous or an allogeneic system was used in the first and the second incubation. A possible explanation of the observed reaction is discussed.
Respective Roles and Interactions of T Lymphocyte and PGE2‐Mediated Monocyte Suppressive Activities in Human Newborns and Mothers at the Time of Delivery
Authors: DURANDY A. , FISCHER A. , MAMAS S. , DRAY F. , GRISCELLI C.
Published: May 2013

ABSTRACT: Recently the concept of a poorly functional humoral immune response in the newborn was proposed. Data have been presented indicating that the impaired newborn B cell maturation, as shown in vitro in a pokeweed mitogen‐induced B cell maturation system, is due both to an immaturity of lymphocyte subsets and to an increased suppressive T activity. In the present work, we present evidence that there exists a predominance of a naturally occurring T lymphocyte suppressive activity in the cord blood in that the removal of the suppressive activity by irradiation allows a normal maturation of newborn B cells. Such normal maturation of newborn B cells can also be obtained using mixed cultures of adult T cells and newborn B cells. Newborn suppressor T cells belong to both EAγ(+) and EAγ(—) fractions, and it is not known whether these two groups do or do not belong to different subsets. The PGE2‐dependent monocyte suppressive activity does not play any role in the suppression observed in newborns since newborn monocytes are poorly suppressive and since they produce a smaller amount of PGE2 than adult monocytes. Some observations suggest, on the contrary, that the suppressive T lymphocytes can regulate the level of the PGE2‐dependent monocyte suppressive activity.

It should be noticed that similar observations about T lymphocyte and PGE2‐dependent monocyte suppressive activities have been made at the same time using mothers' cells. These observations suggest the possibility that such changes in B cell immune regulation may result from an interaction between maternal and fetal lymphoid cells.
Role of Uteroglobin and Transglutaminase in Masking the Antigenicity of Implanting Rabbit Embryos*
Authors: MUKHERJEE ANIL B. , ULANE RODNEY E. , AGRAWAL ARUN K.
Published: May 2013

ABSTRACT: Using rabbit as a model, the roles of uteroglobin (UG) and transglutaminase (TG) in masking the antigenicity of early developing mammalian embryo have been investigated. Maternal lymphocytes in vitro, when mixed with mitomycin‐C inactivated blastomeres, incorporated H3‐thymidine, suggesting recognition of embryonic antigens by these cells. However, pretreatment of blastomeres with pregnant uterine fluid (PUF) or with UG alone or in combination with TG (coagulation factor XIIIa), resulted in a significant and dose‐dependent suppression of H3‐thymidine incorporation into these lymphocytes. A complete suppression was achieved at a concentration of 250 μg of UG/ml, in the absence of TG. However, in the presence of TG, only 1.0 μg of UG/ml was required for total suppression. Neither nonpregnant uterine fluid (NPUF), nor myoglobin, a nonspecific protein similar in molecular weight to UG, had any suppressive effect. Incubation of uteroglobin with anti‐UG or TG with its antiserum prior to the pretreatment of blastomeres eliminated the suppressive effect of these proteins. Inhibition of TG by neopentyl chloroethyl nitrosourea (NPCNU) also eliminated the suppressive effects of uteroglobin on H3‐thymidine incorporation into maternal lymphocytes. These results suggest that in the pregnant uterus UG in conjunction with TG may play a specific role in masking the antigenicity of developing embryos during implantation.
Lysis of Placental Syncytiotrophoblast by Allogenic Leukocytes In Vitro: Effects of Neuraminidase and Chorionic Gonadotropin*
Authors: PAUL S. , JAILKHANI B.L.
Published: May 2013

ABSTRACT: 51chromium‐labeled syncytiotrophoblasts purified from human placentae were lysed by allogenic leukocytes in vitro. The extent of syncytiotrophoblast lysis was dependent upon the dose of the leukocytes, occurred after a lag period of 42 h, and was inhibited by excess of unlabeled syncytiotrophoblasts. Autologous leukocytes failed to lyse syncytiotrophoblasts. Neuraminidase pretreatment of the syncytiotrophoblasts significantly enhanced their lysis by leukocytes. HCG failed to influence the extent of lysis of untreated syncytiotrophoblasts but significantly reduced the lysis of neuraminidase‐treated targets. The significance of these observations in relation to the “immunologic privilege” of the tropho‐blast in vivo is discussed.
Influence of Spermatozoal Antibodies in the Reproduction of Mice*
Authors: SEKI M. , METTLER L.
Published: May 2013

ABSTRACT: Under in vitro and in vivo conditions, the influence of spermatozoal antibodies on isolated gametes and early embryonic stages up to implantation and into postimplantation fetal development was tested.

In the in vitro experiment, a clear‐cut correlation between the amount of antisera added and the reduction of fertilization rates was observed. In the in vivo experiments, female mice were immunized with homologous washed sperms. A correlation between the amount of immunization and the reduction of fertilization rate occurred. In the sperm‐immunized female group, the percentage of large blastocysts showed statistically significant reduction in correlation to the amount of immunization.

Spermatozoal antibodies had an effect on isolated gametes, on fertilization, and on the early development of the embryo as well as on implantation.

No influence of sperm antibodies either in low or high titer sperm antisera on developmental stages occurred. No spermatozoal antibody‐induced abortions occurred. However, an influence of high titer antisera on implantation was evident.
Immunoglobulin Class of Sperm Antibodies in Cervical Mucus From Infertile Women
Authors: INGERSLEV HANS JAKOB , MØLLER NIELS PETER HUNDAHL , JAGER SIEMEN , KREMER JAN
Published: May 2013

ABSTRACT: By immunoaffinity chromatography using anti‐IgG, anti‐IgM, and anti‐IgA coupled to CNBr‐activated sepharose 4B, the immunoglobulin class of sperm‐agglutinating antibodies was investigated in cervical mucus from four infertile women. In all patients, it was found that the sperm antibodies in cervical mucus belonged to the IgA class, whereas in serum, which was studied in two of the patients, IgG sperm antibodies were demonstrated. Absorption of the four cervical mucus samples with anti‐secretory component sepharose 4B revealed that the IgA antibodies in at least two of the samples were SC‐IgA antibodies. Investigation of a third sample by sucrose gradient ultracentrifugation revealed that the IgA sperm antibodies were characterized by a sedimentation coefficient between 9S and 13S, strongly suggesting the presence of SC‐IgA antibodies. Accordingly, the sperm‐agglutinating antibodies were SC‐IgA antibodies in at least three of the four samples studied.
Studies of the Normal Human Placental Syncytiotrophoblast Membrane: A Combined Immunological and Physicochemical Approach*
Authors: EMERSON D. , KANTOR R. , ARNAUD P. , GALBRAITH R.M.
Published: May 2013

ABSTRACT: In view of the importance of the syncytiotrophoblast in the immunobiology of human pregnancy, the composition of this interface between fetus and mother was further studied by a combination of physicochemical and immunological approaches. Trophoblast membranes were solubilized using three classes of detergents: zwitterionic (sulfobetaine14), non‐ionic (Triton X‐100), and anionic (deoxycholate). Quantitative studies of protein released demonstrated the importance of dispersion of membranes into detergent, and optimum solubilization was then obtained at detergent:protein ratios of 1.3:1 for sulfobetaine, 2.5:1 for Triton X‐100, and 4.4:1 for deoxycholate. Analysis of chaotrope‐treated detergent‐solubilized membrane components was performed by preparative isoelectric focusing followed by combined physicochemical and immunological methods. The results revealed three major proteins which were identified as placental alkaline phosphatase, albumin, and transferrin. Certain additional low molecular weight proteins were also evident; one of these components displayed physicochemical properties similar to those of actin, but none appeared to be recognized by conventional heteroantisera raised to trophoblast membrane. These findings and the results of further immunological analysis by affinity chromatography are consistent with the concept that human trophoblast may express limited immunogenicity due in part to the presence of large amounts of absorbed maternal serum components and limited expression of fetal proteins.
Fetal H‐Y Typing Using Human Amniotic Fluid*
Authors: KOO GLORIA C. , REIUY JUDY A. , HAMMERLING ULRICH , CEDERQVIST LARS L.
Published: May 2013

ABSTRACT: The H‐Y (male) antigen is phylogenetically conserved among vertebrate species, including the species man. Previous studies have indicated the presence of a “soluble” H‐Y antigen in male serum and culture fluids of male cells. We examined over 50 samples of amniotic fluid from male and female fetuses to determine if H‐Y typing could be correlated with the sex of the fetus. Samples of amniotic fluid were tested to inhibit the reactivity of monoclonal antibodies in a standard H‐Y assay with protein A sheep red blood cells. We found that amniotic fluids from male fetuses inhibited 40% of the reactivity and that amniotic fluids from female fetuses inhibited 0.5% of reactivity. We could also correctly identify the sex of 90% of male fetuses and 100% of female fetuses. We have not yet identified the exact nature of the inhibiting antigen(s) in the amniotic fluids, but our results clearly indicate the feasibility of fetal H‐Y typing.
The Identification of Suppressor Cells in the Murine Fetal Liver*
Authors: MAIN ELLIOTT K. , PIERCE CARL W.
Published: May 2013

ABSTRACT: Fetal suppressor cells are potentially important for maintenance of pregnancy and for the immune regulation of the identification of self. We have identified and partially characterized a population of murine fetal liver cells which are active suppressors of a variety of immune responses, including mixed lymphocyte responses (MLR), responses to mitogens plaque‐forming cell responses to heterologous erythrocytes. The suppression is non‐H‐2‐restricted and can act via a factor. The cell is preactivated in fetal liver and may represent a T‐cell precursor. The suppression of MLR is maximal (approximately 100%) if cells are added within the first 48 h of culture initiation. The characteristics of this suppressor cell are compared to other known MLR and perinatal suppressor systems.
Inhibition of Tumor Growth and Metastases in Mice Bearing a Malignant Fibrosarcoma by T Cell‐Mediated Immune Response to Oncofetal Antigens
Authors: GAUTAM SAVITA , DEODHAR SHARAD D.
Published: May 2013

ABSTRACT: The presence of fetal antigens on a wide variety of tumors has been well‐documented it has been attributed, for the most part, to de‐repression of genes normally operative in the early stages of embryonic development. Controversy still exists, however, about the role of fetal antigens in antitumor immunity. It is not clear whether the tumor inhibition shown in some systems is due to an immune response. In the present study, conducted in a weakly immunogenic Lewis T241 fibrosarcoma, syngeneic for C57B1/ 6J mice, immunization of normal mice with syneneic fetal cells resulted in striking inhibition of growth and metastases of tumors. On the other hand, immunization with syngeneic normal, adult spleen cells or with allogeneic A/J fetal cells did not inhibit tumor growth or metastases. Mice that had gone through single pregnancy also showed inhibition in tumor growth and metastases. Immunization of female mice with syngeneic tumor cells or fetal cells, prior to pregnancy, resulted in a high incidence of fetal death in these mice. Further studies showed that tumor inhibitory response evoked by fetal cell immunization was due to fetal antigens the male‐specific HY antigen was not responsible for antitumor response. When tumor cells were mixed with spleen cells from fetal antigen‐immunized mice and then injected into normal mice (Winn neutralization assay), significant inhibition of tumor growth and metastases was observed. In this assay, mixing tumor cells with syngeneic fetal cells, normal adult spleen cells, or spleen cells from C57 mice immunized with allogeneic fetal cells did not inhibit the tumor growth or metastases. These results show that inhibition in tumor growth and metastases, following fetal cell immunization, was due to a specific immune response to the oncofetal antigens involved. Analysis of effector cells showed them to be T cells of Lyt‐1+ and Lyt‐2− phenotype.
Specific Suppression of Humoral and Delayed Hypersensitivity Responses by Cyclophosphamide in an Experimental Model of Autoimmunity
Authors: RIERA CLELIA M. , GALMARINI MIRIAN , SERRA HORACIO M.
Published: May 2013

ABSTRACT: The aim of this report is to investigate the effect of cyclophosphamide (CY) in an experimental model of autoimmunity to rat male accessory glands. The results indicated that 100 mg/kg of this drug suppressed humoral immune response that persisted for at least 45 days when administered 3 days after the first immunization of rats with modified rat male accessory glands (MRAG) in complete Freund's adjuvant (CFA). Administration of the drug 3 days before ID injection of antigen caused a shorter suppression of antibody formation. Delayed type hypersensitivity (DTH) studied 13 days after the first immunization was suppressed only in the animals that were administered CY after the antigen.

The specificity of the immunosuppression was studied in rats treated with CY after the first immunization with MRAG using aggregated human γ‐globulin (AHGG) as an unrelated antigen. The studies demonstrated significant suppression of DTH (p < 0.005) and humoral immunity only against MRAG. On the contrary, the response to AHGG was not significantly modified.
Transient Immunologic Effects of Betamethasone in Human Pregnancy After Suppression of Preterm Labor
Authors: HENSLEIGH PAUL A. , HERZENBERG LEONARD A. , LIPMAN SUSAN H. , MALVEHY ROMAN M. , MEDEARIS ARNOLD L. , MOORE MAXINE H. , SUTHERLAND KATHERINE K. , WATERS VIRGINIA BRYAN
Published: May 2013

ABSTRACT: Maternal immune suppression is a potentially significant adverse effect when betamethasone is used to hasten lung maturation of the fetus at risk for preterm delivery. However, increased incidence of infection has not been observed consistently after betamethasone treatment of pregnant women. This study was designed to determine if the cellular immune response to steroids may be modified during pregnancy in a way that would diminish the infection risk associated with steroid treatment.

The effect of betamethasone on immunocytes among patients with preterm labor or in nonpregnant subjects were determined following administration of 12 mg of betamethasone intramuscularly. We measured serially the circulating leukocytes, lymphocytes, T lymphocytes, and their subsets. Measurements were also made of localized leukocyte mobilization to serum‐filled skin chambers covering experimental inflammatory sites. Patients in preterm labor had increased WBC counts prior to treatment with betamethasone but no additional leukocytosis was induced nor was mobilization of leukocytes to the skin chambers decreased. Lymphopenia and depression of T cells was more transient among pregnant patients compared to nonpregnant. Thus, the pregnant patients studied had diminished or more transient potentially adverse immunocyte responses to betamethasone as compared to nonpregnant subjects.
Analysis of Mouse Sperm Isoantigens Using Specific Monoclonal Antibodies
Authors: LEE CHI‐YU GREGORY , WONG ERIC , TEH CHONG‐ZE
Published: May 2013

ABSTRACT: Female mice were isoimmunized with homologous spermatozoa of the same strain. Hybrid cells that secrete monoclonal antibodies to mouse sperm isoantigens were generated by modified hybridoma techniques using a semi‐solid Iscove's modified Dulbecco's medium containing methylcellulose for the initial cloning. Out of more than 1,000 colonies that were initially recovered for subculture, 246 were shown to produce antibodies reacting with various cytological regions of mouse spermatozoa, when methanol‐fixed sperm were employed in an indirect immunofluorescent assay. More than 75% of the generated monoclonal isoantibodies were shown to bind the acrosomal regions of mouse spermatozoa. Some were found to cross‐react with spermatozoa from other mammalian species including those of human, rabbit, rat, and guinea pig. However, none were shown to cross‐react with mouse lymphocytes. Two‐thirds of the generated monoclonal antibodies can also bind live mouse spermatozoa. By an immunohistochemical technique using testicular sections, some of these monoclonal antibodies were shown to react with specific antigens expressed during different stages of spermatogenesis. It is concluded that these mouse sperm isoantigens are sperm‐specific and appear uniquely during spermatogenesis. Monoclonal isoantibodies produced in the present study may have potential applications regarding the investigations of sperm iso‐ or autoimmunity, spermatogenesis, and fertility control.
Requirement of B Lymphocytes in Local Adoptive Transfer of Experimental Allergic Orchitis (EAO) by Lymph Node Cells
Authors: HIRAMINE CHIHARU , HOJO KENJI
Published: May 2013

ABSTRACT: The necessity of T lymphocytes in local adoptive transfer of experimental allergic orchitis (EAO) is an established fact. The present study was undertaken to elucidate the participation of B lymphocytes in the local transfer system of EAO. The capacity of purified lymph node T and B cells to transfer EAO was compared. Donor strain 13 guinea pigs were sensitized with testicular antigen and complete Freund's adjuvant. We then injected 1 × 108 cells just under the tunica albuginea of the testis of a syngeneic recipient. The recipients were killed 5 days after cell transfer. Nylon‐wool nonadherent T cells alone produced only minimal lesions, but could induce more severe mononuclear lesions with the addition of syngeneic, normal macrophages. In contrast, B‐cell enriched populations either alone or combined with a small number of macrophages, were able to transfer extensive lesions. In the combined transfer of immune T and immune B cells the severity of transferred lesions was dependent upon the number of B cells. These results suggest that cooperative interactions among T cells, B cells, and macrophages are involved in the generation of transferred testicular lesions, with emphasis on the participation of B cells.
Incidence of Neutrophil Antigens on Human Cord Neutrophils
Authors: Madyastha Prema R. , Glassman Armand B. , Levine David H.
Published: May 2013

ABSTRACT: Neutrophils isolated from cord blood of healthy newborns (33 blacks and 21 whites) were investigated by EDTA‐microagglutination for their expression of neutrophil specific antigens that have been associated with isoimmune neonatal or autoimmune neutropenia. Equal volumes of various neutrophil anti‐sera (2 μ) and cord neutrophils (3–5 × 106/ml) were mixed in tissue typing microplates under oil and were incubated at room temperature for 6–8 hr, following which the degree of agglutination was noted. Our data revealed that all the currently recognized neutrophil antigens are readily demonstrable by antineutrophil antibodies in cord blood, (NA1, 52–54%; NA2, 81–85%; NB1, 95–96%; NC1, 90%; 9A, 29–30%) suggesting that neutrophil antigens are fully expressed at birth.
Rat Pregnancy Induces Two Suppressor Cell Activities
Authors: Mohammad Mohammad , Saadi May , Balhaa Ghassan Rai El , Mayer Guy , Chateaureynaud Pierrette
Published: May 2013

ABSTRACT: Pregnancy in rat is able to stimulate two suppressor cell activities. One is specific to the paternal histocompatibility antigens and it resides in the T‐Iym‐phocyte population. The second is nonspecific and is of non‐T nature. The use of various methods for pseudo‐pregnancy and deciduoma installation has allowed the demonstration of two inducing circuits: (a) the presence of fertilized ova in the female genital tract and (b) the progestation hormonal status.
Class I Antigens of the Major Histocompatibility Complex on Cytotrophoblast of the Human Placental Basal Plate
Authors: Wells Michael , Hsi Bae‐Li , Faulk W. Page
Published: May 2013

ABSTRACT: The lack of class I antigens of the major histocompatibility complex (MHC) on syncytiotropho‐blast has been proposed as an explanation for the survival of the allogeneic fetus. These antigens, however, have recently been detected on nonvillous trophoblastic columns of the early human placenta. By using a combination of immunofluorescence techniques to identify trophoblast, we have studied transplantation antigens of the cytotrophoblastic shell present in the basal plate of normal full‐term human placentae. With the use of two different monoclonal antibodies to a common determinant of HLA (clones W6/32 and 61D2), it was shown that this subset of trophoblast does express class 1 MHC antigens. However, while these cells reacted uniformly with W6/32, only rare reactivity with 61D2 was found. Reactivity of polyclonal antisera to β‐mi croglobulin correlated with that seen using W6/32. These results are similar to those recently observed in a subset of trophoblast of the amniochorion to which the term “metatrophoblast” has been given.
Identification of Antigenic Components Recognized by “Membrane‐Bound” Antibodies From Ovarian Cancer Patients
Authors: Taylor Douglas D. , Homesley Howard D. , Doellgast George J.
Published: May 2013

ABSTRACT: Immunoglobulins, eluted from ascites fluid‐derived membrane fragments, were used to identify antigens with which they react from ovarian cancer patients. These immunoglobulin preparations were demonstrated to bind antigens from ovarian tumors, but not from normal ovaries. Sodium dodecyl sulfate‐polyacrylamide gel electrophoresis was used to identify the components responsible for the reactivity. The different patients' immunoglobulin preparations were reactive with a similar group of antigens; however, the level of response to each individual component varies. In previous studies, the acid‐eluted immunoglobulin was shown to be reactive with tissues other than ovarian tumors. Relating this cross‐reactivity with the antigens found in ovarian tumors, we found that some components were found only in ovarian tumors, and others appear to be shared by gynecologic tumors, in general. Of these antigens, most are apparently placental antigens. Two proteins were found in normal ovaries.
Immune‐Mediated Migration of Neutrophils Into the Uterine Lumen of Guinea Pigs
Authors: TARGOWSKI STANISLAW P.
Published: May 2013

ABSTRACT: Metritis was elicited by intrauterine infusion of tuberculin or killed Campylobacter fetus ssp. venerealis into vaccinated guinea pigs and lipopolysac‐charide or immune complexes into normal animals. The local inflammatory response to intrauterine infusion of antigens, lipopolysaccharide, and immune complexes was determined by changes in differential cell counts in the uterine lavage fluid and by histopathological examination of uterine tissue. The percentage of neutrophils was significantly (p < 0.01) greater in uterine lavage fluid collected at 4 hr after infusion of tuberculin into animals vaccinated locally (intrauterine) with M. tuberculosis than in animals vaccinated parenterally (subcutaneously). In contrast, the local response to infusion with C. fetus ssp. venerealis was approximately the same in animals vaccinated intrauterine and subcutaneously with Campylobacter. The systemic response, measured by the delayed type hypersensitivity cutaneous reaction to intradermal injection of tuberculin, was significantly (p < 0.01) greater in animals vaccinated subcutaneously than intrauterine. Similarly, the concentration of Campylobacter antibody in the serum of animals vaccinated subcutaneously was significantly (p < 0.01) greater than in guinea pigs vaccinated intrauterine. The intrauterine infusion of immune complexes, composed of C. fetus ssp. venerealis and corresponding antibody, into the uterus of normal guinea pigs stimulated neutrophil migration into the uterine lumen. Infusion of lipopolysaccharide also stimulated neutrophil migration into the uterine lumen. A correlation between an increased percentage of neutrophils in uterine lavage fluid and infiltration of the uterine epithelium with neutrophils was observed.
Detection of Antispermatozoal Antibodies of IgG, IgA, and IgM Immunoglobulin Classes in Cervical Mucus
Authors: CLARKE G.N.
Published: May 2013

ABSTRACT: The immunobead test (IBT) was applied to bromelin‐treated cervical mucus (CM) samples from 78 infertile women. Seven (8.9%) of the patients were positive for IgG and/or IgA class antibodies, whilst none (0/35) were found positive for IgM class antibodies. We found that 57% of the positive samples contained IgG and IgA classes, whilst the remaining samples contained IgA alone. The implications of these results were discussed.
Effect of Pregnancy Plasma and Monoclonal Antibodies to HLA and DR Antigens on Leukocyte Migration
Authors: HEGDE UMASHASHI C. , RAJAN R. , CHITNIS NISHA D.
Published: May 2013

ABSTRACT: We studied the effect of pregnancy plasma and monoclonal antibodies to the histocompatibility antigens HLA and DR on migration of normal leukocytes from capillaries. It was observed that plasma from women in the first trimester of pregnancy significantly enhanced leukocyte migration at a concentration of 10% (mean area of migration = 50.7 ± 9.2 cm2), as compared with plasma from nonpregnant women (22.8 ± 7.0 cm22; p < 0.05). This effect was less during the second trimester (39.5 ± 3.5 cm2; p < 0.05) and no enhancement was noted with plasma obtained from the third trimester of pregnancy. Similar results were obtained with a 20% concentration of plasma also. On the other hand, the monoclonal anti‐HLA and anti‐DR antibodies had an inhibitory effect on migration of leukocytes. These results are discussed in relation to the immunoregulatory role of pregnancy plasma in the nonrejection of the fetal allograft.
Antigens in Bovine Estrual and Cystic Follicles
Authors: HIRSCHEL MARK D. , HUNTER ALAN G.
Published: May 2013

ABSTRACT: The antigenic spectra of estrual or cystic follicular fluid (FF) consisted of 11 blood serum antigens while that of estrual or cystic ovary consisted of 9 identical antigens of which 2 were ovarian specific. The two ovarian‐specific antigens were detected with antisera to estrual or cystic ovary but not with antisera to nonestrual ovaries. They were in higher concentration in estrual ovary than cystic ovary, were localized in bovine oocyte zona pellucida by immunofluorescence and light scattering, and cross‐reacted with prostate tissue. Cystic FF contained a higher concentration (P < 0.05) of IgG than at any stage of the cycle except estrus, and a lower concentration (P < 0.05) of estradiol‐17β than at estrus. It was hypothesized that increased levels of estradiol during estrus alter the permeability of the follicle wall unmasking a zona pellucida antigen in the preovulatory follicle. The appearance of this previously unexposed antigen at estrus could lead to an inflammatory‐like response triggering ovulation.
Suppressive Effect of Pregnancy on the Development of Experimental Allergic Encephalomyelitis in Rabbits
Authors: EVRON SHMUEL , BRENNER TALMA , ABRAMSKY ODED
Published: May 2013

ABSTRACT: In the present study we have investigated the influence of pregnancy on the induction and development of experimental autoimmune encephalomyelitis (EAE) in rabbits in relation to the time of gestation. Randomly bred rabbits were immunized with encephalitogenic bovine brain homogenate in complete Freund's adjuvant before or during pregnancy. The appearance of EAE was delayed and occurred only after delivery, abortion, or fetal resorption. The incidence of the disease was lower and the duration longer. The levels of antibodies to myelin basic protein, an autoantigen of EAE, as measured by solid phase radioimmunoassay, were lower in the pregnant rabbits as compared to the nonpregnant animals. The suppressive influence of pregnancy on the induction and the development of EAE confirms previous reports demonstrating amelioration of autoimmune diseases and other immunological reactions during the second half of human pregnancy. This effect might be partially attributed to the increased level of alpha‐fetoprotein (AFP) and/or other pregnancy‐associated factors in maternal serum.
Comparison of Corynebacterium parvum and Bordetella pertussis With Freund's Complete Adjuvant as Immunopotentiators for β‐Human Chorionic Gonadotropin Linked to an Atoxic Fragment of Tetanus Toxin
Authors: COVEY DANA C. , CHANG C.C. , LAURENCE KENNETH A.
Published: May 2013

ABSTRACT: Corynebacterium parvum and Bordetella pertussis were compared with Freund's complete adjuvant (FCA) for their abilities to potentiate the immune response to haptenic β‐human chorionic gonadotropin covalently coupled to an atoxic 54,000‐molecular‐weight fragment of tetanus toxin (β‐hCG‐TTII). The ability of each adjuvant to enhance production of antibodies to hCG in rabbits was measured by 125I‐hCG radioimmunoassay. At sera dilutions of 1:10,000, analysis of variance for the 8‐week postimmunization course showed that the mean 125I‐hCG binding capacities of the C. parvum group was significantly greater overall than the B. pertussis group (P = .0002) and that the FCA‐treated group had the greatest binding capacity overall (P < .018). The mean binding capacities at 1:40,000 dilution again showed the FCA‐treated group to have significantly higher anti‐hCG titers overall (P < .0015), with C. parvum potentiating a greater overall antibody response than B. pertussis (P = .001). These results indicate that FCA is the most efficacious of the three tested adjuvants in potentiating antibody production to the hapten component of β‐hCG‐TTII. C. parvum was also effective a*t promoting an anti‐β‐hCG response, although not to the same degree as FCA. B. pertussis had only minimal potentiating effect compared to FCA or C. parvum.
Quantitation of Immunoglobulin G on Human Sperm
Authors: HAAS GILBERT G. , D'CRUZ OSMOND J.
Published: May 2013

ABSTRACT: An indirect inhibition assay was devised to quantitate the amount of immunoglobulin molecules on the surface of human sperm. Sperm‐associated IgG was used to inhibit competitively 125I‐labeled polyclonal anti‐human IgG from binding to human IgG affixed to microtissue culture plate wells. Standard curves for the assay were derived by substituting soluble IgG in the supernatant of the tissue culture wells for sperm‐associated IgG. The intraassay coefficient of variation was 6.7%; the interassay coefficient of variation was 5.6–21% depending upon the IgG antisperm antibody‐positive plasma sample assayed. The assay technique was highly correlated (r = 0.99) with the number of antibody‐bound sperm added to the supernatant. When different sperm donors were utilized as an antigen source, the coefficient of variation was 15.6% for positive plasmas and 19.3% for negative plasmas. The indirect inhibition assay showed a strong correlation (r = 0.91) with a previously described radiolabeled antiglobulin assay for sperm‐associated IgG.
Effects of Mouse Testicular Extract on Immunocompetent Cells
Authors: EMOTO MASASHI , YAGYU YOSHIHIKO , NISHIKAWA FUMIKO , KATSUI NORIAKI , KITA EIJI , KASHIBA SHUZO
Published: May 2013

ABSTRACT: We investigated mouse testicular extract (TE) to clarify its biological functions in reproductive immunity. TE, at concentrations of 50–300 μg/ml, enhanced macrophage activities of spreading, glucose consumption, and cytostasis against a susceptible tumor cell line. On the other hand, TE inhibited concanavalin A (Con A)‐induced T‐cell blastogenesis in the dose range of 10–600 μg/ml. To elucidate the origin of TE, W/Wvmice, which genetically lack germ cells, were used. TE obtained from W/Wv mice enhanced the spreadability of macrophages and inhibited Con A‐induced blastogenesis of T cells. The enhancement of macrophage spreading was only achieved by the interstitial fluid (IF), while the suppression of Con A‐induced T‐cell responses was detected in seminiferous tubule fluid (STF) as well as in IF. TE did not affect listerial antigen‐specific responses of lymphocytes in vitro. These results suggest that TE has the capacity to regulate the biological responses associated with reproduction.
Regulation of Immunity to Extraembryonic Antigens in Human Pregnancy
Authors: TORRY DONALD S. , FAULK W. PAGE , McINTYRE JOHN A.
Published: May 2013

ABSTRACT: Pregnancy results in the immunologic challenge of the female to a wide variety of allogeneic antigens. Particular attention has been given to antibodies directed to allotypic trophoblast antigens (TLX), for trophoblast form the true allograft interface between mother and fetus. Studies found that antibodies to paternal TLX allotypes are produced in women suffering from secondary recurrent abortions. These TLX antibodies are not directed to classical HLA private epitopes. In this report, treatment of lymphocytes with papain to remove HLA Class I did not decrease TLX antigen densities. These results suggest TLX antibodies are not directed to Class I epitopes, public or private. The allotypic nature of TLX antigens requires that a pregnant female must be able to regulate TLX immune responses to avoid rejection of the conceptus. One mechanism to specifically and systemically regulate TLX immunity is the idiotype anti‐idiotype network. We provide preliminary evidence in this report for the presence of TLX idiotype network in a normal primigravida. Initially, no antipaternal TLX antibodies were detected in the serum of the primigravida, suggesting no TLX immunization had occurred. However, separation of Ab1 from Ab2 by absorption of primigravida serum with 2° aborter Abl resulted in seroconversion. The primigravi‐da's Abl was cytotoxic for paternal and 3rd‐party lymphocytes in a non‐HLA‐restricted pattern. Primigravida's Ab2 was recovered from the Ab1 matrix by competitive elution by using platelets as source of TLX antigen. The Ab2 was found to inhibit cytotoxicity by 2° aborter Ab1 as well as primigravida Ab1. This is evidence that the Ab2 recognizes a cross‐reactive idiotype (CRI) on TLX antibodies. The presence of TLX anti‐idiotype during normal pregnancy would function to regulate trophoblast immunity and may be required to ensure fetal allograft survival.
Recurrent Spontaneous Abortion
Authors: McINTYRE JOHN A. , COULAM CAROLYN B. , FAULK W. PAGE
Published: May 2013

ABSTRACT: The laboratory diagnosis and clinical management of unexplained recurrent spontaneous abortion (RSA) patients is a controversial issue in contemporary obstetrics. In this report, the results of laboratory investigations and immunotherapy of RSA patients referred to our Center since 1986 are detailed. Our analyses have resulted in grouping RSA patients into primary (1°), secondary (2°), and unexplained classifications. Laboratory evaluation criteria included assays for both complement‐dependent and complement‐independent antipaternal antibodies as well as histocompatibility antigen tissue typing for HLA, A, B, C, and DR antigens. In addition, mixed lymphocyte cultures (MLC) were performed to assess the degree of HLA‐D locus compatibility between couples and to test for the presence of MLC inhibitors in maternal blood. Immunotherapy options and the rationale for their use are given and preliminary outcome data are presented from randomized double‐blinded, placebo‐controlled clinical trials.
Recent Advances in Cancer Research: Drug Targeting Without the Use of Monoclonal Antibodies
Authors: FAULK W. PAGE , HARATS HAVA , McINTYRE JOHN A. , BERCZI ALAJOS , SUN IRIS L. , CRANE FREDERICK L.
Published: May 2013

ABSTRACT: Cancer research in drug targeting has focused on the use of monoclonal antibody conjugates of drugs. This paper discusses the use of ligand conjugates of drugs to deliver to receptors on cancer cells. We have used transferrin coupled to adriamycin, and report these conjugates specifically bind and kill cancer cells in culture. Our studies of the mechanism show targeted plasma membranes are compromised for NADH ferricyanide reduction, and targeted cells lose diferric transferrin reductase activity. These results indicate that the binding of transferrin‐adriamycin conjugates to transferrin receptors on either isolated plasma membranes or viable tumor cells causes an inhibition of redox reactions that are essential for growth. Since transferrin receptors are endocytosable, ligand‐drug conjugates also are delivered to the interior of targeted cells where other mechanisms of killing can be employed. This novel method of drug delivery circumvents the need for monoclonal antibodies, and more investigation of the system may allow a controlled clinical study of its effectiveness.
Human Embryonic Origin Early Pregnancy Factor Before and After Implantation
Authors: NAHHAS FATHALLAH , BARNEA EYTAN
Published: May 2013

ABSTRACT: Early pregnancy factor (EPF) is a factor that has been shown to be involved in the maintenance of the fetal allograft in several mammalian species including man. In that capacity it serves as a link between fertilization and immunomodulation. In the present study we have investigated the secretion of EPF by the human conceptus before and after implantation using rosette inhibition antibody concentration (T11 monocllonal antibody). In isolated trophoblastic cells at gestational week 7–9 there was a significant secretion of EPF. For the first 8 days in culture, secretion was maximal; later, however, at days 13 and 21 these levels declined. Further the EPF content of human embryonal extracts was examined. In various organs, spinal cord, liver, and kidney, significant EPF activity was detected. In women undergoing in vitro fertilization/embryo transfer, a total of 52 preimplantational embryos were cultured for 36 hours. No significant EPF activity was detected in the surrounding media. Two of the 11 patients studied became pregnant during the same cycle after embryo transfer. In conclusion, the preimplantational origin of EPF is maternal, while that of the post‐implantational embryo is of embryonal origin.