bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating Levels of Immunoreactive Cytokines in Women with Preeclampsia
Authors: Conrad Kirk P. , Miles Theresa M. , Benyo Deborah Fairchild 
Published: September 2011

PROBLEM: Circulating inflammatory cytokines have been implicated in the pathogenesis of preeclampsia. To test this hypothesis, we measured plasma levels of immunoreactive tumor necrosis factor (TNF)‐α and ‐β, interleukin (IL)−1α and ‐β, and IL‐6 and −10 in women with preeclampsia, in women with transient gestational hypertension, and throughout normal pregnancy.METHOD OF STUDY: Enzyme‐linked immunosorbent assays were used and subjected to extensive validation studies.RESULTS: The median concentration of plasma TNF‐α was increased by twofold in women with preeclampsia compared with that in normal third‐trimester pregnancy (P < 0.001) and in women with gestational hypertension (P < 0.04). The median concentration of plasma IL‐6 was increased by threefold in women with preeclampsia compared with that in normal third‐trimester pregnancy (P < 0.001) and increased twofold compared with that in women with gestational hypertension (P < 0.1). There were no significant differences observed in the levels of plasma IL‐1β and IL‐10 between the preeclamptic and other subject groups. The level of IL‐1β, but not the levels of IL‐10, TNF‐α, or IL‐6, was significantly changed during normal pregnancy compared with the nonpregnant condition manifesting an overall decline (P < 0.04). TNF‐β and IL‐1α were not detected in any samples, possibly because of the low sensitivity of these particular immunoassays.CONCLUSION: Elevated levels of TNF‐α and IL‐6 may contribute to the putative endothelial dysfunction of preeclampsia.
Apoptosis of T Cells in the First Trimester Human Decidua
Authors: JERZAK MAIGORZATA , KASPRZYCKA MONIKA , WIERBICKI PIOTR , KOTARSKI JAN , GÓRSKI ANDRZEJ 
Published: September 2011

PROBLEM: Apoptosis has been accepted as a mechanism for maintaining tolerance in the immune system. The induction of apoptotic cell death can also be a possible outcome of the lymphocyte activation. Expression of Fas ligand (FasL) by the human trophoblast has been proposed as a mechanism providing protection against the lytic action of decidual immune cells. The aim of this study was to determine whether decidual T cells undergo apoptosis during abortion.METHOD OF STUDY: We studied apoptosis of T cells isolated from the first‐trimester decidua in 12 women after spontaneous or elective abortion. We used gel electrophoresis to detect DNA fragmentation. Cells undergoing DNA fragmentation also were identified by DNA analysis using flow cytometry. This method was based on the accumulation of ethanol‐fixed apoptotic cells in the sub‐GO/G1 peak of the DNA content as a result of the loss of DNA fragments from the cells and because of a reduced DNA ability to be stained by propidium iodide. In addition, the expression of Fas antigen on the surface of decidual T cells (CD3+) also was determined.RESULTS: We did not detect apoptosis by the “ladder” technique. However, the apoptotic index (the percentage of positive cells per total number of cells) ranged from 2% to 24% using flow cytometry.CONCLUSIONS: Trophoblast cells usually fail to stimulate alloantigen‐specific T cells, but they may express nonclassical major histocompatibility complex alloantigens to which mothers can produce immunoglobulin G alloantibody, which requires T helper cell activation. The apoptosis of T cells in the human decidua, probably through Fas‐FasL signaling, may be a defense mechanism against rejection of the fetal allograft by the maternal immune system.
Major Histocompatibility Complex Expression on Human, Male Germ Cells: A Review
Authors: FISZER DOROTA , KURPISZ MACIEJ 
Published: September 2011

PROBLEM: The male reproductive compartment is an immunologically privileged site. The expression pattern of human leukocyte antigens (HLAs) may play an important role in the maintenance of immune tolerance toward differentiating gametogenic cells. This review presents current knowledge about HLA gene expression on human, male germ cells, on mRNA and protein levels, and on their methylation status.METHOD OF STUDY: Different techniques were applied to study HLA gene expression in human testis: (a) protein: e.g., cytotoxicity test, fluorescent labeling techniques, enzyme‐linked immunosorbent assay, and confocal microscopy; (b) mRNA: reverse transcriptase‐polymerase chain reaction, Northern blot hybridization, and in situ hybridization; and (c) methylation status.RESULTS: In normal testicular tissue we observe a lack of HLA‐class I (classical) antigens expression and inversely related expression pattern of HLA class I classical and nonclassical genes. HLA‐A, ‐B, ‐C, and ‐E loci are likewise methylated in somatic and germ cells, whereas ‐F and ‐G genes are less methylated in sperm precursors.CONCLUSIONS: Immunologic tolerance in human testis is actively maintained by the specific expression pattern of HLA genes regulated by hormones and growth factors.
Sexual and Mother‐to‐Child Transmission of the Human Immunodeficiency Virus Type 1: A Review
Authors: CHERMANN JEAN‐CLAUDE 
Published: September 2011

PROBLEM: Sexual and mother‐to‐child transmission of the human immunodeficiency virus (HIV) type 1 occurs only with a low percentage of infection. Many instances of sexual intercourse result in no transmission, and only 20% of children are infected from seropositive mothers (3% in mothers treated with azidothymidine).METHOD OF STUDY: We analyzed the presence of HIV in various ejaculates of the same HIV‐infected patients, as well as in the cervico‐vaginal fluid. We have studied the mechanism of transmission from mother to child, by analyzing the cell‐to‐cell transmission in the trophoblast.RESULTS: Some ejaculates collected at different times from the same HIV‐infected males are free of virus, explaining the low rate of sexual transmission. We never found HIV in mobile spermatozoa. The trophoblast can be infected by HIV with a strain dependence and also transiently. By analyzing the tissue of the fetus, it was found that only some organs are infected, confirming the cell‐to‐cell transmission between the mother and child and not a true vertical transmission through the germinal lines.CONCLUSIONS: HIV is not always present in the genital secretion, explaining the low rate of sexual transmission. Mother‐to‐child transmission occurs during pregnancy but often after the second trimester and at delivery after cell‐to‐cell or blood transmission, respectively.
Epitopes of Human Chorionic Gonadotropin and Their Relationship to Immunogenicity and Cross‐Reactivity of β‐Chain Mutants
Authors: PORAKISHVILI N. , JACKSON A.M. , de SOUZA J.B. , CHIESA M. DALLA , ROITT I.M. , DELVES P.J. , LUND T. 
Published: September 2011

PROBLEM: Human chorionic gonadotropin (hCG) is a placental glycoprotein hormone, a heterodimeric molecule, consisting of α and β chains. It induces the synthesis of progesterone, which is essential for the maintenance of the fertilized egg. Antibodies directed against hCG can, therefore, prevent pregnancy and serve as a vaccine. hCG belongs to the glycoprotein hormone family and shares the α chain with the other members. The β chain is a hormone‐specific subunit that is unique to hCG, but still possesses 85% amino acid homology with the β chain of luteinizing hormone (LH), which means that prolonged immunization with hCG produces antibodies that cross‐react with LH.METHOD OF STUDY: We have taken an approach involving the mutation of βhCG to eliminate cross‐reactive epitopes without affecting the natural folding of the polypeptide chain and thus the unique βhCG‐specific epitopes.RESULTS: Several mutants have been constructed that have maintained the binding to hCG‐specific monoclonal antibodies (mAbs) but have lost the ability to bind to a panel of LH cross‐reactive mAbs. To investigate the immunogenicity of selected mutants, mice were immunized with expression plasmid DNA, containing the gene for wild‐type βhCG and two mutants: mutant 3, with four amino acid substitutions (68 Arg→Glu; 74 Arg→Ser; 75 Gly→His; 79 Val→His), and mutant 7, with a single amino acid substitution (68 Arg→Glu).CONCLUSIONS: Athough both mutants were able to elicit antibody responses in at least some animals, the levels were less than those seen with the wild‐type βhCG DNA, and there seems still to be a residual cross‐reacitivity with LH. Attempts to improve the immunogenicity of the mutants and to further modify the sequence to remove the cross‐reacitivty are currently underway.
Antisperm Antibodies in Prepubertal Boys and Their Reactivity with Antigenic Determinants on Differentiated Spermatozoa
Authors: DOMAGAŁA A. , KAMIENICZNA M. , KOWALCZYK D. , KURPISZ M. 
Published: September 2011

PROBLEM: Antisperm antibodies induced in prepubertal boys with testicular failures were characterized by using four techniques of antibody detection. The reactivity of circulating antisperm antibodies in prepubertal boys and the reactivity of antibodies in sera samples of adult fertile and infertile males were compared against the same sperm antigenic pools (live or fixed spermatozoa, or sperm antigenic extracts).METHOD OF STUDY: The incidence of antisperm antibodies in sera samples of 69 prepubertal boys with testicular failures and 21 samples obtained from adult, male individuals was assessed by indirect immunobead binding test (IDIBT), flow cytometry measurement, enzyme‐linked immunosorbent assay, and Western blotting. Immunoblot analysis was performed by using sperm extracts of glycosylated and deglycosylated solubilized membrane antigens.RESULTS: Sera samples were studied in a group composed of healthy prepubertal boys (n = 7) and prepubertal boys with testicular failures (n = 69). Applied tests of antibody detection revealed striking differences in a group of boys with testicular pathology. With IDIBT, 7% of the sera samples were found positive, whereas with flow cytometry measurement, 48% of the sera samples were positive. Immunosorbent assay (fixed sperm) indicated 32% positive cases in the same group. The sera samples were found to be positive in 65% of immunoblotting reactions with glycosylated antigens and in 70% of immunoblotting reactions with deglycosylated antigens. All applied detection assays were clearly negative on sera samples from fertile, adult males. Western immunoblotting indicated an immunodominant antigenic determinant of 58 kDa.CONCLUSIONS: Tests of antibody detection with the use of live sperm (IDIBT and flow cytometry measurements) presented low sensitivity (8% and 48%, respectively) in a group of prepubertal boys. This observation underlines the difficulties in assigning the prospective prognosis of future fertility status in prepubertal boys with antisperm antibodies.
Expression and Localization of the Th2‐type Cytokine Interleukin‐13 and Its Receptor in the Placenta During Human Pregnancy
Authors: DEALTRY GILLIAN B. , CLARK DAWN E. , SHARKEY ANDREW , CHARNOCK‐JONES D. STEPHEN , SMITH STEPHEN K. 
Published: September 2011

PROBLEM: To investigate the expression of the Th2‐type cytokine interleukin (IL)‐13 and its receptor in human placenta during gestation.METHOD OF STUDY: Expression of IL‐13 and its receptor was analyzed by reverse transcriptase (RT)‐polymerase chain reaction (PCR), in situ hybridization and immunohistochemistry using human placental samples.RESULTS: IL‐13 mRNA was detected by RT‐PCR in placental extracts from all stages of gestation. In situ hybridization revealed IL‐13 mRNA in first trimester cytotrophoblast and syncytiotrophoblast. Few positive cells were found within decidual sections from the same pregnancy. Immunohistochemistry revealed a similar pattern to in situ hybridization. This was largely absent in second‐ and third‐trimester placentae. IL‐13 receptor α chain (IL‐13Rα) was detected by immunofluorescence on the surface of leukocytes in first‐trimester villous core and decidua.CONCLUSIONS: The expression of IL‐13 is spatially and temporally regulated in the placenta, and associated with the close proximity of a receptor‐bearing target leukocyte population.
Expression of a Progelatinase Activator (MT1‐MMP) in Human Fetal Membranes
Authors: Fortunato Stephen J. , Menon Ramkumar , Lombardi Salvatore J. 
Published: September 2011

PROBLEM: The finding of MMP‐2 (which degrades type IV collagen) and TIMP‐2 (the tissue inhibitor of MMP) in fetal membranes suggests the possibility of membrane self‐destruction as an etiology of premature rupture of fetal membranes. MMP‐2 is activated by a membrane‐bound MMP (MT1‐MMP). This study was undertaken to detect the presence of MT1‐MMP in human fetal membranes.METHOD OF STUDY: Fetal membranes were placed in an organ explant system and stimulated with lipopolysaccaride (LPS). MT1‐MMP expression was studied in frozen tissues by reverse transcriptase (RT)‐polymerase chain reaction (PCR) using primers designed in our laboratory. DNA sequence analysis was performed to verify the specificity of PCR products. In situ hybridization and immunocytochemistry were used to localize MT1‐MMP mRNA and peptide, respectively.RESULTS: RT‐PCR data indicated the presence of mRNA for MT1‐MMP in fetal membranes. Although PCR is not quantitative, no differences in mRNA band intensities were noticed after LPS stimulation. MT1‐MMP expression was constitutive throughout the culture period. In situ hybridization demonstrated amnion, chorionic laeve, cytotrophoblast cells, and the cells in the reticular and spongy layer of the extracellular matrix as the origin of MT1‐MMP mRNA and peptide.CONCLUSIONS: This is the first study documenting the amniochorionic membrane as a source of MT1‐MMP mRNA and peptide. Activation of progelatinase A requires the presence of this membrane‐associated MMP. The finding of MT1 ‐MMP in a tissue already known to produce MMP‐2 and TIMP‐2 documents the full system for activation and inhibition of this gelatinase. During infection, an imbalance in the expression of MT1‐MMP, MMP‐2, and TIMP‐2 may constitute an endogenous pathway of membrane degradation.
Histologie Distribution and Biochemical Properties of α1‐Microglobulin in Human Placenta
Authors: Berggård Tord , Enghild Jan J. , Badve Sunil , Salafia Carolyn M. , Lögdberg Lennart , ÅKerströum Bo 
Published: September 2011

PROBLEM: The embryo is protected from immunologic rejection by the mother, possibly accomplished by immunosuppressive molecules located in the placenta. We investigated the distribution and biochemical properties in placenta of the immunosuppressive plasma protein α1‐microglobulin.METHOD OF STUDY: Placental a α1‐microglobulin was investigated by immunohistochemistry and, after extraction, by electrophoresis, immunoblotting and radioimmunoassay.RESULTS: α1‐Microglobulin staining was observed in the intervillous fibrin and in syncytiotrophoblasts, especially at sites with syncytial injury. Strongly stained single cells in the intervillous spaces and variably stained intravillous histiocytes were noted. Solubilization of the placenta‐matrix fraction and placenta membrane fraction released predominantly the free form of α1‐microglobulin, but, additionally, an apparently truncated form from the placenta‐membrane fraction. The soluble fraction of placenta contained two novel α1‐microglobulin complexes.CONCLUSIONS: The biochemical analysis indicates the presence in placenta of α1‐microglobulin forms not found in blood. The histochemical analysis supports the possibility that α1‐microglobulin may function as a local immunoregulator in the placenta.
Immunopathology of the Implantation Site Utilizing Monoclonal Antibodies to Natural Killer Cells in Women with Recurrent Pregnancy Losses
Authors: Kwak Joanne Y.H. , Beer Alan E. , Kim Sung Hee , Mantouvalos Harris P. 
Published: September 2011

PROBLEM: Placental lesions of 71 women with documented recurrent spontaneous abortions of unknown etiology were evaluated using immunohistochemical staining.METHOD OF STUDY: Placental tissue blocks (less than 12 weeks gestation) from prior pregnancy losses were obtained, recut, and analyzed utilizing monoclonal antibody to identify the trophoblast (cytokeratin 8/18) and natural killer (NK) cells (CD57) at the implantation site. The following features were evaluated: trophoblast invasion pattern; syncytium formation; vasculitis and thromboembolism of decidual vessels: decidual inflammation; decidual necrosis; fibrin deposition at the decidual necrosis site; mononuclear‐cell infiltration in villi and intervillous space; perivillous fibrin deposition; trophoblast morphology; and quantitation of CD57 + NK cells within the decidual tissue near the implantation site. Controls consisted of 20 healthy women with no history of recurrent pregnancy losses, who had their pregnancies electively terminated.RESULTS: Of the women studied, 29.6% demonstrated elevated CD57 + NK cells at the implantation site (P = 0.030), 54.1% had inadequate cytotrophoblast invasion depth (P = 0.000), 44.1% demonstrated inadequate syncytium formation (P = 0.004), and 33.9% presented thromboembolism in decidual vessels (P = 0.025).CONCLUSION: Some women with recurrrent spontaneous abortions demonstrate abnormal placental lesions at the implantation site. Immunopathologic evaluation of the placental implantation site that terminated in a spontaneous abortion may reveal the immunopathogenesis of previous pregnancy losses.
The Expression of Human Leukocyte Antigen‐G on Trophoblasts Abolishes the Growth‐Suppressing Effect of Interleukin‐2 towards Them
Authors: Hamai Yoko , Fujii Tomoyuki , Yamashita Takahiro , Miki Akinori , Hyodo Hironobu , Kozuma Shiro , Geraghty Daniel E. , Taketani Yuji 
Published: September 2011

PROBLEM: We have shown the attenuated human leukocyte antigen (HLA)‐G expression on trophoblasts and an aberrant expression of interleukin (IL)‐2, a cytotoxic cytokine, in decidual tissue in preeclampsia, where deteriorated trophoblastic invasion into decidual layers may constitute a crucial pathogenesis. We hypothesized that the absence of HLA‐G might make trophoblasts susceptible to compromise by IL‐2.METHOD OF STUDY: We analyzed the growth of HLA‐G‐negative and ‐positive cell lines, all of which possessed IL‐2 receptors, in the culture with or without IL‐2 supplementation.RESULTS: The proliferation of HLA‐G‐positive trophoblastic cell lines (BeWo and JEG‐3) was not influenced by the addition of IL‐2, whereas a HLA‐G‐negative trophoblastic cell line (JAR) exhibited significantly decreased proliferation when cultured with IL‐2. Interestingly, the transfection of JAR cells with HLA‐G completely eliminates the growth‐inhibitory effect of IL‐2.CONCLUSION: The expression of HLA‐G may commit trophoblasts to evade cell damage by IL‐2, which may be relevant to maternal tolerance of the fetus during pregnancy and its derangement as exemplified by preeclampsia.
Mitogen‐Induced Cytokine Responses of Maternal Peripheral Blood Lymphocytes Indicate a Differential Th‐Type Bias in Normal Pregnancy and Pregnancy Failure
Authors: Makhseed M. , Raghupathy R. , Azizieh F. , Al‐Azemi M. M. K. , Hassan N. A. , Bandar A. 
Published: September 2011

Makhseed M, Raghupathy R, Azizieh F, Al‐Azemi MMK, Hassan NA, Bandar A. Mitogen‐induced cytokine responses of maternal peripheral blood lymphocytes indicate a differential Th‐type bias in normal pregnancy and pregnancy failure. AJRI 1999; 42:273–281 © Munksgaard, CopenhagenPROBLEM: Profiles of Th1‐ and Th2‐type cytokines were studied in women with a history of successful pregnancy and in women with a history of unexplained recurrent spontaneous abortions (RSA) with the objective of elucidating Th1‐ and Th2‐type bias in normal pregnancy and pregnancy failure.METHOD OF STUDY: Peripheral blood mononuclear cells (PBMCs) from 54 women with a history of normal pregnancy and 23 women with a history of unexplained RSA, obtained at delivery or on the day of abortion, respectively, were stimulated with phytohemagglutinin (PHA), followed by the estimation of four Th2 cytokines and four Th1 cytokines.RESULTS: Significantly greater levels of Th2 cytokines were produced by the normal group than by the RSA group. On the other hand, significantly higher levels of Th1 cytokines were produced by the RSA group than by the normal pregnancy group.CONCLUSIONS: These data support the concept that unexplained recurrent spontaneous abortion is associated with an increase in Th1‐type reactivity, while Th2 dominance is a feature of successful pregnancy.
An Inverse Relation Between the Expression of Tumor Necrosis Factor Alpha (TNF‐α) and TNF‐α Receptor in Human Endometrium
Authors: Chegini Nasser , Dou Quigchuan , Williams R. Stan 
Published: September 2011

Chegini N, Dou Q, Williams RS. An inverse relationship between the expression of tumor necrosis factor alpha (TNF‐α) and TNF‐α receptor in human endometrium. AJRI 1999; 42:297–302 © Munksgaard, CopenhagenPROBLEM: To determine whether the expression of tumor necrosis factor (TNF‐α) correlates with TNF‐α receptor expression in human endometrium.METHOD OF STUDY: A multiprimer synthetic cDNA standard template containing complimentary sequences for several cytokines including TNF‐α and TNF‐α receptor type 2 was constructed and used in quantitative reverse transcription polymerase chain reaction (Q‐RT‐PCR).RESULTS: Endometrium from proliferative phase of the menstrual cycle expresses higher levels of TNF‐α mRNA (2.35 ± 0.2 × 105 copies/μg of total cellular RNA) than secretory phase ([1.3 ± 0.08 × 105 copies] P < 0.05), with a significant reduction during menses (1.2 ± 0.1 × 104 copies) and postmenopausal period (8.1 ± 1.6 × 104 copies [P < 0.05]). In contrast, TNF‐α type 1 receptor mRNA expression was higher in endometrium from the secretory phase (6.6 ± 0.6 × 107 copies) compared to the menses (5.1 ± 0.5 × 106 copies), proliferative phase (1.9 ± 0.1 × 106 copies) and postmenopausal period (5.8 ± 0.7 × 104 copies [P < 0.05]). Comparatively, TNF‐α receptor type 2 is expressed 10 to 100 fold higher in the endometrium than TNF‐α (P < 0.05).CONCLUSION: The data confirm that human endometrium expresses TNF‐α; and provide the first evidence that TNF‐α expression is inversely related to TNF‐α type 1 receptor expression during the menstrual cycle. Such an inverse relation between TNF‐α and TNF‐α receptor expression may provide a regulatory mechanism necessary to overcome the detrimental effect of high levels of TNF‐α on various endometrial cell types.