bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Immunosuppressive Cytokines Influence the Fetal Survival in Patients with Pregnancy‐Induced Hypertension
Authors: DEL GOBBO VERA , GIGANTI MARIA GABRIELLA , ZENOBI ROSSELLA , PREMROV MARIA GRAZIA , VILLANI VITTORIO 
Published: December 2003

PROBLEM: The present study examines the hypothesis that the elevated levels of transforming growth factor (TGF)‐β1 and
interleukin (IL)‐10 would be protective for the fetus survival during
pregnancy‐induced hypertension (PIH). Moreover, we evaluate the IL‐12 and
IL‐15 serum concentrations and their relationships with PIH.
METHOD OF STUDY: Serum samples were obtained before the onset of labor
from control and PIH groups. Cytokine concentrations were determined by
Enzyme‐Linked Immunoadsorbent Assay.
RESULTS: Our data show that PIH women have significantly higher
TGF‐β1 and IL‐10 concentrations with respect to control
groups (P=0.0001). Similarly, macrophages from the PIH placentas
produce in vitro more elevated TGF‐β1 and IL‐10
levels compared to normal pregnant ones (P=0.02), also in the absence of LPS stimulation. IL‐12 and IL‐15 serum concentrations were not detectable in all pregnant groups.  CONCLUSION: We have found that PIH women have elevated concentrations of anti‐inflammatory/immunosuppressive cytokines, suggesting their important role in fetal allograft protection during the normal and pathological pregnancy.
Pregnancy Outcome and Ovarian Antibodies in Infertility Patients Undergoing Controlled Ovarian Hyperstimulation
Authors: LUBORSKY J. , PONG R. 
Published: December 2003

PROBLEM: Several endocrine markers are well‐established, but not absolute, predictors of successful outcomes following controlled ovarian hyperstimulation. Another potential predictor for success may be a marker of ovarian autoimmunity. Ovarian antibodies (OVAB) are detected in women with unexplained infertility. We tested the hypothesis that women with OVAB have a poorer pregnancy outcome in in vitro fertilization (IVF).
METHOD OF STUDY: Serum samples (n=47) were assessed by a previously described immunoassay for OVAB in a cross‐sectional, retrospective study design.
RESULTS: Women who became pregnant had a lower frequency of OVAB than women who did not become pregnant (25.0% [4/16] vs. 58.1% [18/31], respectively; P=0.03). There was no significant difference in day 3 estradiol, amount of human menopausal gonadotropin given, peak estradiol, the number of follicles observed, or the number of eggs retrieved between women who achieved pregnancy and those who did not.  CONCLUSIONS: Together with other information such as reproductive hormone levels and measures of follicle growth, OVAB may contribute additional information for prediction of successful IVF outcomes.
Chemotactic Activity for Polymorphonuclear Leukocytes: Meconium Versus Meconium‐Stained Amniotic Fluid
Authors: YAMADA TETSUO , MATSUBARA SHIGEKI , MINAKAMI HISANORI , KOHMURA YASUHIRO , HIRATSUKA MITSUHIRO , SATO IKUO 
Published: December 2003

PROBLEM: Our previous study indicated that meconium‐stained amniotic fluid (turbid AF) possessed a potent chemotactic activity for leukocytes, which may be dependent on interleukin‐8. It is not known, however, whether meconium itself possesses this chemotactic activity.  METHOD OF STUDY: Meconium samples were collected from mature neonates with and without turbid AF. A 5% meconium suspension in phosphate buffered saline was prepared and measured for its chemotactic activity for leukocytes using the blind well chamber technique. Concentrations of IL‐8, TNFα and IL‐1β were also measured with ELISA.  RESULTS: The number of leukocytes that migrated to the meconium suspension (35±27) was comparable with that of the clear AF (31±37), but was significantly lower than that of the turbid AF (184±62, P<0.0001). The meconium suspension contained much lower levels of IL‐8, TNFα and IL‐1β than the turbid AF.
CONCLUSIONS: Meconium itself exhibits a lower chemotactic activity for polymorphonuclear leukocytes than turbid AF in vitro. The leukocyte chemotactic activity of turbid AF does not originate from meconium itself.
Female Sex Hormones Modulate the Function of LPS‐treated Macrophages
Authors: CHAO TZU‐CHIEH , CHAO HSIAO‐HSIANG , CHEN MIIN‐FU , GREAGER JOHN A. , WALTER ROBERT J. 
Published: December 2003

PROBLEM: To study the effects of estradiol (E2) or progesterone on macrophage function in the presence of lipopolysaccharide (LPS).  METHOD OF STUDY: Male rat peritoneal macrophages were treated in vitro with 0.1 μg/mL of LPS and E2 or progesterone.
RESULTS: At 10−2 ng/mL, E2 significantly (P<0.05; n=6) enhanced tumor necrosis factor (TNF) release by LPS‐treated macrophages. TNF release was significantly (P<0.05; n=6) inhibited by 102 ng/mL or 103 ng/mL of E2 and by progesterone at less than 10−3 ng/mL or greater than 10−1 ng/mL. E2 (10−4 and 10 ng/mL) and progesterone (10−6–10−4 ng/mL and 102 ng/mL) each significantly (P<0.05, n=8) enhanced H2O2 release by LPS‐treated macrophages. E2 (<10−2 and >10 ng/mL) and progesterone (10−7–104 ng/mL) each significantly inhibited (P<0.05; n=6) NO2− release by LPS‐treated macrophages.  CONCLUSIONS: Exposure to LPS tended to diminish the effects of E2 and to enhance the effects of progesterone on the parameters determined here. Such LPS‐associated alterations in the dose–response profile of macrophages to female sex hormones may contribute to gender‐related differences in the immune response under normal and pathological conditions.
Nitric Oxide (NO) and Interleukin‐1β (IL‐1β) in Follicular Fluid and Their Correlation With Fertilization and Embryo Cleavage
Authors: BARRIONUEVO MARCELO J. , SCHWANDT RENEE A. , RAO PAPINENI S. , GRAHAM LLOYD B. , MAISEL LAURA P. , YEKO TIMOTHY R. 
Published: December 2003

PROBLEM: Using an IVF model, the goal of the study was to investigate the relationship between follicular fluid (ff) NO and IL‐1β levels, as well as their correlation with fertilization of mature oocytes and embryo cleavage rates.  METHOD OF STUDY: Follicular fluid was collected from 17 patients at the time of transvaginal oocyte retrieval following controlled ovarian stimulation. Oocytes harvested from these follicles were followed through fertilization and embryo cleavage. The NO metabolites nitrate/nitrite (NO3/NO2) were measured using the Griess reaction as an indirect assessment of NO activity. IL‐1β was measured using a high sensitivity ELISA system (Amersham, UK). The Student's t‐test was utilized for unpaired data with the means considered significantly different when P≤0.05.
RESULTS: Follicular fluid NO3/NO2 levels were significantly lower in follicles containing mature oocytes that fertilized (n=30; 9.7±1.0 μM), versus those that did not fertilize (n=23; 15.4±2.4 μM; P<0.05). Follicles that contained oocytes that fertilized and went on to divide beyond the 6 cell stage had significantly lower ff levels of NO3/NO2 (n=18; 7.5±0.9 μM), as compared to ff that contained oocytes that did not fertilize or failed to develop beyond the 5 cell stage (n=35; 14.6±1.7 μM; P<0.01). No correlation was found between ff NO3/NO2 levels (n=28; 13.8±2.0 μM) and ff IL‐1β levels (n=28; 0.5±0.08 pg/mL). An analysis of ff IL‐1β levels in relation to fertilization and embryo cleavage rates revealed no correlation.  CONCLUSIONS: Lower ff NO3/NO2 levels at the time of oocyte retrieval are associated with adequate fertilization and embryo cleavage rates. In our IVF model, no correlation was found between ff IL‐1β levels and ff NO3/NO2, fertilization, or embryo cleavage rates.
The Production and Clinical Evaluation of Macrophage Colony‐Stimulating Factor and Macrophage Chemoattractant Protein‐1 in Human Follicular Fluids
Authors: KAWANO YASUSHI , KAWASAKI FUMIKO , NAKAMURA SATOMI , MATSUI NAOHIKO , NARAHARA HISASHI , MIYAKAWA ISAO 
Published: December 2003

PROBLEM: In order to investigate the role of macrophage colony‐stimulating factor (M‐CSF) and macrophage chemoattractant protein‐1 (MCP‐1) in human ovulation, we measured the concentrations of M‐CSF and MCP‐1 in human follicular fluids (FFs) and correlated them with oocyte maturation.  METHOD OF STUDY: The oocytes were obtained from the FFs of 46 women undergoing in vitro fertilization and embryo transfer (IVF–ET). The concentrations of M‐CSF and MCP‐1 in the FFs were measured by enzyme‐linked immunosorbent assay. In addition, granulosa cells obtained from the FFs of IVF patients were cultured and treated with forskolin and 12‐O‐tetradecanoylphorbol 13‐acetate (TPA) for 24–48 hr.
RESULTS: Concentrations of M‐CSF and MCP‐1 were significantly higher in the FFs than in the serum (P<0.01). M‐CSF concentrations tended to be higher, while MCP‐1 concentrations were significantly higher in the FFs containing mature oocytes than in FFs containing immature oocytes (P<0.05). The production of M‐CSF was markedly increased over the basal level after treatment with forskolin (10 μM) for 24 (P<0.02) and 48 hr (P<0.01); however, the production of MCP‐1 was unchanged.  CONCLUSIONS: Our data suggest that M‐CSF and MCP‐1 may play an important role in human preovulatory processes and that M‐CSF, in particular, may be regulated by cyclic adenosine monophosphate. M‐CSF and MCP‐1 may also be valuable biochemical markers in the evaluation of oocyte maturation.
Inhibition of Murine Sperm‐Oolemma Binding by Antibodies to an Oocyte Membrane (OM) Antigen: Implication in Contraceptive Vaccine Development
Authors: NAZ RAJESH K. , LESLIE MONICA H. , ZHU XIAOLONG 
Published: December 2003

PROBLEM: The present study was conducted to investigate the oocyte membrane protein(s) that is involved in sperm binding in the mouse, and whether or not it can be used for the development of a contraceptive vaccine.  METHOD OF STUDY: The zona‐free oocytes were treated with Triton X‐100 and the extract was analyzed for homogeneity in the sodium dodecylsulfate (SDS)‐polyacrylamide gel electrophoresis (PAGE) after staining with silver nitrate. The appropriate band of 50±4 kD, designated as OM antigen, was excised from the gel and used for the immunization. The female rabbits were immunized with the excised band per se and the female mice were immunized with the OM antigen after conjugation to keyhole limpet hemocyanin (KLH). The affinity‐purified antibodies were analyzed in the enzyme‐linked immunosorbent assay (ELISA), immunoprecipitation procedure, western blot procedure, indirect immunofluorescence technique (IFT), and sperm‐oolemma binding assay. Actively‐immunized mice were analyzed for in vivo fertility.
RESULTS: The Triton X‐100 extract of zona‐free oocytes predominantly showed a single protein band of 50±4 kD in the SDS‐PAGE. Active immunization of female rabbits and of female mice with OM antigen raised high antibody titers (ELISA titer>1:4096) that specifically recognized the OM antigen in the immunoprecipitation and Western blot procedures, and reacted with the oocyte in the IFT. These antibodies demonstrated a significant (P<0.05) up to a complete block of sperm‐oolemma binding in the in vitro binding assay. Binding of both the acrosome‐intact and acrosome‐reacted sperm was inhibited. Mice actively immunized with OM antigen also showed a significant reduction in vivo fertility as seen by the 9‐day implants in uteri. Preliminary data indicate that the antibodies to OM antigen were tissue‐specific and did not react with the specific band in any tissue extract in the western blot procedure.  CONCLUSIONS: These results indicate that the OM antigen is involved in sperm‐oolemma binding and constitute an attractive molecule that needs further investigation for examining its utility in the contraceptive vaccine development.
Differential Expression and Regulation of Inducible Nitric Oxide Synthase (iNOS) mRNA in Human Trophoblasts in vitro1
Authors: HAMBARTSOUMIAN E. , SRIVASTAVA R.K. , SEIBEL M.M. , HAMBARTSOUMIAN E. , SEIBEL M.M. 
Published: December 2003

OBJECTIVES: To determine the expression of inducible nitric oxide synthase (iNOS) in human trophoblast and to examine the possible regulation of iNOS gene by cytokines.  MATERIALS AND METHODS: Total RNA was isolated from: 1) homogenized placental tissue; from 2) isolated and purified cytotrophoblast cells; and 3) cytotrophoblast and syncytiotrophoblast cells treated with cytokines in vitro. RNA was reverse transcribed and amplified by polymerase chain reaction, using specific primers for iNOS. Trophoblast cells were treated in vitro by interferon‐γ (IFN‐γ) in a dose of 10 ng/mL, Interleukin 1β (IL‐1β) (4 ng/mL) and leukemia inhibitory factor (LIF) (1 ng/mL). Trophoblasts were also subjected to immunocytochemistry using iNOS‐specific antibody to detect iNOS protein expression in these cells.
RESULTS: The expression of iNOS mRNA was found both in placental tissue and isolated cytotrophoblast cells. In culture, the highly differentiated syncytiotrophoblast expressed more mRNA than cytotrophoblast cells. IFN‐γ and LIF, but not IL‐1β, induced iNOS mRNA expression in trophoblast cells in vitro. The effects of these cytokines on iNOS mRNA were only observed in syncytiotrophoblast cells, but not in cytotrophoblast cells. Immunocytochemical staining confirmed the trophoblast cells as a major source of the iNOS synthase production.
CONCLUSIONS: 1) Human trophoblast cells are able to express the iNOS mRNA, hence suggesting a role for NO in placental growth and function. 2) LIF and IFN‐γ, but not IL‐1β, induce the iNOS mRNA expression in syncytiotrophoblast cells in vitro, suggesting possible similar regulatory mechanisms in vivo. 3) This study, for the first time, demonstrates the stimulating effect of LIF on iNOS gene expression in human tissue.
Localization and Distribution of Platelet Activating Factor Receptors in the Mouse Ovary and Oviduct During the Estrous Cycle and Early Pregnancy
Authors: LASH GENDIE E. , LEGGE MICHAEL 
Published: December 2003

PROBLEM: This study determined platelet activating factor (PAF) binding to ovaries and oviduct tissues to identify the location of PAF–tissue interaction.  METHOD: Mouse ovaries and oviducts taken during the estrous cycle and days 1, 4 and 7 post‐conception (pc) were analyzed by [
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H]PAF binding using frozen sections and autoradiography.
RESULTS: For the outer epithelium of estrous and metestrous ovaries there was no significant difference in PAF binding (P>0.05); however, both stages were significantly different from proestrous (P<0.001). Ovarian stroma PAF binding was significantly higher (P<0.001) at estrous than metestrous, with no PAF binding at proestrous. Binding of PAF to estrous ovarian follicles was significantly greater (P<0.001) than at proestrous and metestrous. Estrous oviduct binding of PAF was significantly increased for stroma, inner epithelium and lumen (P<0.001 in all cases). At days 1 and 7 pc, all ovarian tissues had the greatest PAF binding with day 4 pc failing to bind PAF except for a significant decrease in corpora luteal binding (P<0.001). Oviduct binding of PAF was greatest at day 1 pc.  CONCLUSION: Ovarian and oviduct PAF receptor expression corresponds to peak embryo PAF synthesis and establishes the basis for PAF–PAF receptor mediated early pregnancy signaling system.
Plasma Antiviral Activity and Interferon‐γ Production by Superantigen‐stimulated Lymphocytes during Normal Human Pregnancy
Authors: GRASSO GIOVANNI , MASSAI LAURETTA , MIGLIACCIO PIERLUIGI , PICCIOLINI ENRICO , MUSCETTOLA MICHELA 
Published: December 2003

PROBLEM: Plasma interferon (IFN)‐γ levels, lymphocyte responsiveness, and evaluation of the relationship between circulating antiviral activity (AA) and IFN‐γ production were studied in pregnant women and nonpregnant age‐matched controls with the objective of elucidating the downregulation of IFN‐γ production in successful pregnancy.METHOD OF STUDY: In plasma and supernatants of peripheral blood mononuclear cell (PBMC) cultures, stimulated with staphylococcal enterotoxin A (SEA) superantigen, from 43 pregnant women with a history of normal pregnancy and 30 healthy nonpregnant age‐matched controls, levels of AA were measured in a micromethod by inhibition of the cytopathic effect (CPE) caused by vesicular stomatitis virus (VSV) in the human amnionic cell line (WISH).RESULTS: Significantly higher plasma AA (60% was IFN‐γ and residual activity was acid‐labile IFN‐like) was present in pregnant women than controls. On the other hand, SEA‐activated PBMCs from pregnant women produced significantly lower IFN‐γ levels than those of nonpregnant women. Furthermore, maternal plasma AA levels correlated negatively with IFN‐γ production by SEA‐stimulated PBMCs.CONCLUSION: The hypothesis that successful pregnancy requires downregulation of IFN‐γ is only partially sustained, suggesting that the immunology of pregnancy is more complex and that murine and human pregnancy have different cytokine profiles.
IgG Anti‐laminin‐1 Autoantibody and Recurrent Miscarriages
Authors: INAGAKI JUNKO , MATSUURA EIJI , KAIHARA KEIKO , KOBAYASHI KAZUKO , YASUDA TATSUJI , NOMIZU MOTOYOSHI , SUGIURA‐OGASAWARA MAYUMI , KATANO KINUE , AOKI KOJI 
Published: December 2003

PROBLEM: The present study assesses the clinical significance of anti‐laminin‐1 auto‐antibodies (auto‐Abs) in recurrent miscarriages.  METHOD OF STUDY: A total of 207 recurrent aborters with a history of two or more consecutive first‐trimester miscarriages were tested for the presence of anti‐laminin‐1 Abs, β2‐glycoprotein I‐dependent anticardiolipin Abs, lupus anticoagulants, anti‐DNA Abs, and anti‐nuclear Abs, before they had conceived again. Recurrent aborters then were followed up during subsequent pregnancies and their outcomes were evaluated relative to their blood test results prior to pregnancy.
RESULTS: Fifty‐five (31.1%) women out of 177 recurrent aborters were positive for IgG anti‐laminin‐1 auto‐Abs. The levels of IgG anti‐laminin‐1 auto‐Abs in recurrent aborters were significantly higher than those in healthy pregnant women and in healthy non‐pregnant women (P=0.0043 and 0.0073, respectively). The live birth rate of subsequent pregnancies in IgG anti‐laminin‐1 auto‐Abs‐positive recurrent aborters was significantly lower than the IgG anti‐laminin‐1 auto‐Abs‐negative recurrent aborters (P=0.0320). There were no specifically significant relationships observed between IgG anti‐laminin‐1 auto‐Abs and other tested auto‐Abs.  CONCLUSION: IgG anti‐laminin‐1 auto‐Abs are associated with recurrent miscarriages and the subsequent pregnancy outcome of recurrent aborters.
TH1/TH2,3 Imbalance due to Cytokine‐Producing NK, γδ T and NK‐γδ T Cells in Murine Pregnancy Decidua in Success or Failure of Pregnancy
Authors: CLARK DAVID A. , CROITORU KENNETH 
Published: December 2003

PROBLEM: Recurrent spontaneous abortion in DBA/2‐mated CBA/J mice has been attributed to the production of Th1 cytokines (tumor necrosis factor [TNF]‐α and interferon [IFN]‐γ) by asialoGM1+ natural killer (NK) cells and Vγ1.1δ6.3+ T cells that infiltrate decidua by day 6.5, during the peri‐implantation period. Abortions can be prevented by a second population of Vγ1.1δ6.3 cells, which infiltrate on day 8.5 of gestation, and produce the Th2 cytokine interleukin (IL)‐10 and Th3 cytokine transforming growth factor (TGF)‐β2. In low abortion rate immunocompetent mice, most of the TGF‐β2 is derived from γδ T cells. However, TGF‐β2‐producing cells are present in the decidua of pregnant severe combined immune deficient (SCID) mice, which lack γδ T cells.
METHODS: The cells in day 13.5 decidua of CBA×DBA/2 matings and SCID×SCID matings were identified using flow cytometry and combined surface staining for γδ and/or asialoGM1, and intracellular cytokine staining for TNF‐α, IFN‐γ, and TGF‐β2,3.
RESULTS: TGF‐β2 and TNF‐α were found in asialoGM1+ NK cells in SCID mouse decidua. In CBA×DBA/2 mated mice, two major and one minor subsets of cytokine‐positive cells were identified: ‐γδ‐only T cells, double positive asialoGM1+γδ+ (NK‐γδ T) cells, and a small number of asialoGM1+γδ− NK‐only cells. The NK‐only and NK‐γδ T subsets showed a greater Th1/Th2,3 pattern of intracellular staining compared with the γδ‐only subset. In the CBA×DBA/2 and SCID×SCID systems, Th1/Th2,3 ratios could not predict actual observed abortion rates but did correlate with susceptibility to abortions (if exposed to an additional stimulus such as stress). The known effect of in vivo administration of anti‐asialoGM1 antibody on abortion rates within groups of mice exposed to such stresses could also be predicted.
CONCLUSION: γδ+ cells in decidua (e.g. Vγ1+ cells which can recognize trophoblasts) differ based on the presence or absence of the NK marker‐asialo‐GM1. NK‐γδ T cells may be quite important in the Th1 response in early pregnancy that predisposes to abortions in CBA×DBA/2 matings, whereas γδ T‐only cells appear to be protective. In pregnant SCID mice, the TNF‐α+/TGF‐β2+ NK population is greatly expanded. An activating stimulus (such as stress or endotoxin) appears to be as important in triggering abortions, as is the Th1/Th2,3 ratio at the feto–maternal interface.
Unique Susceptibility of the Fetal Thymus to Feline Immunodeficiency Virus Infection: An Animal Model for HIV Infection In Utero1
Authors: JOHNSON CALVIN M. , CRAWFORD P. CYNTHIA , PAPADI GEORGE P. , BORTNICK SANDRA J. 
Published: December 2003

PROBLEM: Human infants infected in utero with HIV develop thymus insufficiency and progress to AIDS sooner than infants infected peripartum. However, direct analysis of the thymus is difficult due to limited tissue access and variable timing of vertical transmission.
METHOD OF STUDY: Fetal and neonatal cats were inoculated with feline immunodeficiency virus (FIV) at an equivalent infectious dose. The thymus, blood, and lymph nodes were harvested and compared at 23 and 46 days post‐inoculation (p.i.) and also compared to sham‐inoculated, age‐matched controls. Lymphocyte phenotypes were analyzed by flow cytometry and virus burden was quantified in histologic sections and by virus isolation from plasma.
RESULTS: Fetal cats inoculated with FIV had acute thymus atrophy at birth, which coincided with peak viremia. At 46 days p.i., thymus size and cell composition rebounded and supported increased productive infection. In contrast, neonatal cats inoculated with FIV developed chronic thymus atrophy and degeneration, which was associated with decreasing productive infection and low‐level viremia.
CONCLUSIONS: The fetal thymus is uniquely vulnerable to acute, transient depletion and high‐level productive infection. The neonatal thymus is less vulnerable to acute changes, and responds through progressive atrophy and declining productive infection. Reduced immune competence, as reflected by the failure to control virus replication, may contribute to the accelerated progression of FIV and HIV infections in utero.
Characterization of NKT Cells in Human Peripheral Blood and Decidual Lymphocytes
Authors: TSUDA H. , SAKAI M. , MICHIMATA T. , TANEBE K. , SAITO S. , HAYAKAWA S. 
Published: December 2003

PROBLEM: To examine whether natural killer (NKT) cells are present in human pregnancy decidua.  METHOD OF STUDY: We calculated the percentage of CD3+CD161+Vα 24+‐NKT cells in peripheral blood and early pregnancy decidua, and analyzed intracellular cytokines, interleukin (IL)‐4 and interferon (IFN)γ in NKT cells using flow cytometry.
RESULTS: A distinct subset of CD3+CD161+ lymphocytes expressing an invariant antigen receptor encoded by the Vα24 and Vβ11 segment was accumulated in the decidua. In pregnant subjects the percentages of NKT cells were significantly increased in the decidua compared with peripheral blood. Both NKT cells in the decidua and the peripheral blood had an ability to rapidly produce cytokine associated with Th1 (IFNγ) and Th2 (IL‐4). Interestingly, the percentages of IL‐4 and IFNγ producing NKT cells were significantly higher in the decidua compared with the peripheral blood.  CONCLUSIONS: These findings suggest that NKT cells might control the Th1/Th2 balance by producing IL‐4 and IFNγ at the feto‐maternal interface.