bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased T‐Cell Activation in Decidua Parietalis Compared to Decidua Basalis in Uncomplicated Human Term Pregnancy
Authors: Sindram‐Trujillo A. , Scherjon S. , Kanhai H. , Roelen D. , Claas F. 
Published: December 2004

PROBLEM:  The aim of this study was to quantify and compare activated T cells in term decidua basalis and parietalis using flow cytometry.METHOD OF STUDY:  Term decidua basalis and parietalis samples were obtained from 20 placentas collected after elective caesarean section. Percentages of leukocyte subclasses within the CD45+ cell fraction and activated T cells were determined by flow cytometry.RESULTS:  There was no significant difference in CD45+, CD14+, CD19+, and CD3+ cell percentages. However, within the CD3+ population, there were significantly more T‐cell receptor‐γδ+ (TCR‐γδ+) and CD8+ cells in decidua parietalis compared with decidua basalis. More importantly, percentages of T cells expressing CD25, human leukocyte antigen (HLA)‐DR, CD45RO, and CD69 markers were significantly increased in decidua parietalis.CONCLUSION:  These findings suggest that there are more activated T cells in decidua parietalis than in decidua basalis. Further investigation into differences between the two decidual sites may expand our understanding of the immunology of the maternal–fetal interface.
MD‐1 is a Critical Part of the Mechanism Causing Th1‐Cytokine‐Triggered Murine Fetal Loss Syndrome
Authors: Clark David A. , Yu Gary , Arck Petra C. , Levy Gary A. , Gorczynski Reginald M. 
Published: December 2004

PROBLEM:  Fetal loss syndrome (abortion/resorption) occurring on or after gestation day (gd) 9.5 in CBA/J×DBA/2 matings is dependent upon presence of TNF‐α + IFN‐γ, which act by increasing expression of fgl2 prothrombinase at the feto‐maternal interface. The magnitude by which the abortion rate can be boosted by an injection of these cytokines on gd 7.5 depends on endogenous rate of loss, and appears to depend on microbial flora. Is cytokine‐triggered abortion dependent upon a third signaling pathway that senses ‘danger'?METHODS:  Female CBA/J were mated to DBA/2 males and, C57Bl/6 and C57Bl/6 TNFαR1−/−Mak were mated to C57Bl/6 control or TNFαR1−/−Mak males. LPS from Escherichia coli and Salmonella enteritidis, or the combination of TNF‐α + IFN‐γ, was injected to stimulate abortions. The effect of anti‐MD‐1, which interferes with expression of CD14 and, hence, with signaling by LPS via the CD14‐tlr4 complex, on TNF‐α + IFN‐γ was tested. The presence of MD‐1 in the uterus was evaluated by in situ hybridization, and effect of lipopolysaccharide (LPS) on mice lacking TNF‐αR1 was tested.RESULTS:  Anti‐MD‐1 completely abrogated TNF‐α + IFN‐γ ‐induced abortions. MD‐1 was expressed on trophoblast and in deciduas on gd 8.5 but LPS could not abort mice that lacked the type 1 receptor for TNF‐α. Pregnant CBA/J females had classical resorptions (abortions) countable on gd 13.5–14.5 in response to LPS from E. coli or S. enteritidis, but C57Bl/6 strain mice resorbed only in response to the latter, and E. coli LPS appeared to induce ‘occult’ losses. ‘Occult’ loss did not require TNF‐α R1.CONCLUSIONS:  TNF‐α + IFN‐γ could not induce murine abortions without co‐presence of a ‘danger’ signal such as LPS acting via CD14 on toll receptors, and LPS could not act without co‐signaling by TNF‐α. Classical resorptions/abortions and ‘occult’ losses have a different mechanism in these models as reflected in type of endotoxin and requirement for TNF‐αR1 signaling.
Chemokine Bioactivity of RANTES is Elevated in the Sera of Infertile Women with Past Chlamydia trachomatis Infection
Authors: Shibahara Hiroaki , Hirano Yuki ,   Ayustawati, Kikuchi Kumiko , Taneichi Akiyo , Fujiwara Hiroyuki , Takamizawa Satoru , Sato Ikuo 
Published: December 2004

PROBLEM:  It has been shown that Chlamydia trachomatis infection in infertile women is highly associated with tubal pathology. Chlamydia trachomatis antibody testing is a simple screening test for tubal factor subfertility, however, it is based on the detection of previous infection. Recently, association between some inflammatory diseases and chemokines has been investigated. This study was performed to clarify the relationship between chemokines in the sera of infertile women and past C. trachomatis infection.METHOD OF STUDY:  Serum samples were collected from 10 infertile women having C. trachomatis antibodies [immunoglobulin (Ig)G and/or IgA] in their sera and 10 infertile women without the antibodies. All patients' tubo‐ovarian structures were explored by transvaginal hydrolaparoscopy (THL). A CXC chemokine, interleukin‐8, and six CC chemokines including macrophage inflammatory protein‐1α (MIP‐1α), MIP‐1β, monocyte chemotactic protein‐1 (MCP‐1), MCP‐3, eotaxin, and regulated on activation, normal T cell expressed and secreted (RANTES) concentrations in their sera were analyzed using enzyme‐linked immunosorbent assay.RESULTS:  The serum concentration of RANTES was significantly higher in patients with C. trachomatis antibodies than those without the antibodies (P = 0.019). However, there were no significant differences of the concentrations of other chemokines between the sera of infertile women with and without C. trachomatis antibodies. The concentration of RANTES in the sera of infertile women did not correlate with C. trachomatis antibody titers or tubal pathology diagnosed by THL.CONCLUSIONS:  These findings might indicate significant roles of some chemokines in the pathogenesis of C. trachomatis infection. Further studies are necessary to study the usefulness of evaluations of chemokines in tubal infertility investigations.
Expression of Nuclear Factor of Activated T Cells mRNA in Maternal Peripheral Blood Cells
Authors: Kojima H. , Tamura T. , Okuda T. , Kato C. , Kinoshita Y. , Honjo H. 
Published: December 2004

PROBLEM:  In T lymphocytes, nuclear factor of activated T cells (NF‐AT) regulates the induction of cytokine genes upon antigenic stimulation. This study was designed to analyse the relationship between NF‐AT and pregnancy.METHOD OF STUDY:  With informed consent, peripheral blood cells (PBCs) were obtained from non‐pregnant (n = 114), pregnant (n = 604), and puerperal women (n = 52). The expression of NF‐AT2 and NF‐AT3 mRNAs in PBCs was measured by a quantitative reverse transcriptase‐polymerase chain reaction method.RESULTS:  In the early pregnancy period, in successful pregnancy, both NF‐AT2 and NF‐AT3 mRNAs increased significantly, whereas in cases of spontaneous abortion they did not change significantly. After peaking, they decreased gradually and were re‐elevated in the ninth and tenth gestational month. In the puerperal period, NF‐AT3 mRNAs decreased, but NF‐AT2 mRNA showed a comparatively high expression level.CONCLUSION:  These findings suggested that in humans NF‐AT signal transduction might be involved in alloantigenic recognition and tolerance and play important roles, especially in the early and late period of pregnancy.
TNF‐α Protects Embryos Exposed to Developmental Toxicants
Authors: Torchinsky Arkady , Shepshelovich Jeanne , Orenstein Hasida , Zaslavsky Zeev , Savion Shoshana , Carp Howard , Fein Amos , Toder Vladimir 
Published: December 2004

BACKGROUND:  Tumor necrosis factor α (ΤNF‐α) has been implicated in mediating post‐implantation embryo loss or the embryonic maldevelopment induced by development toxicants or maternal metabolic imbalances. In order to clarify the role of TNF‐α further, a comparative study was performed in TNF‐α knockout and TNF‐α positive mice, exposed to a reference teratogen, cyclophosphamide (CP).METHODS:  Cyclophosphamide was injected on day 12 of pregnancy and 18‐day fetuses were examined for external structural anomalies. Apoptosis and cell proliferation were measured by TdT‐mediated biotin–dUTP nick‐end labeling and 5′‐bromo‐2′‐deoxyuridine incorporation, respectively, in the brain (an organ, sensitive to the teratogen) of embryos 24 hr after CP injection. NF‐κB DNA‐binding activity by electrophoretic mobility shift assay (EMSA) and the expression of RelA (an NF‐κB subunit) and IκBα proteins by Western blot analysis were assessed in the brain of embryos tested 24 and 48 hr after CP treatment.RESULTS:  Surprisingly, the proportion of fetuses with craniofacial, trunk and severe limb reduction anomalies were significantly higher in TNF‐α–/– females, than in TNF‐α+/+ mice. Excessive apoptosis and suppression of cell proliferation was found in the brain, and they were more prominent in TNF‐α–/– than TNF‐α+/+ embryos, when examined 24 hr after CP injection. Finally, CP‐induced suppression of NF‐κB DNA‐binding activity was found to be enhanced in the brain of TNF‐α–/– embryos, and the restoration of NF‐κB DNA‐binding activity was compromised.CONCLUSION:  This work demonstrates for the first time that TNF‐α may act as a protector of embryos exposed to teratogenic stress. One possible mechanism may be restoration of NF‐κB activity in embryonic cells surviving the teratogenic insult.
Hofbauer Cell Activation and its increased Glucose‐6‐Phosphate Dehydrogenase Activity in Second Trimester‐spontaneous Abortion: an Ultrastructural Dual Staining Enzyme‐cytochemical Study
Authors: Matsubara S. , Takayama T. , Yamada T. , Usui R. , Izumi A. , Watanabe T. , Ohkuchi A. , Shibahara H. , Sato I. , Suzuki M. 
Published: December 2004

PROBLEM:  While activated/phagocytosing phagocytes infiltrating to the chorioamnion are considered to be one of the causal agents of preterm labor onset, whether placental villous macrophages (Hofbauer cells) are activated/phagocytosing in this condition is not known.METHOD OF STUDY:  We concomitantly localized two important phagocytosis‐related enzymes, acid phosphatase (ACP) and glucose‐ 6‐phosphate dehydrogenase (G6PD), in Hofbauer cells in second trimester placental villi, and compared them with those from infection‐related second trimester‐spontaneous abortion (miscarriage) placentas.RESULTS:  There were two types of Hofbauer cells. The first cells exhibited ACP stainings confined to the lysosomes, suggesting that they are dormant/non‐activated cells. Approximately two‐thirds of these cells showed weak G6PD labeling on the cytosolic side of endoplasmic reticula, and G6PD labeling was hardly recognizable in the remaining one‐third. The second cells, possessing large phagosomes, showed marked ACP labeling in the phagosomes, suggesting that they are activated/phagocytosing cells. All these cells exhibited G6PD labeling, and in ‘bursting cells’ (possibly hyperactivated cells) G6PD deposits were marked. The percentage of activated cells in miscarriage placentas was significantly higher (44.8 ± 6.0%) than that in gestational age‐matched controls (17.4 ± 5.3%).CONCLUSIONS:  These observations indicated that (1) G6PD activity increased in activated/phagocytosing Hofbauer cells, and (2) the percentage of phagocytosing cells increased in infection‐related miscarriage placentas. Hofbauer activation and G6PD may play an role in the pathogenesis/pathophysiology of preterm labor onset.
Pre‐term Birth and Severe Pre‐eclampsia are not Associated with Altered Expression of HLA on Human Trophoblasts*
Authors: Datema Gert , Van Meir Claudia A. , Kanhai Humphrey H. H. , Van Den Elsen Peter J. 
Published: December 2004

PROBLEM:  The unusual pattern of human leukocyte antigen (HLA) expression on human trophoblasts could play an important role in successful pregnancy outcome. To determine whether alterations in HLA expression are associated with pregnancy abnormalities we have investigated expression of these antigens on chorionic and extravillous cytotrophoblasts.METHODS:  Frozen tissue sections of placenta and fetal membranes were collected after pre‐term spontaneous delivery, severe pre‐eclampsia pre‐term Caesarean section, normal term delivery and term Caesarean section. HLA expression was analyzed by immunohistochemistry.RESULTS:  We did not observe differences in the expression of HLA on chorionic and extravillous cytotrophoblasts in pregnancy abnormalities. However, we noted higher expression levels of HLA class Ia molecules in amnion epithelial cells in pre‐term deliveries. Furthermore, in severe pre‐eclampsia the number of extravillous cytotrophoblast islands were elevated when compared with pre‐term deliveries.CONCLUSIONS:  No alterations in expression of HLA class Ia, HLA‐G and HLA class II on human trophoblasts in pregnancy abnormalities were seen.
Th1 Cytokines and the Prothrombinase fgl2 in Stress‐triggered and Inflammatory Abortion
Authors: Knackstedt M. K. , Zenclussen A. C. , Hertwig K. , Hagen E. , Dudenhausen J. W. , Clark D. A. , Arck P. C. 
Published: December 2004

PROBLEM:  The immune system contributes to the outcome of pregnancy by complex immunological interactions. Cytokines especially influence the immune milieu pro or contra pregnancy. T helper 1 (Th1) cytokines [tumor necrosis factor‐α (TNF‐α) and interferon‐γ (IFN‐γ)] cause inflammation and together are thought to threaten the maintenance of pregnancy. It has been proposed that increased levels of these Th1 cytokines activate coagulation via up‐regulating the novel prothrombinase, fgl2. This study further investigates the Th1 cytokine up‐regulation of fgl2 expression in a pathophysiological, stress induced abortion model, and an inflammatory, interleukin‐12 (IL‐12) triggered abortion model.METHOD:  The DBA/2J‐mated CBA/J female mice were exposed to sonic sound stress or were injected with IL‐12 during early gestation. On day 13.5 of pregnancy the uteri were removed and the resorption rate was calculated. We evaluated TNF‐α, IFN‐γ, fgl2 as well as IL‐12 messenger RNA (mRNA) expression in decidual samples of all mice by quantitative, real‐time polymerase chain reaction (PCR).RESULTS:  A similar resorption rate of 24% was detected in stressed mice, as well as in IL‐12 injected mice compared with approximately 11% in non‐stressed, non‐injected control mice. In stressed mice compared with controls, we observed on day 13.5 up‐regulated TNF‐α, unchanged IFN‐γ down‐regulated fgl2, and a slightly increased levels of IL‐12. In the IL‐12 triggered abortion model, we observed up‐regulated levels of TNF‐α, IFN‐γ and fgl2.CONCLUSION:  These novel data suggest two distinct cytokine patterns leading to similar abortion rates. A physiological cascade associated with up‐regulation of TNF‐α, and an IL‐12‐triggered cascade characterized by persistent up‐regulation of TNF‐α and IFN‐γ as well as a persistent increase in fgl2.
Antiphospholipid Antibodies in Implantation Failures*
Authors: McIntyre J. A. 
Published: December 2004

PROBLEM:  The amino phospholipids (PL), phosphatidylserine (PS) and phosphatidylethanolamine (PE) are distributed asymmetrically in the plasma membranes of eucaryotic cells. This arrangement involves active transport of PS and PE from the outer to inner membrane leaflet by an aminophospholipid translocase (flipase). Cell activation, injury and programmed cell death (apoptosis) cause collapse of the PS/PE asymmetry by activation of another enzyme system, scramblase. Unlike other cells, the developing trophoblast exteriorizes PS during its differentiation.METHODS OF STUDY:  An analysis of published and unpublished data.RESULTS:  The trophoblast is targeted by antiphospholipid antibodies (aPL), especially to PS (aPS). Cardiolipin is not present in the trophoblast plasma membrane, nonetheless, anticardiolipin (aCL) has been implicated in trophoblast pathology. The aPS and aCL are often crossreactive. Both animal and in vitro experimental models have shown monoclonal and polyclonal aPS and aCL to specifically destroy trophoblast, inhibit syncytium formation, halt human chorionic gonadatropin (hCG) production, and limit trophoblast invasion. Antibodies to PE (aPE) have not been well characterized, however, recent reports from several independent laboratories document that aPE are associated significantly with very early (embryonic) recurrent pregnancy loss (RPL). Umeda and coworkers have shown that during cytokinesis (late telophase) of Chinese hamster ovary (CHO) cells, formation of PE rafts in cleavage furrows is required for completion of cell division and formation of daughter cells. This raises the question whether aPE might interfere with implantation and cell division during embryogenesis.CONCLUSIONS:  A role for aPL in implantation failure and occult pregnancy loss constitutes the basis of this overview.
Feasibility to Generate Monocyte‐Derived Dendritic Cell from Coculture with Melanoma Tumor Cells in the Presence of Granulocyte / Macrophage Colony‐Stimulating Factor (GM‐CSF) and Interleukin‐4
Authors: Kim Young T. , Hersh Evan M. , Trevor Katrina T. 
Published: December 2004

OBJECTIVE:  We investigated how melanoma cells and membrane‐bound granulocyte/macrophage colony stimulating factor (mbGM‐CSF) melanoma cell lines affect the differentiation of dendritic cells (DC) from CD14+ monocytes.METHOD OF STUDY:  The malignant melanoma cell lines (Conley and Jorp) and mbGM‐CSF‐positive cell lines (Conley B‐F8 and Jorp C‐E6) were cultured and cell‐free supernatants were collected from each cell line cultures to assess the GM‐CSF level. Adherent monocytes were cocultured for 6–7 days with irradiated mbGM‐CSF and wild type melanoma cells (50 Gy) at each 1 : 1 and 0.1 : 1 ratio in six‐well culture plates in ex vivo culture medium containing interleukin (IL)‐4. Immunophenotyping was performed by triple color immunofluorescence staining with flow cytometry analysis.RESULTS:  GM‐CSF was detected at low levels in the culture supernatants of Conley B‐F8 (0.48 ng/106 cells/24 hr), whereas there was no detectable GM‐CSF in that of Conley melanoma cell line. Monocytes cultured with GM‐CSF/IL‐4 generated the expression of high levels of HLA DR, CD1a and CD86, while the expression of CD14 and CD83 were in low amounts. However, the addition of GM‐CSF to these cultures resulted in an increased expression of these markers and decreased that of CD14. Monocytes cocultured with Jorp C‐E6 illustrated similar expression pattern of CD1a, HLA DR and CD14 in the presence or absence of GM‐CSF as Conley B‐F8 melanoma cell line. Monocytes cocultured with Conley B‐F8 melanoma cells at 1 : 1 and 0.1 : 1 ratio showed no significant difference in expression of CD1a, CD14 and CD83 between the two ratios.CONCLUSION:  Our results illustrate the feasibility to generate monocyte‐derived DC from coculture with melanoma tumor cells in the presence of GM‐CSF and IL‐4. However, mbGM‐CSF tumor cells did not significantly enhance the DC differentiation through juxtacrine stimulation unless soluble GM‐CSF was added in the culture media.
Use of a Highly Specific Monoclonal Antibody Against the Central Variable Amino Acid Sequence of Mammalian Gonadotropin Releasing Hormone to Evaluate GnRH‐I Tissue Distribution Compared With GnRH‐I Binding Sites in Adult Male Rats
Authors: Khan Mohammad A. H. , Ferro Valerie A. , Stimson William H. 
Published: December 2004

PROBLEM:  Recent evidence shows the existence of numerous isoforms of gonadotropin releasing hormone (GnRH), with high sequence homology and a core variable region. This raises the issue that previous GnRH distribution studies may have identified a variety of isoforms. This investigation was carried out to confirm the distribution and binding activity of GnRH‐I only.METHOD OF STUDY:  A monoclonal antibody (7B101D10), with specificity for the core region of GnRH‐I was used to stain formalin‐fixed tissue sections from adult male Sprague–Dawley rats, while a biotinylated GnRH‐I sequence was used with avidin‐labelled HRP to evaluate regions of GnRH‐I binding.RESULTS AND CONCLUSIONS:  GnRH‐I expression was only found in the hypothalamus, cerebellum, anterior/fore brain and in Sertoli cells, while, binding activity was only present in the pituitary, subendocardium and subepicardium, thymic lymphocytes, peripheral blood lymphocytes and neutrophils. There was overlap in the olfactory neurons, liver (Kupffer macrophages and hepatocytes), spleen (lymphocytes and dendritic cells), myocardium and testes (spermatozoa and Leydig cells) and this may be further evidence of the paracrine/autocrine activity of a neuropeptide.
The Role of Cytokines in Endometriosis*
Authors: Wu Ming‐Yih , Ho Hong‐Nerng 
Published: December 2004

PROBLEM:  To review the literature on the role of peritoneal cytokines in the pathogenesis and endometriosis‐related infertility.METHODS OF STUDY:  A MEDLINE search was conducted by the key words of cytokine and endometriosis in the English publications, and references identified within the identified papers were also reviewed.RESULTS:  Several cytokines including interleukin (IL)‐1, 6, 8, 10, tumor necrosis factor (TNF)‐α, and vascular endothelial growth factor (VEGF) were reported to be increased in the peritoneal fluid (PF) of women with endometriosis. Those cytokines may be involved in macrophage activation, inflammatory change and enhanced angiogenesis. However, some cytokines were less expressed such as IL‐2, and interferon (IFN)‐γ. They reflect the impaired T‐ and natural killer (NK)‐cell function. Endometriotic implants produce some factors, e.g. matrix metalloproteinases (MMPs), Bcl‐2, and affect their capacity to implant into the peritoneum.CONCLUSION:  Peritoneal cytokines, which are produced by mesothelial cells, leukocytes and ectopic endometrial cells, interwork locally and systemically in women with endometriosis. More studies about the specific role and interactions of these cytokines are needed to improve the understanding of endometriosis and to develop novel therapies.
Effects of Boar Seminal Immunosuppressive Fraction on Production of Cytokines by Concanavalin A‐Stimulated Spleen Cells and on Proliferation of B Lymphoma Cell Lines
Authors: Veselský L. , Holáň V. , Zajícová A. , Dostál J. , Železná B. 
Published: December 2004

PROBLEM:  The immunosuppressive fraction (ISF) of boar seminal vesicle fluid has recently been demonstrated to inhibit mitogen‐stimulated proliferation of lymphocytes and antibody response to corpuscular and soluble antigens. The effects of ISF on in vitro and in vivo production of cytokines as well as its possible inhibitory effect on proliferation of B lymphoma cells remain to be elucidated.METHODS:  The effect of ISF on proliferation of normal mouse spleen cells stimulated by Concanavalin A (Con A) and on mouse B lymphoma cells was measured by 3H‐thymidine incorporation. Cytokines were determined in the supernatants of mouse spleen cells stimulated with Con A in the presence or absence of ISF by enzyme‐linked immunosorbent assay (ELISA). In vivo cytokine production in the sera samples of mice treated with ISF and immunized with keyhole limpet hemocyanin (KLH) was followed by ELISA, too.RESULTS:  We confirmed the inhibitory effect of ISF on Con A‐stimulated lymphocyte proliferation. ISF affected cytokine production in the Con A‐stimulated spleen cells: production of interleukin‐2 (IL‐2) and interferon‐γ (IFN‐γ) was lowered, but production of IL‐4, IL‐6, and IL‐10 was enhanced. Similarly, in the sera samples of mice immunized with keyhole limpet hemocyanin (KLH), IL‐2 and IFN‐γ levels were decreased by ISF. ISF inhibited proliferation of Ag 8 and X 63‐IL‐2 B lymphoma cells as well.CONCLUSIONS:  ISF inhibited production of T helper1 (Th1) cytokines (IL‐2 and IFN‐γ) and enhanced production of Th2 cytokines (IL‐4, IL‐6, and IL‐10). ISF seems to shift the Th1/Th2 pattern in favor of Th2. ISF exhibited an antiproliferative activity on mouse B lymphoma cells.
Twenty‐three years of labour floor records, Vila Central Hospital, Vanuatu
Authors: Grace Robert F , Vurobaravu Thomas S 
Published: December 2004

AbstractVanuatu is an island nation in the south‐west Pacific. Vila Central Hospital (VCH) is the country's major referral hospital. The handwritten labour floor records from VCH between 1979 and 2001 were examined and collated. During this period 28 638 women received care. The mean Caesarean section and instrumental delivery rate were 5.2% (2.1–8.2% per annum) and 1.8% (0.9–3.2% per annum), respectively. The post‐partum haemorrhage rate fell from >5% in 1979 to <1% in 2001. The overall hospital maternal mortality rate was 7/10 000. These records represent the largest published series of labour floor data collected from any Pacific island nation.