bluuebunny/crossref_metadata_2025_split huggingface dataset:
GRO‐alpha in Human Serum: Differences Related to Age and Sex
Authors: Kanda Yuki , Koike Dr. Koji , Sakamoto Yoshiki , Osako Yasuko , Masuhara Kanji , Watanabe Kazuyoshi , Tsurufuji Susumu , Hirota Kenji , Miyake Akira 
Published: September 2011

PROBLEM: Human GRO‐alpha (GRO‐α) is a new member of the chemokine family that is supposed to play an important role in inflammatory and immune reactions. We established a sandwich enzyme‐linked immunoassay (ELISA) system with polyclonal antibodies against human GRO‐α and investigated the serum level of healthy donors to establish normal ranges for this chemokine in adults.METHODS: GRO‐α concentrations were measured cross‐sectionally in the sera of 240 healthy adults. The variability of serum GRO‐α levels was also measured in normal volunteers, samples from whom were obtained by sequential venipunctures or by a small plastic cannula with a heparin‐saline lock, to determine short‐term variability.RESULTS: Whereas there was no difference between the concentration of human GRO‐α from men (logarithmic mean, 77.6 pg/ml, n = 120) and that from women with normal menstrual cycles (log mean, 71.6 pg/ml, n = 73), the concentration from postmenopausal women (log mean 45.0 pg/ml, n = 31) was lower than that from women with normal menstrual cycles (log mean 71.6 pg/ml, n = 73). However, we could not detect any significant difference between healthy donors' serum levels and those of donors with acute inflammation. Fewer variations were recognized in the case of the sequential venipunctures method than in that of the heparin‐saline lock method.CONCLUSION: We found that the GRO‐α concentration of postmenopausal women was significantly lower than that of women with normal menstrual cycles. These results suggest the GRO‐α serum levels of normal healthy women may have some correlation with sex hormones.
Pathogenetic Implication of Interleukin‐2 Expressed in Preeclamptic Decidual Tissues: A Possible Mechanism of Deranged Vasculature of the Placenta Associated with Preeclampsia
Authors: Hamai Yoko , Fujii Tomoyuki , Yamashita Takahiro , Kozuma Shiro , Okai Takashi , Taketani Yuji 
Published: September 2011

PROBLEM: The purpose of this study is to clarify whether IL‐2 expressed in the decidua in preeclampsia affects the angiogenesis of the placenta.METHOD OF STUDY: We investigated the angiogenic substances released from human trophoblasts obtained from early pregnancy that had been pretreated with either IL‐2, non‐activated lymphocytes from peripheral blood mononuclear cells (PBMCs), decidual lymphocytes, or these lymphocytes activated by lymphokine (LAK cells). Angiogenic activity was determined by evaluating the ability of growth‐promotion of cultured human microvascular endothelial cells (HMvECs) using MTT assay.RESULTS: Trophoblasts pretreated with IL‐2 or non‐activated lymphocytes, irrespective of their origin, released angiogenic factor similar to those without pretreatment. However, trophoblasts pretreated with LAK cells released less angiogenic factor compared with those without pretreatment.CONCLUSIONS: Interleukin‐2 (IL‐2) expressed in preeclamptic decidua might reduce the angiogenic substances arising from trophoblasts by inducing LAK cells from decidual lymphocytes, which might be relevant to deranged vasculature of the placenta, a characteristic histology in preeclampsia.
TGF‐β2 and PGE2 in Rabbit Blastocoelic Fluid Can Modulate GM‐CSF Production by Human Lymphocytes
Authors: Fortin Marylène , Ouellette Marie‐Josée , Lambert Raymond D. 
Published: September 2011

PROBLEM: During normal pregnancy, major changes occur in the production of Th2/Th1 cytokines at the feto‐maternal interface. Th2 cytokines such as interleukin‐4 (IL‐4) or interleukin‐10 (IL‐10) are predominantly produced locally in the uterine and placental tissues, whereas the production of Th1 cytokines such as tumor necrosis factor alpha (TNF‐α) and interferon gamma (IFN‐γ) are decreased. Because these modulations might be induced by the embryo, the current study was carried out to test the effect of rabbit blastocoelic fluid on the production of Th2/Th1 cytokines by lymphocytes, and to investiate the possible implication of transforming growth factor β2 (TGF‐β2) prostaglandin E2 (PGE2) as modulators of the production of these cytokines.METHOD OF STUDY: Human peripheral blood lymphocytes (PBL) were cultured along with ConcanavalinA (Con A), and rabbit blastocoelic fluid was collected on day 12 of gestation (BF d‐12). Concentrations of cytokines in culture media were determined by enzyme‐linked immunoadsorbent assay (ELISA).RESULTS: Addition of BF d‐12 in the culture medium induced a strong inhibition of IL‐2, TNF‐α, IL‐10, and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) production. However, an initial pretreatment of the lymphocytes with BF d‐12, followed by a Con A stimulation, led to a marked increase in GM‐CSF production, whereas IL‐2, TNF‐α, and IL‐10 secretions were inhibited. It was also demonstrated, for the first time, that a pretreatment of the lymphocytes with TGF‐β2 and PGE2 increased GM‐CSF production to the same level reached after the addition of BF d‐12. Furthermore, removal of TGF‐β2 and PGE2 from BF d‐12 by affinity chromatography reduced the effect of BF d‐12 on GM‐CSF production.CONCLUSIONS: Taken together, these findings suggest that the embryo, in modulating harmful and beneficial cytokine production locally, plays an active role in its protection against maternal immune cellular assault. These results also emphasize the importance of growth factors for successfully maintaining pregnancy.
Genetics of Reproduction and Its Evolutionary Significance
Authors: Gill Thomas J. 
Published: September 2011

PROBLEM: To provide an evolutionary perspective on reproductive problems.METHOD OF STUDY: A broad range of evolutionary and reproductive data in the literature were analyzed.RESULTS: Evolutionary considerations provide some insight into two aspects of human reproduction. First, the inefficiency of the reproductive process (20–35% of fertilized ova yield successful pregnancies) may reflect the stress placed on the reproductive process by the relatively short evolutionary time between the hunter‐gatherer and settled agricultural patterns of human life. Second, the immaturity of the immune response of the human newborn is most likely a consequence of its delivery while still in the embryonic/fetal stage of development. Delivery at this time is necessitated by the rapid development of the human brain in utero.CONCLUSIONS: The attempts to develop reproductive technologies should take into account the fundamental limits on the human reproductive process. A variety of in utero preventive and therapeutic techniques should be developed to provide the newborn with enhanced resistance to infectious diseases or to correct congenital defects. All new procedures should be thoroughly investigated and proved before being put into clinical practice.
Immunogenetic and Oncogenic Properties of Rat Trophoblast Cell Lines
Authors: Kunz Heinz W. , Yuan Xiu‐Juan , Salgar Shashikumar K. , Dixon‐McCarthy Barbara , Gill Thomas J. 
Published: September 2011

PROBLEM: The nature of major histocompatibility complex (MHC) antigen expression on rat placentas, trophoblast cell lines, and tumors derived from trophoblast cells was explored.METHOD OF STUDY: Cytohistochemical and flow cytometric analysis and molecular techniques.RESULTS: MHC antigen expression and genomic imprinting on the placenta and on trophoblast cells varies with the time of gestation and with the type of MHC antigen.CONCLUSIONS: There is no correlation in trophoblast cells between class I expression and cell ploidy, on the one hand, and malignant potential, on the other hand. Genomic imprinting of class I antigens in the rat placenta is a quantitative phenomenon.
Progesterone and Non‐specific Immunologic Mechanisms in Pregnancy
Authors: Szekeres‐Bartho Julia , Par G. , Szereday L. , Achatz I. , Smart C.Y. 
Published: September 2011

PROBLEM: Progesterone‐dependent immunomodulation is one of the mechanisms that enables pregnancy to proceed to term. Immunologic effects of progesterone are mediated by a protein named the progesterone‐induced blocking factor (PIBF). Among other effects this protein inhibits natural killer (NK) activity and displays an anti‐abortive effect in mice. Recently we have shown that PIBF induces a Th2 shift in vitro. The present study was aimed at investigating the in vivo effect of PIBF on cytokine production, as well as the relationship between cytokine production, NK activity, and pregnancy loss.METHOD OF STUDY: Balb‐c mice on day 8.5 of pregnancy were injected intraperitoneally with 0.5 mg of rabbit anti‐PIBF immunoglobulin G (IgG). Another group of mice was simultaneously treated with anti‐NK monoclonal antibodies. Mice treated with the same amount of normal rabbit serum or untreated mice of similar gestational age were used as controls. The animals were sacrificed on day 10.5, and their uteri were inspected. The ratio of living and resorbed embryos was determined. NK activity as well as cytokine expression on the spleen cells were determined by immunocytochemistry and enzyme‐linked immunoadsorbent assay (ELISA).RESULTS: Mitogen‐activated spleen cells from anti‐PIBF‐treated mice produced significantly (P < 0.001) less IL‐10 than those of pregnant control mice. A significantly higher percentage (P < 0.001) of spleen cells from anti‐PIBF‐treated mice expressed interferon‐γ (IFNγ) as determined by immunocytochemistry, than those of untreated pregnant mice. There was a positive relationship between the percentage of IFNγ‐positive spleen cells and resorption rates, and an inverse relationship between the latter and interleukin‐10 (IL‐10) production. All these effects were corrected by treatment with anti‐NK antibodies. CONCLUSION: Our data suggest that PIBF contributes to the success of gestation via eytokine‐mediated inhibition of NK activity.
Endothelial Cells as a Target for Antiphospholipid Antibodies: Role of Anti‐Beta 2 Glycoprotein I Antibodies
Authors: Del Papa N. , Raschi E. , Catelli L. , Meroni P.L. , Khamashta M.A. , Ichikawa K. , Tincani A. , Balestrieri G. 
Published: September 2011

PROBLEM: To investigate the role of the plasma cofactor for antiphospholipid antibodies in antibody binding to endothelial cells.METHOD OF STUDY: a) Evaluation of endothelial cell binding of polyclonal and monoclonal anti‐β2 glycoprotein I antibodies; and b) study of the effects of antibody binding: adhesion molecule expression, leukocyte adhesion, and interleukin‐1β secretion. RESULTS: Anti‐β2 glycoprotein I antibodies bind endothelial cell monolayers in vitro by reacting with the cofactor adhered to the cell membranes. Antibody binding induces an upregulation of adhesion molecules, favours leukocyte adherence, and increases interleukin‐1β secretion. Interleukin‐1β plays an active role to mediate adhesion molecule expression through an autocrine loop, as shown by the inhibitory effect of interleukin 1 receptor antagonist.CONCLUSIONS: Antiphospholipid antibodies do react with endothelium through the co‐factor adhered to their cell membranes and induces a pro‐adhesive cell phenotype.
Paternal Leukocytes Selectively Increase Secretion of IL‐4 in Peripheral Blood During Normal Pregnancies: Demonstrated by a Novel One‐Way MLC Measuring Cytokine Secretion
Authors: Ekerfelt Christina , Ernerudh Jan , Matthiesen Leif , Berg Göran 
Published: September 2011

PROBLEM: It has been proposed that immune responses in normal pregnancy are Th2‐like, thereby protecting the fetus and placenta from being rejected. Some studies have shown Th2‐deviated systemic responses to different antigens and mitogens. The aim of this study was to demonstrate the specific T cell cytokine responses directed toward paternal histocompatibility leukocyte antigen (HLA), because this is the most prominent target for rejection of the feto‐placental unit.METHOD OF STUDY: A novel one‐way mixed leukocyte culture (MLC) combined with the detection of cytokine secretion with a sensitive ELISPOT assay was developed. Peripheral blood from 11 pregnant women was investigated with respect to allo‐reactivity toward paternal leukocytes and pooled leukocytes from unrelated blood donors. This was done at three different occasions during pregnancy and 8 weeks after delivery. Nine age‐matched non‐pregnant women served as controls.RESULTS: In the second and third trimesters of pregnancy significantly larger numbers of IL‐4‐secreting cells (Th2) were induced by paternal leukocytes as compared to unrelated leukocytes.CONCLUSIONS: The findings indicate a selective immune deviation toward Th2, which may protect the fetus from rejection and thus may be an important homeostatic mechanism in normal pregnancies.
Stability of Serum Interleukin‐10 Levels During the Menstrual Cycle
Authors: Maskill Joanna K. , Laird Susan M. , Blakemore Alexandra I. F. , Okon M. , Li T. C. 
Published: September 2011

PROBLEM: Menstrual cycle‐associated variability in the circulating levels of several cytokines can be a confounding factor in measurements of in vivo cytokine levels in clinical studies. Since pregnancy‐associated increases in interleukin‐10 (IL‐10) levels are well documented, we have investigated the variability in serum levels of IL‐10 in healthy women at different stages of the menstrual cycle to ascertain whether this is a problem in comparative studies of circulating IL‐10 levels.METHOD OF STUDY: We obtained fifty‐four successive serum samples at points in the menstrual cycles of 12 healthy fertile women, precisely timed by measurement of the luteinizing hormone surge, and measured the interleukin‐10 levels.RESULTS: Levels of IL‐10 in successive serum samples from each woman taken on days LH‐7 (that is seven days prior to LH surge), LH‐4, LH+1, LH+7, and LH+10 showed that IL‐10 does not vary in a systematic way during the menstrual cycle.CONCLUSION: These results validate the sampling of women in studies of IL‐10 levels in various clinical situations and establish that these levels are not dependent on menstrual cycle dates. They also suggest that menstrual cycle‐related changes in IL‐1 are not mediated by IL‐10. The rise in progesterone in the luteal phase of the menstrual cycle is not mirrored by a rise in the circulating IL‐10 level, which implies either that the pregnancy‐associated rise is not related to progesterone or that it is only observed at the higher progesterone levels in pregnancy.
Peritoneal Cellular Immunity and Endometriosis
Authors: Ho Hong‐Nerng , Wu Ming‐Yih , Yang Yu‐Shih 
Published: September 2011

PROBLEM: An immunologic basis has long been considered to be very important in the pathogenesis of endometriosis. Interactions of the peritoneal cells, which comprise macrophages, B cells, T cells, natural killer (NK) cells, and retrograde endometrial cells, are critical, but remain controversial, for exploring the pathogenesis of endometriosis. METHOD OF STUDY: Accumulated data from the literature were reviewed, and our data were analyzed.RESULTS: The data show that peritoneal macrophages are activated by the recurrent reflux of menstrual shedding. Humoral and local endometrial autoantibodies are detected in patients with endometriosis, but B cells are not quantitatively increased. There is decreased NK cell activity in the peritoneal cavity and peripheral blood, and this decreased activity may be related to the failure to clear out the ectopic endometrial tissue. Peritoneal T cells are predominant by Thl inflammatory cells, and these cells are impaired because of a decrease in activation (especially HLA‐DR+ CD4+ CD3+ population) and in the production of interleukin‐2. Inflammatory cytokines such as interleukin‐1, interleukin‐6, and tumor necrosis factor‐α are elevated in the peritoneal fluid of women with endometriosis. CONCLUSIONS: The peritoneal NK and T lymphocytes are suppressed in women with endometriosis, but whether these immunologic deviations are the cause or the result of endometriosis is still unclear. Further studies are required to determine what role immunologic factors play in the pathophysiology of endometriosis.
Transferrin Receptor (CD71) Expression in Peritoneal Macrophages from Fertile and Infertile Women With and Without Endometriosis
Authors: Martínez‐Román Sergio , Balasch Juan , Creus Montserrat , Fábregues Francisco , Carmona Francisco , Vilella Ramón , Vanrell Juan A. 
Published: September 2011

PROBLEM: Hyperactivated macrophages are implicated in the pathophysiology of endometriosis‐associated infertility. This study investigates transferrin receptor expression (CD71) as a marker of hyperactivity in peritoneal macrophages of infertile patients with minimal to mild endometriosis (group 1, n = 25).METHOD OF STUDY: Expression of the activation antigen CD71 on peritoneal fluid macrophages was determined by a specific monoclonal anti‐CD71 antibody using indirect immunofluorescence technique and was analyzed by flow cytometry. Three different control groups of women were used: women with unexplained infertility (group 2, n = 25), fertile women with endometriosis (group 3, n =10), and fertile women without endometriosis (group 4, n = 25).RESULTS: The percentage of CD71 positive cells was significantly increased in infertile women with endometriosis as compared with the three control groups. There were no differences among groups 2, 3, and 4 with respect to the percentage of CD71 positive macrophages.CONCLUSIONS: Our results favor the concept that hyperactivated macrophages play a role in the pathophysiology of endometriosis‐associated subfertility, a feature which is lacking in patients with unexplained infertility.
Soluble Human Leukocyte Antigens, Interleukin‐6, and Interferon‐γ During Pregnancy
Authors: Russwurm G.P. , Mackler A.M. , Fagoaga O.R. , Brown W.S. , Sakala E.P. , Yellon S.M. , Nehlsen‐Cannarella S.L. 
Published: September 2011

PROBLEM: Soluble human leukocyte antigens (sHLA), interferon‐γ (IFN‐γ), and interleukin‐6 (IL‐6) were studied during human pregnancy to test the hypothesis that sHLA concentrations are regulated by these specific cytokines.METHOD OF STUDY: Enzyme‐linked immunoadsorbent assays (ELISA) were used to measure sHLA I and II in maternal circulation, cord blood, and placenta effluents of pregnant and nonpregnant women; maternal serum cytokines were also determined.RESULTS: sHLA in maternal and cord blood were equivalent to that in the placenta. By the third trimester, sHLA I concentrations in maternal plasma were significantly reduced compared to the first or second trimesters. sHLA II was increased during the second trimester relative to that postpartum. Maternal IL‐6 and IFN‐γ concentrations were not statistically different throughout gestation or postpartum.CONCLUSIONS: These data do not suggest a role for maternal plasma IL‐6 or IFN‐γ in regulation of systemic sHLA class I during pregnancy, but they do not address whether such events take place in local tissues of the maternal‐fetal unit.
Lethal Outcome of Uterine Infection in Pregnant but Not in Nonpregnant Rats and Increased Death Rate With Inhibition of Nitric Oxide
Authors: Nowicki B. , Fang L. , Singhal J. , Nowicki S. , Yallampalli C. 
Published: September 2011

PROBLEM: Limited information is available on potential differences in sensitivity to urogenital infections between pregnant and nonpregnant hosts.METHOD OF STUDY: In this study, we evaluated Escherichia coli infectious complications in pregnant and nonpregnant rats and the effect of nitric oxide (NO) inhibitor, NG‐nitro‐l‐arginine methyl ester (l‐NAME), on the outcome of an experimental uterine infection.RESULTS: Of the infected pregnant animals, 31% were found dead in 24–48 hr. The death rate was increased 2‐fold (66%) with l‐NAME treatment. No deaths occurred in nonpregnant animals with or without l‐NAME treatment. The rate of uterine infection in pregnant animals was about 10‐fold higher than in nonpregnant animals.CONCLUSION: We propose that infectious complications of pregnancy may be related to gestation‐dependent sensitivity to the pathogenic microorganism and the host NO status.
Cytokine Expression by First‐Trimester Human Chorionic Villi
Authors: Bennett W.A. , Lagoo‐Deenadayalan S. , Stopple J.A. , Barber W.H. , Hale E. , Brackin M. N. , Cowan B. D. 
Published: September 2011

PROBLEM: Communication at the human maternal‐fetal interface occurs by an intricate cytokine network. This study examines cytokine expression by normal first‐trimester human chorionic villi.METHOD OF STUDY: Tissues were obtained at elective pregnancy terminations (7–9 weeks). Total RNA was isolated from chorionic villi by guanidinium isothiocynate‐acid phenol extraction. A reverse transcriptase‐polymerase chain reaction technique was used to examine cytokine expression. β‐Actin was used as the housekeeping gene, and mitogen‐stimulated lymphocytes served as positive controls.RESULTS: β‐Actin was uniformly expressed by all chorionic villous samples. Interferon (IFN)‐α and ‐β also were highly expressed. Moderate expression was noted for interleukin (IL)‐10, IL‐6, tumor necrosis factor (TNF)‐α, and IL‐1β. In contrast, transforming growth factor‐β1, IFN‐γ, IL‐2, and IL‐1α were either weakly expressed or absent in first‐trimester villi. CONCLUSIONS: Cytokines may contribute to pregnancy immunotolerance (IFN‐α, IFN‐β, and IL‐10), viral resistance (IFNs), hormone secretion (IL‐1 and IL‐6), and cellular remodeling (IFN‐γ and TNF‐α) within the chorionic villous.