bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Immunoregulatory Activity, Biochemistry, and Phylogeny of Ovine Uterine Serpin
Authors: PELTIER MORGAN R. , HANSEN PETER J.
Published: December 2003

PROBLEM: During pregnancy, the endometrium of the ewe secretes a progesterone‐induced member of the serpin superfamily of serine proteinase inhibitors called ovine uterine serpin (OvUS) that has immunosuppressive properties.  METHOD: Review of the literature.  RESULTS AND CONCLUSIONS: OvUS inhibits a wide variety of immune responses, including mixed lymphocyte reaction, mitogen‐stimulated lymphocyte proliferation, and T cell‐dependent antibody production. Recent data have suggested that OvUS functions by inhibiting protein kinase C and interleukin‐2‐mediated events. OvUS and similar genes present in cattle and pigs diverged from other serpins prior to the divergence of artiodactyls. Since this time, the serpins have apparently undergone adaptive evolution that has led to a conformational state and biological functions distinct from prototypical serpins. Thus, it is likely that these proteins have an important role in the reproductive biology of Artiodactyla. Several lines of evidence suggest that, in sheep, OvUS functions to mediate the immunosuppressive effects of progesterone and prevent immunological rejection of the fetal allograft.
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.
Asymmetric Antibodies and Pregnancy
Authors: ZENCLUSSEN ANA CLAUDIA , GENTILE TERESA , MARGNI RICARDO , KORTEBANI GRACIELA , MAZZOLLI ALICIA
Published: December 2003

PROBLEM: Asymmetric IgG antibodies (AAb) possess a mannose‐rich oligosaccharide residue bound to one of the Fab regions, making them unable to activate immunoeffector mechanisms. The proportion of asymmetric antibodies is increased after prolonged immunization with particulate antigens like cellular spleen cells. During pregnancy, AAb were found in serum and bound to placenta with specific activity to paternal antigens. No previous reports about the status of AAb in recurrent spontaneous abortion (RSA) patients have been published to date. Therefore, the aim of the present study was to analyze the percentage of asymmetric IgG molecules in serum samples of (a) healthy pregnant and non‐pregnant women, (b) pregnant women with a history of RSA, and (c) non‐pregnant RSA patients receiving paternal lymphocyte immunotherapy (LIT) or intravenous gammaglobulin therapy (IVIgs).  METHOD OF STUDY: A previously‐described differential ELISA technique was used to determine the percentage of IgG that was of the asymmetric type.  RESULTS: During normal pregnancy, there was an increase in the percentage of high ConA affinity IgG serum molecules with a major increase at the second trimester. Pregnant RSA patients at the second trimester had lower values. When evaluating non‐pregnant RSA patients who received LIT, it was observed that the immunized patients expressed a higher percentage of asymmetric IgG antibodies. The pregnant patients who received IVIgs had a percentage of AAbs comparable to normal pregnant patients. Additionally, the presence of IgG asymmetric molecules was confirmed in commercial gammaglobulin preparations.  CONCLUSION: Results suggest a protective role of AAb during pregnancy.
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.
Murine Stress‐triggered Abortion is Mediated by Increase of CD8+ TNF‐α+ Decidual Cells via Substance P
Authors: JOACHIM R.A. , HILDEBRANDT M. , ODER J. , KLAPP B.F. , ARCK P.C.
Published: December 2003

PROBLEM: Stress is known to induce abortions in mice and humans. Increased levels of abortogenic type 1 helper T‐cell cytokines and decreased levels of pregnancy protective cytokines could be linked to stress‐triggered embryonic loss. Stress promotes neurotransmitter substance P (SP) release in tissues. SP increases the production of decidual tumor necrosis factor (TNF)‐α, whereby the phenotype of these TNF‐α‐producing cells is hypothetical. The objective of the present study was to identify decidual TNF‐α‐producing cell populations that are involved in stress‐induced murine abortion.   METHOD: DBA/2J‐mated CBA/J female mice were exposed to ultrasonic sound stress on day 5.5 of pregnancy. The mice were randomized and half were treated with the SP NK1‐receptor antagonist (SP‐RA) RP 67580 (200 μg/mouse). Frequency and cytokine profile of CD8+ cells were evaluated by immunohistochemistry and flow cytometry. Degranulation of uterine mast cells was examined histologically. 
RESULTS: On day 13.5 of pregnancy, the uteri were removed and the resorption rate was calculated. A mean resorption rate of 38.4% was detected in stressed mice (n=10) compared to 13.1% in non‐stressed control mice (n=11, P<0.01). Injection of SP‐RA decreased the abortion rate to 18.4% in stressed mice (n=19, P<0.01). Flow cytometry revealed a stress‐related increase of TNF‐α+/CD8+ decidual T cells, which could be abrogated by SP‐RA (P<0.05). No significant differences could be observed in numbers of mast cells and total CD8+ cells in situ. 
CONCLUSION: Our data suggest that stress‐triggered abortion is mediated by SP, and SP receptor blockade abrogates stress‐triggered abortion via reduced production of TNF‐α by CD8+ T cells.
Bovine Trichomoniasis as a Model for Development of Vaccines against Sexually‐transmitted Disease
Authors: CORBEIL LYNETTE B. , MUNSON LINDA , CAMPERO CARLOS , BONDURANT ROBERT H.
Published: December 2003

PROBLEM: Human sexually transmitted diseases (STDs) are widespread but effective vaccines are rare. Experimental and commercially available vaccines for bovine trichomoniasis have been well studied. Principles for immune protection of the female genital tract derived from studies of bovine trichomoniasis may be generally applicable to human trichomoniasis and other STDs.  METHOD OF STUDY: A bovine model of trichomoniasis has been developed for study of mechanisms of immunoprophylaxis.  RESULTS: Both systemic and local immunization with an immunoaffinity purified antigen cleared the genital tract of trichomonads significantly earlier than non‐immunized controls. Predominantly IgA responses or predominantly IgG responses in uterine and vaginal secretions were essentially equally protective. Uterine and vaginal IgA responses could be induced by systemic priming and local boosting via either the vaginal or nasal mucosa. In either case, lymphoid aggregates were formed in the uterine and vaginal mucosa which were not present in the genital mucosa of naïve animals.  CONCLUSIONS: Systemic immunization or systemic priming with local boosting protects against bovine trichomoniasis via IgG or IgA antibodies (respectively) to a major surface antigen of trichomonads. Immunization of the genital mucosa results in formation of inductive sites for a local IgA response.
Dysregulation of the Cytokine Network in the Uterus of the Diabetic Rat
Authors: PAMPFER SERGE
Published: December 2003

Insulin‐dependent (type 1) diabetes is an auto‐immune disorder that produces secondary complications in numerous non‐immunological systems. Changes in the synthesis and action pattern of several cytokines have been associated with the development of these alterations. Based on the clinical facts that the pregnant and non‐pregnant functions of the reproductive system are also disrupted by diabetes, our laboratory has decided to concentrate its research activities on the hypothesis that cytokines may be implicated in the uteropathy and embryopathy associated with the metabolic disorder. This review article summarizes our major findings concerning the synthesis of TNF‐α and IL‐1β in the uterus of diabetic rats, and in cultures of rodent uterine cells upon their exposure to high concentrations of glucose. The paper also reviews evidence that both the peri‐implanting embryo and the epithelial cell layer lining the uterine lumen are targets for the deleterious influence of excess TNF‐α. If confirmed in the uterus of diabetic patients, these observations may explain how cytokines contribute to the dysregulation of crucial reproductive events like menstruation and embryo implantation in humans.
Mammalian Expression Cloning of Two Human Trophoblast Suppressors of Major Histocompatibility Complex Genes
Authors: PEYMAN J. A.
Published: December 2003

PROBLEM: Human trophoblasts suppress interferon‐γ (IFN‐γ)‐simulated expression of major histocompatibility complex (MHC) class II genes and thereby protect the conceptus from maternal immune attack. The mechanism of this suppression is poorly understood.  METHOD OF STUDY: IFN‐γ‐responsive HeLa cells were stably transfected with trophoblast cDNA expression libraries and screened by negative immunoselection with an antibody to HLA‐DR.  RESULTS: Two suppressor cDNAs were isolated. One encoded the untranslated RNA trophoblast STAT utron (TSU), which blocked STAT1 nuclear translocation and can theoretically form triplex RNA–DNA at the class II transactivator gene promoters. The other encoded the N‐terminal 28 residues of chorionic somatomammotropin (hCS). TSU‐related genes were detected in human and macaque, but not in mouse, genomic DNA.  CONCLUSIONS: The genetics of two human trophoblast MHC suppressors suggest that these functions have been gained in human placenta in recent evolutionary history. TSU and hCS play critical roles in suppression of MHC genes, which may lead to silencing by DNA methylation.
Stress and Pregnancy Loss: Role of Immune Mediators, Hormones and Neurotransmitters
Authors: Arck Petra Clara
Published: December 2003

This review highlights recent studies investigating the impact of stress on pregnancy health or loss. Spontaneous abortion is the most common adverse pregnancy outcome, and stress has been suggested to be abortogenic in mice and humans. A wealth of information has been published on the effect of stress on the nervous, endocrine and immune systems during the past two decades. Stress‐ and/or pregnancy‐related hormones (corticotropin releasing hormone, adrenocorticotropin, prolactin, and progesterone) might interact with peripheral and local immuncompetent cells, such as certain T cell subsets, mast cells or NK cells, and result in changes of cytokine production. Since a well‐balanced interaction of nervous, endocrine and immune system is crucial for the maintenance of successful pregnancy, putative mechanisms and recent observations on stress‐triggered pregnancy failure have been reviewed.
Thrombophilic Gene Mutations and Recurrent Spontaneous Abortion: Prothrombin Mutation Increases the Risk in the First Trimester
Authors: Pihusch Rudolf , Hiller Erhard , Buchholz Tina , Rogenhofer Nina , Hasbargen Uwe , Thaler Christian J. , Lohse Peter , Rübsamen Heike
Published: December 2003

PROBLEM: Thrombophilic predisposition may be one of the underlying causes of recurrent spontaneous abortions (RSA). We studied the prevalence of five thrombophilic gene mutations in patients with RSA.  METHOD OF STUDY: 102 patients with two or more consecutive abortions and 128 women without miscarriage were analyzed for factor V Leiden mutation (FVL), prothrombin G20210A mutation (PTM), C677T mutation in the 5,10‐methylenetetrahydrofolate reductase (MTHFR) gene, glycoprotein IIIa (GPIIIa) C1565T polymorphism, and β‐fibrinogen G‐455A polymorphism by polymerase chain reaction (PCR) techniques.  RESULTS: No differences in the prevalence of FVL, MTHFR T/T, GPIIIa and β‐fibrinogen polymorphism were detected. Heterozygous PTM occurred more often in patients with RSA. This effect was significant in a subgroup with abortions exclusively in the first trimester (6.7% vs. 0.8%, P=0.027, OR 8.5).  CONCLUSIONS: In contrast to the other mutations and polymorphisms, heterozygous PTM is more common in patients with abortions in the first trimester. This might reflect an influence of PTM on pathogenesis of early pregnancy loss.
High NK Cell Activity in Early Pregnancy Correlates with Subsequent Abortion with Normal Chromosomes in Women with Recurrent Abortion
Authors: Yamada Hideto , Hirayama Kato Emi , Ebina Yasuhiko , Shimada Shigeki , Morikawa Mamoru , Sakuragi Noriaki , Fujimoto Seiichiro , Kobashi Gen
Published: December 2003

PROBLEM: The aim of this study was to assess the role of natural killer (NK) cells in pregnant women with a history of recurrent spontaneous abortion (RSA).  METHOD OF STUDY: Consecutive 66 pregnant women with a history of RSA were prospectively assessed for peripheral NK cell activity, percentage of the NK cell subsets, and subsequent pregnancy outcome.  RESULTS: NK cell activity in women with subsequent live birth (group I) at 4–5 gestational weeks (GW) (mean±SD, 32.5±12.3%) significantly decreased at 6–7 GW (28.1±12.1%) and at 8–9 GW (28.0±11.8%). NK cell activity in women with subsequent abortion with normal chromosomes (group II) at 6–7 GW (41.2±19.0%) was significantly higher than that in group I women, while NK cell activity at 6–7 GW in women with subsequent abortion with abnormal chromosomes (group III) was the same as the level in group I women.  CONCLUSIONS: High NK cell activity at 6–7 GW correlates with subsequent abortion with normal chromosomes.
Choriocarcinoma Cells Modulate the Cytokine Production of Decidual Large Granular Lymphocytes in Coculture
Authors: Rieger Lorenz , Kämmerer Ulrike , Hofmann Jürgen , Sütterlin Marc , Dietl Johannes
Published: December 2003

PROBLEM: How do major histocompatibility complex (MHC) I positive/negative choriocarcinoma (CC) cells affect the production of tumor necrosis factor‐α (TNF‐α), interferon‐γ (IFN‐γ), interleukin‐10 (IL‐10), interleukin‐4 (IL‐4), and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) by decidual CD56++ cells (large granular lymphocytes [LGL]), LGL‐depleted decidual cells (WASH) and unseparated decidual cells (DEC) in cocultures? METHOD OF STUDY: Decidual tissue was obtained by legal abortions. CD 56++ LGL were isolated in a magnetic cell separator. Cytokines were measured by ELISA. Differences were analyzed for significance by Wilcoxons test.  RESULTS: We found a significant increase of IL‐10 in LGL/JEG‐3 and of TNF‐α in LGL/JAR cocultures compared to noncocultured decidual cells. There was a significant increase of IL‐10 and TNF‐α and a significant decrease of GM‐CSF in WASH and DEC cocultures with both JEG‐3 and JAR. IFN‐γ was only found in 3/11 cases of LGL/JAR cocultures. No IL‐4 was found in any experiment.  CONCLUSION: MHC class I positive/negative CC modulate the cytokine production of decidual LGL in different ways.
Expression of Decay Accelerating Factor in Endometrial Adenocarcinoma is Inversely Related to the Stage of Tumor
Authors: Nowicki S. , Nowicki B. , Pham T. , Hasan R. , Nagamani M.
Published: December 2003

PROBLEM: Decay accelerating factor (DAF) is implicated in protection of cell membrane from toxicity of complement. In this study, we investigated a hypothesis that DAF is up‐regulated in the endometrial adenocarcinoma, which could increase potential of malignant cells to escape destruction by complement.  METHODS: DAF density was evaluated in endometrial biopsies of patients with adenocarcinoma at various stages and compared with ten endometrial biopsies from non‐malignant patients at the proliferative phase.  RESULTS: DAF expression in normal proliferative endometrium varied between 1 and 30%. While DAF density in patients with stage I cancer was in the range 56–98% (mean 78%), stage III values varied from 28 to 16% (mean 21%), P<0.05. DAF density in the well‐differentiated Ishikawa cell line was two‐fold higher than in metastatic cell line AN3CA.  CONCLUSIONS: Our findings are consistent with a hypothesis that endometrial adenocarcinoma of early stage that is exposed to complement attack may up‐regulate DAF to protect malignant cells from complement lysis.
Isolation of Antibody to Human Placental Alkaline Phosphatase (PLAP) from Extracts of Human Placentae
Authors: Freeman Jennifer L. , Rhyne Paul W. , Dean Deyrick O. , Beard G. Alan , Doellgast George J.
Published: December 2003

PROBLEM: Human placental alkaline phosphatase (PLAP) is a unique placental antigen bound to the syncytiotrophoblast, which may be able to elicit a specific immune response in pregnancy.  METHOD OF STUDY: Antibody to PLAP was purified from placental extracts by: a) acid elution of membrane vesicles; b) purifying complexes of PLAP with human antibody on monoclonal antibodies to PLAP followed by denaturation of the enzyme; and c) by denaturation of PLAP in placental extracts and purification of antibody to PLAP on PLAP columns.  RESULTS AND CONCLUSIONS: Specific antibody to PLAP is present in placental extracts, and is mostly bound to placental membrane preparations. PLAP is therefore immunogenic in pregnancy and could serve as a useful monitor of pregnancy‐specific immunological responses. Since a similar enzyme appears in some cancers, it is possible that the immunization against PLAP in pregnancy will help to protect against the development of ovarian and endometrial cancer (the ‘fetal antigen’ hypothesis).
Expression of Tumor Necrosis Factor‐α in the Pregnant Uterus of Diabetic Mice: Effect of Maternal Immunopotentiation
Authors: Fein A. , Kostina E. , Savion S. , Orenstein H. , Shepshelovich J. , Torchinsky A. , Toder V. , Ornoy A.
Published: December 2003

PROBLEM: Tumor necrosis factor (TNF)‐α mRNA and protein are expressed in the pregnant uterus of streptozotocin‐induced diabetic mice at various stages of pregnancy. We intend to characterize their pattern and to evaluate whether the potentiation of the maternal immune system alters the pattern of the expression of the cytokine.  METHOD OF STUDY: Diabetes was induced in ICR mice by streptozotocin injection. To modulate maternal immune responses, ICR mice were injected intrauterine with rat splenocytes 3 weeks before mating. The expression of TNF‐α mRNA and protein was evaluated by in situ hybridization and immunohistochemistry techniques.  RESULTS. The population of diabetic mice used in this study demonstrated a reduction in pregnancy rate and an increased number of litters with severely malformed fetuses. It has been observed that these disturbances are associated with a clear increase in TNF‐α mRNA and protein expression in the uterus of these mice. Maternal immunopotentiation, while improving reproductive performance of these diabetic mice, was found to be accompanied by a reduced expression of TNF‐α, both at the mRNA and protein level.  CONCLUSIONS. The results of the present study suggest a possible involvement of TNF‐α in mechanisms underlying diabetes‐associated dismorphogenesis. Normalization of TNF‐α expression by maternal immunopotentiation might represent a mechanism mediating its protective effect against diabetes‐induced embryotoxic insult.
Comparative T‐Cell Responses During Pregnancy in Large Animals and Humans
Authors: Meeusen Els N.T. , Bischof Robert J. , Lee Chee‐Seong
Published: December 2003

PROBLEM: Placentation in different large animal species shows a remarkable diversity in the level of trophoblast invasion into the maternal endometrial tissues. We wish to determine the influence of implantation on T‐cell responses during pregnancy.  METHOD OF STUDY: Review of the literature and current data.  RESULTS: αβ‐TCR+ T cells are only prominent during early pregnancy in species with relatively non‐invasive placentation (pig and horse) but are rapidly downregulated in species with more invasive placentae. γδ‐TCR+ T cells are prominent in species with moderate trophoblast invasion (ruminants) where they increase dramatically during mid and late pregnancy. γδ‐TCR+ T cells remain prominent during late gestation in species with highly invasive placentation (humans) and, in addition, a distinct γδ T‐cell population is present in first trimester decidua where it may play a regulatory role in controlling natural killer cell activity. The γδ‐TCR+ population present in both ruminants and humans shows large granular morphology and contains antimicrobial proteins, suggesting their function may be to protect the uterine environment from infection during pregnancy and parturition.  CONCLUSION: The comparative analysis of T‐cell responses during pregnancy in different large animal species supports an increasing role for cells of the innate immune response (NK and γδ T cells) and a downregulation of the adaptive immune response with increasingly invasive placentation.
Respiratory muscle injury, fatigue and serum skeletal troponin I in rat
Authors: Simpson Jeremy A. , Eyk Jennifer Van , Iscoe Steve
Published: December 2003

To evaluate injury to respiratory muscles of rats breathing against an inspiratory resistive load, we measured the release into blood of a myofilament protein, skeletal troponin I (sTnI), and related this release to the time course of changes in arterial blood gases, respiratory drive (phrenic activity), and pressure generation. After ∼1.5 h of loading, hypercapnic ventilatory failure occurred, coincident with a decrease in the ratio of transdiaphragmatic pressure to integrated phrenic activity (Pdi/∫Phr) during sighs. This was followed at ∼1.9 h by a decrease in the Pdi/∫Phr ratio during normal loaded breaths (diaphragmatic fatigue). Loading was terminated at pump failure (a decline of Pdi to half of steady‐state loaded values), ∼2.4 h after load onset. During 30 s occlusions post loading, rats generated pressure profiles similar to those during occlusions before loading, with comparable blood gases, but at a higher neural drive. In a second series of rats, we tested for sTnI release using Western blot–direct serum analysis of blood samples taken before and during loading to pump failure. We detected only the fast isoform of sTnI, release beginning midway through loading. Differential detection with various monoclonal antibodies indicated the presence of modified forms of fast sTnI. The release of fast sTnI is consistent with load‐induced injury of fast glycolytic fibres of inspiratory muscles, probably the diaphragm. Characterization of released fast sTnI may provide insights into the molecular basis of respiratory muscle dysfunction; fast sTnI may also prove useful as a marker of impending respiratory muscle fatigue.
Chloride secretion in a morphologically differentiated human colonic cell line that expresses the epithelial Na+ channel
Authors: Currid Aoife , Ortega Bernardo , Valverde Miguel A.
Published: December 2003

Cell line models of colonic electrolyte transport have been extensively used despite lacking some of the characteristics of native tissue. While native colonic crypts absorb or secrete NaCl, immortalized cell lines only retain the secretory phenotype. In the present study we have characterized functionally and molecularly, vectorial fluid and electrolyte transport in the morphologically differentiated human colonic cell line LIM1863. LIM1863 cells form morphologically differentiated organoids resembling native human colonic crypts, which secrete fluid and electrolytes across the apical membrane into a centrally located lumen. Net fluid secretion was evaluated by means of morphometric measurement of lumens formed in LIM organoids in response to known secretagogues. Pharmacological profiling of the channels and transporters involved in fluid and electrolyte transport showed that net fluid transport requires Cl− uptake across the basolateral membrane through a Na+–K+–2Cl− cotransporter (NKCC1) and its subsequent exit across an apical cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel. Similar to the native colon, net Cl− secretion in the LIM1863 cell line is activated by cAMP‐mediated agonists. Carbachol, a Ca2+‐mediated agonist, does not induce net Cl− secretion but modulates the cAMP‐activated response. Expression of chloride channels (CFTR and the Ca2+‐dependent Cl− channel, ClCa1), potassium channels (KCNN4 and KCNQ1), epithelial Na+ channel (ENaC) α, β and γ subunits and ion transporters (NKCC1; anion exchanger, AE2; Na+/H+ exchangers, NHE1–3) was detected by RT‐PCR and Western blot in the case of ENaC. Based on this evidence we propose that LIM1863 cells provide a unique model for studying CFTR‐dependent Cl− secretion in a morphologically differentiated human colonic crypt cell line that also expresses ENaC.
Fatigue damage modeling of fibre-reinforced composite materials: Review
Authors: Degrieck and Joris , Van Paepegem Wim
Published: December 2003

This article presents a review of the major fatigue models and life time prediction methodologies for fibre-reinforced polymer composites, subjected to fatigue loadings. In this review, the fatigue models have been classified in three major categories: fatigue life models, which do not take into account the actual degradation mechanisms but use S-N curves or Goodman-type diagrams and introduce some sort of fatigue failure criterion; phenomenological models for residual stiffness/strength; and finally progressive damage models which use one or more damage variables related to measurable manifestations of damage (transverse matrix cracks, delamination size). Although this review does not pretend to be exhaustive, the most important models proposed during the last decades have been included, as well as the relevant equations upon which the respective models are based. This review article contains 141 references.
Developments, ideas, and evaluations based upon Reissner’s Mixed Variational Theorem in the modeling of multilayered plates and shells
Authors: Carrera Erasmo
Published: December 2003

This review article is devoted to the use of the Reissner Mixed Variational Theorem (RMVT) forward two-dimensional modeling of flat and curved, multilayer structures. A thorough review of the literature involving the use in the modeling of multilayered plates and shells using RMVT is also presented. In the first part, the paper overviews relevant key points that should be taken into account for an accurate description of strain and stress fields in multilayered plate and shell analysis. It is then shown that RMVT has been originated in view of the fulfillment of such key points, herein referred to as C0-Requirements (zig-zag form of the displacement fields in the thickness direction and continuity of transverse normal and shear stresses at each layer interface). Classical variational statements are used to introduce Reissner’s Theorem. In the second part, the paper presents various ways in which RMVT can be used to develop plate and shell theories in a systematic manner. The so called layer-wise and equivalent single layer variable description are considered. Both strong and weak (finite element) forms of governing equations have been derived. A Weak Form of Hooke’s Law (WFHL), is also discussed as an idea to eliminate transverse stress variables leading to standard classical models with only displacement unknowns. Two appendices display details of governing equations related to multilayered doubly curved shells and to finite element matrices of multilayered plates. A third part reviews the works that have appeared in literature which make use of RMVT. Mainly papers on multilayered plate and shell modelings have been addressed. The final part of the paper is devoted to giving an overview with selected results of numerical performance that can be acquired by RMVT applications; extensive comparison to elasticity solutions and to other significant analyses, based on classical and refined approaches, are given. It is concluded that Reissner’s Mixed Theorem should be considered as a natural tool for multilayered structure analyses; it plays a similar role to that of the Principle of Virtual Displacement in the analysis of isotropic single-layer structures. This review article includes 119 references.
Topology optimization of continuum structures: A review*
Authors: Eschenauer Hans A , Olhoff Niels
Published: December 2003

It is of great importance for the development of new products to find the best possible topology or layout for given design objectives and constraints at a very early stage of the design process (the conceptual and project definition phase). Thus, over the last decade, substantial efforts of fundamental research have been devoted to the development of efficient and reliable procedures for solution of such problems. During this period, the researchers have been mainly occupied with two different kinds of topology design processes; the Material or Microstructure Technique and the Geometrical or Macrostructure Technique. It is the objective of this review paper to present an overview of the developments within these two types of techniques with special emphasis on optimum topology and layout design of linearly elastic 2D and 3D continuum structures. Starting from the mathematical-physical concepts of topology and layout optimization, several methods are presented and the applicability is illustrated by a number of examples. New areas of application of topology optimization are discussed at the end of the article. This review article includes 425 references.
Some Studies on Energy Savings in Sponge Iron Plants
Authors: Biswas D. K. , Asthana S. R. , Rau V. G.
Published: December 2003

This paper presents the potential for energy savings in various capacity sponge iron plants by estimating heat transfer rates using stabilized and optimized temperature data within the rotary kiln/reactor. Air jet seal instead of mechanical seal arrangements at specific locations in the rotary kiln and cooler are proposed and this is shown to reduce the power consumption and the size of the centralized grease lubricating system. The paper proposes atomized water spray on the post combustion chamber instead of larger droplets to reduce the size of the water handling system, thereby saving energy. The paper also suggests optimization of the performance of a pneumatic coal injector by optimizing coal and air quantities.
Modeling of Slug Dissipation and Generation in Gas-Liquid Hilly-Terrain Pipe Flow
Authors: Zhang Hong-Quan , Al-Safran Eissa M. , Jayawardena Subash S. , Redus Clifford L. , Sarica Cem , Brill James P.
Published: December 2003

Hilly-terrain pipelines consist of interconnected horizontal, uphill and downhill sections. Slug flow experiences a transition from one state to another as the pipe inclination angle changes. Normally, slugs dissipate if the upward inclination becomes smaller or the downward inclination becomes larger, and slug generation occurs vice versa. Appropriate prediction of the slug characteristics is crucial for the design of pipeline and downstream facilities. In this study, slug dissipation and generation in a valley pipeline configuration (horizontal-downhill-uphill-horizontal) were modeled by use of the method proposed by Zhang et al. The method was developed from the unsteady continuity and momentum equations for two-phase slug flow by considering the entire film zone as the control volume. Computed results are compared with experimental measurements at different air-mineral oil flow rate combinations. Good agreement is observed for the change of slug body length to slug unit length ratio.
Multiple scales analyses of the dynamics of weakly nonlinear mechanical systems
Authors: Cartmell, MP , Ziegler, SW , Khanin, R , Forehand DIM
Published: December 2003

This review article starts by addressing the mathematical principles of the perturbation method of multiple scales in the context of mechanical systems which are defined by weakly nonlinear ordinary differential equations. At this stage the paper investigates some different forms of typical nonlinearities which are frequently encountered in machine and structural dynamics. This leads to conclusions relating to the relevance and scope of this popular and versatile method, its strengths, its adaptability and potential for different variant forms, and also its weaknesses. Key examples from the literature are used to develop and consolidate these themes. In addition to this the paper examines the role of term-ordering, the integration of the so-called small (ie, perturbation) parameter within system constants, nondimensionalization and time-scaling, series truncation, inclusion and exclusion of higher order nonlinearities, and typical problems in the handling of secular terms. This general discussion is then applied to models of the dynamics of space tethers given that these systems are nonlinear and necessarily highly susceptible to modelling accuracy, thus offering a rigorous and testing applications case-study area for the multiple scales method. The paper concludes with comments on the use of variants of the multiple scales method, and also on the constraints that the method can bring to expectations of modelling accuracy. This review article contains 134 references.
Recent developments and applications of invariant integrals
Authors: Chen Yi-Heng , Lu Tian Jian
Published: December 2003

Although invariant integrals (path independent integrals) have been used extensively in the 20th century, mainly in the calculation of dominant parameters that govern the initiation and propagation of both linear and nonlinear cracks, new applications are increasingly being identified. This article presents developments and applications of the invariant integrals in recent years, focusing on four major application areas: i) fracture mechanics of functional materials (eg, piezoelectric ceramics and ferromagnets), which exhibit features different from those found in purely mechanical problems due to the coupling of electric, magnetic, thermal, and mechanical quantities; ii) damage mechanics of multiple interacting cracks, and new damage measures; iii) domain integrals, two-state integrals, and their applications in determining the dominant parameters of 3D cracks and in clarifying the role of higher order singular terms in the Williams eigenfunction expansions; and iv) nano-structures (eg, stress driven surface evolution in a heteroepitaxial thin film). In writing this review article, we have been able to draw upon a large number of published works on invariant integrals over the last three decades, and yet it is impossible to cover the whole subject in the limited space available. Consequently, the main aim of the article is to summarize the major developments and applications in the four important areas mentioned above. Still, 261 references are reviewed in the article.
Use of conventional optical fibers and fiber Bragg gratings for damage detection in advanced composite structures: A review
Authors: Kuang and KSC , Cantwell WJ
Published: December 2003

Structurally integrated sensors which are capable of continuous structural health monitoring represent an attractive option in view of their potential for providing real-time assessment/warning of structural damage. In recent years, optical fiber systems have attracted a considerable amount of attention and have been shown to be a very attractive option for health monitoring in advanced composite materials. These sensors have either been embedded or surface-bonded to the host material thereby allowing continuous assessment of the health of the structure. Structural health assessment takes the form of damage detection and/or monitoring of specific health indicators. In the former approach, the optical fiber systems are generally optimized to increase their sensitivity to the presence of damage in the composite structure, while the latter approach relies on the examination of characteristic changes in the monitored parameter to infer a loss in structural integrity. To this end, many investigators have demonstrated the potential of optical fiber sensors, most particularly intensity-based optical fiber systems and fiber Bragg grating sensors for structural health monitoring of advanced composite materials. The initial part of this paper provides an up-to-date review of the applications of optical fiber sensors in composite materials, focussing particularly on the use of intensity-based optical fiber systems and fiber Bragg grating sensors for damage detection. These optical fiber systems have been shown to be capable of detecting impact damage, transverse cracking, and delamination, and have the ability to monitor strain in structures. The introduction of optical fiber sensors into a composite material can inadvertently produce a geometrical discontinuity in the vicinity of the sensor. Numerous experimental investigations have also been performed to assess the possible reduction in the properties of the host structure. A review of the findings of these investigations reported in the literature is also given. This review article cites 161 references.
Innovative Technologies For Managing Oil Field Waste
Authors: Veil John A.
Published: December 2003

Each year, the oil industry generates millions of barrels of wastes that need to be properly managed. For many years, most oil field wastes were disposed of at a significant cost. However, over the past decade, the industry has developed many processes and technologies to minimize the generation of wastes and to more safely and economically dispose of the waste that is generated. Many companies follow a three-tiered waste management approach. First, companies try to minimize waste generation when possible. Next, they try to find ways to reuse or recycle the wastes that are generated. Finally, the wastes that cannot be reused or recycled must be disposed of. Argonne National Laboratory (Argonne) has evaluated the feasibility of various oil field waste management technologies for the U.S. Department of Energy. This paper describes four of the technologies Argonne has reviewed. In the area of waste minimization, the industry has developed synthetic-based drilling muds (SBMs) that have the desired drilling properties of oil-based muds without the accompanying adverse environmental impacts. Use of SBMs avoids significant air pollution from work boats hauling offshore cuttings to shore for disposal and provides more efficient drilling than can be achieved with water-based muds. Downhole oil/water separators have been developed to separate produced water from oil at the bottom of wells. The produced water is directly injected to an underground formation without ever being lifted to the surface, thereby avoiding potential for groundwater or soil contamination. In the area of reuse/recycle, Argonne has worked with Southeastern Louisiana University and industry to develop a process to use treated drill cuttings to restore wetlands in coastal Louisiana. Finally, in an example of treatment and disposal, Argonne has conducted a series of four baseline studies to characterize the use of salt caverns for safe and economic disposal of oil field wastes.
Oxidation Characteristics of Light Hydrocarbons for Underbalanced Drilling Applications
Authors: Ferguson Helen A. , Mehta S.A. (Raj) , Gordon Moore R. , Okazawa Nancy E. , Ursenbach Matthew G.
Published: December 2003

This investigation is directly relevant to various applications associated with the safety aspects of underbalanced drilling operations where de-oxygenated air may be co-injected with oil-based drilling fluid. However, de-oxygenated air often still contains up to 5% oxygen by volume. This residual oxygen can react with oil during the drilling process, thereby forming potentially hazardous oxidized hydrocarbons and compromising the safety of drilling operations. This article examines the conditions and processes by which oxidation reactions occur and may be helpful in reducing risk in drilling operations. This project characterizes the oxidation behavior of several oils and a typical oil-based drilling fluid at atmospheric and elevated pressures using thermogravimetry (TG) and pressurized differential scanning calorimetry (PDSC). Tests performed on mineral matrix (core) from the oil reservoirs showed no reactivity in both inert and oxidizing atmospheres. In an inert atmosphere, tests on all hydrocarbon samples showed only vaporization, no reactivity. In an oxidizing environment, the tests on hydrocarbons showed several oxidation regions. The presence of core had no effect on the behavior of the hydrocarbons tested in an inert atmosphere but accelerated the higher temperature oxidation reactions of the oil samples. The oil-based drilling fluid exhibited the opposite effect—the presence of core material retarded the oxidation reactions. This is perhaps due to the presence of an oxygen scavenger reacting with oxygen-containing clays present in the mineral matrix. In all tests performed on mixtures of hydrocarbon and core in oxidizing atmospheres, elevated pressures resulted in acceleration of the lower and higher temperature reaction regions.
A Ground Resistance for Vertical Bore Heat Exchangers With Groundwater Flow
Authors: Sutton Matthew G. , Nutter Darin W. , Couvillion Rick J.
Published: December 2003

A new ground resistance was developed for use in existing vertical bore heat exchanger VBHEx design algorithms. The new ground resistance accounts for the added heat transfer mode of convection due to groundwater flow by using as its foundation the solution for a moving line heat source. The combined ground resistance is presented in terms of the dimensionless Fourier and Peclet parameters. Results show that significant convection heat transfer may occur within a variety of hydrogeological regimes, particularly when the Peclet number is larger than 0.01. Since the new model captures the influence of groundwater flow, the resulting ground resistance differs markedly from the conduction-only ground resistance currently used in many vertical borehole heat exchanger design algorithms.
Solid/Liquid Phase Change in Presence of Natural Convection: A Thermal Energy Storage Case Study
Authors: Pinelli M. , Piva S.
Published: December 2003

Solid/liquid phase change process has received great attention for its capability to obtain high energy storage efficiency. In order to analyze these systems, undergoing a solid/liquid phase change, in many situations the heat transfer process can be considered conduction-dominated. However, in the past years, it has been shown that natural convection in the liquid phase can significantly influence the phase change process in terms of temperature distributions, interface displacement and energy storage. In this paper, a procedure to analyze systems undergoing liquid/solid phase change in presence of natural convection in the liquid phase based on the utilisation of a commercial computer code (FLUENT), has been developed. This procedure is applied to the study of a cylinder cavity heated from above and filled with a phase change material. It was found that when the coupling with the environment, even if small, is considered, natural convection in the liquid phase occurs. The numerical results are then compared with available experimental data. The analysis shows that the agreement between numerical and experimental results is significantly improved when the results are obtained considering the presence of circulation in the liquid phase instead of considering the process only conduction-dominated. Furthermore, some interesting features of the flow field are presented and discussed.